Kinetics and mechanism of the oxidation of substituted benzylamines by hexamethylenetetramine-bromine

Article abstract of DOI:10.1002/poc.456

The oxidation of substituted benzylamines by hexamethylenetetramine-bromine (HABR) to the corresponding aldimines is first order with respect to each the amine and HABR. It is proposed that HABR itself is the reactive oxidizing species. The oxidation of deuterated benzylamine (PhCD₂NH₂) indicated a substantial kinetic isotope effect (k_H/k_D = 5.60 at 293 K). This confirmed the cleavage of an α-C-H bond in the rate-determining step. Correlation analyses of the rates of oxidation of 20 monosubstituted benzylamines were performed with various single-and multi-parametric equations. The rates of the oxidation showed excellent correlations in terms of the Yukawa-Tsuno and Brown equations. The polar reaction constants were negative. The oxidation exhibited extensive cross-conjugation, in the transition state, between the electron-donating substituents and the reaction centre. A mechanism involving a hydride ion transfer from the amine to HABR, in the rate-determining step, is proposed. Copyright

Full text of DOI:10.1002/poc.456

JOURNAL OF PHYSICAL ORGANIC CHEMISTRY
J. Phys. Org. Chem. 2002; 15: 103–107
DOI:10.1002/poc.456
Kinetics and mechanism of the oxidation of substituted
benzylamines by hexamethylenetetramine-bromine
Rashmi Dubey, Seema Kothari and Kalyan K. Banerji*
Department of Chemistry, J.N.V. University, Jodhpur 342005, India
Received 29 January 2001; revised 7 July 2001; accepted 25 August 2001
ABSTRACT: The oxidation of substituted benzylamines by hexamethylenetetramine-bromine (HABR) to the
corresponding aldimines is first order with respect to each the amine and HABR. It is proposed that HABR itself is the
reactive oxidizing species. The oxidation of deuterated benzylamine (PhCD2NH2) indicated a substantial kinetic
isotope effect (kH/kD = 5.60 at 293 K). This confirmed the cleavage of an a-C—H bond in the rate-determining step.
Correlation analyses of the rates of oxidation of 20 monosubstituted benzylamines were performed with various
single- and multi-parametric equations. The rates of the oxidation showed excellent correlations in terms of the
Yukawa–Tsuno and Brown equations. The polar reaction constants were negative. The oxidation exhibited extensive
cross-conjugation, in the transition state, between the electron-donating substituents and the reaction centre. A
mechanism involving a hydride ion transfer from the amine to HABR, in the rate-determining step, is proposed.
Copyright  2001 John Wiley & Sons, Ltd.
KEYWORDS: kinetics; mechanism; oxidation; benzylamines; correlation analysis
INTRODUCTION
correlate rate and structure in this reaction. A suitable
mechanism is proposed.
Hexamethylenetetramine-bromine (HABR) was first
reported as a synthetic reagent for the oxidation of
alcohols to carbonyl compounds in 1994.1 We have
undertaken a study of the kinetics and mechanism of
oxidations by HABR and some reports have emanated
from our laboratory on the mechanistic aspects of
oxidations by HABR.2–6 It seems that there are no
reports about the oxidation of aromatic amines by HABR.
However, the kinetics of the oxidation of aromatic
amines by many reagents have been studied, e.g. by
permanganate,7 N-chlorosuccinimide (NCS),8 N-bro-
moacetamide (NBA),9 N-chloroacetanilide,10 acid bro-
mate11 and periodate.12 The oxidation of benzylamines
presents interesting possibilities. It is known to yield a
number of products including those resulting from
condensation of the intermediate products of oxidation
with the parent amine.13 In addition, benzamide,
benzaldehyde and benzoic acid are also formed.13 In this
paper, the kinetics of the oxidation of 20 monosubstituted
benzylamines by HABR in dimethyl sulfoxide (DMSO)
as a solvent are reported. Attempts were made to
RESULTS
The oxidation of benzylamines by HABR results in the
formation of corresponding aldimines. Analyses of
products indicate the following overall reaction:
2ArCH2NH2 ‡ ꢀCH2†6N4Br4 ! 2ArCH
ˆ NH ‡ ꢀCH2†6N4 ‡ 4H ‡ 4BrÀ
ꢀ1†
‡
Rate laws
The reactions were found to be first order with respect
to HABR. The individual kinetic runs were strictly
first order in HABR. Further, the pseudo-first-order
rate constants, kobs, do not depend on the initial
concentration of HABR. The reaction rate increases
linearly with increase in the concentration of the amine
(Table 1). Thus the reaction is first order with respect to
amines also.
