carbonyl chemistry i

Carbonyl Chemistry ICarbonyl Chemistry I

Lecture 7Lecture 7Chemistry 391 10/20/02

Chemistry 391 10/20/02

C

O

+C

O-


The Carbonyl GroupThe Carbonyl GroupIn this and several following lectures we study the reactions of classes of compounds containing the carbonyl group, C=O– Aldehydes and ketones – Carboxylic acids – Derivatives of carboxylic Acids – Enolate anions


Resonance Description ofResonance Description ofCarbonyl GroupCarbonyl Group

nucleophiles attack the carbon;

electrophiles attack the oxygen

C

O•• ••

C

O

+

–•••• ••


The Carbonyl GroupThe Carbonyl GroupThe 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

C Oσ

π


Structure of FormaldehydeStructure of Formaldehyde

The molecule is planarbond angles: close to 120°C=O bond distance: 1.22 Å


Bonding in FormaldehydeBonding in Formaldehyde

Carbon and oxygen are Carbon and oxygen are spsp22 hybridizedhybridized


Bonding in FormaldehydeBonding in Formaldehyde

The The pp orbitalsorbitals on carbon on carbon and oxygen overlap to and oxygen overlap to form a form a ππ bond….bond….

Is this the picture of such Is this the picture of such a molecular orbital?a molecular orbital?


NomenclatureNomenclature--AldehydesAldehydesIUPAC names: select as the parent alkane the longest chain of carbon atoms that contains the carbonyl group..subtract e and add al– because the carbonyl group of the aldehyde must be on

carbon 1, there is no need to give it a number

For unsaturated aldehydes, show the presence of the C=C by changing -an- to -en-– the location of the suffix determines the numbering

pattern


NomenclatureNomenclature--AldehydesAldehydes

O

CH3 CHCH2 CH1234

CH3O

CH3 CH2 CH2 CH2 CH12345

3-MethylbutanalPentane Pentanal

O1

2

3

4

5

6

7O

CH2 =CHCH123

H8

(2E)-3,7-Dimethyl-2,6-octadienal (Geranial)

2-Propenal (Acrolein)


Nomenclature ofNomenclature of AldehydesAldehydes

C H

O

when named as a suffix it is

when named as a substituent this is a

formylformyl groupgroup carbaldehydecarbaldehydecarboxaldehydecarboxaldehyde


2-Cyclopentene-carbaldehyde

2,2-Dimethylcyclo-hexanecarbaldehyde

CHO

CH 3CH 3

CHO

3

11

22

NomenclatureNomenclature--AldehydesAldehydesFor cyclic molecules in which the -CHO group is attached to the ring, the name is derived by adding the suffix -carbaldehyde to the name of the ring


Nomenclature ofNomenclature of AldehydesAldehydesO O

H H

4,4-dimethylpentanal 5-hexenal

O

HCCHCH

O

22--phenylpropanedial


ManyMany aldehydesaldehydes and ketones occur naturallyand ketones occur naturally

22--heptanoneheptanone(component of alarm(component of alarmpheromone of bees)pheromone of bees)

O O

transtrans--22--hexenal hexenal (alarm pheromone(alarm pheromoneof of myrmicinemyrmicine ant)ant)


Structure of KetonesStructure of KetonesThe functional group of a ketone is a carbonyl group bonded to two carbon atoms

CH3 -C-CH 3

O

Propanone (Acetone)

O

Cyclohexanone


IUPAC Nomenclature of KetonesIUPAC Nomenclature of Ketones

CH3CH2CCH2CH2CH3

O

CH3CHCH2CCH3

O

CH33-hexanone

4-methyl-2-pentanone

H3C 4-methylcyclohexanoneO


Trivial Nomenclature of KetonesTrivial Nomenclature of Ketones

CH3CH2CCH2CH2CH3

O O

CH2CCH2CH3

ethyl propyl ketonebenzyl ethyl ketone

divinyl ketoneCH CH2

O

H2C CHC


NomenclatureNomenclature--KetonesKetonesIUPAC names:– select as the parent alkane the longest chain that

contains the carbonyl group, – number to give C=O the smaller number and then

subtract e and add onesubtract e and add one

O

CH3 CH2 CCH2 CHCH31 2 3 4 5 6

CH3 O1

2345

6

7

Bicyclo[2.2.1]-2-heptanone

O

CH3 CCH3

5-Methyl-3-hexanonePropanone (Acetone)


