[16182-04-0] · C4H5NO2S · Ethoxycarbonyl Isothiocyanate · (MW 131.49)
(highly reactive isothiocyanate for condensation and cyclization reactions to form thioamides, thioureas, and heterocycles1)
Physical Data: bp 44-46 °C/10 mm Hg; d 1.160 g cm-3.
Solubility: freely miscible in most organic solvents.
Form Supplied in: colorless to pale brown liquid.
Purification: distillation in vacuo.
Handling, Storage, and Precautions: exceedingly pungent odor, irritating to eyes and nose; store at 0 °C; slowly decomposed by water; reacts exothermically with alcohols and amines. This reagents should only be handled in a fume hood.
Ethoxycarbonyl isothiocyanate reacts with stoichiometric amounts of ammonia, primary, and secondary amines to afford the expected thioureas in high yield (eq 1).1
Friedel-Crafts thioacylation of aromatics with ethoxycarbonyl isocyanate mediated by Aluminum Chloride gives moderate to good yields of arylthioamides or N-ethoxycarbonylthioamides, dependent on reaction conditions (eq 2).2
The thioamides synthesized by the reaction of cyclic or acyclic enamines with ethoxycarbonyl isothiocyanate can be isolated or carried on further to 4-thiouracils upon treatment with an additional primary amine (eq 3).3,4
Ethoxycarbonyl isothiocyanate is sufficiently reactive for functionalization of urea nitrogens. Treatment of N,N´-disubstituted ureas with ethoxycarbonyl isothiocyanate followed by base-catalyzed ring closure and S-methylation provides a convenient synthesis of 1,3,5-triazine-2,4-diones (eq 4).5
Ethoxycarbonyl isothiocyanate was used as a key starting point in a convenient and multigram synthesis of 1,2,4-oxadiazolidine-3,5-dione (eq 5), a bioisostere for the carboxylic acid group.6
The synthesis of 5-amino-1,2,3-thiadiazoles can be achieved through [3 + 2] cycloaddition of ethoxycarbonyl isothiocyanate with diazo ketones (eq 6).7
The reaction of 2-alkylamino8 and 2-alkylhydrazino9 aza-heterocycles with ethoxycarbonyl isothiocyanate has been used to generate interesting mesoionic species.
Frank J. Villani, Jr.
The R. W. Johnson Pharmaceutical Research Institute, Spring House, PA, USA