3060 J. Org. Chem., Vol. 42, No.

18, 1977 Burfield, Lee, and Smithers

Desiccant Efficiency in Solvent Drying. A Reappraisal by
Application of a Novel Method for Solvent Water Assay
David R. Burfield,* Kim-Her Lee, and Roger H. Smithers*
Department of Chemistry, University of Malaya, Kuala Lumpur 22-11, West Malaysia
Received J anuary 19,1977
The chemical literature, very inconsistent on the subject of the drying of solvents, abounds with contradictory
statements as to the efficiency of even the more common desiccants. The recent advent of a novel, highly sensitive
method which utilizes a tritiated water tracer for the assay of solvent water content has enabled the first compre-
hensive study to be made of the efficiency of various desiccants which pertains unambiguously to solvents. Ben-
zene, 1,4-dioxane, and acetonitrile, chosen as model solvents, were wetted with known amounts of tritiated water
and treated with a spectrum of desiccants, and the residual water contents were then assayed. The results range
from the expected to the highly surprising. Some anomalous results, obtained for benzene and acetonitrile with
acidic and basic desiccants, respectively, are discussed in terms of isotopic exchange reactions.
The bench chemist is often confronted by the problem
of the selection of desiccants for solvent drying, and although
dry solvents are frequently required for use in both prepara-
tive situations and in physicochemical studies, there is a
paucity of real information in the literature. Some authors2
are content to dismiss drying with statements such as Fre-
quently a liquid can be freed from water by shaking with a
drying agent such as anhydrous calcium chloride or phos-
phorus pentoxide. I n the field of organic synthesis, the sit-
uation is little better; different reference texts are replete with
bewildering contradictions. Thus, magnesium sulfate, de-
scribed as either neutral3a.b~~ or acidic,3c,e is alternately an
excellent drying agent, rapid in its acti ~n, ~a, ~, d, ~ or is ~1 0 ~, 3 h
removing only small amounts of water.4 Aluminum oxide is
recommended mainly for use in desiccators,3f or as being
preferred by many workers for ultimate solvent or reagent
drying.J p Calcium chloride is f a~t , ~~- ~* ~ or alternately not
rapid sf in its action, and in any case, the consensus appears
to be that calcium sulfate isto bepreferred as a and
a more ef f i ~i ent~~. ~ desiccant, even though the only existing
quantitative comparison for solvents4 shows the complete
reverse to be true. Metallic sodium, generally agreed upon3b.d
as being efficient, but slow in its drying action, is ridiculed as
a desiccant by Ple~ch,~E: who states that the widespread use
of sodium as a drying agent by organic chemists is more a
ritual than an effective process. Furthermore, there is no
doubt that many literature prescriptions for desiccation rely,
at least to some extent, on the chemical intuition of the
author, inspired perhaps by the existence of ubiquitous indices
of siccative ef f i ci en~y. ~~~?~?~~, ~ These are usually based on the
results of detailed studies of the comparative drying efficiency
of desiccants which have been made with regard to the dryness
of gases ,3h,6 and direct extrapolation to the condensed phase
often gives misleading if not totally erroneous information.
For example, phosphorus pentoxide, long considered the
ultimate drying standard? is actually quite mediocre in cer-
tain situations (vide infra). In summary, no comprehensive
study of solvent drying comparable to that made for gases
appears to exist, and since the efficiency of a desiccant is de-
pendent on the nature of the solvent, this is a serious omis-
sion.
Re~entl y,~ an extremely sensitive method using a tritiated
water tracer for the determination of solvent water content
has been developed, where essentially drying efficiency is
determined by addition of a specified amount of tritium-
labeled water to a rigorously dried solvent and subsequent
determination of the decrease in activity of the solvent after
treatment with various drying agents. With the limitation
that, owing to the problem of isotopic exchange, the method
is not applicable to protic solvents, it provides a rapid and
extremely precise assay of solvent water content. This has
prompted us to undertake a comprehensive study of the ef-
ficiency of drying of a number of desiccants for the solvents
benzene, l,4-dioxane, and acetonitrile, representative of a
spectrum of others commonly used in the laboratory. Thus,
while benzene is a model for a useful range of aromatic and
hydrocarbon solvents, and dioxane exemplifies commonly
used ethers and bisethers, acetonitrile probably parallels the
solvent behavior of a number of other polar, and, on account
of its very high dielectric constant, perhaps dipolar aprotic
solvents. Although selection of drying agents was generally
made on the basis of common usage, some more esoteric ex-
amples which have been recommended for use in particular
situations were also examined. The results have enabled us
not only to present a sensible evaluation of many time-hon-
ored solvent drying recipes, but also to advocate the use of
novel agents in previously unfamiliar situations.
Results and Discussion
Drying of Benzene. Static Drying. Benzene, despite its
carcinogenic properties, is a widely used solvent, which, be-
cause of its ease of purification and relative inertness in many
chemical systems, has been adopted as a secondary standard.
Benzene has a zero dipole moment and on account of its low
polarity has little affinity for water, the maximum solubility
of water in this solvent being 0.063% wfw at 25 C. Conse-
quently, benzene is a relatively easy solvent to dry. Drying has
been accomplished in the literatures with the following des-
iccants: phosphorus pentoxide, metallic calcium, sodium wire,
calcium hydride, and molecular sieves.
In this study benzene containing 100 ppm of water was
dried with a selection of the more useful and efficient desic-
cants. The results, summarized in Table I, apply to 5% w/v
desiccant loadings and to static drying conditions at ambient
temperatures (25-29 C). Treatment with molecular sieves,
alumina, silica gel, calcium hydride, and lithium aluminum
hydride gave super-dryg solvents within 1 day. Alumina in
particular was found to be an excellent desiccant for benzene,
reducing the solvent water content below 0.01 ppm over this
period. These findings thus corroborate earlier conclusionslO
that alumina is a particularly effective drying agent for hy-
drocarbons, previously exemplified by a-methylstyrene and
&pinene. The apparent increase in water content after drying
for 7 days is most likely due to exchange or equilibria processes
which occur between trace amounts of adventitious mois-
ture-released from the surface of the glass vessel or perhaps
gaining entry via diffusion through the clearfit stopper seal-
and labeled water adsorbed on the desiccant. I n any case, it
is probably unrealistic to attempt to maintain water contents
of below 0.01 ppm outside of totally sealed systems.
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Desiccant Efficiency in Solvent Drying J. Org. Chem., Vol. 42, No. 18, 1977 3061
Table I. Efficiency of Various Desiccants for Static Drying of BenzeneC
-
Residual solvent water content, ppm
Registry no. Desiccant 6h 1 day 7 days
1344-28- 1
7789-78-8
16853-85-3
7440-23-5
1314-56-3
10043-52-4
1151-82-6
4 A molecular sieves
A1203
Silica gel
CaH2
LiAlHI
Na
pzos
CaClz
Na2S04
2 0.03
0.6 0.006
0.3 0.3
0.2
3 2 (0.03)"
1.5 2 ( 2 ) O
7 12
12 0.1
>28 >28
0.06
0.2
0.1
0.03
0.7
4 ( 4) b
>28b
>28
Scintillation solution purged with nitrogen and recounted. Distilled sample. Desiccant loading 5% w/v; initial water content
100 ppm (0.01% w/w).
Table 11. Effect of Stirring on the Drying Efficiencies of
Desiccants for Benzeneb
Residual solvent water content, ppm
- - .
-- 6h 1 day ~~
Desiccant Static Stirred Static Stirred
CaC12 12 0.8 0.1 1
LiAlH4 3 0.7 1.6 0.3 (0.02)"
a Purged with nitrogen and reassayed. Desiccant loading 5%
w/v; initial water content 100 ppm (0.01% w/w).
Calcium and lithium aluminum hydrides are both effective
desiccants. The values for the complex metal hydride are
apparently high through contamination of the solvent with
labeled hydrogen resulting from interaction of the hydride
with the labeled water. This was confirmed by recounting the
sample after purging with nitrogen whereupon the apparent
water content was reduced dramatically from 2 to 0.03 ppm.
Interestingly, purging had little or no effect on samples dried
with calcium hydride and sodium, and this parallels a quali-
tative observation that lithium aluminum hydride, perhaps
because of its finely divided form, appears to bind the hy-
drogen, viz., gas bubbles can still be released from the desic-
cant long after the solvent is essentially dry.
Sodium is observed to reduce the water content extensively
within the first 6 h, but subsequently the apparent water
content is seen to increase significantly. Since purging with
nitrogen and distilltition do not reduce the figure it may be
speculated that sodium is actually able to metalate benzene,
necessarily at an extremely low rate. Tritiation could then
occur by reaction of organosodium intermediates with trace
amounts of newly formed tritiated water, whose genesis would
be identical with that proposed above.
Phosphorus pentoxide appears to be an ineffective drying
agent. However, this conclusion must be tempered by the
significant increase in apparent water content with time of
drying. An increase of such magnitude can only reasonably
be explained by the presence of exchange reactions. Indeed,
phosphoric acid catalyzed exchange reactions have been used
elsewherell for the synthesis of tritiated aromatic compounds.
The presence of exchange reactions thus unfortunately pre-
cludes any conclusion as to the efficiency of phosphorus
pentoxide as a desiccant for benzene.
Calcium chloride is seen to be an effective drying agent,
quite capable of giving super-dry benzene. In contrast, sodium
sulfate is completely inept, and the samples obtained after
drying were too active for direct counting, indicating little or
no drying.
Effect of Stirring. The effect of stirring on rapidity of
drying was investigated for calcium chloride and lithium
aluminum hydride (Table 11). In both cases stirring has an
\ 3
4 8 I 2 16 2 0
Durotion d drying ( hr )
Figure 1. Drying of dioxane with various desiccants. Experimental
conditions as for Table 111. 1, MgS04; 2, KOH pellets; 3, P205; 4,
CaC12; 5,4 8, molecular sieves; 6, CaH2.
accelerating effect on drying. This is most likely due to
breakdown of particle size which increases the effective des-
iccant surface rather than diffusion control of the drying
process, since finely divided silica gel is a very rapid desiccant
even under static drying conditions (Table I).
Drying by Distillation. Fractionation of benzene with
retention of the middle fraction, a time-honored process, has
frequently been advocated as a method of drying. In this work
it was found that the middle fraction, after discarding the first
20%, contained 15 ppm of water. This is significantly drier
than the initial water content, but the drying pales in com-
parison with static drying by the majority of desiccants (Table
I).
Drying of Dioxane. Static Drying. Dioxane, although not
a very polar solvent ( p =0.45), is completely miscible with
water and is consequently far more difficult to dry than ben-
zene. Drying is frequently tackled in at least two stages. Pre-
liminary drying agent@ include potassium hydroxide, calcium
chloride, sodium hydroxide, and magnesium sulfate, whereas
final drying8 has been accomplished almost exclusively with
sodium and occasionally with sodium-lead alloy.
In this study dioxane with an initial water content of 2300
ppm (0.23% w/w)12 was dried with a selection of both pre-
liminary and final drying agents. The initial rate of drying for
a selection of desiccants is displayed in Figure 1. I t is imme-
diately apparent that magnesium sulfate is almost completely
ineffective as a drying agent, whereas calcium hydride is both
rapid and efficient. It is also interesting that, for the first 24
h at least, the speed of drying parallels desiccant efficiency.
Remarkably, phosphorus pentoxide does not excel as a drying
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3062 J. Org. Chem,., Vol. 42, No. 18, 1977 Burfield, Lee, and Smithers
Table 111. Efficiency of Various Desiccants for Static Drying of DioxaneC
Residual solvent water content, ppm
Registry no. Desiccant 6h 1 day 7 days
Na
Na-K alloy
CaH2
4 A molecular sieve
CaC12
p205
LiAlH4
KOH (pellets)
Silica gel
A1203
1118-18-9 Cas04
Na2S04
1481-88-9 MgS04
1310-58-3 KOH (ground)
132 (22)
50
200
204
450
1050
1200
1300
1300
20
22 ( 1 l ) O
30
40
150
300
400
900
1100
1300
1700
1600
1900
2200
6
22 (6)b
23
26
14 (8Ib
300
60
1100 (340)b
200
1200
1400
1500
1800
2200
a After purging to remove H2. b After distillation fromdesiccant. Desiccant loading 5% w/v; initial water content 2300 ppm (0.23%
w/w).
agent, being surpassed in both speed and efficiency by even
calcium chloride.
Results for a wider range of desiccants and drying times are
summarized in Table 111. Sodium, sodium-potassium alloy
(containing 80% by weight of potassium), calcium hydride, and
molecular sieves are all seen to be very effective drying agents,
although at these initial water loadings none of them dry di-
oxane to super-dry levels, which, however, could undoubtedly
be achieved by repetitive drying. Sodium-potassium alloy,
typically described as possessing a higher drying intensity
than metallic s0dium,3~has been advocated as a siccative in
situations where extrcbme desiccation is required,13 where its
principal advantage over sodium, i.e., its liquid state at am-
bient temperatures, should expedite very efficient drying of
solvents boiling below the melting point of the alkali metal.
I t is somewhat remarkable therefore that the alloy is not su-
perior to sodium granules under static drying conditions.
Powdering of KOH pellets is seen to have a dramatic effect
on the rapidity and efficiency of drying, and supports a pre-
vious report3c that drying of diethyl ether and THF solely by
treatment with powdered KOH gives material which is im-
mediately suitable for the preparation of reactive organo-
metallics. I t is striking that powdered KOH, although slightly
slower in action, actually surpasses calcium hydride and mo-
lecular sieves in ultimate efficiency.
LiAlH4, though described as highly effective for drying
ethers,3h actually appears strangely ineffective. The very high
residual water contents cannot be explained in terms of la-
beled hydrogen contamination, and it is difficult to invoke any
other interferences. A probable conclusion is that unlike CaH2,
LiAlH4 is not effective under conditions of high initial water
content, and this result, must cast some doubt on its unqual-
ified recommendation as a desiccant for THF.I 4
The almost complete ineffectiveness of alumina and silica
gel for dioxane drying is a complete reversal of their behavior
with benzene. This underscores the risks involved in extrap-
olating the results of gas drying to the liquid phase.
Magnesium and sodium sulfates are again4 found to beslow
and ineffective at these water concentrations. Sodium sulfate,
in particular, has earlier4 been shown to be an almost com-
pletely inept desiccant for ethers at much higher water con-
centration, viz., the water content of diethyl ether was reduced
from 2.07% w/w to merely 1.83% w/w after a period of several
weeks. The value of sodium sulfate, even as a preliminary
drying agent, must therefore be questionable. In view of its
unanimous recommendation, calcium sulfate also rates sur-
prisingly poorly.
Effect of Stirring and Refluxing on Drying. Since sol-
Table IV. Effect of Conditions on the Drying of Dioxane
Residual solvent water content,
Drying time, ppm
Desiccant h Static Refluxed Stirred
CaH2 2 200 110
6 50 29
24 30 14 4
168 23 2
Na 24 20 5
48 3
0 Desiccant loading 5% w/v; initial water content 2300 ppm
(0.23% w/w).
Table V. The Use of Visual Indicators in Dioxane Drying
Residual solvent
water content
Desiccant- after distillation,
indicator PPm
Sodium-benzophenone 20
BuLi b-triphenylmethane 22
BuLi-phenanthroline 17
Trityl fluoroborate 650 (800)O
2300 ppm (0.23% w/w). b Registry no., 109-72-8.
As determined by the near IR method. Initial water content
Registry no.,
341-02-6.
vents are frequently dried by refluxing over desiccants such
as sodium and calcium hydride, the effect of refluxing was
briefly investigated. I t can be seen (Table IV) that while re-
fluxing dioxane over CaHz results in moderate increases in
efficiency and speed of drying, stirring is seen to bemuch more
effective.
Refluxing over sodium (Table IV) is seen to give an im-
provement in efficiency compared to static drying but pro-
longed refluxing is not particularly beneficial.15 I t is worthy
of note that stirring over calcium hydride at ambient tem-
peratures is as effective as refluxing over molten sodium.
Drying Agents wi th Visual I ndication. Although desic-
cation prescriptions which include a visual indication of sol-
vent dryness have become fairly common in recent years, no
quantitative measure of their efficiency appears to have been
made. These methods generally involve the in situ generation
of small amounts of colored, highly moisture-sensitive inter-
mediates, often by the action of the desiccant on an added
indicator, and the solvent presumed anhydrous when the
indicator color persists. Table V, which displays a selection
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Desiccant Efficiency in Solvent Drying J. Org. Chem., Vol. 42, No. 18, 1977 3063
Table VI. Efficiency of Various Desiccants for Static Drying of Acetonitrile
Residual solvent water content, ppm
Registry no. Desiccant 1 day 7 days
1303-86-2
584-08-7
pzo5
3 A molecular sieves
Bz03
K COS
4 X molecular sieves
CaC12
Silica gel
A1203
CaH2
KOH (powdered)
KOH (pellets)
Cas04
Ph3C+-BF4
9 (12)Q.b
49
59
250
450
1200
1300
1600
1900
2200sb2d
2500
2500
2700 (2800)7c
5
27
1300
500
2200
1300
1700
1900 (1300),c
1300
2200
Distilled sample. Colored residue. By near IR method. Strong amine smell in distillate. e Desiccant loading 5% w/v; initial
water content 2800 ppm (0.28% w/w).
of those investigated for dioxane, reveals that although none
of them give super-dry solvent (see, however, discussion
below), the first three entries give comparable results to the
best of those obtained for dioxane after static drying for 1 day
(Table 111). The intense blue sodium ketyl of benzophenone
(entry l ), often used in the preparation of absolute diethyl
ether,6 where it presumably also serves to remove peroxides,
gives similar results to butyllithium. The appearance of the
red triphenylmethyl anion (entry 2) has been advocated as an
indicator in the preparation of anhydrous THF.17 We have
found that if no special precautions, e.g., anaerobic conditions,
are utilized, then the amount of butyllithium required to
impart a persistent color to the solvent is excessively high,
owing perhaps to corisumption of the indicator by molecules
other than water, e.g., oxygen. This shortcoming led to an
experiment with 1, LO-phenanthroline (entry 3), previously
suggested as an indicator in the alcohol method of assaying
BuLi.l8 The formation of the derived rust-red complex re-
quired only about half the butyllithium used in entry 2, and
since the result was a slightly drier solvent, the use of this in-
dicator is to be preferred. In the general context of the bu-
tyllithium experimeats, i t must also be pointed out that i t is
known that alkyllithiums react relatively slowly with THF,lg
to give, initially, 2-lithiotetrahydrofuran, which, if the anal-
ogous reaction were to occur with dioxane, may serve to label
the ether, and hence raise the apparent water content, by
reaction of metalated dioxane with tritiated water. While this
reaction has not been reported for dioxane, and in any case
would be expected to be extremely slow compared to reaction
of the alkyllithium with water, some inflation of the apparent
water content by this means cannot be altogether ruled out.
