10_alcohols_post

Sec. 11 -alcohols 1

Conversion of Alcohols into Alkyl Halides

Hydroxyl groups are poor leaving groups, and as such, are often converted to alkyl halides when a good leaving group is needed

Three general methods exist for conversion of alcohols to alkyl halides, depending on the classification of the alcohol and the halogen desired

Reaction can occur with phosphorus tribromide, thionyl chloride or hydrogen halides

Sec. 11 -alcohols 2

Alkyl Halides from the Reaction of Alcohols with PBr3 and SOCl2

These reagents only react with 1° and 2° alcohols in SN2 reactionsIn each case the reagent converts the hydroxyl to an excellent leaving groupNo rearrangements are seen

Reaction of phosphorous tribromide to give alkyl bromides

Sec. 11 -alcohols 3

Reaction of thionyl chloride to give alkyl chlorides

Often an amine is added to react with HCl formed in the reaction

Sec. 11 -alcohols 4

Tosylates, Mesylates, and Triflates: Leaving Group Derivatives of Alcohols

The hydroxyl group of an alcohol can be converted to a good leaving group by conversion to a sulfonate ester

Sulfonyl chlorides are used to convert alcohols to sulfonate estersBase is added to react with the HCl generated

Sec. 11 -alcohols 5

A sulfonate ion (a weak base) is an excellent leaving group

If the alcohol hydroxyl group is at a stereogenic center then the overall reaction with the nucleophile proceeds with inversion of configuration

The reaction to form a sulfonate ester proceeds with retention of configuration

Sec. 11 -alcohols 6

Alcohols by Reduction of Carbonyl Compoundswith LiAlH4 and NaBH4

R-OH

The carbonyl group is susceptible to nucleophilic attack.

Nucleophile(base)

Electrophile(acid)

Sec. 11 -alcohols 7

Mechanism with LiAlH4 and NaBH4

C

O

RR

Li H3Al- H+

Nucleophile(base)

Electrophile(acid)

C OAlH3 Li

R

R

H+ C

O

RR

3

C O

R

R

H Al

O

O

O

CR

H

R

C

C

R

R

R R

H

H

a tetra-alkyl aluminate

H3O+

C OH

R

R

H

C

O

RR

Na H3B- H+

+ H2O

Nucleophile(base)

Electrophile(acid)

Sec. 11 -alcohols 8

Examples

O

H

1) LiAlH4/Et2O

2) H3O+

NaBH4/H2Oor

O

O

HO

NaBH4/H2O

1) LiAlH4/Et2O

2) H3O+

OO

O

OH

O1) LiAlH4/Et2O

2) H3O+

OS = +1

OS = +2

OS = +3

OS = +2

OS = +3

OS = +3

Reduction - gain of electronsor add hydrogens

Sec. 11 -alcohols 9

Oxidation of Alcohols

CH3CH2CH2OHKMnO4 / OH¯ / heat

orNaCr2O7 / H2SO4

orH2CrO4

very hard tostop oxidation

propanol

OH

or CrO3 Jones reagent

H2CrO4

acetone

OHH2CrO4

acetone

CH3CH2CH2OH + PCCCH2Cl2

CH3CH2CH

O

HC

Cl

Cl

Haprotic solvent

stops at aldehyde

Oxidation - loss of electronsor add oxygens

OS = -1

OS = -1

Sec. 11 -alcohols 10

Organometallic Compounds

C M+

C M- +

C M

M = Na+ or K+

Primarily ionic

explosive with water

M = Mg or Lipolar covalent

relative stable in ether

M = Pb, Sn, Hg, or TlPrimarily covalent

much less reactive

Organolithium Compounds

Br

Br

+ 2 Li

+ 2 Li Li

Li + LiBr

+ LiBr

ether

ether


Grignard Reagents

Br

Br

+ Mg

+ Mg MgBr

MgBrether

ether

General Reactions

The actual structure of the Grignard reagents are more complex than the formula

2 RMgX R2Mg + MgX2

It also forms a complex with the solvent, ether

For convenience we will represent the Grignard reagent as RMgX


Grignard reagents as well as organolithium compounds are very strong bases. They act as if they have free carbanions. Organolithium

compounds will react as a Bronsted-Lowry base or as a nucleophile.

CH3MgBr + CH3CH2O-H

carbon with a negative charge is a stronger base than an oxygen with a negative charge

C C H +

OSN2

dilute HCl


Grignard Reagents and Carbonyl Compounds

Mechanism

R MgX

nucleophile(base)

R

C O

R

electrophile(acid)

+

nucleophilic attackon carbonyl carbon

Step One

halomagnesium alkoxide

Step Two

R

C O

R

R Mg2+ X

ether

H O

H

H

+

X

alcohol

Order of Reactivity RI > RBr > RCl

RI and RBr mostly used RCl reacts sluggishly


General Reactions

R1MgBr- + - H

C O

H

+ -+

ether

formaldehyde

HBr(dilute)

+ MgBr2

1° alcohol

R1MgBr- + -

C O

H

+ -+

ether

an aldehyde

HCl(dilute)

+ MgBrCl

2° alcohol

R2

R1MgBr- + -

C O+ -

+ether

a ketone

HCl(dilute)

+ MgBrCl

3° alcohol

R2

R3


General Reactions

R1MgBr- + -

C O+ -

+ether

a ester

HCl(dilute)

3° alcohol

R2

R3O

R1MgBr- +

Grignard Reagent add twice because a ketone is created as an intermediate that can react with the second equivalence of the Grignard Reagent




Because Grignard reagents are very strong bases they can not be made from compounds that have acidic hydrogens -OH, -NH2, -SH, -CO2H, -SO3H etc.

Limited to alkyl halides or organic compounds containing carbon-carbon double bonds, internal triple bonds, ether linkages and -NR3 groups.

Although we can make acetylenic Grignards through an acid base reaction and use it to our advantage.

Examples

CH3CH2C CHCH3MgBr

CH3CH2C CMgBr

O

Hether

+

-

1)

2) H3O+

OH

O

+ CH4(g)

H3C

CH

H3C

CH2Li1)

2) H3O+ OH


Examples

Sometimes a Grignard reaction can be completed with a compound containing an acidic hydrogen if two equivalents of the reagent is used

CH3MgBr +ether

HOCH2CH2CCH3

OCH3MgBr

2) H3O+

CH3CH2C CH Na NH2

O

CCH3H3C1)

2) NH4Cl, H2O

N

H

H

H

H+

Cl

acidH2 / Pd

a lot missing

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