FUNCTIONAL GROUP INTERCONVERSION

1. Done by
SHOBANA.N.S
QUEEN MARY’S COLLEGE

3.  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

4.  Alcohols that form stable carbocations will react
faster
 Tertiary chloroalkane formed is insoluble and so it
looks cloudy

5.  It’s just the SN1 reaction of an alcohol with
HCl.
 The Lucas reagent is ZnCl2 in concentrated
HCl.

6. For comparison :

7. OH
primary
OH
secondary
OH
tertiary
ZnCl2, HCl
Cl
>10 minutes
(if at all)
Cl
<5 minutes
Cl
1-2 seconds

8. LUCAS TEST

9.  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.

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

11.  The most frequently used of these reagents is HF-pyridine
(Olah’s Reagent)

12. GENERAL FORMAT

13. • SN1indicates substitution, nucleophilic, unimolecular
reaction
• It involves two steps
STEP 1
• Loss of the leaving group, LG, to generate a
carbocation intermediate

14. 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-

15.  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
HBr
Br
+
Br
cis & trans

16. HO
H-Br
Br
+
Br
cis & trans
H
HO
H
- H2O
Br
Br

17.  SN2 indicates
a substitution, nucleophilic, bimolecular reaction.
 This is a concerted process (single step).

18.  REACTIVITY ORDER:
CH3- > CH3CH2- > (CH3)2CH- > (CH3)3C-
 Primary alcohol will proceed via SN2 Mechanism

19. PX3
PX5
SOCl2
SOCl2
PCl3
PCl5

20.  3R - OH + PX3 3R - X + H3PO3
 R - OH + PX5 R - X + POX3 + HX

21.  3R - OH + PCl3 3R - Cl + H3PO3
 R - OH + PCl5 R - Cl + POCl3 + HCl
C2H5OH
PCl5
C2H5Cl
POCl3
HCl
+ + +
C2H5OH
+
+
PCl3

27. REACTION MECHANISM

28.  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.
LiCl
Acetone
RT, 72 h
73 %
EXAMPLE 1: Synthesis of Taxol

29. Synthesis of Strychnine
O
O
N
O
N
N
H3C
CH3
O
Ms
t-Bu
O
O
N
O
N
N
H3C
CH3
O
H
t-Bu
O
O
N
Br
N
N
H3C
CH3
O
t-Bu
MsCl LiBr

30. Synthesis of Doliculide
NaI
MEK
85 °C, 15 h
Synthesis of Cristatic Acid
MsCl, LiBr
CH2Cl2, THF
0 °C, 3 h
76 %

31. SYNTHESIS OF HIRSUTENE
n-Bu4N+ I-PhH
Reflux, 2 h
75 %
SYNTHESIS OF AIGIALOMYCIN
NaI
MEK
Reflux, 24 h
99 %

35. • 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.