Correlation analysis in the benzylation of sulfur nucleophiles

Article abstract of DOI:10.3184/030823407X191985

In the nucleophilic substitution reaction of benzyl bromides with three sulfur nucleophiles a linear relationship between the nucleophile discrimination parameter (s) and the Hammett substituent constant (σ) is observed.

Full text of DOI:10.3184/030823407X191985

JOURNAL OF CHEMICAL RESEARCH 2007
FEBRUARy, 115–116
RESEARCH PAPER 115
Correlation analysis in the benzylation of sulfur nucleophiles
P. Kalyani and P. Manikyamba*
Department of Chemistry, Kakatiya University, Warangal – 506 009, India
In the nucleophilic substitution reaction of benzyl bromides with three sulfur nucleophiles a linear relationship
between the nucleophile discrimination parameter (s) and the Hammett substituent constant (s) is observed.
Keywords: nucleophile discrimination parameter, Hammett substituent constan, benzylation, sulfur nucleophile
Nucleophilic substitution at benzylic carbon atom is of
broad synthetic utility. A literature survey on the kinetics
of nucleophilic substitution on benzyl halides shows that a
wide range of nucleophiles have been used. Some of these
nucleophiles are thioureas,1-3 thiobenzamides,3,4 anilines,5
pyridine,6,7sulfate,8sulfite,8urea,8thiosulfate,8,9ands-triazole.10
In some of these studies the Swain and Scott relationship11 has
been applied and the nucleophile discrimination parameters
have been determined. The present study is aimed at the kinetic
study of nucleophilic substitution reaction at substituted benzyl
bromides using three structurally similar sulfur nucleophiles,
2-mercaptobenzimidazole (2-MBIZ), 2-mercaptobenzothiazole
(2-MBTZ) and 2-mercaptobenzoxazole (2-MBOZ) and
determining their nucleophilicity constants which are not
available in the literature.
and 3.18 respectively. Correlation of the rate constants of the
reactions between p-nitro-, p-bromo- and p-methyl- benzyl
bromides and these nucleophiles with their nucleophilicity
constants resulted in the following relationships.
log k = –7.80 + 1.38 n
;
r = 0.98
(0.23)
(0.88) (0.22)
with p-nitrobenzyl bromide
log k = –6.89 + 1.21 n ; r = 0.99
(0.26) (0.07) (0.07)
with p-bromobenzyl bromide
log k = –6.05 + 1.03 n ; r = 0.98
(0.42) (0.10) (0.11)
Results and discussion
with p-methylbenzyl bromide.
Second-order rate constants of the reaction between benzyl
bromides (p-NO2, p-Br, p-CH3 and –H) and the sulfur
nucleophiles 2-MBIZ, 2-MBTZ, 2-MBOZ, thiourea and
N-methylthiourea were determined in methanol medium
at 303 K and are presented in Table 1. The nucleophilicity
constants of thiourea (4.10)11 and N-methylthiourea (4.00)12
and the substrate constant ‘s’ for benzyl bromide12 are
available in the literature. Using these values, and the Swain–
Scott relationship,11 the nucleophilicity constants of 2-MBIZ,
2-MBTZ and 2-MBOZ were determined. These are 4.58, 3.70
The values in parentheses are standard errors of the regression
coefficients.
The nucleophile discrimination parameters (substrate
parameters), s11, which are a measure of the susceptibility
towards nucleophilic substitution of the different benzyl
bromides are in the order p-NO2 > p-Br > –H > p-CH3. The
electron-withdrawing group on the benzene ring increases
its susceptibility towards nucleophilic substitution while the
electron-releasing group decreases this nature. An attempt to
Table 1 Second-order rate constants, and nucleophile discrimination parameters [Benzyl bromide] = [Nucleophile] = 2.00 × 10-2 mol
dm-3 Solvent = Methanol Temp = 303 K
Substituent
–H
Nucleophile
k × 104/dm3 mol-1 s-1
s
sa
Thiourea
N-methylthiourea
2-MBIZ
2-MBTZ
2-MBOZ
113.02
87.54
401.26
37.24
10.62
1.10b
0.00
p-CH3
p-Br
Thiourea
N-methylthiourea
2-MBIZ
2-MBTZ
2-MBOZ
166.64
87.25
392.32
70.83
13.42
1.03
1.21
1.38
–0.17
0.23
0.78
Thiourea
N-methylthiourea
2-MBIZ
2-MBTZ
2-MBOZ
145.00
97.65
416.70
33.42
8.92
p-NO2
Thiourea
N-methylthiourea
2-MBIZ
2-MBTZ
2-MBOZ
125.02
60.04
250.32
10.43
4.26
aFrom ref. 13.
bFrom ref. 12.
* Correspondent. E-mail: mani_prerepa@yahoo.co.in
PAPER: 06/4430