Although trityl fluoroborate (entry 4) has not been previously
used as a desiccant for ethers, it has been used to dry aceto-
nitrile (vide infra), amdthis experiment was run to determine
its efficiency in a different solvent type. Even though, at this
solvent water concentration, the deep yellow color of the salt
solution was not discharged, the recovered ether contained
a surprisingly large amount of residual water, and this result
was cross-checked by the near IR method. Compared to
entries 1 to 3, trityl fluoroborate gives poor ultimate drying,
which however, is still better than that obtainable with lithium
aluminum hydride (Table 111).
Drying of Acetonitrile. Static Drying. Acetonitrile, a
polar aprotic solvent ( f i =3.44) of high solvating power and
favorable physical ]properties, has been widely used as a sol-
vent both in the study of chemical reactions and for physical
measurements involving spectrophotometric and electro-
chemical techniques. However, because of its high affinity for
water it is an outstandingly difficult solvent to completely dry.
Drying is conventionally accomplished8 by treatment with
preliminary drying agents such as anhydrous sodium or po-
tassium carbonate, anhydrous calcium chloride, silica gel, or
3 A molecular sieves, and final drying with calcium hydride,
phosphorus pentoxide, or more recently with trityl fluo-
roborate.20
The results of static drying with a range of desiccants are
displayed in Table VI. In contradistinction to the other sol-
vents investigated phosphorus pentoxide is seen to excel in
its drying efficiency, but even so super-dry acetonitrile is not
obtained. I t is interesting to note that the residual water
content is of similar order of magnitude to an earlier result
which also utilized P Z O ~. ~~ The only disadvantage to phos-
phorus pentoxide drying is the partial loss of solvent through
polymerization, and possible contamination by desiccant
residues.22 Reasonably effective drying can also be achieved
with 3 8, molecular sieves which reduce the water content to
less than 30 ppm after 1 week. The relative inefficiency of 4
8, sieves emphasizes the need for careful selection of sieve pore
size for effective drying. A hitherto little mentioned3f but
useful desiccant is boric anhydride. Direct sampling proved
impossible in this case since soluble desiccant residues in-
terfered visually with the scintillant, but the sample distilled
after 1 day stirring with the anhydride had a water content of
59 ppm. This reagent is advantageous compared to phos-
phorus pentoxide since it does not induce polymerization of
the solvent nor does it appear to be significantly volatile. It
also offers advantages in its ease of handling and disposal.
Silica gel and alumina are again, as with dioxane, largely
ineffective. This may reflect their rather low capacity for ef-
fective drying at high water ~ontents,~g but in any case makes
them an unlikely choice for preliminary drying. Calcium sul-
fate, although generally strongly recommended for efficient
drying, is seen to be the least effective of the examined des-
iccants, and is clearly surpassed by the underrated calcium
chloride.23
The ineffectiveness of the previously excellent desiccants
potassium hydroxide and calcium hydride seems anomalous.
Careful examination of the results reveals that all the basic
siccatives, potassium hydroxide, calcium hydride, and po-
tassium carbonate, give apparently little drying. In addition
the apparent water content in the presence of the weakly basic
potassium carbonate increases very significantly from 251 to
1300 ppm over the course of 1 week. These observations ap-
pear indicative of a base-catalysed exchange reaction, viz.
-OH
CH3CN +T20 CHzTCN +HOT
Such base-catalyzed exchange reactions of the 1y hydrogens
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3064 J. Org. Chem., Vol. 42, No. 18, 1977 Burfield, Lee, and Smithers
have been previous1.y encountered with b-hydroxypropioni-
trile24 but rather surprisingly it has been claimed25 that ace-
tonitrile itself does not exhibit similar behavior. In an attempt
to confirm the presence of exchange reactions, the tracer ex-
periment was cross-checked by the near IR method for the
calcium hydride case. The near IR value of the water content
is significantly lower, and this is suggestive of the presence of
exchange reactions. Most unexpectedly, this determination
also revealed that calcium hydride is largely ineffective for
drying acetonitrile. 'This remarkable observation, together
with the resuits for phosphorus pentoxide drying, undermines
the intuitive assumption that the relative efficiencies of des-
iccants should, barring chemical incompatibility, be inde-
pendent of solvent type.
The interference, by exchange reactions, unfortunately
makes it impossible to draw many conclusions on the effi-
ciency of the basic desiccants save that potassium carbonate
is clearly a reasonable desiccant, at least for preliminary
drying.
I t is worthy of mention that drying with finely powdered
potassium hydroxide gave rise to a colored residue and a sig-
nificant amine content in the distilled fractionsz6
Tri tyl Fluoroborate. The use of this stable, orange car-
benium ion salt as a desiccant for acetonitrile would seem to
be advantageous; it can be stored in a desiccator for extended
periods without deco~nposi ti on,~~ and is used as a siccativez0
simply by adding it in small batches to the wet nitrile until a
strong yellow color persists, thus furnishing a visual indication
of dryness. The results obtained by using this and the IR
method are displayed in Table VI, and indicate that, at these
water concentrations, the carbocation salt is a spectacularly
ineffective desiccant. The reason for this impotence seems
obscure, although acetonitrile, by virtue of its solvation ability,
has a well-known moderating influence on the stability of
carbenium ions,28 and indeed, the drying of dioxane by trityl
fluoroborate (vide supra) is significantly better than the
present solvent. Whatever the true reason, it is clear that, as
a desiccant for acetonitrile, the salt is completely worthless.
Meri ts of the Study. The present study should be of con-
siderable heuristic value, particularly to the bench chemist
in the provision of directly relevant data, and it is also
worthwhile briefly emphasising again' that for reasons which
include (1) contamination of the solvent by desiccant residues
and possibly labeled hydrogen, (2) exchange reactions, and
(3) the kinetic isotope effect, the apparent water contents, as
reported above, will always represent the upper limits of the
true content. Of course, this in no way detracts from the value
of the work, and, to cite an example, merely means that it is
entirely possible that alumina is able to dry benzene to below
6 X lo--" ppm!
Experimental Section
Radioactive samples were assayed in a scintillation solution con-
taining 0.4 g of 1,4-bis(5-phenyloxazol-2-yl)benzene (POPOP) and
4.0 g of 2,5-diphenyloxazole (PPO) per liter of toluene with a Beckman
Model IJS-lOO liquid scintillation spectrometer. Determination of
water content by the near IR method was performed using a Unicam
SP700 spectroph~tometer.~~ Tritium-labeled water was purchased
from the Radiochemical Centre, Amersham, England, at an initial
activity of 5 Ci/mL and was diluted with appropriate quantities of
inactive water.
Desiccants. Lithium aluminum hydride and phosphorus pentoxide
were used as supplied; calcium hydride (99.5%) and reagent grade
potassiumhydroxide were rapidly powdered immediately prior to use
in a mortar and a mechanical blender, respectively. Chromatographic
grades of neutral alumina (activity 1) and silica gel, as well as calcium,
magnesium, and sodium sulfates, calcium chloride, potassium car-
bonate, and 3 and 4 8, molecular sieves were activated for 15 h at
300-320 OC before use. Since hydration occurs rapidly on cooling of
these desiccants in moist air, cooling was carried out in a phosphorus
pentoxide desiccator, and the samples then used immediately. Sodium
metal, whose oxide crust had previously been removed by melting
under xylene, was cut into 2-mm cubes under dry petroleum ether.
Sodium-potassium alloy was prepared as detailed elsewhere308 from
oxide-free metals. (It is worth noting that the fire hazard associated
with destroying excess alloy is completely avoided if the disposal is
carried out in two steps. Addition of a little dry ethyl acetate to the
alloy in dioxane smoothly consumes potassium-presumably via an
acyloin reaction. Unreacted sodium can then be destroyed conven-
tionally using ethanol.) Trityl fluoroborateZ7 and boric anhydride3f
were respectively prepared from triphenylcarbinol and tetrafluo-
roboric acid, and by high-temperature (900 "C) dehydration of boric
acid.
Solvents. Benzene. AR grade reagent was stirred for 24 h with
finely ground calcium hydride, refluxed, carefully fractionated (bp
80.0 "C), and stored over 4 8, molecular sieves.
1,4-Dioxane. Commercial 1,4-dioxane was purified and dried ac-
cording to a method cited by F i e~er , ~* ~ whereby the glycol acetal
impurity is removed by hydrolysis to acetaldehyde, which is itself
voided by purging with nitrogen gas. Preliminary drying with potas-
sium hydroxide pellets followed by fractionation (bp 101-101.5 "C)
from sodium gave material which was stored in a dark bottle over 4
A molecular sieves.
Acetonitrile. Following well-documented procedures: reagent
grade material, after being given a preliminary drying with potassium
carbonate (24 h), was decanted on to phosphorus pentoxide and
stirred at reflux for 2 h. Fractionation gave material of bp 81.5 "C,
which was not stored, but used immediately.
Techniques. The procedure used for benzene serves as an example.
A stock solution of benzene containing 100ppm of labeled water was
prepared by the addition of 18 WL of tritiated water, specific activity
40 mCi/mL, to 180 g of purified benzene; homogenization was ac-
complished by stirring overnight. Aliquots of the stock solution (15.0
f 0.1 mL) were syringed directly onto 0.75 f 0.03 g of activated des-
iccant contained in a 25-mL clear-fit round-bottom flask, which was
then stoppered. Where appropriate samples were stirred magnetically.
Samples (1.00 f 0.02 mL) were taken at time intervals specified in
the text-care was taken to avoid disturbing the desiccant-and
syringed directly into the counting vials. Where possible, samples were
distilled from the desiccant so as to provide a cross-check against
contamination of the solvent by labeled desiccant residues. Samples
were accumulated and assayed batchwise.
Similar procedures were used with dioxane and acetonitrile, except
that higher water contents were examined and tritiated water of low
specific activity (0.5 mCi/mL) was employed.
Registry No.-Benzene, 71-43-2; dioxane, 123-91-1; acetonitrile,
75-05-8.
References and Notes
Abstracted in part fromtheHonours Project Work of K. H. Lee, 1975-
1976.
F. Daniels, R. A. Alberty, J . W. Williams, C. D. Cornwell, P. Bender, and
J . E. Harriman. "Experimental Physical Chemistry" 7th ed, McGraw-Hill,
New York, N.Y., 1970, p 641.
(a) T. L. Jacobs, W. E. Truce, andG. R. Robertson, "Laboratory Practice
of Organic Chemistry", Macmillan, New York, N.Y., 1974; (b) R. M. Roberts,
J . C. Gilbert, L. B. Rodewald, and A. S. Wingrove. "An Introduction to
Modern Experimental Organic Chemistry", 2nd ed, Holt, Rinehart and
Winston, NewYork, N.Y., 1974; (c) L. Brandsma, "PreparativeAcetylenic
Chemistry", Elsevier, Amsterdam, 1971; (d) R. S. Monson, "Advanced
Organic Synthesis", Academic Press, NewY wk, N.Y., 1971; (e)L. F. Fieser
andM. Fieser, "Reagents for Organic Synthesis", Wiley, New York, N.Y.,
1967; (f) A. I . Vogei, "A Text-Book of Practical Organic Chemistry", 3rd
ed, Longmans, London, 1964; (g) P. H. Plesch, Ed., "TheChemistry of
Cationic Polymerisation", Pergamon Press, Oxford, 1963, p 682 f f ; (h)
"Dryingin theLaboratory", E. Merck, Darmstadt.
B. D. Pearson, and J . E. Ollerenshaw, Chem. Ind., (London), 370 (1966).
(a) G. Brauer, Ed.. "Handbook of Preparativeinorganic Chemistry", Vol.
I , 2nd ed, translated by ScriptaTechnicaInc., Academic Press, NewYork.
N.Y., 1963, p 80; (b) "Handbook of Chemistry and Physics", 53rded,
Chemical Rubber PublishingCo., Cleveland, Ohio, 1972, p E35.
(a) F. Trusell and H. Diehl. Anal. Chem., 35, 674 (1963); (b) J . H. Bower,
J. Res. Natl. Bur. Stand., 12, 241 (1934).
D. R. Burfield, Anal. Chem., 48, 2285 (1976).
See references contained in J . A. Riddlck andW. B. Bunger, "Organic
Solvents", 3rd ed, Wiley-lnterscience, NewYork, N.Y ., 1970.
The term superdry has been used earlier in a qualitativesense,3f but in
this context it denotes solvents containing less than 1 ppm of water.
T. H. Bates, J . V. F. Best, and T. F. Williams, Nature (London). 88, 469
(1960).
See E. A. Evans, "Tritium and ItsCompounds", 2nd ed. Butterworths,
London, 1974.
This isclose to themaximumwater content specified for AR gradediox-
ane.
For example, after standing for 5 days over the alloy, bothdiethyl- anddi-
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Perhydrogenation of 2,8-Diaminopurine J. Org. Chem., Vol. 42, No. 18,1977 3065
methylamineare dehydrated sufficiently that spincoupling of theadjacent
N-H andC-H protons is observable in their NMR spectra: K. L. Henold,
Chem. Commun., 1340 (1970).
(14) H. Baumgarten, Ed., "Organic Syntheses", Collect. Vol. V, Wiley, NewYork.
N.Y., 1973, p 976.
(15) Ina peculiar sense, this result confirms anearlier statement that "Oneday
drying over calciumhydrideisfoundto beas effective as six months re-
fluxing over sodium". See A. S. Brown, J. Chem. Phys.. 19, 1226
(1951).
(16) See, for example, G. Kobrich. W. E. Breckhoff, H. Heinemann. and A .
Akhtar, J. Organornet. Chem., 3, 492 (1965).
(17) W. R. Purdum andG. .I. Bartling, J. Chem. Educ., 52, 120 (1974).
(18) S. C. WatsonandJ . F Estham, J. Organomet. Chem.. g, 165 (1967).
(19) (a) I. FlemingandT. Mah, J. Chem. Soc., Perkin Trans. 7, 964 (1975); (b)
R. B. Bates, L. M. Kroposki, and D. E. Potter, J. Org. Chem., 37, 560
(1972).
(20) Y. Pocker andW. H. VVong,J. Am. Chem. Soc., 97,7097 (1975).
(21) J . F. Coetzee and G. R. Padmanabhan, J. Phys. Chem.. 66, 1708
(1962).
(22) Subsequent distillation frompotassiumcarbonate has been recommended
for removal of phosphorus pentoxideresidues. See P. WaldenandE. J .
Birr, Z. Phys. Chem. (Lei pzi g), 144A, 269 (1929).
(23) Dryingover calciumchloridefor "at least a week" has been advocated
as a methodfor obtaining "thoroughly dry" acetonitrile. A. H. Blatt. Ed.,
"Organic Syntheses", Collect. Voi. i , 2nd ed, Wiley, NewYwk. N.Y., 1946,
pp 5-6.
(24) A. Lapidot. J . Reuben, andD. Samuel, J. Chem. Educ., 41, 570 (1964).
(25) See ref 11, p 759.
(26) Theseobservations appear to support theearlier contention that "pre-
treatment with potassiumhydroxidedoes moreharmthangood". See J .
F. Coetzee, PureAppl. Chem., 13, 429 (1966).
127) H. J . DaubenJ r., L. R. Honnen, andK. M. Harmon, J. Org. Chem., 25, 1442
(1960).
Wiley, NewYork, N.Y., 1968, p 140.
(28) N. Lichtinin "CarboniumIons". Vol. I , G. A. OlahandP. v. R. Schleyer, Ed.,
(29) R. L. Meeker, F. Critchfield, and E. T. Bishop, Anal. Chem., 34, 1510
(1962).
(30) (a) See ref 3e, p 1102. (b) See ref 3e, p 333.
Perhydrogenation of 2,8-Diaminopurine
Mark M. Wegner and Henry Rapoport*
Department of Chemistry, University of California, Berkely, California 94720
Received March 7, 1977
2,8-Diaminopurine (7) can be hydrogenated over Pt02 in acidic medium to give 2-imino-4-guanidinomethyl-5-
imidazolidinone (1 1) which can itself be further hydrogenated to 2-imino-4-guanidinomethylimidazolidine (12).
The structures of 11 and 12 were proven by unambiguous synthesis. 2,8-Diamino-6-methylpurine (37) also can be
hydrogenated in a similar manner to two analogous compounds, as isomeric mixtures, whose structures are inferred
by comparison with 11 and 12. A superior method has been developed for synthesizing the diaminopurines 7 and
37, involving the condensation of the appropriate triaminopyrimidine with N-(methylmercaptochloromethy1)-p -
toluenesulfonimide (20) followed by ring closure via the carbodiimide and detosylation with HF.
Saxitoxin is one of the most potent naturally occurring
neurotoxins. I t is the sole toxin produced by the marine di-
noflagellate Gonyauiax catenella and is a minor constituent
of the toxins produced by G. tamarensis. Ingestion of these
dinoflagellates by several species of normally edible shellfish
is frequently responsible for their toxicity to man. X-ray
crystallographic analysis of two derivatives, the bis-p-bro-
mobenzenesulfonate3 and the ethyl hemiketal dihydrochlo-
ride,4 have established structure 1 for crystalline saxitoxin
hydrate, and 13C NMR studies have also established this
structure for the molecule in s~l uti on.~ Recently5 the major
toxins of G. tamarensis, gonyautoxins I1 and 111, also existing
as the hydrates, were postulated to have the closely related
structures 2 and 3, respectively.
Saxitoxin and the gonyautoxins are unique among natural
products in that their structures incorporate a tetrahydro-
purine moiety composed of two guanidine units fused together
in an azaketal linkage which remains intact under ordinary
conditions. We were therefore interested in preparing a simple
model of the tetrahydropurine backbone of saxitoxin, devoid
of the fused ketone bearing ring and the peripheral carbamate,
for both chemical and biological investigations. We chose to
study the catalytic hydrogenation of 2,8-diaminopurine (7),
which conceivably could lead to 2,8-diiminotetrahydropurine
(10) or its tautomers, the simplest possible tetrahydropurine
model of saxitoxin. We now report the results of our study of
the heterogeneous catalytic hydrogenation of 2,8-diamino-
purines.
The literature relating to the catalytic reduction of purines
is relatively meager. 1,6-Dihydropurine ( 5) has been pre-
pared"' from purine and 6-chloropurine (4), and in weak acid
5 was hydrolyzed to 4(5)-aminomethyl-5(4)-aminoimidazole
(6). Similarly a tetrahydropurine is claimed8 to result from
catalytic reduction of 2,6,8-trichloropurine. More recently?
the catalytic reduction of 2&diaminopurine (7) is reported
to yield a compound whose structure was assigned as 2-
amino-5-guanidino-l,4,5,6-tetrahydro-6-oxopyrimidine (8).
These authors also report the preparation of 2,8-diamino-
4,5,6,9-tetrahydro-l,7,9-trimethylpurine by sodium borohy-
dride reduction of 2,8-diamino-1,7,9-trimethylpurine, and
claim to have electrolytically reduced 7 to 8 plus tetrahydro-
purine 10, obtained as an inseparable mixture with another
reduction product 9.
