Carbonyl Compounds

O C

The carbonyl double bond is analogous to the alkene double bond, i.e. the carbon involve in the double bond formation is Sp2 hybridized.
p

sp2

Triginal carbon; three sp2 orbitals in a o plane with 120 angle between them

p orbital perpendicular to the plane

p sp2 sp
2

C
C

O C

1.22 A
O

C
p

C
p

120

1.43 A

The carbonyl group has a large dipole moment

C O C O

Classification Aldehydes:
R O C H

R = alkyl &/or aryl (except for methanal (formaldehyde), R = H

Ketones:
C R R'

R & R = alkyl &/or aryl

Nomenclature
Aldehydes Systematic names are derived by replacing the terminal e of the corresponding alkane with al. Trivial names are derived from the name of the corresponding carboxylic acid by replacing the ic or oic at the end with aldehyde
O H3C C H

O CH3CH2CH2 C H

CH3 CH3CH2CHCH2

O C H

(ethane) ethanal (acetic) acetaldehyde

(butane) butanal (butyric) butyraldehyde

(3-methylpentane) 3-methylpentanal (-methylpentanoic) -methylpentanaldehyde

Ketones Systematic names are derived by replacing the terminal e of the corresponding alkane with one. The chain is numbered such that the carbonyl carbon atom is given the lowest possible number. Trivial names are derived by adding ketone to the aryl or alkyl prifix.
O H3C C CH3

O CH2CH C CH3

O CH3 CH3CH2CCH CH3

propanone Dimethyl ketone

3-buten-2-one

2-methyl-3-pentanone

vinylmethyl ketone (ethyl isopropyl ketone)

CH3

cyclohexanone

2-methyl cyclopentanone

Aromatic ketones are called phenones and are named as substituents of the corresponding carboxylic acid by droping ic and adding ophenone.
O C CH3
O C

(acetic) Acetophenone methyl phenyl ketone

(benzoic) benzophenone diphenyl ketone

Preparation of Aldehydes
(i) Oxidation of 1o alcohols using a mild oxidant a
R CH2 OH CrO3/pyridine R O C H

PCC =

(ii) Ozonolysis of alkenes (see C10J )

R R O3 H H R H O O O R AcOH/Zn H O O H R'

R' H

(iii) Reduction of Acid Chlorides Lithium tri-t-butoxyaluminum hydride (LiAlH[OC(CH3)3]3 or LiAlH(OtBu)3) is often used for this reduction, this is a mild hydride reducing agent. O R C Cl LiAlH(tBuO)3 R O C H

Reduction is effected by transfer of a hydride ion from the aluminium atom to the carbonyl carbon of the acyl chloride. Subsequent hydrolysis free the aldehyde as shown in the mechanism on the next slide

O LiAl[OC(CH3)3]3 C R Cl H R C

Li + Al[OC(CH3)3]3

Cl

Li O R C Cl - LiCl Al[OC(CH3)3]3 H + Li R O C Cl H Al[OC(CH3)3]3

O C R

Al[OC(CH3)3]3 H 2O H R

O C H

Preparation of ketones
(i) Oxidation of 2o alcohols The most commonly used reagent for this oxidation is H2CrO4, chromic acid (Jones reagent), prepared from CrO3 or Na2Cr2O7 and H2SO4.
OH R CH R' H2CrO4 R O C R'

The alcohol donates an electron pair to the chromium atom, as an oxygen accepts a proton. Proton exchange occurs followed by loss of H2O to give the chromate ester. The chromate atom then leaves to produce the ketone (oxidized alcohol).

mechanism
H O R C R' O H O (Cr ) H H R C R' chromate ester O Cr O O R' O H OH R C O Cr O H OH2 OH O
VI

H H O Cr O

R C R'

H O H

OH OH Cr O O

R O R' +

O Cr OH O (CrIV)

(ii) Ozonolysis of alkenes

R R" (i) O3 (ii) AcOH/Zn R' R''' R' R O R"

O R'''

Tetrasubstituted alkenes will produce two ketones Trisubstituted alkenes will produce one ketone and one aldehyde Alkene carbons which bear two alkyl groups always become ketone carbonyls on ozonolysis. (iii) Hydration of Alkynes
O R C C H H2SO4/H2O Hg
2+

H CH2 R

O C (ketone) CH3

C (enol)

(iv) From organometallic compounds Replacement of chloride in acyl chlorides by nucleophilic alkyl groups of the organometallic compounds. (a) Dialkyl Cadmium (R2Cd)
O + R' Cl R2Cd R' R O

(b) Lithium dialkyl cuprates (R2CuLi)

O + R' Cl R2CuLi R' R O

Reactions of carbonyl compounds

Two main types of reactions (A) Reaction of the carbonyl double bond (B) Reactions due to the acidity of the - hydrogen

(A) Reaction of the carbonyl double bond.

