Benzoyl Isothiocyanate1

[532-55-8]  · C8H5NOS  · Benzoyl Isothiocyanate  · (MW 163.19)

(reactive isothiocyanate for condensation and cyclization reactions to form thioamides, thioureas, and heterocycles)

Physical Data: bp 133-136 °C/18 mmHg; d 1.214 g cm-3.

Solubility: freely sol most organic solvents.

Form Supplied in: liquid or prepared in situ from benzoyl chloride and ammonium thiocyanate.2

Purification: distillation in vacuo.

Handling, Storage, and Precautions: toxic; lachrymatory; handle in fume hood. Moisture sensitive; reacts exothermically with strong bases and amines.

Thiourea Synthesis.

The reaction of anilines and aromatic heterocyclic amines with benzoyl isothiocyanate affords the corresponding N-aryl-N-benzoylthioureas, which can be hydrolyzed under basic conditions to give good to excellent yields of the N-arylthioureas (eq 1).2,3

Reactions of benzoyl isothiocyanate with more basic amines or hydrazines often give mixtures of products derived from reaction at the carbonyl, thus giving rise to benzamide or benzhydrazide derivatives.4

Synthesis of Thioamides.

Benzoyl isothiocyanate reacts with active methylene compounds to give the expected thioamide derivatives. For example, reaction with ethyl cyanoacetate (as the sodium salt) affords thioamide (3) which was readily cyclized with hydrazine to partially protected heterocycle (4) in good yield (eq 2).5 Adducts analogous to (3) are obtained starting with malonitrile (40%) and acetylacetone (55%).

Synthesis of Heterocycles.

Benzoyl isothiocyanate is used in a concise synthesis of biologically active isoguanosine (5) (eq 3).6 Other guanosine analogs can be prepared in similar fashion.7

Aminoguanidine hydrochloride reacts preferentially at the hydrazino group with benzoyl isothiocyanate to give benzoylthiosemicarbazide (6). Cyclization of (6) to either thiadiazole (7) or to triazole (8) is dependent on reaction conditions (eq 4).8

A number of pyrimidines can be synthesized employing benzoyl isothiocyanate as a key reagent. Condensation/cyclization reactions of benzoyl isothiocyanate with imidates9 (eq 5), S,N- and N,N-ketene acetals,10 activated enamines,11 and acetonitriles12,13 give rise to structurally diverse pyrimidine derivatives, in moderate to good yields.

Related Reagents.

Ethoxycarbonyl Isothiocyanate; Methyl Isocyanate.

1. Goerdeler, J. Q. Rep. Sulfur Chem. 1970, 5, 169.
2. Frank, R. L.; Smith, P. V. OSC 1955, 3, 735.
3. Rasmussen, C. R.; Villani, Jr., F. J.; Weaner, L. E.; Reynolds, B. E.; Hood, A. R.; Hecker, L. R.; Nortey, S. O.; Hanslin, A.; Costanzo, M. J.; Powell, E. T.; Molinari, A. J. S 1988, 456.
4. Durant, G. J. JCS(C) 1967, 92.
5. Mohareb, R. M.; Habashi, A.; Ibrahim, N. S.; Sherif, S. M. S 1987, 228.
6. Chern, J.; Lee, H.; Huang, M.; Shish, F. TL 1987, 28, 2151.
7. Bhattacharya, B. K.; Robins, R. K.; Revankar, G. R. JHC 1990, 27, 787.
8. Kurzer, F. JCS(C) 1970, 1805.
9. Elghandour, A. H. H.; Ramiz, M. M. M.; Elnagdi, M. H. S 1989, 775.
10. Aggarwal, V.; Ila, H.; Junjappa, H. S 1982, 65.
11. Mohamed, M. H.; Ibrahim, N. S.; Elnagdi, M. H. H 1987, 26, 899.
12. Elgemeie, G. H.; Abd-El-Aal, F. A. H 1986, 24, 349.
13. Ibrahim, N. S.; Mohamed, M. H.; Elnagdi, H. CI(L) 1988, 270.

Frank J. Villani, Jr.

The R. W. Johnson Pharmaceutical Research Institute, Spring House, PA, USA

Copyright 1995-2000 by John Wiley & Sons, Ltd. All rights reserved.