Indian Journa l of Chemistry Vol. 4013, Janu ary 200 I, pp. 32-36

Kinetics and mechanism of the nucleophilic substitution reactions of 2-chloro­I-methylpyridinium iodide with primary and secondary amines

A Awwal , M Kabi r*, M Enamullah , D Hossain & M M Morshed Department of Chemi stry. Jahan girn:1gar Unive rsity, S:1v:1r, Dhaka 1342. l3 :lI1gladesh

Receil'ed 5 April 1999; accetJ/ed (re l'ised ) 2 Ma rch 2000

Rate constants fo r the SN2A r reactions of 2-ch loro- l-methy lpyrid inium iodide wit h MeNH,. EtNH,. PrN II" BuNH , . Me , NII and Et,N II in water, at I mol dm-J const3nt ioni c strength and 25°C h:lVe bee n determined. The observed rate of react ion is firs t order with respect to amine as we ll as the pyridinium iodi de i.e., the overall reac ti on is second order. The relat i\'e re:1ctiv ity of the am ines towards the reac ti ons is Me2N II » MeN I1 2 > EtNHl > BuN II l > PI' ' II : > Et, NII. The I3 ronsted ~ coeffic ient is 0.67 and the Taft' s correlat ion coef'lic ient P!5* is 4.39 for the primary :l mines. Two oppos itely charged spccies seem to be in volved in the transiti on-state of the substituti on reactions. A two-step reaction mechanism is eonsistcnt wit h the obse rved resul ts in which the format ion of:1n intermediate is believed to be the rate determini ng step.

Kinelics and mec hani sm of the nucleophil ic substilulion reac ti ons have been studi ed ex tensive ly1.2 . It was found earli er that the conjugative interacti on of an elec lron releas ing substituent and electron withdraw in g substituent plays a key role in the re;tc ti vity of thi s type of reac ti ons l.J -6. Relati ve pos iti on of th e leaving groups in a heterocyc lic ring also has a signi ficant errect on the rate6

-X

• Substituent effects wit h different aliphatic and aromati c eo mpoll nd s have been studi ed wide ly. For so me reactions of the pyridine deri va ti ves, Meisenheimer­type complexes have been iso lated'!. Bronsted co rrelation coefficient6.lo. 11 for some reacti ons was found to be within the range for nucleophili c substituti on reac ti on proposed by Bordwell et. a/. 12

•

Attempt was made ll.1.l to eorrelGte the obtained results

'vvi th the Hamlllett I~ correlati on. Di fferent groups of workers also proposed mechan ism, studyi ng reac ti ons with different heterocyc li c co mpou nds IS. Persson et. a/. I

!> de lermined flu orine kine ti c isotope effect (FK ISs) usin g the accelerator-prod uced short-li ved radion uclide 'XF in combination wit h normal I'!F. They proposed ;~dd iti o n of the nucl eophile to the aromati c substrate as the rate- li miting step. The present paper reports an in vestiga ti on of the reac ti ons of 2-chl oro-l-methylpy ridinium iodide (PI ) with MeN II ~, E t NH ~, PrNH 2, B u NH ~, Me2 NH , and E t~NH .

Our res ults show th at the presence of qu atern ary ni troge ll atolll in th e arom;l ti c ri ng of 2-ch /0 1'0 -1-mcthy lpyridinium iodide sufficientl y act iva les it to

undergo nucleophili c substituti on oy an additi on­elimination mechani sm.

Materials and Methods

2-C hloro- l -methylpyridinium iodide and the ami nes used were of A. R. grade and obtained from E. Mark Co. (Germany) . Pi cri c ac id (reagent grade) and KCI (A. R. grade) were obtained from BDH (Eng land). Doubl y disti lled w< ter was used th roughout the experiments.

