J . Am. Chem. SOC.1993, 115, 1739-1744
1739
On the Importance of Carbocation Intermediates in Bimolecular Nucleophilic Substitution Reactions in Aqueous Solution John P.Richard* and Paul E.Yeary Contribution from the Department of Chemistry, University of Kentucky, Lexington, Kentucky 40506-0055. Received October 28, 1992
Abstract: The effect of nucleophilic anions on the rate constants for reaction of 1-(4-methoxyphenyl)-2,2,2-trifluoroethyliodide (1-1) and bromide (1-Br) in water at 25 OC and a constant ionic strength of 6.00maintained with perchlorate ion has been determined. These substrates react by a DN + AN (SNl) mechanism through the I-(4-methoxyphenyl)-2,2,2-trifluoroethyl carbocation intermediate (2), which is captured by I-, N3-, and SCN- in diffusion-limited reactions. There are also reactions of 1-1 in the presence of the strong nucleophiles N3- and SCN- that are kinetically bimolecular at low nucleophileconcentrations (0-1.00M), but higher nucleophile concentrations (2.00-4.00 M) cause decreases in the velocity of the reaction. Decreases in velocity are observed for the reaction of 1-1 in the presence of the weak nucleophilesC1-, A&-, and Sod2and for the reaction of 1-Br in the presence of N3-. These data are consistent with a stepwise preassociation mechanism for the bimolecular substitution reactions of N3- and SCN- with 1-1 because this pathway will be significant only when the reactions of both the leaving group ion (I-) and the nucleophile (N3- or SCN-) with the free carbocation 2 are diffusion limited. The fit of the data for the reaction of N3- with 1-1 to a rate equation derived for the stepwise preassociation mechanism gives Kaa= 0.67 M-' for the formation of the [N3--1-I]preassociation complex and the rate constant ratio kNU/kdv= 2 for reaction of 1-1 with N3- within this complex (kNu)and for reaction of 1-1 in the presence of solvent alone (kwlv). The largest rate increase observed at [Nu-] = 1.00 M is only 40% for the reaction of 1-1 in the presence of SCN-, so the rate accelerations resulting from bimolecular nucleophilic substitution reactions through a carbocation intermediate are small even when this reaction is favored by the choice of nucleophile and leaving group.
Introduction It has been over 20 years since the provocative suggestion of Sneen that all aliphatic nucleophilic substitution reactions that are kinetically bimolecular proceed by a stepwise mechanism in which the nucleophile traps an ion pair or an ion-dipole pair intermediate in the rate-detennining step.] This extreme proposal has been discredited by the demonstration that many bimolecular nucleophilic substitution reactions proceed by a concerted mechanism which avoids the formation of a carbocation reaction intermediate.2" Bimolecular nucleophilic substitution reactions that proceed through carbocation reaction intermediates are not expected to be common because strict conditions must be met if the reaction of the nucleophilic reagent with an ion pair intermediate is to give a detectable increase in the rate of disappearance of the ~ubstrate.~ These conditions may be summarized with reference to Scheme I: (1) The rate of formation of the carbocation intermediate (by k l or k,') must be faster than the rate of formation of nucleophile adducts by a concerted reaction mechanism (by K,, and kc). (2)The formation of the ion pair intermediate [R+.X-] from substrate must be reversible in order for its reaction with nucleophilic reagents to lead to an increase in the rate of disappearance of substrate. This requires that the rate constant for the return of ion pair to substrate ( k - l ) be larger than the rate constants for the irreversible reactions of the ion pair ( k 4 and k i ) , i.e., k-, > k4 + k i . (3) In order for the reaction through the triple ion complex [Nu-.R+.X-] to lead to a detectable increase in the rate of disappearance of the substrate, the rate of formation of products from this complex must be faster than that for the formation of products from the ion pair [R+-X-], i.e., k2 > k4 + k i . These conditions will be most easily met in nonpolar solvents in which free ions are relatively unstable so that the rate constant ( I ) Sneen, R. A. Arc. Chem. Res. 1973,6, 46-53. (2) McLennan, D. J. Arc. Chem. Res. 1976, 9, 281-287. (3) Richard, J. P.; Jencks, W . P. J. Am. Chem.Soc. 1984,106, 1383-1396. (4) Dietze, P. E.; Jencks, W . P. J. Am. Chem.Soc. 1986,108.4549-4555. ( 5 ) Amya, T. L.; Jencks, W. P. J. Am. Chem. Soc. 1989,111,7900-7909. (6) Amya, T. L.; Richard, J. P. J. Am. Chem. Soc. 1990. 112,9507-9512.
