The reaction of guanosine with 3,4-epoxy-1-butene in acetic acid gives two main products of N-7 alkylation. After acidic hydrolysis the two aglycones have been isolated by h.p.l.c. and shown to be the regioisomeric 7-(2-hydroxy-3-buten-1-yl) guanine (I) and 7-(1-hydroxy-3-buten-2-yl) guanine (II), arising through nucleophilic attack by N-7 of the purine at the two oxirane carbons of 3,4-epoxy-1-butene. Spectral characteristics of both compounds are presented, including u.v., 1H-n.m.r. and mass spectra. Deoxyguanosine reacts with 3,4-epoxy-1-butene in 50% methanol-water at 37 degrees C to give the N-7 alkylated deoxynucleosides corresponding to I and II in a 59:41 ratio. The reaction rate depends on the nucleoside concentration, with second order rate constants at 37 degrees C of 1.6 X 10(-2) and 1.1 X 10(-2) h-1 M-1 for the formation of the two deoxynucleoside adduct corresponding to I and II, respectively. The same two compounds I and II in a similar (54:46) ratio have been identified after acidic or thermal hydrolysis of DNA which had been reacted with 3,4-epoxy-1-butene under similar conditions. The half life for the spontaneous depurination of I and II in the adducted DNA under physiological conditions (37 degrees C, pH 7.2) is 50 h.

Rates and products of electrophilic bromination of ring-substituted cis- and trans-stilbenes have been investigated in acetic acid, trifluoroethanol, ethanol, methanol, and water−methanol mixtures. The mY Br relationships (linear for nucleophilic solvents only, with m = 0.8), the deviations of the two nonnucleophilic solvents from the mY Br plots (ΔAcOH and ΔTFE positive, negative, or negligible), the kinetic solvent isotope effects (k MeOH/k MeOD = 1.1−1.6), the chemoselectivity (predominant dibromide, DB, or solvent-incorporated adducts, MA), and the high dependence of the stereochemistry on the solvent and the substituents (from stereoconvergency to stereospecificity) are discussed and interpreted in terms of a mechanistic scheme, analogous to the Jencks scheme for aliphatic nucleophilic substitutions, in which preassociation, free-ion, and ion-pair pathways compete. In particular, the stereochemical outcome of these reactions is consistent with a marked change in the nucleophilic partners of the product-forming ionic intermediate arising from different ionization routes. Return, i.e. change in the rate-limiting step from ionization to product formation, is shown to be related to substituent-dependent, but not solvent-dependent, bromine bridging.

The kinetics and the products of bromination of several substituted stilbenes with tetrabutylammonium tribromide (TBAT) have been investigated in aprotic solvents at different temperatures. Stilbenes bearing electron-withdrawing or moderately electron-donating substituents gave stereospecifically the anti addition products. The reactions followed a second-order rate law, and an inverse kinetic isotope effect (KIE), k(H)/k(D) = 0.85(0.05), was found for the bromination of cis-stilbene. The reactions of cis- and trans-4,4-dimethoxystilbenes yielded mixtures of meso and d,l dibromides both in chloroform and 1,2-dichloroethane. The rate constants (k(Br)()3()-) measured for the latter olefins deviated considerably from the Hammett correlations, and added bromide had a significant effect on the rates. The reactions of these activated stilbenes with molecular Br(2), carried out at low Br(2) concentration, followed a mixed second/third-order rate law. The kinetic and product distribution data for the reaction, with TBAT, of stilbenes bearing electron-withdrawing or moderately electron-donating substituents are interpreted on the basis of the known mechanism involving a product- and rate-determining nucleophilic attack by bromide on the olefin-Br(2) pi-complex. The data related to the bromination of the more activated methoxystilbenes are rationalized considering that, for these olefins, even in aprotic solvents, the ionization of the initially formed 1:1 pi-complex to a bromocarbenium bromide ion pair can compete both with the formation of a bromonium-tribromide ion pair and with the nucleophilic attack by Br(-). For this second-order process (first order in Br(2)), the kinetic constants and the activation parameters have been measured in chloroform and 1,2-dichloroethane and the activation parameters have been compared with those related to the third-order Br(2) addition and to the reaction with TBAT.