P-Chlorophenyl Isothiocyanate

Caution p-Chlorophenyl isothiocyanate may cause severe dermor-iitis if allowed to come in contact with the skin. This preparation should he carried out in a good hood, and rubber gloves should be worn throughout. 

A refluxing soln. of p-chlorophenyl isothiocyanate in dimethyl sulfoxide treated with water during 10 min. 1,3-di-p-chlorophenylthiourea. Y 87%. F. e., also in dimethylformamide, s. D. Martin and W. Mucke, Monatsber. Deut. Akad. Wiss. Berlin 6, 362 (1964) C. A. 62, 3960a. 

A mixture of p-chlorophenyl isothiocyanate and pyridine warmed to 65°, then iodine pentafluoride added dropwise at such a rate as to maintain a temp, of 75-80°, finally stirred 10 min. at 80° thiobis-N-(p-chlorophenyl)-N-(trifluoro-methyl)amine. Y 94-95%. F. e. s. T. E. Stevens, J. Org. Ghem. 26, 3451 (1961). 

The chloroform is then evaporated under reduced pressure and the residual p-chlorophenyl isothiocyanate is recrystallized from ethanol. Yield of this step is 70% of theory, mp 46.5 C. 

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. ... 

The creamy suspension is allowed to cool to room temperature, and the electrodes of a pH meter are inserted (Note 4). A solution of 20.5 g. (0.15 mole) of zinc chloride (Note 5) in 75 ml. of water is added dropwise with vigorous stirring over a period of 45 minutes, while the pH is maintained at 7 by the simultaneous dropwise addition of a 4A aqueous solution of sodium hydroxide (Note 6). The mixture is stirred for 1 hour and is then filtered with suction the solid product is dried under reduced pressure over phosphorus pentoxide. The dry material is slurried with 200 ml. of petroleum ether (b.p. 30-60°), and the solvent is decanted. This process is repeated five times, and the combined extract is evaporated at reduced pressure. The yield of almost pure -chlorophenyl isothiocyanate, obtained as a readily crystallizing oil with a pleasant anise-like odor, is 33-35 g. (65-68%), m.p. 44-45°. The product can be recrystallized from the minimum amount of ethanol at 50°. 

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. ... 

The yields from the reactions, carried out at room temperature and a pressure of 2-4 at, increase with increasing electronegativity of the substituent X. The yield with phenyl isocyanate is 13%, with p-chlorophenyl isocyanate 55% and with p-nitrophenyl isocyanate it is 100%. Primary and secondary carba-moylphosphines cannot be isolated even when equi-molar quantities of phosphine and isocyanate are used. Their intermediate formation is probable but apparently they are more reactive towards isocyanates than phosphine itself. Similarly, phosphine does not react with free cyanic acid whereas primary and secondary phosphines react with cyanic acid, as with isocyanates, to form the corresponding carbamoylphosphines Attempts to make phosphine react with phenyl isothiocyanate did not succeed... 

Perhydro-imidazo[l,5-fl]pyridines of type 109 are obtained from -p-chlorophenyl-2-piperidyl ketone (108) and phenyl isocyanate. The 3-thioxo analogues (110) are prepared using phenyl isothiocyanate (70USP3494926). 

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