Reagent
Function
Notes
-OH
Good Nuc, Strong Base
Converts R-L to R-OH for 1
and activated 2 R-L
SN2 conditions, normal 2 R-L leads to E2
(use synth. eq. acetate)
-OR
Good Nuc, Strong Base
Converts R-L to R-OR for 1
and activated 2 R-L
SN2 conditions, normal 2 R-L leads to
E2. Known as Williamson Ether
Synthesis
CH3CO2
Fair Nuc, Weak Base
Is a synth. eq. for OH
(unmasked with KOH/H2O)
SN2 conditions, will work fine for any 1
or 2 R-L
Na (also Na)
Sodium metal acts as a base,
removing H+ from ROH to
create RO (alkoxide)
Harsh conditions that require p/p alcohol
as the solvent (the CA of RO)
K2CO3
Weak base used to
deprotonate (remove H+) from
phenols
Will not work for normal alcohols, only
phenols
H2SO4
Strong acid which can
protonate alcohols, allowing
SN1 ether formation
The CB of H2SO4 is not a Nuc or a
strong base
RCO2-
Fair Nuc, Weak Base (E2
competition minimized)
SN2 conditions, will work well for 1 and
any/all 2 R-L
HBr, HI
Strong acids which convert OH
into X (Br or I)
Can be used on 1 (SN2), or 2 and 3
(both SN1) alcohols
HCl
Strong acid which converts OH
into Cl
Can be used only on 3 alcohols. Must
add ZnCl2 for 1 or 2 ROH
SOCl2
Converts OH into Cl
PBr3
Converts OH into Br
All three work well for 1 and 2 alcohol
conversion. If 3 ROH, H-X is the best
reagent.
PI3
Converts OH into I
Converts a leaving group into
an NH2. This reagent is a
synthetic equivalent for NH3,
used to make 1 amines.
Known as the Gabriel Synthesis. Avoids
the problem of multiple alkylations.
Reagent
Function
Notes
LiAlH4
Gives an H which replaces a
leaving group with H
Very reactive, cannot be used around
water or alcohols
NaBH4
Gives an H which replaces a
leaving group with H
Less reactive, compatible with water or
alcohols
-CN
Fair nucleophile, weak base
SN2 reagent, works well with both 1 and
2 R-L
-C=CH
Acetylide
Good nucleophile, strong base
SN2 reagent, works with 1 only, if 2, E2
is the major product
NaNH2 or -NH2
Very strong base
Can remove H from R--C=C--H
SR or Ph3P
Fair nucleophiles, weak bases
SN2 reagents, works well with both 1
and 2 R-L
HBr or HI
Strong acids that cleave ethers
1 (SN2) and 2 & 3 (SN1)
-OH or -OR
Strong bases, Good Nuc
Lead to SN2 when 1 or 2 (aprotic); but
E2 when 2 (p/p solvent) or 3
(regardless of solvent)
t-BuO- or LDA
Sterically hindered base
Poor Nuc, leads to E2 for 1, 2, 3
(Hofmann product)
-OH, or NaNH2
Very strong basic conditions
Used to prepare alkynes (E2 twice)
H2SO4, or H3PO4,
Dehydration reaction
E1 mechanism (Zaitsev product), Watch
out for rearrangements
Na2Cr2O7
K2Cr2O7 in H2SO4
CrO3
1 ROH --> carboxylic acid
2 ROH --> ketone
Strong Oxidizing Agent
1 ROH --> aldehyde
2 ROH --> ketone
Sensitive Oxidizing Agent
H2CrO4 (Jones Reagent)
KMnO4 (often hot with H+ or OH-)
Reagent
Function
Notes
Ag2O
aldehyde-->carboxylic acid
Incompetent Oxidizing Agent
NaOCl
Only does 2 ROH --> ketone
Environmentally friendly Oxidizing Agent
HF, HCl, HBr, or HI
Acids that add H-X to alkenes
(or alkynes)
Markovnikov addition via carbocation, so
watch out for rearrangements!
H2O with H2SO4
Adds H2O to alkenes to yield
alcohols (hydration)
Markovnikov addition via carbocation, so
watch out for rearrangements!
