Formamides reaction 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). 

The reaction with disubstituted formamides and phosphorus oxychloride, called the Vilsmeier or the Vilsmeier-Haack reaction,is the most common method for the formylation of aromatic rings. However, it is applicable only to active substrates, such as amines and phenols. An intramolecular version is also known.Aromatic hydrocarbons and heterocycles can also be formylated, but only if they are much more active than benzene (e.g., azulenes, ferrocenes). Though A-phenyl-A-methyl-formamide is a common reagent, other arylalkyl amides and dialkyl amides are also used. Phosgene (COCI2) has been used in place of POCI3. The reaction has also been carried out with other amides to give ketones (actually an example of 11-14),... 

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. ... 

Isoselenocyanates and selenoamides. Formamides are converted to isoseleno-cyanates by reaction with Se, EtjN, and phosgene in toluene. Selenoamides are obtained" from secondary amines, Se, and 1,1-dihaloalkanes in the presence of NaH in HMPA. An oxidation is involved. 

The following section highlights some selected recent applications of the use of phosgene equivalents in the preparation of Vilsmeier-type chlorinated derivatives of amides and ureas. Thionyl chloride, carbonyl bromides, phosphorus oxychloride, phosgene, triphosgene, oxalyl chloride, and p-toluenesulfonyl chloride are all efficient oxophilic promoters capable of generating Vilsmeier-type chloro imi-nium ion intermediate 1770 by reaction with formamides, particularly dimethyl-formaraide, and ureas. 

From a practical point of view, isocyanates, together with carbamates and ureas (Chapter 3), are the most important organic products discussed in this book. Their synthesis from nitroarenes has indeed been the subject of many patents. There are also limited examples of aliphatic isocyanates obtained by this route. Organic mono- and diisocyanates may be prepared in a continues liquid phase method by treating the appropriate amine with phosgene. However, the reaction is rather complex [6] and, besides the use of the dangerous phosgene, the formation of the corrosive hydrochloric acid creates several problems. Aliphatic isocyanates can also be obtained from olefins with isocyanate ion in the presence of a salt of a coordination compound of palladium or platinum [7], from olefins with isocyanic acid in the vapour phase over Pt/ALOs [8], and from formamides, by oxidation over a silver catalyst [9]. Apparently only the last reaction seems to have some potential practical applications [10]. 

Preparative Methods by the reaction of 2-morpholinoethylamine with Formic Acid in boiling toluene with a water separator, to yield the formamide which is treated either with Phosgene and Triethylamine in CH2CI2 or with Phosphorus Oxychloride and Diisopropylamine.The use of diisopropylamine as base is favored as yields are improved, typically to 68%. Trichloroacetic Anhydride has also been used as an alternative for COCI2, giving a yield of 74%. ... 

However the reaction is rather complexfl233i and besides the use o-f the dangerous phosgene, the presence o-f the corrosive HCl creates several problems. Aliphatic isocyanates can be also obtained -from ole-fins with isocyanate ion in the presence o-f a salt or coordination compound o-f palladium or platinum 024], -from ole-fins with isocyan I c acid in the vapor phase over Pt/Al2O3025], and -from -formamides by oxidation over a silver catalystfl26]. However apparently these methods cannot compete with the phosgene route. 

The Vilsmeier-Haack reaction leads to the formation of aromatic aldehydes starting from reactive aromatic compounds. The usual reagent combination is phosphoryl chloride or phosgene together with V-methylformanilide (MFA) or VA -dimethyl-formamide (DMF) [139,140]. First, a V,V-dimethyliminium salt, e.g. 63, is formed which, after basic hydrolysis, gives carbaldehyde. 

Acylation—Acylations of alkyl groups other than base-catalysed ones are not numerous. An interesting case is the reaction of 4-picoline with dimethyl-formamide and phosgene or phosphoryl chloride. The product (29) gives the dialdehyde on alkaline hydrolysis. ... 

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