Isothiocyanates, reaction with malonate

Dihydrazide 231 was also used in the synthesis of thienothiophenes containing triazole substituents. For example, the reaction with phenyl isothiocyanate in ethanol produces di(A -phenylthiocarbamoyl)carbohydrazide 238, whose treatment with KOH followed by acidification affords compound 239. Diazotization of dihydrazide 231 with 10% sodium nitrite in acetic acid gives diazide 240. The reactions of the latter with compounds containing the active methylene group, viz., ethyl cyanoacetate, malononitrile or diethyl malonate, in the presence of sodium ethoxide, yield the corresponding ditriazole derivatives 241-243. 

Dimethyl malonate was first treated dropwise with phenyl isothiocyanate in the presence of sodium hydride in N,7V-dimethylacetamide at 0°C. The reaction mixture was stirred at ambient temperature for 1.5 hr and then cooled to 0°C, and methyl iodide was added dropwise. After stirring for 4 hr at room temperature, (methylthio)(phenylamino)methy-lenemalonate (341) was obtained in 79% yields (69T4649). 

Diethyl sodiomalonate, prepared from diethyl malonate and sodium hydride, was reacted with isothiocyanate (528) in DMF by dropwise addition at 5°C. The reaction mixture was then stirred at ambient temperature for 1 hr to give (l,3,5-thiadiazepin-2-ylidene)malonate (529) in 76% yield (86S817). 

A similar reaction was carried out with 3a-iodo-5a-androstan-2/3-yl isothiocyanate and di-(7er/-butyl) malonate to give (andost-2-eno[2,3-[Pg.132]

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