US006686494B1 (12) United States Patent (10) Patent No.: US 6,686,494 B1 Wynne et al. (45) Date of Patent: Feb. 3, 2004 (54) SYNTHESIS OF S-ALKYLANDS-ARYL Hitoshi Kuniyasu, Hiroshi Hiraike, Masaki Morita, Aoi THIOCARBAMATES, ONE-POTTWO-STEP Tanaka, Kunihiko Sugoh & Hideo Kurosawa, “Palladium GENERAL SYNTHESIS Catalyzed Azathiolation of Carbon Monoxide,” J. Org. Chem., 1999, 64, 7305-7308. (75) Inventors: James W. Wynne, Alexandria, VA Achim Bohme & Hans-Joachim Gais, “Palladium(O) cata (US); Arthur W. Snow, Alexandria, VA lyzed enantioselective rearrangement of O-allylic thiocar (US) bamates to S-allylic thiocarbamates: asymmetric Synthesis (73) Assignee: The United States of America as of allylic thiols.” Tetrahedron: Asymmetry, 1999, 10, represented by the Secretary of the 2511-2514. Navy, Washington, DC (US) Josemon Jacob, Kelly A. Reynolds, William D. Jones, Stephen A. Godleski & Ronald R. Valente, “Nickel-Medi (*) Notice: Subject to any disclaimer, the term of this ated Selective Carbonylation Routes to Thiocarbamates.” patent is extended or adjusted under 35 Organometallics, 2001, 20, 1028-1031. U.S.C. 154(b) by 0 days. Robert A. Batey, Chiaki Yoshina-Ishii, Scott D. Taylor & V. Santhakumar," A New Protocal for the Formation of Car (21) Appl. No.: 10/384,928 bamates and Thiocarbamates using Carbamoyl Imidazolium Salts.” Tetrahedron Lett., 1999, 40, 2669-2672. (22) Filed: Mar. 6, 2003 T. Indrasena Reddy, B. M. Bhawal & S. Rajappa, “A Facile (51) Int. Cl." ..................... C07C 315/00; CO7C 317/00; General Method for the Preparation of S-Methyl Thiolcar C07C 229/00; CO7C 333/00 bamates using Zeolite Catalysts.” Tetrahedron Lett., 1992, (52) U.S. Cl. ....................... 558/232; 562/555; 562/556; 33, 2857-2860. 562/27; 560/12; 560/132 M. Beiji, H. Sbihi, A. Baklouti & A. Cambon, “Synthesis of (58) Field of Search ................................. 562/553,555, F-alkyl N-sulfonyl carbomates and thiocarbamates,” J. 562/556, 27; 558/232; 560/12, 132 Fluorine Chem., 1999, 99, 17–24. E. N. Zil Berman & A. Ya. Lazaris, “The Reaction of (56) References Cited Organic Thiocyanates with Water in Presence of Hydrogen U.S. PATENT DOCUMENTS Chloride,” J. Gen. Chem. USSR, 1963, 33, 1012–1014. Advanced Organic Chemistry 5th Ed., Michael B. Smith and 3,582,314 A 6/1971 Konnai et al. Jerry March, Eds., Wiley Interscience: New York, 2001, OTHER PUBLICATIONS Chapter 16. Maeda, DE-Pat. 1,817,662, Kumiai Chemical Industry Co., Primary Examiner Shailendra Kumar LTD., Chem. Abstr. 74, 12864 (1970). ASSistant Examiner Karl Puttlitz Harold Kwart & E. Robert Evans, “The Vapor Phase Rear rangement of Thioncarbonates and Thioncarbamates,” J. (74) Attorney, Agent, or Firm John J. Karasek; Rebecca Org. Chem., 1966, 31, 410–413. L. Forman Melvin S. Newman & Harold A. Karnes, “The Conversion (57) ABSTRACT of Phenols to Thiophenols via Dialkylthiocarbamates,” J. Org. Chem., 1966, 31, 3980–3984. A method for preparing S-alkyl and S-aryl thiocarbamates Melvin S. Newman & Frederick W. Hetzel, “Preparation of comprising reacting a precursor thiol reagent with trichlo Olefins by Pyrolysis of O-Alkyl Dimethylthiocarbabmates.” roacetyl chloride to produce an S-alkyl and S-aryl trichlo J. Org. Chem., 1969, 34, 3604-3606. roacetyl thioester intermediate, which is reacted with an R. E. Hackler & T. W. Balko, “The 3.3-Sigmatropic amine to yield the corresponding thiocarbamate product. Rearrangement of Allylic Dialkylthiocarbamates,” J. Org. Also disclosed is the method for preparing S-alkyl and Chem., 1973, 38, 2106-2109. S-aryl thiocarbamates comprising reacting an amine with William D. Jones, Kelly A. Reynolds, Caroline K. Sperry, trichloroacetyl chloride to produce a trichloroacetamide Rene J. Lachicotte, Stephen A. Godleski & Ronald R. intermediate, which is then reacted with the precursor thiol Valente, “Selective Carbonylation Routes to Thiocarbam to yield the corresponding thiocarbamate product. ates. An Alternative to Phosgene,” Organometallics, 2000, 19, 1661-1669. 20 Claims, No Drawings US 6,686,494 B1 1 2 SYNTHESIS OF S-ALKYLAND S-ARYL gaseous carbonyl sulfide (COS), which condenses with a THIOCARBAMATES, ONE-POTTWO-STEP Secondary amine, followed by Subsequent treatment with GENERAL SYNTHESIS base and an alkyl halide. This three-step process is limited to secondary amines. See Reddy, T, I., Bhawal, B. M.; Rajappa, S. Tetrahedron Lett. 1992, 33, 2857-2860, incor BACKGROUND OF THE INVENTION porated herein by reference. 