Nucleophilic substitution reactions of meta- and para-substituted benzylamines with benzyl bromide in methanol medium

Article abstract of DOI:10.1002/kin.20890

The rates of reactions of para- and meta-substituted benzylamines with benzyl bromide were measured using conductivity technique in methanol medium. The reaction followed a total second-order path. The end product of the reaction is identified as dibenzylamine (X-C₆H₄CH₂NHCH₂C₆H₅) (where X = 4-OCH₃, 4-CH₃, H, 4-Cl, 4-CF₃, 3-CF₃, 4-NO₂). Electron-withdrawing groups such as chloro, trifluoromethyl, and nitro in the benzylamine moiety decrease the rate of the reaction, whereas the electron-donating groups, such as methoxy and methyl, increase the rate compared to the unsubstituted compound. A mechanism involving formation of an SN 2-type transition state between the amine nucleophiles and the benzyl bromide and its subsequent decomposition is proposed. Hammett's reaction constant ρ of the reaction decreases with an increase in temperature. Activation parameters were calculated and discussed.

Full text of DOI:10.1002/kin.20890

Nucleophilic Substitution
Reactions of Meta- and
Para-Substituted
Benzylamines with Benzyl
Bromide in
Methanol Medium
R. RAVI,1 R. SANJEEV,2 V. JAGANNADHAM,1 ADAM A. SKELTON2
1Department of Chemistry, Osmania University, Hyderabad 500 007, India
2Department of Pharmacy, School of Health Science, University of KwaZulu-Natal, Durban, South Africa
Received 9 May 2014; revised 31 July 2014; 18 October 2014; accepted 19 October 2014
DOI 10.1002/kin.20890
Published online 10 November 2014 in Wiley Online Library (wileyonlinelibrary.com).
ABSTRACT: The rates of reactions of para- and meta-substituted benzylamines with benzyl
bromide were measured using conductivity technique in methanol medium. The reaction fol-
lowed a total second-order path. The end product of the reaction is identified as dibenzylamine
(X-C6H4CH2NHCH2C6H5) (where X = 4-OCH3, 4-CH3, H, 4-Cl, 4-CF3, 3-CF3, 4-NO2). Electron-
withdrawing groups such as chloro, trifluoromethyl, and nitro in the benzylamine moiety de-
crease the rate of the reaction, whereas the electron-donating groups, such as methoxy and
methyl, increase the rate compared to the unsubstituted compound. A mechanism involving
formation of an SN2-type transition state between the amine nucleophiles and the benzyl bro-
mide and its subsequent decomposition is proposed. Hammett’s reaction constant ρ of the
reaction decreases with an increase in temperature. Activation parameters were calculated and
ꢀC
discussed. 2014 Wiley Periodicals, Inc. Int J Chem Kinet 47: 36–41, 2015
zylic carbon is of broad synthetic utility and has re-
INTRODUCTION
ceived considerable attention from organic chemists.
Literature survey shows that applications of the Ham-
mett equation on different nucleophilic substitution re-
actions involving nucleophiles, namely thiourea [3],
thiobenzamide [4], pyridines [5], quinolines [6], dif-
ferent aliphatic and aromatic primary and secondary
amines [7], and 2-mercapto benzimidazole [8] have
been reported. In continuation of our earlier work on
The Hammett equation [1,2] had received a success-
ful application in reaction mechanisms in physical or-
ganic chemistry. Nucleophilic substitution at the ben-
Correspondence
to:
V.
Jagannadham;
e-mail:
jagannadham1950@yahoo.com.
C
ꢀ
2014 Wiley Periodicals, Inc.

RATES OF REACTIONS OF META- AND PARA-SUBSTITUTED BENZYLAMINES WITH BENZYL BROMIDE
37
Figure 1 Order in [benzyl bromide], plot of log [benzyl bromide] versus time [benzyl bromide] = 0.01 M, [benzylamine] =
0.1 M, temp. = 303 K.
Figure 2 Order in [benzylamine], plot of log Kobsd versus log[benzylamine] [benzyl bromide] = 0.01 M, temperature =
303 K.
the benzylation of N-substituted benzylamines with
benzyl bromide [9], we are reporting herein the effect
of substituents attached to the benzene ring of benzy-
lamine on the reaction rates.
son Electronics (Hyderabad, India) with an accuracy
of 0.01 mho. The constant temperature bath was pur-
chased from Biotech Electronics (New Delhi, India)
and maintained at constant temperature with an ac-
curacy of 0.1°C. All other experimental details are
similar to that reported in our previous publication [9].
EXPERIMENTAL
All the chemicals and solvents used in the present
work were purchased from Aldrich (Bangalore, In-
dia) and used as received. The conductivity meter and
the conductivity cell used were obtained from Digi-
PRODUCT ANALYSIS
Benzyl bromide (0.1 M) was reacted with benzylamine
(0.1 M) in a methanol medium at 30°C. After more
International Journal of Chemical Kinetics DOI 10.1002/kin.20890

