Aliphatic bimolecular nucleophilic mechanism

The Sn2 reaction involves the attack of a nucleophile from the side opposite the leaving group and proceeds with exclusive inversion of configuration in a concerted manner. In contrast to the popular bimolecular nucleophilic substitution at the aliphatic carbon atom, the SN2 reaction at the vinylic carbon atom has been considered to be a high-energy pathway. Textbooks of organic chemistry reject this mechanism on steric grounds [175]. 

Studies have shown that the HDN of 1,2,3,4-tetrahydroquinoline and 1,2,3,4-tetrahydroisoquinoline catalyzed by sulfided NiMo/Al203 occur via a nucleophilic substitution mechanism [121]. On the other hand, HDN of aliphatic amines with the same catalyst—N1M0/AI2O3—occurs by -elimination [117]. The nature of the base and the amine structure dictate whether the elimination will proceed via a monomolecular (El) or a bimolecular (E2) mechanism. Similarly, for HDN reactions that occur via nucleophilic substitution, these same factors determine if the reaction will follow a monomolecular (Sn 1) or a bimolecular (Sn2) mechanism. 

Kinetic studies of the nucleophilic reactions of azolides have demonstrated that the aminolyses and alcoholyses proceed via a bimolecular addition-elimination reaction mechanism, as does the neutral hydrolysis of azolides of aromatic carboxylic acids. Aliphatic carboxylic acid azolides which are subject to steric hindrance can be hydrolyzed in aqueous medium by an 5n1 process. There have been many studies of these reactions, and evidence supporting both 5n1 and 5n2 processes leaves the impression that there are features of individual olysis reactions which favour either an initial ionization or a bimolecular process involving a tetrahedral intermediate (80AHC(27)241, B-76MI40701). 

For the bimolecular reaction with Ac cleavage, two reasonable mechanisms have been suggested. The first is a direct displacement analogous to the 8 2 mechanism of aliphatic nucleophilic substitution. This route is shown in Eq. (4) structure 2 is the transition state (I), although it is oversimplified because... 

The mechanisms that occur in aliphatic electrophilic substitution reactions are less well defined than those that occur in aliphatic nucleophilic substitution and aromatic electrophilic reactions. There is still, however, the usual division between unimolecular and bimolecular pathways the former consisting of only the SE1 mechanism, while the latter consists of the SE2 (front), SE2 (back) and the SEi mechanism. 

When Bunnett and Zahler [1] published their landmark review in 1951, only two mechanisms of nucleophilic aromatic substitution were known. These were the unimolecular S l process, typically observed with arenediazonium salts, as in Scheme 6.1, and the bimolecular S,.jAr pathway, which is shown in Scheme 6.2 involving substitution of a halide ion by an anionic nucleophile and involving an anionic intermediate (1). As in aliphatic substitutions, both unimolecular and bimolecular pathways are possible. 

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