Scheme I
R-OH R-NU
tI Nu-. R - X
Nu-* R+* X--
R-OH k2
NU-R X-
k4 for their formation from ion pairs is relatively small. They are much more unlikely to be met in water or largely aqueous solvents in which the free ions are more stable and k4 is very large.5-s There are several examples of bimolecular aliphatic nucleophilic substitution reactions in organic solvents that proceed through ion-molecule or ion pair intermediates:v1° but it is not clear whether stepwise pathways are ever followed for kinetically bimolecular nucleophilic substitution reactions in largely aqueous solutions. This paper addresses the question of whether stepwise pathways are viable for bimolecular nucleophilic substitution reactions in water or largely aqueous solutions. The substrate used in these iodide (1-I), was studies, 1-(4-methoxyphenyl)-2,2,2-trifluoroethyl chosen because it can be shown to satisfy the stringent requirements for detectable bimolecular nucleophilic substitution through ion pair and/or triple ion complex intermediates in aqueous solution. We report that 1-1 shows weak bimolecular reactions with azide and thiocyanate ions in water at a high constant ionic (7) Richard, J. P.; Jencks, W . P. J. Am. Chem. Soc. 1984,106, 1373-1383. (8) Richard, J. P. J. Org. Chem. 1992, 57, 625-629. (9) Katritzky, A. R. Chem. SOC.Reu. 1990, 19, 83-105.
(IO) Katritzky, A. R.; Sakizadeh, K.; Ou,Y.-X.; Jovanovic, B.; Musumarra, G.; Ballistreri, F. P.; Crupi, R. J. Chem. Soc., Perkin Trans. 2 1983, 1427-1434. Katritzky, A. R.;Sakizadeh, K.; Gabrielson, B.;Le Noble, W . J. J. Am. Chem. SOC.1984, 106, 1879-1880.
0002-7863/93/15 15-1739$04.00/0 0 1993 American Chemical Society
Richard and Yeary
1140 J . Am. Chem. SOC.,Vol. 115, No. 5, 1993
Table I. Effect of Sodium Azide on the Pseudo-First-Order Rate Constants for the Reactions of
1-(4-Methox~~hen~ll-2.2,2-trifluoroethvl Derivatives in Watef' koW/10-3 S-1 b 4-MeOArCH(CF3)I 4-MeOArCH(CF1)Br 1.98 21.9
[ N L " /M 0.00
0.20
2.38 2.62 2.12 2.90 3.02
0.40
21.0 19.5 20.9 20.6 19.3
0.60 0.80 1 .oo "At 25 OC and I = 1.00 (NaCIO,). *The slope of a logarithmic plot of the change in absorbance at 280 nm against time. N
6
5 4
I
3 I
0.002
I
I
I
0,006
I
0,010 M
2
[ 1-1 Figure 1. (A) Dependence of koW (s-I) on the concentration of added iodide ion for the solvolysis of 1-1 in water at 25 'C and I = 6.00 (NaC104). (B) The linear reciprocal replot of the data from A according to eq 1 of the text.
Scheme 11 ksolv
2
1-1 k1[1-1
kS
1-OH
strength of 6.00 maintained with NaC104. Evidence is presented that these reactions proceed by a stepwise preassociation mechanism" through triple ion complexes [Nu-.2-1-] (Scheme I).
Experimental Section Materials. Reagent grade inorganic salts were used without further purification. The water used for kinetic studies was distilled and then passed through a Milli-Q water purification system. I-Br and 1-1 were prepared according to published procedures.'2b Kinetic Analyses. Kinetic studies were done at 25 OC, and constant ionic strength was maintained with NaC104. Solutions of salts in mixed methanol/water solvents were prepared by diluting a measured volume of methanol with an aqueous solution of NaC104 or N a N J to the appropriate final volume. The progress of the reactions of 1-Br and 1-1 was followed by monitoring the decrease in absorbance at 280 nm. Solutions of substrates were prepared in acetonitrile, and the reactions were initiated by making a 100-fold dilution into the reaction mixtures. The final concentration of 1-1 was - 5 X lod M. There is a decrease in the solubility of 1-Br in solutions of increasing [NaN3]. The final concentration of 1-Br was 4 X M for reactions at [NaN,] = 0-1.00 M, and this was reduced to 1 X M for reactions at [NaN,] > 1.00 M. The reactions at the lower concentrations of 1-Br were monitored in cuvettes with a 6-cm path length instead of the standard 1-cm cells. Observed first-order rate constants for these reactions were determined as the slope of a semilogarithmic plot of reaction progress against time. The plots were linear for 2 3 half-lives of the reaction. The rate constants were reproducible to * 5 % . The NFIT nonlinear curve fitting program from Island products was used to fit kinetic data to the rate equation derived for a preassociation reaction mechanism.