NomenclatureNomenclature--KetonesKetonesCCH2 CH2 CH2 CH3

O1 2 3 4 5

1-Phenyl-1-pentanone

Even the IUPAC system retains the common names acetone, acetophenone, and benzophenone

CCH3

O OC-CH3 CCH3

O

AcetophenoneAcetone Benzophenone


Order of PrecedenceOrder of Precedence(Pecking order)(Pecking order)

For compounds that contain more than one functional group indicated by a suffix

Prefix if Lower in Precedence

Suffix if Higher in Precedence

Functional Group

C=O

-CO 2 H

-OH-NH 2-SH

Prec

eden

e

-oic acid-CHO oxo--al

oxo--onehydroxy-

-amine-ol

mercapto-amino-

-thiol

IUPAC Nomenclature of KetonesIUPAC Nomenclature of Ketones

CH3CHCH2CCH3

O

CH3CH3CH2CCH2CH2CH3

O

3-hexanone 4-methyl-2-pentanone

O

O

H

4-oxohexanal

CH3CH2CCH2CH2CH3

O

ethyl propyl ketone

NomenclatureNomenclature--KetonesKetones

Even the IUPAC system retains the common Even the IUPAC system retains the common names acetone,names acetone, acetophenoneacetophenone, and , and benzophenonebenzophenone

1-Phenyl-1-pentanone

CCH2 CH2 CH2 CH3

O1 2 3 4 5

BenzophenoneAcetophenone

CCH3

OOC-CH3 CCH3

O

Acetone

Synthesis ofSynthesis of AldehydesAldehydes and Ketonesand Ketones

•• from alkenes• by ozonolysis

• from alkynes• by hydration (via enol)

• from arenes• via Friedel-Crafts acylation

•

A number of A number of reactions alreadyreactions alreadystudied providestudied provide

efficient syntheticefficient syntheticroutes toroutes to

aldehydesaldehydes and and ketones.ketones.

Reaction ThemeReaction ThemeThe most common reaction of a carbonyl group is addition of a nucleophile to form a tetrahedral addition compound

Tetrahedral carbonyl addition compound

+ CR

RO CNu

O -

RR

Nu -

Here it is an acid or electrophile

Reaction ThemeReaction ThemeA second common reaction is with a proton or Lewis acid to form a resonance-stabilized cation

– protonation increases the electron deficiency of the carbonyl carbon and makes it more reactive towardnucleophiles

+fast +

••••

••

+C OR

RC O

R

RH B-H-B

Here it is a base or Nucleophile!


Carbon Carbon NucleophilesNucleophilesAddition of carbon nucleophiles is one of the most important types of nucleophilic additions to a C=O group; a new carbona new carbon--carbon bondcarbon bond is formed in the process!!!!

We will study the addition of these carbonnucleophiles

A Grignard reagent

An organolithium reagent

An anion of a terminal alkyne

Cyanide ion

RC C - NRMgX RLi - C


Victor Victor GrignardGrignard

Shared Nobel Prize with

Sabatier in 1912

“student” of Philippe Barbier


GrignardGrignard ReagentsReagents

Given the difference inGiven the difference in electronegativityelectronegativitybetween carbon and magnesium, the Cbetween carbon and magnesium, the C--Mg bond Mg bond is polar covalent, with Cis polar covalent, with Cδδ-- and Mgand Mgδδ++– Grignard reagents behave like a carbanions

CarbanionCarbanion: an anion in which carbon has an unshared : an anion in which carbon has an unshared pair of electrons and bears a negative chargepair of electrons and bears a negative charge– a carbanions are good nucleophiles and add efficiently to the

carbonyl group of aldehydes and ketones


GrignardGrignard ReagentsReagentsAddition of a Grignard reagent to formaldehyde followed by H3O+ gives a 1° alcohol

This sequence (mechanism) is general and important!

Mg+2H3O+

CH3CH2- MgBr+

HC

HO CH3CH2 C

H

H

O- MgBr+CH3CH2 C

H

H

OH +THF dil.


GrignardGrignard ReagentsReagentsAddition to any other RCHO gives a 2° alcohol

Mg+2H3O+

CH3CH2- MgBr+ C

HO CH3CH2 C

H

O- MgBr+ +THF dil.

CH3CH2 C

H

OH

• You may change decorations at will…review pages 263-264

– but, be careful of acidic functions like -OH


GrignardGrignard ReagentsReagentsAddition to CO2 gives a carboxylic acid

This is a great way to add a carbon

Mg+2H3O+

CH3CH2- MgBr+ CH3CH2 C O- MgBr+

O

+THF dil.

