isotope effects in nucleophilic substitution reactions. v. the mechanism of the decomposition of...

Isotope effects in nucleophilic substitution reactions. V. The mechanism of the decomposition of 1-phenylethyldimethylphenylammonium halides in chloroform

HELEN ALMA JOLY AND KENNETH CHARLES WESTAWAY' Chemistry Department, Laurentian University, Sudbury, Ont., Canada P3E 2C6

Received November 1, 1985 This paper is dedicated to Professor Arthur N . Bourns

HELEN ALMA JOLY and KENNETH CHARLES WESTAWAY. Can. J. Chem. 64, 1206 (1986). Secondary a and P hydrogen-deuterium kinetic isotope effects have been used together to show that the SN reaction between

1-phenylethyldimethylphenylammonium ion and bromide or iodide ion in chloroform occurs by way of an SN2 mechanism within a triple ion in spite of the fact that it reacts faster than the primary substrate, benzyldimethylphenylamrnonium bromide. The very loose transition state and steric effects in the ground state appear to be responsible for the unusually fast SN2 reactions between 1-phenylethyldimethylphenylammonium ion and halide ions in chloroform.

HELEN ALMA JOLY et KENNETH CHARLES WESTAWAY. Can. J. Chem. 64, 1206 (1986). On a fait appel h une combinaison des effets isotopiques cinCtiques secondaires des hydrogknes et (ou) deutCriums en a ainsi

qu'en p pour montrer que le mCcanisme de la rkaction SN qui se produit dans le chloroforme entre l'ion dimCthyl phCnyl-1 kthyl phCnylammonium et les ions bromure ou iodure est SN2, dans un ion triple, et ce en dCpit du fait que cette r6action soit plus rapide que celle du substrat primaire, le bromure de benzyl dimkthyl phCnylammonium. 11 semble que 1'Ctat de transition trks lsche et que les effets sttriques dans 1'6tat fondamental soient responsables pour la kaction SN2 exceptionnellement rapide des halogknures de dimCthyl phtnyl-1 Cthyl phCnylammonium dans le chloroforme.

[Traduit par la revue]

Introduction Leffek and co-workers have extensively studied the decomposition of aralkyldimethylphenylammonium halides to aralkyl halides

and dimethylaniline (the reverse of the Menschutkin reaction) in chloroform (1-5), eq. [I].

These workers concluded that the rate-determining step of the decomposition was the conversion of a quaternary ammonium ion into a carbocation and dimethylaniline inside a positively charged triple ion consisting of the two quaternary ammonium ions and one halide ion, eq. [2] (1-6).

+ slow + [ ( A I C H ~ N ( C H ~ ) ~ C ~ H S ) ~ X-I+ - [ A I C H ~ N ( C H ~ ) ~ C ~ H ~ X- + Ar-CH2+ + (CH3)2NC6H5]+

fast + A I C H ~ N ( C H ~ ) ~ C ~ H ~ + kCH2-X + (CH3)2NC6H5

This mechanism was suggested for two reasons, i.e., because (i) very large secondary a-deuterium kinetic isotope effects of 1.25 (1.12 per a-D) and 1.20 (1.10 per a-D) were found for the decomposition of benzyldimethylphenylammonium bromide in chloroform and acetone, respectively (3) (the maximum value expected for a secondary a-deuterium kinetic isotope effect in an $42 reaction at this time was 1.04 per a-D or 1.08 per CDz group (7)), and (ii) because the reactivity of these salts was that observed for carbocation ion SN reactions, i.e., the secondary substrate, 1-phenylethyldimethylphenylammonium bromide, reacted 22.5 times faster than the primary substrate, benzyldimethylphenylammonium bromide in chloroform.

More recent work, however, has shown that the benzyldimethylphenylammonium salts decompose by an SN2 mechanism in dipolar aprotic solvents (8) and that unusually large secondary a-deuterium kinetic isotope effects are observed in the SN2 reactions of benzyldimethylphenylarnrnonium ions. In fact, Westaway et al. (9, 10) observed a secondary a-deuterium isotope effect of 1.18 (1.09 per a-D) in the SN2 reaction with thiophenoxide ion in the dipolar aprotic solvent, DMF, eq. [3].

+ 0°C [3] C6H5S- + C6H5CH2N(CH3)2C6H5 C6H5SCH2C6H5 + (CH3)2NC6H5

DMF

Thus, the isotope effects for the SN reactions of benzyldimethylphenylammonium ion in DMF, chloroform, and acetone are very similar, i.e., they vary from 1.09 to 1.12 per a-D and suggest that all three SN reactions occur by the same mechanism, i.e., an SN2 mechanism.

Theoretical calculations by Hartshorn and Shiner (1 1) support this conclusion. Their calculations predict that the maximum secondary a-deuterium kinetic isotope effect for the ionization of the methylammonium ion to a methyl carbocation and ammonia should be 1.19 per a-D (1.42 per CDz group). This means the minimum isotope effect for the formation of the methyl carbocation would be (1. 19)0.75 = 1.14 per a-D or 1.30 per CDz group (10, 12). In the light of these facts, Westaway and Ali concluded that the substitution reaction in the decomposition of the benzyldimethylphenylammonium bromide in chloroform occurs by a simple SN2

'Author to whom correspondence may be addressed.

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reaction within the triple ion (lo), eq. [4].

Finally, Islam and Leffek in a later publication (5) indicated that they believe the benzyl substrate reacts by the mechanism shown in eq. 141.

If the substitution reaction in the decomposition of benzyldimethylphenylammonium halides in chloroform occurs by an SN2 mechanism within the triple ion, the observation that the secondary substrate, 1-phenylethyldimethylphenylarnmonium bromide reacts 22.5 times faster than the primary compound, benzyldimethylphenylammonium bromide, is surprising. This study was undertaken in an effort to determine the mechanism of the faster reaction and to learn why the rate of reaction is greater for the more highly substituted quaternary ammonium salt.