116 JOURNAL OF CHEMICAL RESEARCH 2007
correlate s and the Hammett substituent constant s13 resulted
in the following relation
Experimental
Materials
Benzyl bromide (Riedel), p-nitrobenzyl bromide (Fluka),
p-methylbenzyl bromide (Fluka), p-bromobenzyl bromide (Fluka),
s = 1.10 + 0.37 s
(0.01) (0.02)
n = 4
;
r = 0.99
(0.02)
2-mercaptobenzimidazole
(Aldrich),
2-mercaptobenzothiazole
(Aldrich), 2-mercaptobenzoxazole (Aldrich), thiourea (BDH AnalaR),
N-methyl thiourea (Fluka) were used without further purification.
Methanol (Sd Fine) was distilled using a literature method.
This excellent correlation indicates that the nucleophile
discrimination parameter, s, increases with the increase in the
Hammett substituent constant s.
The second-order rate constants presented in Table 1 suggest
that with each substrate the order of reactivity is
Kinetic measurements
The rates of the reactions between benzyl bromides and the nucleophiles
were studied conductometrically at 303 K. The concentration of both
the reactants was 2.00 ¥ 10-2 mol dm-3. The second-order rate constants
Ct −Co
(k) were obtained by plotting
against time according to the
C
∞ −Ct
2-MBIZ >> 2-MBTZ > 2-MBOZ
relation14
Ct −Co
∞ −Ct
The highest reactivity of 2-MBIZ among the three is probably
due to the presence of two nitrogen atoms holding a pair of
electrons on either side of >C=S.
k = C
where ‘a’ is the initial concentration of the reactants and C0, Ct and
C∞ are the conductances of the reaction mixture at the beginning,
at time ‘t’ and after completion of the reaction respectively.
With each nucleophile used the corresponding S-benzyl derivative
was obtained as the product. This was identified by recording the ir
spectrum of the product separated from the reaction mixture. This
showed absorption bands around 2700 cm-1 and 1400 cm-1 indicating
the presence of the S-CH2 group.15
H
N
C
S
2-MBIZ
N
H
which increases the electron-donating capacity of the sulfur
atom to form a bond with a benzylic carbon atom. In the other
two nucleophiles, only one nitrogen atom and either a sulfur
(in 2-MBTZ) or an oxygen atom (in 2-MBOZ) are present.
Received 26 January 2006; accepted 22 February 2007
Paper 07/4430
doi:10.3184/030823407X191985
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H
N
H
N
1
2
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4
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Among these two nucleophiles 2-MBTZ reacts faster than 2-
MBOZ. This difference in rates is attributed to the difference
in the electro-negativities of the oxygen and the sulfur atoms
present adjacent to the >C=S group. In 2-MBOZ, the more
electronegative oxygen atom pulls electrons towards itself
making the electron availability less on S for bond formation
with the benzylic carbon atom of the substrate. However, in 2-
MBTZ, the less electronegative sulfur atom adjacent to >C=S
makes the electron donation easier compared to 2-MBOZ.
Therefore 2-MBTZ reacts faster than 2-MBOZ.
7
8
9
10 P. Manikyamba, Indian J. Chem., 1992, 31A, 959.
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