Indian Journal of Chemistry Vol. 41A, March 2002, pp. 541-546

Correlation analysis of reactivity in the oxidation of substituted benzylarnines by

benzy I trirnethy larnrnoni urn tribrornide

Rekha Sankhla & Seema Kothari*

Department of Chemistry, J.N.V. University , Jodhpur 342 005, India

Received 2 May 2001; revised 4 October 2001

The oxidation of benzyl amine and twenty-seven ortho-, meta­and para-monosubstituted benzylamines by benzyltrimethylam­monium tribromide (BTMAB), in dimethylsulphoxide (DMSO), leads to the formation of corresponding aldimines. The reaction is first order with respect to both BTMAB and the amine. The oxi­dation of deuterated benzylamine exhibited a substantial kinetic isotope effect. Addition of benzyltrimethylammonium bromide does not affect the rate. Tribromide ion has been postulated as the reactive oxidizing species. The rates of the oxidation of para- and meta-substituted benzylamines showed excellent correlation in terms of both Taft 's dual substituent-parameter and Charton's triparametric LDR equations, whereas the ortho-substituted com­pounds exhibited the best correlation with the Charton's tetra­parametric LDRS equation. The oxidation of para-substituted benzylamines is more susceptible to the delocalization effect than is the oxidation of ortho- and meta-substituted compounds, which display a greater dependence on the field effect. The low positive value of the 1'] suggests the presence of an electron-deticient cen­tre in the rate-determining transition state with less charge separa­tion. A suitable mechanism has been proposed.

Benzyltrimethylammonium tribromide (BTMAB) has been used as an effective halogenating and oxidizing agent in synthetic organic chemistry l.3. We are inter­ested in the kinetic and mechanistic studies of the oxidations by polyhalide ions and have reported re­cently the kinetics of the oxidations of organic sul­phides4

, formic and oxalic acids5, benzyl aIcohols6

and aliphatic aldehydes7 by BTMAB. The oxidation of benzylamine presents interesting possibilities. It is known to yield a large number of products including those resulting from the condensation of the interme­diate products of the oxidation of the parent amine8

.

In addition benzamide, benzaldehyde and benzoic acid are also formed 8

. We now report the kinetics and mechanism of the oxidation of benzylamine and twenty-seven monosubstituted benzylamines by BTMAB in dimethylsulphoxide (DMSO). The major emphasis of this investigation is to correlate the structure and reactivity in this oxidation.

Experimental BTMAB was prepared by the reported method I and

its purity was checked by an iodometric method . [a,a-2H2]benzylamine was prepared by the reduction of phenyl cyanide with lithium aluminium deuteride9

.

Its isotopic purity, determined by the IH NMR spec­tra, was 93±2%. m-Amino- and o-nitrobenzylamines were prepared by the reported methods 10.11 . The other amines were commercially available and were puri­fied by distillation and recrystallization. DMSO was purified by the usual methods 12.

Product analysis The oxidation of benzylamines leads to the forma­

tion of the corresponding aldimines. The quantitative product analysis was carried out under kinetic condi­tions. In a typical experiment, benzylamine (1.07 g, 0.01 mol) and BTMAB (0.39 g, 0.001 mol) were made up to 50 ml in DMSO and kept in the dark for ca. 12 h to ensure completion of the reaction . The amount of aldimine formed was then determined by the reported 2,4-dinitrophenylhydrazine method 13. In this method the aldimine is hydrolysed to the alde­hyde and then isolated as 2,4-dinitrophenylhydrazone (DNP), vacuum dried, weighed, recrystallized from ethanol and weighed again. The yields of DNP before and after recrystallization were 0.20 g (91 %) and 0.17 g (74%) respectively. The DNP was found identical (m.p. and mixed m.p.) with the DNP of benzalt1ehyde. In similar experiments, with the other substituted ben­zylamines the yields of DNP, after recrystallization, were in the range of 69-82%.

Kinetic measurements The reactions were studied under pseudo-first order

conditions by keeping an excess (x 15 or greater) of the substrate over BTMAB. The solvent was DMSO. The reactions were studied at constant temperature and in the presence of an excess of potassium bromide (0.02 mol dm'\ They were followed by monitoring the decrease in the concentration of BTMAB at 354 nm for up to 80% reaction. Pseudo-first-order rate constants, kobs , were evaluated from linear plots (r > 0.990) of 10g[BTMAB] against time. Duplicate ki­netic runs showed that the rate constants are repro­ducible to within ±3%. Simple and multivariate re-

542 INDIAN J. CHEM., SEC. A, MARCH 2002

gression analyses were carried out by the least­squares method .

