Organic Chemistry II

Aldehydes

Ketones

7th March, 2012

Chapter 16

Aldehydes Rod cells in the human eye. Inset: a model of 11& cis-retinal, an oxidized Ketones form of vitamin A.

The Carbonyl Group

In

this and several following chapters, we study the physical and chemical properties of classes of compounds containing the carbonyl group, C=O
aldehydes and ketones (Chapter 16) carboxylic acids (Chapter 17) acid halides, acid anhydrides, esters, amides (Chapter 18) enolate anions (Chapter 19)

The Carbonyl Group

the carbonyl group consists of one sigma bond formed by the overlap of sp2 hybrid orbitals and one pi bond formed by the overlap of parallel 2p orbitals

Structure
the functional group of an aldehyde is a carbonyl group bonded to a H atom and a carbon atom the functional group of a ketone is a carbonyl group bonded to two carbon atoms
O HCH Methanal (Formaldehyde) O CH3 CH Ethanal (Acetaldehyde) O CH3 CCH3 Propanone (Acetone)

Nomenclature
IUPAC

names:

the parent chain is the longest chain that contains the functional group for an aldehyde, change the suffix from -e to -al for an unsaturated aldehyde, change the infix from -anto -en-; the location of the suffix determines the numbering pattern for a cyclic molecule in which -CHO is bonded to the ring, add the suffix -carbaldehyde

Nomenclature: Aldehydes

O H 3-Meth ylb utanal

O
7

O
5 6 4 3 2 1

2-Propen al (2E)-3,7-D imeth yl-2,6-octad ienal (A crolein ) (Geran ial)

Nomenclature: Aldehydes

CHO Cyclopentanecarbaldehyde

HO

CHO

trans -4-Hydroxycyclohexanecarbaldehyde

Nomenclature: Aldehydes
the IUPAC retains the common names benzaldehyde and cinnamaldehyde, as well formaldehyde and acetaldehyde

CHO

C6 H5

CHO

Benzald ehyde t rans-3-Ph enyl-2-prop enal (Cin namaldeh yd e)

Nomenclature: Aldehydes

Benzaldehyde

Cinnamaldehyde

Benzaldehyde is found in the kernels of bitter almonds. Cinnamaldehyde is found in Ceylon and Chinese cinnamon oils.

Nomenclature: Ketones
IUPAC

names

the parent alkane is the longest chain that contains the carbonyl group indicate the ketone by changing the suffix -e to -one number the chain to give C=O the smaller number the IUPAC retains the common names acetone, acetophenone, and benzophenone
O O O O

Prop anone (Aceton e)

A cetophen on e

Benzophen on e

1-Phenyl-1-pen tanone

Order of Precedence
For

compounds that contain more than one functional group indicated by a suffix
Function al Grou p Carb oxyl Ald ehyde Ketone Alcoh ol Amino Su ffix if Prefix if higher low er priority priority -oic acid -al -one -ol -amine oxooxohydroxyaminomercapto 3-Oxoprop anoic acid H O Example w h en the function al group h as a low er p riority O COOH

Su lfh yd ryl -thiol

3-Oxobutan oic a COOH cid COOH 4-Hydroxybu tanoic HO acid NH2 COOH 3-Aminobu tanoic acid 2-Mercaptoethan ol HS OH

I n c r e a s i n g p r e c e d e n c e

Common Names
for an aldehyde, the common name is derived from the common name of the corresponding carboxylic acid for a ketone, name the two alkyl or aryl groups bonded to the carbonyl carbon and add the word ketone

O HCH Formaldehyde

O HCOH Formic acid

O CH3 CH A cetaldeh yd e

O CH3 COH Acetic acid

O O

Ethyl isopropyl ketone

Diethyl ketone

Dicyclohexyl ketone

Physical Properties
Oxygen

is more electronegative than carbon (3.5 vs 2.5) and, therefore, a C=O group is polar

aldehydes and ketones are polar compounds and interact in the pure state by dipole-dipole interaction they have higher boiling points and are more soluble in water than nonpolar compounds of comparable molecular weight

Reaction Themes
One

of the most common reaction themes of a carbonyl group is addition of a nucleophile to form a tetrahedral carbonyl addition compound
R Nu
-