Cl2 or Br2
Halogens that add X2 to
alkenes (or alkynes)
Use inert solvents; Follows the
borderline SN2 mechanism, results in
anti addition
Br2/H2O or Cl2/H2O
Adds 1 X and 1 OH to a C=C
(produces a product called a
halohydrin)
Anti addition (inversion) occurs through
the bromonium (or chloronium) ion, the
water attacks 3>2>1 (borderline SN2)
1)
Adds H and OH to a C=C
Markovnikov addition, with NO
rearrangements
H2O, H2SO4, Hg2+(often
HgSO4 or HgO)
Adds H and OH to an alkyne-> results in the formation of a
ketone
Markovnikov addition, an enol initially is
formed, but spontaneously tautomerizes
to the keto form as the product
1)
2)
BH3, THF
H2O2, NaOH
Adds an H and OH to alkenes
or internal alkynes
Anti-Markovnikov addition, with syn
(same side) addition; watch out for enolketo tautomerization with the internal
alkynes
1)
disiamylborane
Adds H and OH to a terminal
alkyne --> results in the final
formation of an aldehyde
Anti-Markovnikov addition, the enol
forms first, then tautomerizes the keto
form (forms aldehyde)
Adds a CH2 (carbene) to a
C=C --> forms a cyclopropane
Adds with syn addition, which is
important when product is chiral
Ch2I2 with Zn(Cu) alloy
Adds a CH2 (carbene) to a
C=C --> forms a cyclopropane
Simmons-Smith reaction; adds with syn
addition
CHX3 with strong bases
Adds a CX2 (carbene) to a
C=C --> forms a cyclopropane
Adds with syn addition; make sure to
add CX2, NOT CH2
2)
Hg(O2CCH3)2,
H2O
2)
CH2N2
NaBH4, NaOH
H2O2, NaOH
Cu2+
---------->
or or hv
Reagent
Function
Notes
RCO3H or MCPBA
Adds the 3rd (extra) oxygen to
a C=C --> forms an epoxide
Adds with syn addition, which is
important when product is chiral
1)
OsO4
KMnO4
----------> or --------->
2)Na2SO3
H2O
NaOH
Adds 1 OH group to each
carbon of a C=C --> forms diol
Addition occurs with syn (same side)
addition
1) O3
-------->
2) (CH3)2S
Breaks a C=C, adds a =O to
each carbon, called ozonolysis
Understand the retrosynthetic technique
to know what alkene underwent
ozonolysis (turn the two C=O back into a
C=C)
H2
-------->
Pd, or Pt
Breaks a C=C, adds an H to
each carbon (will convert
alkynes to alkanes when >
moles of H2 are used)
Under normal conditions, H2 does not
add to C=C in a phenyl (aromatic) ring.
Addition is primarily syn
H2
-------->
Lindlar Catalyst
Adds only one H to each
carbon of a C=C (alkyne),
converting it to an cis-alkene
Addition is syn, giving a cis-alkene.
Without a Lindlar catalyst, the reaction
cannot stop at the alkene
HNO3 + H2SO4
(Nitration)
Substitutes -NO2 on aromatic
rings
No limitations; heat reaction or use more
vigorous conditions to get disubstituted
product
O
||
CH3CCl
------------>
pyridine
Protects amines (and alcohols)
Remove group with KOH/H2O
Br2 or Cl2 + Lewis Acid
(AlX3, FeX3)
(Halogenation)
Substitutes -Br or -Cl on
aromatic rings
Requires Lewis acid unless ring is
strongly activated (e.g. phenol and
aniline, in which case, beware of
disubstitution)
H2SO4
(Sulfonation)
Substitutes -SO3H on aromatic
rings (mainly para if already
substituted
Reaction is reversible, heat in the
presence of H2SO4 and H2O remove the
-SO3H group
Reagent
R-Cl
------->
AlCl3
Function
Notes
Substitutes an (-R) on an
aromatic ring
1.
Substitutes a
/
O=C
\
R
on an aromatic ring
1.
Converts NH2 to N2, which can
be replaced by nucleophile
N2 is a good leaving group and can be
replaced with a variety of reagents
Carbocation (usually
formed by alkyl chloride AlCl3 or alcohol losing
water when acid is added)
Product of alkylation is more
reactive than starting material, often
leading to disubstitution.
2.
Rings with moderately or
strongly deactivating groups will not
undergo alkylation
3.
Watch out for carbocation
rearrangements
Friedel-Crafts Alkylation
O
||
R--C--Cl
------------>
AlCl3
2.
Very sensitive to sterics, major
product is always para
Rings with moderately or
strongly deactivating groups will not
undergo alkylation
Acyl cation (usually
formed by acetyl chloride
+ AlCl3)
Friedel-Crafts Acylation
NaNO2/H+
Reagent
Function
Notes
Nucleophile + aromatic
halide (Nucleophilic
Aromatic Substitution:
Addition-Elimination)
Nucleophile replaces halide in
a 2-step process; Nuc attacks,
and then halide leaves
The ring must have an electron
withdrawing group o- or p- to the halide.
Leaving group ability:
F > Cl > Br > I
Very strong base (e.g.
NaNH2) or base and high
heat (NaOH, )
(Nucleophilic Aromatic
Substitution: EliminationAddition)
Eliminates H-X on an aromatic
ring, creating a reactive
benzyne intermediate which
then is attacked by anion
Results in 2 different products if the ring
is asymmetric because both carbons of
the intermediate alkyne will be attacked.
