Chloromethyleneiminium Chlorides

Phosgene, as well as the easier to handle diphosgene (chloroformic acid trichloromethyl ester) or triphosgene (carbonic acid bis(trichloromethyl) ester) transform primary, secondary and tertiary amides and thioamides to chloromethyleneiminium chlorides (25 equation 15), whereby the reaction with thioamides is of broader scope and proceeds with fewer side reactions. The amide chlorides derived from primary and secondary amides can lose HCl, giving nitriles or imidoyl halides, respectively. /V-Sub-stituted formamides can be converted to isonitriles via amide halides. ... 

Wallach was the first (1874) to report on the transformation of carboxylic acid amides to amide chlorides by treatment with PCls " various types of amides were converted by this reagent to chloromethyleneiminium chlorides (30 equation 5j(jg reactions can include the a-chlorination of... 

A(./V-Disubstituted chloromethyleneiminium chlorides (compare Section 2.1.2.2) react with alcoholic alkoxides at temperatures below 0 C to give amide acetals (433 Scheme 79, yields 30-70%)7" 9,24,28,30,32,35 gy the same method lactam acetals (435) are accessible. From dimethylformamide chloride and catechols the amide acetals (434) were prepared. - The bicyclic amide acetals (436) have been obtained from phenols, formamide and POCb. ... 

Wallach was the first (1874) to report on the transformation of carboxylic acid amides to amide chlorides by treatment with PCls various types of amides were converted by this reagent to chloromethyleneiminium chlorides (30 equation lg). - > Side reactions can include the a-chlorination of the amide chloride. If excess PCIs is used, the formation of iminium salts with complex ions (31) has been reported. The very labile bromomethyleneiminium bromides (32 equation 19) can be obtained by action of PBrs on tertiary amides. The iodomethyleneiminium salt (33) was prepared from DMF and diphosphorus tetraiodide in CS . ... 

N,N-Dimethylformamide is a particularly effective catalyst for the formation of acid chlorides with SOCI2 and is now commonly the catalyst of choice. The chloromethyleneiminium chloride intermediate is the active chlorinating species (see Dimethylchloromethyleneammonium Chloride). 

A reaction sequence starting with the interaction of dialkyl-chloromethyleneiminium chloride with diphenylchlorophosphine, followed by the reaction of the adduct so formed with dialkylformamide to give (dialkylaminochloromethyllphosphine oxides, was investigated in detail (Scheme 15). ... 

Conductivity measurements have revealed that DMF and carboxylic acid chlorides form salt-like adducts (22) in an equilibrium reaction (equation 12). Such adducts can be prepared either from DMF and acid halides (chlorides and bromides) or from chloromethyleneiminium salts and salts of carboxylic acids. Acyloxyiminium salts (23) can be prepared in the pure state by reacting acid amides with carboxylic acid chlorides in the presence of silver trifluoromethanesulfonate (equation 13). Salts of type (24 equation 14) are regarded as being intermediates in the synthesis of ketones from carboxylic acids and Grignard reagents in the presence of a-chloroenamines as well as in the preparation of acyl halides (F, Cl, Br, I) by action of a-haloenamines on carboxylic acids. ... 

Vilsmeier acylation of pyrroles, formylation with dimethylformamide/phosphoryl chloride in particnlar, is a generally applicable process. The actual electrophilic species is an Al,Al-diaIkyl-chloromethyleneiminium cation (the chloride is available commercially as a solid). " Here again, the presence of a large pyrrole-A-substituent perturbs the intrinsic a-selectivity, formylation of A-tritylpyrrole favonring the P-position by 2.8 1 and trifluoroacetylation of this pyrrole giving only the 3-ketone " the nse of bulky iV-silyl substituents allows P-acylation with the possibility of subsequent removal of the N-snbstituent." The final intermediate in a Vilsmeier reaction is an iminium salt requiring hydrolysis to prodnce the isolated product aldehyde. When a secondary lactam is used, hydrolysis does not take place and a cyclic imine is obtained." ... 

The classical Vilsmeier-Haack reaction - involves electrophilic substitution of a suitable carbon nucleophile with a chloromethyleneiminium salt, for example salt (1). Suitable carbon nucleophiles are generally electron-rich aromatic compounds such as V,N-dimethylaniline (2), alkene derivatives such as styrene (3) or activated methyl or methylene compounds such as 2,4,6-trinitrotoluene (4 Scheme I). These compounds (2-4) react with salt (1) giving, after loss of hydrogen chloride, the corresponding im-inium salts (5-7). Hydrolysis of iminium salt (5) affords aldehyde derivative (8) and this transformation (Ar—H - Ar—CHO) is the well-known Vilsmeier-Haack formylation reaction. Hydrolysis of iminium... 

A large number of acid chlorides have been used to convert formamide derivatives into their corresponding chloromethyleneiminium salts (13). These include POCI3 (the most popular), SOCI2, phosgene, oxalyl chloride and many others. 

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