CH3CH2 C OH

O

C OO


GrignardGrignard ReagentsReagents

Addition to a ketone gives a 3° alcohol

Please try this with other Grignard reagents and other ketones

Mg+2H3O+


CH3

CH2

CH2

CH3

+THF dil.

CH3CH2 C OH

CH3

CH2

CH2

CH3

C O

CH3

CH2

CH2

CH3


GrignardGrignard ReactionsReactions

Mg+2H3O+

CH3CH2- MgBr+

HC

HO CH3CH2 C

H

H

O- MgBr+CH3CH2 C

H

H

OH +THF dil.

Mg+2H3O+

CH3CH2- MgBr+ C

HO CH3CH2 C

H

O- MgBr+ +THF dil.

CH3CH2 C

H

OH

Mg+2H3O+


CH3

CH2

CH2

CH3

+THF dil.

CH3CH2 C OH

CH3

CH2

CH2

CH3

C O

CH3

CH2

CH2

CH3

GrignardGrignard ReagentsReagentsProblem: 2-phenyl-2-butanol can be synthesized by three different combinations of a Grignard reagent and a ketone. Show each combination

C-CH 2 CH3

OH

CH3


Grignard Reactions

Mg+2H3O+


O

+THF dil.

CH3CH2 C OH

O

C OO

MgBrO

THFO-MgBr+

H3O+

Dilute

OH

These are valuable and important reactions…

Please add to your card stock!


Salts of Terminal AlkynesSalts of Terminal AlkynesAddition of an acetylide anion followed by H3O+ gives an α-acetylenic alcohol

Mg+2H3O++

THF dil.C O

CH3

CH2

CH2

CH3

C O- MgBr+

CH3

CH2

CH2

CH3

C OH

CH3

CH2

CH2

CH3

RC C- Na+ RC C RC C


Salts of Terminal Salts of Terminal AlkynesAlkynes

HO C

OCCH3HO

HO CH2 CH

O

H2 SO 4 , HgSO4

H2 O

2 . H 2O2 , NaOH

An α-hydroxyketone

α

β

α

CH

1 B2H6

A β-hydroxyaldehyde

Write the mechanism using the arrow convention

GrignardGrignard reagents react with estersreagents react with esters

––++

RR CC

OO••••

•••• ••••

OCHOCH33••••••••

R'R'

RR

MgXMgX

CC

OO

••••••••

δδ–– δδ++ OCHOCH33••••••••

R'R' diethyldiethyletherether

MgXMgX

but species formed is but species formed is unstable and dissociates unstable and dissociates under the reaction under the reaction conditions to form a ketoneconditions to form a ketone

GrignardGrignard reagents react with estersreagents react with esters

––++

RR CC

OO••••

•••• ••••

diethyldiethyletherether OCHOCH33

••••••••

R'R'

––CHCH33OOMgXMgX

RR

MgXMgX

CC

OO

••••••••

δδ–– δδ++ OCHOCH33••••••••

R'R'

MgXMgX

this ketone then goes this ketone then goes on to react with a on to react with a second mole of thesecond mole of theGrignardGrignard reagent to reagent to give a tertiary alcohol

CC

OO

RR R'R'

••••••••give a tertiary alcohol

ExampleExample

2 CH2 CH33MgBrMgBr ++ (CH(CH33))22CHCCHCOCHOCH33

OO

1. diethyl ether1. diethyl ether

2. H2. H33OO++

Two of the groups Two of the groups attached to the attached to the tertiary carbon tertiary carbon come from thecome from theGrignardGrignard reagent

(CH(CH33))22CHCCHCCHCH33

OHOH

CHCH33reagent

(73%)(73%)


GrignardGrignard reagents react with:reagents react with:

formaldehydeformaldehyde to give primary alcoholsto give primary alcohols

aldehydesaldehydes to give secondary alcoholsto give secondary alcohols

ketonesketones to give tertiary alcoholsto give tertiary alcohols

estersesters to give tertiary alcoholsto give tertiary alcohols

COCO22 to give acidsto give acids

epoxidesepoxides


HH22CC CHLiCHLi CHCH

OOOrganolithiumOrganolithium ReagentsReagents

++

1. diethyl ether1. diethyl ether

2. H2. H33OO++

CHCH22CHCHCHCH

OHOH(76%)(76%)


Salts of Terminal AlkynesSalts of Terminal AlkynesAddition of an acetylide anion followed by H3O+ gives an α-acetylenic alcohol

