Nucleophilic substitution reactions amine formation

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... 

Normal nucleophilic substitution reactions of alkyl and aryl chloropyrazines have been examined as follows 2-chloro-3-methyl- and 3-chloro-2,5-dimethyl(and diethyl)pyrazine with ammonia and various amines (535, 679, 680) 2-chloro-3(and 6)-methylpyrazine with methylamine and dimethylamine (681, 844), piperidine and other amines (681, 921) 2-chloro-5(and 6)-methylpyrazine with aqueous ammonia (362) alkyl (and phenyl) chloropyrazines with ammonium hydroxide at 200° (887) 2-chloro-3-methylpyrazine with aniline and substituted anilines (929), and piperazine at 140° (759) 2-chloro-3-methyl(and ethyl)pyrazine with piperidine (aqueous potassium hydroxide at reflux) (930,931) [cf. the formation of the 2,6-isomer( ) (932)] 2-chloro-3,6-dimethylpyrazine with benzylamine at 184-250° (benzaldehyde and 2-amino-3,6-dimethylpyrazine were also produced) (921) 2-chloro-3,5,6-trimethylpyrazine with aqueous ammonia and copper powder at 140-150° (933) and with dimethylamine at 180° for 3 days (934,935) 2-chloro-6-trifluoromethylpyrazine with piperazine in acetonitrile at reflux (759) 2-chloro-3-phenylpyrazine with aqueous ammonia at 200° (535) 2-chloro-5-phenylpyrazine with liquid ammonia in an autoclave at 170° (377) 2-chloro-5-phenylpyrazine with piperazine in refluxing butanol (759) but the 6-isomer in acetonitrile (759) 5-chloro-2,3-diphenylpyrazine and piperidine at reflux (741) and 5-chloro-23-diphenylpyrazine with 2-hydroxyethylamine in a sealed tube at 125° for 40 hours (834). 

It has been suggested that micellar catalysis could be exploited in analytical chemistry to increase the rate of derivative formation prior to spectroscopic measurement of the product [223, 224]. This has been attempted in the assay of amino acids and peptides following reaction with l-fluoro-2,4-dinitrobenzene (this undergoes aromatic nucleophilic substitution by amines to give arylated amines) [225]. For this reaction some amines require up to 20 min. In the presence of cetrimonium bromide, catalysis was achieved, although absorbances some 10% higher were obtained in the presence of surfactant. 

In the nucleophilic substitution reactions of alkylsulfonyl chlorides and ring-substituted benzylsulfonyl chlorides, the operation of two competing reaction pathways has been established (a) E-A (sulfene) mechanism and (b) direct nucleophilic substitution at sulfur (general base catalysis). The relative significance of these competing mechanisms depends on the nature of the substrate and the precise reaction conditions. In the hydrolysis of cyclopropane-sulfonyl chloride 11 with tertiary amines in organic media, the sulfene 12 appears to be the crucial intermediate in the formation of cyclopropanesulfonic acid 13 (Equation 12). ... 

Bromo-N-alkylnaphthalimides undergo aromatic nucleophilic substitution reaction with amines, alkoxides and thiols under microwave irradiation in the presence of KF/AI2O3 under solvent-free conditions to afford a number of fluorescent 4-sub-stituted-l,8-naphthalimide dyes. This is an efficient method for C-N, C-0 and C-S bond formation by applying suitable nucleophiles. Adducts were produced in good to excellent yields (70-95%) and relatively in short times (Bardajee, 2013). 

Formation, transamination, and mutual transitions of aminomethyl derivatives of phosphines, representing nucleophilic substitution at the carbon atom in the P—C—O(N) fragment, take place under milder conditions than similar reactions of alcohols and amines. The reason is likely the participation of a phosphino group in intramolecular interactions (86MI1). 

Although the Capdevielle reaction for one-pot conversion of aldehydes to nitriles is a very convenient and widely applicable synthetic procedure, 3-substituted furoxans appear to be susceptible to rearrangement when substitutions with amine nucleophiles are attempted, even under relatively mild conditions (Scheme 29) <1999JOC8748>. The formation of the final product 107 in this reaction was explained via phenyl abstraction by carbamoyl radical cation from the second molecule of intermediate product 106 < 1999JOC8748>. 

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