Results and discussion Four different mechanisms, all occumng within the triple ion,

could account for the surprisingly fast rate of decomposition found for the 1 -phenylethyldimethylphenylarnrnonium bromide in chloroform, Scheme 1. The first possibility is that this reaction occurs by the same SN2 mechanism as the benzyldimethylphenylammonium bromide but that there is some factor that makes it faster than expected. The second possibility is that the substitution reaction in the decomposition of the 1 -phenylethyldimethylphenylamrnonium bromide occurs via the carbocation SN mechanism originally suggested by Leffek and co-workers. If this were the case, the carbocation SN reaction would simply occur faster than the SN2 reaction of the benzyldimethylphenylammonium bromide.

The rate constant could also be larger for the 1-phenylethyl compound if the only products of the reaction, l-phenylethyl- bromide and dimethylaniline, were produced in a two-step elimination-addition reaction. In the first step, the bromide ion would act as the base and abstract a P-hydrogen from the substrate in an E2 elimination reaction to give styrene, hydrobromic acid, and N,N-dimethylaniline in the triple ion complex. In the second step, the hydrobromic acid would add across the a bond of the styrene in a Markovnikov addition to give the observed product, 1 -phenylethyl bromide. If the reaction occurred via the elimination-addition mechanism, the first (elimination) step of the reaction would have to be rate determining for several reasons. First, no elimination product (styrene) could be found either during or after the reaction. This a

means that any hydrobromic acid that formed during the reaction must add quantitatively to the styrene. Since the acid could also react with the other elimination product, dimethylaniline, to form dimethylanilinium bromide in a fast acid-base reaction, the hydrobromic acid would have to react instantaneously with the styrene. Although this might seem unlikely, a simple experiment showed that hydrobromic acid does add instantaneously to styrene in chloroform at room temperature.2 The addition reaction would be expected to be especially fast in the elimination-addition mechanism because the hydrobromic acid is formed immediately beside the a bond of the styrene and, in fact, the proton of hydrobromic acid is removed from the carbon that accepts the proton in the addition step. Finally, the reaction between hydrobromic acid and dimethylaniline might not occur because the hydrobromic acid is released on the opposite side of

. . - . ...

2 ~ . C. Westaway. Unpublished results.

the a bond from the dimethylaniline in a trans, coplanar E2 elimination reaction.

The last possibility is that the observed rate of decomposition is the sum of the rate constants for the elimination-addition and the substitution reaction. If this was the case, the rate constant for the SN reaction of the 1 -phenylethyldimethylphenylarnmonium bromide might even be smaller than that found for the SN2 reaction of the benzyl substrate.

Normally, a kinetic study would distinguish between most of the mechanistic alternatives for this reaction. However, because the reaction occurs within the triple ion, the same kinetic expression would be obtained for all of the mechanisms. As a result, the problem had to be resolved with other mechanistic criteria.

The initial attempt to distinguish between these four mechanisms involved determining the P-deuterium kinetic isotope effect for the reaction. If the substitution reaction occurred via an SN2 mechanism within the triple ion, a small secondary P-deuterium kinetic isotope effect of between 1.02 and 1.10 would be e~pec t ed ,~ Table 1. If the substitution reaction involved the formation of a carbocation triple ion intermediate, a large, hyperconjugative secondary (3-deuterium isotope effect of between 1.15 and 2.5 should be observed. If the elimination- addition mechanism is followed, the P-hydrogen (deuterium) is removed in the rate-determining step of the overall reaction and a large primary hydrogen-deuterium kinetic isotope effect of between three and ten would be expected (1 3). Finally, even if a small percentage of the reaction were to proceed via the

'elimination-addition pathway with a very small primary deuterium kinetic isotope effect of 3.0, a significant P-deuterium kinetic isotope effect would be observed.

The observed (3-deuterium kinetic isotope effect for the reaction of the 1-phenylethyldimethylphenylammonium bromide in chloroform at 25OC was 1.144 + 0.0097 per CD3 (1.0461P-D), Table 2. This small isotope effect clearly eliminates any appreciable contribution from the elimination-addition mechanism, which would have a primary isotope effect of at least 3.0, Table 1. If one assumes the average secondary P-deuterium kinetic isotope effect found for an SN2 reaction (1 .06/CD3 group) and an average primary isotope effect of 5.0 for the E2 elimination reaction, the isotope effect would be 1.14 when 9% of the reaction occurred via this route. Even if one uses the minimum secondary P-deuterium isotope effect of 1.021CD3 group for the SN2 reaction and a minimum primary isotope

3See ref. 12, pp. 122-126.

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TABLE 1 . The P-deuterium kinetic isotope effects expected for the different decomposition mechanisms of 1 -phenylethyldimethylphenyl-

ammonium bromide in chloroform at 25OC.

Decomposition mechanism within the triple ion

Expected ( ~ H I ~ D ) / @ - D ~

S N ~ 1.02-1.11 Carbocation SN

with k2 rate determining 1.34-1.52 with kl, k3, or k4 rate determining 1.16-1.34

Elimination-addition 3.0-10 Elimination-addition-substitution witha

(kH/kD)pS= 1.02"d(kH/kD)pE= 3.0 and PHE = 16% 1 . 1 4 ~

(kH/kD)pS = 1.06 and (kH/kD)pE = 5 .0 and PHE = 9% 1 . 1 4 ~

OPHE is the percent elimination-addition mechanism for the undeuterated substrate, (kH/kD)pS and (kHlkD)pE are the P-deuterium kinetic isotope effects for the substitution and elimination reactions, respectively.

m e observed isotope effect is calculated from k ~ l k ~ = ~ O O [ ( k ~ l k ~ ) p ~ ( k ~ l k ~ ) p ~ ] I [ ( k ~ ~ k ~ ) p s

x PHE + ( k ~ l k ~ ) p ~ x (100 - Pm)I

effect of 3.0 for the E2 elimination reaction. the observed isotope effect is 1.14 when 16% of the reaction occurs via the elimination-addition pathway. Thus, the P-deuterium isotope effect indicates that less than 16% of the reaction occurs via the elimination-addition pathway and suggests that less than 9% of the reaction occurs via this route if the SN reaction occurs via an $42 mechanism within the triple ion. If the SN reaction occurs via a carbocation - triple ion intermediate, on the other hand, none of the product forms in an elimination-addition reaction

because the secondary P-deuterium isotope effects for carbocation SN reactions range from 1.05-1.151P-D (1.16- 1.52/CD3 g r ~ u p ) , ~ i.e., are larger than the isotope effect observed in this reaction. Thus, the P-deuterium isotope effect demonstrates that the decomposition must occur via one of the SN mechanisms.

