Conversion of Alcohols to Halide

CONVERSIONOF

ALCOHOLS INTO HALIDE

Done by

SHOBANA.N.SQUEEN MARY’S COLLEGE

REAGENT 1: HX

Possible to make tertiary chloroalkanes But to make primary or secondary ones you

really need to use a different method.

Tertiary alcohol + HCl Tertiary chloroalkanes

HYDROCHLORIC ACID

Alcohols that form stable carbocations will react faster

Tertiary chloroalkane formed is insoluble and so it looks cloudy

It’s just the SN1 reaction of an alcohol with HCl. 

The Lucas reagent is ZnCl2 in concentrated HCl.

What is the Lucas test? 

ROLE OF ZnCl2

For comparison :

Lucas test

OHprimary

OH

secondary

OH

tertiary

ZnCl2, HCl

Cl

Cl

Cl

1-2 seconds

<5 minutes

>10 minutes(if at all)

LUCAS TEST

Instead of hydrobromic acid, usually alcohol is treated with a mixture of sodium or potassium bromide and concentrated sulfuric acid.

This produces hydrogen bromide which reacts with the alcohol.

HYDROBROMIC ACID

Alcohol reacts with mixture of sodium or potassium iodide and conc. phosphoric(V) acid, H3PO4.

HYDROIODIC ACID

HYDROFLUORIC ACID The most frequently used of these reagents is HF-pyridine (Olah’s Reagent)

GENERAL FORMAT

• SN1indicates substitution, nucleophilic,  unimolecular reaction

• It involves two steps

STEP 1

SN1 REACTION

• Loss of the leaving group, LG, to generate a carbocation intermediate

STEP 2

• Rapid attack of a nucleophile on the electrophilic carbocation to form a new sigma bond

REACTIVITY ORDER :

(CH3)3C-  >  (CH3)2CH-   >  CH3CH2-  >  CH3-

Polar solvents which can stabilize carbocations which can favor the SN1 reaction 

• Hydrogen halide reactivity order :

HI > HBr > HCl > HF

• Secondary and tertiary alcohols will proceed via SN1 reaction

HO

HBrBr

+

Br

cis & trans

SOLVENT

HO

H-BrBr

+

Br

cis & trans

HO

H

H- H2O

Br

Br

SN2 indicates a substitution, nucleophilic, bimolecular  reaction.

This is a concerted process (single step).

SN2 REACTION

REACTIVITY ORDER:  CH3-  >  CH3CH2-  >  (CH3)2CH-  >  (CH3)3C-

Primary alcohol will proceed via SN2 Mechanism

PX3

PX5

SOCl2

OTHER REAGENTS USED

SOCl2

PCl3PCl5

3R - OH + PX3  3R - X + H3PO3

R - OH + PX5  R - X + POX3 + HX

PX3 AND PX5

3R - OH + PCl3 3R - Cl + H3PO3

R - OH + PCl5  R - Cl + POCl3 + HCl  

C2H5OHPCl5

C2H5Cl

POCl3

HCl

+ ++

C2H5OH

++

PCl3

MECHANISM OF ALCOHOL WITH PX3

MECHANISM WITH PX5

EXAMPLE 1 MECHANISM

EXAMPLE 2 MECHANISM

Finkelstein Reaction

REACTION MECHANISM

AcetoneRT, 72 h73 %

LiCl

EXAMPLE 1: Synthesis of Taxol

 It involves the exchange of one halogen atom for another

The reaction works well for primary halides, allyl, benzyl, and α-carbonyl halides. 

Secondary halides are far less reactive.

Vinyl, aryl and tertiary alkyl halides are unreactive.

O

O

N

N

N

H3C

CH3

O

O

Ms

t-Bu

O

O

N

N

N

H3C

CH3

O

O

H

t-Bu

O

O

N

N

N

H3C

CH3

O

Br

t-Bu

Synthesis of Strychnine

MsCl LiBr

CH2Cl2, THF0 °C, 3 h76 %

MsCl, LiBr

 Synthesis of Doliculide

NaI

MEK85 °C, 15 h

Synthesis of Cristatic Acid

n-Bu4N+ I-

PhHReflux, 2 h75 %

SYNTHESIS OF HIRSUTENE

NaI

MEKReflux, 24 h99 %

SYNTHESIS OF AIGIALOMYCIN

OTHER EXAMPLES:

WHY ALCOHOL TO HALIDE ??

• This is a useful reaction, because the resulting alkyl halides are versatile compounds that can be converted into many compounds that are not directly accessible from the alcohol itself.

THANK YOU !