Isothiocyanates from thiophosgene

Propargyl Isothiocyanate from Pnopargylamine and Thiophosgene CH1CI7, H 0... 

Chlorophenyl isothiocyanate has also been prepared by treating an alcoholic solution of sym-di-/)-chlorophenyl thiourea with iodine/ from ammonium -chloroplienyldithiocarbamate and lead nitrate/ (p. 72), and from the action of thiophosgene with /)-chloroaniline. ... 

In carbohydrate chemistry, the most described method for the preparation of saccharidic thionocarbamates involves preliminary introduction of the amine function on a partially or non-protected saccharidic template. The condensation of amino sugars with carbon disulfide or thiophosgene leads to cyclization in 1,3-oxazolidine- or l,3-oxazine-2-thiones. This reaction involves the formation of an intermediate isothiocyanate, which reacts further with a 3- or y-located hydroxyl group. The viability and facility of this process depends on the saccharidic ring size and the inherent strain. Some major rules can be put into light from the cases studied 30... 

The procedure given here is essentially that described previously by the submitters. -Chlorophenyl isothiocyanate has been prepared from sym-di-p-chloiophenyl thiourea with iodine in alcoholic solution, from ammonium p-chlorophenyldithio-carbamate and lead nitrate [cf. also Org. Syntheses, Coll. Vol. 1 447 (1932)], by the action of thiophosgene on />-chloroaniline and from -chloroaniline with thiocarbonyl tetrachloride in the presence of stannous chloride. ... 

Cyclization of the isothiocyanates obtained from alicyclic )8-amino esters with thiophosgene and 2-chloroethyl or 3-chloropropylamine gave the thia-zolopyrimidinones 464-467 (96UP2). 

Isothiocyanate sulfides, (RNCS)2S, arise similarly from isothiocyanates by successive treatment with bromine in anhydrous chloroform, and hydrogen sulfide158,160 or ethanol.161 The phenyl homolog has also been obtained by the action of thiophosgene on diphenyl-thiourea,162 or aluminum chloride on phenyl isothiocyanate.103... 

Isothiocyanates can be prepared from support-bound primary amines by treatment with thiophosgene [14] or synthetic analogs thereof (Entry 5, Table 14.2). In an alternative two-step procedure, the amine is first treated with CS2 and a tertiary amine to yield an ammonium dithiocarbamate, which is subsequently desulfurized with TsCl or a chloroformate (Entry 6, Table 14.2 Experimental Procedure 14.1). Highly reactive acyl isothiocyanates have been prepared from support-bound acyl chlorides and tetra-butylammonium thiocyanate (Entry 7, Table 14.2). These acyl isothiocyanates react with amines to give the corresponding 7V-acylthiourcas, which can be used to prepare guanidines on insoluble supports (Entry 6, Table 14.3). 

Treatment of o-aminoesters 338 with thiophosgene in chloroform afforded isothiocyanates 339, which were either refluxed with 2-methyl-allylamine in dichloromethane to afford 3-(2-methyl-2-propenyl)thieno-[3,4-d]pyrimidin-4-ones 340, or treated with ethanolamine to yield the 3-(2-hydroxyethyl) derivatives 341. Derivatives 340 were obtained directly from o-aminoesters 338 by heating with allylisothiocyanate in propan-1-ol (89CPB2122). 

The synthesis of BIT was accomplished from etonitazene (51) in two steps. Catalytic hydrogenation afforded the amino derivative (53) [101], which was converted into the isothiocyanate (52) by reaction with thiophosgene [96]. 

Cyclic derivatives have also been prepared from quinoxaline-2,3-dithiones by reaction with phosgene (COClj), thiophosgene (CSCI2), and thionyl chloride (SOCI2). 2,3-Disubstituted quinoxalines result from the reaction of the dithiones with isocyanates, isothiocyanates, and imidoyl chlorides (e.g., PhCCl=NMe). Derivatives of quinoxaline-2,3-dithiones incorporating arsenic, antimony, and tin have been prepared for example, with BujSnCl the 2,3-disubstituted quinoxaline 22 is obtained, and... 

The synthesis of dithioxopyrimidine nucleosides 138 from acetylated /0-D-glucopyranosyl isothiocyanate 89 has been reported by Fuentes and co-workers [149]. J -Glucosylthioamides 137, prepared by reaction of 89 with N-aryl-enaminoesters or enaminones 136 in basic medium, were transformed into glucosyl dithioxopyrimidines nucleosides 138 by treatment with thiophosgene (Scheme 30). The concomitant glycosylamides formation... 

Proquinazid can be prepared starting from 5-iodoanthranilic acid (Scheme 22.3) [27, 32, 33]. Cyclization with n-propyl isothiocyanate affords 2,3-dihydro-6-iodo-3-propyl-2-thioxo-4(lH)-quinazolinone. Alternatively, this key intermediate can be obtained by reaction of an appropriate anthranilate with thiophosgene and n-propylamine. Subsequent introduction of the propoxy substituent via a methyl-ation displacement sequence concludes the synthesis. 

Nitrofluorescein is prepared by the method of Coons and Kaplan [220] from resorcinol and 4-nitrophthalic acid. The two isomers formed are separated by fractional crystallization. The nitro group is reduced as described by McKinney el al. [221]. Finally, fluorescein isothiocyanate is obtained from aminofluorescein by treatment with thiophosgene [222]. 

A few drug discovery synthesis routes were used to diversify the thiohydantoin structures. The first route exploited a convergent concept where a three-component Strecker reaction of an amine, a ketone and trimethylsilyl cyanide was used to generate (he cyanoamine analog 24 (Scheme 1). Isothiocyanate prepared from the amine with thiophosgene was added to the cyanoamine to give thiohydantoin -imine 25 which was hydrolyzed to afford the desired thiohydantoins 26. 

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