The maximum kinetic isotope effect for a particular leaving group is observed in normal (not occurring in a triple ion) carbocation SN reactions when the slow step is the formation of the solvent-separated ion pair or the free carbonium ion and hyperconjugation is a maximum (ref. 10 and footnote 3). Smaller isotope effects are found when formation of the intimate ion pair or the destruction of a carbocation intermediate is rate detirmining. The smaller isotope effect is presumably found in these reactions because the positive charge has not been developed fully or has been partially destroyed in the transition state of the rate-determining step of the reaction and hyperconjugation is not a ma~imurn .~

Although a carbocation intermediate in a triple ion cannot exist as a solvent-separated ion pair, the carbocation could react either as an intimate ion-molecule pair or as a free carbocation. Thus, a carbocation SN reaction occurring within the triple ion, Scheme 2, could have any of the kl , the k2, the k3, or the k4 steps rate-determining .

In fact, the secondary P-deuterium kinetic isotope effect found when the k,, the k3, or the k4 step of a carbocation reaction is rate determining is only about 1.05lP-D (1.161CD3 group) or 60% of the isotope effect found when the k2 step is rate dete~mining.~ Since the observed isotope effect of 1.144 is within experimental error of the minimum value expected for a carbocation SN reaction, one cannot eliminate a carbocation mechanism where the rate-determining step is the formation of

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TABLE 2. The a- and P-deuterium kinetic isotope effects for the decomposition of l-phenylethyldimethylphenylammonium bromide in chloroform at 25OC

kH x lo4, S-' kDg X lo4, S-' (kH/kD)IP-D3 kDa x lo4, s-' (kH/kD)Ia-D

The error limits are the standard deviation. %e error limits were calculated using the equation

Error = l / kD[ (hkH)2 + ( k H ~ k D ) ~ ( h k D ) ~ ] ~ ~ where AkH and AkD are the standard deviations for the rate constants of the undeuterated and deuterated substrate, respectively.

the intimate ion-molecule pair or the destruction of a carbocation intermediate.

The secondary P-deuterium isotope effects for SN2 reactions normally range from 1 .O1 to 1.03lP-D (1.03-1 .09/CD3 group). However, much larger secondary P-deuterium isotope effects have been found in some SN2 reactons. For example, an isotope effect of 1. 13/CD3 group was reported for the ethanolysis of isopropyl brosylate3 and an isotope effect of 1. 16/CD3 group was found in the acetolysis of ethyl triflate at 25OC (14). Although the observed isotope effect of 1.14 is larger than those found in most normal SN2 reactions, it is smaller than the largest isotope effects that have been foond and one cannot rule out the SN2 mechanism for the reaction within the triple ion. Thus, the P-deuterium kinetic isotope effect eliminates the elimination- addition mechanism as a significant pathway for the reaction and reduces the problem to distinguishing between an SN2 mechanism and a carbocation SN mechanism with the k, (an SNlllm mechanism), or the k3 or k4 step (SN2C+ mechanisms), rate determining.

The second criterion of mechanism that was used to distinguish between the carbocation and the SN2 mechanisms for the SN reaction between 1-phenylethyldimethylphenylarnrnonium ion and bromide ion in the triple ion was the secondary a-deuterium kinetic isotope effect. The large isotope effect of 1.178 + 0.0061~~-D found for this reaction, Table 2, is significantly larger than the isotope effect of 1.12 found for the SN2 reaction of the benzyl derivative in chloroform. In spite of this, the SN2 mechanism cannot be ruled out for several reasons. Adding a methyl group to the a-carbon of primary substrates that react via SN2 mechanisms increases the secondary a-deuterium kinetic isotope effect by 1.036 k 0.003 (15). Adding a methyl group to the a-carbon of the benzyldimethylphenylammonium ion should, therefore, raise the isotope effect for an

SN2 reaction of the 1-phenylethyldimethylphenylammonium bromide from 1.12 to 1.16. Since one would expect the increase in isotope effect to be greater when the substrate is more sterically crowded, i.e., adding a methyl group to the a-carbon of a more crowded substrate would increase the frequency of the out-of-plane C,-H(D) ground state bending vibrations and the zero-point energy difference more than adding a methyl group to a less crowded substrate, one would expect an even larger isotope effect than 1.16 for the 1-phenylethyl compound. Thus, the expected (kHlkD > 1.16) and the observed isotope effect (kHlkD = 1.178) are close enough so that one cannot rule out the SN2 mechanism. This conclusion is supported by the large secondary a-deuterium isotope effects found in SN2 reactions by Craze et al. (16) and by Knier and Jencks (17). Craze et al. reported secondary a-deuterium kinetic isotope effects as large as 1.161~~-D in the SN2 reactions of I-methoxymethoxy-2,4- dinitrobenzene and Knier and Jencks found isotope effects as large as 1.18/a-D in the SN2 reactions of the quaternary ammonium ion, methoxymethyldimethyl-m-nitroanilinium ion.