In contrast to that report, wehave found that 7 is slowly
hydrogenated with a Pt02 catalyst in hydrochloric acid (pH
1.5) at room temperature and 20 psi pressure to give a single
product, A, in quantitative yield. A could be further reduced
under more drastic conditions (60 "C, 100 h) to give another
product, B, also in quantitative yield. The l H NMR spectrum
of A.2HC1 consisted of a doublet (2 H, J =5 Hz) and a triplet
(1 H, J =5 Hz); its 13C NMR spectrum is tabulated in Table
I.
These NMR data suggested that A was not a reduced purine
with an intact bicyclic ring system but rather the five-mem-
bered monocyclic imidazolidinone 11, The 13C NMR ab-
sorption at 6 173 is clearly assigned to the amide carbonyl, and
the simple doublet-triplet pattern of the l H NMR spectrum
implies the freely rotating methylene group of 11. The alter-
native six-membered ring structure 8 previously proposedg
for the 2,8-diaminopurine reduction product should display
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J. Org. Chem. 1982,47, 3821-3824 3821
under Nz for 3.5 h in an oil bath maintained at 100 "C. The
reaction mixture was poured onto an excess of ice, and after the
ice had melted HzO was added to bring the total volume to 1500
mL. The solution was extracted with CHzClz (5 X 100 mL), and
the combined organic layers were extracted with saturated
NaHC03 untiI the extracts werecolorless. The combined NaHC03
extracts were back-washed with CHzC12 (100 mL) and then
acidified to pH 1 with 12 M HCl. The product was extracted into
CHzClz (5 X 100 mL), the organic layer was dried (Na2SO4) and
filtered, and solvent was removed on a rotary evaporator followed
by a vacuum pump to yield 6.3 g of 3-hydroxy-5-methylbenzo-
cyclobutenedione in 63% overall yield from dienophile 5: light
yellow crys&, mp 191-193 OC (EtOAc); IR (CHzC12) 3540,1789,
1755; 'H NMR (60 MHz, acetone-ds) 6 7.29 (s, 1 H), 6.95 ( 8, 1 H),
2.46 (s,3 H). Anal. Calcd for CBH603: C, 66.66; H, 3.73. Found
C, 66.56; H, 3.90.
Cycloaddition of l-Methoxy-3-(trimethylsiloxy)-1,3-bu-
tadiene (13) to 1,4-Dichloro-3,3,4-trifluorocyclobutene (5).
(A) Preparation of Enone 15. 1,4-Dichloro-3,3,4-trifluoro-
cyclobutene (5; 3.08 g, 17.4 mmol) and Danishefsky's diene (13;
4.50 g, 26.1 mmol) were placed in a 3-02 Fischer-Porter pressure
vessel equipped with a magnetic stirring bar, and the mixture was
saturated with dry Nz for 5 min. The tube was sealed, placed
in an oil bath maintained at 120 "C, and stirred for 3.5 h. After
cooling to 25 OC, the tube was opened, and the contents were
transferred to a 100-mL round-bottomed flask with the aid of a
small amount of MeOH. To this mixture was added 100 mL of
1:l MeOH/1.2 N HC1, and the solution was stirred at room
temperature for 2 h. The dark solution was poured into a sep-
aratory funnel, diluted with 200 mL of HzO, and extracted with
CHzClZ (3 X 75 mL), and the combined organic layers were dried
(Na804), filtered, and condensed on a rotary evaporator to yield
3.11 g of crude 14 as a dark oil. The compound is contaminated
with diene decomposition products as well as some enone 15, but
the following spectroscopic absorptions of 14 are apparent: IR
-1 H), 3.30 ( 8, -3 H), 2.6-2.7 (m, -4 H). Without purification,
crude 14 (3.11 g) was placed in a 250-mL round-bottomed flask
and dissoved in dry benzene (175 mL). After addition of p -
toluenesulfonic acid (166 mg, 0.87 mmol), the mixture was refluxed
under Nz for 27 h, cooled to room temperature, transferred to a
separatory funnel, washed with saturated NaHC03 (2 x 25 mL),
dried (Na2SO4), filtered, and condensed on a rotary evaporator,
and the residue was chromatographed on silica gel (3 cmx 0.75
m; 3 2 hexane/CHzC12) to yield enone 15: 2.25 g (53% yield from
dienophile 5); white needles; mp 44-45 OC (sublimed); IR (CHzCIJ
1695; 'H NMR (60 MHz, CDC1,) 6 6.63 (d, J =10 Hz, 1 H with
smaller splittings), 6.15 (d, J =10 Hz, 1 H with smaller splittings),
3.90-3.13 (m, 1 H), 2.71 (apparent d, J =4 Hz, 2 H); mass
spectrum, m/ e (relative intensity) 244 (M'), 246 (M' +2, 66).
(CH2ClZ) 1720; 'H NMR (60 MHz, CDC13) 6 4.72 (t, J =5 Hz,
(B) Aromatization of Enone 15 to 2,2-Difluoro-4-
hydroxybenzocyclobutenone (16). A solution of enone 15 (2.25
g, 9.2 mmol) in 60 mL of MeOH was cooled to 0 "C in a 250-mL
round-bottomed flask and the solution was saturated with dry
N2 for 5 min. The flask was fitted with a pressure equalizing
addition funnel and a nitrogen inlet tube and the addition funnel
was charged with a solution freshly prepared from sodium (0.846
g, 36.8 mmol) and MeOH (30 mL). The NaOMeIMeOH solution
was added dropwise with stirring over 30 min, and after the
addition was complete, the reaction mixture was allowed to warm
to room temperature and stirred an additional 3 h. An equal
volume of 1.2 N HCl(90 mL) was added, and the mixture was
refluxed for 3 h to hydrolyze the intermediate ketal. After cooling
to roomtemperature, the reaction mixture was diluted with 200
mL of HzO and the product extracted into CHZClz (3 x 75 mL).
The combined CHzClz layers were dried (Na2S04), filtered, and
evaporated to dryness on a rotary evaporator followed by a vacuum
pump to give 16: 1.5 g (96%); white crystals; mp 163-164 "C
(EtOAcIhexane); IR (CHZCl2) 3570, 1795, 1770; 'H NMR (60
MHz, acetone-d6) 6 9.8 (br s, 1 H), 7.70-7.16 (m, 3 H); mass
spectrum, ml e 170 (M').
(C) Hydrolysis of 16 to 4-Hydroxybenzocyclobutenedione
(17). The sample of 16 prepared above (1.50 g, 8.82 mmol) was
placed in a 250-mL round-bottomed flask with 1:l concentrated
Hfi04/HOAc (90 mL) and stirred at 90"C under N2 for 3 h. The
reaction mixture was poured onto an excess of ice and diluted
with HzO to a total volume of 350 mL. The solution was extracted
with Et20 (3 X 100 mL), and the combined organic layers were
dried (NafiO,), filtered, and condensed to a crude solid on a rotary
evaporator. This material was chromatographed on a silica gel
column (3 cm X 1 m; EhO) to yield 4-hydroxybenzocyclo-
butenedione: 1.10 g (84% yield, 43% overall from dienophile 5);
light yellow crystals; mp 174.5-175 "C (EtOAc) (lit.7 mp 167-170
"C); IR (CHC13) 3600-3000 (br), 3575,1808 (sh), 1790,1769,1755
(sh); 'H NMR (60 MHz, CD,CN) 6 7.81 (d, J =8 Hz, 1 H),
7.3G7.06 (m, 2 H), 6.23 (br s, 1 H); mass spectrum, m/ e 148 (M+).
Acknowledgment is made to the National Cancer I n-
stitute, DHEW (Grant No. CA 26374), for support of this
work.
Registry No. 1, 6383-11-5; 3, 3469-06-5; 4, 82431-14-9; 5, 2927-
72-2; 6a, 63383-46-0; 6b, 73912-36-4; 7a (isomer l), 82431-15-0; 7a
(isomer 2), 82468-19-7; 7b (isomer l), 82431-19-4; 7b (isomer 2),
82468-20-0; 8a, 82431-16-1; 8b, 82444-39-1; Qb, 82431-20-7; 108,
82431-17-2; lob, 82431-21-8; lla, 82431-18-3; llb, 82431-22-9; 12a,
82431-25-2; 17, 75833-48-6; anthranilic acid, 118-92-3; 2-carboxy-
benzenediazoniumchloride, 4661-46-5; 1,l-dichloroethylene, 75-35-4;
1,l-dichlorobenzocyclobutene, 68913-13-3; 3-methyl-2-butenal, 107-
86-8; 2-methyl-3-buten-2-01, 115-18-4.
62416-21-1; 12b, 82431-23-0; 13, 59414-23-2; 15, 82431-24-1; 16,
Deperoxidation of Ethers. A Novel Application of Self-Indicating
Molecular Sieves
David R. Burfield
Department of Chemistry, University of Malaya, Kuala Lumpur 22-11, West Malaysia
Received January 18, 1982
The removal of peroxides from contaminated ethers by treatment with self-indicating molecular sieves (IMS)
is proposed as a safe and facile method of ether purification. Quantitative analysis of peroxide content before
and after treatment with IMS show that ethers such as THF, diethyl ether, and diisopropyl ether can be readily
decontaminated by an ambient-temperature or reflux process. The deperoxidation process is enhanced under
nitrogen and has been safely carried out on a bulk scale and with initial peroxide contents as high as 0.5 M. IMS,
in common with most other chemical reducing agents used for ether deperoxidation, are, however, ineffective
for the decomposition of unreactive species such as dialkyl peroxides.
Aliphatic ethers, with their characteristic solvation
abilities, excel as inert reaction media in numerous syn-
thetic procedures. However, in practice this usefulness is
0022-326318211947-3821$01.25/0
often tempered by an unfortunate proclivity to facile air
oxidation at ambient temperatures which leads to peroxide
formation.' The presence of peroxides is not only po-
0 1982 American Chemical Society
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3822 J. Org. Chem., Vol. 47, No. 20, 1982 Burfield
Table I. Deperoxidation of Tetrahydrofuran wi th I ndicating Molecular Sieves (IMS) at Ambient Temperatures
peroxi de content,c mmol /L
sieve
scale, loading,
run mL 5% w/v initial 1 day 2days 3 days 4 days 7 days 90 days
1 50 10 7.8 0.9 0.1 N.D.
2a 50 10 7.8 3.3 0.5 0.26
3 24 00 5 1.1 0.22 0.10 0.06 0.014 d
4 100 5 1.1 0.07 0.007 0.018 0.012 d
5 50 5 22 7.8 5.5
6b 50 5 22 7.1 4.9
7 50 5 124 2.8
8 50 10 176 14
9 7 50 5 88 20 6 3 d
10 100 10 96 4
a Performed under an atmosphere of air. IMS activated at 300 " C i n air oven. As determi ned by the spectrophoto-
metri c method. Not determi ned.
tentially hazardous,l12 but also frequently undesirable for
chemical reasons, and although possible hazards may be
avoided by the routine disposal of time limit expired3 or
proven peroxide contaminated4 ethers, the need for rig-
orously purified solvents as well as economic and logistic'
constraints may frequently necessitate peroxide removal.
To this end a bewildering arrayla of safe (and not so safe!6)
physical and chemical methods have been proposed.
Column chromatographic purification whereby peroxides
are removed by adsorption on substrates such as alumina,1
ion-exchange resins'l or 13X molecular sieved2 have var-
iously been reported, and the use of activated alumina in
particular has been widely endor~ed. ~~J ~ However, such
methods, though effective and generally applicable, are
disadvantaged by the necessity of using substantial
amounts14 of nonregenerable and relatively expensive ad-
(1) See, for example, the brief review by N. V. Steere in 'The Chem-
istry of the Ether Link", S. Patai, Ed., Interscience, London, 1967.
(2) See for example: (a) A. G. Davies, J. R. Znst. Chem., 80,386 (1956);
(b) "Guide for Safety in the Chemical Laboratory", 2nd Ed., Van Nost-
rand-Reinhold, New York, 1972, p 302; (c) 'Safety in Academic Chem-
istry Laboratories", 3rd ed., American Chemical Society, Washingtan, DC,
1979; (d) L. Bretherick, "Handbook of Reactive Chemical Hazards", 2nd
ed., Butterworths, London, 1979.
(3) I t has been proposed6 that unused ethers in opened containers
should be disposed of within 1 week of opening (uninhibited grades) or
3 or 6 months (inhibited grades). ElsewhereZc a blanket time limit of 1
month has been suggested for ethyl or isopropyl ethers. In one labora-
t oeit isstandard practice to use only THF from unopened bottles and
to discard the remainder within 2-3 days.
(4) It has been recommended that diethyl etherJ containing morethan
0.005% peroxide (yellow color with KI test) and THF containing 'larger
than trace amounts of peroxiden6 should be discarded.
(5) N. V. Steere, J. Chem. Educ., 41, A575 (1964).
(6) H. E. Baumgarten, 'Organic Syntheses", Collect. Vol. V, Wiley,
New York, 1973: (a) p 796, (b) p 695.
(7) For laboratories situated outside the main industrial centers,
chemical delivery times exceeding 6 months are not uncommon. As such
ethers from unopened bottles are frequently significantly contaminated
on receipt.
(8) Potassium hydroxide, which in its finely powdered form is a pow-
erful desiccant: has been advocated for peroxide removal. However,
serious explosions may occur when treating impure THF with solid or
concentrated aqueous potassium hydroxide.E Similarly, LiAlH,, a less
efficient p g agent: has proved distinctly hazardous in the purification
of ethers.
(9) D. R. Burfield, K. H. Lee, and R. H. Smithers, J. Org. Chem., 42,
3060 (1977).
(10) W. Dasler and C. D. Bauer, Znd. Eng. Chem. Anal. Ed. , 18, 52
(1946).
(11) R. N. Reinstein, J. Org. Chem., 24, 1172 (1959).
(12) N. Rabjohn, "Organic Syntheses", Collect. Vol. IV, Wiley, New
York, 1963, p 475.
(13) (a) A. I. Vogel, "A Text-Book of Practical Organic Chemistry", 4th
ed., Longmans, London, 1978; (b) "Purification of Solvents by Adsor-
bents Woelm", WoelmPharma, Eschwege, West Germany; (c) "Drying
in the Laboratory", E. Merck, Darmstadt, West Germany; (d) D. D.
Perrin, W. L. F. Armarego, and D. R. Perrin, 'Purification of Laboratory
Chemicals", Pergamon, Oxford, 1980.
sorbents and the need for the subsequent safe disposal of
the contaminated residue upon which the peroxides are
adsorbed chemically unchanged.1
Chemical methods encompass a wide spectrum of
which effect reductive decomposition of per-
oxides. These include classical redox systems such as
sulfites, bisulfites, amines, metal salts (e.g., FeS04, CuCl,
Ce(OH)3, SnC12), traditional reducing couples (e.g., Sn/
HCl, Na/EtOH), and the more recently used complex
metal hydrides (LiAlH,, NaBH,). Treatment with aque-
oud5 ferrous s~l f at e, ~~* ~J ~* , ~J ~ or sodium sulfite/bi-
sulfite'wl6 has received approbation as a safe and effective
method of deperoxidation, but their use is restricted to
water-immiscible ethers,l* and in any case such procedures
necessitate an additional desiccation step. For water-
miscible ethers such as dioxane, diglyme, and THF, reflux
over solid cuprous6b chloride, stannous ~hl ori de,~~",~ or
LiAlH4& has been advocated. The use of these procedures,
however, appears to be distinctly hazardous for heavily
peroxidized ethers, and preliminary small-scale purifica-
tions are normally advisedS6" Interestingly, an earlier
methodlg employing solid cerous hydroxide, which is ap-
parently effective and widely applicable, does not appear
to be generally used probably because of the necessity for
preparation of fresh reagent and the inaptitude of the
methodology for application to bulk purification.
In the context of these various shortcomings, wepropose
the useof indicating molecular sieves (IMS) as an effective,
safe, and readily available reagent which is generally ap-
plicable to the problem of peroxide removal from ethers.
Results and Discussion
Deperoxidation of Tetrahydrofuran (THF). The
deperoxidation of THF was most thoroughly studied since
of the common ethers discussed below this solvent has the
highest proclivity toward peroxide formation.20 Table I
(14) The adsorbent loading required for effective deperoxidation is
dependent on the grade of initial alumina and ether type, as well as on
the initial water and peroxide content. However, for dry THF or dioxane
of moderate peroxide content basic alumina of activity I will only purify
less than an equal weight of ether.13bsc
(15) As opposed to cuprous and stannous chlorides, solid ferrous
sulfate is apparent1 ineffective16 in peroxide removal, and an explosion
has been reported17 on distilling THF from the solid salt. The effec-
tiveness of solid inorganic reagents may perhaps berelated to their sol-
ubilities in ethers since both cuprous and stannous chlorides are appre-
ciably more soluble than the ferrous salt.
(16) A. C. Hamstead, Znd. Eng. Chem., 56 (6), 37 (1964).
(17) J. Schurz and H. Stubchen, Angew. Chem., 68, 182 (1956).
(18) The useof aqueous ferrous sulfate for deperoxidation of THF,'"
is surely impractical as this ether is completely miscible with water.
(19) J . B. Ramsey and F. T. Aldridge, J. Am. Chem. Soc., 77, 2561
(1955).
(20) This conclusion has been drawn from the analysis of some 30
samples of stored ethers of various types and from monitoring the rate
of peroxide formation in purified ether samples exposed to the atmo-
sphere.
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Deperoxidation of Ethers J. Org. Chem., Vol. 47, No. 20,1982 3823
Table 11. Deperoxidation of Various Ethers with IMS
sieve peroxide content,c mmol/L
run (I ether % w/v initial 3 h 1 day 2 days 3 days 7 days 90 days conditionsd
loading,
1 dioxane 10 1. 7 0. 22 0. 44 A
2 10 5. 5 4. 0 0.6 A
R
R
A
R
A
A
A
~
3
4
5
6
7
8
9
10
11
5 10. 3 0. 61
5b 10. 3 0. 44
5 12. 8 0. 24
diethyl ether 5 12. 8 0.05 e
diisopropyl ether l oc 53 0.3
trimethylene glycol 10 29 5.5
10 109 1.1
dimethyl ether
5 27 <0.1
dibenzyl ether 5 37 <0. 15
a Scale =100 mL except as indicated. Scale =1500 mL. Scale =50 mL. As m asured by sp
method; A =ambient temperature, R =at reflux, and H =at ca. 110 "C. e Not determined.
summarizes some representative results for the addition
of IMS to peroxide-contaminated THF obtained from a
variety of sources. In every case addition of IMS leads to
a reduction in the peroxide content which decreases to a
negligible level over extended periods of time (runs 1, 3,
4,9). The efficiency of deperoxidation is enhanced under
nitrogen. (cf. runs 1,2) but is somewhat reduced by in-
creased scale (cf. runs 3, 4).
Activation of the supplied IMS by heat treatment at 300
O C only marginally increases the efficiency of deper-
oxidation (runs 5, 6) . However, deactivation of the IMS,
by exposure to the atmosphere until the blue indicator
decolorizes, renders this material completely impotent for
peroxide removal.21
Deperoxidation of THF under reflux proceeds far more
rapidly than by static deperoxidation at ambient tem-
peratures. Thus peroxide contents as high as 500 mmol/L
were dramatically reduced (95% peroxide removal) within
4 h of refluxing over 5% w/v IMS.
