6265 cation-stabilizing solvent molecule by the anion of the special salt (Le., Clod-) from the same side. This is plausible, since (a) the energy is not very sensitive to displacement (particularly lateral) of the cation stabilizing H20 in H 2 0 protonated isopropyl alcohol reaction, and (b) the very existence of a special salt effect implies that the interaction of Clod- with the ACSI must be extremely stabilizing. Formation of this new C104-/ACSI should ultimately lead to loss of the leaving group followed by formation of product either with retained configuration (the nucleophile immediately takes the place of the leaving group) or racemization due to the formation of symmetrically solvated carbocations. The above description is summarized in Scheme I. This scheme has certain similar-
+
Scheme
I
-
s o . . . H-x+-R.
R-X
11 SO.
R-N (inverted)
HoS
. . H2XR AS1
. . cio;
ACSI/C104-
:N
HOS -L
I
ClO,
SO.. . = t - R . . ASCI
1:.
. 0SSolvated ions H
1
R-N (inverted)
R-OS (inverted)
N = a n y nucleophile (including HOS)
ities and differences with those recently proposed by Sneen,2 B ~ r d w e l l and , ~ S~h1eyer.I~ In particular, only substitution with inversion is possible from the ACSI. Sneen2 similarly suggested that the solvent-separated ion pair could collapse to product, but his scheme requires a product with retention of configuration. We have also included the direct s N 2 substitution, which may be particularly important in primary and methyl solvolyses. The structure of the ACSI bears a strong resemblance to the “solvated ion sandwich” proposed by B ~ r d w e l l . ~ Sch1eye1-l~proposes that the solvent-separated ion pair can only
give retained R-OS, but either inverted or racemized R-N. One should note that R-N could be formed with inversion using the scheme proposed in this paper if N- acts as a special salt and forms an ACSI/N- analogous to the ACSI/C104of Scheme I. This scheme has the particular advantage of putting the nucleophilic “solvent assistance” proposed by Schleyer14 into a general context. In addition it accommodates the suggestion that the low nucleophilicity of trifluoroacetic acid and the high degree of internal return in this solvent might be due to nonnucleophilic cation stabilization by the CF3 group.’
Acknowledgment. The author gratefully acknowledges the hospitality of 1’Universite Pierre et Marie Curie (Paris VI), the Centre de Mtcanique Ondulatoire AppliquCe, arid particularly that of Professor R. Daudel. Also, many fruitful conversations with Dr. E. Evleth, Dr. 0.Chalvet, and Professor F. Metras. He is also especially indebted to Drs. M . Chaillet, A. Dargelos, and D. Liotard for providing a copy of their geometrical optimization program. References and Notes (1) Professeur Associe a I‘Universite Pierre et Marie Curie (Paris VI) 19741975; permanent address: Department of Chemistry, Hunter College of the City University of New York, 695 Park Avenue, New York, N.Y., 10021. (2) R . A. Sneen. Acc. Cbem. Res., 6, 46 (1973), and references cited therein. (3) For a comprehensive review, see D. J. Raber, J. M. Harris, and P. v. R. Schieyer, “Ions and Ion Pairs in Organic Reactions”, M. Szwarc, Ed., Wiley, New York, N.Y., 1974, p 247. (4) S. Winstein and G. C. Robinson, J. Am. Chem. SOC.,EO, 169 (1958). (5) F. G. Bordwell, P. F. W h y , and T. G. Mecca, J. Am. Cbem. SOC.,97, 132 (1975). (6) P. Cremaschi, A. Gamba, and M. Simonetta, Theor. Chim. Acta, 25, 237 ( 1972). (7) A. Dedieu and A. Veillard, J. Am. Chem. Soc., 94, 6730 (1972). (8) J. A. Pople, D. L. Beveridge, and P. A. Dobosh, J. Cbem. fbys., 47, 2026 (1967). (9) J. A. Popie and M. S. Gordon, J. Am. Chem. SOC.,89, 4253 (1967). (10) J. J. Dannenberg and T. D. Berke, Theor. Cbim. Acta, 24, 99 (1972). (11) M. Chailiet, A. Dargelas, and D. Liotard, to be published. (12) J. P. Daudey. J. P. Malrieu, and 0. Rojas, h t . J. Quantum Cbem., E, 17 (1974). (13) Reference 3, p 363. (14) F. L. Schadt and P. v. R. Schieyer, J. Am. Cbem. SOC.,95, 7860 (1973); P. v. R. Schleyer and C. J. Lancelot, ibid., 91, 4297 (1969). (15) J. J. Dannenberg, Angew. Cbem., int. Edfngi., 14, 641 (1975).