Kinetic Measllrelllents The substituti on reactions were studied

spectroplotometrically in water under pseudo-first order condition , where [al:1 ine] » [PIl. The ionic strength was maintained constant at I mol dm-J with addition of KCI. The pH of the reac tion mixture wa~ made equa l to the pK" of the allline by the additi on of hal f equivalent of hydrochloric acid to the amine solution. All kinetic runs we re carried out at 25°C. The reactions were foll owed for sevc ral hal f-I i ves and the observed rate constants were ca lcul ated using standard rate ex press ion and the meth od of least squares. Suitable initial concentrati on (3 x IO-~ mol dm-') of pyridinium iodid e for kin etic measurement s was obtai ned by direc tly injecting 0.05 IllL or stock so lution into the Illeasuring ce ll containing amine solution (2 mL). The reactions w;:: re foll owed by

A WWAL el al. : REACTION OF 2-CHLORO- I -METHYL PYRIDINIUM IODIDE WITH AMINES 33

monitoring the appearance of a UY absorbance band in the region 298- 327 nm employing a computer control led Shimadzu UY-160lPC UY-visible spectrophotometer. The spectrophotometer was equipped with a thermoelectrical-temperature controller (Shimadzu TCC-240A) which maintained constant temperature of the reaction mixture to 25 0 ±O.l°C. IR spectra of the reaction products were recorded using a Shimadzu IT JR-470 infrared spectrophotometer.

Product identification 2-chloro-l-methylpuridinium iodide and the

amines were added under the experimental condition and left for the completion of the reaction. Then picric acid solution in water was added to the reaction mixture. As the isoelectric pH of the corresponding amine was reached, the picrate salts were precipitated. These were collected and washed with methanol-ether solvent several times. IR spectra of these picrate salts were recorded in KBr. For 2-(N-methylamino)-I­methylpyridiniumpicrate salt, the IR spectrum showed absorption bands at 3086.5 (s) and 3078.8 cm- I (s), which may be due to the presence of two types of aromatic VC- II stretch ing (one in the pyridinium ring and another in the picric acid ring). IR spectra also showed bands at 2822.2 cm- I (w) due to aliphatic VC-II

stretching, and at 1628.1 (s) and 1608 cm- I (s), due to aromatic VC=C stretch ing. The bands between 1560.6 (s) and 1369.6 cm- I (s) may be for the V N0

2

stretching. Similar IR spectra were found for other

picrate salts of the products. The obtained results were comparable with those observed by Moran et. al. 6

.

Results and Discussion Under the present experimental condition, where

[amine] » [PI], the plots of In(A~ - AI) versus time were linear for all the amines, indicating the order of the reaction with respect to [PI] to be unity . Here. A~ is the absorbance of product at infinite time and AI is the absorbance of the product at ti me 1. From the slope of the above plots pseudo-first order rate constants (kobs) were calcu lated. In order to in ves tigate the effect of PI concentration on the reaction rate, the [PI] were varied with in the range of 7.32 x 10-6 to 3.00 X 10-4 mol dm-J keeping the amine concentration and the other reaction conditions constant. It \-vas found that k obs remai ned ullchanged wi thi n the range of experimental error, indicating that k obs values are independent of initial concentration of PI as expected from the pseudo-first order reaction conditions.

The effects of [amine] on kob, were also investigated under the condition of [amine] » [PI]. The free am ine concentrations were varied within the range of 0.005 - 0.06 mol dm-3 keeping the [PI] constant at 3 x 10-4 mol dm-3

. In all cases the ionic strength ()l) was kept constant at I mol dm-3 in water and half equivalent of the amines were neutralised by adding requisite amount of hydrochloric acid. The pseudo-first order rate constants (kobs) were found to increase linearly with increasing amine concentrations (Table I).

Table I- Rate constants for the reactions of 2-chloro-l-mcthylpyridinium iodide with different amincs.

I Tcmp. = 25° ± O. 1°C, Il = I mol dm-3, Sol vcnt = water, [PI] = 3 x 10-4 mol dm-3

}

Aminc pK" 0 * kobs / 10-3 (S- I) kJ 10-3 k,/1 0-3

Aminc concentration (mol dm-3) (5- 1) (mol dl11- J )

0.01 0.02 0.03 0.04 0.05 0.06

MeNH 2 10.66 0.00 1.41 2.9 4.26 5.92 7.48 0.00 164.3 ± 0.004 ± 0.018 ± 0.038 ± 0.053 ± 0.277

EtNH, 10.65 - 0.10 1.08 1.56 2. 13 2.39 2.58 0.42 52 .6 ±0.010 ±0.010 ± 0.017 ± 0.008 ± 0.047

PrNH2 10.54 -0. 12 1.12 1.52 1.94 2.47 2.86 0.21 42.22 ± 0.01 3 ± 0.016 ± 0.024 ± 0.034 ± 0.087