O C O Nu C

+ R

R R Tetrahedral carbonyl add ition comp ou nd

Reaction Themes
A

second common theme is reaction with a proton or other Lewis acid to form a resonancestabilized cation
protonation increases the electron deficiency of the carbonyl carbon and makes it more reactive toward nucleophiles
R R C O
+

fast H-B

R
- + B

R R O-H

C O H R

C O H

R B
+

H-Nu + R

C O H

s low

Nu

C R

H-B

R Tetrah edral carbonyl addition compoun d

Reaction Themes
often the tetrahedral product of addition to a carbonyl is a new chiral center if none of the starting materials is chiral and the reaction takes place in an achiral environment, then enantiomers will be formed as a racemic mixture
Ap proach from the top face Nu O Nu R R R' C O R' A pproach from the bottom face R'
+

Nu OH H3 O
+

R'
+

R O

R'

R OH

Nu A n ew chiral cen ter is created

Nu A racemic mixture

Addition of C Nucleophiles
Addition

of carbon nucleophiles is one of the most important types of nucleophilic additions to a C=O group
a new carbon-carbon bond is formed in the process we study addition of these carbon nucleophiles
RMgX A Grign ard reagent RLi RC C An organ olith ium A n alk yn e reagent an ion
-

C N Cyan ide ion

Grignard Reagents
Given

the difference in electronegativity between carbon and magnesium (2.5 - 1.3), the C-Mg bond is polar covalent, with C- and Mg+
in its reactions, a Grignard reagent behaves as a carbanion

Carbanion:

an anion in which carbon has an unshared pair of electrons and bears a negative charge
a carbanion is a good nucleophile and adds to the carbonyl group of aldehydes and ketones

Grignard Reagents
addition of a Grignard reagent to formaldehyde followed by H3O+ gives a 1 alcohol
O CH3 CH2 -MgBr + H-C-H ether

Formaldehyde O [ MgBr] CH3 CH2 -CH2 A magn esium alkoxide

+

HCl H2 O

OH
2+ CH3 CH2 -CH2 + Mg

1-Prop anol (a 1 alcoh ol)

Grignard Reagents
addition to any other RCHO gives a 2 alcohol
MgBr O + ether

H Acetaldehyde (an ald ehyde) O [ MgBr]

+

OH HCl H2 O + Mg2 +

A magn esiu m alk oxid e

1-Cycloh exyleth anol (a 2 alcohol; (racemic)

Grignard Reagents
addition to a ketone gives a 3 alcohol
O Ph-MgBr Ph enylmagnesiu m b romide + Aceton e (a ketone) O [ MgBr] Ph A magnes ium alk oxid e
+

eth er

HCl H2 O

OH

+ Mg 2+

Ph 2-Phenyl-2-propanol (a 3 alcohol)

Grignard Reagents
Problem: 2-phenyl-2-butanol can be synthesized by three different combinations of a Grignard reagent and a ketone. Show each combination.
OH C-CH2 CH3 CH3

Organolithium Compounds
Organolithium

compounds are generally more reactive in C=O addition reactions than RMgX, and typically give higher yields
Li + Phenyl- 3,3-D imeth yl-2lithiu m butan on e A lithiu m alk oxid e (racemic) O O- Li+ HCl H2 O 3,3-D imethyl-2-phen yl2-bu tanol (racemic) OH

Salts of Terminal Alkynes

Addition

of an alkyne anion followed by H3O+ gives an -acetylenic alcohol

O HC C O Na
+

HC C OH HCl H2 O

HC C: Na+ + S od ium acetylid e Cycloh exanone A sodium alkoxide

1-Eth yn ylcyclohexan ol

Salts of Terminal Alkynes

O H2 O HO C CH H2 SO4 , HgSO4 An -hydroxyketone HO 1 . (sia) 2 BH 2 . H2 O2 , NaOH CH2 CH O HO CCH3

A -h yd roxyaldehyde

Addition of HCN
HCN

adds to the C=O group of an aldehyde or ketone to give a cyanohydrin Cyanohydrin: a molecule containing an -OH group and a -CN group bonded to the same carbon
O CH3 CH + H C N OH CH 3 C- C N H 2-Hydroxypropanenitrile (Acetaldehyde cyanohydrin)