Deperoxidation of Various Ethers. The effects of
ambient temperature and reflux treatment of various
ethers with IMS are summarized in Table 11. Generally
at ambient temperatures peroxide removal from dioxane
is relatively inefficient and considerably slower than for
THF. On the other hand, under these conditions, de-
peroxidation of diethyl ether and diisopropyl ether is facile,
proceeding more readily than with THF.
At reflux temperatures the deperoxidations of the var-
ious ethers are considerably accelerated, the effect being
most noticeable for the higher boiling ethers. It is con-
ceivable that this may in part be due to an uncatalyzed
thermal decomposition. At the same time the effects of
scale become less apparent (cf. runs 3, 4), and 1.5 L of
dioxane is decontaminated as rapidly as 0.1 L. Refluxing
diethyl ether shows little advantage over the comparable
static purification, which in any case is already very effi-
cient.
Nature of Peroxide Removal. Earlier studies12 have
shown that ethers may be deperoxidized by selective ad-
sorption with 13X (10 A) molecular sieves. Purification
of THF with nonindicating sieves of varying pore sizes
(Table 111) confirms the possibility of preferential peroxide
adsorption for 10A and to a lesser extent for 5A sieves.
However, sieves of 4-A pore size, i.e., equivalent in pore
structure to the IMS, are completely ineffective. The
ctrophot
H
H
metric
Table 111. Effect of Sieve Type on THF Deperoxidation
peroxide content,b
mmol/L
30 days run sieve type 15 days
~
1 no added sieve 8.7 14.8
2 4A 7.6 19. 6
3 5A 2.9 3. 1
4 10A 0.14 0. 16
5 4A (with indicator) 0. 26
Scale 50 mL; sieve loading 10% w/v; at ambient tem-
perature under air.
photometric method. The initial content was 7. 8 mmol/
L in all cases.
As determined by the spectro-
Table IV. Dialkyl Peroxide Content of
Deperoxidized Ethers
peroxide content, mmol/L
after treatmentC
total
sample initiala ROOHa peroxideb
THF 124 0. 95 2.4
96 0.60 2.8
diisopropyl ether 109 1. 1 3. 3
diethyl ether -1 0. 2 1.1
17
Analysis
dioxane 52 e
a Analysis by spectrophotometric method.
by acid reflux.
temperature. e Not determined.
Treated with 5% w/v IMS at ambient
effectiveness of IMS for deperoxidation must therefore be
attributed to some alternative mechanism, and it seems
not unreasonable to suppose that peroxides are decom-
posed by interaction with the impregnated indicator, which
is probably a cobalt salt, through redox reactions such as:
ROOH +Co2+ - RO- +-OH +Co3+
The implication of this conclusion is that in contrast to
the residues from normal chromatographic purifications,
the IMS should be peroxide free and thus capable of
hazard-free disposal or reactivation.
Formation, Detection, and Removal of Dialkyl
Peroxides. Most methods employed for testing ether
purity, including the standard acidified KI test,22 and the
(21) IMS are similarly ineffective for the treatment of grossly wet
(>l% w/v water) ether samples, wherein water uptake by the molecular
sieves leads to deactivation. Such samples require either predrying or
addition of higher loadings (>5% w/v) of IMS to prevent saturation and
deactivation of the indicator.
(22) In this test peroxides are deemed present if a faint yellow color
develops on shaking 6 mL of the ether with an equal volume of 2% w/v
KI solution in the presence of a few drops of dilute hydrochloric acid.
(The detection limit of this test in our hands corresponds to a value of
about 0.2 mmol/L as measured by the spectrophotometric method.
(23) R. D. Mair and A. J. Graupner, Anal. Chem. 36, 194 (1964).
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3824 J. Org. Chem., Vol. 47, No. 20, 1982
spectrophotometric method used in this study are inef-
fective for the detection of dialkyl peroxides. The sig-
nificance of this observation is that all the methods re-
ported in the literature to date for the removal of peroxides
have in fact been proven only for hydroperoxides.
For evaluation of the relative importance of dialkyl
peroxide formation, several badly contaminated ether
samples were deperoxidized with IMS and the deconta-
minated ethers analyzed for both active peroxide (hydro-
peroxide) and dialkyl peroxide (Table IV). In every case,
except dioxane, the total peroxide content is very much
reduced by treatment with IMS. However, the acid-reflux
analysis indicates the presence of small but detectable
amounts of dialkyl peroxide in these samples. In the case
of dioxane there is a very large concentration (>30% of
original content) which is not analyzed by the spectro-
photometric method and is not decomposed by IMS during
the period of treatment. It would appear, therefore, that
oxidation of dioxane leads to the formation of much higher
concentrations of dialkyl peroxides than other ethers or
to hydroperoxides which are much less reactive.
In summary, it appears that predominant contaminants
of ethers such as THF and diisopropyl and diethyl ethers
are active peroxides which can be readily removed by
treatment with IMS. Deperoxidation of dioxane is very
much less efficient. Almost certainly, the inapplicability
of IMS to the problem of dialkyl peroxides is also a lim-
itation with other commonly used redox purification sys-
tems such as those based on CuC1, SnC14, FeS04, etc.
Applicability of IMS to Ether Deperoxidation. The
prime criteria for deperoxidation methods are effectiveness
and safety. Since most purifications are accompanied by
distillation, which technique already allows a means of
peroxide removal, the key aspect is safety. In this con-
nection, IMS have proved effective in the deperoxidation
of ethers with peroxide concentrations as high as 0.5 M
without hazard. Compared to other methods IMS provide
a relatively slow rate of peroxide decomposition, and this
feature is almost certainly an important aspect of safe
deperoxidation.
Since it has already been shown that molecular sieves
are particularly effective in removing water24 and other
polar impurities% from ethers, as applied to diethyl ether
Burfield
(24) D. R. Burfield, G. H. Gan, and R. H. Smithers, J. Appl. Chem.
Biotechnol., 28, 23(1978).
for example, the use of IMS provides a safe and effective
method of concomitant deperoxidation, deethanolization,
and drying of the solvent. In the case of dioxane or other
ethers where the presence of significant quantities of alkyl
peroxide are suspected, IMS may be used for pretreatment
before more rigorous deperoxidation is executed.
Experimental Section
Materials. Indicating activated Type 4A molecular sieve,26
(4-8 mesh) were kindly supplied by J . T. Baker Chemical Co. and
were used as received. Ethers were typical reagent grade solvents.
High peroxide levels were induced by aging purified samples in
the presence of air over a period of days or weeks at ambient
temperatures.
Deperoxidation Method. ( i ) Static Deperoxidation.
Ethers, in their original containers, were first deoxygenated by
bubbling with oxygen-free nitrogen for about 5 min in a fume
cupboard. Subsequently, 5% w/v of indicating molecular sieves
was added and the ether tightly capped and set aside.
(i i ) Reflux Deperoxidation. Ethers were charged into a
distillation flask and deoxygenated with a slow stream of nitrogen.
Subsequently, 5 % w/v of indicating molecular sieves was added
and the ether brought slowly to reflux under nitrogen.
Peroxide Analysis. (i) Spectrophotometric Analysis.
Hydroperoxides were analyzed by a modified spectrophotometric
method based on the procedure of Wagner et This ferrous
ion oxidation method permits quantitative analysis of hydro-
peroxides (confirmed for tert-butyl hydroperoxide) but is com-
pletely insensitive to dialkyl peroxides such as di-tert-butyl
peroxide.
(ii) Total Peroxide Analysis. An acid-reflux method pro-
posed by Mair and Graupnera was used and was found to provide
a quantitative assay for dialkyl peroxides such as di-tert-butyl
peroxide.
Acknowledgment. I acknowledge the assistance of Mr.
Lee Meng Lay in conducting the peroxide analyses.
Registry No. Tetrahydrofuran, 109-99-9; dioxane, 123-91-1; di-
ethyl ether, 60-29-7; diisopropyl ether, 108-20-3; trimethylene glycol
dimethyl ether, 17081-21-9; dibenzyl ether, 103-50-4.
(25) D. R. Burfield and R. H. Smithers, Chem. Ind. (London), 240
(1980).
(26) Indicating molecular sieves (Type 4A) as supplied byMerck and
Sigmawerefound to be equally effective. The product of the latter
company is, however, only provided as a mixture(approximately 10%
w/w) with nonindicating molecular sieves. Generally smaller bead sizes
are moreefficient for deperoxidation dueto increased surface area.
(27) C. D. Wagner, H. L. Clever, and E. D. Peters, Anal. Chem., 19,
980(1947).
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J. Org. Chem. 1981,46,629-631 629
(50 mL) afforded 0.400 g (80%) of 15: mp 249-250 C (C2H5OH);
IR (KBr) v, 1709,1600 cm-; H NMR (Me2SO-ds) 6 2.68 (2 H,
t, CH2), 3.04 (2 H, t, H2CC02H), 7.34-7.56 (3 H, m, Ar HI, 7.86
(1 H, s, Ar H), 7.96-8.12 (3 H, m, AI H), 8.50 (2 H, d, Ar H); UV
(anhydrous C2H50H) A, 376 nm (e 3800), 357 (4400), 340 (320%
325 (1900), 255 (200000), 247 (90000).
Anal. Calcd for C1,H1402: C, 81.60; H, 5.60. Found: C, 81.33;
H, 5.84.
5-(2-Anthryl)pentanoic Acid (16). Ester 6 (0.548 g, 2 mmol)
was hydrogenated over 10% Pd/C inanhydrous CZHSOH (50 mL),
and the product obtained was boiled with o-chloranil (0.590 g,
1.2 mmol) for 3 h under NP Hydrolysis of the product from the
above reaction with 10 alcoholic KOH solution (20 mL) afforded
0.410 g (71%) of acid 16: mp 191-192 C (C2H50H); IR (KBr)
v- 1695,1575 cm-; H NMR (DCCld 6 1.6 (4 H, m, CHJ 2.2-2.3
(2 H, m, CH2), 2.82 (2 H, m, CH2), 7.3-7.5 (3 H, m, Ar H), 7.72
(1 H, m, Ar H), 7.88 (3 H, m, Ar H), 8.00-8.32 (2 H, m, Ar H);
UV (anhydrous C2H50H) A, 377 nm (e 5400), 358 (6100), 341
(4400), 327 (2500), 291 (700), 254 (237000), 249 (88900).
Anal. Calcd for C19H1802: C, 82.01; H, 6.44. Found C, 82.13;
H, 6.56.
3-(9-Anthryl)propanoic Acid (22).20 Hydrogenation of acid
20 (0.496 g, 2 mmol) over 10% Pd/C (50 mg) in anhydrous
C2H50H (20 mL) afforded 0.450 g (90%) of acid 22: mp 188-190
C (C2H50H-H20, lit.20 mp 191-192 C); IR (KBr) 1695,1600
cm-; H NMR (DCClJ 6 2.78-2.96 (2 H, br t, CH2), 3.8-4.0 (2
H, br t, CH2), 7.40-7.55 (5 H, m, Ar H); 7.9-8.1 (2 H, m, Ar H),
8.2-8.4 (2 H, m, Ar H); UV (anhydrous C2H50H) A, 386 nm
( e 5000), 361 (5180), 347 (380), 332 (1450), 256 (95700).
5-(I)-Anthryl)pentanoic Acid (23). Hydrogenation of acid
21 (0.556 g, 2 mmol) in anhydrous CzH50H (30 mL) over 10%
Pd/C (70 mg) afforded 0.440 g (79%) of acid 23: mp 112-113
C (ether-petroleum ether); IR (KBr) vmar 1695, 1613 cm-; H
NMR (DCClJ 6 1.70-1.98 (4 H, d, CHJ , 2.42 (2 H, m, CHJ , 3.58
(2 H, m, CH2), 7.16 (1 H, s, Ar H), 7.26-7.60 (4 H, m, Ar H),
7.94-8.20 (2 H, m, Ar H), 8.10-8.32 (1 H, m, Ar H), 11.14 (1 H,
s, C0,H); UV (anhydrous C2HSOH) A, , 387 nm (e 8830), 382
(4640), 367 (8990), 348 (5420), 331 (2490), 318 (1020), 257 (169000),
250 @OW), 236 (21 600), 223 (6700).
Anal. Calcd for Cl ~l sOz: C, 82.01; H, 6.44. Found C, 81.87;
H, 6.65.
Acknowledgment. We gratefully acknowledge partial
support of this work from the Presidental Challenge Grant
Program at O.S.U. in the form of salary (to K.D.B.) and
from the U.S.P.H.S., National Institutes of Health, via a
grant from the Institute of General Medical Sciences
(Grant GM 25353 to M.G.R.).
Registry No. 1, 2143-81-9; 2, 1099-45-2; 3,42997-19-3; 5,75802-
25-4; 6, 75802-26-5; 7, 75802-27-6; 8, 75802-28-7; 9, 75802-29-8; 10,
75802-30-1; 11, 75802-31-2; 12, 75802-32-3; 13, 75802-33-4; 14,
75802-34-5; 15, 75802-35-6; 16, 75802-36-7; 17,642-31-9; 18, 75802-
37-8; 19,75802-38-9; 20,5335-33-1; 21,75802-39-0; 22,41034-83-7; 23,
75802-40-3; [6-(methoxycarbonyl)hexa-2,4-dien-l-yl]triphenyl-
phosphonium bromide, 75802-41-4.
Desiccant Efficiency in Solvent and Reagent
Drying. 5.
David R. Burfield, Roger H. Smithem,* and
Andrew Sui Chai Tan5
Department of Chemistry, University of Malaya,
Kuala Lumpur 22-11, W. Malaysia
Reeeived September 9, 1980
The use of amines in synthesis can be divided into three
principal areas: (i) as basic agents for the promotion of
(1) Part 1: D. R. Burfield, K. H. Lee, and R. H. Smithers, J. Org.
Chem., 42, 3060 (1977).
0022-326318111946-0629$01.00/0
dehydroeliminations, (ii) as nucleophiles in simple dis-
placements, and (iii) as precursors of various metalated
derivatives. Because of strong N-H hydrogen bonding, in
all these uses, water present in the amine system may exert
damaging, i.e., yield lowering, effects by interfering with
absolute basicity and nucleophilicity6 and/or reacting
either as free water or hydroxide ion with unstable in-
termediates or sensitive products. However, despite the
existence of an arsenal of desiccants, the presence of water
in these systems continues to be a problem for the syn-
thetic chemist. This is because the recommended agents
for removal of water and polar impuritiesg from other
solvent and reagent typed4 may not be suitable for
amines. Therefore the radiotracer method for water assay
previously developed by uslo has now been applied to ob-
tain quantitative data on the drying of some representative
amines.
The Pyridine Group. For pyridine, and indeed gen-
erally for the amine class, the traditionally recommended
siccatives are the alkali and alkali earth hydroxides and
0xides.l Thus, literature prescriptions commonly advo-
cate distillation from KOH,12a*b standing over Ba0,lZc or
distillation from CaH2,13 the employment of the latter
procedure reportedly yielding samples containing 18-20
ppm of residual water. The use of A1203 has also been
occasionally reported.14 Our results for pyridine obtained
by application of the radiotracer technique are summarized
in Table I. The results are largely self-explanatory, and
as can beseen, a horizontal line drawn under the entry for
KOH sharply demarcates serious desiccants from those
which are less efficaceous. Surprisingly perhaps, alumina
is seen to be rather unimpressive; however, this ineffec-
tiveness in the drying of polar reagents has been noted
previously.J It is also worth noting that the use of sodium
is to be avoided; it is not particularly efficient and con-
tributes to material loss by a wasteful side reaction which
produces bipyridyls.
Alkylated derivatives of pyridine are more basic and
often less nucleophilic than pyridine itself, and these at-
tributes are considered advantageous in synthesis. We
therefore thought it of interest to compare the difficulty
(2) Part 2: D. R. Burfield, G. H. Gan, and R. H. Smithers, J. Appl.
Chem. Biotechnol., 28, 23 (1978).
(3) Part 3: D. R. Burfield and R. H. Smithers, J. Org. Chem., 43,3966
(1978).
(4) Part 4 D. R. Burfield and R. H. Smithers, J. Chem. Technol.
Biotechnol., in press.
(5) Abstracted in part from the Final Year Project of Andrew S. C.
Tan, 1978-1979.
(6) As is well-known, solvation effects play a vital part in determining
both basicity and nucleophilicity; aee, for example, C. Reichardt Solvent
Effects in Organic Chemistry, Verlag Chemie, Weinheim, Germany,
1979, pp 55-60, 148-155.
(7) In a pertinent example from our own laboratories, the literature
preparation of methyl diphenylphosphinite calls for reaction between
chlorcdiphenylphosphine and methanol in the presence of pyridine and
gives a reported yield of 5270.8 In our hands, the use of rigorously dried
pyridine and methanol increased the yield to 75%.
(8) A. E. Arbuzov and K. V. Nikonorov,, Zh. Obsch. Khim., 18,2008
(1948).
(9) D. R. Burfield and R. H. Smithers, Chem. Ind. (London), 240
(1980).
(10) D. R. Burfield, Anal. Chem., 48 2285 (1976).
(11) See, for example: (a) D. Todd Experimental Organic
Chemistry, Prentice-Hall Inc., NJ , 1979; (b) R. S. Monson, Advanced
Organic Synthesis, Academic Press, New York, 1971; (c) J . A. Riddick
and W. B. bunger, Organic Solvents, 3rd ed., Wiley-Interscience, New
York, 1970.
(12) See, for example: (a) G. A. Olah and M. Watkins, Org. Synth.,
68, 75 (1978); (b) W. H. F. Sasse, Organic Synthesis, Collect. Vol. V,
Wiley, New York, 1973, p 102; (c) R. F. Evans, H. C. Brown, H. C. Van
der Plas, ibid., p 977.
(13) D. J erchel and E. Bauer, Angew. Chem., 68, 61 (1956).
(14) D. N. Glew and N. S. Rath, Can. J. Chem., 49, 837 (1971).
