C10K Carbonyl Chemistry Email

8/3/2019 C10K Carbonyl Chemistry Email

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C

O

Carbonyl Compounds

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

C

p orbital perpendicular

to the plane

Triginal carbon; three sp2

orbitals in a

plane with 120o

angle between them

sp2

CC

p

CCsp

2

p

sp2

p p

120o

C O

C C

1.22 A

1.43 A

O

O


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C O C O

Classification

The carbonyl group has a large dipole moment

C

O

R H

Aldehydes: R = alkyl &/or aryl (except for

methanal (formaldehyde), R= H

C

O

R R'

Ketones: R & R = alkyl &/or aryl


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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

Nomenclature

C

O

H3C H

(ethane)

ethanal

(acetic)

acetaldehyde

C

O

CH3CH2CH2 H

(butane)

butanal

(butyric)

butyraldehyde

C

O

CH3CH2CHCH2 H

CH3

(3-methylpentane)

3-methylpentanal

(-methylpentanoic)

-methylpentanaldehyde


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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.

C

O

H3C CH3

propanone

Dimethyl ketone

C

O

CH2CH CH3

3-buten-2-one

CH3CH2CCH

O

CH3

CH3

2-methyl-3-pentanone

(ethyl isopropyl ketone)vinylmethyl ketone


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Aromatic ketones are calledphenones and are named as

substituents of the corresponding carboxylic acid by droping

ic and adding ophenone.

O

CH3

O

cyclohexanone 2-methyl cyclopentanone

(acetic)

Acetophenone

methyl phenyl ketone

(benzoic)

benzophenone

diphenyl ketone

C

O

CH3

C

O


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(i) Oxidation of 1o alcohols using a mild oxidant

R CH2 OH R C

O

HCrO3/pyridine

Preparation of Aldehydes

a

b

PCC =


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H

R

H

R

O O

O

H

R'R

H

O3 AcOH/Zn

H

R

O O

H

R'

(ii) Ozonolysis of alkenes (see C10J )


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(iii) Reduction of Acid Chlorides

O

LiAlH(tBuO)3

O

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.

Reduction is effected by transfer of a hydride ion

from the aluminium atom to the carbonyl carbon of theacyl chloride. Subsequent hydrolysis free the aldehyde as

shown in the mechanism on the next slide


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Cl

C

R

OLiAl[OC(CH3)3]3

H

CR

O Al[OC(CH3)3]3

H +

Cl

CR

O

Al[OC(CH3)3]3

H

Li

+

O

Al OC CH

Li

Cl

H

C

R

O Al[OC(CH3)3]3

H

C

R

O

- LiCl

H2O

Cl

CR H


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C

R

R' O

H

H

Cr

O

O O

O

H

(CrVI

)

C

R

R' O

H

Cr

OH

O

OH

OH

HO

H

H

mechanism

C

R

R' O

H

Cr

OH2

O

O

OHC

R

R' O

H

Cr

OH

O

Ochromate ester

R

R'

O + Cr

O

O

OH(Cr

IV)


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R'

R

R'''

R"

O3

R'

R

O O

R'''

R"

(i)

(ii) AcOH/Zn

+

(ii) Ozonolysis of alkenes

Tetrasubstituted alkenes will produce two ketones

Trisubstituted alkenes will produce one ketone and one aldehyde

(iii) Hydration of Alkynes

R C C R C

O

CH2HH2SO4/H2O

Hg2+

H

R C

O

CH3

(enol) (ketone)

Alkene carbons which bear two alkyl groups always becomeketone carbonyls on ozonolysis.


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O

'

O

R2Cd+

(a) Dialkyl Cadmium (R2Cd)

(iv) From organometallic compounds

Replacement of chloride in acyl chlorides by nucleophilic alkyl

groups of the organometallic compounds.

(b) Lithium dialkyl cuprates (R2CuLi)

RR'

O

ClR'

O

R2CuLi+

R


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Two main types of reactions

(A) Reaction of the carbonyl double bond

(B) Reactions due to the acidity of the - hydrogen

Reactions of carbonyl compounds

OCNuONu +

(A) Reaction of the carbonyl double bond.The chemistry that characterizes the reactivity of the

carbonyl group is nucleophilic addition


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OCO

This happens because;

'

O

Nu+

-

slowR C

O

R' R C

OH

R'H+

R.D.S.

Nu Nu

as

H

H

O

H

R

O

R

R

O

Decreasing reactivity towards nucleophiles

Reactivity towards nucleophiles

WHY?


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R'R

O

Nu+

-

slow

R.D.S.R C

O

Nu

R'

(1) Addition under neutral or basic conditions

General mechanisn for nucleophilic addition

(i)

R C

OH

Nu

R'H+

(fast)R C

O

Nu

R'

alkoxide ion

(ii)

Nucleophile attack the electrophilic carbon

The formed alkoxide is then protonated


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R'R

O

H

R'R

O

H

R'R

O

H

(2) Addition under acidic conditions

(i)

The nucleophilic oxygen of the carbonyl is protonated

R C

OH

Nu

R'Nu

R'R

O

H

(ii)

.

The protonated carbonyl is subjected to nucleophilic

attack


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(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

Examples of nucleophilic addition

R'R

O

R'R

OH

KCN

CN

cyanohydrin

H2O

pro ona e .


19/37

(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 orhemiketal is first formed, and the final product is an acetal or ketal


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R'

C

R

O

R'CR

OHH

O

R'

C

R

OH

O

H R" H R"

'

OH

H'

OH2-H2O

R'CR

1. Protonation of the

carbonyl.