Large secondary a-deuterium kinetic isotope effects at or near the maximum are found in carbocation SN reactions where the formation of the solvent-separated or the free carbonium ion is rate determining, whereas smaller isotope effects, approximately 75% of the maximum, are found in carbonium ion SN reactions where the k, step is rate-determining (12). The maximum and minimum isotope effect for a carbonium ion mechanism of a primary ammonium salt is 1.191~~-D (1 1) and 1. 19°.75 = 1.141~~-D. The maximum and minimum isotope effects for a secondary substrate would be approximately 1.04 times greater, i.e., 1.24 and 1.17la-D, respectively. Thus, although the isotope effect of 1.178 is too small to be indicative of a carbocation mechanism where the formation of the free carbocation within the triple ion is rate determining, it is

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TABLE 3. The rate constants and Hammett p value for a series of para-substituted phenyl-I-phenylethyldimethylammonium bromides in chloroform at 34.88"C

para-Substituent in the leaving group k x lo5, S-' p (leaving group)

CH30 7.681 &0.0004" CH3 17.36&0.007 H 41.49k0.15 C1 103.4&0.1 2.20*0.07" Corr. coeff. = 0.989

"The error limits are the standard deviation.

consistent with a carbocation mechanism where the k l , the k3,

or the k4 step is rate determining. Unfortunately, both the secondarj a- and P-deuterium kinetic isotope effects are at the borderline between the values expected for an SN2 and a carbocation SN reaction, with the formation of the intimate ion-molecule pair or the destruction of a carbocation intermediate rate determining. Thus, while measuring these isotope effects limited the mechanistic options to three SN mechanisms, they did not distinguish between a simple SN2, an SNllim, and an SN2C+ mechanism for the triple ion substitution reaction.

The next criterion that was used to determine the mechanism of the triple ion SN reaction between l-phenylethyldimethylphenylamrnonium ion and bromide ion was the Hammett p value found by changing the para substituent on the benzene ring of the leaving group. If the reaction occurs via an SN2 or a carbocation mechanism with the kl step rate determining, the C-N bond breaks in the slow step of the reaction and a small Hammett p value would be observed. If the reaction occurs via a carbocation mechanism with the kl step reversible and the k3 or the k4 step rate determining, the C-N bond is broken in a fast, reversible step and a large, equilibrium p value would be observed. The Harnmett p value of +2.20, Table 3, is significantly smaller than the p values found for the complete destruction of a positive charge on a nitrogen atom. In fact, the p values found for the equilibrium dissociation of para-substituted N,N-dimethylanilinium ions to dimethylanilines and a proton, i.e., for the complete destruction of a positive charge on nitrogen, range from + 3.43 to +4.19 in various solvents (8). Thus, one would expect a p value of at least 3.4 if the positive charge had been completely destroyed in the transition-state of the rate-determining step of the SN reaction between l-phenylethyldimethylphenylammonium ion and bromide ion. The much smaller p value of +2.20 indicates that the C,-N+ bond is breaking in the rate-determining step of the reaction and rules out a carbocation mechanism where the k3 or the k4 step is rate determining. Thus, the SN reaction between the l-phenylethyldimethylphenylammonium ion and bromide ion in the triple ion must proceed by way of an SN2 mechanism or a SNllim mechanism with the k , step rate determining.

The mechanism for the-reaction was finally determined by comparing the secondary a- and secondary P-deuterium kinetic isotope effects for the bromide ion reaction with those found when the nucleophile was iodide ion. If the SN reaction within the

secondary a- and secondary P-deuterium kinetic isotope effects would be different in the two reactions. A comparison of the secondary a- and P-deuterium kinetic isotope effects for the bromide ion (Table 2) and iodide ion reactions, Table 4, show that the isotope effects do change when the nucleophile is changed. In fact, a Wilcoxin test and the Student's t test (18, 19) show that the secondary a-deuterium kinetic isotope effects of 1.178 k 0.006 for the bromide ion reaction and 1.184 t- 0.0077 for the iodide ion reaction, respectively, are significantly different at the 92% confidence level if one uses the average isotope effects obtained by combining each kH value with each kD value, and are significantly different at the 53-81% confidence level if one uses the worst and best combinations of the three isotope effects, respectively, in the statistical analysis. While the a-deuterium kinetic isotope effects are not significantly different at a high confidence level, the same two statistical tests indicate that the secondary P-deuterium kinetic isotope effects of 1.144 * 0.0097 for the bromide ion reaction and 1.172 * 0.0072 for the iodide ion reaction are significantly different at the 99.9% confidence level. The different isotope effects for these two reactions clearly demonstrate that the nucleophile is in the transition state of the rate-determining step of these reactions and it has been concluded that the decomposition of the l-phenyldimethyl- phenylammonium halides in chloroform occurs via an SN2 mechanism within a triple ion.

Once it had been established that the SN reaction of both the benzyl- and the 1-phenylethyldimethylphenylamrnonium bromides in chloroform occurred by an SN2 mechanism within a triple ion, attention was turned to determining the relative structures of the transition states for these two reactions. The transition states for these two reactions were estimated in two ways. First, the relative lengths of the a-carbon-leaving group transition state bonds were determined by comparing the Harnmett p values found by changing the substituent in the leaving group. The results in Tables 3 and 5 show that the Hammett p values for these two reactions are very different. In fact, the p value for the 1-phenylethyl reaction is more than twice that found for the reaction of the benzyl substrate. This clearly indicates that there is a greater change in electron density on the nitrogen atom in going from the reactant to the transition state of the 1-phenylethyldimethylphenylammonium ion reaction and that the a-carbon-nitrogen bond is significantly longer in the 1-phenylethyldimethylphenylammonium bromide transi-

triple ion occurred via the rate-determining formation of the tion state. intimate ion-molecule pair, the transition state would be Next, the relative lengths of the nucleophile-a-carbon bonds independent of the nucleophile and one would find the same a - in the two transition states were estimated by determining the and P-deuterium isotope effects in both reactions. If the reaction selectivity of the reactions to a change in nucleophile. Both we proceeded via an SN2 mechanism on the other hand, the (20) and Hanis et al. (21) have used the selectivity of a reaction nucleophiles are a part of the transition states, the transition to a change in nucleophile to estimate the lengths of nucleophile- states would be different, and the magnitude of both the a-carbon bonds in SN reactions. In fact, it is believed that the

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TABLE 4s The secondary a- and P-deuterium kinetic isotope effects for the decomposition of 1-phenylethyldimethylphenylammonium iodide in chloroform at 25°C

"The error limits are the standard deviation. %e error limits were calculated using the equation

Error = 11 kD[(A kH)' + (kHl kD)'(A kD)2]1'2 where AkH and AkD are the standard deviations for the rate constants of the undeuterated and deuterated substrate, respectively.