Results and discussion The rate and other experimental data were obtained

for all the amines. Since the results are similar, only representative data are reproduced here.

The oxidation of benzylamines results in the for­mation of the corresponding aldimines. The overall reaction may be represented as follows .

ArCH2NH2+PhCH2Me3N+Br3 -~ ArCH=NH+2HBr +PhCH2Me3N+Br- ... (1)

The reactions are of first order with respect to BTMAB. Further, the values of k obs are independent of the initial concentration of BTMAB. The reaction rate increases linearly with an increase in the concen­tration of the amine (Table I).

The oxidation of benzylamine, in an atmosphere of nitrogen, failed to induce the polymerization of acry­lonitrile. Further, an addition of acrylonitrile had no effect on the rate of oxidation (Table I).

The rates of oxidation were determined at different temperatures and the activation parameters, at 298 K, were calculated (Table 2).

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 was studied. Results, recorded in Table 2, showed the presence of a sub­stantial primary kinetic isotope effect (kH/kD = 3.37 at 303 K). The rate of deuterated amine was corrected for amount of the protio amine present.

An addition of benzyltrimethylammonium chloride (BTMACI) had no effect on the rate of oxidation.

A linear correlation (r2 = 0.9960; slope = 0.866±0.011) between the log k2 at 293 K and at 323 K for the benzyl amine and twenty-seven monosub­stituted benzylamines indicated that all the amines are oxidised by the same mechanism l4

. A linear isokinetic relationship is a necessary condition for the validity of linear free energy relationships. The value of the iso­kinetic temperature is 994±93 K. At the isokinetic temperature, the reactions of all the compounds, so correlated, will proceed at almost equal rates. The fact that the isokinetic temperature, obtained in this reac­tion, is much higher than the experimental tempera­ture range suggests that the difference in the reactivity of the amines decreases with an increase in tempera­ture.

Table I-Rate constants for the oxidation of benzylamine by

103[BTMAB]!mol dm·3

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

BTMAB at 313 K [amine]! mol dm·3

0.10 0.20 0.30 0.50 1.00 1.50 2.00 1.00 1.00 1.00 1.00 1.00 1.00

2.36 4.65 6.90 11.0 22.6 33.8 46.3 23.2' 22.9" 22.0 21.7 23.0 22.4

*and **contained 0.005 and 0.0 I mol dm·3 acrylonitrile respec­tively

We have carried out some conductivity measure­ments to determine the nature of BTMAB in DMSO. It was observed that DMSO has very low conductiv­ity. Addition of BTMAB increases the conductivity of the solution sharply . Therefore, BTMAB can be con­sidered as an ionic compound, which exists under our reaction conditions as benzyltrimethylammonium and tribromide ions [Eq. (2)]. No effect of added benzyl­trimethylammonium ion also indicates that the fol­lowing equilibrium lies far towards the right.

. . . (2)

Tribromide ion is known to dissociate, in solution [Eq. (3)] and the values of dissocia[ion constant have been reported 15.

. .. (3)

The probable oxidizing species in a solution of BTMAB are, therefore, tribromide ion or molecular bromine. To suppress the equilibrium (3), the reac­tions have been carried out in the presence of an ex­cess of bromide ions. Therefore, the most likely reac­tive oxidizing species, in this reaction, is tribromide ion.

The rates of the para- and meta··compounds failed to exhibit significant correlations in terms of Ham­mett l6 cr and Brown'sl? cr+substituent constants.

log k2=-1.65±0.1 Ocr-4.09 r2=0.9423; sd=0.12; n=19; \)f=0.18; T=293 K ... (4)

NOTES 543

log k2=-1.1l±0.1O(Y+-4.28 r2=0.8758; sd=0.18; n=19; \jf=0.26; T=293 K ... (5)

It has been stated 18 that in the absence of proximity effects, the polar effects of the ortho-substituents ought to be parallel to those of para-substituents. However in the present case it was found that the rate constants of the ortho- and para-substituted com­pounds are not linearly related [Eq. (6)]. This indi­cated that polar effects alone are not sufficient to ex­plain the observed effect of the ortho-substituents on the reaction .

log kmtho=-0.86±0.21 log kpara-4.45 / =0.6752; sd=0.33; 11= 10; \jf=0.45 ; T=293 K ... (6)

The rate constants of the ortho-compounds were analysed in terms of (Yo values of Tribble and Trayn­ham l9 also, but the correlation was not satisfactory

[Eq. (7)] . The unsatisfactory correlation and the fact that the value of k2 for an ortho-substituted benzyl­amine is always more than that of the corresponding para-compound indicate that there is a significant steric effect of the ortho-substituents in this reaction .

log k2=-0.57±0.26 (Yo-3 .63 r2=0.4152; sd=0.32; 11=9; \jf=0.63; T=293K ... (7)

The datum of nitro group was not included in this correlation since the (Yo value was not available.

