KIMIA ORGANIK FISIK

CARBANION

Kinds of Carbanion

1. Simple ionic

2. Resonance-stabilised carbanions

3. Resonance-stabilised carbanions containing heteroatoms

4. Carbanion with some Covalent Character

3

Simple ion Alkynides

Recall that acetylenic hydrogens have a pKa of about 25

and are much more acidic than most other C-H bonds

The relative acidity of acetylenic hydrogens in solution is:

Acetylenic hydrogens can be deprotonated with relatively

strong bases (sodium amide is typical)

The products are called alkynides

4

Bond Lengths of Ethyne, Ethene and Ethane

The carbon-carbon bond length is shorter as more bonds hold the

carbons together

With more electron density between the carbons, there is more “glue” to hold

the nuclei of the carbons together

The carbon-hydrogen bond lengths also get shorter with more s

character of the bond

2s orbitals are held more closely to the nucleus than 2p orbitals

A hybridized orbital with more percent s character is held more closely to the

nucleus than an orbital with less s character

The sp orbital of ethyne has 50% s character and its C-H bond is shorter

The sp3 orbital of ethane has only 25% s character and its C-H bond is longer

Resonance-stabilised carbanions

C

H

+ NH2-

+C - NH3

C- C

-

C

-

etc

Resonance-stabilised carbanions

containing heteroatoms

The Acidity of the a Hydrogens of Carbonyl Compounds:

Enolate Anions

Hydrogens on carbons a to carbonyls are unusually acidic

The resulting anion is stabilized by resonance to the carbonyl

7

The enolate anion can be protonated at the carbon

or the oxygen

The resultant enol and keto forms of the carbonyl are

formed reversibly and are interconvertible

8

Keto and Enol Tautomers

Enol-keto tautomers are constitutional isomers that are easily

interconverted by a trace of acid or base

Most aldehydes and ketones exist primarily in the keto form because of

the greater strength of the carbon-oxygen double bond relative to the

carbon-carbon double bond

9

b-Dicarbonyl compounds exist primarily in the enol form

The enol is more stable because it has a conjugated p system and

because of stabilization of the enol through hydrogen bonding

Chapter 16 10

Reaction of triphenylphosphine with a primary or

secondary alkyl halide produces a phosphonium salt

The phosphonium salt is deprotonated by a strong base to

form the ylide

Several other groups can increase the acidity of –

hidrogen.

pKa Comparation pKa

CH3CN 25 HCCH 25

CH3NO2 10 Ph-OH 10

CH2(NO2)2 3,6 CH3COOH 4,8

CH(CN)3 < 1

REACTION OF CARBANIONS

(A) AS A BASES:

R- + H-A → R-H + A-

(B) AS NUCLEOPHILES

(I) AT A SATURATED CARBON

(II) AT A CARBONYL GROUP

(III) AT AN α,β-UNSATURATED CARBONYL GROUP

As a Bases

As a nucleophile

15

Replacement of the Acetylenic Hydrogen Atom of

Terminal Alkynes

Sodium alkynides can be used as nucleophiles in SN2

reactions

New carbon-carbon bonds are the result

Only primary alkyl halides can be used or else elimination

reactions predominate

Chapter 16 16

Addition of the ylide to the carbonyl leads to

formation of a four-membered ring oxaphosphetane

The oxaphophetane rearranges to the alkene and

triphenylphosphine oxide

The driving force for the last reaction is formation of the

very strong phosphorus-oxygen double bond in

triphenylphosphine oxide

Chapter 16 17

The overall result of a Wittig reaction is formation of a

C=C bond from a C=O bond

Chapter 16 18

Solved Problem: Make 2-Methyl-1-phenylprop-1-ene

by a Wittig reaction

Chapter 16 19

The Horner-Wadsworth-Emmons reaction employs a

phosphonate ester and generally leads to formation of

an (E)-alkene

Chapter 16 20

The Addition of Organometallic Reagents: The

Reformatsky Reaction

The Reformatsky reaction involves addition of an

organozinc reagent to an aldehyde or ketone

The organozinc reagent is made from an a-bromo ester;

the reaction gives a b-hydroxy ester

The b-hydroxyester is easily dehydrated to an a,b-

unsaturated ester

Chapter 12 21

Organometallic Compounds

Carbon-metal bonds vary widely in character from

mostly covalent to mostly ionic depending on the metal

The greater the ionic character of the bond, the more

reactive the compound

Organopotassium compounds react explosively with water

and burst into flame when exposed to air

Chapter 12 22

Preparation of Organolithium and Organo-

magnesium Compounds

Organolithium Compounds

Organolithium compounds can be prepared by

reaction of an alkyl halide with lithium metal in an

ether solvent

The order of reactivity of halides is R-I > R-Br > R-Cl (R-F

is seldom used)

