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Org. Synth. 1965, 45, 19
DOI: 10.15227/orgsyn.045.0019
p-CHLOROPHENYL ISOTHIOCYANATE
[Isothiocyanic acid, p-chlorophenyl ester]
Submitted by G. J. M. van der Kerk, C. W. Pluygers, and G. de Vries1.
Checked by W. S. Wadsworth, Jr. and William D. Emmons.
1. Procedure
Caution! 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.
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 (Note 1), 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 (Note 2). 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 water 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 (Note 3). 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 (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 4N 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 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°.
2. Notes
1. A commercial grade (Eastman Organic Chemicals, white label) of p-chloroaniline was used without further purification.
2. The reaction is conveniently started by dipping the flask in a hot-water bath. The reaction temperature is easily maintained by occasional dipping of the flask in a cold-water bath.
3. Any free chloroacetic acid leads to the formation of N-p-chlorophenylrhodanine.
4. A Beckman pH meter (Model N) was used.
5. The anhydrous zinc chloride used was obtained from Baker and Adamson, reagent grade.
6. The pH must not drop below 7, although a slightly higher pH does no harm; addition of the zinc chloride in a shorter time lowers the yield.
3. Discussion
The procedure given here is essentially that described previously by the submitters.2 p-Chlorophenyl isothiocyanate has been prepared from sym-di-p-chlorophenyl thiourea with iodine in alcoholic solution,3 from ammonium p-chlorophenyldithiocarbamate and lead nitrate4 [cf. also Org. Syntheses, Coll. Vol. 1 447 (1932)], by the action of thiophosgene on p-chloroaniline5 and from p-chloroaniline with thiocarbonyl tetrachloride in the presence of stannous chloride.6
4. Merits of the Preparation
The present method has the advantage that the whole process can be carried out in aqueous medium at low temperatures. The procedure is also attractive because of the reagents used and the relatively simple isolation procedure employed. The only restriction observed is that the formation of the aromatic dithiocarbamate must be possible.
Other isothiocyanates obtained by this method are: phenyl isothiocyanate (65%), p-phenylene diisothiocyanate (71%), p-acetylaminophenyl isothiocyanate (73%), p-ethoxyphenyl isothiocyanate (64%), and p-bromophenyl isothiocyanate (55%).

References and Notes
  1. Organisch Chemisch Instituut T.N.O., Utrecht, Nederland.
  2. G. J. M. van der Kerk, C. W. Pluygers, and G. de Vries, Rec. Trav. Chim., 74, 1262 (1955).
  3. S. M. Losanitsch, Ber., 5, 156 (1872).
  4. F. B. Dains, R. Q. Brewster, and C. P. Olander, Univ. Kansas Sci. Bull., 13, 1 (1922) [C.A., 17, 543 (1923)].
  5. G. M. Dyson, Org. Syntheses, Coll. Vol. 1, 165 (1932).
  6. J. M. Connolly and G. M. Dyson, J. Chem. Soc., 679 (1935).

Appendix
Chemical Abstracts Nomenclature (Collective Index Number);
(Registry Number)

petroleum ether

sym-di-p-chlorophenyl thiourea

ethanol (64-17-5)

ammonia (7664-41-7)

ammonium chloride (12125-02-9)

sodium hydroxide (1310-73-2)

sodium carbonate (497-19-8)

stannous chloride

chloroacetic acid (79-11-8)

iodine (7553-56-2)

lead nitrate (10099-74-8)

carbon disulfide (75-15-0)

zinc chloride (7646-85-7)

Thiophosgene (463-71-8)

PHENYL ISOTHIOCYANATE (103-72-0)

p-Chlorophenyl isothiocyanate,
Isothiocyanic acid, p-chlorophenyl ester (2131-55-7)

thiocarbonyl tetrachloride

p-chloroaniline (106-47-8)

phosphorus pentoxide (1314-56-3)

ammonium p-chlorophenyldithiocarbamate

p-bromophenyl isothiocyanate (1985-12-2)

N-p-chlorophenylrhodanine

p-phenylene diisothiocyanate (4044-65-9)

p-acetylaminophenyl isothiocyanate

p-ethoxyphenyl isothiocyanate (3460-49-9)