Acylisocyanates

Acylisocyanates or isothiocyanates undergo cycloaddition with 5-hydroxy-THISs under so mild conditions that isolation of the initial adducts becomes possible (23). In cycloaddition reactions the 5-hydroxy-THISs can be replaced by their precursors (23). 

Of the new methods of preparation of oxo derivatives of the 5,6-dihydro-4//-1,3-oxazines, the most important is that developed by Martin and co-workers 169 the reaction of acylisocyanates with enol ethers at room temperature under nitrogen yields 48 [Eq. (35)] (see also Arbuzov et a/.170-171) together with an isomeric azetidinone. The... 

By reacting an acylisocyanate with dimethylketene, 4,6-dioxo derivatives of 1,3-oxazine (49) were obtained172 [Eq. (36)]. The reaction is exothermic and the temperature was kept below 40°C. 

In contrast to the unreactive 2-(l//)-pyridinone (27), the much more reactive 4-hydroxy-2-( H )-pyridinone (31) (cf. 7 and 8 in Section III,A) is easily aminated by boiling it in excess benzylamine to give 32 in 89% yield (84S765). Some heterocycles, such as methyl-4-oxo-l, 4-dihydroquinoline-2-carboxylate (33), are transformed by ihe very reactive chlorosulfonyl-isocyanate (CSl) or other reactive sulfonyl- or acylisocyanates in acetonitrile of 1,2-dichloroethane at room temperature with evolution of carbon dioxide to intermediates such as 34, which are hydrolyzed by aqueous hydrochloric acid to methyl-4-aminoquinoline-2-carboxylate (35)... 

It is noteworthy that, in the course of our studies on the preparation of acylisocyanates, we put some improvements to the known procedure by condensation of aroyl chlorides with sodium cyanates. We found that special catalysts and solvants must be used for receiving satisfactory yields as depicted in scheme 162 (Ref. 216, 217). 

Amide—> Isocyanate. A general procedure for the conversion of amides into acylisocyanates" provides a route to these compounds more convenient than the reaction of acid chlorides with silver cyanate. In the example formulated a mixture of u-chloroucelamide ami 100 ml. of ethylene dichloride is chilled to about 2" and timiH u/hiia D.6 mala of oxalvl uhlorldo li added all at on c. The mixture I removed... 

During the past twelve months a number of new phosphonium betaines and zwitterions has been reported. Reaction of ylides with acylisocyanates or acylisothiocyanates in methanol proceeds via a cyclization yielding pyrimidine substituted triphenylphosphonium salts (5) which can be converted into the corresponding betaines. The crystal structures of triphenylphosphonium-car-boxylate betaines 6 and 7 have been reported. Betaines 6 and 7 were obtained... 

Addition of phosgene to silyl substituted iminoesters results in the formation of N-chlorocarbonyl-iminoesters, which are decomposed thermally into acylisocyanates [1409] ... 

While an (in terms of the chemical result) analogous formation of azo-arenes does not succeed from 1,4-diaryltetraazadienes 152), nitrogen displacements from N-nitrosoimines are well known and have occasionally been used for the synthesis of carbonyl compounds 153). The early impressive synthesis of 296 (90%)1541 illustrates this clearly. Closely related are the [2,3,l,(2)3]-eliminations of acylthioketenes such as 297 155), acylisocyanates such as 299 (quant.)156), and of thioacylisocyanates such as 301l57), which produce acetylenes (298) and nitriles (300). In all these cases heterocyclobutenes (cf. Scheme 8) have been postulated as intermediates. 

Hetero-l-oxabutadiene systems that have been shown to participate as 47t components of Diels-Alder reactions include vinylnitroso compounds (31, 2-aza-l-oxabutadiene, Chapter 9, Section 3), fV-acylimines (32) as well as aromatic and aliphatic acylisocyanates (33, X = O) and isothiocyanates (33, X = S, 3-aza-l-oxabutadiene, Chapter 9, Section 3), acylnitroso compounds (34,2-aza-l, 4-dioxabutadiene, Chapter 9, Section 3), selected 4-aza-l-oxabutadienes, e.g., 35, including o-quinone monoimines (36,... 

This is in contrast to the reaction of acylisocyanates(RCONCO) with these substrates which as a result of [2+2] cycloaddition followed by loss of carbon dioxide yield acylimines (384). 

Ureas. Acylisocyanates are formed when silver cyanate reacts with acid chlorides. With proper substituents, such products are precursors of uracils. 

The [4+2] cycloaddition of acylisocyanates to isocyanates to give 2,4-dioxo-2,4-2/-l,3 5-oxadiazines is well established <1981BSF28, 1970ZNB1180>. Thus, the water-sensitive 1,3,5-oxadiazine 61, formed from acylisocyanate 284 and phenyl isocyanate, reacts with 0,0-diethyl dithiophosphate to afford the oxadiazine 92 (Scheme 59) <1996SC783>. However, these oxadiazines are difficult to isolate as they undergo rapid decomposition. 

Acylaminoalcohols Acyl formimidates N-Acyliminoesters Acylisocyanates Acyloximes... 

Acylisocyanates from carboxylic acid amides CONHg CON C O... 

Via intermediates Acylisocyanates from iminoesters via N-(chloroglyoxyloyl)immoesters... 

A soln. of oxalyl diloride in CCI4 added dropwise with stirring to a soln. of ethyl nicotinimidate in the same solvent, warmed 0.5 hr. at 50°, the solvent distilled off in vacuo, and the remaining N-(diloroglyoxyloyl)iminoester heated at 110-130° until gas evolution ceases nicotinoylisocyanate. Y 77%. F. e., also from imino-ester hydrochlorides, s. L. I. Samarai et al., Zh. Org. Khim. 6, 85 (1970) C. A. 72, 90006 review of acylisocyanates s. K. A. Nuridzhanyan, Russ. Chem. Rev. 39, 130 (1970) (Eng. transl.). 

PClg added all at once under Ng in the dark to a suspension of vitamin A acid in abs. benzene, stirred 3 hrs. at 20-25°, the resulting soln. of the acid chloride treated with Ag-cyanate, stirred vigorously 5 hrs. in a closed flask in the dark, filtered, the soln. of the acylisocyanate obtained added dropwise during 15 min. to a soln. of hydroxylamine hydrochloride in abs. pyridine, and stirred overnight at room temp, in a closed flask in the dark N-retinoyl-N -hydroxyurea. Y 89.4%. R. Miller, Chem. Therap. 9, 298 (1974). 

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