The chemistry that characterizes the reactivity of the carbonyl group is nucleophilic addition

Nu

Nu

This happens because;

O C O

O + R' Nu slow R.D.S. R

O C Nu R' H+ fast R

OH C Nu R'

Reactivity towards nucleophiles

H O H H R O R R O

WHY?

Decreasing reactivity towards nucleophiles

General mechanisn for nucleophilic addition

(1) Addition under neutral or basic conditions
O

(i)
R + R' Nu

O slow R.D.S. Nu alkoxide ion R C R'

Nucleophile attack the electrophilic carbon

O OH R' H+ (fast) Nu Nu R C R'

(ii)

The formed alkoxide is then protonated

(2) Addition under acidic conditions

H O O H R R' R R' R R' O H

(i)

The nucleophilic oxygen of the carbonyl is protonated to produce a hybrid of two resonance forms.
H O OH Nu R R' Nu R C R'

(ii)

The protonated carbonyl is subjected to nucleophilic attack

Examples of nucleophilic addition

(i) Addition of hydrogen cyanide (neutral-basic conditions). CN- is a very good nucleophile (ionic nucleophile). The use of the actual compound HCN is not experimentally feasible, as it a lethal gas therefore KCN or NaCN is used. Firstly CN- adds to a C=O group to form an alkoxide which is then protonated.
O KCN R R' H2O CN cyanohydrin R OH R'

(ii) Addition of alcohol (ROH) This is an acid-catalyzed nucleophilic addition. Two equivalents of an alcohol (ROH) is added to an aldehyde (RCHO) or ketone (R2CO) under acidic conditions. A hemiacetal or hemiketal is first formed, and the final product is an acetal or ketal

1. Protonation of the carbonyl.

R

O C R' H R

O C

H OH R' R C O R" H R" R'

2. Nucleophilic addition of the alcohol to the protonated carbonyl and loss of a proton from the addition product. 3. Protonation of the OH of the hemiacetal and loss of H2O.

O H

-H2O R C OR" R' R

OH2 C OR" R' H R

OH C R'

OR" hemiacetal (from aldehyde) hemiketal (from ketone)

O H R'''

OR''' -H C OR" R' R

OR''' C R'

4. A second equivalent of R the alcohol then adds followedby loss of a proton.

OR" acetal (from aldehyde) ketal (from ketone)

e.g.
O C H3C CH3 + CH3CH2OH H H3C OH ROH C CH3 H3C C CH
3

OCH2CH3

OCH2CH3 hemiketal

OCH2CH3 ketal

O O H HO CH2CH2CH2 C H OH

OH

O lactol

(iii) Addition of Grignard reagents

O + R R R' CH2 + MgX R OH R' CH2R'

Methanal ---- 1o alcohols Aldehydes ---- 2o alcohols Ketones ---- 3o alcohols

(iv) Addition of derivatives of ammonia (NH3)

This reaction can be regarded as a condensation between the carbonyl compound and ammonia or the amine to form an imine or Schiff base, with the net expulsion of a molecule of water. Mechanistically, the process entails nucleophilic addition of ammonia or the amine (molecular nucleophiles) to the electrophilic carbon of the carbonyl group.

Addition of derivatives of ammonia (NH3) continues Nucleophilic addition of the amine (a molecular nucleophile) to the carbonyl compound followed by a proton shift within the initial adduct.

Protonation of the addition product on oxygen, followed by loss of H2O, then deprotonation to yield the IMINE or SCHIFF BASE.

(v) Olefination (Wittig reaction) RHO and R2CO react with phosphorus ylids to yield alkenes. This reaction actually entails nucleophilic addition to the carbonyl carbon In the first step, triphenylphosphine (Ph3P, a nucleophile) reaction with the alkyl halides (RX) to produce a phosphonium salt. The hydrogens on the carbon bonded to phosphorous are acidic, and one of these is removed by base. This yields a phosphorous ylide.

