Relative Leaving Group Abilities Research Articles

Regioselective Synthesis of 4‐Nitro‐ or 4‐Chloro‐Tetrasubstituted Pyrazoles from Hydrazones and β‐Halo‐β‐nitrostyrenes

AbstractWe report an acid‐catalyzed cycloaddition reaction of hydrazones with β‐bromo‐ or β‐chloro‐β‐nitrostyrenes for the regioselective synthesis of 4‐nitro‐ or 4‐chloro‐tetrasubstituted pyrazoles. Arising from a common 4‐halo‐4‐nitropyrazolidine intermediate, the identity of the pyrazole product formed is dependent on the relative leaving group abilities of the halo and nitro substituents.

ChemInform Abstract: Active‐Latent Thioglycosyl Donors and Acceptors in Oligosaccharide Syntheses

AbstractReview: 109 refs.

1-Aryl-3-alkyl-1,4,5,6-tetrahydro- pyrimidinium Salts. Part 2. Reactions with Nucleophiles

The reactivity of 1-aryl-3-alkyl-1,4,5,6-tetrahydropyrimidinium salts (1) towards nucleophiles was studied. Hydrolysis of salts (1) afforded initially compounds (2, kinetic products) through the corresponding amidinium hydroxides (4). The regioselectivity of the reaction was analyzed considering the relative leaving group abilities and the stereoelectronic control theory. Amino amides (2a-c) in the reaction medium underwent spontaneous formyl migration, affording compounds (3, thermodynamic products). Reduction of salts (1) with sodium borohydride led to acyclic trimethylenediamines (5) or to the corresponding hexahydropyrimidines (6), according to the reaction conditions. Aminolysis of compound (1f) with isopropylamine yielded an acyclic formamidine (7f).

On the relative leaving group abilities of imidazole and the substituted phenoxide ions. The effect of the acyl group

AbstractRate coefficients for the imidazole‐catalysed hydrolysis of substituted phenyl acetates, chloroacetates and dichloroacetates have been determined in 40% (v/v) acetonitrile‐water. It is shown that the increasing electron‐withdrawal by the acyl group makes the general base‐catalysed nucleophilic reaction of imidazole detectable beside the uncatalysed nucleophilic attack of the amine. This is attributed to the acyl group‐induced change of the partitioning ratio of imidazole and the ester leaving group. A kinetic evidence is obtained of a change in the rate‐limiting step with increasing imidazole concentration for the imidazole‐catalysed reactions of 4‐chloro‐ and 4‐methoxyphenyl dichloroacetates.

A surprising effect of leaving group on the nucleophilic aromatic substitution reaction catalyzed by 4-chlorobenzoyl CoA dehalogenase

We have begun our mechanistic studies of 4-chlorobenzoyl-CoA dehalogenase with a determination of the relative leaving group abilities for bromide, chloride, and fluoride in the dehalogenation reaction. Dehalogenation of 4-bromobenzoyl-CoA is twice as fast as dehalogenation of 4-chlorobenzoyl-CoA, while dehalogenation of 4-fluorobenzoyl-CoA is over 400-fold slower. These data are in striking contrast to the relative leaving group abilities observed for the glutathione-S-transferase-catalyzed dehalogenation of 4-halo-3-nitro-1-(trifluoromethyl)benzenes. Our data also differ from those observed for nonenzymic nucleophilic aromatic substitution reactions that occur by the S[sup N]Ar mechanism. The most reasonable mechanism for the enzymic dehalogenation reaction is probably the S[sub N]Ar mechanism. Nucleophilic aromatic substitution reactions that take place by this mechanism generally proceed fastest when the leaving group is fluoride, even though fluoride is the poorest leaving group among the halogens. The nucleophilic aromatic substitution reaction catalyzed by 4-chlorobenzoyl-CoA dehalogenase shows leaving group abilities in the order opposite that expected on the basis of nonenzymic S[sub N]Ar reactions and the glutahione-S-transferase reaction. Two alternative explanations may account for these data. Our data do not permit a distinction between the various possible mechanisms for the dehalogenation reaction. 17 refs., 1 tab.

Intrinsic alkyl radical properties inferred from the study of unimolecular dissociations of gaseous carboxylic acid cation radicals

The study of metastable carboxylic acid cation radicals (lifetime 10 -5s) in the gas phase provides a detailed insight into a chemistry which is best described in terms of “free radical chemistry”. In addition to the well-known 1, n-hydrogen migrations ( n = 4,5) of radicals evidence is presented that even the longsought 1,2-hydrogen migration may take place in appropriate cases. Examples for 1, n-migrations of protonated carboxyl groups ( n = 2,4,5) are also discussed, while (l, n) alkyl migrations do not occur. For all n-alkyl elimination processes studied, ene-1,1-diol cation radicals were identified as the essential intermediates ; the mechanism of dissociation is the exact counterpart to the addition of nucleophilic alkyl radicals to deactivated double bonds. The study of metastable carboxylic acids in the gas phase provides the following ordering of relative leaving group abilities for n-alkyl radicals: C 2H 2 ≫ > C 3H 7 > C 4H 9 > C 5H 11 > C 6H 13 > C 7H 15 > C 8H 17 ⋙> CH 3

Mechanism of formation and breakdown of amine tetrahedral addition compounds of a phthalimidium cation. Relative leaving group abilities of amines and alkoxide ions

Mechanism of formation and breakdown of amine tetrahedral addition compounds of a phthalimidium cation. Relative leaving group abilities of amines and alkoxide ions