Ray
Tasks
1. Carboxylic acids to acyl chlorides O 1. OH 2.
Reactions
SOCL2
Notes O CL
2. Alcohols to alkyl halides
R-OH
O OH
SOCL2 (COCL)2
R-CL
O CL
Addition of Hydrides R Catalytic Hydrogenation
O R O
O1. LiAlH4 R C R H
2. H3O+
OH R C R H
H2, Raney Ni H
OH
Additions of 1 Amines (Imines)
O C
*non Aqueous favors imine
R'NH2
H+ C
R'
*Aqueous favors ketone and amine
Imine Product Derivatives
Ph-HN N
NH2NHPh/H+
N O
NH2OH/H+
OH
O
NH2NH-C-NH2/H+
NH2NH2/H+
O N H N NH2
NH2
Additions of 2 Amines (Enamines)
*follows ZAITSEV'S RULE
(R)2NH
H3O+
(R)2N
Ray
Tasks
Oxidation of Aldehydes to Carboxylic Acids: Silver Reagents O CH2OH H O Carboxylation of Grignard Reagents
X= halide
Reactions O Ag2O/THF/H2O R H R OH O CH2OH OH O O X
1. Mg / ether 2. CO2 / ether 3. H3O+
Notes O
*KMnO4 or *CrO3/H2SO4/H2O/acteone or *Na2Cr2O7/H2SO4/H2O
OR
1. Ag(NH3)2+ OH- (Tollen's Reagent) 2. H+
OH
1 MgX
2 and 3
Hydrolysis of Nitriles
CN
H3O+
heat
O OH O OO
R Ester Formation from Acid Chlorides R Amide Formation from Acid Chlorides O
CN
OHheat
R' OH
CL R O
R'
O CL O CL O CL NH3
O NH2 O
*1
R' NH2
O
N H
R'
!2
!3
R2' NH2
NR2'
Synthesis of Esters: Fischer Esterification R
O OH
1. R'-OH 2. H+ R
O O R'
Ray
Tasks
Esterication with Diazomethane O OH
Reactions
Notes
O CH2N2 OCH3
*SN2 *Great Yield
Direct Amide Synthesis
O OH
R' NH2
NHR'
Reduction of Carboxylic Acids H3C
O OH NH2 O O 1. LiAlH4/Et2O 2. H3O+ 1. LiAlH4/Et2O 2. H3O+ H3C
OH OH CH2NH2
NC
H2NH2C
*reacts with aldehydes, ketones, esters, carboxylic acids, and epoxides (with H3O+ or H2O) *BUT nitriles, amides, and N3 produce R-NH2 (with H2O)
R'
Diborane Reduction H3C NC O Decarboxylation: Hunsdiecker Reaction O O
OR"
R'CH2OH +
O
R"OH
*VERY SELECTIVE!
OH NH2
1. B2H6 / diglyme 2. H3O+
H3C NC O
OH NH2
*Carboxylics reacts faster with B2H6 than any other functional group
1. HgO or Ag2O or Pb(OAC)4 2. heat / Br2 / CCl4 OH O
lose
R Br
*converts Carboxylic acids into alkyl halides with 1 less carbon
R
Carboxylic Acid from Acid Chlorides R
OH
O Cl
H2O R
O OH
Anhydrides from Acid Chlorides R
O O Cl
R'
OR
O O
R'
Ray
Tasks
Cyclic Anhydrides O HO O OH
Reactions O ! O
Notes
*5,6 member rings are best
O Alpha Halogenation of Ketone
*X= Cl2 / I2 / Br2
X2 / CH3COOH
* NO FREAKING ALDEHYDES
*Most SUB ALKENE:MAJOR *Least SUB ALKENE:MINOR
Alpha Bromination of Carboxylic Acid: Hell Volhard Zelinksy
O OH
1. PBr3 / Br2 2. H2O
O OH Br
*carboxylics do not enolize under acidic or basic conditions
Aniline with Nitrous Acid (HNO2)
1. HNO3 / H2SO4
2. Zn, Fe, or Sn / HCl
NO2
NH2
N Cl or Br
3. NaNO2 / HCl
Act.
Act.
CuCl or CuBr
I
KI
NCL OH
H3 O+/!
