Lecture 10 Aldehydes and Ketones: Nucleophilic Addition Reaction Kinds of Carbonyl Compounds

O O O

C C C R H R R' Carbonyl group Aldehyde Ketone

O O O

C C C R OH R X

Acyl group Carboxylic group Derivatives of carboxylic acids The acyl groups in these two families are bonded to substituents (‐Hand–R) that can’t stabilize a negative charge Aldehydes (RCHO) and therefore can’t act as leaving groups. Ketones (R2CO) Aldehydes and ketones behave similarly and undergo many of the same reactions.

The acyl groups in the carboxylic acids and Carboxylic acids (RCOOH) derivatives are bonded to substituents Acid chlorides (RCOCl) (oxygen, halogen, nitrogen) that can stabilize Acid anhydrides (RCOOCOR’) a negative charge and can serve as leaving groups Esters (RCOOR’) in substitution reactions. Amides (RCONH2) The chemistry of these compounds is therefore similar.

O O O CHO

HCH CH3CH ClCH2CH2CH2CH 4 3 2 1 Cyclohexanecarbaldehyde Methanal Ethanal 4‐Chlorobutanal (Formaldehyde) (Acetaldehyd) OH

OMe

2 4‐Hydroxy‐3‐methoxybenzenecarbaldehyde 5 3 1 H 7 6 4 4,6‐Dimethylheptanal O CHO Cl 5 3 1 2 3 O 4 7 5 1 6 4 2 C

CH3CH2 CH2CH3 O O

3‐Pentanone 2‐Pentanone 4‐Chloro‐6‐methyl‐3‐heptanone

2 1 O CH3 O O C O C C 1 C 2 CH3 CH3CH2 CH3 CH3

2‐butanone Benzophenone Acetophenone 2,2‐Dimethylcyclopentanone

O O

RC HC Formyl O O An acyl group CH CH CH CH 3 2 2 CH3CH2CH2CHO H O Butanal C O Benzoyl O

CH3C CH3CH2CCH3 CH3CH2COCH3 Acetyl 2‐Butanone O Structure of the Carbonyl Group

short strong polar

+   - C O C O or C O

electrophilic nucleophilic

Na2Cr2O7 KMnO4 OH O

CrO3, H2SO4, aceton, 0ºC CH3CHC C(CH2)3CH3 CH3CC C(CH2)3CH3

O OH O Cr(VI), H+ H2O Cr(VI) RCH2OH RCH RCOH RCOH

H

O O O PCC, CH2Cl2, CH3COONa O O CH2OH CH

Ozonolysis

Hydration of Terminal Alkyne

O HO H HOH, H+, Hg2+ RC CH C C RCCH3 R H

Markovnikov rule

Friedel‐Crafts Acylation O O 1. AlCl3 + 2. H , H2O + CH3CCl CCH3 + HCl

Oxidation of Aldehydes

Tollens’ Test O O

+ NH3, H2O R CH + Ag Ag + R COH Mirror Fehling’s Test O O NaOH, tartrate, H2O 2+ R CH + Cu Cu2O + R COH Brick‐red Baeyer‐Villiger Oxidation peroxycarboxylic acid

O O O CF3COOH C O CH CH C 9 CH 5 CH CH CH 3 3 2 3 dichloromethane 3 2 Ethyl acetate 2‐Butanone methyl < primary < phenyl ̴ secondary < tertiary

O O

C O C R 5 R` R 5 R` Reactions of Aldehydes and Ketones: Nucleophilic Addition

carbon O nucleophilic Reactions of Aldehydes and Ketones: C Nucleophilic Addition C R H electrophilic Acidic proton

Aldehyde or ketone Tetrahedrally hybridized intermediate

Nucleophilic Addition of Water: Hydration

H+ or OH- C O + HOH COH K HO

Geminal diol

Acetone Geminal diol Nucleophilic Addition of Alcohol: Hemiacetal and Acetal Formation

O OH

C + R'OH RCOR' R H H A hemiacetal

O OH

C + R'OH RCOR' RR R A hemiacetal

ROH = CH3OH, C2H5OH, … O OR' H+ C C + 2R'OH R OR' + H2O R R R

An acetal

ROH = CH3OH, C2H5OH, … Nucleophilic Addition of Amines: Imine Formation HH R H N N

H H

Ammonia Primary amine

Nucleophilic Addition of Amines: Imine Formation R' R'

RNH2 + O C RN C + H2O R'' R''

imine

CH CH 3 H+ 3

NH2 + O C N C + H2O

CH3 CH3 95%

Imine Derivatives of Aldehydes and Ketones

Cyanohydrin Formation O HO CN

+ Conc. HCl + Na CN- -NaCl

1‐Hydroxycyclohexanecarbonitryle

Slow addition of HCl to an excess of the strongly basic NaCN Nucleophilic Addition of Grignard Reagents: Alcohol Formation

H H + (CH3CH2)2O H , H2O + C O C OH CH3CH2CH2CH2MgBr CH3CH2CH2CH2 H H

CH CH3 3 (CH3CH2)2O H+, H O + C O 2 C OH CH3CH2CH2CH2MgBr CH3CH2CH2CH2

CH3 CH3

Addition of Hydride

O 1. LiAlH4, (CH3CH2)2O, -10°C + 2. H , H2O H OH