Organic compounds -- part of the class 532-570 series – Organic compounds – Amino nitrogen containing
Reexamination Certificate
2001-12-17
2003-04-01
O'Sullivan, Peter (Department: 1621)
Organic compounds -- part of the class 532-570 series
Organic compounds
Amino nitrogen containing
C548S263200
Reexamination Certificate
active
06541667
ABSTRACT:
FIELD OF THE INVENTION
This invention relates to processes for preparing thioamides. More particularly, the invention relates to process for preparing a thioamide of the formula (I):
wherein R is an aryl or a heteroaryl radical. The process includes the step of mixing a nitrile with an aqueous solution comprising a sulfide and water.
BACKGROUND OF THE INVENTION
Thioamides may be used as fungicides, herbicides or as intermediates in the synthesis of thiazoles. Thioamides may also be employed as intermediates for preparing pharmaceuticals and crop protection agents.
Abbas and Edward, Can. J. Chem., 63:3075-3078 (1985) teach that thioamides may be prepared from nitriles by heating under pressure with an alcoholic solution of an alkali-metal hydrosulfide or an ammonium or substituted ammonium hydrosulfide. Abbas and Edward also teach that thioamides may be prepared by bubbling hydrogen sulfide through solutions of substituted benzonitriles in pyridine containing triethylamine.
Levesque et al., U.S. Pat. No. 4,618,416, teach thioamides can be prepared by dissolving a thioester into a solvent and adding amine.
Linker et al., U.S. Pat. Nos. 5,475,115, 5,639,891 and 5,739,349, teach that triazolinethiones can be prepared by reacting carboxylic acids with alkylthiosemicarbazides.
Linker et al., U.S. Pat. No. 6,077,813, disclose substituted aromatic thiocarboxcylic acid amides and their use as herbicides. Linker et al. teach the substituted aromatic thiocarboxcylic acid amides are prepared by, reacting substituted aromatic nitriles with hydrogen sulfide (H
2
S) or with thioacetamide.
Jackson et al., U.S. Pat. No. 5,723,663, disclose a process for preparing an aliphatic thioamide which entails reacting an aliphatic nitrile with hydrogen sulfide.
Lai et al., U.S. Pat. No. 5,945,436, teach thioamides can be prepared by treating a nitrile in an inert solvent with a steady stream on hydrogen sulfide gas, catalyzed by a secondary amine.
Unfortunately, many of the prior art processes for the preparation of thioamides require the use of large amounts of hydrogen sulfide gas, and thus raise concerns regarding safety and/or difficulty of handling the gas. Many prior art processes require solvents such as dry ethanol or pyridine, and the presence of water adversely affects the reaction. Other prior art processes require that the process occur under high pressure. Thus there is a need for improved methods of preparing thioamides, particularly methods which do not require organic amines or large amounts of hydrogen sulfide gas.
SUMMARY OF THE INVENTION
Accordingly, it is an object of the present invention to obviate problems of the prior art.
It is a further object of the present invention to provide processes for the preparation of thioamides which do not require high pressures.
It is another object of the present invention to provide processes for the preparation of thioamides which do not require the use of and/or generate large quantities of hydrogen sulfide gas.
These and additional objects are provided by the processes of the present invention.
In accordance with one aspect of the invention there are provided processes for preparing a thioamide of the formula (I):
wherein R is an aryl or a heteroaryl radical, comprising the step of mixing a nitrile of the formula (II):
R—CN (II)
wherein R is an aryl or a heteroaryl radical, with an aqueous solution comprising a sulfide and water.
In accordance with another aspect of the invention there are provided processes for preparing a thioamide of the formula (I):
wherein R represents an aryl or a heteroaryl radical, comprising the step of reacting under pH controlled conditions a nitrile of the formula (II):
R—CN (II)
wherein R represents an aryl or a heteroaryl radical, with a compound selected from the group consisting of sodium hydrogen sulfide, potassium hydrogen sulfide, ammonium sulfide, disodium hydrogen sulfide, dipotassium hydrogen sulfide, and combinations thereof.
The processes of the invention are advantageous in that the process can occur in the presence of water, and in that handling of large quantities of hydrogen sulfide gas is avoided.
The processes of the invention are advantageous in that the process can occur without the need for high pressures.
These and additional aspects, objects and advantages of the invention are more fully described in the following detailed description.