TABLE 5. The rate constants and Hammett p value for a series of para-substituted phenylbenzyldimethylarnmonium bromides in chloroform at 34.88"C

para-Substituent in the leaving group k x lo5, s-' p (leaving group)

CH30 1.958+0.006" CH3 2.16620.048 H 2.870k0.011 C1 5.57620.021 0.918+0.04aCorr. coeff. = 0.982

"The error limits are the standard deviation

TABLE 6. The rate constants and selectivity for the decomposition of benzyl and l-phenyl- ethyldirnethylphenylamrnonium bromides and iodides in chloroform

Substrate

Parameter c & s c H ~ ~ ( c H ~ ) ~ c ~ H ~ ~ C S H S C H ~ ( C H ~ ) ~ C ~ H ~

kBr x lo5, s-i 6.1 at 40°C 11.61 at 25°C 12.3 at 45°C

kd k ~ , 7.8 at 40°C 2.4 at 25°C 7.6 at 45°C

'The rate constants are from ref. 5.

selectivity does not indicate the total structure of the transition state but is related to the length of the bond nearest to the point of structural change. The rate constants for the S . 2 reactions of the benzyl and 1-phenylethyl substrates with bromide ion and iodide ion, Table 6, give the selectivity of each reaction to a change in nucleophile. Although the rate constants for the two reactions were measured at different temperatures, the tkmpera- ture effect on the selectivity (kIlkBr) for the benzyldimethyl-. phenylammonium ion reaction is small and it is clear that the 1-phenylethyldimethylphenylammonium ion reaction is much less sensitive to change in nucleophile than the benzyldimethylphenylammonium ion reaction. A greater selectivity is indicative of a shorter nucleophile-a-carbon transition state bond because the difference in energy of the two transition states (the rate constants) will be greater when the nucleophile-a-carbon bonds are more complete in fie transition state. Thus, the selectivities indicate that the nucelophile-a-carbon transition state bond is significantly longer in the l-phenylethyldimethylphenylammonium ion transition state than in the benzyldimethylphenylammonium ion transition state.

The selectivities and the Hammett p values indicate that the 1-phenylethyldimethylphenylarnmonium ion reaction has a much looser transition state with longer nucleophile-a-carbon and acarbon-leaving group bonds than the corresponding benzyl salt. In fact, Schowen and co-workers (22) had indicated that adding a methyl group to the a-carbon of the substrate in an SN2 reaction would lead to a looser transition state and this is what has been found. However, this study has gone further by demonstrating that both of the reacting bonds in the S N ~ transition state become longer when a methyl group is added to the a-carbon.

Finally, it is interesting to speculate on the reason the 1-phenylethyldimethylphenylammonium ion reacts faster than the corresponding primary benzyl substrate. This is unusual because secondary compounds normally react from 25 to 150 times slower than primary compounds in SN2 reactions (23) because the SN2 transition state for a secondary substrate is more sterically crowded. It would appear that the l-phenylethyldimethylphenylammonium ion reacts faster than the benzyl substrate for two reasons. One contributing factor is undoubtedly

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1212 CAN. 1. CHEM. VOL. 64, 1986

that the transition state is very loose. In fact, both the secondary a - and P-deuterium kinetic isotope effects are unusually large for an SN2 reaction, i .e. , they are almost in the range expected for a carbocation SN reaction and confirm that the transition state for this reaction is very loose. Thus, the steric crowding that is present in the SN2 transition states of most secondary substrates is not present in the 1-phenylethyldimethylphenylarnmonium ion SN2 transition state; the transition state will be lower in f ~ e e '

energy and the reaction will be faster than expected. Another factor contributing to the faster rate of reaction is steric crowding in the initial state. Westaway and Ali attributed the very large secondary a-deuterium kinetic isotope effects in the SN2 reactions of benzyldimethylphenylammonium ions to steric hindrance of the C,-H(D) out-of-plane bending vibrations in the initial state (10). Obviously, the steric crowding would be greater in the initial state of the 1-phenyl substrate. This would increase the ground state energy of the l-phenylethyldimethylphenylammonium ion, further reducing the free energy of activation. Thus, the reaction is probably faster than expected for two reasons, steric acceleration due to steric crowding in the initial state and a looser (less sterically crowded) SN2 transition state within the triple ion.

Experimental Preparation of reagents

Preparation of 1 -phenylethyldimethylphenylammonium bromide Anhydrous hydrogen bromide gas (Matheson) was bubbled with

occasional cooling into 56.80 g (0.546 mol) of styrene for approximately 3 h at room temperature. The product, 1-phenylethyl bromide, was washed several times with distilled water, dried over magnesium sulfate, and distilled, bp 55.5-56.0°C at 3.5 Torr (1 Torr = 133.3 Pa) (lit. (24) bp, 202-203°C). The yield was 91.2 g (90%).

Twenty-five grams (0.135 mol) of 1-phenylethyl bromide was added to 18.2 g (0.150 mol) of freshly distilled N,N-dimethylaniline and left under dry nitrogen in the dark for four days. Then the solid product was filtered and washed with anhydrous ether. The crude product (35.4 g (86%)) was recrystallized to a constant melting point of 119.5- 120.5"C (lit. (4) mp 125-126°C) by dissolving it in a minimum of acetonitrile at room temperature and precipitating the salt with ether. The discrepancy between the reported and experimental melting point arose because a change in the heating rate of the melting point apparatus altered the melting point markedly. For example, a sample melting between 119.5 and 120.5"C melted at 129-130°C when the heating rate was higher. As a result all of the melting points were determined on the same melting point apparatus at the same heating rate. Finally, all of the quaternary ammonium salts used in this study were stored in a desiccator in the dark until they were used in a kinetic run.