0 1981 American Chemical Society
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630 J. Org. Chem., Vol. 46, No. 3, 1981 Notes
Table I. Desiccant Efficiency in the Dryinga,b of a PyridineC Series
residual water content,d ppm
desiccant
CaH,
CaC,
BaO
4A sieves
3A sieves
benzene azeotrope
KOH powder
Na
CaO
silica gel
- 4 1 2 0 3
2-methyl-
pyridine pyridine
39 (14)e 84
44 (i oj e
101
106 (0.3)f
117
125
152
388
962
926
1306
71
27
55
40
176
2,g-dimethyl-
pyridine
248 (138)
519
360
268 (1 26)
200 (128)
20 7
325
93 5
2,4 ,g-trimethyl-
pyridine
132
8
33
47
390
27
a Static drying modes unless specified otherwise. Water content assayed by the radiotracer technique. Desiccant
24-h drying times unless specified otherwise. e 168-h loading 5% w/v; initial water content 2500 ppm (0.25% w/w).
drying time. f Sequentially dried sample, 24 h.
of drying of some of the more commonly used alkylated
derivatives. A survey of the literature revealed that al-
though the alkylpyridines are usually subjected to similar
drying procedures as pyridine itself, fractionation alone
and fractionation from BF3 (!) have been advocated for
2-meth~lpyridine~ and 2,6-dimethylpyridine,16 respec-
tively. The results summarized in Table I exhibit a
clear-cut trend; whereas one alkyl group at the 2-position
gives results of similar overall order to pyridine, when N
is flanked by two such groups (as in the lutidine) there is
a marked increase in difficulty of drying, with 2-10-fold
greater water levels being observed. Interestingly, the final
member of series, the collidine, gave rise to some of the
lowest residual water levels recorded. Not only is 2,4,6-
trimethylpyridine the most basic of the series examined,17
it is also the easiest example to dry. Clearly then, there
seems to be no relation between increasing basicity and
drying difficulty, and instead this property appears to be
determined by the interplay of water-solubility factors and
of steric crowding about the N atom. Thus, for 2,6-di-
methylpyridine, an infinitely water-miscible base, an ob-
vious speculation is that the two flanking methyl groups
present a serious impediment to the close approach of a
siccative to the water-coordinating site. For trimethyl-
pyridine, a drop in residual water concentrations is par-
alleled by a corresponding large decrease in water solu-
bility.18
Triethylamine. Triethylamine, commonly used as a
mild base in dehydrohalogenations, has been dehydrated
by the alkaline earth KOH,lgb CaH2,1gC and
molecular sievedgd as well as by alumina and sodium
metal.11c The results summarized in Table I1 require little
comment beyond the fact that, despite being considerably
more basic than the pyridines, triethylamine (pKb =3.1)
appears very much easier to dehydrate.
Diisopropylamine. Diisopropylamine is the precursor
of lithium diisopropylamide, a powerful highly hindered
(15) L. A. Walter, Organic Syntheses, Collect. Vol. 111,Wiley, New
York, 1955, p 757.
(16) A. N. Sharpe and S. Walker, J. Chem. SOC. 2974 (1961).
(17) The relevant pKb values for pyridine, 2-methylpyridine, 2,6-di-
methylpyridine, and 2,4,6-trimethylpyridine are 8.8, 8.0, 7.3, and 6.6,
respectively.
(18) While pyridine itself, as well as ita mono- and dialkyl derivatives,
is essentially completely water miscible, the solubility of the trimethylated
pyridine is only about 3%. See Beilsteine, 4th ed., 20, 164 (1953).
(19) (a) R. Breslow and J . Posner, Organic Syntheses, Collect. Vol.
V, Wiley, New York, 1973, p 514; (b) H. Rinderknecht and M. Guten-
stein, ibid, p 822; (e) M. E. J ung and C. A. McCombs, Org. Synth., 58,
163 (1978); (d) T. J. Atkins, R. E. Richman, and W. F. Oettle, ibid., 58,
87 (1978).
Table 11. Desiccant Efficiency in the Dryinga
of Various Aminesb
residual water content,c ppm
(Me,CH),-
desiccant Et,Nd NHe NH,(CH,),NH,e
KOH powder 37 ( 23)f
4A sieves 33 ( 28)h
3A sieves 34
CaH, 68 ( 34)f
Na 83
BaO 89 (53)f
CaC, 98 ( 80) f
CaO 165 ( 56)f
-4120,
silica gel
CaSO,
223 (223)j
451
750g 1370 (3700)g
<25 <25
<25 <25
150 500
<25 150
50 1100
<25 <25
>2500
a Static drying modes unless specified otherwise.
Desiccant loading 5% w/v, initial water content 2500
ppm (0.25% w/w).
otherwise. Water content assayed by the radiotracer
method. e Water content assayed by the near-IR method.
f 168-h drying time. , g Aged desiccant used.
tially dried sample. t Stirred samples. 72-h drying time.
24-h drying times unless specified
Sequen-
base which is freely soluble in many organic solvents and
which has achieved prominence in synthesisz0 in the con-
tinuing search for potent bases of low nucleophilicity.
Curiously, drying prescriptions for the parent amine are
infrequently mentioned, but desiccation with KOH and
storage over CaHz is probably a typical expedient.21
Because this drying problem was not amenable to inves-
tigation using the radiotracer method, due to interference
by isotopic exchange, the near-IR method1~6~zz was applied
and yielded the results summarized in Table 11. In view
of the high water solubility (-40%) and basicity (pKb =
2.9) of this amine, it may seem surprising that dehydration
is so facile. However, an examination of models of the
water-amine complex suggests that the avoidance of steric
congestion between the water molecule and the adjacent
methyl groups can only occur with the imposition of severe
entropy constraints, with the probable result that the
equilibrium between complex and free amine lies largely
to the left.
~~ ~
(20) For usage see, for example: (a) B. M. Trost, C. D. Shuey, F.
DiNinno, Jr., and S. S. McElvain, J. Am. Chem. Soc., 101, 1284 (1979);
(b) R. A. Olofson and C. M. Dougherty, ibid., 95, 582 (1973).
(21) D. Enders, R. Pieter, B. Renger, and D. Seebach, Org. Synth., 58,
113 (1978).
(22) R. L. Meeker, F. Critchfield, and E. T. Bishop, Anal. Chem., 34,
1510 (1962).
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J. Org. Chem. 1981,46, 631-632 63 1
1,3-Propanediamine. This is another example of an
amine which has sprung to prominence in synthesis be-
cause of unique reactions brought about by a derivative,
in this case its monopotassium SalkB Desiccation has been
achieved by vacuum distillation alone,% distillation from
alkali metal or distillation from KOH.24c Our
results using the near-IR method are displayed in Table
I1 and indicate that, not surprisingly, this amine with two
coordinating centers is one of the more difficult examples
to dry. I t is worth noting that freshly ground KOH gives
a drier sample than aged material stored in a desiccator,
although as may be seen, in comparison with several other
siccatives, e.g., CaCz or sieves, KOH is not particularly
good. In addition, although seldom recommended for use
in these situations, CaS04 (Drierite) was investigated in
view of some of the more extravagant claims which have
been made on its behalf.25 As may be seen, the results
are rather dismal.
Desiccation of Amines. General Recommendations.
Perhaps not surprisingly, the results from this study lend
support to the current usage of molecular sieves and CaH2
as serious and widely applicable siccatives for amines.
Apart from this, it is fitting to draw attention to the high
efficiency of CaC2 in these studies, which, though infre-
quently prescribed as a desiccant, is often seen to surpass
CaH2 in potency and is more desirable than the hydride
from consideration of cost and safety in storage. On the
other hand, the performance of alumina is uniformly
disappointing and it cannot be advocated as a serious
desiccant for amines.
Experimental Section
Details of the water assay techniques as well as the source,
activation, and handling of most of the desiccants have already
been described.14 Determination of water content by the near-IR
method22 was carried out on a Varian Cary 17 Instrument.
Calcium carbide was of industrial grade and was crushed in a
mortar immediately prior to use. Appropriate venting was prc-
vided for desiccants producing gases, e.g., CaC2, CaH2.
Amines were of laboratory reagent grade and purified by
standard methods.llc The pyridines and triethylamine were stood
over KOH for 24 h, decanted, fractionated, and stored in dark
bottles over 20% w/v 3A molecular sieves. Pyridine had bp
115-116 OC, 2-methylpyridine 128-129 "C, 2,6-dimethylpyridine
145-146 "C, and 2,4,6-trimethypyridine 176-178 "C. EtaN had
bp 89-89.5 "C. Diisopropylamine was first allowed to stand over
20% w/v 3A molecular sieves, decanted, stirred overnight with
CaH2, fractionated, and finally stored as above, bp 84 OC. 1,3-
Propanediamine was mixed with 20% v/v benzene, fractionated,
stirred overnight with CaH2, and fractionated again, bp 135-136
"C.
Acknowledgment. We thank the Department of
Chemistry, University of Malaya, for support of this work
and Miss Lim Siew Heong for her able technical assistance.
Registry No. Pyridine, 110-86-1; 2-methylpyridine, 109-06-8;
2,6-dimethylpyridine, 108-48-5; 2,4,64rimethylpyridine, 108-75-8
EhN, 121-44-8; (Me2CH)2NH, 108-18-9; NH,(CH2)3NH2, 109-76-2;
CaH2, 1789-78-8; CaC2, 15-20-1; BaO, 1304-28-5; benzene, 71-43-2;
KOH, 1310-58-3; Na, 7440-23-5; CaO, 1305-78-8; A1203, 1344-28-1;
CaS04, 7778-18-9.
(23) Potassium3-aminopropylamide possesses the singular property
of bringing about the conversion internal alkyne- 1-alkyne in essentially
quantitative yields. See C. A. Brown and A. Yamashita, J. Am. Chem.
soc., 97,891 11975).
(24) (a) A. Gero, J. Am. Chem. SOC. 76,5159 (1964); (b) L. R. Dalton,
J. L. Dve. E. M. Fielden. and E. J. Hart, J. Phvs. Chem., 70,3358 (1966);
(c) K. k'Badri and L. Y. Goh, Inorg. Chim. Act a, in press.
pany, Xenia, OH.
(25) W. A. Hammond, "Drierite", the W. A. Hammond Drierite Com-
0022-3263/81/1946-0631$01.00/0
Trapping of I ntermediates i n the Thermolysis of
a-Azidochalcone. I nsight into the "Zwittazido
Cleavage" Reaction
Benjamin A. Belinka, J r., Alfred Hassner,* and
J . M. Hendler
Department of Chemistry, State University of New York at
Binghamton, Binghamton, New York 13901
Received July 28, 1980
The "zwittazido cleavage" reaction (Scheme I) has re-
cently been the subject of considerable study' because this
novel rearrangement possesses both interesting mecha-
nistic and advantageous synthetic characteristics. Al-
though a large amount of work with cyclic and acyclic
ketoazides has been reported,lV2 the mechanism of this
reaction is still somewhat obscure, especially the question
of whether a concerted or stepwise process (or both) occurs.
In the rearrangement of cyclic keto vinyl azides op-
portunity exists for an intramolecular ring closure following
an initial ring cleavage (Scheme I). In acyclic systems
formation of azirines, indoles, or rearranged cyano ketones
can take place.2 In transformation 1-2, the reaction has
been postulated to occur via intermediate 3. An alternate
pathway would involve a cleavage to ions 4 and 5, which
may recombine to 2 (Scheme 11).
Our interest in the chemistry of vinyl azides3 led us to
investigate this reaction and to show that even in the
acyclic case cleavage can occur and that the intermediates
can be trapped with alcohols or amines.
Thermolysis of a-azidochalcone (1) in o-dichlorobenzene
for 24 h produced a-cyano-a-phenylacetophenone (2) in
70% yield. When the reaction was carried out in the
presence of 10 equiv of either ethanol or benzyl alcohol,
the yield of 2 decreased while ethyl benzoate (6) and benzyl
benzoate (7), respectively, were isolated. Thermolysis with
10 equiv of benzylamine yielded N-benzylbenzamide (8).
In all three trapping experiments, considerable quantities
of 2 were also obtained along with benzyl cyanide (9) and
polymeric materials. The results are recorded in Table I.
The formation of compounds 6-9 indicates that at least
part of the thermolysis of the acyclic a-azidochalcone
proceeds by a cleavage mechanism as shown in Scheme I1
which allows for an acyclic cation intermediate 4 to react
with the alcohols and amine. Protonation of 5 leads to
benzyl cyanide (9).
We showed that the azido ketone 1 did not react with
ethanol in boiling toluene to produce ethyl ben~oate.~
Furthermore, no ethyl benzoate (6) was detected by GC
when either the cyano ketone 2 or the crude mixture re-
sulting from heating 1 in o-DCB was subjected to trapping
reaction ~ondi ti ons.~
(1) H. W. Moore, Acc. Chem. Res., 12,125 (1979), and references cited
there in.
(2) D. Knittel, Hemetsberger, R. Leipert, and H. Weidman, Tetrahe-
dron Lett., 1459 (1970).
(3) For instance (a) G. L'Abb6, and A. Hassner, Angew. Chem., Int.
Ed. Engl., 10, 98, (1971); (b) A. Hassner, E. S. Ferdinandi, and R. J .
Isbister, J. Am. Chem. SOC., 92,1672 (1970); (c) A. Hassner, Acc. Chem.
Res., 4, 9 (1971).
(4) Azidochalcone(1) reads with nucleophiles such as sodiumsulfide
or ylides at the azide rather than at the carbonyl function; B. A. Belinka,
J r., and A. Hassner, J. Org. Chem., 44, 4712 (1979), and unpublished
results in this laboratory; G. Mathys, S. Toppet, and G. L'abbd, Chem.
Ind. (London), 6,278 (1975).
(5) G. L'abbg and A. Hassner, J. Org. Chem., 36, 258(1971).
0 1981 American Chemical Society
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3966 J. Org. Chem., Vol. 43, No. 20,1978
Notes
Other acetals which are commonly used as protecting groups for alcohols
are the tetrahydropyranyl ether (ref 4, p 104), ethoxyethyl ether (S. Chladek
and J . Smtt, Chem. Ind. (London), 1719 (1964)), 2-methoxyisopropyl ether
(ref 4, p 107), and 4-methoxytetrahydropyranyl ether (ref 4, p 108). Removal
of all of these groups can be accornpllshed with dilute, aqueous acid. They
are prepared from the corresponding vinyl ether with acidcataiysis. The
methoxymethyl ether,' as well as our tert-butoxymethyl ether, is prepared
from the chloro ether with base catalysis.
See, for example, (a) the synthesis of chloromethyl methyl ether: C. S.
Marvel and P. K. Potter, "Organic Synthesis", Collect. Vol. I, 2nd ed, A.
H. Blatt, Ed., Wiley, New York, N.Y., 1941, p 377; (b) the preparation of
methoxyethyl chloromethyl ether: E. J . Corey, J .-L. Gras, and P. Ulrich,
Tetrahedron Lett., 809 (1976); and (c) a review on a-halo ethers: L. Sum-
mers, Chem. Rev., 55, 301 (1955).
Ethers are halogenated on the (Y carbon: M. L. Poutsma in "Methods in Free
Radical Chemistry", Vol. 1, E. S. Huyser, Ed., Marcel Dekker, New York,
N.Y., 1969, p 137.
Methods for the free-radical halogenation of organic compounds have been
reviewed: E. S. Huyser, Synthesis, 7 (1970).
Sulfuryl chloride has been used to chlorinate tetrahydrofuran (THF): C. G.
Kruse, N. L. J . M. Broekhof, and A. van der Gen, Tetrahedron Lett., 1725
(1976).
All attempts to isolate the chloro ether by concentration have led to de-
composition.
J . F. Norris and G. W. Rigby, J. Am. Chern. SOC., 54, 2088 (1932).
There is no reaction at 0 O C after 4 h but a satisfactory reaction rate is
obtained at room temperature. The water bath is used for cooling purposes
only.
The 'H NMR spectra of the tert-butoxymethyl ethers show singlets at 6
4.1-4.7 (2 H) and 1.2-1.25 (9 H). The corresponding l 3C NMR spectra are
also consistent with the proposed structures. For example, the acetal and
quaternary carbons are found at 6 89.248 and 74.251, respectively, for
the benzyl alcohol acetal and 6 90.038 and 74.068, respectively, for the
1-hexanol acetal.
Desiccant Efficiency in Solvent Drying. 3.
Dipolar Aprotic SolventslJ
David R. Burfield* and Roger H. Smithers
Department of Chemistry, University of Malaya,
Kuala Lumpur 22-11, Malaysia
Received May 2, 1978
I t is generally acknowledged that dipolar aprotic solvents
are the media of choice in some reactions and are unique in
facilitating others.3 The special solvent effects of molecules
such as DMF and Me2SO are attributable to their large di-
electric constants coupled with the absence of solvation by
hydrogen bonding and typically manifest themselves in
properties such as poor anion solvation, voracious cation
solvation, and a marked hydrophilicity. For the chemist, this
latter feature is unfortunate since small amounts of water in
these systems can diminish314 their nucleophilicity and may
even be hazardous to some operations.5 The drying of these
solvents is thus of paramount importance, but in these cases,
as previously,' the chemical literature contains little reliable
quantitative data.
We have recently developed a method of solvent water assay
which utilizes a tritiated water tracer for the determination
of water content.6 The method circumvents many of the
problems encountered in other assay methods and has pro-
vided some new correlations on the efficiency of desiccants.lS*
For example, i t has been shown that, rather surprisingly, the
efficiency of a given desiccant is strongly dependent upon the
solvent type,' and there is thus much uncertainty in extrap-
olating generalizations from one solvent type to another.
The method has now been applied to the desiccation of the
dipolar aprotics acetone, DMF, MeZSO, and HMPT. Since the
dielectric constants of these solvents range between 20.7
(acetone) and 46.7 (MeZSO), their rigorous desiccation is ex-
pected to be difficult.
Results and Discussion
Drying of Hexamethylphosphoric Triamide (HMPT).
Caution! HMPT is a suspected carcinogen. Although in re-
cent years the favored desiccant for HMPT appeared to be
calcium h~dri de, ~ drying has also been previously accom-
plished with alkali metal^,^^^alkali metal earth oxides,s and
4A9* and 13Xgb molecular sieves.
The results with the siccatives summarized in Table I are
largely self-evident, but the following points are worth noting.
The extreme resistance to desiccation is demonstrated by the
impossibility of obtaining super-dry lo HMPT under any of
the conditions used here. Even sequential drying,ll which was
previously found to be effective with acetonitrile,2 falls short
in this case. The use of sodium-potassium alloy as a drying
agent seems questionable in view of the thermal instability
of solutions of alkali metals in solvents of this type.lZ
Since phosphorus pentoxide causes loss of material through
side reactions, the best procedure for drying HMPT appears
to be distillation from calcium hydride followed by storage
over molecular sieves.
Drying of Dimethylformamide One sources observes that
it is doubtful whether distillation alone can remove water from
this solvent and recommends a chemical method for the
elimination of protonic impurities. 4A molecular sieves, alu-
mina, potassium hydroxide, and calcium hydride have all been
endorsed as siccativess for DMF.
The results in Table I1 indicate the powerful hydrophilicity
of this solvent, although sequential drying with 3A sieves al-
most achieves super-dryness. Interestingly, and contrary to
an earlier suggestion,'3 while some of the basic dessiccants
investigated are totally inept, e.g., alumina and potassium
carbonate, others such as calcium hydride and potassium
hydroxide achieve quite reasonable drying levels. Also, al-
though seldom advocated for use in this circumstance, phos-
phorus pentoxide is a commendable desiccant. For DMF,
however, barring impurities other than water, by far the
Table I. Efficiency of Desiccants in the Drying" of HMPTb
residual solvent water content, ppm
desiccant 6h 24 h 72 h 144 h other conditions
p205 184OC 22d
CaHz 1750 857 347 248 80d
Bz03 190e
3A molecular sieves 1380 595 307 239
4A molecular sieves 1167 610 344 269 295
KOH (powdered) 1380 840 404 321f
Na-K 162Od.g
BaO 2190 1540 1040
CaO 2360 2034 1890 1380
A1203 2134
a Static drying modes unless otherwise specified.