2. Nucleophilic addition

of the alcohol to the

protonated carbonyl

and loss of a proton

from the addition

OR"

hemiacetal (from aldehyde)

hemiketal (from ketone)

OR"OR"

O

H R'''

R'CR

OR'''

OR"

H

R'CR

OR'''

OR"

acetal (from aldehyde)

ketal (from ketone)

-H

product.

3. Protonation of the OH

of the hemiacetal and

loss of H2O.

4. A second equivalent of

the alcohol then adds

followedby loss of a proton.


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CH3

C

H3C

O

HCH3CH3C

OH

OCH2CH3hemiketal

CH3

CH3C

OCH2CH3

OCH2CH3ketal

+ CH3CH2OHROH

e.g.

O

HO CH2CH2CH2 C

O

H

OH

H

O

OH

lactol


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RR

O

R'R

OH

CH2R'

+ R' CH2 MgX- +

(iii) Addition of Grignard reagents

Methanal ---- 1o alcohols

Aldehydes ---- 2o

alcoholsKetones ---- 3o alcohols


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(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 orSchiff 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 electrophiliccarbon of the carbonyl group.


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Nucleophilic addition of the amine (a molecular nucleophile)

to the carbonyl compound followed by a proton shift within

the initial adduct.

Addition of derivatives of ammonia (NH3) continues

Protonation of the addition product on oxygen, followed by loss of

H2O, then deprotonation to yield the IMINE or SCHIFF BASE.


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(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.

Ph3P R CH2 X+ Ph3P CH2 R Ph3P CH R base

Ph3P CH R

posphorus ylid

The hydrogens on the carbon bonded to phosphorous are acidic, andone of these is removed by base. This yields a phosphorous ylide.


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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

Ph3P CH R

O

O C

Ph3P CH R

oxaphosphetane

P

O

+

H R

Ph Ph

Ph

alkenetriphenyl

phosphine

oxide

from a C=O bond.


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Ph P CH3 I+ Ph3P CH3 Ph3P CH2base

+

O

CH3I PPh3+NaOH

CH2

mechanism

e.g.

posphorus ylid

H2C PPh3

O

H2C

O

PPh3CH2


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R H

O

R CH2 OH

1o

alcoholaldehyde

R R

O

R CH2

2o

alcohol

OH

R

Reduction of carbonyls

(i) To alcohols

e one

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


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Metal hydride reduction:

Aldehydes and ketones are reduced relativelyeasily to 1o and 2o

alcohols respectively, using metal hydride reducing agentssodium borohydride (NaBH4) or lithium aluminum hydride (LiAlH4)

The ke ste in this reduction is the reaction of

H

Al HH

H

O+

R

C OH

R

R

C OHH

R

H OR

alkoxide ion

hydride (H-) with the carbonyl carbon.


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R R

O

R CH2 R

alkane

(ii) To alkanes

Two methods are commonly used for this reduction.

Wolff-Kishner Reduction

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.


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(iii) Reductive amination

The C=N of imines is very easily reduced.

This provides a route to amines, starting with aldehydes or

ketones.


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(B) REACTIONS DUE TO ACIDITY OF -HYDROGEN

Carbons adjacent to the carbonyl group are known as carbons, andthe attached hydrogens are hydrogens

Next to carbons are carbons, with attached hydrogens

C C

O

C CC

HH

RR

H H

HHH H

Carbons carry a small positive charge because of the inductive

effect. The C-H bonds to carbons are weakened hydrogens aretherefore acidic, and can be removed with base


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CR CH

O

R CR CH

O

R CR CH

O

R

keto enolate

(carbanion)

CR CH

OH

R

B

H

H+

(B) REACTIONS DUE TO ACIDITY OF -HYDROGEN continues

eno

The carbanion resulting from removal of a hydrogen to a

carbonyl group is known as an enolate anion which has two

resonance forms


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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 lace. The roduct is called an aldolbecause it has both an

aldehyde and an alcohol function group present.

C HCH2

O

R CH2R CH CH2NaOH/H

2O

C

ROH O

H


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C HCH3

O

CH3 CH CH22

NaOH/H2O

C

OH O

H

Eg.

CC H

O

CH2C H

O

CH2C H

O

enolate

(i) Carbanion (enolate)formation

H

H

H

OH

Mechanism

Hydroxide removes

the acidic proton toform an enolate

CHCH3 CH2

O

C

(ii)

CCH3 H

O

+ CH2C H

O O

H

alkoxide ion

(iii) Protonation

CHCH3 CH2

O

C

O

H H O H CHCH3 CH2

OH

C

O

H

3-hydroxybutanal

Nucleophilic attack on carbonyl

- OH

(aldol)

The enolate (nucleophile)

attacks the carbonyl

carbon of another

molecule of aldehyde

The alkoxide then

removes a proton

from H2O


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CH CH3CHC

O

HCH CH3CH

OH

C

O

H-H2O

Dehydration of the Aldol Product

If the aldol reaction mixture is heated, dehydration takes place

to form an unsaturated carbonyl compound.

-

(conjugated)H

OH

Dehydration is favorable because the product is stabilized by

conjugation of the alkene with the carbonyl group


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Cross Aldol

When an aldol reaction is done with two different aldehydes it

is called a cross aldol reaction.

CC6H5 H

O

CC6H5COH/H2OCCH3CH2 H

O

+

HOH

C

O

H

H CH3

CC6H5C

H CH3

C

O

H

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C10K Carbonyl Chemistry Email