Carbamoylation

The ester 870 is prepared by the cross-coupling of the chloroformate 869 with an organotin reagent. Some chloroformates are easily decomposed by a Pd catalyst, and hence the reaction should be carried out by slow addition of the chloroformates. Similarly, the amide 872 is prepared by the reaction of the carbamoyl chloride 871 [742]. The coupling of alkylcopper with ethyl chloroformate catalyzed by Pd affords esters[743]. 

The nucleophilic reacbvity of the C-5 oxygen is well documented however, no quantitative data are available. A-2-Thiazoline-5-ones (212) react at oxygen with acetyl chloride or acetic anhydride (447. 452). benzoyl chloride (447). methyl or phenyl isocyanate (467). carbamoyl chloride (453, 467). or phosphorus derivatives (468, 428) in the presence of bases to give 213, 214, 215. or 216 (Scheme 109). Strong bases such as... 

Butylidyne Butyryl or butanoyl) Camphoroyl Carbamoyl Carbazolyl Carbazoyl Carbonimidoyl Carbonohydrazido preferred to carbohydazido or carbazido)... 

Preparation from Amines. The most common method of preparing isocyanates, even on a commercial scale, involves the reaction of phosgene [75-44-5] and aromatic or aUphatic amine precursors. The initial reaction step, the formation of N-substituted carbamoyl chloride (1), is highly exothermic and is succeeded by hydrogen chloride elimination which takes place at elevated temperatures. 

A variation of this method involves the conversion of the amine into the amine hydrochloride prior to treatment with phosgene. This method has the advantage of producing generally cleaner products by retarding the secondary reaction of the free amine with carbamoyl chloride. 

Oligomers of phosgene, such as diphosgene [503-38-8] (COCl2)2, have found use in the laboratory preparation of isocyanates. Carbamoyl chlorides, A[,A/-disubstituted ureas, dimethyl- and diphenylcarbonates, and arylsulfonyl isocyanates have also been used to convert amines into urea intermediates, which are subsequendy pyroly2ed to yield isocyanates. These methods have found appHcations for preparation of low boiling point aUphatic isocyanates (2,9,17). 

Low boiling isocyanates, such as methyl isocyanate [624-83-9] are difficult to prepare via conventional phosgenation due to the fact that the A/-alkyl carbamoyl chlorides are volatile below their decomposition poiat. Interestingly, A/-ethyl carbamoyl chloride decomposes at its boiling poiat whereas the A/-propyl carbamoyl chloride is thermoly2ed cleanly into isocyanate and hydrogen chloride. 

CONH2 amides carbamoyl cyano -amide or carboxamide ... 

Other unsymmetrical peroxides can be prepared by this reaction by employing other acylating agents, eg, alkyl chloroformates, organosulfonyl chlorides, and carbamoyl chlorides (210). Unsymmetrical and symmetrical di(diacyl peroxides) also are obtained by the reaction of dibasic acid chlorides directiy with peroxycarboxyhc acids or monoacid chlorides directiy with diperoxycarboxyhc acids in the presence of a base (44,187,203). 

Bis(carbamoyl) peroxides of the foUowiag structure were prepared by reaction of the corresponding carbamoyl chlorides and hydrogen peroxide—urea complex in the presence of pyridine (211). 

Phosgene reacts with a multitude of nitrogen, oxygen, sulfur, and carbon centers. Reaction with primary alkyl and aryl amines yield carbamoyl chlorides which are readily dehydrohalogenated to isocyanates. Secondary amines also form carbamoyl chlorides. 

The tautomeric character of the pyrazolones is also illustrated by the mixture of products isolated after certain reactions. Thus alkylation normally takes place at C, but on occasion it is accompanied by alkylation on O and N. Similar problems can arise during acylation and carbamoylation reactions, which also favor C. Pyrazolones react with aldehydes and ketones at to form a carbon—carbon double bond, eg (41). Coupling takes place when pyrazolones react with diazonium salts to produce azo compounds, eg (42). 

The principal additive shrink-resist treatment uses the polymer Synthappret BAP (Bayer AG) which is a polypropylene oxide polyurethane containing reactive carbamoyl sulfonates (or isocyanate bisulfite adduct groups, —NHCOSO —Na" ). An aqueous solution of this polymer is padded onto woven fabrics, which are immediately dried. Other polymers may be appHed at the same time to modify the handle. 

R" = -H, 5-0-carbamoyl-2-amino-2-deoxy-L-xylonic acid or the 3-deoxy derivative... 

Cyclization of o-formamidoaldehydes with ammonia leads to unsubstituted [2,3-, whilst another type of aminocyclization involves the 2-halo-3-carbamoyl derivatives such as (176) (75JAP(K)75160296). 

An interesting method for the substitution of a hydrogen atom in rr-electron deficient heterocycles was reported some years ago, in the possibility of homolytic aromatic displacement (74AHC(16)123). The nucleophilic character of radicals and the important role of polar factors in this type of substitution are the essentials for a successful reaction with six-membered nitrogen heterocycles in general. No paper has yet been published describing homolytic substitution reactions of pteridines with nucleophilic radicals such as alkyl, carbamoyl, a-oxyalkyl and a-A-alkyl radicals or with amino radical cations. 

An interesting illustration of a bielectrophile contributing two heteroatoms to the resultant five-membered ring is the 2-alkyl-2-chloro- (or fluoro-) sulfonylcarbamoyl chlorides (212). With methylhydrazine initial attack by the more basic nitrogen occurred on the carbamoyl chloride, and this was followed by base-induced cyclization to 1,2,3,5-thiatriazolidine derivative (213) (77JCR(S)238, 77JCR(M)2813). Other reactions of this type are discussed in Chapter 4.28. 

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