Preparation of 1-phenylethyl-2,2,2-d3-dimethylphenylammonium bromide

This compound was synthesized by adding a mixture of 12.5 g (0.0862 mol) of iodomethane-d3 (Merck, Sharp and Dohme) in 20 mL of sodium-dried ether, dropwise, to 2.72 g (0.01 12 mol) of clean magnesium and lOmL of sodium-dried ether in a dry, 250-mL three-necked round-bottom flask fitted with a condenser and a dropping funnel. When the addition was complete, the mixture was refluxed for 30 min, cooled to below -5°C with an ice-salt bath, and a solution of 8.748 (0.0824mol) of "purified" benzaldehyde (25) in 25 mL of sodium-dried ether was added so that the temperature did not exceed -5°C. When the addition was complete, the reaction mixture was stirred for 30 min and then decanted onto 38 g of crushed ice. After acidification with 10% sulfuric acid, the ether layer was separated. The aqueous layer was extracted with three 20-mL portions of anhydrous ether. Then, the combined ether extracts were washed three times with

10% sodium hydroxide, once with distilled water, and dried with anhydrous magnesium sulfate. A distillation gave 5.38 g (52%) of 1-phenylethyl-2,2,2-d3 alcohol, bp 62°C at 3Torr (lit. (26) bp 71-72°C at 2 Torr). The nrnr spectrum was identical to that reported for the product (27).

After anhydrous hydrogen bromide (Matheso had been bubbled through a solution of 5.38 g (0.0423 mol) of 1-p "i enylethyl-2,2,2-d3 alcohol in 10 mL of benzene for 90 rnin, the benzene-1-phenylethyl- 2,2,2-d3 bromide solution was washed several times with water and dried with anhydrous magnesium sulfate. After the benzene had been removed on the rotary evaporator, a distillation gave 3.70 g (69%) 1-phenylethyl-2,2,2-d3 bromide, bp 50.5"C at 3 Tom (lit. (24) bp 202-203°C at 760Torr). An analysis of the nrnr spectrum indicated that the product was 99% deuterated at the 2 position.

In the third step, 2.93 g (0.0155 mol) of 1-phenylethyl-2,2,2-d3 bromide was added to 1.65 g (0.0136 mol) of freshly distilled N.N- dimethylaniline and left for several days in a dry, nitrogen atmosphere. The ~roduct was filtered. washed with several D O ~ O ~ S of anhvdrous , - - -

ethk, and crystallized from a mixture of acetonithle - anhydrous ether, vide supra. This gave 2.59 g (63%) of 1-phenylethyl-2,2,2-d3-dimethylphenylammonium bromide, mp 119.5-120.5"C.

Preparation of 1 -phenylethyl-1 -dI-dimethylphenylammonium bromide

A solution containing 15.07 g (0.126 mol) of acetophenone and 150 mL of sodium-dried ether was added dropwise to a mixture of 3 g (0.07 mol) of lithium aluminium deuteride in 200 mL of sodium-dried ether. After refluxing overnight, the reaction mixture was slowly poured onto crushed ice. The solution was made basic by adding sodium hydroxide pellets and the ether layer separated. The aqueous phase was extracted twice with 50-mL portions of ether.Then the ether layers were combined and dried over anhydrous magnesium sulfate. After the ether had been removed on a rotary evaporator, distillation gave 13.31 g (0.1081 mol) of pure 1-phenylethyl-1-dl alcohol, bp 66°C at 2Torr (lit. (26) bp 71-72°C at 2Torr).

Anhydrous hydrogen bromide was bubbled through 13.3 1 g (0.108 1 mol) of 1-phenylethyl-1-dl alcohol for 3 h. The two phases were separated and the organic layer was washed several times with distilled water, dried with anhydrous magnesium sulfate, and then distilled to give 18.5 g (92%) of 1-phenylethyl-1-dl bromide, bp 60°C at 2 Torr. An analysis of the C,-H absorption at 4.56 ppm in the nmr spectrum suggested that the 1-phenylethyl-1-dl bromide was 99.4% deuterated.

Finally, 18.03 g (0.0969 mol) of 1-phenylethyl-1-dl bromide and 13.29 g (0.109 mol) of freshly distilled N,N-dimethylaniline were mixed in a dry nitrogen atmosphere and left at room temperature for 1 week. The solid product was filtered, then washed several times with anhydrous ether. The 25.43 g (85.4%) of crude 1-phenylethyl-1-dl- dimethylphenylamrnonium bromide was recrystallized from aceto- nitrrile - anhydrous ether to a constant melting point of 120-120.5"C.

Preparation of the a-deuterated, P-deuterated, and undeuterated 1-phenylethyldimethylphenylammonium iodides

The a-deuterated, P-deuterated, and undeuterated quaternary ammonium iodides were obtained by converting the appropriate quaternary ammonium bromides into the quaternary ammonium hydroxides with silver oxide and then titrating the hydroxides with hydriodic acid.

Preparation of 1 -phenyIethyldimethylphenylammonium iodide A 99% excess (3.255g, 0.01403 mol) of nitrate-free silver oxide

(28) was stirred with a solution of 2.15g (7.03 x l ~ - ~ m o l ) of 1-phenylethyldimethylphenylamrnonium bromide in 60 mL of distilled water for 3.5 h. After the solution was filtered through a 934 AH Reeve Angel glass fiber filter, the filtrate was taken to a pH of 3.9 by adding hydriodic acid and left overnight in the dark. After the solution was filtered through another 934 AH Reeve Angel glass fiber filter, the filtrate was taken to dryness on the rotary evaporator. The crude product (I 8 g, 74%) was dried in an evacuated desiccator overnight and then recrystallized from an acetonitrile-ether mixture, mp 101- 102°C. All of the quaternary ammonium iodides were stored in the dark (28) in a vacuum desiccator until they were used for kinetics.

