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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

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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'

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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'

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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

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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

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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

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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.

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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

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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!