Spiro Meisenheimer Complex from Catechol 2,4,6-Trinitrophenyl Ether. Rate-Limiting Proton Transfer as a Consequence of a Very Fast Intramolecular Nucleophilic Attack’ Claude F. Bernasconi* and Hsien-chang Wang Contribution from the Thimann Laboratories of the Unicersity of California, Santa Cruz, California 95064. Received August 1 I , 1975
Abstract: Temperature-jump experiments in 50% Me2SO-50% water (v/v) show that the proton transfer is rate limiting in the formation of the spiro Meisenheimer complex (9) from catechol 2,4,6-trinitrophenyl ether. This is not because of an abnormally slow proton transfer but a consequence of a very fast rate of complex formation (kl = 1.2 X lo9 s-l). This rate is the highest measured to date for nucleophilic attack on an aromatic carbon.
The formation of spiro Meisenheimer complexes involves both intramolecular nucleophilic attack and proton transfer, as depicted in reaction 1. When Y = 0, as in the prototype Bernasconi, Wang
reaction 2, proton transfer is a rapid equilibrium step preceding the rate-limiting nucleophilic attack in all cases reported to date.2-6When Y = N R , however, as in the prototype reaction
/ Meisenheimer Complex f r o m Catechol 2,4,6-Trinitrophenyl Ether
6266
0.8 -
0
0.6
0
c 0
-2
E
% 0.4
[ClCH,COOH],
0.2
,M
Figure 2. Representative plots of 1 /T vs. total chloroacetate buffer concentration: 0 pH 4.06; 0 pH 4.36.
400 500 nm Figure 1. Spectra of 7 in equilibrium with 9 at various pH values in water. M, ionic strength 0.5 M (NaCI), 25 OC. [710 = 3.94 X
300
n
6:
+
B
A
BH
3
2
3, proton transfer occurs after ring closure and is (partially) rate limiting;','
ko2
NI 4
4
5
6
+ kPoHaoH- + kpB[B] = k-pSaH+ + k-,OH + k-,B[BH]
k , = kpS k-,
(4a)
(4b) kPS, kPoH,and kPBrefer to the deprotonation of 5 by the solvent, the hydroxide ion, and the buffer base, respectively, whereas k-,S, k-,OH, and k-,B refer to the protonation of 6 by the solvated proton, the solvent, and the buffer acid, respectively. We now report data on reaction 5 in 5090 Me2SO-50% water
NO2
7
NO2 9
a
(v/v); note that k , and k - , are defined similarly as in eq 3, Le., they are given by eq 4a and 4b, respectively. System 5 is unique Journal of the American Chemical Society
/
98.20
Results General Features. When catechol 2,4,6-trinitrophenyl ether (7) is dissolved in water, one observes partial formation of the spiro Meisenheimer complex 9 even in neutral solution, indicating a high apparent equilibrium constant K,K,, where K , is the acid dissociation constant of 7 and K I = k l / k - l . This is borne out by the spectra taken as a function of pH, shown in Figure 1. A plot, a t 470 nm, according to the equation
(on, - OD)/OD = aH+/KaKI
(2)
1
in that it is thefirst case of the general reaction I with Y = 0, where proton transfer is rate limiting.
(6)
where OD is the optical density a t a given p H and OD, is the optical density in strongly basic solution where complex formation is quantitative, is linear, and affords K,KI = (1.39 f 0.02) X M at 25 OC and ionic strength of 0.5 M. By employing the same procedure in 50% Me2SO-50% water (v/v) we obtain K,Kl = (5.24 f 0.10) X M, at the same temperature and ionic strength. Our initial plans called for a kinetic study in aqueous solution, but the rates were too high even for the temperature-jump relaxation method. When a reaction system is too rapid for the temperature-jump method, it is usually because of a very fast unimolecular step, the rate of which cannot be manipulated by a judicious choice of concentrations. In the case a t band, it is the k-l step. However, by exploiting the well-known fact that the addition of Me2SO decreases the dissociation rate ( k - I ) of Meisenheimer complexes,* we were able to study the kinetics of system 5 in 50% Me2SO-50% water (v/v). Temperature-Jump Experiments. Solutions prepared by dissolving 7 in acetate, chloroacetate, or formate buffers were allowed to reach thermal equilibrium at 22.7 OC and subjected to temperature jumps of 2.3 OC,givhg an end temperature of 25 OC. Chemical relaxation was monitored at 436 or 470 nm. A single relaxation time was observed and determined as a function of total buffer concentration at various p H values. The results are summarized in Table I. Figure 2 shows two representative plots of 1 / vs. ~ total buffer concentration. There are two noteworthy features about the kinetic data. (1) There is a very strong buffer dependence; e.g., a t p H 5.74, 1 / T increases 380-fold when the acetate buffer concentration is increased from 0.001 to 1.0 M. This is typical for protontransfer reactions a t p H values not too far from neutrality.' (2) All plots of 1 / vs. ~ total buffer concentration are curved downwards, as shown in Figure 2. Such curvature usually indicates a mechanism where there is a change in the rate-limiting step. In our case the change is from rate-limiting proton
