J . Org. Chem. 1987,52, 3042-3050
3042
Nucleophilic Addition to Olefins. 21.’ Substituent and Solvent Effects on the Reaction of Benzylidene Meldrum’s Acids with Piperidine and Morpholine Claude F. Bernasconi* and Markandeswar Panda Thimann Laboratories of the University of California, Santa Cruz, California 95064 Received March 23, 1987 Rate (k,)and equilibrium constants (Kl) for piperidine and morpholine addition to benzylidene Meldrum’s acid (BMA) and substituted BMA’s (Z = 4-NO2,3-C1,4-CN, 4-OMe, 4-NMe2,4-NJ3t4 were determined in water and in 50%, 70%, and 90% aqueous Me2S0. The equilibrium for addition is highly favorable, with K , values (piperidine) as high as 7.8 x 10’ M-l, which is the highest value measured in a series of olefins of the type PhCH=CXY. The rates are also quite high (k,up to 2.1 X lo6 M-l s-l), indicating a relatively high intrinsic rate constant (ko= kl for Kl = 1)which ranks BMA second among seven PhCH=CXY-type olefins with respect to kinetic reactivity. This ranking is “reasonable” based on a correlation between ko for nucleophilic addition to PhCH=CXY and ko for deprotonation of carbon acids of the type CH2XY. p,” (d log kl/d log K,, variation of amine) is very small, particularly in aqueous solution. This result appears to be part of a trend toward lower &,” values with increasing thermodynamic stability of the adducts of PhCH=CXY. an,,,”(d log k,/d log K1, variation of Z) is significantly larger than p,,“, implying a substantial imbalance in these reactions. However, after correction of a” , for the effect of the developing positive charge on the amine nitrogen the remaining “true” imbalance is quite small. The small imbalance as well as the high ko value are consistent with the Meldrum’s acid anion deriving most of its exceptional stability from its bislactone structure rather than from resonance. Strong a-donor substituents (4-NMe2,4-NEtJ have a strong stabilizing effect on the olefin, leading to a large reduction in Kl. Contrary to expectations based on the principle of nonperfect synchronization(PNS), this rwnance effect does not lead to a strong reduction of the intrinsic rate constant, probably because the polarization in the olefin (Me2N+=C6H4=CHC(COO),-c(CH,)z) helps in partially offsetting the PNS effect caused by delayed development of resonance on the carbanionic side of the adduct.
In an attempt to improve our understanding of the factors that determine reactivity in carbanion forming reactions we have studied a number of nucleophilic addition reactions of the type shown in eq l.1-5 Our main
emphasis has been on determining the effect of the carbanion-stabilizing groups X and Y on the intrinsic rate constants (ko = k , = k,when K1 = 1)which are estimated by linear interpolation or extrapolation of Bransted-type plots ( k , and K1 as functions of nucleophile basicity). For amine nucleophiles the order of decreasing ko as function of XY was found to be (CN), > (CN, C6H,-4-N02)> (CN, C6H3-2,4-(N02)z)> (H, NOz) > (C6H5, NO2). This order, which is the same as that found in proton transfers of the type of eq 2,2,6suggests that the intrinsic rate constant decreases as the resonance stabilization and solvation of the carbanion increases. CH2XY
+
X1
BY t .BH”” k-
1
+
X
+. Y
HCT-
(2)
These trends can be understood as a manifestation of the principle of nonperfect synchronization (PNS)6if one assumes that the development of carbanion resonance and (1)Part 20 Bemasconi, C. F.; Renfrow, R. A. J. Org. Chem.,preceding paper in this issue. (2) For recent reviews, see: (a) Bernasconi, C. F. Pure Appl. Chern. 1982,54, 2335. (b) Bernasconi, C. F. In Nucleophilicity; Harris, J. M., McManus, P., Eds.; Advances in Chemistry 215; American Chemical Society: Washington, DC, 1987; p 115. (3) Bernasconi, C. F.; Renfrow, R. A.; Tia, P. R. J . Am. Chern. SOC. 1986, 108, 4541. (4) Bernasconi, C. F.; Stronach, M. W. J . Org. Chern. 1986,51, 2144. (5) Bernasconi, C. F.; Kanavarioti, A. J . Am. Chem. SOC.1986, 108, 7744. (6) For a recent review, see: Bernasconi, C. F. Tetrahedron 1985, 41, 3219.