Addition of HCN
Mechanism

of cyanohydrin formation

Step 1: nucleophilic addition of cyanide to the carbonyl carbon

H3 C C O + C N H3 C

H3 C C H3 C

C N

Step 2: proton transfer from HCN gives the cyanohydrin and regenerates cyanide ion
H3 C C H3 C C N O
-

H3 C
+ H C N

O-H C
+

C N

H3 C

C N

Cyanohydrins
The

value of cyanohydrins
OH CH3 CHC N acid catalyst

acid-catalyzed dehydration of alcohol gives an alkene

CH2 = CHC N + H2 O Propenenitrile (Acrylonitrile)

2-Hydroxypropanenitrile (Acetaldehyde cyanohydrin)

catalytic reduction of the cyano group gives a 1 amine

OH CHC N + 2 H2 Ben zaldeh yd e cyanohydrin (racemic) Ni OH CHCH2 NH2 2-Amino-1-ph enylethanol (racemic)

Wittig Reaction
The

Wittig reaction is a very versatile synthetic method for the synthesis of alkenes from aldehydes and ketones
O + + Ph3 P-CH2 CH2 + Ph 3 P=O

Cycloh exanone A p hosp honium ylide

MethyleneTrip hen ylcycloh exane phosp hine oxide

Phosphonium Ylides
Phosphonium

ylides are formed in two steps:

Step 1: nucleophilic displacement of iodine by triphenylphosphine

Ph 3 P + CH3 -I SN 2 + Ph3 P-CH3 I

Trip henylph os phin e

Methyltriphen ylp hosph on ium iod ide (an alk yltriph enylph os phin e salt)

Step 2: treatment of the phosphonium salt with a very strong base, most commonly BuLi, NaH, or NaNH2
CH3 CH2 CH2 CH2 Li Bu tyllith ium
+

+ H-CH2 -PPh3 I+ CH 3 CH2 CH2 CH3 + - CH2 -PPh3 + LiI Bu tane A phosp honium ylide

Wittig Reaction
Phosphonium

ylides react with the C=O group of an aldehyde or ketone to give an alkene
Step 1: nucleophilic addition of the ylide to the electrophilic carbonyl carbon
O CR2
+ -

:O
+

CR2 CH2

O Ph3 P

CR2 CH2

Ph3 P

CH2

Ph3 P

A betaine

An oxaph os ph etane

Step 2: decomposition of the oxaphosphatane

O CR2 Ph3 P CH2 Ph3 P=O
+

R2 C=CH2 An alkene

Triphen ylp hosph ine oxide

Wittig Reaction
Examples:
O + Ph3 P Acetone
+ Ph 3 P=O

2-Methyl-2-hepten e

Ph

Ph3 P

H Phen ylacetald ehyde

+ Ph + Ph P=O Ph 3 (Z )-1-Ph enyl-2- (E)-1-Phen yl-2b utene b utene (87%) (13%)

H Ph O + Ph3 P Phen ylacetald ehyde

O OEt Ph

O + Ph 3 P=O OEt Eth yl (E)-4-phen yl-2-b utenoate (only the E is omer is formed)

Wittig Reaction
some Wittig reactions are Z selective, others are E selective Wittig reagents with an anion-stabilizing group, such as a carbonyl group, adjacent to the negative charge are generally E selective
O Ph3 P OEt Ph3 P O OEt

Resonance contribu ting structu res for an ylide stab ilized by an ad jacent carbon yl group

Wittig reagents without an anion-stabilizing group are generally Z selective

Wittig Reaction
Horner-Emmons-Wadsworth

modification

uses a phosphonoester
O Br-CH2 -C-OEt an -b romoester ( MeO) 3 P Trimeth ylph os phite O Br-CH2 -C-R an -bromoketone O O ( MeO) 2 P-CH2 -C-OEt + MeBr An -p hosph on oes ter O O (MeO) 2 P-CH2 -C-R + MeBr An -phosp honoketone

Wittig Reaction
phosphonoesters are prepared by successive SN2 reactions
( MeO) 3 P O SN 2 + CH2 -C-OEt Br OMe O CH3 -O-P-CH2 -C-OEt Br OMe SN 2 O O ( MeO) 2 P-CH2 -C-OEt + MeBr An -p hosph on oes ter

