AB-INITIO THEORETICAL INVESTIGATION OF THE MECHANISM FOR ALPHA-LACTONE FORMATION FROM ALPHA-HALOCARBOXYLATES - LEAVING GROUP, SUBSTITUENT, SOLVENT AND ISOTOPE EFFECTS

Structures and energetics of geometry optimized species occurring alon g the reaction pathway for halide elimination from alpha-halocarboxyla tes XCHRCO2- (R = H, X = F, Cl and Br; X = Cl, R = CH3 and CH = CH2) h ave been determined by means of ab initio MO calculations using the HF /6-31++G(d,p) and MP2/6-311++G(d,p) methods, Endothermic heterolysis o f the C-alpha-X bond yields halide and alpha-lactone by means of a tra nsition structure leading to an ion-molecule complex lying in a shallo w well, The ion-molecule complexes are all essentially planar about C- alpha and possess an almost completely formed C-alpha-O bond in the al pha-lactone ring, The transition structures are also essentially plana r about C-alpha, but show only partial ring-closure, The maximum degre e of charge separation occurs in the transition structure, which has c onsiderable positive charge about C-alpha sandwiched between the negat ively charged leaving group and internal nucleophile. Aqueous solvatio n, as treated by the self-consistent reaction field IPCM method, accen tuates the charge-separated character of the transition structure but raises the barrier to heterolysis since the localized charge of the re actant is preferentially stabilized; the calculated value of Delta H-d ouble dagger = 112 kJ mol(-1) for reaction of alpha-chloroacetate in w ater compares favourably with experimental values for hydrolyses of al pha-bromophenylacetic acids, Calculated secondary alpha-D kinetic isot ope effects suggest an S(N)2 transition state for reaction of alpha-ch loroacetate but a more S(N)1-like transition state for alpha-chloropro pionate, while the alpha-C-14 effects are typical of S(N)2 processes. The calculated secondary beta-D-3 kinetic isotope effect for alpha-chl oropropionate is inverse.