Synthesis of S-alkyl and S-aryl thiocarbamates, one-pot...

Details Synthesis of S-alkyl and S-aryl thiocarbamates, one-pot... Synthesis of S-alkyl and S-aryl thiocarbamates, one-pot...

2003-03-06

2004-02-03

Kumar, Shailendra (Department: 1621)

Organic compounds -- part of the class 532-570 series

Organic compounds

Esters having the thiocarboxylate group, -cx-, wherein the...

C562S555000, C562S556000, C562S027000, C560S012000, C560S132000

Reexamination Certificate

active

06686494

ABSTRACT:

BACKGROUND OF THE INVENTION
1. Field of the Invention
The present invention relates to thiocarbamates and, more specifically, to a synthetic method for preparing S-alkyl and S-aryl thiocarbamates.
2. Description of Related Art
The importance of S-alkyl and S-aryl thiocarbamate compounds as herbicides, pesticides and other biological applications has been recognized for many years. The basic S-alkyl and S-aryl thiocarbamate (S-alkylthiourethane) structure is as follows:
Such compounds have been of interest due to their numerous biological effects including anesthetic, fungicidal, bactericidal, pesticidal and antiviral activity. These compounds are most noted for their use as commercial herbicides and thus have received considerable attention in the literature. See Maeda, T., DE-Pat. 1817662, Kumiai Chemical Industry Co., LTD.;
Chem. Abstr
. 74, 12864 (1970); and U.S. Pat. No. 3,582,314 to Konnai et al., which are incorporated herein by reference. They have been used for control of annual grasses and broadleaf weeds and in large-scale on crops such as rice, celery and lettuce.
Earliest reports make use of phosgene as a starting material; however, this reagent is extremely toxic and hazardous to handle, especially in large quantities. Many reports illustrate the intramolecular rearrangement of various derivatives to afford S-alkyl thiocarbamates; however, these rearrangements are extremely limited in starting substrates. See Kwart, H.; Evans, E. R. J.
Org. Chem
. 1966, 31, 410-413; Newman, M. S.; Karmes, H. A. J.
Org. Chem
. 1966, 31, 3980-3984; Newman, M. S.; Hetzel, F. W. J.
Org. Chem
. 1969, 34, 3604-3606; Hackler, R. E.; Balko, T. W. J.
Org. Chem
. 1973, 38, 2106-2109, all of which are incorporated herein by reference. Similarly, transition metal catalysts containing elements such as palladium, nickel, and rhodium have also been employed to promote rearrangement and product formation. See Jones, W. D.; Reynolds, K. A.; Sperry, C. K.; Lachicotte, R. J.; Godleski, S. A.; Valente, R. R.
Organometallics
2000, 19, 1661-1669; Kuniyasu, H.; Hiraike, H.; Morita, M.; Tanaka, A.; Sugoh, K.; Kurosawa, H. J.
Org. Chem
. 1999, 64, 7305-7308; Böhme, A.; Gais, H.-J.
Tetrahedron: Asymmetry
1999, 10, 2511-2514; and Jacob, J.; Reynolds, K. A.; Jones, W. D.; Godleski, S. A.; Valente, R. R.
Organometallics
2001, 20, 1028-1031, all of which are incorporated herein by reference. There are a variety of other known methods; however, most require the preparation of complex starting materials. See Batey, R. A.; Yoshina-Ishii, C.; Taylor, S. D.; Santhakumar, V.
Tetrahedron Lett
. 1999, 40, 2669-2672, incorporated herein by reference. Carbon monoxide and elemental sulfur are frequently employed in such preparation; however, these methods involve multi-step approaches, which incorporate metal catalysts, or proceed in low yields. The most widely used method for preparation of these compounds makes use of gaseous carbonyl sulfide (COS), which condenses with a secondary amine, followed by subsequent treatment with 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, incorporated herein by reference.
Condensation of a thiol with an isocyanate affords the corresponding thiocarbamate; however, this route was only demonstrated when alkoxy and aroxysulfonyl isocyanates were employed. See Beji, M.; Sbihi, H.; Baklouti, A.; Cambon, A. J.
Fluorine Chem
. 1999, 99, 17-24, incorporated herein by reference. Moreover, the hydration of a variety of organic thiocyanates have been reported to afford the desired compound in the presence of hydrogen chloride; however, this method is limited to only N,N-unsubstituted thiocarbamates. See Zil'berman, E. N.; Lazaris, A. Y.
J. Gen. Chem. USSR