Wittig Reaction
treatment of a phosphonoester with a strong base followed by an aldehyde or ketone gives an alkene a particular value of using a phosphonoester-stabilized anion is that they are almost exclusively E selective
O O 1. strong bas e O O OEt O MeO-P-O

( MeO) 2 P-CH2 -C-OEt

2.
H

OMe On ly th e E isomer D imethylphosp hate is formed an ion

Addition of H2O
Addition

of water (hydration) to the carbonyl group of an aldehyde or ketone gives a geminal diol, commonly referred to a gem-diol
gem-diols are also referred to as hydrates
acid or b ase H2 O OH C OH A hydrate (a gem-diol)

C O + Carbonyl group of an aldeh yd e or k eton e

Addition of H2O
when formaldehyde is dissolved in water at 20C, the carbonyl group is more than 99% hydrated
H O + H2 O H Formaldehyde H OH OH

H Formald ehyde h yd rate (>99%)

the equilibrium concentration of a hydrated ketone is considerably smaller

O + H2 O Acetone (99.9%) OH OH 2,2-Propanediol (0.1%)

Continue next week

Addition of Alcohols
Addition

of one molecule of alcohol to the C=O group of an aldehyde or ketone gives a hemiacetal Hemiacetal: a molecule containing an -OH and an -OR or -OAr bonded to the same carbon
O + H-OEt acid or base OH OEt A hemiacetal

Ar = aryl group

Addition of Alcohols
hemiacetals are only minor components of an equilibrium mixture, except where a five- or sixmembered ring can form
O
4 1

OH (S)-4-Hydroxypentanal

OH

OH

Cyclic hemiacetals (major forms present at equilibrium)

6

OH OH O HO
6 5 4 3 2 1

CH2 OH HO + OH HO

CH2 OH anomeric carbon OH

HO H HO

OH OH
D -Glucos e

4 5 O 3 2 1

4 5 O 3 2 1

(open chain form)

OH A nomer of D -glucos e cyclic hemiacetal (p red ominates at equ ilibrium)

OH Anomer of D -glu cos e cyclic h emiacetal

Addition of Alcohols
at equilibrium, the anomer of glucose predominates because the -OH group on the anomeric carbon is equatorial
6

CH2 OH

HO HO

4 5 O 3 2 1

redraw as anomeric a chair carb on con formation HO

OH
4 6 5 2

O
1

anomeric carb on OH (eq uatorial)

OH

HO
3

OH An omer

OH

CH2 OH

HO HO

4 5 O 3 2 1

redraw as a chair anomeric con formation HO carb on

OH
4 6 5 2

O
1

anomeric carb on

OH

HO
3

OH A nomer of

HO OH (axial)

Addition of Alcohols
Formation

of a hemiacetal is base catalyzed

fas t and reversible

Step 1: proton transfer from HOR gives an alkoxide

B
-

+ H OR

B H +

OR

Step 2: attack of RO- on the carbonyl carbon

O CH3 -C-CH3 + O:

:O-R

CH3 -C-CH3 OR

Step 3: proton transfer from the alcohol to O- gives the hemiacetal and generates a new base catalyst
O: CH3 -C-CH3 + H OR OR OH CH3 -C-CH3 + OR
-

OR

Addition of Alcohols
Formation

of a hemiacetal is also acid catalyzed

fast and reversible + O H A
-

Step 1: proton transfer to the carbonyl oxygen

O CH3 -C-CH3 + H-A
+ H O

CH3 -C-CH3 +

Step 2: attack of ROH on the carbonyl carbon

CH3 -C-CH3 + H-O-R O-H CH3 -C-CH3 O+ H R

Step 3: proton transfer from the oxonium ion to A- gives the hemiacetal and generates a new acid catalyst
OH CH3 -C-CH3 + O H R OH CH3 -C-CH3 + H-A OR

Addition of Alcohols
Hemiacetals

react with alcohols to form acetals

Acetal: a molecule containing two -OR or -OAr groups bonded to the same carbon
OH + H-OEt H
+

OEt

OEt A h emiacetal

OEt A d iethyl acetal

+ H2 O

Addition of Alcohols
Step 1: proton transfer from HA gives an oxonium ion
HO R-C-OCH3 + H A H H + H O R-C-OCH3 H An oxonium ion + A:
-