Cas04 2080
Desiccant loading 5% w/v; initial water content 2620 ppm (0.262% w/w). Strongly
Distilled sample. e Stirring for 24 h followed by distillation. f Sequentially dried sample, 72 h. Significant quantities colored solution.
of dimethylamine are released on distillation.
0022-3263/78/1943-3966$01.00/0 0 1978 American Chemical Society
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Notes J . Org. Chem., Vol. 43, No. 20,1978 3967
Table 11. Efficiency of Desiccants in the Drying" of
DMFb
residual solvent water
content, ppm
other
desiccant 6 h 24h 72h conditions
3A molecular sieves 500 167 98 1.5c
pzo6
879 105 2d
CaH2 641 227 102 94d
4A molecular sieves 454 134 108
KOH (powdered) 1360 1110 303
B203
890e
BaO 2060 1520 1140
CaO 2090
A1203
1970
Cas04 2310 2030 1420
KzC03 2500
a Static drying modes unless otherwise specified. Desiccant
loading 5% w/v; initial water content 2860 ppm (0.286% w/w).
Sequentially dried sample, 72 h. Distilled Sample. e Stirring
for 24 h followed by distillation.
simplest and most effective method is sequential drying with
3A molecular sieves.
Drying of Dimethyl Sulfoxide (MezSO). Although cal-
cium hydride14a and molecular sieves14b appear to be approved
desiccants, the drying of Me2SO has also been accomplished
with a large variety of other siccatives.8 Calcium sulfate, alkali
earth metal oxides, alkali metal hydroxides, alumina, and,
surprisingly perhaps, fractional distillation alone15 have all
been utilized.
Perhaps the most unexpected result (Table 111) is that
fractional distillation, discarding the first 20?h of the distillate,
affords desiccation of similar magnitude to that obtained with
molecular sieves! This result is most surprising in view of the
high dielectric constant and hygroscopicity of MezSO.
The interpretation of other results for MezSO is not so
straightforward. For many of the basic desiccants, e.g., calcium
hydride and calcium and barium oxides, initial dehydration
is followed by an increase in apparent water content, and this
indicates a base-catalyzed exchange between the acidic a
protons of Me2SO and labeled water. This suggestion is sup-
ported by a desiccation experiment with powdered potassium
hydroxide which gave very little apparent drying. In this case,
standing for 2 or 3 h over the desiccant produced yellow so-
lutions, most likely indicating the presence of the dimsyl ion,
which would of course lead to labeled solvent through ex-
change processes.
Although the results with the basic desiccants are therefore
not very conclusive, a necessary corollary in the case of calcium
hydride is, however, that drying is relatively slow, and perhaps
not very efficient. A similar result for this desiccant was noted
earlier with acetonitrile.'
I n summary, although phosphorus pentoxide gave the best
drying, i t also induced significant decomposition, and the
method of choice for Me2SO would appear to be initial frac-
tional distillation followed by sequential drying with molec-
ular sieves.
Drying of Acetone. Acetone has been dried with a wide
spectrum of desiccants.8 Thus, alumina, calcium chloride,
phosphorus pentoxide, and 4A molecular sieves,16 as well as
calcium and (anhydrous) cupric sulfate, have all been used.
Since acetone has the lowest dielectric constant of the sol-
vents investigated here, it might be predicted that its drying
should be relatively easy. In fact, in many respects the drying
of acetone proved to be the most difficult case. As with MezSO,
the root of the difficulty is the acidic a protons, which in this
case compounds the drying problem not only by inflating
apparent water content by exchange process but also by
providing a pathway to self-condensation through enol in-
termediates. This facet of acetone chemistry makes the choice
of a successful desiccant a delicate process. As Table IV shows,
mild siccatives such as calcium sulfate are inept; more potent
desiccants such as molecular sieves exhibit a short initial
drying action but thereafter actually cause disastrous in-
creases in water content by displacement of the condensation
equilibrium. This interpretation was confirmed for molecular
sieves and other basic desiccants such as barium oxide by gas
chromatographic analysis which demonstrated the presence
of mesityl oxide in the dried solvent (see Table IV).
I n summary, while both cupric sulfate and 3A molecular
sieves are clearly at least useful preliminary desiccants, the
agent par excellence for acetone is powdered boric anhydride.
Using stirring and sequential drying conditions, this siccati
gave a solvent containing only 18 ppm of water and caused
detectable condensation. I n fact, the true water content
likely to be lower as even with the premise that drying OCCL
considerably faster than other processes, some labeling via t
enol surely occurs on preparation of the standard wet sol
tion.
I n view of the remarkable efficiency of this desiccant f
acetone and acetonitrile,l i t is puzzling that boric anhydri
is not particularly outstanding for other members of this ser
(Tables 1-111). This finding emphasizes once more the danger
in assuming the existence of any kind of absolute scale in the
efficiency of desiccants for solvent drying.
Table 111. Efficiency of Desiccants in the Dryinga of MezSOb
residual solvent water content, ppm
desiccant 6h 24 h 72 h 144 h other conditions
4A niolecular sieves 978 471 332 318 1o c
3A molecular sieves 1050 448 269 226
none 261
P205 1.4e3f
B203 897g
CaH2 1560 1820 1740 1802e
BaO 1450 1330 1770 2251
CaO 2060 1740 1800
A12013 1840 1900 1920
KOH (powdered) 2130h 2190e
Cas04 2140
KzCQ3 2280 2200
Static drying modes unless otherwise specified. Desiccant loading 5% w/v; initial water content 2560 ppm (0.256% w/w). Se-
quentially dried sample, 72 h. d Fractionally distilled sample. e Distilled sample. f Contaminated by decomposition products. g Stirring
for 24 h followed by distillation. Yellow colored solutions.
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3968 J. Org. Chem., Vol. 43, No. 20, 1978 Notes
Table IV. Efficiency of Desiccants in the DryingD of
Acetone
residual solvent water
content, ppm
other
desiccant 6 h 24 h 72 h conditions
Bz03 i 8C.d
47c. e
107f
3A molecular sieves 115 152 322g 322h
CuSO4 (anhydrous) 1920 972 579 1700h
Cas04 1590 1600
BaO 1910 1870'
pzo5 j
1970f
KzC03 2057 2250
Desiccant
loading 5% w/v; initial water content 2710 ppm (0.271% w/w),
unless specified otherwise. c Initial water content 2890 ppm
(0.289% w/w). d Stirred, distilled, and sequentially dried, 24 h.
e Stirred for 24 h and distilled. f Dried for 24 hand then distilled.
g Contamination (2%) by mesityl oxide. Fractionated sample.
i Contamination (12%) by mesityl oxide. j Brown-black solu-
tions.
4A molecular sieves 331 887 1720
a Static drying modes unless specified otherwise.
Experi mental Section
Desiccants. Details of the source, activation, and handling of most
of the desiccants have already been described.' Reagent grade cupric
sulfate was activated by heating at 320 "C for 15 h before use. Barium
and calciumoxides wereof reagent grade, and a fresh batch was used
directly without activation.
Solvents, DMF, MeZSO, and HMPT werecommercial synthetic
grades of 99% purity (Merck). Acetonewas of analytical grade (M&B).
All solvents wererigorously purified by standard methods.*
HMPT and Me2SO were treated by standing over bariumoxide
overnight, followed by filtration, distillation fromcalciumhydride,
and subsequent storage over 20% w/v 4A molecular sieves. MezSO had
bp 74.5-75.0 O C at 12 mmHg, and HMPT had bp 89.0-89.5 "C at -3
mmHg.
Commercial DMF was allowed to stand over 4A molecular sieves
overnight and was filtered, distilled fromphosphorus pentoxide (bp
55.8-56.0 "C at 20mmHg), allowed to stand over anhydrous potas-
siumcarbonate, and subsequently stored over 4A molecular sieves.
Analytical grade acetone was allowed to stand over anhydrous
potassiumcarbonate for one day and then over 4A molecular sieves
overnight. Fractionation gave material, bp 56.2 OC, which was not
stored but used immediately. Gas chromatographic analysis of this
material showed it to be free of impurities.
Techniques. The procedure used for HMPT serves as an example.
A stock solution of HMPT containing 2620 ppmof labeled water was
prepared by the addition of 0.50 g of tritiated water, specific activity
0.5 mCi/mL, to the appropriate mass of purified rigorously dried
HMPT. Aliquots of the stock solution (15.0 i 0.1 mL) weresyringed
directly onto the appropriate desiccant contained in a 25mL clear-fit
round-bottomflask, which was immediately stoppered. Experiments
wereconducted at ambient temperatures (26-30 "C). Where specified,
samples werestirred magnetically. Aliquots (1.00 f 0.02 mL) were
taken at time intervals as specified in Table I and assayed directly by
liquid scintillation counting, as previously Where nec-
essary, viz., in the caseof colored solutions or suspected contamination
by soluble desiccant residues, samples weredistilled before assay.
Sequential drying2 was accomplished by decanting monosiccated
solvent onto a fresh charge of 5% w/v desiccant. Sampling was then
effected at the time intervals given in the table footnotes.
Registry No.-HMPT, 680-31-9; DMF, 68-12-2; MeZSO, 67-68-5;
acetone, 67-64-1.
References and Notes
(1) Part I: D. R. Burfield, K. H. Lee, and R. H. Smithers, J. Org. Chem., 42,3060
( 1977).
(2) For Part 2, see D. R. Burfield. G. H. Gan, and R. H. Smithers, J. Appl. Chem.
Biotechnol., 28, 23 (1978).
(3) See, for example, Heinz Becker et ai., "Organicum, Practical Handbook
of Organic Chemistry", translated by B. J . Hazard, Pergamon Press,
Braunschweig. 1973, pp 185. 190. See also L. F. Fieser and M. Fieser.
"Reagents for Organic Synthesis", Vol. 1-5, Wiley, New York. N.Y., 1967,
0022-3263/78/1943-3968$01.00/0
1969, 1972, 1974and 1975.
(4) For an interesting recent study involving Me2SO-H20 mixtures, see L. F.
Blackwell and J . L. Woodhead, J. Chem. Soc.. Perkin Trans. 2, 1218
(1975).
(5) The reaction of sodiumhydride with Me2S0 has been reported to sometimes
give rise to violent explosions: inter alia, see L. Brandsma, "Preparative
Acetylenic Chemistry", Elsevier, Amsterdam, 1971, p 24. However, in our
hands, the same reaction has been carried out a number of times using
stringently dried solvent with no untoward effects. While thecause of these
accidents remains undetermined, it is noteworthy that the equilibrium water
content of Me2S0 is lo%, and it thus seems not unlikely that the origin
of these mishaps may lie in the use of insufficiently dried solvents.
(6) D. R. Burfield, Anal. Chem., 48, 2285 (1976).
(7) See, for example, B. M. Trost and Y. Tamaru, J. Am. Chem. Soc., 99,3101
(1977).
(8) See references contained in J . A. Riddick and W. B. Bunger, "Organic
Solvents", 3rd ed., Wiley-lnterscience, New York, N.Y., 1970.
(9) (a) F. Trondlin and C. Ruchardt, Chem. Ber., 110, 2949 (1977); (b) T. J .
Wallace and A. Schriesheim, Tetrahedron, 21, 2271 (1965).
(10) Here, as the term super-dry denotes solvents containing less
than 1 ppm of water.
(1 1) See Experimental Section.
(12) C. A. Young and R. R. Dewald, J. Chem. Soc., Chem. Commun., 186
(1977).
(13) See S. S. Pizey, "Synthetic Reagents", Vol. 1. Ellis Horwood Ltd., Chi-
Chester, 1974. This author reports that the use of calcium hydride and other
basic desiccants in the drying of DMF could produce significant amounts
of dimethylamine. However, the presence of this amine would give rise
to inflated apparent water contents, and the values observed here, both
for statically dried and distilled samples, suggest that this side reaction is
of minor importance for these desiccants.
(14) (a) D. Martin and H. G. Hauthal, "Dimethyl Sulphoxide", translated by E.
S. Halberstadt, Wiley-Halsted, New York, N.Y., 1975. (b) H. E. Baumgarten.
Ed.. "Organic Syntheses", Collect. Vol. 5, Wiley, New York. N.Y., 1973,
pp 243, 756.
(15) W. H. Smyrl and C. W. Tobias, J. Electrochem. Soc., 115, 33 (1968).
(16) R. L. Meeker, F. Critchfield, and E. T. Bishop, Anal. Chem., 34, 1510
(1962).
3,4-Dimethyl-cis- bicyclo[ 3.3.0]-3-octene-2,8-dione:
A Potenti al l y Useful Pentalenolactone Synthon
Martha L. Quesada, Richard H. Schlessinger,* and
WilliamH. Parsons
Department of Chemistry, University of Rochester,
Rochester, New York 14627
Received March 13.1978
Pentalenolactone (1) is an acidic lipophylic antibiotic iso-
lated from the fermentation broth of Streptomyces UC 5319
- 1
which exhibits inhibitory activity against nucleic acid syn-
thesis in bacterial cells.1t2 Both the novel structural nature of
pentalenolactone together with its biological activity
prompted us to consider possible routes to the synthesis of this
molecule.
Inspection of the literature revealed a number of potential
pentalene ~ynthons,~ the most interesting of which was the
pentalenedione 2 reported first by Stetter4 and more recently
0
3
2 -
-
by E at~n. ~ The salient feature of both the Stetter and Eaton
routes was the base-induced internal Claisen condensation
of the ester 3, which in Eaton's hands gave an excellent yield
of the dione 2. These data inspired us to consider the possi-
0 1978 American Chemical Society
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3852 J . Org. Chem. 1984,49, 3852-3854
(23.8), 94 (26.0), 93 (61.4), 80 (25.0), 79 (27.1), 31 (100.0), 29 (50.2).
Anal. Calcd for CI2Hl8O: M, 176.1202. Found (high-resolution
mass spectrometry): M, 176.1201.
The following spectra data were obtained for 14: 'H NMR
(CDCl,) S 0.8-1.3 (m, 2 H), 1.68 (s, 3 H), 1.8-3.0 (m, 9 H), 3.3 (m,
1 H), 5.28 (s,1 H); 13C NMR (CDC1,) 6 16.26 (q), 37.45 (d), 39.28
129.8 (d), 139.0 (s), 220.6 (9); IR (neat) 3040 (w), 2940 (s), 1735
(s), 1650 (w), 1440 (m), 1410 (m), 1140 (m), 1020 (m), 820 (m) cm-';
mass spectrum (70 eV), m/ e (relative intensity) 176 (molecular
ion, 43.6), 147 (23.4), 106 (50.2), 95 (84.3), 94 (38.9), 93 (56.9), 91
(49.4), 82 (21.7), 80 (31.8), 79 (44.4), 77 (28.7), 41 (37.9), 39 (26.2),
31 (100.0), 29 (59.5).
Anal. Calcd for Cl2HI60: M, 176.1202. Found (high-resolution
mass spectrometry): M, 176.1205.
Hydrogenation of 13 and 14. A solution of either 13 or 14
(10 mg, 0.56 mmol) in ethyl acetate (2 mL) was hydrogenated over
10% palladized charcoal catalyst (2 mg) at a hydrogen pressure
of 12 psig for 40 min. The reaction mixture was filtered to remove
catalyst, and the filtrate was concentrated i n vacuo to afford 15
(10 mg, 100%) which was purified via bulb-to-bulb distillation
under reduced pressure: bp 130 "C (0.5 mm); 'H NMR (CDCl,)
6 1.2 (d, 3 H, J =6 Hz), 1.6-3.0 (m, 15 H); IR (neat) 2945 (s), 2870
(w), 1740 (s), 1460 (m), 1410 (m), 1380 (w), 1160 (m) cm-l; mass
spectrum (70 eV), ml e (relative intensity) 178 (molecular ion, 17.4),
95 (27.3), 82 (48.6), 81 (24.9), 41 (20.3), 31 (100.0), 29 (55.9).
Anal. Calcd for CI2Hl8O MI 178.1358. Found (high-resolution
mass spectrometry): MI 178.1358.
Acknowledgment. Financial support of our study by
the Naval Air Systems Command, the Robert A. Welch
Foundation (Grant B-963), the Air Force Office of Scien-
tific Research (Grant No. AFOSR-84-0085), and the North
Texas State University Faculty Research Committee is
gratefully acknowledged. K.S.R. gratefully acknowledges
receipt of a fellowship from the CSIR, New Delhi, India.
We thank Professor H.-J . Liu (University of Alberta) for
kindly obtaining the high-resolution mass spectra of com-
pounds 6, 7, 8, l l b, and 12b and Mr. N. Omkaram for
kindly obtaining the high-resolution mass spectra of com-
pounds 13-15.
Registry No. 5, 87830-51-1; 6, 91632-94-9; 7, 91632-95-0; 8,
91632-96-1; 9,91632-97-2; 10, 25282-60-4; l l a, 91632-98-3; l l b,
91632-99-4; 12a, 91633-00-0; 12b, 91633-01-1; 13,91633-02-2; 14,
(t), 39.57 (t), 42.39 (d), 44.44 (t), 44.62 (d), 45.67 (t), 52.72 (d),
91633-03-3; 15, 91633-04-4.
Desiccant Efficiency in Solvent and Reagent
Drying.'S2 9. A Reassessment of Calcium Sulfate
as a Drying Agent
David R. Burfield
Department of Chemistry, University of Malaya,
Kuala Lumpur 22-11, Malaysia
Received March 1, 1984
Anhydrous calcium sulfate (Drierite) has been applied
to the problem of solvent desiccation for over 50 years3 and
has received general endorsement4 as an efficient and
generally applicable low cost drying agent. However, many
of the extravagent claims5 made for the efficiency of this
(1) Part 7: Burfield, D. R.; Smithers, R. H. J. Org. Chem. 1983, 48,
2420.
(2) Part 8: Burfield, D. R.; Hefter, G. T.; Koh, S. P. J. Chem. Technol.
Biotechnol. 1984, 34A, 187.
(3) Hammond, W. A.; Withrow, J . R. Ind. Eng. Chem. 1933,25,1112.
(4) See: (a) Fieser, L. F.; Fieser, M. 'Reagents for Organic Synthesis";
Wiley; New York, 1967; p 107,1103. (b) Vogel, A. I. "Vogel's Textbook
of Practical Organic Chemistry"; Longmans: London, 1978; p 139. (c)
Perrin, D. D.; Armarego, W. L. F.; Perrin, D. R. "Purification of Labo-
ratory Chemicals"; Pergamon: Oxford, 1980; p 23.
0022-326318411949-3852$01.50/0
Table I. Effect of Calcium Sulfate Activation Temperature
on Its Efficiency in Dioxane Dryin@
residual solvent water content,
activation
temperature, PPm
O C l h 6 h 24 h 72 h
no activation 1700 1140 540 240
100 1820 1460 1190 1130
150 2000 1230 485 240
200 1690 1080 500 250
225 1950 1200 535 250
250 1770 1290 660 310
300 1930 1430 970 970
DI nitial water content =2500 ppm; desiccant loading =5% w/v;
desiccant samples activated overnight (16 h).