38
RAVI ET AL.
Table I Second-order rate constants (k2) for the Reaction of Substituted Benzylamines with Benzyl Bromide at
Different Temperatures, BA = 0.2 mol dm−3, BB = 0.01 mol dm−3, Solvent: Methanol
k2 (dm3 (mol min)−1) T (K)
Substituent (X)
σ
298
303
308
313
Ea (kJ mol−1
)
*ꢀH# (kJ mol −1
)
*ꢀS# (J (mol K)−1
)
4-OMe
4-Me
H
−0.27 0.0880 0.1272 0.2090 0.3860
−0.17 0.0616 0.0911 0.1757 0.3321
0.00 0.0576 0.0851 0.1350 0.3040
0.23 0.0424 0.0621 0.1010 0.1957
74.2
86.5
82.6
76.6
81.5
69.3
70.8
71.7
83.9
79.8
74.2
78.9
66.7
68.3
−25.3
12.9
−1.69
−22.8
−9.01
−50.7
−49.5
4-Cl
3-CF3
4-CF3
4-NO2
0.43
–
0.0520 0.0941 0.1537
0.54 0.0296 0.0434 0.0620 0.1206
0.78 0.0163 0.0324 0.0420 0.0708
*T = 303 K.
than 15 half-lives, a product was isolated by a sol-
vent extraction process using an ethyl acetate (50 mL)
and water (10 mL) mixture after several attempts. The
ethyl acetate solution was dried over anhydrous NaSO4
and filtered and concentrated under vacuum to get the
compound, which was subjected to column chromatog-
raphy using ethyl acetate/n–hexane (1:9) as an eluent.
The solvent was removed under reduced pressure, and
a light yellow oily product was found. Analysis of the
product gave the following results:
methanol. The second-order rate constants, k2, were
obtained as the slope of the plot of kobsd against the ben-
zylamine concentration. The second-order rate con-
stants [k2 (dm3 mol−1 min−1)] are summarized in
Table I.
ꢀ
ꢁ
kobsd = k0 + k2 benzylamine
(1)
Therefore, the simple rate equation would be
N,N-Dibenzylamine: 1H NMR (400 MHz, CDCl3),
δ 1.65 (s, H, N-H), 3.8 (s, 4H, (PhCH2)2N), 7.25–
7.39 (m,10H, aromatic protons); IR (KBr): 3269, 3060,
3026, 2921, 2835, 1953, 1872, 1809, 1742, 1714, 1602,
1581, 1556, 1521, 1490, 1452, 1331, 1268, 1217, 1143,
ꢀ
ꢁ ꢀ
ꢁ
Rate = k2 benzylamine benzyl bromide
(2)
1108, 1027, 1000, 980, 948, 906, 802, 729, 695 cm−1
;
where k2 is the second-order rate constant. Under oth-
erwise similar conditions, the solvolysis reaction of
benzyl bromide in the absence of benzylamine was
checked and the rate was found to be 10 times less
than the rate of the second-order reaction. Hence the
rates of background reaction of benzyl bromide were
neglected in these studies.
mass spectrum (m/z): 198 (M – H)+.
RESULTS AND DISCUSSION
The conductivity of the reaction mixture increases
with time as the reaction produces HBr as one of the
end products. Under the conditions [benzylamine] ꢀ
[benzyl bromide], the plot of log (Cꢁ – Ct) versus time
was linear until three half-lives with a correlation coef-
ficient of 0.999 (Fig. 1), indicating the order in [benzyl
bromide] was unity.
Here Cꢁ and Ct are the conductivities of the reaction
mixture at infinite time and at regular intervals of time,
respectively. From such plots, the pseudo–first-order
rate constants (kobsd/min) were calculated for all the
benzylamines. The plot of log (kobsd/min) versus log
[benzylamine] was again found to be linear with a
correlation coefficient of 0.995 (Fig. 2), indicating the
order in [benzylamine] was unity.
Reaction Mechanism and
Substituent Effects
Since the total order of the reaction is two, a bimolec-
ular type of reaction scheme is proposed as shown in
the following mechanism via an SN2-type transition
state:
X = p − OCH3,p − CH3, H, p − Cl,
m − CF3, p − CF3, p − NO2
The pseudo–first-order rate constants (kobsd) for all
reactions obeyed Eq. (1) with negligible k0 (ࣈ0) in
Rate = k2 [X − C4H4CH2NH2] [C6H5CH2Br]
International Journal of Chemical Kinetics DOI 10.1002/kin.20890

