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 !
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