*Correspondence to: K. K. Banerji, Department of Chemistry, J.N.V.
University, Jodhpur 342005, India.
Spectral studies
Contract/grant sponsor: Council of Scientific and Industrial Research
(India).
The UV–visible spectra of HABR (0.001 mol dmÀ3) and
Copyright  2001 John Wiley & Sons, Ltd.
J. Phys. Org. Chem. 2002; 15: 103–107

104
R. DUBEY, S. KOTHARI AND K. K. BANERJI
Table 1. Rate constants for the oxidation of benzylamine by
HABR at 303 K
[Amine]
103[HABR]
105 kobs
(sÀ1
(mol dmÀ3
)
(mol dmÀ3
)
)
0.1
0.2
0.3
0.5
1.0
1.5
2.0
2.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
2.0
4.0
6.0
8.0
1.0
1.0
9.62
19.6
28.5
49.0
95.8
150
204
200a
96.2
94.8
97.0
96.0
96.2b
95.7c
Figure 1. UV±visible spectra of *A) 0.001 mol dmÀ3 HABR
and *B) 0.002 mol dmÀ3 bromine; Temperature, 293 K;
solvent, DMSO
a
Contains 0.005 mol dmÀ3 acrylonitrile.
Contains 0.02 mol dmÀ3 HXA.
changed. This confirmed that HABR retained its integrity
in DMSO.
b
c
Contains 0.02 mol dmÀ3 sodium bromide.
Induced polymerization of acrylonitrile
an equivalent amount of bromine (0.002 mol dmÀ3), in
DMSO at ꢁ293 K showed that there is some difference in
the nature of the spectra of HABR and bromine. There is
a broad peak for HABR in the range 300–310 nm and for
bromine there is a peak at 278 nm. Their optical densities
showed large variations (Fig. 1). Hexamethylenetetra-
mine (HXA) had no appreciable absorption in this range.
Further, the spectrum of HABR did not show any change
during the experimental time period (ca 2 h). When a
solution of HABR in DMSO was evaporated to dryness
under reduced pressure, HABR was recovered un-
The oxidation of benzylamine, in an atmosphere of
nitrogen, failed to induce the polymerization of acryloni-
trile. Further, the addition of acrylonitrile had no effect
on the rate of oxidation (Table 1).
Effect of hexamethylenetetramine
Addition of HXA had no effect on the rate of oxidation
(Table 1).
Table 2. Rate constants for the oxidation of substituted benzylamines by HABR and the activation parameters
104 k2 (dm3 molÀ1 sÀ1
303 K 313 K
0.62
)
DH*
DS*
DG*
Substituent
293 K
0.23
323 K
3.98
4.07
7.24
27.5
(kJ molÀ1
)
(J molÀ1 KÀ1
)
(kJ molÀ1
)
p-NO2
p-CF3
p-CO2Me
p-Br
1.70
1.74
2.95
72.8 Æ 0.7
70.0 Æ 0.7
68.4 Æ 0.6
63.9 Æ 1.0
57.0 Æ 0.6
59.8 Æ 0.3
58.0 Æ 0.9
51.3 Æ 1.2
39.5 Æ 0.8
19.8 Æ 1.0
22.3 Æ 2.0
74.2 Æ 0.1
67.0 Æ 0.7
67.4 Æ 0.3
66.8 Æ 0.1
67.2 Æ 0.3
69.0 Æ 0.6
61.3 Æ 0.3
60.0 Æ 0.5
58.0 Æ 0.6
À86 Æ 2
À94 Æ 2
À95 Æ 2
À97 Æ 3
À119 Æ 2
À106 Æ 1
À109 Æ 3
À123 Æ 4
À143 Æ 3
À183 Æ 3
À166 Æ 7
À88 Æ 1
À99 Æ 2
À97 Æ 1
À98 Æ 1
À96 Æ 1
À89 Æ 2
À105 Æ 1
À103 Æ 2
À106 Æ 2
98.2 Æ 0.6
98.0 Æ 0.5
96.5 Æ 0.6
92.8 Æ 0.8