/ September 29, 1976
6267 Table I.
1 / as ~ Function of Buffer Concentration and pH in 50% MezSO-50% Water (v/v) at 25 'C, Ionic Strength 0.5 M (KCI) 10 X [Blo,"
10-3/~,
M
PH
10-3/~,
10 X [Blot"
M
PH
S-1
S-'
5.43 5.43 5.43 5.43 5.43 5.43 5.43 5.43 5.43 5.43 5.74 5.74 5.74 5.74
0.036 0.072 0.120 0.168 0.240 0.360 0.840 1.20 2.40 4.80 0.010 0.020 0.040 0.10
0.174 0.321 0.530 0.729 1.02 1.60 2.99 4.73 7.45 11.8 0.069 0.139 0.221 0.532
A. Acetate Bufferb 5.74 5.74 5.74 5.74 5.14 6.04 6.04 6.04 6.04 6.04 6.04 6.04 6.04 6.04
0.20 0.40 2.00 6.00 10.0 0.036 0.072 0.120 0.240 0.360 0.840 1.20 2.40 4.80
1.07 2.06 7.87 18.5 26.2 0.224 0.482 0.715 1.55 2.17 4.95 7.50 11.6 24.2
4.13 4.13 4.13 4.13 4.13 4.13 4.13 4.13 4.13 4.13 4.43 4.43 4.43 4.43 4.43
0.036 0.072 0.120 0.168 0.240 0.360 0.840 1.20 2.40 4.80 0.020 0.040 0.050 0.10 0.20
0.175 0.290 0.432 0.566 0.796 1.07 2.35 3.08 4.84 7.33 0.083 0.127 0.141 0.272 0.514
B. Formate Bufferb 4.43 4.43 4.43 4.43 4.43 4.13 4.73 4.73 4.73 4.73 4.73 4.73 4.73 4.73 4.73
0.40 0.50 1.oo 3.00 5.00 0.036 0.072 0.120 0.168 0.240 0.360 0.840 1.20 2.40 4.80
1 .oo 1.17 2.23 5.24 6.37 0.092 0.154 0.236 0.327 0.484 0.660 1.38 1.99 3.29 4.93
4.06 4.06 4.06 4.06 4.06 4.06 4.06 4.06 4.06 4.06
0.036 0.072 0.120 0.168 0.240 0.360 0.840 1.20 2.40 4.80
C. Chloroacetate Bufferb 0.108 4.36 0.167 4.36 0.231 4.36 0.293 4.36 0.359 4.36 0.502 4.36 1.oo 4.36 1.38 4.36 2.36 4.36 3.37 4.36
0.030 0.060 0.100 0.140 0.200 0.300 0.700 1.oo 2.00 4.00
0.055 0.08 1 0.115 0.144 0.208 0.276 0.537 0.7 12 1.26 1.99
[BIo = [B]
+ [BH].
The pK,'s of the buffers are in Table V.