1963, 33, 1012-1014, incorporated herein by reference. S-alkyl thiocarbamates have also been prepared from salts of dithiocarbamic acid, which are prepared by the addition of secondary amines to carbon disulfide (CS
2
). See
Advanced Organic Chemistry
5
th
Ed.; Smith, M. B.; March, J., Eds.; Wiley Interscience: New York, 2001; Chapter 16, incorporated herein by reference. Despite being a novel approach, this method is limited to N,N-disubstituted thiocarbamates. Although there are numerous variations, there lacks a simple comprehensive synthetic approach for the facile preparation of both N-substituted, N,N-disubstituted and N,N-unsubstituted S-alkylthiocarbamates.
SUMMARY OF THE INVENTION
It is the object of this invention to teach a new synthesis method for the preparation of S-alkylthiocarbamate and S-arylthiocarbamate compounds. This is a one-pot two-step general synthesis of thiocarbamate compounds having two routes to the same product compound depending on the order of reagent addition. In the preferred route, a precursor thiol reagent is first reacted with trichloroacetyl chloride to produce an isolatable S-alkyl or S-aryl trichloroacetyl thioester intermediate, which is then reacted with an amine to yield the corresponding thiocarbamate product. In the alternate route, the amine is first reacted with trichloroacetyl chloride to produce an isolatable trichloroacetamide intermediate, which is then reacted with the precursor thiol to yield the corresponding thiocarbamate product. This new method has the following features and advantages: (1) structural generality (i.e. aliphatic or aromatic thiol used in combination with ammonia, a primary or a secondary amine whose substituents may also be aromatic or aliphatic); (2) facile purification; (3) high isolated yields; (4) one-pot two-step simplified procedures; and (5) avoidance of toxic and environmentally objectionable reagents (e.g. phosgene, carbon monoxide, carbonyl sulfide, carbon disulphide).
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
A method of preparing S-alkyl and S-aryl thiocarbamates according to a preferred embodiment of the present invention takes advantage of very facile chemistry involving adduct formation between trichloroacetyl chloride (Cl
3
COCl) and a thiol (1) or an amine (4) followed by a very unique and unexpected chemistry involving nucleophilic displacement of the trichloromethyl moiety as chloroform to yield a variety of thiocarbamate products (3) with various substitutions (R
1
, R
2
and R
3
) on the sulfur and amine sites as illustrated in Scheme 1.
It is the unique and unexpected chemistry of the trichloroacetyl thioester adduct (2) and the trichloroacetamide adduct (5) that form the basis of this invention. These adducts undergo nucleophilic substitution reactions resulting, not in regeneration of the initial thiol or amine precursors as might be expected from the general behavior of esters and amides, but in displacement of the trichloromethyl group as chloroform and formation of the thiocarbamate product (3). As depicted in Scheme 1, these adducts serve as intermediate compounds in two complementary routes to the same product. In the upper route adduct 2 undergoes a nucleophilic displacement reaction with an amine reagent, while in the lower route adduct 5 undergoes a nucleophilic displacement reaction with a thiol. The identity of substituents R
1
, R
2
and R
3
is determined by the selection of the thiol (1) and amine (4) reagents. This new chemistry provides for a preferred (1→2→3) route and an alternate route (4→5→3); the basis for the prefer route being the higher yield.
In the preferred route, the thiol-Cl
3
COCl adduct (2) is prepared by slow addition of an alkyl or aryl thiol to an excess of the Cl
3
COCl at 20° C. and stirred under dry atmosphere until adduct formation is complete. The molar excess of Cl
3
COCl may range from a factor of 1.05 to 10 with 2 being preferred. The adduct formation reaction is mildly exothermic and some external temperature control is advisable, although the temperature need not be rigorously maintained at 20° C. The formation of compound (2) proceeds rapidly without solvent, and the rate of consumption of the thiol is dependent on the thiol chemical s

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