92.2 Æ 0.5
91.2 Æ 0.2
90.2 Æ 0.7
87.9 Æ 1.0
81.9 Æ 0.7
74.2 Æ 0.8
71.5 Æ 1.6
100 Æ 1.0
96.5 Æ 0.5
96.2 Æ 0.2
95.8 Æ 0.1
95.6 Æ 0.3
95.5 Æ 0.5
92.5 Æ 0.2
90.5 Æ 0.4
89.4 Æ 0.6
0.26
0.48
2.24
2.88
4.20
6.61
0.66
1.23
5.12
6.76
9.62
14.1
33.9
354
12.9
p-Cl
H
p-F
13.8
21.5
30.9
70.8
28.2
45.0
66.1
p-Me
18.0
214
5240
138
p-OMe
p-NH2
p-NMe2
m-NO2
m-CF3
m-CO2Me
m-Cl
631
1050
12000
40800
7080
10000
31700
16600
20000
0.11
0.30
0.79
1.95
0.49
0.54
0.63
0.68
0.71
2.45
5.62
8.91
1.20
1.38
1.62
1.78
1.86
5.75
2.95
3.31
3.89
4.27
4.47
6.92
7.76
8.89
9.66
m-I
m-F
m-OMe
m-Me
m-NH2
11.0
13.2
27.7
60.3
88.7
12.6
19.1
28.8
42.7
Copyright  2001 John Wiley & Sons, Ltd.
J. Phys. Org. Chem. 2002; 15: 103–107

OXIDATION OF BENZYLAMINES
105
Table 3. Kineticisotope effect in the oxidation of benzylamine by HABR
104 k2 (dm3 molÀ1 sÀ1
)
DS*
DG*
Compound
293 K
303 K
313 K
323 K
DH* (kJ molÀ1
)
(J molÀ1 KÀ1
)
(kJ molÀ1
)
PhCH2NH2
PhCD2NH2
kH/kD
4.20
0.75
5.60
9.62
1.77
5.44
21.5
4.05
5.31
45.0
8.70
5.17
59.8 Æ 0.3
61.8 Æ 0.3
À106 Æ 1
À113 Æ 1
91.2 Æ 0.2
95.5 Æ 0.2
Effect of bromide ion
Correlation analysis of reactivity
The rate of oxidation of the amine was not affected by the
addition of added sodium bromide (Table 1).
The rate constants for the oxidation of the meta- and
para- substituted compounds were correlated in terms of
the Hammett16 equation [Eqn. (3)], but no significant
correlation was obtained. We used the standard deviation
(sd), the coefficient of determination (C2 or c2) and
Exner’s17 parameter as the measures of goodness of fit:
Kinetic isotope effect
To ascertain the importance of the cleavage of the a-C—
H bond in the rate-determining step, the oxidation of
[1,1-2H2]benzylamine (PhCD2NH2) by HABR was
studied. The results (Table 3) showed the presence of a
substantial primary kinetic isotope effect (kH/kD = 5.60 at
293 K).
log k2 ˆ Àꢀ3:03 Æ 0:21†ꢀ À 2:65
c2 ˆ 0:9238; sd ˆ 0:37; n ˆ 20; ˆ 0:28; T ˆ 303 K
ꢀ3†
The main deviating points correspond to para-substitu-
ents capable of electron donation by resonance, viz.
methoxy, amino and dimethylamino. Their rates are
higher than those required by their Hammett s values.
This indicates that in the transition state of the reaction,
there is an electron-deficient centre, which is stabilized
by cross-conjugation with the electron-donating substi-
tuents at the para-position. The substituent effects in such
systems can be described by the Yukawa–Tsuno18
equation:
Effect of substituent
The rates of oxidation of benzylamine and 19 mono-
substituted benzylamines were determined at different
temperatures and the activation parameters were calcu-
lated (Table 2).