Step 2: loss of water gives a resonance-stabilized cation

H +H O R-C OCH3 H + R-C OCH3 + R-C OCH3

+ H2 O

H H A resonan ce-stabilized cation

Addition of Alcohols
Step 3: reaction of the cation (an electrophile) with methanol (a nucleophile) gives the conjugate acid of the acetal
+ CH3 -OH + R-C OCH3 H H + CH3 O R-C OCH3 H A p rotonated acetal

Step 4: proton transfer to A- gives the acetal and generates a new acid catalyst
H + CH3 O A:- + R-C OCH3 H (4) OCH3 R-C-OCH3 + H-A H An acetal

Addition of Alcohols
with ethylene glycol and other glycols, the product is a five-membered cyclic acetal
HO O + OH H
+

O O Cyclic acetal + H2 O

Dean-Stark Trap

Acetals as Protecting Grps

Suppose

you wish to bring about a Grignard reaction between these compounds

O H + Br O H ?? OH O H 5-Hydroxy-5-phen ylpen tanal (racemic)

Benzald ehyde

4-Bromobutanal

Acetals as Protecting Groups

a

Grignard reagent prepared from 4bromobutanal will self-destruct!

first protect the -CHO group as an acetal
O Br H + HO OH H
+

O Br O A cyclic acetal + H2 O

then do the Grignard reaction

O- MgBr+ O O Br O 1 . Mg, ether 2 . C6 H5 CHO A chiral magnesiu m alk oxide (produced as a racemic mixtu re) O

hydrolysis (not shown) gives the target molecule

Acetals as Protecting Groups

Tetrahydropyranyl

(THP) protecting group

THP group H+ RCH2 O O

RCH2 OH + O Dihydropyran

A tetrahydropyranyl ether

the THP group is an acetal and, therefore, stable to neutral and basic solutions, and to most oxidizing and reducting agents it is removed by acid-catalyzed hydrolysis

Addition of Nitrogen Nucleophiles

Ammonia,

1 aliphatic amines, and 1 aromatic amines react with the C=O group of aldehydes and ketones to give imines (Schiff bases)
O CH3 CH + H2 N Acetaldehyde Aniline
+

CH3 CH=N An imine (a Schiff base )

+ H2 O

N H3

N H + H2 O An imine (a Schiff base )

Cyclohexanone Ammonia

Addition of Nitrogen Nucleophiles

Formation

of an imine occurs in two steps

O:- H + N-R C H H N-R H

Step 1: carbonyl addition followed by proton transfer

O C + H2 N-R O C

Step 2: loss of H2O and proton transfer to solvent

H H + O H + O H + H H O C N-R H O H H H + C N-R + H O + H2 O H A n imin e

C N-R H

Addition of Nitrogen Nucleophiles

a value of imines is that the carbon-nitrogen double bond can be reduced to a carbon-nitrogen single bond
O + H2N H+ - H2 O

Cyclohexanone Cyclohexylamine
H N (An imine) H2 / N i N Dicyclohexylamine

Addition of Nitrogen Nucleophiles

Rhodopsin

(visual purple) is the imine formed between 11-cis-retinal (vitamin A aldehyde) and the protein opsin
11 12

+ H2 N-opsin O Rhodops in (V isual p urple) H N-opsin

11-cis- Retin al

Addition of Nitrogen Nucleophiles

Secondary

amines react with the C=O group of aldehydes and ketones to form enamines
O Cyclohexanone
+

H-N

N An enamine

H2 O

Piperidine (a s econdary amine )

the mechanism of enamine formation involves formation of a tetrahedral carbonyl addition compound followed by its acid-catalyzed dehydration we discuss the chemistry of enamines in more detail in Chapter 19

Addition of Nitrogen Nucleophiles

the carbonyl group of aldehydes and ketones reacts with hydrazine and its derivatives in a manner similar to its reactions with 1 amines
O + H2 NNH2 Hydrazine
Reagen t, H 2N -R H2 N-OH H2 N-NH H2 N-NH O2 N O H2 N-NHCNH2 S emicarbazid e Semicarbazone NO2 N ame of Reagen t Hydroxylamine Phen ylh yd razine