Mg+2H3O++

THF dil.C O

CH3

CH2

CH2

CH3

C O- MgBr+

CH3

CH2

CH2

CH3

C OH

CH3

CH2

CH2

CH3

RC C- Na+ RC C RC C


Addition of HCNAddition of HCNMechanism of cyanohydrin formation

N C- H3O+

THF dil.C O

CH3

CH2

CH2

CH3

C O-

CH3

CH2

CH2

CH3

N C Mg+2+C OH

CH3

CH2

CH2

CH3

N C


CyanohydrinsCyanohydrinsThe value of cyanohydrins is for the new functional groups into which they can be converted– acid-catalyzed dehydration of the 2° alcohol gives a

valuable monomer

Propenenitrile (Acrylonitrile)

+

acid catalyst

2-Hydroxypropanenitrile (Acetaldehyde cyanohydrin)

CH3 CHC N

OH

NCH2 =CHC H2 O


CyanohydrinsCyanohydrins– acid-catalyzed hydrolysis of the cyano group

gives an α-hydroxycarboxylic acid

acid catalyst

Benzaldehyde cyanohydrin (Mandelonitrile)

2-Hydroxy-2-phenyl- ethanoic acid

(Mandelic acid)

+N

OH

CHC CHCOH

HO OH2 O


CyanohydrinsCyanohydrins– catalytic reduction of the carbon-nitrogen

triple bond converts the cyano group gives a 1° amine

Benzaldehyde cyanohydrin 2-Amino-1-phenylethanol

Ni+CHC

OH

NOH

CHCH2 NH22 H2

LiAlH4 also works well...LiAlH4 also works well...

But…what about Pd/C and H2But…what about Pd/C and H2


WittigWittig ReactionReactionThe Wittig reaction is a very versatile synthetic method for the synthesis of alkenes fromaldehydes and ketones.

Triphenyl- phosphine oxide

Methylene- cyclohexane

A phosphonium ylide

+

+-+

+

O

CH2 Ph 3 P-O -

Ph 3 P-CH 2


Phosphonium YlidesPhosphonium YlidesYlideYlide: a molecule which, when written in a Lewis structure showing all atoms with complete valence shells, has positive and negative charges on adjacent atoms

Phosphonium ylidesPhosphonium ylides are formed in two steps: 1. treatment of triphenylphosphine with a 1° or 2°

alkyl halide to form a phosphonium salt followed by 2. treatment of the phosphonium salt with strong base,

typically butyllithium


Phosphonium YlidesPhosphonium Ylides

••

A phosphonium ylide

Butane

Butyllithium

+++-

+I -

CH2 -PPh 3 CH3 CH2 CH2 CH3 Li + I -

CH3 CH2 CH2 CH2 Li + + H-CH 2 -PPh 3

Triphenyl-phosphine

An alkyltriphenyl-phosphonium iodide

++Ph 3 P CH3 -I Ph 3 P-CH 3 I-S N2

Ph3P+ CH2-

Ph3P CH2


WittigWittig ReactionReactionPhosphonium ylides react with the C=O group of aldehydes or ketones to give alkenes

Triphenylphosphine oxide

An alkene

+

-••+

An oxaphosphetane

•••• •• ••

-

+•• ••

••

CH2

CR2 O

CH2

CR2

CH2

CR2O

Ph 3 P Ph 3 P

O

Ph 3 P


WittigWittig ReactionReactionExamples:

++ -

+2-Methyl-2-heptene

+

O

CH3

CH3 CCH3 Ph 3 P-CH(CH 2 ) 3 CH3

CH3 C=CH(CH2 ) 3 CH3 Ph 3 P-O -


WittigWittig ReactionReactionMore examples

-++

+ 1-Phenyl-2-butene (87% Z isomer; 13% E isomer)

+

O

PhCH 2 CH Ph 3 P-CHCH 3

PhCH 2 CH=CHCH 3 Ph 3 P-O -

Don’t plan to control the E/Z ratio…you get generally get a mixtureDon’t plan to control the E/Z ratio…you get generally get a mixture


TheThe WittigWittig ReactionReactionSee... sometimes you can control it but…we won’t try in this class

++ -

+

Ethyl (E)-4-phenyl-2-butenoate (only the E isomer is formed)

+

O O

Ph 3 P-O -

PhCH 2 CH Ph 3 P-CHCOCH 2 CH3

H

C CCOCH2 CH3

PhCH 2 H

O

carbonyl chemistry i

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