Imidoyl halides, elimination reactions

Intramolecular azomethine ylide cycloaddition to the C—O double bond of an aldehyde was reported in 197369 and cycloaddition to the C—C double bond was first reported in 1975.70 Competition between 1,1- and 1,3-cycloaddition is observed in intramolecular reactions, although intermolecular reactions give only 1,3-cycloaddition. Photolysis of 2//-azirines is one generation method of nitrile ylides applicable to intramolecular cycloaddition.70 Another method involves the base-catalyzed 1,3-elimination of hydrogen halide from alkenyl imidoyl halides. Still other procedures involve thermolytic and photolytic cycloreversions of oxazolinones and dihydrooxazaphospholes. 

The chemistry of imidoyl halides is centered around the mobile halo group which can either be displaced or eliminated. Thus, imidoyl halides resemble very much carboxylic acid halides, except that the scope of their reactions is enlarged by the possibility of substitution on the nitrogen. 

Perhaps more important than the substitution reactions are the elimination reactions of imidoyl halides. Three types of reactions are encountered, depending upon the substituents attached to the imidoyl moiety. For example, if R = H, elimination of hydrogen chloride occurs quite readily and the corresponding nitrile is obtained. 

The thermal elimination of alkyl halides to form nitriles is perhaps the best known reaction of imidoyl chlorides. J. v. Braun investigated this reaction in detail over a period of 40 years, and he developed a host of useful new synthetic procedures for the synthesis of compounds, which are otherwise more difficult to obtain. Unfortunately, most of his work has been written up in detailed form in Chemische Berichte and it requires some effort to retrieve this information. However, he wrote one review article in 1934 which is most informative. The elimination of alkyl halides on heating of imidoyl chlorides was recognized by Wallach in 1877 and v. Pechmann and Ley and Holzweissig reported examples of this reaction prior to the work of J. v. Braun. The elimination reaction, in its most general terms, can be described by the following sequences ... 

The limited-rate data indicate that the order of reactivity of cyclic imidoyl halides with regard to nucleophilic substitution reactions is the following F > Cl > Br > I. As expected, elimination reactions are of no significance in the cyclic series. 

If the elimination of hydrogen halide is prevented by halogen substitution, the corresponding imidoyl halides are obtained. For example, the reaction of hexafluoroglutarimide with phosphorus pentachloride produces the imidoyl chloride XLVI in high yield. TTie reaction proceeds via the... 

From the reaction of imidazole 161 and aromatic acid halides (Scheme 63), imidoyl chlorides 162 are obtained, which eliminate methyl chloride to form imidazo[2,l-6]l,3,4]thiadiazoles 163 upon extended heating (88H1935). 

The classical example of this type of reaction is the v. Braun method of degradation, by which a secondary amine can be transformed into a primary amine, and finally into ammonia, via the imidoyl chloride intermediates. This reaction has been used for the structure elucidation of alkaloids. Although degradative studies are not conducted to any extent today due to the convenience of spectral methods, the v. Braun elimination is still used in organic synthesis to prepare nitriles as well as alkyl halides. 

The reactions of carbonimidoyl dihalides can be divided into nucleophilic substitution reactions, whereby the halo groups are replaced stepwise by other nucleophiles, and addition reactions. The substitution reactions are often accompanied by elimination, depending upon the stability of the formed imidoyl derivatives. For example, the monosubstitution products can eliminate hydrogen halide, alkyl halide, or sulfenyl chloride, i.e.,... 

The reaction of iminium chloride with alcohols affords imidoyl ester hydrochlorides LXXXVI as intermediates, which eliminate alkyl halides upon heating, thereby regenerating the corresponding carboxylic acid amide... 

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