BuNH 2 10.60 -0.13 1.31 1. 84 2.33 2.84 3.41 0.27 51.26 ± 0.062 ±0.012 ± 0.023 ±0.019 ± 0.030

MC2NH 10.73 0 .005 ~ 0.006~ o.ooi 0.0085 ~ 0.0 1# 0.00 471 7.22 2.25 2.84 3.83 4.2 6.52

± 0.037 ± 0.029 ± 0.04 1 ± 0.028 ± 0.061 Etl II 10.84 0.92 1.1 1.17 1.21 1.33 0.77 13.97

± 0.006 ± 0.004 ± 0.006 ± 0.006 ± 0.004

' Concentrati on of dimelhyl uminc

34 INDIAN J CHEM . SEC S, JANUA RY 200 1

The second order rate constants (k2) were calculated from the intercepts of the plots of In(kobs -ko) versus In[NHR IR2], by using the equati on kobs = ko + k2[NHRIR2]

or In (kobs -ko) = In k2 + In[NHRIR2] .. . (1) where ko is the rate of hydrolys is6 of PI. Here (i) RI = H, R2 = Me, Et, Pr, Bu ; (ii ) R 1 = R2 = Me; and (iii) R 1

= R2 = Et, respecti vely . The results are given in Table I.

The plots of In(kobs - ko) versus In[NHRIR2] are linear with gradients around I for all the amines, confirming that the order with respect to each amine is un ity in accordance with Eqn ( I). Thus, the substitution reactions are first order with respect to PI and the amines, indicating that the overall reaction is second order. The values of second order rate constant (k2) fo r the nucleophilic substitution reaction between 2-chloro-l-methylpyridiniumiodide and the amines are summarized in Table I. The values of k2 follow the sequence, Me2NH » MeNH 2 > EtNH2 > BuNH2 > PrNH2 > Et2NH.

The relati ve reactivity or nucieophilicity of the amines can be ex plained in terms of the inducti ve and steric effects3

. The second order rate constants for Me2NH is very high compared to MeNH2 and other amines. Methyl is an electron releasing group as well as small in size. The presence of two methyl groups in

Me2NH makes it very reactive compared to MeNH2•

Here, inductive effect predominates over any steric effect. However, MeNH2 is in the second pos ition in the reactivity order, while EtNH2 is in the third position. This may be due to the la,ger size of the ethyl group compared to the methyl group though it has more electron-donating capacity. But for PrNH2 and BuNH2 it is found that BuNH2 is more reac ti ve than PrNH2. This may be due to the fac t that in the case of BuNH2, the field effec t i:> added to the electron releasing inducti ve effect. Again the reactivity of Et2NH is least among the amines. Though ethyl group has electron-do:1ating tendency, the presence of two ethyl groups on the same nitrogen makes the steric fac tors predominating over inductive effec t.

Bronsled Relationship

The Bronsted plots 17.18 were constructed fo r both primary and secondary amines (Table I, Figure 1) by using the Eqn (2).

10g k=[3pK,, +C ... (2) The Bronsted free energy relationship holds good fo r structurally closely related compounds. The results fo r the secondary amines do not fit to the Bronsted correlation (Fig. 1). This may be attributed to the significant di fference in inducti ve and steric effects

1.5~----------------------------------·-------------------,

1.0

0.5

0.0

.:::s::N -0.5 0> .Q

-1.0

-1 .5

-2.0

10.55 10.60 10.65 10.70

pKa 10.75

•

10.80 10.85 10.90

Figure I-Bronsled plot for the reac ti ons of 2-chloro- l-mcthylpyridinium iodidc with ami nes in water; (!l = I mol dm-3; Temp. = 25°C)

A WWAL el al.: REACTION OF 2-CHLORO-I-METHYL PYRIDINIUM IODIDE WITH AMINES 35

between primary and secondary amjnes. The value of the Bronsted constant for the primary amines obtained

from the slope of the plots (Fig. 1) is positive (~ = 0.67). According to Bordwell et. al. 19 this is in agreement with the nucleophilic substitution reaction . Since ~ values are generally associated with the degree of bond formation in the transition state, its value indicates the appreciable degree of bond formation in the transition state during the reaction of PI with aliphatic amines I7,18,20, Me2NH and Et2NH are found not to fit the relation. This may be due to electronic factor for Me2NH and steric factor for Et2NH.