Results Figure 1A shows the effect of increasing concentrations of iodide ion on the observed first-order rate constants,kow, for the reaction ( 1 1 ) Jencks, W. P. Acc. Chem. Res. 1980, 13, 161-169. Jencks, W. P. Chem. SOC.Rev. 1981, 345-375. (12) (a) Richard, J. P. J. Am. Chem. SOC.1986, 108, 6819-6820. (b) Richard, J. P. J. Am. Chem. SOC.1989, 1 1 1 , 1455-1465.
0
0
2
I
3
4
[salt]
Figure 2. Dependence of koW
on the concentration of added nucleophilic salts for the reaction of 1-1 in water at 25 O C and I = 6.00 (NaC104). (s-I)
of 1-1 in water at 25 OC and I = 6.00 (NaC104). Figure 1B shows the fit to eq 1, derived for Scheme 11, of the data from Figure ksolv/kobsd = 1 + (kI/ks)[I-I
(1)
IA: ksOlv in eq 1 is k o w at [NaI] = 0 M. The data define a line of slope k l f k , = 210 M-I, where kl and k, are the rate constants for the capture of 2 by iodide ion and solvent, respectively. A rate constant ratio of k,,fk, = 220 M-' for partitioning of 2 between reaction with azide ion and solvent in water ( I = 6.00, NaC104) was determined in an earlier study.* This can be combined with the value of k l / k , obtained from Figure 1B to give klfk,, = 1.2 for partitioning of 2 between reaction with iodide and azide ions. MeO X -
Me0m H
1-x 2 The observed first-order rate constants kobsd for the reaction of 1-1 and 1-Br in water at 25 OC and I = 1.00 (NaC104) and at increasing concentrations of sodium azide are given in Table I. The observed first-order rate constants kobsdfor the reaction of 1-1 in water at 25 "C and I = 6.00 (NaC104) and at increasing concentrations of several nucleophilic salts or for the reaction of 1-1 in the presence of increasing concentrations of NaC104 in water that contains no other salt are given in Table 11. Figure 2 is a plot of some of the data from Table 11. Figure 3 shows the effect of increasing concentrations of added sodium azide on kobsdfksolv for the reaction of 1-Br in water at 25 O C and I = 6.00 (NaC104), for which kSol,= 0.049 s-'.~ These data were fit to eq 2 to give a value of b = -0,104 for the specific salt effect of replacing C104- with N3-. (2) kobsd/ksolv = 1 + b[N,-I The observed first-order rate constants kobsd for the reaction of 1-1 in mixed methanolfwater solvents at 25 OC and constant
J. Am. Chem. Soc.. Vol. 115, No. 5, 1993
Bimolecular Nucleophilic Substitution Reactions
1741
Table 11. Effect of Added Salts on the Pseudo-First-Order Rate Constants for the Reaction of 1-(4-Methoxyphenyl)-2,2,2-trifluoroethylIodide in
[Nul (M) 0.00
0.13 0.20 0.27 0.40 0.53 0.60 0.67 0.80 0.93
NaN3
NaSCN
NaOAc
Na02CCF3
Na2S04
NaCl
NaC104c
4.02 4.28
3.91 4.12
4.01
3.93
3.88
4.08 3.99
1.08
4.40 4.79 4.77
4.75 4.98 5.21
5.12 5.03 5.12
5.28 5.72 5.59
5.20 5.28 5.28 5.37 5.31 5.26 5.58 5.51 5.38 5.39 5.49 5.59 5.55 5.51 5.51
5.64 5.95 5.81 5.71 6.15 5.93 5.91 5.65 5.48 5.67 5.64 5.73 5.89 5.92 5.62
5.56 5.21 5.39 5.13 5.28 5.23 4.97 5.21
5.70 5.34 5.59 5.59 5.53 5.59 5.40 5.27
1.35
3.64 4.01
4.09
3.82 3.76 3.84
3.47
1.56
1.83
3.23
1 .oo
4.05
3.86
3.79 3.61 3.44
2.95
1.98 2.12
1.07 1.20 1.33 1.47 1.60 1.73 1.87 2.00 2.13 2.27 2.40 2.53 2.67 2.80 2.93 3.00 3.07 3.20 3.33 3.47 3.60 3.73 3.87 4.00 5.00 6.00
3.79
3.81
3.56
3.31
3.08
3.25
2.87
3.72
2.40
2.68
3.52 3.43 3.38 3.39 2.99 2.97 2.92 2.64
2.87
3.37 2.19
2.24
1.81
2.04
1.49
1.70
3.77 3.91 4.02
"At 25 OC and I = 6.00 (NaCI04). bThe slope of a logarithmic plot of the change in absorbance a t 280 nm against time. 'Sodium perchlorate was the only salt added.