0022-3263/87/1952-3042$01.50/0
solvation lags behind bond formation at the transition state. The PNS states that if the development of a product stabilizing factor (resonance and solvation in the case at hand) lags behind bond formation at the transition state, the intrinsic rate constant is depressed. The same holds true for early loss of a reactant stabilizing factor.’ A lag in the development of resonance and solvation at the carbanion is in fact strongly indicated by imbalances in the structure-reactivity coefficients, i.e., by Brransted in the proton transfers, (YCH values8 being larger than and cynu: being larger than @”, in the nucleophilic addition reactions. One olefin of particular interest in the present context is benzylidene Meldrum’s acid (BMA). Even though rate and equilibrium data for amine addition to BMA are available,’O it is difficult to evaluate ko and compare it with the intrinsic rate constants of other olefins. The difficulty arises from the extremely high stability of the amine adducts of BMA (e.g., piperidine and morpholine)loawhich necessitates a long extrapolation to obtain ko and the unusually low” , ,@, value (compared to all other systems studied so far) which gives this extrapolation a questionable meaning. The problem is compounded by the fact that the available data were obtained in water at 25 “C while those for all the other olefins were determined in 50% MezSO-50% water at 20 0C.1-5 In this paper we report new rate and equilibrium data for piperidine and morpholine addition t o BMA in water and in 50%, 70%, and 90% aqueous Me2S0. A nonlinear (7) Product and reactant destabilizing factors have the opposite effect on k, and so have product-stabilizing factors that develop early or reactant-stabilizing factors that are lost late. (8) C ~ C H= d log kJd log KSCH(CH = carbon acid), PB d log kl/d pKaBH,see eq 2. (9) anucn = d log kl/d log K 1(change in Z),fin,,” = d log kl/d log K1 (change in nucleophile), see eq 1. (10) (a) Bernasconi, C. F.; Forarini, S. J. Am. Chern. SOC.1980, 102, 5329. (b) Bernasconi, C. F.; Murray, C. J. J . Am. Chern.SOC.1986,108, 5251. 0 1987 American Chemical Society
J. Org. Chem., Vol. 52, No. 14, 1987 3043
Nucleophilic Addition to Olefins extrapolation method for estimating ko is suggested that leads to a "reasonable" ko value. We also report extensive data regarding substituent effects on kl, k+ and K1from and hence the imbalance a,,," ",@,-, can be which anUcn estimated. One point of particular interest is that our results allow us to probe whether remote substituents (Z in eq 1)which are capable of resonance interactions may have a special effect on the intrinsic rate constant. For example, a p-NO2or p-CN group in phenylnitromethane" and in the N-methyl cation of benzyl 4-pyridyl ketone12 reduces k, for proton transfer and so does the introduction of an 0-NO2 group into the phenyl ring of (4-nitropheny1)a~etonitrile.l~Similarly, in S N 2 reactions of ArSions with n-BuC1 in Me2S0 the p-NO2 substituent leads to a decrease in k0,14and ko for nucleophilic addition to a-cyano-4-nitrostilbene is lowered by introducing a nitro group in the 2-p0siti0n.l~ All these effects can again be understood in the context of the PNS;2b*6 i.e., ko is reduced because the resonance contribution of the remote substituent has made less progress than bond formation at the transition state. It is not unreasonable to expect that in reactions such as eq 1 remote substituents in the phenyl group of the substrate may also affect the intrinsic rate constant by a PNS effect. Likely candidates would be strong ?r donors that can stabilize the olefins by through-conjugation as shown in lb.
la
lb
Such effects on ko by remote 7r-donor substituents should manifest themselves by deviations from Br~nsted-typeplots of log kl vs. log K1 that are based on a series of polar substituents devoid of resonance effects. On the basis of limited data for the reaction of substituted benzylidene Meldrum's acids with amines,loa OH-,16 and water16 it appears that the p-OMe substituent may in fact induce small negative deviations from the Bransted plots. On the other hand, positive deviations have recently been observed for the p-OMe and p-NMe2 substituents in the reaction of piperidine with substituted ,f3-nitrostyrenes.a
Results General Features. Kinetic and equilibrium data for the reaction of piperidine and morpholine with benzylidene Meldnun's acid (BMA) and the 4NO2,4-CN, 3-C1,4OMe, 4-NMe2,and 4-NEt, derivatives were determined in water, 50% Me2SO-50% water (v/v), 70% Me2SO-30% water (v/v), and 90% Me2SO-10% water (v/v). Most data were collected at 20 "C because the availability of a good pH calibration scale in Me2SO-water mixtures at this temperature." However the substituent dependence in water was studied at 25 "C since data on several substituents were already available from a previous study.loa Our approach was very similar to that reported earlier'O and is only briefly described here. Pseudo-first-order (11) Keeffe, J. R.: Morev, J.; Palmer, C. A.: Lee, J. C. J. Am. Chem. SOC.1979,101, 1295.
(12)Bunting, J. W.;Stefanidis, D. Proc. 8th IUPAC Conf.Phys. Org. Chem., in press. 113) Bernasconi. C. F.:Hibdon. S. A. J. A m . Chem. Soc. 1983,105. 4343. (14)Bordwell, F. G.;Hughes, D. L. J. Org. Chem. 1982,47, 3224. (15)Bernssconi, C. 9.;Murray, C. J.; Fox,J. P.; Carr6, D. J. J.Am. Chem. SOC.1983,105,4349. (16)Bernasconi, C. F.;Leonarduzzi, G. D. J. Am. Chem. SOC.1982, 104,5133. (17)Hall6, J. C.;Gaboriaud, R.; Schaal, R. Bull. SOC.Chem. Fr. 1970, 2047.
conditions were used throughout with the amine as the excess component. In water and 50% Me2S0 the ionic strength was kept at 0.5 M with KC1; due to reduced solubility the ionic strength was 0.25 M in 70% Me2S0, 0.06 M in 90% Me2S0. The reaction can be described by eq 3, with the reciprocal relaxation time for equilibrium approach being given by eq 4.
2-BMA
R2NH Tf
R2N T-
7-l
= kl[R2NH]
+ kl K,' UH+ + UH+
(4)
kl was obtained from experiments in which the substrate was reacted with a buffered amine solution in the stopped-flow apparatus. Because of the high reactivity of most of the substrates (klvalues up to 2.1 X lo6 M-ls-l) these experiments were typically conducted at a pH value substantially below the pK, of the amine, in order to keep the free amine concentration low. This necessitated the use of an external buffer such as Dabco, cacodylic acid, or N-methylmorpholine. In these experiments 7-l was usually completely dominated by the kl[R2NH] term. The data are collected in Tables S1, S2, S6-S8, and S1218 (178 7-l values). In order to determine k-, and, in some cases, Ka*, a solution of TA-was first generated under conditions similar to those used in measuring K1. This solution was then placed into the stopped-flow apparatus and mixed with an acidic buffer or, more often, with an HCl solution. Under these conditions 7-l was dominated by the k-laH+/(K,* + uH+) term, which typically simplifies to k-, because Kai
