Han Joong Koh

Reactivity–selectivity relationship and kinetic solvent isotope effects in nucleophilic substitution reactions

Selectivity plots, log(Kx1/Kx2)vs. σy, have been obtained for various nucleophilic substitution reactions: (i) with anilines (N) in methanol (S), kN/kS, using literature data for YC6H4CH2Cl, YC6H4COCl, YC6H4SO2Cl, YC6H4COCH2Br, YC6H4CH(CH3)Cl and YC6H4CH[C(CH3)3]OSO2C6H4NO2; and (ii) with kinetic solvent isotope effects (KSIE) in water and methanol, kSOH/kSOD, determined in this work for the same compounds (except for the latter two). The two selectivity plots are shown to be equivalent in applying mechanistic criteria based on four reactivity–selectivity regions identified by the, slopes of the selectivity plots. Δρy. Straightforward applications were possible in most cases except for the aminolysis of phenacyl bromides and 1-phenylethyl chlorides. For these two, detailed analyses of kinetic results were required, in addition to the reactivity-selectivity considerations, before deciding the reaction mechanism.

Kinetics and mechanism of aminolysis of phenyl acetates and phenyl trimethylacetates in dimethyl sulfoxide

Kinetic studies have been carried out on the reactions of phenyl acetates and phenyl trimethylacetates in dimethyl sulfoxide. The rate ratios between the two acyl compounds, and the positive sign and large magnitude of the cross-interaction constants, ρXZ, between substituents X in the nucleophile and Z in the leaving group are considered to favour the rate-limiting expulsion of aryl oxide from the tetrahedral intermediate T±. The aprotic solvent used makes the proposed mechanism with a cyclic transition state more attractive especially in view of the greater charge dispersion and assistance to leaving group departure provided in such a structure.

Nucleophilic substitution reaction of cumyl arenesulfonates with anilines

The nucleophilic substitution reaction of cumyl arenesulfonate with aniline has been investigated. The reaction in acetonitrile proceeds by the SN2 mechanism with probable frontside nucleophilic attack. The large magnitude of ρxz(=–0.75) obtained results in an observable sign reversal of ρz at x= 0.83, with a negative ρz value for σx > x. This rather unusual phenomenon can be rationalized by a strong interaction between the nucleophile and leaving group due to their close proximity in the transition state, which in turn is a result of the frontside nucleophilic attack. The reactions in methanol indicate that the SN1 channel competes with the SN2 pathway and ion-pair return is observed when the aniline nucleophile concentration is low.

Substituent effects on transition-state structures for dissociative and associative SN2 reactions

α-Deuterium secondary kinetic isotope effects (KIEs) have been investigated for the reactions of anilines with benzyl, methyl and ethyl benzenesulfonates involving deuteriated aniline nucleophiles and substrates. The secondary KIEs observed are normal, kH/kD > 1.0, only for the deuteriated benzyl system and are of an inverse type, kH/kD < 1.0, for the deuteriated methyl and ethyl systems as well as for all the deuteriated nucleophiles. These results suggest that the relief of steric strain by bond breaking of the leaving group prevails over the steric congestion incurred by bond formation of the nucleophile in the reactions of the benzyl compound (dissociative SN2 mechanism), in contrast to the reverse trend, i.e., the strain incurred by bond formation of the nucleophile is greater than the relief of steric congestion by bond breaking of the leaving group in the reactions of alkyl compounds (associative SN2 mechanism). The effects of substituents in the nucleophile (X) and leaving group (Z) on the secondary KIEs are in complete agreement with the transition-state variation predicted by the sign and magnitude of the cross-interaction constant, ρxz.

Bimolecular nucleophilic substitution (SN2) reactions of neopentyl arenesulfonates with anilines and benzylamines in methanol

Bimolecular nucleophilic substitution (SN2) reactions of neopentyl arenesulfonates with anilines and benzylamines in methanol at 55.0 °C are reported. The tightness of the transition state (TS) is similar to that for other typical SN2 processes at a primary alkyl carbon centre based on the magnitude of the cross-interaction constant ρxz(0.30) between the substituents in the nucleophile (X) and leaving group (Z). The TS variation is in accord with that predicted by the potential energy surface diagram, which in turn is consistent with the positive sign of ρxz; a later TS is obtained with a weaker nucleophile and nucleofuge. Tafts polar substituent constant, σ*, for the trimethylsilyl group is estimated to be –0.48 by using a factor of 1.875 for the fall-off of σ* from the tert-butyl to the neopentyl group and extrapolating from the experimental Taft plot.

Nucleophilic substitution reactions of allyl arenesulphonates with anilines and N,N-dimethylanilines

Kinetic studies of the reactions of allyl arenesulphonates, I, with anilines and N,N-dimethylanilines in acetonitrile at 45.0 °C are reported. The sign and magnitude of the cross-interaction constants ρxz(andβxz) between substituents in the nucleophile (X) and leaving group (Z) indicate that the transition state (TS) for I is relatively tight and is similar to that for the corresponding reactions of ethyl systems, rather than for benzyl systems. Variations of the simple Hammett (and Bronsted) coefficients ρx(βx) and ρx(βx) with substituents Z and X, respectively, are consistent with the trend expected from a positive ρxzi.e., that predicted by the potential energy surface diagram. The kinetic isotope effects involving N-deuteriated anilines support the mechanism proposed based onρxz(βxz) for the reactions of I, i.e., an associative SN2 process with an earlier TS for a stronger nucleophile and/or a better leaving group.