Table 11. Effect of Calcium Chloride Activation
TemDerature on Its Efficiency in Dioxane Dryin@
residual aolventwater content,
activation
temperature, PPm
O C l h 6 h 24h 72h
no activation 1820 1020 430 350
150 1840 1230 420 290
225 1700 1090 370 290
300 1750 1040 385 325
OInitial water content =2500 ppm; desiccant loading =5% w/v;
desiccant samples activated overnight (16 h).
product are based on very early results,3,6 and in our recent
studies,7-1 where calcium sulfate has been examined
alongside other desiccants it has been found to have only
very modest efficiency. Thus Drierite approaches the foot
of the "drying league" in a recentg evaluation of 12 desic-
cants for the drying of wet ether extracts and is similarly
placed in studies of the drying of benzene, dioxane, ace-
tonitrile: various dipolar aprotic solvents*, and amines.1
However, in our earliest studies7sJ 0 in an attempt to attain
uniform and hence comparable experimental conditions
desiccants were activated at 300-320 OC for 15 h before
use. Since it is possible that such activation conditions
may have had a deleterious effect on the activity of the
calcium sulfate" and in view of the widespread utilization
of this product it appeared pertinent to reevaluate its
desiccant potential. This paper thus centers on a reap-
praisal of Drierite as a desiccant for solvent drying with
particular attention being payed to the effect of activation
temperature. Comparison with two other important de-
siccants, viz., calcium chloride and molecular sieves, is also
made.
Results and Discussion
Influence of Desiccant Activation Temperature.
Dioxane was choosen for initial tests as it is moderately
~~
(5). For example: "The last detectable traces of water are removed by
Drierite fromany liquid which is sufficiently fluid to make intimate
contact with the porous solid" and "Regular Drierite is unsurpassed for
the drying of organic liquids in the liquid or vapour phase. Moisture
residue after treatment with Drierite is so low it cannot be measured,
leaving the organic liquid truly anhydrous". Quoted in; Hammond, W.
A. "Drierite"; W. A. Hammond Company: Xenia, OH.
(6) Thus calciumsulfate was surpassed only by barium oxide, mag-
nesiumperchlorate, and calciumoxide in evaluations based on gas drymg
efficiency reported by: Bower, J . H. J. Res. Natl. Bur. Stand. 1934,12,
241.
(7) Burfield, D. R.; Lee, K. H.; Smithers, R. H. J . Org. Chem. 1977,
42, 3060.
(8) Burfield, D. R.; Smithers, R. H. J. Org. Chem. 1978, 43, 3966.
(9) Burfield, D. R.; Smithers, R. H. J. Chem. Educ. 1982, 59, 703.
(10) Burfield, D. R.; Smithers, R. H.; Tan, A. S. C. J. Org. Chem. 1981,
46, 629.
(11) Thus it has been shown"* that calciumsulfate heated above 400
"C rehydrates only slowly and it has been suggested'lb that the transition
to the inactive formoccurs at around 313 "C. (a) Glasenapp, M. J. SOC.
Chem. Ind., London 1908,27,858. (b) Chassevent, L. Liebigs Ann. Chem.
1927, 7, 43.
0 1984 Ameri can Chemi cal Soci ety
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Notes J. Org. Chem., Vol. 49, No. 20, 1984 3853
Table 111. Deuendence of Drying Efficiency on Desiccant Loading in the Drying of Grossly Wet Diethyl Ether"
desiccant
loading capacityd
residual solvent water content, ppm
desiccant % w/v 5 min 15 min 30 min 60 min 360 min % w/w
CaSO, l o b 11400 9200 10200 10700 2.8-3.9
20b 6400 3800 2100 4.5
20' 9700 7500 5800 3.1
CaCl, 5c 2100 2100 850 19.6
10c 2400 2100 1900 390 10.1
20c 2100 1400 900 4.9
"Initial water content =14700 ppm; drying temperature =22 "C. Activation temperature: =220 "C. =350 "C. dGiven by weight of
water absorbed per unit of desiccant expressed as a percentage.
Table IV. Dependence of Drying Efficiency on Desiccant
Loading in the Drying of Dioxane"
desiccant
1 o a d i n g
desiccant % w/v
CaSOlb 1.24
2.5
5
10
20
CaC12' 1.25
2.5
5
residual solvent water
content, ppm
l h 6 h 24h 72h
2600 2300 2020 1950
2020 1610 1220 1130
1700 1140 540 240
2140 760 150 110
1600 510 120 80
2250 1880 2320d 2500d
1940 1340 540 390
1750 1040 385 325
capacity
4.5
5.6
4.7
2.5
1.3
9.1
4.5
% w/w
" Initial water content =2500 ppm; drying temperature u 27-30
"C. bActivated at 225 OC. cActivated at 350 "C. dCaC12 granules
observed to disintegrate.
difficult to dry and a fairly extensive set of drying data
has already been accumulated for this solvent.'J 2J 3 Ac-
tivation of the desiccant was carried out at temperatures
in the range 100-300 "C. The marked influence of acti-
vation temperature on drying efficiency is shown in Table
I. Activation of Drierite in the temperature range 150-225
"C provides a product whose activity islittle different from
the as-received material. However, activation at tem-
peratures of 250 "C and above is accompanied by a distinct
deterioration in drying efficiency. Interestingly, a similar
reduction in efficiency is observed on activation at 100 O C
and this must be ascribed to the absorption of water by
the desiccant when equilibrated in an air oven at the high
ambient humidities experienced in Malaysia. This sup-
ports the earlier contention3 that Drierite binds water at
temperatures up to at least 107 "C. The optimum acti-
vation temperature for this material would appear to be
in the range 200-225 "C.
An examination of another commonly used desiccant,
calcium chloride, reveals that in this case the use of high
activation temperatures does not have a deleterious effect
on the drying activity (Table 11).
Since the drying activities of these two materials under
optimum activation conditions appear quite similar, the
earlier poor showing of calcium sulfate in our desiccant
evaluation studies7v8J0 must in part be ascribed to the
inactivation of the material by inappropriate high-tem-
perature treatment.
Drying Capacity of Desiccant Materials. The ove-
rall drying efficiency of a desiccant is determined not only
by its intrinsic affinity for water but also by its capacity
to contain the bound water. The drying capacity is an
important parameter since it will dictate the appropriate
desiccant loadings for practical use. Determination of the
drying efficiency as a function of desiccant loading (Tables
(12) Burfield, D. R.; Gan, G. H.; Smithers, R. H. J. App. Chem. Bio-
(13) Burfield, D. R.; Smithers, R. H . J. Chem. Technol. Biotechnol.
technol. 1978, 28, 23.
1980, 30, 491.
Table V. Comparison of Desiccant Drying Efficiency for
Dioxane and Acetonitrilea
residual solvent water
content, ppm
desiccant dioxane acetonitrile
CaSo4* 240 180
CaC12b 290 d
3A molecular sieveC 19 52
4A molecular sievec 30 450
"Initial water content =2500 ppm; drying time 72 h. Activation
temperature: =225 "C. =350 "C. Drying temperature 27-30
"C. dCaC1, induces a base-catalyzed tritium exchange with aceto-
nitrile which precludes determination;' desiccant loading =5%
WJV.
I11and IV) gives a measure of the inherent capacity of the
material.
In the drying of grossly wet ether samples the maximum
observed water capacity is only 4.5% w/w for Drierite
compared to nearly 20% w f w for calcium chloride (Table
111). Interestingly at low desiccant loadings the Drierite
is observed to lose its effectiveness with increasing drying
time and this may be symptomatic of a breakdown of this
material in the presence of large water excesses. I t is also
clear (Table 111) that activation of Drierite at 350 "C leads
to a reduction in drying capacity, and this again empha-
sises the importance of moderate activation temperatures
for this material.
A somewhat similar maximum drying capacity of 5.6%
w/w is observed for the Drierite drying of dioxane (Table
IV). In contrast, for calcium chloride the maximum ob-
servable drying capacity is sharply reduced to about 9%
and at low desiccant loadings the granular material is
observed to break up with complete loss of water retention.
Since calcium chloride appears quite stable in the presence
of water-saturated diethyl ether, it would appear that some
specific interaction with dioxane must occur. The some-
what higher ambient temperatures (27-30 "C) encountered
during the dioxane drying experiments may also have
adversely affected the capacity of the calcium chloride.
Overall, it appears that calcium chloride has a signifi-
cantly higher water capacity than Drierite. The optimum
value for calcium chloride is quite similar to the 18-20%
w/w capacity observed12 for 3A molecular sieves in the
drying of dioxane.
Comparative Drying Efficiency. By employing
suitably high desiccant loadings it is possible to offset the
effects imposed by variable capacity and hence to probe
the inherent drying efficiency of the desiccant materials.
The relative efficiencies for the drying of dioxane and
acetonitrile by Drierite, calcium chloride, and molecular
sieves are summarized in Table V. I t is apparent that
calcium chloride and calcium sulfate are quite similar in
drying ability but that the residual water content is of an
order of magnitude higher than that attainable with mo-
lecular sieves. I t is of some interest however that Drierite
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3854 J. Org. Chem. 1984,49, 3854-3856
is more efficient than 4A molecular sieves in the desicca-
tion of acetonitrile. The inefficiency of the 4A sieves is
brought about by competitive adsorption of acetonitrile
at the water binding sites. This apparently does not occur
with Drierite.
Summary
Anhydrous calcium sulfate (Drierite) is a moderately
efficient desiccant for the drying of organic solvents. The
material loses drying activity if heated to about 250 OCand
has a limited water capacity (-5% w/w). It is therefore
not appropriate for efficiently drying grossly wet solvents
as earlier ob~erved.~
Experimental Section
Solvent water content was determined by the radiotracer
method previously des~ri bed.~J ~J ~ Anhydrous calcium sulfate
(Drierite), 1C-20 mesh, waskindly supplied as a gift fromW. A.
Hammond Drierite Company. Details of solvents and other
desiccants have already been described.
Registry No. CaSO,, 7778-18-9.
(14) Burfield, D. R. Anal. Chem. 1976, 48, 2285.
Carbon Monosulfide Chemistry in Solution. 2.
Synthesis and Reactions of Trichloromethyl
Chlorodithioformate
Ejner K. Moltzen,2a Alexander Senning,*2a
Michael P. Kramer,2b and Kenneth J . Klabunde*2b
Departments of Chemistry, Aarhus University, DK-8000
Aarhus C, Denmark, and Kansas St at e University,
Manhat t an, Kansas 66506
Received February 3, 1984
Recently wewere able to demonstrate that the insertion
of CS into the sulfur-chlorine bond of sulfenyl chlorides
appears to be a general and synthetically useful reaction.
While our previous examples (1) and (2) involve highly
C,H,SCl+ CS -+ CBH,SC(S)Cl (1)
ClSSCl +2cs - ClC(S)SSC(S)Cl (2)
reactive sulfenyl chlorides, it was not obvious that tri-
chloromethanesulfenyl chloride 1 would react according
to (3). In a number of reactions 1 is considerably less
(3)
reactive than typical aliphatic or aromatic sulfenyl
chlorides; for instance, the normally rapid uncatalyzed
addition of sulfenyl chlorides to ethylene does not take
place in the case of l;3 moreover, 1 can be steam distilled
with little decomposition4 while typical sulfenyl chlorides
must be protected from moisture. On the other hand, 1
does react readily in the a-addition to isocyanides5 (it
C1,CSCl +cs - C1,CSC(S)C1
1 2
(1) Paper 1 in this series: Klabunde, K. J .; Kramer, M. P.; Senning,
(2) (a) Aarhus University, Denmark. (b) Kansas State University.
(3) Douglass, I. B.; Martin, F. T.; Addor, R. J. Org. Chem. 1951, 16,
(4) Klason. P. Ber. 1887. 20. 2376.
A.; Moltzen, E. K. J. Am. Chem. SOC. 1984, 106, 263.
1297.
(5) Enders, E.; Kuhle, E.: Malz, H. Belg. Patent 610 175, 1960; Chem.
Abstr 1962, 57, 13694.
Scheme I
S
(C,H,CH,),NC /I SCC I c13cscc12scI
9 10
/i\
s SCCI,
8
should be noted that isocyanides are isoelectronic with CS)
and, according to very recent reports,6 1 and S2C12 add to
certain thiocarbonyl compounds with comparable ease.
It should be noted that there are no obvious alternative
synthetic pathways leading to 2. While the perfluoro
analogue 3 is accessible by potassium fluoride catalyzed
dimerization of thiocarbonyl fluoride8 and by treatment
of thiocarbonyl chloride fluoride with mercury(I1) tri-
fluor~methanethiolate,~ the photochemical dimerization
of thiophosgene leads to 2,2,4,4-tetrachloro-1,3-dithietane
(4),O and there is no reaction between thiophosgene and
s
CFBSCX I1 Cl,C<;>CCl,
-
4
3, X - F
5, X=CI
KF. Unlike Hg(SCF,),, mercury(I1) trichloromethane-
thiolate, Hg(SCC13),, is unknown because of the inherent
instability of trichloromethanethio1.2 Likewise, the re-
ported synthesis of trifluoromethyl chlorodithioformate
(5)13 does not lend itself to any modification leading to 2.
We can now report that reaction 3 does in fact occur
readily and in good yield.14 Trichloromethyl chlorodi-
thioformate (2) is a distillable liquid once preliminary silica
gel chromatography has been carried out (distillation of
crude 2 only gave a small amount of 10) and can be stored
at room temperature for several months. It could be
characterized spectroscopically and by derivatization.
As a minor byproduct some pale-yellow crystals could
be isolated. According to our preliminary data this yellow
solid is most likely the new thiirane 6, which probably is
formed according to (4) in analogy with the formation of
2,2,3,3-tetrachlorothiirane.15 This reaction mechanism is
also supported by recent results of our work on reactions
between CS and thiocarbonyl compounds. The 1,4-dit-
hiane structure 7 is also consistent with the analytical and
spectral data, but according to the mass spectrum 6 is the
most probable structure.
(6) We are very grateful to a referee who made us aware of these
reports (Barany et al. J . Org. Chem. 1983,48,4750; J. Org. Chem. 1984,
49, 1043).
(7) Previously the dimerization product 4 of thiophosgene was erro-
neously believed to possess structure 2 (Beilsteins Handbuch der Or-
ganischen Chemie, Val. 3,4th ed.; Springer-Verlag: Berlin, 1921; p 215).
(8) Haas, A.; Klug, W. Chem. Ber. 1968, 101, 2609.
(9) Haas, A.; Klug, W.; Marsmann, H. Chern. Ber. 1972, 105, 820.
(10) Schonberg, A.; Stephensen, A. Ber. 1933, 66, 567.
(11) Moltzen, E. K.; Senning, A., unpublished results.
(12) Senning, A. Chem. Reu. 1965, 65, 385.
(13) Haas, A,; Yazdanbakhsch, M. Chem. Ber. 1976,109, 1976.
(14) No effort was made to optimize the yields of the reported reac-
tions, but it is important to note the absence of significant amounts of
byproducts.
(151 Seyferth, D.; Tronich, W. J . Am. Chem. SOC. 1969, 91, 2138.
0022-3263/84/1949-3854$01.50/0 0 1984 American Chemical Society
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2420 J. Org. Chem. 1983,48, 2420-2422
2 Hz), 1.18 (d, 3 H, J =7 Hz); mass spectrum, ml e 110 (M).
Acknowledgment. We are grateful to Professor Sam-
uel Danishefsky, Yale University, for encouragement and
support through Grant No. AI 16943-03.
Registry No. 1, 85736-25-0; 2, 43124-56-7; 3, 15331-05-2;
(+)-pulegone, 89-82-7.
Desiccant Efficiency in Solvent and Reagent
Drying. 7. Alcohols
David R. Burfield and Roger H. Smithers*
Department of Chemistry, University of Malaya,
Kuala Lumpur 22-11, West Malaysia
Received October 22, 1982
For many of their applications in synthesis, the lower
monohydric alcohols are required to be scrupulously dry,
and in contrast to alcohols containing six C atoms or more,
whose desiccation does not appear difficult, alcohols
containing one to four C atoms have long been recognized
as posing a formidable drying problem. In the case of
ethanol for instance, numerous synthetic procedures con-
tain statements such as traces of water depress the yield
considerably? a practical result of which is that samples
dried with CaO, for example (containing up to 5000 ppm
of water), are often completely una~ceptable.~ There is
also no doubt that for this group, as with other cases,l*
the problem of dedlccant selection has been compounded
by a lack of reliable quantitative data. As an illustration,
when discussing the efficiency of magnesium or alkyl
phthalateNa as desiccants, many auth~ri ti es~~ continue
to quote figures for water contents which were obtained
in the original investigations1 and which must now be
viewed with some scepticism. In the light of this, wenow
(1) Part 1: Burfield, D. R.; Lee, K. H.; Smithers, R. H. J. Org. Chem.
1977, 42, 3060.
(2) Part 2: Burfield, D. R., Gan, G. H.; Smithera, R. H. J. Appl. Chem.
Biotechnol. 1978, 28, 23.
(3) Part 3: Burfield, D. R.; Smithers, R. H. J. Org. Chem. 1978,43,
3966.
(4) Part 4: Burfield, D. R.; Smithers, R. H. J. Chem. Technol. Bio-
technol. 1980, 30, 491.
(5) Part 5: Burfield, D. R.; Smithers, R. H.; Tan, A. S. C. J. Org.
Chem. 1981,46,629.
(6) Part 6 Burfield, D. R.; Smithers, R. H. J. Chem. Educ. 1982,59,
703.
(7) The useof K2C03 as adesiccant is often considered adequate in
these cases. Seefor example: (a) Calzada, J . G.; Hooz, J. Org. Synth.
1974,54,63. (b) Paul, R.; RiobC, 0; Maumy, M. Ibid. 1976,55, 62. (c)
Vogel, A. I. Vogels Textbook of Practical Organic Chemistry; Long-
mans: London, 1978; p 270. See also, however: Crandall, J . K.; Rojas,
A. C. Org. Synth. 1976,55, 1.
(8) See: Weiner, N. Organic Syntheses; Wiley: New York, 1943;
Collect. Vol. 11, p 279. Also relevant are the following quotations. (a)
Yields are poor if the alcohol is not completely dehydrated; Lycan, W.
H.; Puntambeker, S. V.; Marvel, C. S. Organic Syntheses; Wiley: New
York, 1943; Collect. Vol. 11, p 319. (b) Moisturein the reagents affects
the yield seriously: Dox, A. W. Organic Syntheses; Wiley: New York,
1941; Collect, Vol. I, p 5. (c) The useof 98% alcohol results in alowering
of yield by 1/3 : Kaufmann, W. E.; Dreger, E. E. Ibid., p 258. (d) The
quality of absolute ethanol used has avery marked effect upon the yield:
Adams, R.; Kamm, R. M. Ibid., p 250.
(9) Thus, Alcohol dried over limegives very low yields: Ford, S. G.;
Marvel, C. S. Organic Syntheses; Wiley: New York, 1943; Collect. Vol.