RATES OF REACTIONS OF META- AND PARA-SUBSTITUTED BENZYLAMINES WITH BENZYL BROMIDE
39
Scheme 1
ࣔ
ࣔ
Figure 3 Plot of ꢀH versus ꢀS showing the isokinetic relationship.
Figure 4 Exner plot of log k303 versus log k313
.
From the mechanism, one can predict a linear cor-
relation would be observed between log k2 and Ham-
mett’s σ with a negative Hammett reaction constant
(ρ) because the rates would increase as the substituent
(X) on the amine nitrogen becomes more and more
electron donating, which facilitates the availability
of the lone pair of electrons on nitrogen for the at-
tack on the benzylic carbon of benzyl bromide (see
Scheme 1).
The reaction between benzylamine and benzyl bro-
mide has been studied at temperature 298–313 K
in a methanol medium, and the rate constants
were computed. Electron-withdrawing groups such as
chloro, trifluoromethyl, trifluoromethy, and nitro in
International Journal of Chemical Kinetics DOI 10.1002/kin.20890

40
RAVI ET AL.
Figure 5 Hammett plot of log k against Hammett sigma (σ) at 303 K.
Figure 6 Bro¨nsted plot of log k versus pKa of X-substituted benzylamines at 303 K.
X-C6H4CH2NH2 decrease the rate of the reaction,
whereas the electron-donating groups such as methyl
and methoxy increase the rate compared to the un-
substituted compound. To verify the applicability of
Hammett’s linear free energy relationship, “log k2”
is correlated with Hammett’s substituent constant in
the temperature range 298–313K. Hammett’s reaction
constant ρ of the reaction decreases with an increase
in the temperature.
slope of which corresponds to an isokinetic tem-
perature β of 266 K, which is well below the ex-
perimental temperature range (298–313 K) used in
the present reactions to study the effect of temper-
ature on reaction rates. According to isokinetic the-
ory [10], this means that the effect exerted by the
meta- and para-substitution of benzylamines, both
the processes, i.e., formation and the heterolysis of
the transition state, are controlled predominantly by
entropy.
It has been asserted that apparently linear correla-
Isokinetic Relationship
ࣔ
tions of ꢀH with ꢀS# are sometime misleading, and
ࣔ
the evaluation of β by means of the equation ꢀH
An isokinetic plot is obtained in the present work
ࣔ
ࣔ
ࣔ
= βꢀS + constant lacks statistical validity [11].
(Fig. 3) when ꢀH is plotted against ꢀS accord-
ࣔ
ࣔ
Exner [12] describes an alternative method for the
ing to the equation ꢀH = βꢀS
constant, the
+
International Journal of Chemical Kinetics DOI 10.1002/kin.20890

RATES OF REACTIONS OF META- AND PARA-SUBSTITUTED BENZYLAMINES WITH BENZYL BROMIDE
41
treatment of experimental data. If the rates of sev-
eral reactions in a series have been measured at differ-
ent temperatures and log k2 (at T2) is linearly related
to log k1 (at T1), i.e., according to the equation, log
k2 = a + b log k1, so that β can be evaluated using
the equation, β = T1T2 (b – 1)/(T2b – T1). We have
calculated the isokinetic temperature β as 270 K by
plotting log k2 at 313 K versus log k1 at 303 K as
shown in Fig. 4; the value of β (270 K) is lower than
the experimental temperature 298 K. This indicates
that the rate is governed by the entropy of activation
[13].
The Bro¨nsted βX value was calculated by corre-
lating log k2 with pKa [14]. The substituent effects
(X) of the nucleophiles upon the aminolysis rates are
compatible with those for a typical nucleophilic sub-
stitution reaction, and the stronger nucleophile leads
to a faster rate with positive charge development at the
nucleophilic N atom in the transition state, resulting
in negative ρX (−0.526; Fig. 5) and positive βX (0.52;
Fig. 6) values at 30°C.
One of the authors (RR) is grateful to University Grants Com-
mission, New Delhi, India, for providing financial assistance
in the form of a fellowship.
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CONCLUSION
The reactions of para- and meta-substituted ben-
zylamines with benzyl bromide follow a SN2-type
reaction.
International Journal of Chemical Kinetics DOI 10.1002/kin.20890