NNH2 + H2 O A hydrazone
N ame of D erivative Formed Oxime Ph enylhyd razone

2,4-D initroph enyl- 2,4-D initrop henylhydrazon e hydrazine

Acidity of -Hydrogens
Hydrogens

alpha to a carbonyl group are more acidic than hydrogens of alkanes, alkenes, and alkynes but less acidic than the hydroxyl hydrogen of alcohols

T yp e of Bond

p Ka 16 20 25 44 51

CH3 CH2 O-H O CH3 CCH2 -H CH3 C C-H CH2 =CH-H CH3 CH2 -H

Acidity of -Hydrogens
-Hydrogens

are more acidic because the enolate anion is stabilized by

1. delocalization of its negative charge 2. the electron-withdrawing inductive effect of the adjacent electronegative oxygen
O CH3 -C-CH2 - H + :AO CH3 -C CH2 O
-

CH3 -C=CH2 + H-A

Resonance-stabilized enolate anion

Keto-Enol Tautomerism
protonation of the enolate anion on oxygen gives the enol form; protonation on carbon gives the keto form
O CH3 - C-CH2 H- A OCH3 - C= CH2 H- A

Enolate an ion O A + CH3 - C-CH3 Keto form OH CH3 - C= CH2 + A Enol form

To be continued

Keto-Enol Tautomerism
acid-catalyzed equilibration of keto and enol tautomers occurs in two steps Step 1: proton transfer to the carbonyl oxygen
O fas t and reversib le + O H + A

CH3 -C-CH3 + H-A Keto form

CH3 -C-CH3

The conjugate acid of the ketone

Step 2: proton transfer to the base A+ O H

-

CH3 -C-CH2 -H + :A

slow

OH CH3 -C=CH2 + H-A En ol form

Keto-Enol Tautomerism
Keto-enol

equilibria for simple aldehydes and ketones lie far toward the keto form

Keto form
O CH3 CH O CH3 CCH3 O

Enol form
OH CH2 = CH OH CH3 C= CH2 OH

% Enol at Equilibrium

6 x 10-5 6 x 10-7 1 x 10-6

OH

4 x 10-5

Keto-Enol Tautomerism
For

certain types of molecules, however, the enol is the major form present at equilibrium
for -diketones, the enol is stabilized by conjugation of the pi system of the carbon-carbon double bond and the carbonyl group for acyclic -diketones, the enol is further stabilized by hydrogen bonding

Oxidation of Aldehydes
Aldehydes

are oxidized to carboxylic acids by a variety of oxidizing agents, including H2CrO4

CHO Hexanal H2 Cr O4 COOH Hexanoic acid

They

are also oxidized by Ag(I)

in one method, a solution of the aldehyde in aqueous ethanol or THF is shaken with a slurry of silver oxide
CH3 O HO Vanillin O CH + A g2 O CH3 O O COH + Ag HO Vanillic acid

T HF, H 2 O N aOH

HCl H2 O

Oxidation of Aldehydes
Aldehydes

are oxidized by O2 in a radical chain

reaction
liquid aldehydes are so sensitive to air that they must be stored under N2
O 2 CH Benzaldehyde + O2 2 O COH Benzoic acid

Oxidation of Ketones
ketones are not normally oxidized by chromic acid they are oxidized by powerful oxidants at high temperature and high concentrations of acid or base
O
OH O

HN O 3 H O
Cyclohexanone Cyclohexanone (keto form) (enol form)

OH

O H exanedioic acid (Adipic acid)

Reduction
aldehydes can be reduced to 1 alcohols ketones can be reduced to 2 alcohols the C=O group of an aldehyde or ketone can be reduced to a -CH2- group
Aldehydes O RCH RCH3 Can Be Reduced to

Ketones
O RCR'

Can Be Reduced to

OH RCH2 OH
RCH R' RCH2 R'

Metal Hydride Reduction

The

most common laboratory reagents for the reduction of aldehydes and ketones are NaBH4 and LiAlH4
both reagents are sources of hydride ion, H:-, a very powerful nucleophile
H Na
+

H Li
+

H- B- H

H- A l - H

H:

H H Sodium Lithium aluminum H ydride ion borohydride hydride (LAH)

NaBH4 Reduction
reductions with NaBH4 are most commonly carried out in aqueous methanol, in pure methanol, or in ethanol one mole of NaBH4 reduces four moles of aldehyde or ketone
O 4 RCH + NaBH4 methanol ( RCH2 O) 4 B Na A tetraalkyl borate
+