DETAILED DESCRIPTION
Processes in accordance with the present invention comprise the step of mixing a nitrile of the formula (II):
R—CN (II)
wherein R is an aryl or a heteroaryl radical, with an aqueous solution comprising a sulfide and water to obtain a thioamide of the formula (I):
wherein R represents an aryl radical or a heteroaryl radical.
While not being bound by theory, it is believed that the nitrile reacts with a first sulfide to form a thioamide salt, and that the thioamide salt deprotonates a second sulfide and generates Na
2
S. The reaction is believed to be as set forth in Reaction Sequence 1, below:
The reaction can occur in the absence of added acid, however, the slow addition of acid to the mixture of nitrile, sulfide and water is believed to assist in driving the reaction to completion.
The aryl and heteroaryl radical contain from about 5 to about 7, preferably from about 5 to about 6, atoms in the ring moiety. As used herein, “heteroaryl radical” refers to an aromatic ring comprising at least one ring atom which is other than carbon, such as a ring comprising a sulfur, oxygen or nitrogen atom. As used herein, “aryl radical” is intended to include substituted and unsubstituted aryl radicals, and “heteroaryl radical” is intended to include substituted and unsubstituted heteroaryl radicals. Suitable substituents include, but are not limited to, halogen, hydroxyl, alkyl, alkenyl, alkinyl, alkoxy, aryl, aryloxy, alkylsulphonyl, arylsulphonyl, alkanediyl, alkenediyl, alkinediyl, cycloalkanediyl, cycloalkenediyl, arenediyl, amino, cyano, isocyano, thiocyano, nitro, carboxyl, carbamoyl, thiocarbamoyl, sulpho, halogensulphonyl, alkylsulphinyl, alkylsulphonyl, alkylamino, dialkylamino, alkoxycarbonyl, dialkoxy(thio)phosphoryl, alkenyl, alkenyloxy, alkenylamino, alkylideneamino, alkenyloxycarbonyl, alkinyl, alkinyloxy, alkinylamino, alkinyloxycarbonyl, cycloalkyl, cycloalkyloxy, cycloalkylalkyl, cycloalkylalkoxy, cycloalkylideneamino, cycloalkyloxycarbonyl, cycloalkylalkoxycarbonyl, arylalkyl, arylalkoxy, aryloxycarbonyl, arylalkoxycarbonyl, heterocyclyl, heterocyclylalkyl, heterocyclylalkoxy or heterocyclylalkoxycarbonyl, and monocyclic or bicyclic, saturated or unsaturated heterocyclyl, heterocyclylamino and heterocyclylimino.
The aryl or heteroaryl radical may be substituted with fluorine, chlorine, bromine, iodine, hydroxyl, C
1-4
-alkyl, C
3-4
-alkenyl, C
3-4
-alkinyl, C
1-4
-alkoxy, phenyl, or C
1-4
-alkylsulphonyl or phenylsulphonyl. The aryl or heteroaryl radical may be also be substituted with unsubstituted or substituted fluorine- or chlorine-substituted C
1-6
-alkanediyl, C
2-6
-alkenediyl, C
2-6
-alkinediyl, C
3-6
-cycloalkanediyl, C
3-6
-cycloalkenediyl or phenylene; unsubstituted or halogen- or C
1-4
-alkoxy-substituted alkyl, alkoxy, alkylthio, alkylsulphinyl, alkylsulphonyl, alkylamino, dialkylamino, alkoxycarbonyl or dialkoxy(thio)phosphoryl having in each case 1 to 6 carbon atoms in the alkyl groups; unsubstituted or halogen-substituted alkenyl, alkenyloxy, alkenylamino, alkylideneamino, alkenyloxycarbonyl, alkinyl, alkinyloxy, alkinylamino or alkinyloxycarbonyl having in each case 2 to 6 carbon atoms in the alkenyl, alkylidene or alkinyl groups; unsubstituted or halogen-, cyano-, carboxyl-, C
1-4
-alkyl- and/or C
1-4
-alkoxy-carbonyl-substituted cycloalkyl, cycloalkyloxy, cycloalkylalkyl, cycloalkylalkoxy, cycloalkylideneamino, cycloalkyloxycarbonyl or cycloalkylalkoxycarbonyl having in each case 3 to 6 carbon atoms in the cycloalkyl groups and optionally 1 to 4 carbon atoms in the alkyl groups; or unsubstituted or nitro-, cyano-, carboxyl-, halogen-, C
1-4
-alkyl-, C
1-4
-halogenoalkyl-, C
1-4
-a
Bayer Corporation
Gil Joseph C.
Henderson Richard E. L.
O'Sullivan Peter
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