Chapter 12 23

Grignard Reagents

Grignard reagents are prepared by the reaction of

organic halides with magnesium turnings

An ether solvent is used because it forms a complex with

the Grignard reagent which stabilizes it

Chapter 12 24

Reactions of Organolithium and Organo-magnesium

Compounds

Reactions with Compounds Containing Acidic Hydrogen Atoms

Organolithium and Grignard reagents behave as if they were

carbanions and they are therefore very strong bases

They react readily with hydrogen atoms attached to oxygen, nitrogen or

sulfur, in addition to other acidic hydrogens (water and alcohol solvents

cannot be used)

Chapter 12 25

Organolithium and Grignard reagents can be used to

form alkynides by acid-base reactions

Alkynylmagnesium halides and alkynyllithium reagents are

useful nucleophiles for C-C bond synthesis

Chapter 12 26

Reactions of Grignard Reagents with Oxiranes (Epoxides)

Grignard reagents are very powerful nucleophiles and can react

with the d+ carbons of oxiranes

The reaction results in ring opening and formation of an alcohol product

Reaction occurs at the least-substituted ring carbon of the oxirane

The net result is carbon-carbon bond formation two carbons away from

the alcohol

Chapter 12 27

Reaction of Grignard Reagents with Carbonyl Compounds

Nucleophilic attack of Grignard reagents at carbonyl carbons is

the most important reaction of Grignard reagents

Reaction of Grignard reagents with aldehydes and ketones yields a new

carbon-carbon bond and an alcohol

Chapter 12 28

Alcohols from Grignard Reagents

Aldehydes and ketones react with Grignard reagents

to yield different classes of alcohols depending on the

starting carbonyl compound

Chapter 12 29

Esters react with two molar equivalents of a Grignard

reagent to yield a tertiary alcohol

A ketone is formed by the first molar equivalent of

Grignard reagent and this immediately reacts with a

second equivalent to produce the alcohol

The final product contains two identical groups at the

alcohol carbon that are both derived from the Grignard

reagent

Chapter 12 30

Chapter 12 31

Planning a Grignard Synthesis

Example : Synthesis of 3-phenyl-3-pentanol

The starting material may be a ketone or an ester

There are two routes that start with ketones (one is shown)

Chapter 12 32

Solved Problem: Synthesize the following compound

using an alcohol of not more than 4 carbons as the only

organic starting material

33

Restrictions on the Use of Grignard Reagents

Grignard reagents are very powerful nucleophiles and bases

They react as if they were carbanions

Grignard reagents cannot be made from halides which contain acidic

groups or electrophilic sites elsewhere in the molecule

The substrate for reaction with the Grignard reagent cannot contain any

acidic hydrogen atoms

The acidic hydrogens will react first and will quench the Grignard reagent

Two equivalents of Grignard reagent could be used, so that the first equivalent is

consumed by the acid-base reaction while the second equivalent accomplishes

carbon-carbon bond formation

Chapter 17 34

The Acidity of the a Hydrogens of Carbonyl Compounds:

Enolate Anions

Hydrogens on carbons a to carbonyls are unusually acidic

The resulting anion is stabilized by resonance to the carbonyl

Chapter 17 35

The enolate anion can be protonated at the carbon

or the oxygen

The resultant enol and keto forms of the carbonyl are

formed reversibly and are interconvertible

Chapter 17 36

Keto and Enol Tautomers

Enol-keto tautomers are constitutional isomers that are easily

interconverted by a trace of acid or base

Most aldehydes and ketones exist primarily in the keto form because of

the greater strength of the carbon-oxygen double bond relative to the

carbon-carbon double bond

Chapter 17 37

b-Dicarbonyl compounds exist primarily in the enol

form

The enol is more stable because it has a conjugated p

system and because of stabilization of the enol through

hydrogen bonding

Chapter 17 38

Reactions via Enols and Enolate Anions

Racemization

An optically active aldehyde or ketone with a

stereocenter at the a-carbon can racemize in the

presence of catalytic acid or base

The intermediate enol or enolate has no stereocenter at the

a position

Chapter 17 39

The mechanisms of base and acid catalysed

racemization are shown below

Chapter 17 40

Halogenation of Ketones

Ketones can be halogenated at the a position in the

presence of acid or base and X2

Base-promoted halogenation occurs via an enolate

Chapter 17 41

Acid-catalyzed halogenation proceeds via the enol

Chapter 17 42

Haloform Reaction

Reaction of methyl ketones with X2 in the presence of

base results in multiple halogenation at the methyl

carbon

Insert mechanism page 777

Chapter 17 43

When methyl ketones react with X2 in aqueous

hydroxide the reaction gives a carboxylate anion and

a haloform (CX3H)