Ph3P

CH2

Ph3P

CH2

base

Ph3P

CH

posphorus ylid

Ph3P

CH

Wittig reaction continues The dipolar of the ylide (a very strong nucleophile) attack the electrophilic carbonyl carbon. The product of addition of the ylide to the carbonyl produce a betaine which cyclizes to give an oxaphosphetane. The oxaphosphetane fragments to an alkene and triphenylphosphine oxide. The overall result of a Wittig reaction is the formation of a C=C bond from a C=O bond.

O O Ph3P CH R Ph3P C

O P CH R Ph Ph Ph triphenyl phosphine oxide H R alkene +

oxaphosphetane

e.g.
O + CH3I + PPh3 NaOH CH2

mechanism base Ph3P CH2

Ph3P

CH3

Ph3P

CH3

posphorus ylid

H 2C

PPh3 H2C O O PPh3 CH2

Reduction of carbonyls (i) To alcohols

O R CH2 OH 1 alcohol
o

H aldehyde O

OH R R CH2 R 2 alcohol
o

R ketone

Catalytic hydrogenation -: H2/Pt or Ni or Pd This reaction is very slow and experimentally very difficult, therefore carbonyl compounds are usually reduced to alcohols with sodium borohydride or lithium aluminum hydride

Metal hydride reduction: Aldehydes and ketones are reduced relativelyeasily to 1o and 2o alcohols respectively, using metal hydride reducing agents sodium borohydride (NaBH4) or lithium aluminum hydride (LiAlH4) The key step in this reduction is the reaction of hydride (H-) with the carbonyl carbon.
H H Al H H + O H R C R alkoxide ion O H OR H R C R OH

(ii) To alkanes
O R CH2 alkane R

Two methods are commonly used for this reduction. Wolff-Kishner Reduction Reaction of the aldehyde or ketone with hydrazine followed by treatment of the resultant hydrazone with strong base (NH2-NH2 / OH-) Clemmensen Reduction Reduction of the carbonyl compound with zinc amalgam, in acid (Zn(Hg)/HCl) You are not required to know the mechanism of this reaction.

(iii) Reductive amination The C=N of imines is very easily reduced. This provides a route to amines, starting with aldehydes or ketones.

(B) REACTIONS DUE TO ACIDITY OF -HYDROGEN Carbons adjacent to the carbonyl group are known as carbons, and the attached hydrogens are hydrogens Next to carbons are carbons, with attached hydrogens
H R C H H C H O C H C H H C H R

Carbons carry a small positive charge because of the inductive effect. The C-H bonds to carbons are weakened hydrogens are therefore acidic, and can be removed with base

(B) REACTIONS DUE TO ACIDITY OF -HYDROGEN continues

O R C keto H B CH R R C CH enolate (carbanion) R R C H+ CH R O O

OH R C enol CH R

The carbanion resulting from removal of a hydrogen to a carbonyl group is known as an enolate anion which has two resonance forms

Aldol Condensation The Aldol Reaction is the addition of an enolate anions to aldehydes and ketones

When aldehydes react with dilute NaOH at room temp. dimerization takes place. The product is called an aldol because it has both an aldehyde and an alcohol function group present.
O OH H NaOH/H2O R CH2 CH R CH O C H

2 R

CH2

Eg.
2 CH3

O C H NaOH/H2O CH3

OH CH CH2

O C H

Mechanism
(i) Carbanion (enolate)formation

Hydroxide removes the acidic proton to form an enolate

H H C H

O C H OH H 2C

O C H enolate H2C

O C H

(ii) Nucleophilic attack on carbonyl

The enolate (nucleophile) attacks the carbonyl carbon of another molecule of aldehyde The alkoxide then removes a proton from H2O

O CH3 C H + H2C

O C H CH3

O CH CH2

O C H

alkoxide ion (iii) Protonation O CH3 CH CH2 O C H H O H - OH CH3 CH CH2 C H 3-hydroxybutanal (aldol) OH O

Dehydration of the Aldol Product If the aldol reaction mixture is heated, dehydration takes place to form an unsaturated carbonyl compound.
O H C CH H OH OH CH CH3 -H2O H O C CH CH CH3

2-butenal (conjugated)

Dehydration is favorable because the product is stabilized by conjugation of the alkene with the carbonyl group

Cross Aldol When an aldol reaction is done with two different aldehydes it is called a cross aldol reaction.
O C6H5 C H + CH3CH2 O C H OH/H2O OH C6H5C H H C CH3 O C H

O C6H5C H C CH3 C H