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Preparation of 1-phenylethyl-2,2,2, -ds-dimethylphenylammonium 101- 102°C. The chemical shifts and the integration of the peaks in the iodide nmr spectrum were consistent with the structure 4-methylphenyl-l-

1-Phenylethyl-2,2,2-d3-dimethylphenylammonium bromide, 2.352 phenylethyldimethylphenylammonium bromide. g (7.61 ~ l 0 - ~ m o l ) was dissolved & approximately 50 mL of distilled water and stirred with 3.53 g (0.0152 mol) of nitrate-free silver oxide for 6 h. Then the solution was filtered through a 934 AH Reeve Angel glass fiber filter and the filtrate acidified to a pH of 3.04 with hydriodic acid. The next day, the solution was filtered through a 934 AH glass fiber filter and the filtrate taken to dryness on the rotary evaporator. The crude product (18 g, 65%) was dried in a vacuum desiccator and recrystallized from acetonitrile-ether, mp 10 1 - 102°C.

Preparation of I -phenylethyl-1 -dl-dimethylphenylammonium iodide

1-Phenylethyl-1 -dl-ammonium bromide, 6.02 g (0.0196 mol), was stirred with 120 mL of distilled water and 9.08 g (0.0391 mol) of silver oxide for 3.5 h, filtered through a 934 AH Reeve Angel glass fiber filter, and the filtrate taken to a pH of 5.40 with hydriodic acid. After the solution had been stored overnight, it was filtered through a 934 AH Reeve Angel glass filter and the water removed on the rotary evaporator. The resulting solid (6.0 g, (86%)) was dried overnight in an evacuated desiccator and recrystallized from acetonitrile-ether, mp 101.5-103°C.

Preparation of a series of 4-substituted phenyl-l-phenylethyldimethylammonium bromides

The 4-methoxy-, the 4-chloro-, and the 4-methylphenyl- 1 -phenylethyldimethylammonium bromides were prepared by reacting l-phenylethyl bromide with an excess of 4-methoxy-, 4-chloro-, and 4-methyl- N,N-dimethylanilines, respectively. The N,N-dimethyl-4-methylaniline (Aldrich) was purified by distillation under reduced pressure. The synthesis of the N,N-dimethyl-4-methoxy- and N,N-dimethyl- 4-chloroanilines are described elsewhere (8).

Preparation of 4-methoxyphenyl-I-phenylethyldimethylphenylammonium bromide

N,N-dimethyl-4-methoxyaniline (4.24 g, 0.280 mol) and 5.31 g (0.0287 mol) of 1-phenylethyl bromide were sealed in an Erlenmeyer flask that had been flushed with dry nitrogen, and stirred overnight. The solid product was filtered, washed several times with anhydrous ether, and dried in an evacuated desiccator. The 9.3 g (99%) of crude 4-methoxyphenyl-l-phenylethyldimethylphenylammonium bromide was recrystallized by dissolving it in a minimum of acetonitrile, placing 4-mL portions into 25 mm x 150 mm test tubes, filling the tubes with anhydrous ether, and allowing the salt to precipitate overnight (recrystallization on a larger scale yielded a sticky oil). Repeated recrystallizations gave a product with a melting point of 107-109°C. The nmr spectrum was consistent with that expected for 4-methoxyphenyl-1-phenylethyldimethylphenylamrnonium bromide.

Preparation of 4-chlorophenyl-I-phenylethyldimethylphenylammonium bromide

N,N-dimethyl-4-chloroaniline (4.25 g, 0.0273 mol) and 5:04 g (0.0272 mol) of 1-phenylethyl bromide were mixed and left sealed in a dry nitrogen atmosphere overnight. Then the product was filtered, washed with anhydrous ether, and dried in an evacuated desiccator. The 8.88 g (96%) of crude 4-chlorophenyl-1-phenylethyldimethylammonium bromide was recrystallized with acetonitrile - anhydrous ether to a constant melting point of 112.5-1 13.5"C. The nmr spectrum of the solid was consistent with that expected for the product.

Preparation of 4-methylphenyl-I-phenylethyldimethylphenylammonium bromide

The reactants, 5.06g (0.0273 mol) of 1-phenylethyl bromide and 4.74 g (0.035 mol) of freshly distilled N,N-dimethyl-4-methylaniline were mixed together in a nitrogen atmosphere. The solid that formed in one day was filtered, washed with anhydrous ether, and dried in an evacuated desiccator. Finally, the 6.3 g (72%) of 4-methylphenyl- 1-phenylethyldimethylphenylammo~urn bromide was recrystallized using the method described for the 4-methoxyphenyl-1-phenylethyldimethylphenylammonium bromide. The mp of the pure product was

Kinetic measurrements The electrolytic conductivity apparatus used to measure the rate

constants for the decomposition of the quaternary ammonium salts consisted of three units, a 1-kHz/s sine wave oscillator (Heath Kit IG-72), a conductivity bridge capable of measuring resistances ranging from 0.1 to 110 000 ohms, and a detector consisting of a 1-lcHz low noise, transistorized amplifier and an X-Y oscilloscope. The decade resistance of the measuring arm, which was in parallel with variable capacitors to obtain a sharp balance point, measured the resistance to within 0.1%. The conductivity dip cell (cell constant of 0.1) that was used as the unknown arm of the conductivity bridge was equipped with a thermometer adapter and a bushing adapter so that the cell could be sealed completely into the 25 mm X 150 rnrn ground glass topped test tube that was used as the reaction vessel. These precautions were taken to minimize evaporation of the solvent because the reactions were followed for several hours.