‡
log k2 ˆ ꢁꢀꢂ ‡ ꢁrꢀꢀ À ꢀꢂ† ‡ log k0
ꢀ4†
DISCUSSION
Where s° is the normal substituent constant, which does
not involve any additional p-electronic interaction
between the substituent and the reaction centre, s Às°
The values of logk2 at 293 K for the oxidation of 20
benzylamines are linearly related to logk2 at 323 K
(slope = 0.8174 Æ 0.0059; c2 = 0.9990). The value of the
isokinetic temperature, calculated by Exner’s14 method,
is 597 Æ 19 K. A linear isokinetic relationship implies
that all the compounds so correlated react by the same
mechanism. Further, the linear relationship is also a
necessary condition for the validity of linear free energy
relationships.15
‡
is the resonance substituent constant measuring the
capability for p-delocalization of the p-electron donor
substituent and r is characteristic of the given reaction
measuring the extent of resonance demand, i.e. the degree
of resonance interaction between the aryl group and the
reaction centre in the rate-determining transition state.
The correlation of the rate of oxidation of the para- and
meta-substituted benzylamines in terms of Eqn. (4) is
excellent (Table 4) with the value of r ranging from
À1.72 to À2.03 and the value of r being ꢁ1.03. The value
of r indicates that the resonance demand is slightly more
In solution, HABR may dissociate to form molecular
bromine and HXA:
ꢀCH2†6N4Br4 „ 2Br2 ‡ ꢀCH2†6N4
ꢀ2†
‡
The observed effects of added HXA or bromide ion on
the rate of oxidation are reminiscent of the results
obtained earlier in the oxidation of other reductants by
HABR,5,6 and indicate that the reactive oxidizing species
is HABR itself. This is supported by the spectral data and
isolation of unchanged HABR.
than that for the model reaction19 for s values, i.e.
solvolysis of 2-aryl-2-chloropropanes for which the value
of r is, by definition, 1.0. In view of this, an attempt was
made to correlate the rates of the oxidation of meta- and
‡
para-substituted amines with Brown’s s values. The
correlation is very good [Eqn. (5)]. In fact, the
Copyright  2001 John Wiley & Sons, Ltd.
J. Phys. Org. Chem. 2002; 15: 103–107

106
R. DUBEY, S. KOTHARI AND K. K. BANERJI
Table 4. Correlation of rates of oxidation of meta- and para-substituted benzylamines by HABR in terms of the Yukawa±Tsuno
equationa
Temperature (K)
r
r
C2
sd
293
303
313
323
À2.03 Æ 0.09
À1.91 Æ 0.08
À1.81 Æ 0.08
À1.73 Æ 0.08
1.06 Æ 0.08
1.05 Æ 0.09
1.03 Æ 0.08
0.98 Æ 0.08
0.9939
0.9941
0.9933
0.9926
0.09
0.07
0.08
0.08
0.08
0.08
0.09
0.09
a
No. of data points = 19.
significance of the two correlations is almost equal.
reaction constants in the present reaction may well be due
to the presence of an electron-donor group (NH2)
adjacent to the cationic carbon. The non-bonded pair of
electron on nitrogen can delocalize the positive charge on
the carbon and, therefore, reduce the electronic demand
of the reaction centre. In the acid-catalysed solvolysis of
acetophenone acetals,21 where electron-donating alkoxy
and methyl groups are present adjacent to the cationic
carbon, the values of r and r are À1.7 and 0.6,
respectively.
‡
log k2 ˆ Àꢀ1:95 Æ 0:04†ꢀ À 3:03
ꢀ5†
c2 ˆ 0:9939; sd ˆ 0:08; n ˆ 19; ˆ 0:08; T ˆ 303 K
The data for the p-N,N-dimethylamino compound were
not included in the correlations with Eqn. (4) and
‡
Brown’s s values, as the substituent constants are not
available.
The mechanism depicted in Scheme 1 accounts for the
experimental results. The values of activation parameters
support the proposed mechanism. The large negative
entropy of activation indicated a rigid activated complex
in the transition state. When two species come together to
form a single activated complex, they lose the indepen-
dence to move singly and there is a loss of entropy.
Further, as the charge separation takes place in the
transition state, the charged ends become highly solvated.
This results in the immobilization of a large number of
solvent molecules. This also results in a loss of entropy.
The large enthalpies of activation indicated that the
formation of the activated complex involves a greater
degree of bond cleavage.
