Friedel Crafts with phosgene

Aromatic and heterocycHc compounds are formylated by reaction with dialkyl- or alkylarylformamides in the presence of phosphoms oxychloride or phosgene (Vilsmeier aldehyde synthesis) (125). The Vilsmeier reaction is a Friedel-Crafts type formylation (126), since the intermediate cation formed by the interaction of phosphoms oxychloride with formamide is a typical electrophilic reagent. Ionic addition compounds of formamide with phosgene or phosphoms oxychloride are also known (127). 

Preparation of Arylcarboxylic Acids and Derivatives. The general Friedel-Crafts acylation principle can be successfully appHed to the preparation of aromatic carboxyUc acids. Carbonyl haUdes (phosgene, carbonyl chloride fluoride, or carbonyl fluoride) [353-50-4] are diacyl haUdes of carbonic acid. Phosgene [75-44-5] or oxalyl chloride [79-37-8] react with aromatic hydrocarbons to give aroyl chlorides that yield acids on hydrolysis (133) ... 

Ketone formation can also be avoided if one of the functional acyl halogens ia phosgene is blocked. Carbamyl chlorides, readily obtained by the reaction of phosgene with ammonia or amines, are suitable reagents for the preparation of amides ia direct Friedel-Crafts acylation of aromatics. The resulting amides can be hydroly2ed to the corresponding acids (134) ... 

Synthetic routes that access appropriately substituted thienobenzazepines are also quite important for medicinal chemistry stracture activity relationship studies, and many involve similar bond connectivity strategies. One notable example employs the use of conunercially available 4-methyl-3-nitrophenol (Scheme 6.3). Methylation of the phenol followed by bromination, hydrolysis, and oxidation of the benzylic alcohol afforded aldehyde 9 in quantitative yield. Treatment of this aldehyde with 5-lithio-2-methylthiophene provided, after dehydroxylation, nitro intermediate A in good overall yield. Reduction of the nitro functionality and treatment with phosgene presented the corresponding isocyanide which upon cychzation using aluminum trichloride in a Friedel-Crafts fashion afforded the... 

The oxazolidinediones 94 are crystalline, stable solids that are a convenient source of dipeptides when heated in THF with amino adds. The compounds are prepared fiom N-protected amino adds and phosgene or triphosgene <99JOC2S32>. The diiral oxazolidinediones 95 act as Friedel-Crafts reagents with aromatic hydrocarbons and aluminium chloride, giving the ketones 96 in moderate yield but with high ee <99S423>. ... 

Another example is the Friedel-Crafts phosgene reaction with 0.xylene giving 3,3, 4,4 -tetramethylbenzophenone in high yield and free of isomers (Ref. 14). This substituted benzophenone is easily oxidized into benzophenone tetra-carboxylic acid dianhydride (BTDA) widely used for the manufacture of polyimides [Scheme 18] ... 

Friedel-Crafts reaction of phosgene with heterocyclic aromatic compounds is also difficult to stop at the acid chloride stage. However, under selected conditions, heteroaromatics such as thiophene can be directly acylated to give thiophenecarbonyl chloride [Scheme T9] (Ref. 15) ... 

Phosgene can react with arenes, when in the presence of a Friedel-Crafts catalyst such as aluminium(III) chloride [1556,2026], to give predominantly benzoyl chlorides or benzophenones, depending on the reaction conditions [2196] ... 

Phosgene in toluene reacts with azulene at room temperature in the absence of a Friedel-Crafts catalyst according to [2052a] ... 

The preparation of berbines (Scheme 38) through treatment of 1-benzyl-1,2,3,4-tetrahydro-iso-quinolines with phosgene gas to yield the iV-chloroformyl derivatives (208) is another example of the use of intramolecular Friedel-Crafts reactions in the construction of quinolizidine systems. These intermediates gave berbin-8-ones (209) by intramolecular ring closure in the presence of several Lewis acid catalysts (Scheme 38) <85T169>. 

The polyarylesterketones can be produced by means of interaction between bisphenylsulfide, dibenzo rane and bisphenyloxide with monomers of electrophylic nature (phosgene, terephthaloylchloride) or using homopolycondensation of 4-phenoxybenzoylchloride and 4-phenoxy-4-chlorcarbonyl-bisphenyl in the presence of dichloroethane at 25 °C [282-285], Aromatic polyesterketones form after the polycondensation of 4-phenoxybenzoylchloride with chloranhydrides of tere- and isophthalic acids, 4,4 -dicarboxybisphenyloxide in the environment of nitrobenzene, methylchloride and dichloroethane at temperatures from -70 till 40 °C during 16-26 h according Friedel-Crafts reaction. 

Upon protracted contact with aluminium(III) chloride at higher temperatures, and especially if the aromatic hydrocarbon is itself used as the solvent, the product of the reaction between phosgene and aromatic hydrocarbons is usually the corresponding benzophenone [2026]. Friedel and Crafts [686aa] found that COCI, reacts with benzene in the presence of a stoicheiometric amount of aluminium(III) chloride to give benzophenone ... 

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