H2/metal catalyst or Metal
(Fe, Sn, SnCl2) + HCl
Converts NO2 --> NH2
Important synthetic step as a diazonium
ion precursor
Reagent
Function
Notes
Clemmensen: Zn(Hg) +
HCl or
Wolf-Kishner: NH2NH2 +
KOH, or H2/metal
catalyst
Converts C=O --> CH2
H2/metal catalyst will work only if the
C=O is attached directly to the aromatic
ring
1)KMnO4, NaOH,
2) H3O+
Converts an R on an aromatic
ring --> CO2H
Reaction will not work if the substituent
C is quaternary (4)
[CN]
HCN ------------->
H2O
Adds a CN to the C and an H
to the O of a C=O, forming a
cyanohydrin
Only catalytic amounts of -CN are
needed; follows the basic mechanism
Mg or Li
Converts a R-X into a R-M;
which acts like a R-
X=Cl, Br, I; solvent must be aprotic,
usually ether or THF is used
NH4Cl
A weak acid (H+ donor) used to
protonate the Td of carbonyl
addition reactions
Avoids the E1 result for 3 alcohols
+ Ph3P--CR2
Ylide attacks C=O, resulting in
its eventual conversion to C=C
(P loves O!)
Witting reaction; BuLi is usually the base
used to make the ylide from its
phosphonium salt precursor
NR2
N attacks C=O, resulting in its
final conversion to C=N
1 amines --> imines
NH2OH --> oximes
2 amines --> enamines
H2/metal or NaBH3CN
C=N reacts more easily than
C=O, allowing conversion of
imines to amines
Either reagent can be used in the initial
reaction mixture, so the imine is never
isolated
LiAlH4
Reacts with all C=O
compounds from table 19.1
Has 4 H- available, converts C=O to CH2OH (except for ketones)
NaBH4
Reacts only with ketones and
higher on table 19.1
Has 4 H- available, can use in presence
of H2O, ROH, etc.
LiAlH(Ot-Bu)3
Converts acyl chlorides to
aldehydes at -78 C
Doesnt over-reduce to R-OH
Diisobutylaluminum
hydride (DIBAH)
Converts esters to aldehydes
at -78 C
Work up with H3O+ to complete reaction
Reagent
Function
Notes
2 mol Grignard + acyl
chloride, anhydride, or
ester
Reacts twice (cannot stop at
ketone) to yield alcohol.
Use NH4Cl as workup acid to avoid E1
elimination if 3 ROH
(R)2CuLi
Adds only 1 R group to an acyl
chloride, yielding a ketone.
Same reagent that gave conjugate
addition (Sec. 18.10)
Grignard + nitrile
Grignard adds to the nitrile
once, and the resulting imine is
hydrolyzed back to a ketone by
H3O+.
Hydrolysis is exact reverse of imine
formation (Fig. 18.3)
TsCl or MsCl
Converts -OH into -OTs or
-OMs, which are much better
leaving groups.
Reaction proceeds just like acyl
chlorides, but attack is at S
X2 w/ acid
a-halogenation of aldehydes or
ketones
reaction useful for adding only 1 halogen
x2 w/ base
a-halogenation of aldehydes or
ketones
Excess (>3 mol) of X2 will convert
methyl groups a to the carbonyl to
carboxylates (haloform/iodoform
reaction)
BuLi
Strongest base pKa = 50
Also acts like a nucleophile, so must
avoid using when C=O present
LDA, NaNH2, NaH
Very strong bases
pKa=35-38
Used to deprotonate Hs a to the C=O.
LDA is used most often because it is
totally non-nucleophilic (steric hindrance)
NaOR
NaOH
Moderate bases
pKa~16
Can be used to completely deprotonate
1,3-dicarbonyl compounds
Both reagents attack R-X as Nuc- in
typical Sn2 reactions. The final step
involves loss of CO2 gas via a 6-member
transition state (make & break bonds
around the ring). The enol which results
Reagent
Function
Notes
then tautomerizes to the more stable
keto form
1,3-dithiane attacks R-X in typical SN2
reactions or C=O carbonyl reactions.
The dithiane ring can be removed
(regenerating the C=O by adding Hg2+
in H2O
Carboxylates are oxidized at
the anode, resulting in a
fragmentation reaction where
CO2 is lost
Known as Kolbe electrolysis. Because a
high concentration of Ro forms at the
anode, the coupling reaction is
prevalent, resulting in a new R-R bond.
Replaces H with a Br at the
location of the most stable
radical.
Cl2 is too reactive (not selective enough)
to be synthetically useful.
Known as NBS. Replaces H
with a Br at the location of the
most stable radical.
NBS is especially useful when
attempting to brominate allylic systems
because it will not add (addition reaction)
to the C=C
Replaces X with H
Autoxidation - adds an OOH
group to the most stable
radical position
Not often synthetically useful, but
important in food spoilage and chemical
decomposition
Anti-markovnikov addition of
HBr to a C=C
HF, HCl, HI do NOT work well. Antimarkovnikov regio-chemistry is followed
because a more stable radical is formed
Each group adds to one side
of the C=C. The larger group
(boxed) adds first, the smaller
group adds second and goes
to the carbon which would
have the more stable radical.
Reagent
Function
Notes
Reduces benzene into 1,4butadiene (not conjugated), or
reduces the C=C of an a,Bunsaturated carbonyl, or
reduces an alkyne into a transalkene
Known as Birch reduction. Also useful in
alkylating a to the carbonyl in a,Bunsaturated carbonyl systems.