transfer ( k , , k - , ) to rate-limiting C-0 bond formation/ breaking ( k 1, k - 1). Data at High Buffer Concentration. The expression for the reciprocal relaxation time ( 1/ 7 ) , derived under the assumption that 8 is a low concentration ("steady-state") intermediate, is given by -1= 7
k,kl + k-,k-l k - , kl k - , kl
+
+
(7)
As shown in the Appendix, at relatively high buffer concentrations, eq 7 can be transformed into
where KaBis the acid dissociation constant of the buffer acid, [ B l 0 is the total buffer concentration, and 7 h i is the plateau value of 7 which would be reached at very high buffer concentrations, Le., when k - , = k - p B [ B ]>> k l ; 7 h i is given by (9) Bernasconi, Wang
All of our plots of 7 vs. [B],-I were linear as required by eq 8; Figure 3 shows two representative examples. From the intercepts one obtains 7hi, from the ratios of slope/intercept one obtains k according to the equation
+
slope kl KaB aH+ -=(10) intercept k-,B aH+ Table I1 summarizes the results of this analysis. We can now estimate kl as follows. It is known that the rate constants for proton transfer between oxygen acids and bases reach the diffusion-controlled limit of N 1 O l o M-' s-* in the thermodynamically-favored direction when ApK = pK(Acceptor) - pK(Donor) becomes large.9a.10As shown below, the pK, of 7 is 10.3, while that of our strongest buffer acid, viz. chloroacetic acid, is 3.76 in the present medium. Hence for the reaction
8
+ CICHzCOOH %7 + C 1 C H 2 C 0 0 -
(1 1)
we have ApK = 10.3 - 3.76 = 6.54, which is large enough to assure that the reaction is diffusion controlled. Thus, from
/ Meisenheimer Complex from Catechol 2,4,6-Trinitrophenyl Ether
6268 Table 11. Analysis of Data According to Equations 8 and l o a Buffer Acetate Acetate Acetate Formate Formate Formate C hloroacetate C hloroacetate a
lo5 x
PH 6.04 5.74 5.43 4.73 4.43 4.13 4.36 4.06
Thi
= intercept, s
lo5 X slope, M s
kllk-pB, M
i.62 i b.03 1.84 f 0.04 2.22 f 0.05 5.12 f 0.08 3.74 f 0.04 2.71 f 0.06 11.6 f 0.2 6.60 f 0.14
0.39 0.40 0.42 0.21 0.23 0.21 0.12 0.13
1.4 f 0.6 2.3 f 0.2 3.5 f 0.5 8.0 f 1.6 8.2 f 1.6
2:,:,:i.4 17\ f
The pKaBvalues of the buffers are in Table V.
Table 111. Analysis of Data According to Equations 12 and 14 Intercept, Buffer
PH
Acetate Acetate Acetate Formate Formate Formate Chloroacetate C hloroacetate
6.04 5.74 5.43 4.73 4.43 4.13 4.36 4.06
X slope,
M-I
S-I
a
1 9 % 11 24.0 f 4.2 26.5 f 3.2 28.1 f 5.7 58.2 f 6.4 31.6 f 1.9 62.2 f 5.1
10-9
x L,B,
M-I
s-I
6.26 f 0.20 5.23 f 0.07 4.1 8 f 0.03 1.79 f 0.06 2.43 f 0.02 3.02 f 0.04 0.90 f 0.03 1.40 f 0.05
s-I
2.10 3.10 2.94 4.77 4.86 4.83 4.58 4.52
Could not be determined due to too high experimental error.
Initial slopes and intercepts,of plots of 1/ T vs. [B],,(eq 12) are summarized in Table 111. They can be exploited as follows. At p H I5 the kpoH,k-,OH pathway becomes negligible compared to the kpS,k - 2 pathway. Hence the intercept of the plot according to eq 12 is
+
intercept = k p S ( k - l / k l ) k - p S a H + = k p S ( k p S / K , K l ) a H + (13)
0
0
10
20
[CI CH,COOH]:,
40
30
M-'
+
A plot according to eq 13 (not shown) is linear. The intercept of this new plot affords k p S = 5 f 2 s-I, i.e., a value with a rather high uncertainty; however the slope is more accurate and, in conjunction with the known K,Kl, affords k p S = 3.9 f 0.5 s-I. From this we also obtain k-pS = k : / K , = 8 X 1O'O M-I s-1 Now we turn to the slopes of the plots according to eq 12. Taking into account that kpB = k - p B K , / K , B the slopes can be written as
Figure 3. Representative plots of T vs. [B],-' according to eq 8 for chloroacetate buffer: 0 pH 4.06; 0 pH 4.36.
k l / k - = 0.12 (Table 11) and assuming k w p B(chloroacetate) N l o l l M-l s-l, one calculates kl N 1.2 X lo9 s-I. From a plot (not shown) of l / ~ h vs. i U H + - I according to eq 9 we also obtain intercept = k-1 = (1.0 f 0.3) X lo4 s-l and slope = K,kl = ( 5 . 5 f 1.0) X M s-l W e note that the ratioK,kI/k-l = 5 . 5 X 10-2/104=5.5X 10-6isinexcellent agreement with K,Kl = 5.24 X determined spectrophotometrically. Finally, combining K,k 1 with k 1 calculated earlier affords K , N 4.6 X lo-" M or p K , N 10.34 for 7. Data at Low Buffer Concentration. At low buffer concentration we have kl >> k - p , so that eq 7 simplifies to
+ (k-l/kl)k-p k-1 = k p S+ kpoHaoH- + -(k-psaH+ + k-,OH) ki
1 / =~ k p
Journal of the American Chemical Society
with k-pB being the only remaining unknown. The k - p Bvalues calculated on the basis of eq 14 are also summarized in Table 111.