H2 O

4 RCH2 OH + borate salts

NaBH4 Reduction
The

key step in metal hydride reduction is transfer of a hydride ion to the C=O group to form a tetrahedral carbonyl addition compound
This H comes from w ater du rin g hydrolys is H H O O BH3 Na R-C-R' H
+

+ Na H-B-H + R-C-R'

H2 O

O-H R-C-R' H

This H comes from the hydride reducing agen t

LiAlH4 Reduction
unlike NaBH4, LiAlH4 reacts violently with water, methanol, and other protic solvents reductions using it are carried out in diethyl ether or tetrahydrofuran (THF)
O ether 4 RCR + LiAlH4 ( R2 CHO) 4 Al Li A tetraalk yl alu min ate
+

H2 O H+ or OH-

OH 4 RCHR + aluminum salts

Catalytic Reduction
Catalytic

reductions are generally carried out at from 25 to 100C and 1 to 5 atm H2

O + H2 Pt 25 oC, 2 atm Cyclohexanol 2 H2

OH

Cyclohexanone O

H Ni trans-2-Butenal (Crotonaldehyde)

OH

1-Butanol

Catalytic Reduction
A

carbon-carbon double bond may also be reduced under these conditions

O 2 H2 H Ni trans-2-Butenal (Crotonaldehyde) OH 1-Butanol

by careful choice of experimental conditions, it is often possible to selectively reduce a carbon-carbon double in the presence of an aldehyde or ketone
O 1 . NaBH4 RCH=CHCR' 2 . H2 O
O RCH=CHCR' + H2 Rh

OH RCH=CHCHR'
O RCH2 CH 2 CR'

Clemmensen Reduction
refluxing an aldehyde or ketone with amalgamated zinc in concentrated HCl converts the carbonyl group to a methylene group
OH O Zn( Hg) , HCl OH

Wolff-Kishner Reduction
in the original procedure, the aldehyde or ketone and hydrazine are refluxed with KOH in a high-boiling solvent the same reaction can be brought about using hydrazine and potassium tert-butoxide in DMSO
O + H2 NN H2 Hydrazine KOH diethylen e glycol (reflux)

+ N 2 + H2 O

Racemization
Racemization
O

at an -carbon may be catalyzed by either acid or base

OH Ph An achiral enol O

Ph (R)-3-Phenyl-2b utanone

Ph (S)-3-Phenyl-2butan one

omit

Deuterium Exchange
Deuterium
O CH 3 CCH 3 Acetone

exchange at an -carbon may be catalyzed by either acid or base

+ 6 D2 O D
+ -

O CD 3 CCD 3 + 6 HOD Acetone-d 6

or OD

omit

-Halogenation
-Halogenation:

aldehydes and ketones with at least one -hydrogen react at an -carbon with Br2 and Cl2
O + Br2 Acetop henone CH 3 COOH -Bromoacetoph enone O Br + HBr

reaction is catalyzed by both acid and base

omit

-Halogenation
Acid-catalyzed

-halogenation
slow H-O C R' C R R

Step 1: acid-catalyzed enolization

OH R'-C-C-R R

Step 2: nucleophilic attack of the enol on halogen

H-O C R' C R R + Br Br fast R' H O Br C C R R + Br:-

Step 3: (not shown) proton transfer to solvent completes the reaction

omit

-Halogenation
Base-promoted

-halogenation
O C O: C C R + H2 O

Step 1: formation of an enolate anion

OH R'-C-C-R + - :OH R slow - R C

R' R R' R Res on ance-stab ilized enolate anion

Step 2: nucleophilic attack of the enolate anion on halogen

O: C R' C R R + Br Br fast R' O C Br C R + R Br

omit

-Halogenation
Acid-catalyzed

halogenation:

introduction of a second halogen is slower than the first introduction of the electronegative halogen on the carbon decreases the basicity of the carbonyl oxygen toward protonation
Base-promoted

-halogenation:

each successive halogenation is more rapid than the previous one the introduction of the electronegative halogen on the -carbon increases the acidity of the remaining hydrogens and, thus, each successive -hydrogen is removed more rapidly than the previous one

omit

End