Taft's correlation

According to Taft's Correlation l7.18 (Eqn 3)

log k - log kref = p*a* + Es ... (3) where cr* represents polar effect of the substituent, p* represents the sensitivity of rates to the polarity, Es is a steric substituent constant, kref is the rate constant for the reference compound and k is the rate constant for the sample compound. It is found that P2S* = 4.39. Since the plots of logk2 versus cr* leads (Figure 2) to a good correlation (r = 0.9759), both steric and electronic effects' are important in determining relative reactivi ty I7. The high positive value of P2S* indicates that the negatively charged Meisenheimer

complex interacts with a positively or parti ally positively charged species in the intermediate stage which is rate determining3

, I7 . The involvement of oppositely charged species in the rate-determining step is further substantiated by the observed dependency of k2 on ionic strength (11). A plot of log k2 versus ..J1l is linear with a negative slope as expected for such reactions21.

Mechanism of nucleophilic substitution reactions

The chlorine on PI acts as an electron withdrawing as well as a good leaving group when the nearby positively charged quaternary nitrogen helps to produce a partially positively charged carbon centre1S. The quaternary nitrogen atom activates to undergo nucleophilic aromatic substitution by an addition­elimination mechanism. The experimental observations and the kinetic data indicate that the reaction between PI and aliphatic amines follow second order kinetics with a two stage mechanism. (Scheme I) The first stage is assumed to be rate determining. It greatly resembles the tetrahedral mechanism3 displaying second order kinetics. In PI partially positively charged carbon centre acts as an electrophile.

Rate Equation

Under steady state condition the rate at which PI

~.6r---------------------------------------------------~

~.8

-1 .0

N ~

~ -1 .2

BuNH2 • • EtNH2

-1.4

-1.6 L...---1-_--'-_---lI....-_-'--_-.l...._---' __ ..1..-_--'-_---l __ .L...-_-l

~. 16 ~.12 ~.08 ~.04 0.00 0.04

cr· Figure 2--Taft's plot for the reactions of2-chloro-l-methylpyridinium iodide with primary ami nes in wate r; (~t = I mol dm-J ; Te mp .

= 25°C)

36 IND IAN J CHEM. 5EC 13, JANUA RY 2001

U + NHR1R2 ~ aNHR1R2 __ ~'--l"~ U+; NR1R2 +HCI +N CI 1<r + N CI I

CH3 CH3 CH3

r n m

Scheme I

reacts wit h am ines can be written as in Eqn (4).

~[PI] = ~[Product] = k [Intermediate] cit dt P

k rp[][NHRIR 2] But as the [fntermediate] = ---'-.f -----­

k +k r P

kp» kr the Eqn (4) reduces to Eqn (5).

... (4)

and

~[PI]= kr[PI][NHR IR"] ... (5) dt

The deri ved rate express ion (5) explains the observed second order kinetics, being first order with respect to each reactant. Under the pseudo-first order condition , when lamine] » lPI] the Eq n (5) becomes

~[PI] = k . [PI] cit ' "hs

where I 2 I 2· k"b, = kf [NHR R ] = k2 [NHR R ] .. . (6)

In the Jbove Eqn (6), kr has been replaced by second order rate constant, k2 for the present system. According to Eqn (6), the plot of k obs versus [aminel shoull! be li near pass ing through the origin and thi s was observed only for reactions with methyl am ine and dimeth yl ami ne. However, results for the other fou r of the six amines show definite intercepts indicating a side reac ti on (presumably hydrolysis6 of Pi\ Therefore , fo r the present system. Eqn (6) can be p;writlen ,IS

, , . NI-l R1R21 . no" = f\() + h'2t .. . (7)

\\ !l~ re i..'l j;;: ti le rate of hydrol ysis wh ich is ;:~oq:e nd 'Ill of the free amine concentration as (H20 'l ',,> I ,1 111 i nc J, end ko is also independent of P

concentration as [H2O] » [PI]. For MeN H2 and Me2NH, ko IS zero or negl igible within the ex peri mental errors .

Acknowlcdgemcnt

Authors thank Dr M N Absar for helpful discussions in respect of the IR spectra.

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