Cyanoketenes

If the substituent at the 3-position is a group that can be eliminated as an anion (such as Cr, CN and NJ), the reaction proceeds without the cleavage of the C(3)—C(4) bond in the isoxazole ring and involves the ejection of the 3-substituent as an anion. For example, 3-cyanoisoxazole (114) reacted with sodium ethoxide at room temperature to give ethyl cyanoacetate (115) via an intermediate cyanoketene (32G436). 

The first /3 -lactam was produced by addition of a ketene to an imine and there are now many examples of this type of approach. The ketenes are most frequently generated in situ from acid chlorides by dehydrohalogenation, but have also been produced from diazo ketones, by heating of alkoxyacetylenes and in the case of certain cyanoketenes by thermolysis of the cyclic precursors (162) and (163). 

The Discussion contains comments on the stability of ierl-butyl-cyanoketene in various solvents. 

A novel synthesis of alkylsulfanylisothiazoles 230 starts with sodium a-cyanoketene dithiolates 227, obtained by the reaction of cyanoacetamides 226 with carbon disulfide in the presence of sodium ethoxide <06SC825>. Treatment of 227 with sulphur and piperidine acetate generates sodium isothiazole-3,5-dithiolates 229. The formation of 229 is assumed to arise from the addition of anionic sulphur to the nitrile group in 227 to give the intermediate 228, which cyclizes upon elimination of anionic sulphur to yield 229. Salts 229 are readily alkylated to furnish 3,5-bis(alkylthio)isothiazole derivatives 230. 

Another reactive ketene which undergoes efficient cycloaddition with allenes is tert-butyl-cyanoketene (TBCK). Again mixtures of isomeric cycloadducts are obtained when unsymmet-rically substituted or 1,3-disubstituted allenes are employed.10-12... 

Cyanoketen dimethyl acetal Acid hydrolysis w 1968 Also general catalysis by acetic acid... 

Diphenylketene . s0-151.155-156) 9-fluorenylidene ketene156) and cyanoketenes (112)l53) have been thoroughly studied. In all cases, the silylated, germylated and stannylated ynamines add across the carbonyl group of ketenes to furnish a whole series of new vinyl ynamines 67 and of ynamine ketones 68 (110) upon mild hydrolysis (110-113). 

General acid catalysis is also clearly observable [47] in the hydration of cyanoketene dimethylacetal and other ketene acetals (24), viz. 

Cyanoketenes are conveniently prepared - by thermolysis of 2,S-diazido-l,4-quinones or 4-azido-3-halo(or phenoxy)-5-methoxy-(5 -furan-2-ones in refluxing benzene (Scheme 5). 

With the exception of r-pentyl- and r-butyl-cyanoketenes, which are stable to self-condensation, cyanoketenes are generally generated in situ Reactions with imines, formimidates and thioformimidates yield the corresponding 3-cyano-2-azetidinones (equations 16-18). The reactions proceed stereoselec-tively, yielding p-lactams having the 3-cyano and 4-protio substituents in a trans relationship. ... 

The dicyanomethylene substituent as well as its ester analog can cause a substantial shift of the tautomeric equilibrium in the pyrimidine moiety. Dicyanomethylene derivatives and their ester analogs 38 were prepared (1988GEP249020, 1988GEP249021, 1988GEP249022) by reactions of compounds 35 successively with (di)cyanoketene dithioacetal followed by cyclization of intermediate 39 in the presence of bases. 

Values for Acetic Acid Catalysis of Hydrolysis of Cyanoketen Dimethyl Acetal... 

Figure 26 The thermal rearrangement of 3,4-dihydro- laH-azirinef 2,3-cJpyrrol-2-one to yield the cyanoketene-formaldimine complex (Reproduced by permission of Wiley)...

The unusual incorporation of the cyano group of l-butyl cyano ketene was observed in the reaction of an azomethine with excess of r-butyl cyanoketene resulting in pyrimido[6,l-d][l,3,5] dioxazine (29). It was said to proceed via an intermediate adduct (98), which further underwent [2 + 2 + 2] cycloaddition in the presence of two molecules of ketene (Scheme 10) <78CC820). 4-Isothiocyanato-4-methyl-2-pentanone and A -(2-hydroxyethyl)hydrazine in refluxing ethanol led to... 

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