The trihalomethyl anion is a relatively good leaving group

because the negative charge is stabilized by the three

halogen atoms

Chapter 17 44

The Aldol Reaction: The Addition of Enolate

Anions to Aldehydes and Ketones

Acetaldehyde dimerizes in the presence of dilute

sodium hydroxide at room temperature

The product is called an aldol because it is both an

aldehyde and an alcohol

Chapter 17 45

The mechanism proceeds through the enolate anion

Chapter 17 46

Dehydration of the Aldol Product

If the aldol reaction mixture is heated, dehydration to an a,b-

unsaturated carbonyl compound takes place

Dehydration is favorable because the product is stabilized by conjugation of

the alkene with the carbonyl group

In some aldol reactions, the aldol product cannot be isolated because it

is rapidly dehydrated to the a,b-unsaturated compound

Chapter 17 47

Synthetic Applications

The aldol reaction links two smaller molecules and

creates a new carbon-carbon bond

Chapter 17 48

Aldol reactions with ketones are generally unfavorable

because the equilibrium favors the starting ketone

The use of a special apparatus which removes product

from the reaction mixture allows isolation of a good yield

of the aldol product of acetone

The Reversibility of Aldol Additions

Aldol addition products undergo retro-aldol reactions in

the presence of strong base

Chapter 17 49

Acid-Catalyzed Aldol Condensation

This reaction generally leads directly to the

dehydration product

Chapter 17 50

Crossed Aldol Reactions

Crossed aldol reactions (aldol reactions involving two

different aldehydes) are of little use when they lead to

a mixture of products

Chapter 17 51

Practical Crossed Aldol Reactions

Crossed aldol reactions give one predictable product when one of

the reaction partners has no a hydrogens

The carbonyl compound without any a hydrogens is put in basic solution,

and the carbonyl with one or two a hydrogens is added slowly

Dehydration usually occurs immediately, especially if an extended

conjugated system results

Chapter 17 52

Claisen-Schmidt Reactions

Crossed-aldol reactions in which one partner is a

ketone are called Claisen-Schmidt reactions

The product of ketone self-condensation is not obtained

because the equilibrium is not favorable

Chapter 17 53

Chapter 17 54

Cyclization via Aldol Condensations

Intramolecular reaction of dicarbonyl compounds proceeds to form

five- and six-membered rings preferentially

In the following reaction the aldehyde carbonyl carbon is attacked

preferentially because an aldehyde is less sterically hindered and more

electrophilic than a ketone

Chapter 17 55

Lithium Enolates

In the presence of a very strong base such as lithium

diisopropyl amide (LDA), enolate formation is greatly

favored

Weak bases such as sodium hydroxide produce only a

small amount of the enolate

Chapter 17 56

Regioselective Formation of Enolate Anions

Unsymmetrical ketones can form two different enolates

The thermodynamic enolate is the most stable enolate i.e. the

one with the more highly substituted double bond

A weak base favors the thermodynamic enolate because an

equilibrium between the enolates is estabilished

The kinetic enolate is the enolate formed fastest and it

usually is the enolate with the least substituted double bond

A strong, sterically hindered base such as lithium diisopropyl

amide favors formation of the kinetic enolate

Chapter 17 57

Lithium Enolates in Directed Aldol Reactions

Crossed aldol reactions proceed effectively when a

ketone is first deprotonated with a strong base such as

LDA and the aldehyde is added slowly to the enolate

Chapter 17 58

An unsymmetrical ketone can be selectively

deprotonated with LDA to form the kinetic enolate and

this will react with an aldehyde to give primarily one

product

Chapter 17 59

Direct Alkylation of Ketones via Lithium Enolates

Enolates can also be alkylated with primary alkyl

halides via an SN2 reaction

Unsymmetrical ketones can be alkylated at the least

substituted position if LDA is used to form the kinetic

enolate

Chapter 17 60

a-Selenation: A Synthesis of a,b-Unsaturated

Carbonyl Compounds

A lithium enolate can be selenated with benzeneselenyl

bromide

Chapter 17 61

The a-selenyl ketone is converted to the a,b-

unsaturated carbonyl compound by reaction with

hydrogen peroxide

Elimination of the selenoxide produces the unsaturated

carbonyl

Chapter 17 62

Additions to a,b-Unsaturated Aldehydes and

Ketones

a,b-Unsaturated aldehydes and ketones can react by

simple (1,2) or conjugate (1,4) addition

Both the carbonyl carbon and the b carbon are

electrophilic and can react with nucleophiles

Chapter 17 63

Stronger nucleophiles such as Grignard reagents favor

1,2 addition whereas weaker nucleophiles such as

cyanide or amines favor 1,4 addition

Chapter 17 64

Chapter 17 65

Michael Additions

Addition of an enolate to an a,b-unsaturated carbonyl

compound usually occurs by conjugate addition

This reaction is called a Michael addition

Chapter 17 66

A Robinson annulation can be used to build a new six-

membered ring on an existing ring

Robinson annulation involves a Michael addition followed

by an aldol condensation to close the ring

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