1. Field of the Invention Condensation of a thiol with an isocyanate affords the The present invention relates to thiocarbamates and, more corresponding thiocarbamate; however, this route was only Specifically, to a Synthetic method for preparing S-alkyl and demonstrated when alkoxy and aroxySulfonyl isocyanates S-aryl thiocarbamates. were employed. See Beiji, M.; Sbihi, H.; Baklouti, A.; Cambon, A. J. Fluorine Chem. 1999, 99, 17-24, incorpo 2. Description of Related Art rated herein by reference. Moreover, the hydration of a The importance of S-alkyl and S-aryl thiocarbamate com variety of organic thiocyanates have been reported to afford pounds as herbicides, pesticides and other biological appli the desired compound in the presence of hydrogen chloride; cations has been recognized for many years. The basic 15 however, this method is limited to only N,N-unsubstituted S-alkyl and S-aryl thiocarbamate (S-alkylthiourethane) thiocarbamates. See Zilberman, E. N.; Lazaris, A.Y.J. Gen. Structure is as follows: Chem. USSR 1963, 33, 1012–1014, incorporated herein by reference. S-alkyl thiocarbamates have also been prepared O from Salts of dithiocarbamic acid, which are prepared by the addition of Secondary amines to carbon disulfide (CS). See R us Y R2 Ns N Advanced Organic Chemistry 5' Ed.; Smith, M.B.; March, J., Eds.; Wiley Interscience: New York, 2001; Chapter 16, Ye incorporated herein by reference. Despite being a novel approach, this method is limited to N,N-disubstituted thio Such compounds have been of interest due to their numerous 25 carbamates. Although there are numerous variations, there biological effects including anesthetic, fungicidal, lacks a simple comprehensive Synthetic approach for the bactericidal, pesticidal and antiviral activity. These com facile preparation of both N-substituted, N,N-disubstituted pounds are most noted for their use as commercial herbi and N,N-unsubstituted S-alkylthiocarbamates. cides and thus have received considerable attention in the literature. See Maeda, T, DE-Pat. 1817662, Kumiai Chemi SUMMARY OF THE INVENTION cal Industry Co., LTD.; Chem. Abstr. 74, 12864 (1970); and U.S. Pat. No. 3,582,314 to Konnai et al., which are incor It is the object of this invention to teach a new synthesis porated herein by reference. They have been used for control method for the preparation of S-alkylthiocarbamate and of annual grasses and broadleaf weeds and in large-scale on S-arylthiocarbamate compounds. This is a one-pot two-step crops. Such as rice, celery and lettuce. 35 general Synthesis of thiocarbamate compounds having two Earliest reports make use of phosgene as a starting routes to the same product compound depending on the material; however, this reagent is extremely toxic and haz order of reagent addition. In the preferred route, a precursor ardous to handle, especially in large quantities. Many reports thiol reagent is first reacted with trichloroacetyl chloride to illustrate the intramolecular rearrangement of various produce an isolatable S-alkyl or S-aryl trichloroacetyl derivatives to afford S-alkylthiocarbamates; however, these 40 thioester intermediate, which is then reacted with an amine rearrangements are extremely limited in Starting Substrates. to yield the corresponding thiocarbamate product. In the See Kwart, H.; Evans, E. R. J. Org. Chem. 1966, 31, alternate route, the amine is first reacted with trichloroacetyl 410-413; Newman, M. S.; Karmes, H. A. J. Org. Chem. chloride to produce an isolatable trichloroacetamide 1966, 31,3980–3984; Newman, M. S.; Hetzel, F. W. J. Org. intermediate, which is then reacted with the precursor thiol Chem. 1969, 34, 3604-3606; Hackler, R. E.; Balko, T. W. J. 45 to yield the corresponding thiocarbamate product. This new Org. Chem. 1973, 38, 2106–2109, all of which are incor method has the following features and advantages: (1) porated herein by reference. Similarly, transition metal cata Structural generality (i.e. aliphatic or aromatic thiol used in lysts containing elements Such as palladium, nickel, and combination with ammonia, a primary or a Secondary amine rhodium have also been employed to promote rearrangement whose Substituents may also be aromatic or aliphatic); (2) and product formation. See Jones, W. D.; Reynolds, K. A.; 50 facile purification; (3) high isolated yields; (4) one-pot Sperry, C. K.; Lachicotte, R. J.; Godleski, S.A.; Valente, R. two-step simplified procedures; and (5) avoidance of toxic R. Organometallics 2000, 19, 1661-1669; Kuniyasu, H.; and environmentally objectionable reagents (e.g. phosgene, Hiraike, H., Morita, M.; Tanaka, A., Sugoh, K., Kurosawa, carbon monoxide, carbonyl Sulfide, carbon disulphide). H. J. Org. Chem. 1999, 64, 7305-7308; Böhme, A.; Gais, H.-J. Tetrahedron: Asymmetry 1999, 10, 2511-2514; and 55 DETAILED DESCRIPTION OF THE Jacob, J.; Reynolds, K. A.; Jones, W. D., Godleski, S. A.; PREFERRED EMBODIMENTS Valente, R. R. Organometallics 2001, 20, 1028–1031, all of which are incorporated herein by reference. There are a A method of preparing S-alkyl and S-aryl thiocarbamates variety of other known methods;