Carbamoyl isothiocyanates

Synthesis.—From Thid)carbamoyl Isothiocyanates. Carbamoyl isothiocyanates and thiocarbamoyl isocyanates are thermally interconvertible X-CS NCO X CO NCS.i2 In an extensive study of the preparation and chemical behaviour of these reagents, their use in heterocyclic synthesis was evaluated. 2 ... 

A recent paper from Katritsky summarises all the preparations of achiral dissymmetrical thioureas and proposes a new one, based on l-(alkyl/arylthio-carbamoyl)benzotriazoles, which act as masked isothiocyanates. As described in the previous section, other N-heterocyclic derivatives can be used instead... 

Ethyl 4-oxo-6,7,8,9-tetrahydro-4//-pyrido[l,2-n]pyrimidine-3-carboxyl-ate was alkylated at position 9 with isocyanates and isothiocyanates, occasionally in the presence of sodium hydride.306,320 The 9-carbamoyl compounds exhibited triple tautomerism between forms 251 and 253.320... 

Another variation of the dipolar cycloaddition approach is reaction of carbamoyl isothiocyanates with diazomethane (equation 28) (73SST(2)717). Yields in these reactions are in the range 40-60%, making this route most worthy of synthetic note. 

Trimethylindolenine and its 5-methyl-, 5-chloro- and 7-chloro derivatives react with phenyl isocyanate and various acyl isocyanates and isothiocyanates to give 75-97% of the corresponding l-carbamoyl-2-methyleneindolines (52), which isomerize to the 2-(carbamoylmethylene) indolines (53) (41-85% yield).52 Whether these Fischer s base derivatives after further N-alkylation will condense with salicylaldehydes to form spiropyrans is not known. 

Primary or secondary aminopyrazines may be converted directly into ureido- or thioureidopyrazines by treatment with isocyanates or isothiocyanates primary aminopyrazines may also be converted into such products indirectly via the corresponding isocyanato- or isothiocyanatopyrazines piperazines may be converted into 1/4-carbamoyl- or thiocarbamoylpiperazines by treatment with isocyanates, A-nitrourea, or isothiocyanates and aminopyrazines may be converted into guani-dinopyrazines by treatment with. S -methylisothiourcas or cyanamide. These processes (and some subsequent intramolecular cyclizations or other reactions) are illustrated in the following examples ... 

With isocyanates and isothiocyanates, attack at the nitrogen is again observed. Phenyl isocyanate reacted with 2-alkyl-3-aminoacroleins to afford the JV-carbamoyl derivatives which could not be cyclized to pyrimidinones244 (equation 174). 

In contrast to the acylation with carboxylic acid chlorides, secondary 1,1-enediamines react with isocyanates and isothiocyanates to give cleanly the /7-carbon acylated products. Carbamoyl-substituted enediamines (175) have been obtained from 174 and arylsulfonyl isocyanates (equation 67)140,141. 

The final step in the degradation of uracil requires the presence of /3-ureidopropionase, the enzyme that catalyzes the hydrolysis of TV- carbamoyl-/3-alanine to /3-alanine, CO2, and ammonia. This assay measures the phenyl-isothiocyanate (Edman reagent) derivative of /3-alanine. 

Some ureido- and thioureidopyrazines have been prepared from aminopyrazines with phenyl isocyanate in pyridine, potassium thiocyanate in acid solution, and with phenyl or isopropyl isothiocyanate in pyridine. Thus 2-amino-3-carbamoyl(and jV-benzylcarbamoyl)-5,6-diphenylpyrazines refluxed with phenyl isocyanate in... 

The kinetics of the carbamoylation reaction of alkyl isothiocyanates with diphenylphosphinic hydrazide, Ph2P(0)NHNH2, in benzene, and of the same reaction in the presence of saturated nitrogen heterocycles (as catalysts), have been studied in detail. 

Trioxopyrido[3,2, 4,5]thieno[3,2-<7]pyrimidin-4(3//)-ones were synthesized by the reactions of 3-amino-2-ethoxycarbonylthieno[2,3-Z>]pyridines with isothiocyanates (1997JHC937) or by the reactions of 3-amino-2-cyano(carbamoyl)thieno[2,3-Z>]pyridines with carbon disulfide (1998M523). An analogous reaction of 2-amino-thiophene-3-carboxamide with carbon disulfide yielded thioxopyrimidinone 10 (1990PS181, 1993MI1). 

The amino nitrogen of 2,3,4,5-tetrahydropyridazines behaves normally and reacts with methyl isothiocyanate to give the 2-(Af-methylthiocarbamoyl) derivative <84JHC889>. Similarly, both 1,2,3,6-tetrahydropyridazine and its 1 -ethoxycarbonyl derivative react with arylisocyanates (Scheme 43) to give high yields of aryl carbamoyl derivatives <93JHC45>. 

Various alkyl isothiocyanates formed on enzymatic hydrolysis of non-indolyl glucosinolates of rapeseed were determined by GC-MS d70 Carbamoyl isothiocyanates (24) in solution exist in equilibrium with thiocarbamoyl cyanates (25). This equilibrium is well established at 80-90 °C. The species have distinct absorption bands in the IR region at 1980 and 2240 cm for 24 and 25, respectively ... 

However, the reaction proceeds preferentially via route (a), as evidenced by the isolation of 72 % of the tetrameric cyanogen chloride XXXVIII. The triazine derivative XXXVIII can also be obtained by chlorination of the corresponding isothiocyanate C% A somewhat lower yield of the triazinyl-bis-carbonimidoyl chloride was obtained in the chlorination of 2,6-bis(di-methylamino)-4-chloro-l,3,5-triazine ( ). If cyclic carbamoyl chlorides, or carbamoyl chlorides having alkyl substituents other than methyl are chlorinated, the expected imidoyl chlorides are obtained For... 

Equimolar amounts of imidazoline-2-thione, Hg-bis(phenylacetylide), and phenyl isothiocyanate refluxed ca. 0.5 hr. in pyridine 3-phenyl-7-phenyl(thio-carbamoyl)-5,6-dihydroimidazo[2,l-b]thiazolium betaine. Y 75%. W. Ried, W. Merkel, and S. Park, A. 1975, 79. 

Carbamoyl isothiocyanates (6) similarly afford 40—60% yields of substituted 1,2,3-thiadiazoles of type (7), the structure of which is confirmed by an independent synthesis from the appropriate urethane (8). 

The carbamoyl isothiocyanates (6) thus react without isomerizing to the corresponding thiocarbamoyl isocyanates (compare thiazoles, p. 616). 

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