Since the rates of oxidation of the monosubstituted benzylamines failed to show satisfactory correlation with any single substituent parameter equation, the rates of para- and meta-substituted benzylamines were subjected to analyses in terms of dual substituent parameter (DS P) equation of Tafeo. The rates of oxi­dation of the para- and meta-compounds were sepa­rately correlated with (YI and four different (YR values

Table 2-Rate constants for the oxidation of substituted benzylamines by BTMAB and the activation parameters

Subs!. 105 k2/dm J mor l S·I !1H' !1S' !1C'

293 K 303 K 313 K 323 K (kJ mor l) (1 mor l K· I

) (kJ mor l)

H 6.00 11.9 22.6 45.7 50.4±0.9 -154±3 96.3±0.8 p-NHCOMe 11.6 21.4 39.6 79.1 47.6±1.4 -159±4 94.7±1. 1 p-OMe 23.5 40.9 72.9 145 44.9±0.6 -153±2 86.8±0.5 p-N02 0.47 1.10 2.33 5.26 60.4±0.8 -1 41±3 102±0.7 p-Me 10.7 20.1 37.8 75.0 48.3±1.1 -157±4 94.9±0.9 p-F 7.0 1 13.4 25.3 52.5 49.9±1.5 -155±5 95.9±1.I p-CI 4.64 8.43 16.6 34.2 49.9±1.7 -159±6 97.0±1.4 p-Br 4.10 8.42 16.6 35 .3 53.6±1.2 -147±4 97.2±0.9 p-CFJ 1.20 2.56 5.20 11.0 55.3±0.8 -151±3 lOO±O.6 p-COOMe 1.62 4.23 12.0 29.8 74.4±1.0 -64±4 93.5±0.8 m-NH2 17.8 31.5 52.4 99.5 42.0±1.4 -174±5 93.7±1.I IIl-OMe 7.95 14.4 25.3 50.2 45 .3±1.5 -169±5 95.7±1.2 Ill-Me 9.01 17.3 31.7 63.5 48.3±1.2 -158±4 95.3±0.9 IIl-F 2.81 5.42 9.95 20.1 48.6±1.2 -167±4 98.2±1.0 IIl-CFJ 1.18 2.57 5.17 10.8 55.2±O.6 -151±2 lOO±O.5 m-N02 0.44 1.02 2.11 4.45 57.8±0.5 -151±2 102±0.4 IIl-CI 2.30 4.64 8.75 17.3 50.1±0.7 -163±2 98.6±0.6 Ill-I 2.61 5.21 9.92 20.5 5l.1±1.1 -159±4 98.3±0.9 IIl-COOMe 1.52 3.26 6.50 13.3 54.1±0.5 -153±2 99.6±0.4 a-Me 46.9 86.4 150 282 44.1± 1.0 -159±3 91 .3±0.8 a-F 8.21 14.9 30.0 56.5 48.5±1.2 -159±4 91.3±0.8 a-CI 12.8 24.9 47 .1 91.7 48.9±2.4 -153±2 94.4±O.7 a-Br 17.7 32.8 60.7 120 47.4±1.2 -156±4 93.7±1.0 a-N02 0.89 2.00 4.23 9.37 58.9±0.8 -141±3 101 ±0.6 o-NHCOMe 61.0 104 181 335 42.0±1 .3 -164±4 90.7±1.0 a-CFJ 12.3 25.1 47.3 95.2 50.7±0.8 -147±3 94.4±0.7 a-OMe 38.0 66.6 118 2 15 42.8±0.9 -163±3 91.8±O.7 a-COOMe 5.21 10.5 20.4 42.0 51.9±1.0 -150±3 96.6±0.8 [a,a-2H21 1.83 3.53 7.02 13.8 50.5±0.9 -164±3 99.2±0.7 kHlkD 3.28 3.37 3.22 3.31

544 INDIAN 1. CHEM., SEC. A, MARCH 2002

Table 3-Correlation of rate constants of the oxidation of para- and meta- substituted benzylamines with dual substituent-parameters

