Formamides dehydration

F.M. Faus, B. Zhou, H. Matralis, and B. Delmon, Catalytic cooperation between M0O3 and Sb204 inN-ethyl formamide dehydration. III. Comparison of a mathematical model based on the remote control mechanism with experimental results, J. Catal. 132, 200-209 (1991). 

BASF, Degussa and Knapsack have developed an efricienl process based on formamide dehydration (2) in the presence of Fe or Al promoters (Equation (2 . 

The reaction is mn for several hours at temperatures typically below 100°C under a pressure of carbon monoxide to minimise formamide decomposition (73). Conversions of a-hydroxyisobutyramide are near 65% with selectivities to methyl a-hydroxyisobutyrate and formamide in excess of 99%. It is this step that is responsible for the elimination of the acid sludge stream characteristic of the conventional H2SO4—ACH processes. Because methyl formate, and not methanol, is used as the methylating agent, formamide is the co-product instead of ammonium sulfate. Formamide can be dehydrated to recover HCN for recycle to ACH generation. 

Hydrogen cyanide has been manufactnied from sodium cyanide and mineial acid, and from formamide by catalytic dehydration. As of this writing. 

The formamide is dehydrated to HCN which is recycled back to make acetone cyanohydrin. The overall reaction is acetone + methyl formate — MMA + H2O. 

Furfuryl dimethyl amine is first produced. This may conveniently be accomplished by employing the Leuckart synthesis known to those skilled in the art, which involves the use of an aldehyde or a ketone, and formate of ammonia or an amine, or corresponding formamide derived by dehydration of formate of ammonia or an amine. 

Arenediazoisocyanides (Ar —N2NC) were synthesized by Ignasiak et al. (1975) by reaction of arenediazonium ions with formamide and dehydration of the resulting l-aryl-3-formyltriazene with thionyl chloride (Scheme 6-19). These compounds are interesting in the context of the (Z)/( )-isomerism of diazocyanides (see Sec. 6.6). 

Dehalogenation of l,l,2-trichloro-2,3,3-trifluorocyclobutane, 43,45 Dehydration of formamides with phosphorus oxychloride to isocyanides, 41, 13, 101... 

Phosphorus oxychloride, dehydration of formamides with, 41, 13, 101 removal from reaction of cyanoacetic acid and phosphorus pentachlo-ride, 41,5,7... 

Potassium amide ip conversion of o-acetoacetochloroanilide to 3-acetyk)xindole, 40, 1 Potassium ierf-butoxide, 41, 101 in dehydration of formamides to isocyanides, 41, 101... 

Toluenesulfonylhydrazide, 40, 93 o-Toluidine, conversion to N-o-tolyl-formamide, 41, 102 N-o-Tolylformamide, 41, 102 dehydration to o-tolyl isocyanide, 41, 102... 

An alternative approach towards the PASP synthesis of isocyanides was developed by Bradley [100,101]. It involved the use of a polymer-supported sul-fonyl chloride in the presence of base to afford the dehydration of formamides (Scheme 21). The formamides required could be easily prepared by reaction of the corresponding amines with a formylated benzotriazole resin. Opti-... 

The use of the triphenylphosphine-carbon tetrachloride adduct for dehydration reactions appears to be a very simple way of synthesizing nitriles from amides, carbodi-imides from ureas, and isocyanides from monosubstituted formamides. All of these reactions involve the simultaneous addition of triphenylphosphine, carbon tetrachloride, and tri-ethylamine to the compound to be dehydrated. The elimination of the elements of water is stepwise. An adduct, e.g. (46), is first formed, chloroform being eliminated, which decomposes to produce hydrogen chloride and the dehydrated product. 

Ring D inversion seems to be a crucial step in biogenetic transformations of protoberberines to related alkaloids such as rhoeadine, retroprotoberberine, spirobenzylisoquinoline, and indenobenzazepine alkaloids. 8,14-Cyclober-bin-13-ol 478 derived from berberine (15) was successively treated with ethyl chloroformate, silver nitrate, and pyridinium dichromate (PDC) in dimethyl-formamide to give the keto oxazolidinone 479 (Scheme 98). Heating of 479 with 10% aqueous sodium hydroxide in ethanol effected hydrolysis, retro-aldol reaction, cyclization, and dehydration to provide successfully the... 

The potential power of Fukuyama s method is illustrated by the synthesis of biindolyl 168 which was used in a synthesis of indolocarbazoles [176]. The isonitriles (e.g., 167) are generally prepared by dehydration of the corresponding formamides with POCI3. 

Dehydrative condensation of pyrrole-2-carboxaldehyde 77 and ethyl carbazate afforded carbethoxyhydrazone 78 in quantitative yield. Cyclization of 78 in the presence of a catalytic amount of sodium hydride (10mol%) in dimethyl-formamide (DMF) at 100°C led to the formation of pyrrolo[l,2-tf][l,2,4]triazin-4-one 27 in 75% yield (Scheme 8) <1999T13703>. 

The ACH process has recently been improved, as stated by Mitsubishi Gas. Acetone-cyanohydrin is first hydrolized to 2-hydroxyisobutylamide with an Mn02 catalyst the amide is then reacted with methylformiate to produce the methyl ester of 2-hydroxyisobutyric acid, with coproduction of formamide (this reaction is catalyzed by Na methoxide). The ester is finally dehydrated with an Na-Y zeolite to methylmethacrylate. Formamide is converted to cyanhydric acid, which is used to produce acetone-cyanohydrin by reaction with acetone. The process is very elegant, since it avoids the coproduction of ammonium bisulphate, and there is no net income of HCN. Problems may derive from the many synthetic steps involved, and from the high energy consumption. 

In a dehydration reaction (Scheme 12.4), the IR band of the formamide carbonyl group at 1684 cm in (7) decreased and eventually converted to the isonitrile band at 2150 cm in (8) (Fig. 12.8). In a separate example (Scheme 12.5), the conversion of the IR band from the carbonate carbonyl group in (9) to the IR band of the carbamide carbonyl group in (10) can be monitored to assure the reaction completion (Fig. 12.9). Based on FTIR analysis, the reaction time course can be analyzed by integrating peak areas of the IR bands from the starting resin and the product. From the point of view of kinetics, the side reaction product formation can be excluded if the pseudo first order rates of the starting material consumption and the product formation are identical. 

Formamido esters and amides can be generated in two steps starting from (natural) a-amino acids (7). Owing to the wide availability of optically pure formamides, the s)mthesis of optically pure a-substituted a-acidic isocyano amides (2) and esters (1) has been envisioned using the dehydration route. 

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