Alpha-substitution reaction mechanism

Reactivity of Ends The Mechanism of Alpha-Substitution Reactions 84... 

Reactivity of Ends The Mechanism ol Alpha-Substitution Reactions 905... 

Both in the laboratory and in living organisms, the reactions of carbonyl compounds take place by one of four general mechanisms nucleophilic addition, nucleophilic acyl substitution, alpha substitution, and carbonyl condensation. These... 

The first evidence that an elimination-addition mechanism could be important in nucleophilic substitution reactions of alkanesulfonyl derivatives was provided by the observation (Truce et al., 1964 Truce and Campbell, 1966 King and Durst, 1964, 1965) that when alkanesulfonyl chlorides RCH2S02C1 were treated in the presence of an alcohol R OD with a tertiary amine (usually Et3N) the product was a sulfonate ester RCHDS020R with exactly one atom of deuterium on the carbon alpha to the sulfonyl group. Had the ester been formed by a base-catalysed direct substitution reaction of R OD with the sulfonyl chloride there would have been no deuterium at the er-position. Had the deuterium been incorporated by a separate exchange reaction, either of the sulfonyl chloride before its reaction to form the ester, or of the ester subsequent to its formation, then the amount of deuterium incorporated would not have been uniformly one atom of D per molecule. The observed results are only consistent with the elimination-addition mechanism involving a sulfene intermediate shown in (201). Subsequent kinetic studies... 

Supporting evidence for the mechanism comes from the observation that the bromination and iodination proceed at the same rates. The deuterium exchange is also comparable in absolute rate. Very extensive work with the optically active sec-butyl phenyl ketone, C2H5—CH(CH3)COC6H6, has shown that the acid-catalyzed iodination, bromination, and inversion have identical rates. The base-catalyzed, OD, rates of deuteration and inversion have also been shown to be equal. If the enol and enolate ion can be considered to be planar about the a carbon atom, then these results provide very strong support for the slow enolization step. In fact it is difficult to find any other reasonable interpretation of the data. The enol mechanism is also compatible with the well-known susceptibility of H atoms, in the alpha position to one or more C==0 groups, to substitution reactions. 

Most reactions of carbonyl groups occur by one of four general mechanisms nucleophilic addition, nucleophilic acyl substitution, alpha substitution, am carbonyl condensation. These mechanisms have many variations, just a alkene electrophilic addition reactions and 8 2 reactions do, but the varia tions are much easier to learn when the fundamental features of the mechanisms are understood. Let s see what the four mechanisms are and what kinds of chemistry carbonyl groups undergo. 

Pyrazines are formed from transamination reactions, in addition to carbon dioxide and formaldehyde. A requirement is that the carbonyl compound contains a dione and the amino group is alpha to the carboxyl group (16). If the hydrogen on the ct-carbon oI the amino acid is substituted, a ketone is produced. Newell (17) initially proposed a pyrazine formation mechanism between sugar and amino acid precursors. (See Figure 3). The Schiff base cation is formed by addition of the amino acid to the anomeric portion of the aldo-hexose, with subsequent losses of vater and a hydroxyl ion. Decarboxylation forms an imine which can hydrolyze to an aldehyde and a dienamine. Enolization yields a ketoamine, vhich dissociates to amino acetone and glyceraldehyde. 2,5-Dimethylpyrazine is formed by the condensation of the tvo molecules of amino acetone. 

The high negative value of p indicates that the reaction is strongly accelerated by groups with electron-releasing inductive effects (negative a ). In the sequence CH2 (OC2 Hs )2 rate coefficient is increased by approximately 3.5 powers of ten for each substitution of H by CH3 in the alpha position. This strong inductive effect and the complete absence of steric hindrance can be taken as evidence for an A1 mechanism [177]... 

The hydrocarbon portion of an aliphatic acid can undergo the free-radical halogenation characteristic of alkanes, but because of the random nature of the substitution it is seldom used. The presence of a small amount of phosphorus, however, causes halogenation (by an ionic mechanism) to take place exclusively at the alpha position. T his reaction is known as the Hell-Volhard-Zelinsky reaction, and it is of great value in synthesis. 

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