Subst. PI PR R2 sd IjI n"

(i) para-substituted

a" aR 0 - 1.24±0.06 -2.45±0.06 0.9958 0.04 0.05 10

ai, aR SA -1 .27±0.08 - 1.63±0.07 0.9911 0.06 0.07 10

a" aR -1.00±0.17 -1.32±0.1 2 0.9667 0.11 0.14 9b

a" aR + -1.I7±0.21 -0.99±0.11 0.9485 0.13 0.19 10

(ii ) meta-substituted

a" aR 0 -1.47±0.05 -1 .20±0.05 0.9961 0.03 0.05 10

a" aR SA -1.45±0.08 -0.85±0.05 0.9913 0.05 0.Q7 10

a" aR -1.37±0.13 -0.84±0.09 0.9747 0. 13 0.09 10

a" aR + -1.40±0.15 -0.48±0.06 0.9671 0.10 0.14 10

"Temperature 293 K, sd = standard deviation ; al and aR values are from ref. 16. bDatum for NHCOMe not considered; no aR' value is available

in Taft's equation2o. The results are summarized in Table 3.

Both the meta- and para-series of substituted ben­zylamines meet the requirement of minimum number of substituents for analysis by DSP equations2'.

The rates of oxidation of the meta- and para­substituted benzylamines showed a good correlation with both CJR

0 and CJR BA values. We have used the standard deviation (sd), coefficient of multiple deter­mination (R2) and Exner's statistical parameter22

, \jf,

as the measures of goodness of fit. Since the analysis in terms of Taft's DSP equation23 failed to give a clear-cut picture, it is difficult to assign any mecha­nistic significance to these results. Therefore, we have analysed the rate data in terms of Charton's LDRlLDRS equations23.

. .. (8)

Here, h is the intercept term, CJ, is a localized (field and/or inductive) effect parameter, CJd is the intrinsic delocalized (resonance) electrical effect parameter when active site electronic demand is minimal and CJe

represents the sensi tivity of the substituent to changes in electronic demand by the active site. The latter two substituent parameters are related by Eq. (9) .

... (9)

Here 11 represents the electronic demand of the re­action site and is given by 11 = RID, and CJD represents the delocalized electrical parameter of the dipara­metric LD equation.

For ortho-substituted compounds, it is necessary to account for the possibility of steric effects and Char­ton therefore, modified the LDR equation to generate the LDRS Eq. (10)23.

... (10)

where u is the well-known Charton's steric parameter based on Van der Waals radii24.

The rates of oxidation of ortho-, meta- and para­substituted benzylamines show exceUent correlations in terms of the LDRlLDRS equations Cfable 4). There is no significant collinearity between the various sub­stituent constants for the three series.

The comparison of the Land D values for the sub­stituted benzylamines showed that the oxidation of para-substituted benzylamines is more susceptible to the delocalization effect than to the localized effect. However, the oxidation of ortho- and meta-substituted compounds exhibited a greater dependence on the field effect. In all cases, the magnitude of the reaction constants decreases with an increase in the tempera­ture, pointing to a decrease in selectivity with an in­crease in temperature.

All the three regression coefficients, L, D and R, are negative indicating an electron-deficient carbon centre in the activated complex for the rate­determining step. The positive value of 11 adds a negative increment to CJd [Eq . (9)), increasing the electron-donating power of the substituent and its ca­pacity to stabilise a cationic species . The positive value of S indicates that the reaction is subject to steric acceleration by an ortho-substituent.

NOTES 545

Table 4-Temperature dependence for the reaction constants for the oxidation of substituted benzylamines by BTMAB