1.20
*
O'*O
1
1
t
Table 111. Effect of Sodium Azide on the Pseudo-First-Order Rate Constants and Apparent Second-Order Rate Constants for the Reactions of 1 -(4-Methoxyphenyl)-2,2,2-trifluoroethylIodide in Methanol/ Water Solvents",*
lNaNtl /M
0.00 0.20 0.40 0.60 0.80 1 .oo 1 ,o
2,o
3,O
40 M
[NaN31 Figure 3. Dependence of ka/klolvon the concentration of added sodium azide for the reaction of I-Br in water at 25 OC and I = 6.00 (NaC104), for which k,,, = 0.049 S - I . ~ The slope of the line gives 6 = -0.104.
ionic strength (NaC104) and at increasing concentrations of sodium azide are given in Table 111. Apparent second-order rate constants [(kN&p] for the reaction of sodium azide with 1-1in these solvents, determined as the slopes of linear plots of kobsd against [NaN,], are also listed in Table 111.
Discussion The following observations show that the reactions of 1-X proceed by stepwise DN + AN (SN1)I4mechanisms through the (13)Richard, J. P. J. Am. Chem. SOC.1989,111, 6735-6744.
]OWe 3.28 19.3 21.9 23.5 23.9 25.3 26.6
20'# 3.02 5.87 6.61 6.94 7.26 7.52 7.86
307& 2.75 2.48 2.69 2.93 3.08 3.27 3.36
40%h 2.39 1.05 1.19 1.30 1.38 1.45 1.52
50%' 1.97 0.50 0.56 0.60 0.63 0.65 0.69
(k&,p/104M-' s-" 6.7 1.86 0.90 0.46 0.178 "Columns of kowvalues are labeled with % MeOHd/V. bAt 25 OC and constant ionic strength maintained with NaC104. 'The slope of a logarithmic plot of the change in absorbance at 280 nm against time. dPercent methanol in water. ' 1 = 5.00. ' 1 = 4.00. P I = 3.00. h I= 2.00. 'I = 1.00. 'The Grunwald-Winstein Y value for the mixed methanol/water solvent (ref 19). 'The slope of a plot of kow against [NaNjI.
common reaction intermediate 2. (1) The reactions of these substrates with azide ion and other nucleophilic anions'* or aminesI3give good yields of the nucleophile adducts by a pathway that is kinetically zero order in the concentration of the nucleophilic reagent. (14)Commission on Physical Organic Chemistry, IUPAC. Pure Appl. D.;Jencks, W.P. Ace. Chem. Res. 1989,
Chem. 1989,61.23-56.Guthrie, R. 22, 343-349.
Richard and Yeary
1742 J. Am. Chem. SOC.,Vol. 115, No. 5. 1993 (2) The yields of the nucleophile adducts from the reactions of 1-X are independent of the leaving group X- for X- = I-, Br-, mesylate ion, and tosylate ion.'2 (3) The reactions of 1-Br8,12and 1-1 (Figure 1) are subject to strong inhibition by added bromide and iodide common ions, respectively. Most of our previous studies on the stepwise nucleophilic substitution reactions of 1-X were a t the relatively low concentrations of nucleophilic anions that were required to trap the carboation reaction intermediate 2 [kT>> k, (Scheme I) for Nu= I-, Br-, and N k4 for partitioning of [2.I-], so this ion pair must be formed reversibly from 1-1 and undergo internal return to reactant.2i (2) The partitioning of the triple ion complex [Nu--2.1-]to products [k2/(k2+ k-,' + k,)] must be more favorable than the partitioning of the ion pair [2.I-] to products for the reaction in for internal the absence of Nu- [(k-d/(k-d+ k-,)].Since k-' = kI' return and k4 = k, for diffusional separation of ions, this requires k2 > kd. This condition is equivalent to that for a diffusion-limited reaction of Nu- with the free carbocation 2, which requires that the encounter complex [2-Nu-]collapse to products (with a rate constant = k2)much faster than it separates to reform free ions (with a rate constant ==k& This requirement is met by both N
