Carboxamides phosgene

Specialty Isocyanates. Acyl isocyanates, extensively used in synthetic appHcations, caimot be direcdy synthesized from amides and phosgene. Reactions of acid haUdes with cyanates have been suggested. However, the dominant commercial process utilizes the reaction of carboxamides with oxalyl chloride [79-37-8]. CycHc intermediates have been observed in these reactions which generally give a high yield of the desired products (86). 

To this end, the diazoimidazole carboxamide compound 32 was transformed first by methylamine to the methyl-triazene derivative 39, which was reacted with 11 (". -phosgene to give the desired product 40 <2002JME5448>. In another approach, 32 was directly cyclized to the bicyclic product by using 1 C-labeled methyl isocyanate. This route allowed the synthesis of both the C-2-labeled 40 and the (7-methyl-labeled samples 41 <1997JLR371, 2002JME5448> (Scheme 13). 

Carbamazepine Carbamazepine, 5H-dibenz[b,f]azepine-5-carboxamide (9.5.2), is synthesized by reacting 5H-dibenz[b,f]azepine and phosgene, which forms 5-chlorcarboxy-5H-dibenz-[b,f]azepine (9.5.1), and its subsequent reaction with ammonia to give the... 

Azetidiniminium salts - ° are available from the reaction of imines with iminium salts derived from tertiary carboxamides. These smoothly react with phosgene "- to yield a-chloroiminium... 

Phosgene and tertiary carboxylic acid amides form very labile adducts (17 equation 6 not yet isolated or used for preparative purposes as such), which decompose with loss of CO2 very rapidly to give amide chlorides (see Section 2.7.2.2.1.i). Decomposition with evolution of CO2 is a common fate of primary adducts of carbonic acid chloride derivatives. Primary adducts from DMF and chloroformic acid esters (18), for example, decompose immediately to give alkoxymethyleneiminium chlorides, which react to give alkyl chlorides and DMF (equation 7). Adducts (19) from secondary and tertiary carboxamides... 

The N-monosubstituted carboxamides, on reaction with phosgene, form imidoyl chlorides [2083a] ... 

The reaction of phosgene with W,W-disubstituted carboxamides proceeds generally according to ... 

Finally, it should be noted that Vilsmeier intermediates can be used to generate nitriles. Thus, the nitrile compounds MejNCRCCN) (R = H, Me, Ph, SMe or NMe ) were prepared by the reaction of a tertiary carboxamide with phosgene to form the [Me 2N=CRC1]C1 salt, followed by treatment with copper(I) cyanide suspended in MeCN [81]. 

Diacyl chlorides can often be either singly or doubly amidated. Carbamoyl chlorides are obtained from phosgene and ammonia or an amine under conditions that must be rigidly adhered to 596 they can then be applied to preparation of aromatic carboxamides by a Friedel-Crafts reaction or to the synthesis of unsymmetrically substituted ureas. 

Finally, acyl isocyanates have been prepared from carboxamides by use of oxalyl chloride in place of phosgene.636... 

Phosgene, complexed with pyridine,261 and 6-amino-l,2,4-triazine-5-car-boxamide, warmed in dioxane, gave a moderate yield of pyrimidino[5,4-e]-as-triazine (157).262 Thiophosgene acted on l-methyl-4-methylaminoimida-zole-5-(lV-methyl)carboxamide to produce, not a thioxopurinone as had been claimed earlier, but an imidazo[4,5-d][l,3]thiazine.263... 

Ureas and Carbonates. Reagent (1) may be used as a direct replacement for the highly toxic Phosgene in reactions with alcohols and amines. Reaction of (1) with two equivalents of a primary aliphatic or aromatic amine at room temperature rapidly yields a symmetrical urea (eq 9). If only one equivalent of a primary amine is added to (1), then the imidazole-Al-carboxamide (4) is formed (eq 10). These compounds can dissociate into isocyanates and imidazole, even at room temperature, and distillation from the reaction mixture provides a useful synthesis of isocyanates (eq 10).7 Secondary amines react only at one side of (1) at room temperature, again giving the imidazole-Al-carboxamide of type... 

Preparation of Acyl Isocyanates and Aryl Isocyanates. Certain primary carboxamides can be converted to acyl isocyanates in yields from 36-97% with the reagent (eq 22) Phosgene gives nitriles under similar conditions. Oxalyl chloride has found limited application for the preparation of triazine and quinone isocyanates. ... 

The preparation of cyanides by dehydration is best accomplished from aldoximes (standard method) rather than from carboxamides, because the former require milder reaction conditions. However, carboxamides, as carboxylic acid derivatives, are more easily accessible. Phosgene has been applied in the dehydration of carboxamides rather than of aldoximes. 

In a series of syntheses of potential antisecretory antidiarrheals, the thiazohne moiety in 1383 was constructed by condensation of 2-aminoethanethiol 1382 with the cyano group in 1381, which was generated from the carboxamide group in 1380 by dehydration with phosgene in 88% yield [1049]. 

Tri-0-acetyl-j8-D-ribofuranosyl)-l,2,3-triazole-4,5-dicarbonitrile 1386, an analogue of the human myeloid leukemia cell growth inhibitor Ribavirin 1384, has been prepared from its carboxamide 1385 by dehydration with phosgene [1050). 

Typical procedure. 2-(2,3,5-Tri-O-acetyl-P-D-ribofuranosyl)-7,2,3-triazole-4,5-dicarbonitrile 1386 [1050] To a cold (—5 °C) solution of carboxamide 1385 (4.7 g, 11.4 mmol) in anhydrous dichloromethane (75 mL) and pyridine (10 mL), a solution of 20% phosgene in toluene (for a safe source, see Chapter 7) (14.7 mL, 30 mmol) was added dropwise with stirring. After the addition was complete (30 min), the reaction mixture was stirred at 0 °C for 2 h. The resulting brown solution was poured onto crushed ice (200 g) and extracted with dichloromethane (3 x 100 mL). The combined organic layers were washed successively with cold 1 n HCl (10 mL), 10% aqueous NaHCOs (2 x 100 mL), and water (2 x 50 mL), and then dried (Na2S04) and concentrated to dryness. Crystallization of the residue from EtOH furnished 3.9 g (90%) of 2-(2,3,5-tri-0-acetyl-/ -D-riboftiranosyl)-l,2,3-triazole-4,5-dicarbonitrile 1386 mp 121 °C. 

Carbamazepine [298-46-4], antiepileptic, anticonvulsant, 31. Phosgene is used to convert 51-f-dibenz[fo,/]azepine 29 to the corresponding 5-carboxamide 31 [31]. 

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