It is of interest to compare the results of this
investigation with earlier reports on the oxidation of
benzylamine. In the permanganate7 ion oxidation and
Ru(III)-catalysed oxidation by acid bromate,11 the
reaction constants are À0.28 and 0.87, respectively,
indicating the possibility of a one-electron oxidation. The
oxidations by NCS8 and NBA9 exhibited large negative
polar reaction constants and substantial primary kinetic
isotope effects. The mechanism proposed for the
oxidation by NBA, NCS and HABR is essentially same,
i.e. transfer of a hydride ion from the amine to the oxidant
resulting in the formation of a cationic species in the rate-
determining step.
Mechanism
The absence of any effect of the radical scavenger on the
reaction rate and the failure to induce polymerization of
acrylonitrile point against a one-electron oxidation,
giving rise to free radicals.
The presence of a substantial kinetic isotope effect in
the oxidation of [1,1-2H2]benzylamine confirmed the
cleavage of the a-C—H bond in the rate-determining
step. The large negative values of the reaction constants
and a significant resonance interaction between the aryl
group and the reaction centre in the rate-determining
transition state suggest that the activated complex has a
considerable carbocationic character. Therefore, transfer
of a hydride ion from the methylene group of the amine to
HABR, in the rate-determining step, is indicated.
Formation of a benzylic carbocationic activated complex
generally leads to higher magnitudes of reaction
constants, e.g. in the bromination of styrene20 in acetic
acid at 298 K, the values of r and r are À4.61 and 1.25,
respectively. The relatively lower magnitudes of the
EXPERIMENTAL
Materials. HABR was prepared by the reported method1
and its purity was checked by an iodimetric method and
melting-point determination. Contrary to the earlier
report,1 we found that, in DMSO solution, the active
bromine content of this complex is 2 mol per mole of the
Scheme 1.
Copyright  2001 John Wiley & Sons, Ltd.
J. Phys. Org. Chem. 2002; 15: 103–107

OXIDATION OF BENZYLAMINES
107
reagent. [1,1-2H2]Benzylamine was prepared by the
reduction of phenyl cyanide with lithium aluminium
a Hewlett-Packard diode-array rapid scanning spectro-
photometer (Model 8452A) with a scanning speed of
600 nm sÀ1. The solvent was DMSO and the temperature
was ꢁ293 K.
1
deuteride.22 Its isotopic purity, determined from the H
NMR spectrum, was 93 Æ 2%. m-Aminobenzylamine
was prepared by the reported method.23 The other amines
were commercial products and were purified by distilla-
tion. DMSO was purified by the usual method.24
Acknowledgements
Product analysis. The oxidation of benzylamines leads to
the formation of the corresponding aldimines. Quantita-
tive product analysis was carried out under kinetic
conditions. In a typical experiment, benzylamine
(0.1 mol) and HABR (0.01 mol) were made up to 50 ml
of DMSO and kept in the dark for ꢁ12 h to ensure
completion of the reaction. The amount of aldimine
formed was then determined by the reported 2,4-
dinitrophenylhydrazine method.25 According to this
method, the aldimine is hydrolysed to the aldehyde and
then isolated as the 2,4-dinitrophenylhydrazone (DNP),
vacuum dried, weighed, recrystallized from ethanol and
weighed again. The yields of DNP before and after
recrystallization were 5.5 g (96%) and 4.5 g (78%),
respectively. The DNP was found to be identical (m.p.
and mixed m.p.) with the DNP of benzaldehyde. In
similar experiments with the other substituted benzyla-
mines the yields of DNP, after recrystallization, were in
the range 70–81%. Attempts were made to detect the
formation of bromination products in amines containing
electron-donating substituents. The results indicated that
no noticeable amount of bromination product was
formed.
Thanks are due to the Council of Scientific and Industrial
Research (India) for financial support.
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Kinetic measurements. The reactions were studied
under pseudo-first-order conditions by keeping an excess
(Â20 or greater) of the amine over HABR. The solvent
was DMSO. The reactions were studied at constant
temperature (Æ0.1 K) and were followed by monitoring
the decrease in [HABR] spectrophotometrically at
380 nm for up to 80% reaction. Beer’s law was found
to be valid within the concentration range used in our
experiments. Pseudo-first-order rate constants, kobs, were
evaluated from linear plots (c2 >0.995) of log[HABR]
against time. Duplicate kinetic runs showed that the rates
were reproducible to within Æ3%.
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Copyright  2001 John Wiley & Sons, Ltd.
J. Phys. Org. Chem. 2002; 15: 103–107