Phosgeniminium chloride

A new synthesis of pterins based on the acylation of 4-amino-5-nitrosopyrimidines with dienoic acid chlorides, followed by a high-yielding intramolecular hetero DA cycloaddition and cleavage of the N—O bond has been reported <06HCA1140>. Several new substituted pterins have been obtained in an efficient one-pot procedure using N,N dimethyldichloromethyleniminium chloride (phosgeniminium chloride) and a suitable pyrazine <06H933>. 

Treatment of 1-methyl-4-cyano-5-aminoimidazole with phosgeniminium chloride produced an imidazoloamidine (64% yield) that cyclized when exposed to dry hydrogen chloride gas (95% yield) to give 6-chloro-2-dimethylamino-9-methylpurine <1997T8269>. Elaboration of this material led to the first synthesis of the natural product purine heteromine A (see Section 10.11.12.1). 

The pyrazolo-fused pyrimido[4,5-< ]-l,2,4-triazine 35 was synthesized using the 5-amino-6-cyano triazine 131 (Scheme 21) as the precursor. Reaction with phosgeniminium chloride gave the amide halide intermediate 132 which in turn produced the pyrimido[4,5-< ]-l,2,4-triazine 35 upon treatment with gaseous hydrogen chloride <1996T3037>. 

The last step in a stereospecific total synthesis of ( )-biotin consists of the facile reaction of the precursor diamine with phosgene (equation 5) (77JA6754). The reaction of a cyclic amidrazone precursor with phosgeniminium chloride gives thiazolo[3,2-6]-s-triazoles (equation 6) (73AG(E)405). Treatment of 4,5-diaminopyrazoles with thionyl chloride forms pyrazolo[3,4-c][l,2,5]thiadiazoles (equation 7) (68JMC1164). 

Dichloromethine cyanine 17 which can be obtained in high yield from phosgeniminium chloride (PI) and N,N-dimethylacetamide has proven to be a particularly versatile source of push-pull ynamines. Arylamines, however cyclise on the aryl group and 2,4-bis(dimethylamino)quinolines are the final products80). The intermediary ynamines can only be detected by the IR. The process is catalysed by traces of hydrogen chloride see also (5.3). 

The l,2-diamino-4-methylthiazole 73 with phosgeniminium chloride gives the thiazolo[3,2-A [l,2,4]triazole derivative 74 (Scheme 45) <1973AGE806>. Reaction of the sulfimide 75 with nitrile oxides forms [l,2,4]triazolo[l,5- ] pyridine 3-oxides 76 in good yields (Scheme 46). This method is applicable to analogous pyrimidines and pyrazines <1976J(P1)2166, 1978BCJ563>. 

The yields are lower because of competing hydrolysis during the aqueous work-up. Lithioynamines 44 must be used with unreactive halides such as carbamoyl chlorides and imidoyl halides (93) The scope of this reaction seems to be limited only by the availability of the requisite acyl chlorides. It is less surprising, therefore, that a single paper reports the preparation of about sixty push-pull acetylenes In contrast, silylated ynamines, react only with very strong acylation agents, e.g. trichloroacetyl and nitrobenzoyl chloride as well as with phosgeniminium chloride. 

A, A -Dialkyl-4-chloroquinazolin-2-amines 18 can be prepared in 85 to 95% yield under mild one-pot reaction conditions from 2-aminobenzonitriles 17 and phosgeniminium chlorides in anhydrous dichloromethane. ... 

From 2-Ammobenzonitriles, Grignard Reagents, and Carbonyl Compounds or Phosgeniminium Chlorides... 

Aminobenzonitriles 17 react with Grignard reagents to give the intermediate iminium salt 20, which can be readily trapped in situ by carbonyl compounds (e.g., acid chlorides, anhydrides, formates, carbonates, and oxalates) or phosgeniminium chlorides and cyclized to quinazolines. With this method various 2-unsubstituted quinazolines, 2,4-disubstituted quinazolines, and quinazolines with certain functional groups (e.g., COjEt, NMe ) in the 2-position are readily available. 

Recently, " a novel and convenient one-pot synthesis of 8-(arylamino)theophyllines starting from l,3-dimcthyluracil-6-amine through reaction, successively, with phosgeniminium chloride, azidotrimethylsilane and arylamines, has been reported, e.g. formation of 8-anilino-theophylline (16)." ... 

Amines 2 are also only moderately basic but react with strong electrophiles as exemplified for phosgeniminium chloride (PI) (Scheme 32). 

Aryl-6-phenyl-2-methylthio/secondary amino substituted-4(3//)-pyrimidinones were derived from a reaction of N-arylamino substituted 1,3-diaza-1,3-butadienes with substituted ketenes that was analyzed by computational methods <97T13829>. 1,3-Diazines related to 6-amino-4-chloro-5-cyano-2-(dimethylamino)pyrimidine were prepared in one-pot fashion from 1,1-diamino-2,2-dicyanoethylene and phosgeniminium chloride <97SC1223>. Pyrazolo[3,4- /]pyrimidines were derived from 4-substituted 5-aminopyrazole-l-carbothioamides <97JCR(S)352>. Amino-5-(trifluoromethyl)-l,2,4-triazole gave polysubstituted 2-... 

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