Chloromethyleneiminium salts

Table 10 Typical Examples of 1,3,5-Triazines (106) Synthesized from JV-Cyanoamidines (103) and Chloromethyleneiminium salts (105)... 

The standard Vilsmeier-Haack reaction involves combination of POCI3 with DMF or yV-methylformanilide to form a chloromethyleneiminium salt which efficiently formylates a variety of electron-rich aromatic and heteroaromatic... 

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. ... 

It is well known that the action of mercapto group containing compounds on chloromethyleneiminium salts affords alkylmercaptomethyleneiminium salts, e.g. (117 equation 73) this type of reaction has only rarely found application. ... 

REACTIONS OF AROMATIC COMPOUNDS WITH CHLOROMETHYLENEIMINIUM SALTS... 

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... 

The Vilsmeier-Haack reaction, as depicted in Scheme 1, is an important method for synthesizing aldehyde derivatives. Numerous other transformations of iminium salts into products other than aldehydes have been achieved, and these additional transformations add considerable scope and versatility to the Vilsmeier-Haack reaction. The Vilsmeier-Haack reaction is not restricted to carbon nucleophiles oxygen and nitrogen nucleophiles also react with chloromethyleneiminium salts. 

Formamide derivatives can sometimes be replaced with other amides, and examples include N,N-di-methylacetamide (DMA), V-methylpyrrolidone and VA -dimethylbenzamide. The resulting chloromethyleneiminium salts react with suitable nucleophiles yielding iminium salts, but self-condensation reactions are frequently encountered when proton loss from the iminium salt can occur. This is illustrated in Scheme 2 for DMA. 

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. 

The Vilsmeier-Haack reaction of electron-rich carbocyclic aromatic compounds (Ar—H) with chloromethyleneiminium salt (1) gives aldehyde derivatives (Ar—CHO), generally in good yield. The intermediate iminium salt (cf. salt 5 Scheme 1) can be treated with hydroxylamine to obtain nitrile derivatives (Ar—CN). Benzene and naphthalene are not sufTiciently electron rich to participate in the Vilsmeier-Haack reaction, but polycyclic hydrocarbons, such as anthracene, do react. Benzene and naphthalene derivatives that possess an electron-releasing substituent (—OMe,—SMe,—NMe2, etc.) af-... 

The reaction of ketone derivatives (89) with chloromethyleneiminium salt (1) gives iminium salts (90) which yield, after hydrolysis, P-chloroacrolein derivatives (91 Scheme 7)." Numerous P-chloroacrolein derivatives have been prepared by this method and yields are generally moderate to good. p-Chloroacryl-onitrile derivatives (92) are also available in good yield from iminium salts (90 = H) by treatment... 

Formates have been prepared by the reaction of chloromethyleneiminium salts with derivatives of alcohols and phenols. Yields are generally good. ... 

Hydrazones (166) react with chloromethyleneiminium salt (I) giving, after hydrolysis, aldehydes (167 Scheme 12). In this transformation the hydrazones (166) are clearly behaving as aza-enamines. - Hydrazones (168) and (169) react with chloromethyleneiminium salt (1) at both the methyl group and at nitrogen to yield the corresponding iminium salts (170) and (171), which cyclize with loss of dimethylamine to provide iminium salts (172) and (173), respectively. Hydrolysis of these salts (172) and (173) affords pyrazole-4-carbaldehyde derivatives (174) and (175 72-96% Scheme 13). Pr uct (174) can also be prepared from semicaibazone (176). 

Other groups that react with chloromethyleneiminium salts include hydroxylamines, hydrazines, oximes, imines, azines, anhydrides, imides and ketene O-alkyl-O -silyl acetal derivatives however, reactions with these compounds have been relatively infrequent. 

Heterocycles represented by the general structure (179) afford ring-expanded products (180) in the Vilsmeier-Haack reaction with chloromethyleneiminium salt (13). 

REACTIONS OF ALKENE DERIVATIVES WITH CHLOROMETHYLENEIMINIUM SALTS 781... 

REACTIONS OF NONCARBON NUCLEOPHILES WITH CHLOROMETHYLENEIMINIUM SALTS 790... 

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