11, p 373. Ethanol dried only by a limeprocess gives a low yield:
Adkins, H.; Gillespie, R. H. Zbid., 1955; Collect. Vol. 111, p 672.
(IO) For the useof magnesiumsee: Lund, H; Bjerrum, J . Ber. Dtsch.
Chem. Ges. 1931, 64, 210. For the useof asodium-alkyl ester combi-
nation see: (a) Smith, E. L. J. Chem. SOC. 1927, 1288. (b) Manske, R.
H. J. Am. Chem. SOC. 1931,53, 1106.
report the results of a study of desiccant efficiency for this
important group.
General Indications.7cJ1 Both chemical and absorp-
tive-type desiccants have been proposed for drying alco-
hols, and these i nc l ~de~~J ~* ~~ Al, BaO, CaO, Mg, Na, and
K2C03, while molecular sieves of Type 3A and 4A have
been recommended for further drying.*lb CaH2 is also
widely quoted,lld although some sources11a advise caution
in its use with the lower alcohols.
While bearing in mind the well-known hygroscopic and
hydrophilic properties of these compounds, the experi-
ments reported below were not carried out by using any
special techniques to obviate the entry of the atmosphere
into drying systems other than those routinely used by the
bench chemist.
Methanol. As one authority has observed,ld water is
the dominant impurity in this solvent, and, unless ex-
t raordi nary care is exercised, this content increases each
time MeOH is handled. I t is therfore quite remarkable
that a survey of the literature on the drying of EtOH and
MeOH points up a curious dichotomy: while references
to EtOH8vg are characterized by numerous strictures as to
the importance of achieving perfectly dry solvent, in con-
trast, MeOH is treated in a rather offhand manner, even
though many of its applications parallel those of ita higher
homologue. All MeOH used must be anhydrous is a
typical comment,12 although information on how to realize
this is lacking. The cause may lie in the belief that frac-
tionation alone gives a solvent of adequate dryness, al-
though the water content is still an admitted 1000
ppm.7cJ1d Where drying methods have been indicated, the
use of Mg seems most often advised.J 3
The results shown in Table I certainly suggest that, on
the whole, MeOH is more difficult to dry than its higher
homologue. These figures require little comment, but it
is worth highlighting the poor performance of 3A molecular
sieve powder for MeOH in comparison with other alcohols.
This is almost certainly an effect of molecular size and
nonselective adsorption on the large surface area which
occurs ext remel y rapi dl y with this desiccant.14 On ac-
count of ita small size, MeOH is able to compete with water
for entry into the sieve pore. Similar reasons also explain
the relative ineffectiveness of the 4A and 5A bead forms
of molecular sieve. On the other hand, the 3A bead form
constitutes a useful desiccant, whose success is presumably
due to a much slower rate of absorption which occurs with
greater selectivity. I t is also worth noting that a combi-
nation of methods is often the most effective strategy: a
1-L sample of MeOH distilled from Mg/12 onto 10% w/v
3A molecular sieve beads and then allowed to stand 48 h
had residual water content of only 12 ppm. Finally, the
unimpressive results obtained with BaO and CaO tend to
support an earlier assessment of these agents as tedious
and wa~teful.~
Ethanol. As stated above, references to the use of
ethanol as a nucleophile,16 as a solvent for Bouveault-Blanc
(11) See: (a) Rickert, H.; Schwartz, H. In Methoden der Organischen
Chemie(Houben-Weyl); Mueller, E., Georg Thieme Verlag: Stuttgart,
1968; Band I/2, p 873. (b) Loewenthal, H. J. E. Guidefor the Perplexed
Organic Experimentalist; Heyden: London, 1980; p 50. (c) Drying in
the Laboratory; E. Merck Co.: Darmstadt. (d) Riddick, J . A.; Bunger,
W. B. Organic Solvents, 3rd ed.; Wiley-Interscience: New York, 1970
pp 638465.
(12) Helferich, B.; Schafer, W. Organic Syntheses; Wiley: New York,
1941; Collect. Vol. I, p 365.
(13) (a) Murray, J. I. Organic Syntheses; Wiley: New York, 1963;
Collect. Vol. IV. p 744. (b) Baumgarten, H. E.; Petersen, J. M. Ibid., 1973;
Collect. Vol. V, p 912.
(14) See ref 6
(15) SeeRef l l d, p 642.
0022-3263/83/1948-2420$01.50/0 0 1983 American Chemical Society
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Notes J. Org. Chem., Vol. 48, No. 14, 1983 2421
Table 1. Desiccant Efficiency in Dryingaib of Some Common Lower AlcoholsC
desiccant
residual water content, ppm
methanold ethanol e !&butanolf tert-butyl alcoholg
3A sieves (bead) 95 99 645 (9)h 428 (160)'
3A sieves (powder)] 94 0 18 14 13
Mg/I,
97 (12)' 50 (53)m
Nap
Na/dicarboxylic acid esterQ 92" 36"
4A sieves (bead) 44 0 401 4 06
5A sieves (bead) 475 875
CaC, 490 333 (199)' 409 430" (662)O
BaO 1000 s
Ca 1000 s 86 0
KZCO, s s 750
CaO s s 770
ion exchange resin s 640
Desiccant
loading 5% w/v with a drying period of 24 h unless specified otherwise. Initial water content 1010 ppm. e Initial water
content 1500 ppm. f Initial water content 1000 ppm. g Initial water content 1030 ppm. 96-h drying period. 168-h
drying period. I Analysis was performed after settling of desiccant, 3-6 h. Weight of magnesium in accord with general
practice, i.e., 0.5% w/v. See text. Weight of magnesium 2% w/v. " Distilled sample. O Initial water content 1670
ppm, distilled sample. P Weight of sodium 3% w/v. See ref 32. Ratio of sodium to 2-butyl succinate for 2-BuOH and
to diethyl phthalate for ethanol in accord with general practice (see ref 7c), i.e.; Na, 0.3 mol L-'; dicarboxylic acid ester,
0.14 mol L-l. I Stirred sample. No apparent drying.
125 99 17" 406 ( 2 0 ) O
1800" 2400" 406 (10)'
C dZ
KOH powder s
a Static drying modes unless specified otherwise. Water content assayed by the Karl Fischer method.
or oxime type reducti0m,1~or as a suitable medium for the
preparation of metal ethoxides"' invariably include warn-
ings as to the lowered yields which are obtained through
the use of inadequately dried solvent. Desiccants most
frequently prescribed16-18 include Ca0,lB Mg," Na,2l or Na
in conjuction with a high-boiling ethyl ester such as the
phthalic acid derivative. The results (Table I) show that
the desiccant par excellence both from the viewpoint of
residual water levels and convenience is 3A molecular sieve
powder.22 Sieves of larger pore size are again seen to be
inappropriate. Of the more traditional siccatives, Mg and
CaH2 are both efficaceous while the performance of the
alkaline earth oxides was once more disappointing. The
poor result with sodium is not unexpected and is attrib-
utable to the equilibrium shown between alkoxide and
NaOH +ROH H20 +RONa
hydroxide. On the other hand, the ploy of refluxing the
solution obtained after sodium treatment with a high-
boiling ethyl ester works well, because saponification of
the ester irreversibly removes hydroxide ion.
(16) See for example: (a) Croxall, W. J.; Fegley, M. F.; Schneider, H.
J. 'Organic Syntheses"; Wiley: New York, 1963; Collect. Vol. IV, p 98.
(b) Moffett, R. B. Ibid., p 427. (c) Ford-Moore, A. H.; Perry, B. J. Ibid.,
p 955. See also ref 8b.
(17) See: Maneke, R. H. "Organic Syntheeee"; Wiler New York, 1943;
Collect. Vol. 11, p 154. See also ref 8a and 9.
(18) See for example: (a) Holmes, H. L.; Trevoy, L. W. "Organic
Syntheses"; Wiiey: New York, 1955, Collect. Vol. 111,p 300. (b) Meyer,
K.; Bloch, H. S. Ibid., p 637. (c) Zuidema, G. D.; Van Tamelen, E.; Van
Zyl, G. Ibid., 1963; Collect. Vol. IV, p 10. (c) Daeniker, H. U.; Grob, C.
A. Ibid., 1973; Collect. Vol. V, p 989. See also ref 8 and 9.
(19) In addition see: (a) Kimball, R. H.; Jeffereson, G. D.; Pike, A. B.
"Organic Syntheses"; Wiley New York, 1943; Collect. Vol. 11, p 284. (b)
Fuson, R. C.; Wojcik, B. H. Ibid., p 260.
(20) In addition see: Lund, H.; Voigt, A. "Organic Syntheses"; Wiley
New York, 1943; Collect. Vol. 11,p 694. See also ref 8 and 9.
(21) In addition see: (a) Marvel, C. S.; Hager, F. D. "Organic
Syntheses"; Wiley: New York, 1941; Collect. Vol. I, p 248. (b) Levene,
P. A.; Meyer, G. M. Ibid., 1943; Collect. Vol. 11, p 288. See also ref 8.
(22) Removal of the laat traces of thie desiccant froma dried solvent
probably necesaitates distillation or filtration. However, if left to stand
for perioda of several daye, the desiccant usually from a compacted mass
at the bottomof the container, leaving a completely clear solvent layer.
In many procedures, the traces of powder remaining in suspension are
probably of little consequence, and dried material can bedispensed by
simple decantation.
Butanols. With some notable exce~tions,2~ perfectly
dry 2-butanol is probably less widely required than the
other alcohols in this study but is included for purposes
of comparison. In contrast, completely anhydrous tert-
butyl alcohol is always required for its most common use
in the preparation of the potassium derivative. An early
source24 observes that "it is difficult to prepare t-BuOH
free from water". Later authors recommend tackling
drying by refluxing over Ca0,26a*b Na, or K25"*d or more
recently by distillation from CaHz6 or 3A sieves.27 The
results for both butanols on using most of the absorptive
type siccatives under static conditions (Table I) indicate
a very much slower rate of water absorption than with
methanol or ethanol. It seems likely that this is due to the
increased viscosity of the C-4 alcohols compared with their
lower homologues, and thus the use of 3A sieves in the
powder form (which operates as a dispersion) is able to
circumvent this difficulty and again appears to be the
desiccant of choice.=Interestingly, and in striking contrast
to 2-butanol, the use of Na alone does efficiently remove
water from tert-butyl alcohol, and this must mean that the
equilibrium shown above lies predominantly to the left,
presumably as a consequence of the greater disparity be-
tween the acidities of the two protonated species in this
case.28 I t should be emphasized, however, that sodium
(23) The "alcohol method" for the standardization of alkyllithium
solutions requires perfectly dry 2-butanol. See: Watson, S. C.; Eastham,
J . F. J . Organomet. Chem. 1967, 165.
(24) Norrie, J. F.; Olmated, A. "Organic Syntheses"; Wiley: NewYork,
1941; Collect. Vol. I, p 144.
(25) (a) Wayne, W.; Adkins, H. "Organic Syntheses"; Wiley: New
York. 1955: Collect. Vol. 111.D 48. (b) Hauser. C. R.: Hudson. B. E.:
AbrakoviGh, B.; Shivers, J. C.-Ibid., p 142. (c) Spassow, A. Ibid.; p 145:
(d) McElvain, 5. M.; Kundiger, D. Ibid., p 506. (e) Johnson, W. S.;
Schneider, W. P. Ibid., 1963; Collect. Vol. IV, p 134. (f) Raha, C. Ibid.,
p 264.
(26) (a) Homing, E. C.; Fmelli, A. F. 'Organic Syntheses"; Wiley: New
York, 1963; Collect. Vol. IV, p 461. (b) Mikol, G. J.; Russell, G. A. Ibid.,
1973; Collect. Vol. V, p 937. (c) Ireland, R. E.; Chaykovsky, M. Ibid., p
171. (d) Crowther, G. P.; Kaiser, E. M.; Woodruff, R. A.; Hauser, C. R.
Org. Synth. 1971,51, 96. (e) Crockett, G.; Koch, T. H. Ibid., 1979, 59,
132.
(27) Itoh, M.; Hagiwara, D.; Kamiya, T. Org. Synth. 1979, 59, 95.
(28) pK, values for EtOH and t-BuOH relative to H20 havebeen
reported as -1.94 and -2.6, respectively. See: (a) Lee, D. G.; Cameron,
R. J. Am. Chem. SOC. 1971,93,4724. (b) Deno, N. C.; Turner, J . 0. J.
Org. Chem. 1966,31, 1969.
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2422 J. Org. Chem., Vol. 48, No. 14, 1983 Notes
Table 111. Relative Difficulty in Dryinga of Some Diolsb
residual residual
water water
content, content,
d io1 diol
Table 11. Desiccant Efficiency in Dryinga*b of
1, 2-Ethanediolc
residual water content, ppm desiccant
3A sieves (bead)
3A sieves (powder)
4A sieves (powder)
CaC,
BaO
CaO
distillation
benzene azeotrope
Mg
A1
1900 (1200,d 540e)
MgSO,
B203
360f'
1900 (2070)d
3600
a Static drying modes unless specified otherwise.
Water content assayed by the Karl Fischer method.
Dessicant loading 5% w/v with a drying period of 72 h
unless s ecified otherwise; initial water content 2700
ppm. 168-h drying period. e 600-h drying period.
8 Distilled sample, cqntamination by acetylene.
67 "C (0.1 mmHg). ' Sample contaminated by - 0.02%
v/v benzene.
followed by treatment with Mg/I,.
drying.
does in fact react with tert-butyl alcohol under reflux at
an appreciable rate, and, in our opinion, the quite severe
solvent losses which can result constitute a drawback se-
rious enough to discourage ita use under these conditions.
1,2-Ethanediol. Although the main thrust of this work
was concerned with the lower alcohols, it was thought of
interest to investigate 1,2-ethanediol as a comparison. This
material does in fact possess a high solvation power for
particular ions such as fluoride, and the use of dry diol is
prescribed for a general synthesis of primary alkyl fluorides
which utilizes this solvent property.2e I t might be an-
ticipated that the effective drying of ethanediol would
prove more problematical than the simple monohydric
alcohols, and, indeed, the powerfully hydrophilic nature
of this material is indicated by a reference in the patent
1iterature3O where the diol itself is recommended as a
dessicant for acetonitrile! There appears to be a paucity
of methods used for desiccation, due no doubt to the fact
that the use of many effective agents such as CaHz is ruled
out because of their reaction with this solvent. Most in-
vestigators have advocated simple di ~ti l l ati on,~~ and, in
fact, the results show this to be fairly efficaceous (Table
11). With sieves, trends similar to those noted earlier are
again observed; thus, due to reasons of slowness of ab-
sorption and inappropriate pore size respectively, the 3A
bead form and 4A powder form are ineffective, while 3A
powder once more demonstrates attributes of powerful
desiccant action and simple application. Other noteworthy
results were achieved with the use of the benzene azeotrope
and with Mg. It would appear that a residual water level
of - 70 ppm represents the lower limit for the desiccation
of thi s material under practical conditions.
Other Diols. Finally, i t was thought of i nterest to
compare the difficulty of drying 1,2-ethanediol with some
selected examples of other diols where factors of a changed
Analysis was performed after settling of desiccant, - 6 h.
Bp 66-
Sample size 1 L; benzene azeotroping
Little apparent
(29) Vogel, A. I.; Leicester, J.; Macey, W. A. T. 'Organic Syntheses";
Wilev: New York. 1963: Collect Vol. IV. D 525.
(36) Derdulla, H. J .; Sommer, M. Ger: (East) 90 136 (Cl. CO~C), May
20,1972; Appl. WP C07c/155952, J une 21,1971; Chem. Abstr. 1972, 77,
151525r.
(31) See for example: Dickinson, C. L.; Melby, L. R. 'Organic
Syntheses"; Wiley: New York, 1963; Collect, Vol. IV, p 276. Seealso ref
28.
(32) Monson, R. S. "Advanced Organic Synthesis"; Academic Press:
New York, 1971; p 141.
140 HO- OH' 220
HC
Dr ing agent was 3A MS powder at a loading of 5%
w/v. i: Analysis performed by the Karl Fischer method
after settling of desiccant, 3-6 h. Initial water content
3600 ppm. Initial water content 4000 ppm. e Initial
water content 3700 ppm. f Initial water content 4200
PPm.
positional relationship between the two hydroxyl groups
and an increased hydrophobic content might give rise to
variations in residual water content. The results (Tabl e
111) suggest that 1,2-diols are easier to dry than comparable
diols where the hydroxyl groups are situated more remotely
(cf. 1,2-ethanediol and 1,6butanediol), and this seems
reasonable from the viewpoint of preferred intramolecular
interactions i n 1,2-diols rather than the intermolecular
alternatives involving water which are presumably more
favorable in other cases. I ncreasing the nonhydrophilic
character by the inclusion of more carbon atoms results
in an understandably easier drying process (cf. 1,2-
ethanediol and 2,3-butanediol; l,4-butanediol and 1,5-
pentanediol). Extension to higher simple diols was pre-
cluded by the limit of their liquid ranges.
Experimental Section
Details of the source, activation, and handling of most desic-
cants have already been described>* Materials such as Ci Hz and
CaCz obtained in an aggregate form were crushed rapidly in a
mortar and with a hammer, respectively, immediately prior to
use. Where drying methods call for procedures other than simple
static interaction, e.g., Mg/Iz, the customary directives were
fol l ~wed.'~
Water contents were determined throughout by the standard
Karl Fischer method with a potentiometrically determined end
point.
Alcohols. Chemically pure or AFt grades of material were used
without further purification. In the normal procedure the water
content of a freshly opened Winchester bottle was first determined
followed by wetting or by drying and wetting to obtain required
water concentrations.
Dryi ng Experiments. Investigations were carried out on
100-ml samples except where stated otherwise in the tables.
Reflux and distillation were carried out under dry nitrogen or
argon, and material collected from distillations for analysis was
usually a middle cut of 60-75-m1. volume. Where powdered
molecular sieves were used as the desiccant, charging of the
material into a flask of suitable dimensions was followed by
addition of solvent, stoppering of the flask, and vigorous agitation.
A clear upper layer suitable for sampling was generally obtained
in 3-6 h of standing.
Acknowledgment. We thank the Department of
Chemistry and University of Malaya for thei r support of
thi s work under Vote No. F124/80.
Registry No. Mg, 7439-95-4; Iz, 7553-56-2; CaHz, 7789-78-8;
Na, 7440-23-5; CaC2, 75-20-7; BaO, 1304-28-5; Ca, 7440-70-2;
K2C03, 584-08-7; CaO, 1305-78-8; KOH, 1310-58-3; MgS04,
7487-88-9; B203, 1303-86-2; Al, 7429-90-5; methanol, 67-56-1;
ethanol, 64-17-5; 2-butanol, 78-92-2; tert-butyl alcohol, 75-65-0;
1,2-ethanediol, 107-21-1; 2,3-butanediol, 513-85-9; 1,4-butanediol,
110-63-4; 1,5-pentanediol, 111-29-5; di-2-butyl succinate, 626-31-3;
diethyl phthalate, 84-66-2.
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