1. HBF4 2. !
CuCN
CN
H3PO2
Ray
Tasks
Cyclic Anhydrides O O O Synthesis and Reactions of Anhydrides O R OH
Reactions O CH3OH O O
NaOH
Notes
OCH3 OH
O R O-
R Cl R
O O O 2x R
O R
*Friedel Crafts acylation: NO DEACTIVATING OR AMINO GROUPS
O R O R O R O R Synthesis and Reactions of Esters R O O O O O O
O R O R O R O R
H2O
OH O R O OH
R' OH
R
O OR'
AlCl3
NH3 or R'NH2 or R'2NH
R O R O NH3 OH R R" OH
1. R"MgX or R"Li 2. H3O+
+ R R"
O OH
O Cl
R'OH R'OH / H+
OH O-
+ R'OH
or
O
H2O H+ or OHR"MgX or R"Li
O OR'
1. DIBAH 2. H3O+
+ R'O-
R
1. LiAlH4 2. H3O+
R"
O R OR''
R"OH / H+ xs
O R
NH3 or R''NH2 or R''2NH
RCH2OH + R'OH
O R H
*5,6 membered ring
NH2
Cyclic Esters O O HO OH H+ O
Ray
Tasks
Cyclic Anhydrides 1. O O OH OH
Reactions O ! >100C O ! ~800C O O O O O CH3OH O O NR2 O NHR O NH2
(3) Br2 / NaOH / H2O
(4) POCl3 or SOCl2 or P2O5
Notes
1. maleic anhydride
2.
2x CH3CO2H
3.
OCH3 OH
Synthesis and Reactions of Amides
*rxn 1 reacts ONLY WITH AMIDES
R
3 2 1
R R R
NR2 NHR NH2
(2) H2O / Heat H+ or OH(1) 1. LiAlH4 2. H2O or H3O+
R
1
*rxn 2 nucleophilic acyl substitution and get AMINE PRODUCT
R C N
*rxn 3 get AMINE PRODUCT
*rxn 4 reacts ALL 1" AMIDES and get NITRILE PRODUCT
ACID PRODUCT:
BASE PRODUCT:
NH4 Synthesis and Reactions of Nitriles
OR
OH
NH2
O1. LiAlH4 2. H2O or H3O+
or
R CH2NH2
LiAlH4
H2 / Pt or Ni
R CH2NH2
H2O / Heat H+ or -OH
ACID PRODUCT: BASE PRODUCT:
NH4
OH
OR
O-
NH3
*REACTS ONLY WITH METHYL KETONES
Haloform Reaction R
CH3
X2 (xs) NaOH (xs)
O R O+ HCX3
Ray
Tasks
Alkylation of Ketones, Esters, and Nitriles: LDA
(lithium diisopropyl amide)
Reactions O H3C CH3
1.
Notes O H3CH2CH2C
2.
1. LDA 2. CH3CH2Br
CH3
OH2C C O O
1. LDA 2. CH3Br
O O
CH3CH2CN
1. LDA 2. CH3Br
CN H3C
O
Ha
O CH3
Hb
1. LDA 2. CH3Br
Ha MAJOR (less bulky)
CH3
+
O
Hb Minor (more bulky)
CH3 CH3
O O Hydrolysis of Nitriles (extended) CHO
1. LDA 2. CH3Br
CN
O O CHO
CN
R CN
OHH2O
R
O
NH2
OHH2O
R
O
O-
*Basic conditions: Carboxolate Anion watch out for dimerization.
R CN
H+ (non-aqueous)
H+ (non-aqueous)
NH2
OH
*Acidic conditions: must be non-aqueous. nitrile group unaffected if H3O+ is utilized.
Ray
Tasks
Electrophilic Aromatic Substitution of Aniline NH2 1.
Reactions NH2 Br2 / H2O Br Br
Notes
2. NO AMINO NOR DEACTIVATING 3. EXPLODE !
Br NH2 2. O Cl AlCl3 NH2 3. Add Groups to Anilines O Cl NH O Cl AlCl3
-OH
NO F.C.
HNO3 / H2SO4
BOOM!
O NH /!
NH2
O Br2 / FeBr3 NH2
O NH
-OH
NH2 /! Br
Br Hofmann Elimination NH2
1. CH3I (xs) 2. Ag2O / H2O / !
(MAJOR)
* Has to make 3 AMINE and serves as a LG! *Least
+
(minor)
sub alkene is MAJOR
*Most sub Alkene is minor
Formation and Reduction of Azides
Br 1.
1. NaN3 2. LiAlH4 3. H2O
NH2
*Forms 1 amines only
N3
2/3
Ray
Tasks
Hofmann Rearrangement R O
Reactions
Notes
X2 / H2O / NaOH NH2
R NH2
O NH2
X2 / H2O / NaOH O NH2
lose
NH2
Curtius Rearrangement
O Cl 1. NaN3 2. H2O / !
NH2
GOOD LUCK ON CH. 22 REACTIONS!