Para-substituted

T/K

293

303

313

323

L

-1 .28 to.03 -1.20 to.02 -l.l5 to.OI -1.09 to.02

D

-1.67 to.02 -1.54 to.OI -1.47 to.OI -1.42 to.02

R

-0.77 to.14 -0.76 to.09 -0.70 to.05 -0.71 to.11

S

0.46

0.49

0.48

0.50

sd Po Ps

0.9993 0.02 0.022 56.6

0.9997 0.01 0.015 56.2

0.9999 0.01 0.014 56.1

0.9995 0.01 0.019 56.6

Meta-substituted

293

303

313

323

-1.48 to.OI -1.41 to.OI -1.37 to.OI -1.34 ±0.01

-0.98 to.OI -0.89 to.OI -0.81 to.OI -0.77 to.OI

-0.37 to.04 -0.39 to.05 -0.33 to.04 -0.29 to.07

0.38

0.44

0.41

0.38

0.9998 0.01 0.012 39.8

0.9998 0.01 0.012 38.7

0.9997 0.01 0.015 37.2

0.9996 0.02 0.017 36.5

Ortho-substituted

293

303

313

323

-1.60 to.OI -1 .53 ±0.02 -1.43 to.OI -1 .38 to.02

-1.43 ±D.OI -1.31 ±D.OI -1.25 to.OI -1.17 ±D.OI

-0.76 ±D. 09 -0.69 ±D.09 -0.55 ±D.07 -0.57 ±D. 09

1.24 ±0.01 1.21

±D.OI 1.15

to.01 1.12

to.OI

0.53

0.53

0.44

0.49

The percent contribution23 of the delocalized effect, Po, is given by following Eq. (11).

P, = (I D 1 x 100)

o (ILI+IDj) ... (11)

Similarly, the percent contribution of the steric pa­rameter23 to the total effect of the substituent, Ps, was determined by using Eq. (12).

P _ (I S IxlOO)

s - (I L 1 + 1 D 1 + 1 S j) ... (12)

The values of Po and Ps are also recorded in Table 4. The value of Po for the oxidation of para­substituted benzylamines is ca. 56% whereas the cor­responding values for the meta- and ortho-substituted aldehydes are ca. 38 and 46% respectively. This shows that the balance of localization and delocaliza­tion effects is different for differently substituted ben­zylamines. The less pronounced resonance effect from the ortho- position than from the para-position may be due to the twisting away of the methylamino group from the plane of the benzene ring. The magnitude of

0.9998 0.01 0.013 47.2 29.0

0.9997 0.01 0.016 46.1 29.9

0.9999 0.01 0.010 46.6 30.0

0.9997 0.01 0.016 45.9 30.5

the Ps value shows that the steric effect is significant in this reaction.

It is of interest to compare the values of reaction constants of the three series of compounds. The val­ues of L of the ortho-, meta- and para-substituted compounds, at 293 K, are -1.60, -1.48 and -1.28 re­spectively i.e. the magnitude of the reaction constant decreases as the substituent moves away from the re­action centre. On the other hand the values of D are -1.43, -0.98 and -1.67 respectively. This showed that the magnitude of D follows the order para> ortho> meta. Both the trends are in the expected direction.

A hydrogen abstraction mechanism leading to the formation of the free radicals is unlikely in view of the absence of any effect of the added acrylonitrile on the reaction rate. The presence of a substantial kinetic isotope effect confirms the cleavage of an a-C-H bond in the rate-determining step.

The negative polar reaction constant points to an electron-deficient carbon centre in the transition state of the rate-determining step. However, the low mag-

546 INDIAN J. CHEM., SEC. A, MARCH 2002

nitudes of the polar reaction constants indicate a less pronounced charge separation in the transition state. The positive steric reaction constant indicates a steric acceleration of the reaction. Thi s may be explained on the basis of the high ground state energy of the steri­cally crowded amines. Since the crowding is relieved in the product aldimine as well as in the transition state leading [0 it, the transition state energy of the crowded and uncrowded amines do not differ much and steric acceleration, therefore, results.

The temperature invariance of the primary kinetic isotope effect (cf Table 2) can be interpreted in terms of a mechanism in which two bonds are cleaved more or less synchronously. Therefore, a rate-determining step involving cleavage of both the C-H and N-H bonds can be envisaged. The low magnitude of the polar reaction constants also supports the occurrence of a synchronous mechanism. However, the correla­tion analysis of the substituent effect indicated the presence of an electron-deficient carbon centre in the transition state. It seems, therefore, that in the transi­tion state the cleavage of the C-H bond, yielding an electron-deficient carbon centre, is somewhat ahead of the cleavage of the N-H bond. The low positive value of 11 supports the above postulation. The transi­tion state remains polar in this mechanism. A non-• linear transition state, implied in the synchronous mechanism, is supported by the relatively low mag­nitude of the kinetic isotope effect (kHlkD "" 3.3) also. The oxidation of benzyl alcohol by BTMAB also was reported6 to involve a synchronous cleavage of both C - Hand 0 - H bonds via a non-linear transition state and the kinetic isotope effect was found to be about 3.2. The mechanism depicted in Scheme 1 ac­counts for all the observed results .

Acknowledgement Thanks are due to the University Grants Commis­

sion (India) for financial assistance and to Professor K.K. Banerji for helpful discussions.

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