p-Chlorophenyl isothiocyanate (CAS NO.: ), which is also known as , p-chlorophenyl ester, could be produced through the following synthetic routes.

In a 250-ml. round-bottomed flask fitted with mechanical stirrer, reflux condenser, and thermometer are placed 38.3 g. (0.30 mole) of p-chloroaniline, 41 ml. (0.6 mole) of concentrated aqueous ammonia (sp. gr. 0.9), and 21 ml. (0.35 mole) of carbon disulfide. The mixture is stirred vigorously, and when it is heated to 30° the reaction starts. The temperature is maintained at 30–35° by external cooling. The reaction mixture turns into a deep-red turbid solution within a few minutes, and then suddenly a heavy yellow precipitate of ammonium p-chlorophenyldithiocarbamate separates. To the mixture 15 ml. of is added, and stirring is continued for 1 hour. The mixture is filtered with suction, and the residue is washed with two 30-ml. portions of a 3% aqueous solution of ammonium chloride and with two 15-ml. portions of 96% ethanol.

The ammonium p-chlorophenyldithiocarbamate obtained is transferred immediately to a 1-l. beaker fitted with an efficient mechanical stirrer. Water (250 ml.) is added, and the temperature is raised to 30°. A solution of 28.4 g. (0.30 mole) of chloroacetic acid in 30 ml. of water is neutralized with sodium carbonate [18.6 g. (0.15 mole) of Na₂CO₃·H₂O in 70 ml. of water] and is added to the well-stirred dithiocarbamate suspension over a 10-minute period. In the beginning the suspension gradually becomes less viscous, but at the end of the addition it rapidly turns into a creamy mass. Another 250 ml. of water is added to facilitate stirring, which is continued for 1 hour after the addition at about 30°.

The creamy suspension is allowed to cool to room temperature, and the electrodes of a pH meter are inserted. A solution of 20.5 g. (0.15 mole) of zinc chloride 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 4N aqueous solution of sodium hydroxide. 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 p-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°.

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