In a typical reaction, approximately 15 mL of distilled chloroform was placed in the reaction vessel. The reaction vessel was sealed with the conductivity dip cell and temperature equilibrated for 30min at 25.00 ? 0.02"C. Then, a weighed amount (between 0.22 and0.25 g) of quaternary ammonium salt was dissolved in the temperature equilibrated chloroform. After waiting at least 10 min for the quaternary ammonium salt - chloroform solution to equilibrate, the bridge was balanced and the timer started. Resistance measurements were made every "x" minutes according to the Guggenheim method (6, 29). The first-order rate constants were determined from the linear least-squares slope of the Guggenheim plot (6). Care was taken to collect the resistance measurements for each bromide salt over the same range of resistances (concentrations), i.e., from 2747 k 6 ohms to 445 18 * 198 1 ohms, to eliminate any ionic strength effects on the rate constants.

The procedure used to measure the rate constants that were required for determining the Hammett p value for the Csubstituted phenyl-l- phenylethyldimethylphenylammonium bromides was slightly different. The changes were (i) that 20 mL of distilled chloroform was placed in the reaction vessel, (ii) that the temperature was 34.88 -t 0.02"C, (iii) that between 0.31 and 0.39 g for the 4-substituted phenyl-l-phenylethyldimethylphenylammonium bromides was used in these runs, and (iv) that the time and resistance readings were begun when the quatekary ammonium salt was added to the ~Thloroform &d continued every "x" minutes until the capacity of the bridge (1 10 000 ohms) was exceeded or until the concentration of the substrate was less than 0.0246 mol/L. The rate constants for these reactions were obtained by applying the Guggenheim method to the resistances found over the concentrations ranges 0.0508-0.0379 mol/L and from 0.0329-0.0246

Acknowledgements The authors thank the Natural Sciences and Engineering Re-

search Council of Canada for the financial support required to complete this study and for providing a scholarship to H.A.J.

1. J. T. BURNS and K. T. LEFFEK. Can. J. Chem. 47,3725 (1969). 2. E. C. F. KO and K. T. LEFFEK. Can. J. Chem. 48, 1865 (1970). 3. E. C. F. KO and K. T. LEFFEK. Can. J. Chem. 49, 129 (1971). 4. E. C. F. KO and K. T. LEFFEK. Can. J. Chem. 50, 1297 (1972). 5. M. N. ISLAM and K. T. LEFFEK. J. Chem. Soc. Perkin Trans. 2,

952 (1977). 6. K. T. LEFFEKandF. H. C. TSAO. Can. J. Chem. 46,1215 (1968). 7. K. HUMSKI, V. SENDIJAREVIC, and V. J. SHINER, JR. J. Am.

Chem. Soc. 96, 6187 (1974). 8. K. C. WESTAWAY and R. A. POIRIER. Can. J. Chem. 53, 3216

(1975). 9. K. C. WESTAWAY and R. A. POIRIER. 58th Canadian Chemical

Conference, Toronto, Ont . 1975.

Can

. J. C

hem

. Dow

nloa

ded

from

ww

w.n

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64.1

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onal

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onl

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CAN. J. CHEM. \

10. K. C. WESTAWAY and S. F. ALI. Can. J. Chem. 57,1089 (1979). 11. S. R. HARTSHORN and V. J. SHINER, JR. J. Am. Chem. Soc. 94,

9002 (1972). 12. V. J. SHINER, JR. In Isotope effects in chemical reactions. Am.

Chem. Soc. Monograph 166. Edited by C. J. Collins and N. S. Bowman. Van Nostrand - Reinhold, New York. 1971. p. 137.

13. P. J. SMITH. In Isotopes in hydrogen transfer processes. Vol. 2 of the Isotopes in Organic Chemistry series. Edited by E. Buncel and C. C. Lee. Elsevier, Amsterdam. 1976. pp. 231-237.

14. J. M. HARRIS. Prog. Phys. Org. Chem. Vol. 11. Edited by A. Streitwieser, Jr. and R. W. Taft. J. Wiley and Sons, Toronto. 1974. pp. 89-168.

15. K. C. WESTAWAY. In Isotopes in chemistry. Vol. 7. Edited by C. C. Lee and E. Buncel. Elsevier, Amsterdam. In press.

16. G. A. CRAZE, A. J. KIRBY, and R. OSBORNE. J. Chem. Soc. Perkin Trans. 2, 357 (1978).

17. B. L. KNIER and W. P. JENCKS. J. Am. Chem. Soc., 102,6789 (1980).

18. R. D. G. STEEL and J. H. TORRIE. Principles and procedures of statistics with special reference to biological sciences. McGraw- Hill, Toronto. 1960. pp. 404 and 470.

19. C. WHITE. Biometries, 8, 33 (1950). 20. K. C. WESTAWAY and H. A. JOLY. 63rd Canadian Chemical

Conference, Ottawa, Ont. 1980. 21. J. M. HARRIS, S. G. SHAFER, J. R. MOFFAT, and A. R. BECKER..

J. Am. Chem. Soc. 101, 3295 (1979). 22. C. H. GRAY, J. K. COWARD, K. B. SCHOWEN, and R. L.

SCHOWEN. J. Am. Chem. Soc. 101,4351 (1979). 23. A. STREITWEISER, JR. Solvolytic displacement reactions.

McGraw-Hill Co., Toronto. 1962. p. 12. 24. R. C. WEAST (Editor). Handbook of chemistry and physics. 48th

ed. CRC Press, Boca Raton, Florida 1967-1968. p. 196. 25. A. I. VOGEL. Practical organic chemistry. 3rd ed. Longmans,

Green and Co., Toronto. 1954. p. 694. 26. V. J. SHINER, JR., W. E. BUDDENBAUM, B. L. MURR, and G.

LAMATY. J. Am. Chem. Soc. 90,418 (1968). 27. C. J. POUCHERT. The Aldrich library of NMR spectra. 2nd ed.

Aldrich Chemical Co., Milwaukee, WI. 1983. p. 921. 28. K. C. WESTAWAY and A. N. BOURNS. Can. J. Chem. 50, 2332

(1972). 29. A. A. FROST and R. G. PEARSON. Kinetics and mechanism. 2nd

ed. J. Wiley and Sons, New York. 1961. pp. 49-50.

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