Discussion All rate and equilibrium constants of system 5 are summarized in Tables IV and V. Reliability of Analysis. In view of several potential sources of error in our data analysis, it is important to get some idea of the reliability of the calculated parameters. One such source is that the intercepts of the inversion plots according to eq 8 (Figure 3) are relatively small and thus have a relatively high uncertainty. A second is that in changing from a medium of low buffer concentration to one of high concentration a differential salt effect may somewhat distort our data even though the ionic strength was kept constant. The third is the assumption of k w p B= 1Olo M-' s-l when B = chloroacetate.
/ 98:20 / September 29, 1976
6269 Table IV.
Equilibrium and Rate Constants for Reaction 5 in 50% Me2SO-50% Water (v/v) at 25 "C Constant
~
Comments
~~~~~
~~
KaK1 = (5.24 f 0.10) X M K,K1 = ( 5 . 5 f 2.0) X M K, N 4.6 X lo-" M (pK, N 10.34) Kakl = (5.5 f 1.0) X M s-' kl 1.2 x 109s-1 k-1 = (1.0 f 0.3) X lo4 s-I K, 1.2 x 105 kpS = 3.9 f 0.5 s-l k8 X 1O1OM-I s-I kp8H 1010 M-I S-1 OH 1.7 x 105 s - l
Table V. Rate Constants for Reaction 7 MezSO-50% Water (v/v) at 25 "C
Acetate Formate Chloroacetate
5.74 4.43 3.76
4.60 5.91 6.58
+B
6.gd 0.59d 0.12d
Spectrophotometric (eq 6) Kinetic (eq 9) From Kak I and k I From eq 9 From kl/k-pB (B = chloroacetate, k-pB N 1Olo M-I From eq 9 From K I = kl/k-l From eq 13 From k-pS = kpS/K, Estimated (ref 9a) From k-,OH = kpoHK,/K, ( K , = aH+aOH- 8 X ref 22)
~i 8
+ BH in 50%
2.71d(3.0)e 4.82d(5.45)e 4.55d( 10.0)f
Determined potentiometrically. ApK = pK, - pKaB. kpB= Kak-pB/KaB. k-pB from eq 14, average of two or three values from TableIII. e k-pBfrom k l / k - p B a n d k l = 1.2 X lO9s-'.fEstimated, ref 9a and 10.
It is rewarding that our data offer some ways to check for internal consistency and thus to exclude the possibility of gross errors. We first note the close agreement between K,Kl determined kinetically at high buffer concentration, with K,KI determined spectrophotometrically at low buffer concentration. Second, there is satisfactory to good agreement between k-,B calculated from eq 14 (data at low buffer concentration) and k-,B calculated from kl/k-,B ratios (data at high buffer concentration). Thus we estimate that the parameters summarized in Tables IV and V are reliable within a factor of two or better.' Comparison with Literature Data. Our pK, of 7 is about one unit more acidic than that of phenol in the same solvent,I2 a result which is in agreement with the expected acidifying effect of the picryl group. On the other hand, Drozd et al.I3 report a spectrophotometrically determined pK, = 5.83 (K, = 1.48 X lod6) for 7 in 50% ethanol-50% water. This value is totally unreasonable. It appears that what these authors assume to be K, is in fact K,KI; with this interpretation their value of 1.48 X comes rather close to our K,Kl = 5.24 X That KaKI is somewhat higher in 50% Me2SO-50% water compared to 50% ethanol-50% water is expected. Rate-Limiting Proton Transfer. It is instructive to analyze the reasons why proton transfer is rate limiting in reaction 5 , but not in any other case of the general reaction 1 with Y = 0 reported to date. Let us compare our data with those of reaction 2. For this latter, K,kl = 1.6 X M s-I 5,14 and k-l = 0.095 s-I in water at 25 O C . Although K, is not known, a reasonable estimate is K, N 3 X M;I5 this then leads to an estimated kl = 5 X lo6 s-I. If one defines k, and k-, for reaction 2 the same way as for reaction 5 , the requirement for rate-limiting proton transfer is that kl > k-,. In reaction 2 there are no experimental conditions where such a relation between k ] and k-, is possible. This is mainly because of the low K, N 3 X which implies that the protonation of 2 even by the weakest acid in the system, viz. the solvent, is very fast, with k-,OH N lo9 Bernasconi, Wang
S-I)
s - ' . ~ ,Thus k-, can never be lower than = l o 9 s-'. Since furthermore kl = 5 X lo6 s-l is appreciably smaller than kl in system 5, we have kl
