Organic compounds -- part of the class 532-570 series – Organic compounds – Amino nitrogen containing
Reexamination Certificate
1999-12-10
2001-12-04
Padmanabhan, Sreeni (Department: 1621)
Organic compounds -- part of the class 532-570 series
Organic compounds
Amino nitrogen containing
C564S183000
Reexamination Certificate
active
06326517
ABSTRACT:
BACKGROUND OF THE INVENTION
1. Field of the Invention
This invention relates to improvements in a method of producing benzamides which are useful for intermediate products of medicines and agricultural chemicals.
2. Description of the Prior Art
Hitherto, benzamides have been able to be produced by reacting ammonia or ammonium salt with benzoic halides, benzoic anhydrides or benzoic acids.
U.S. Pat. No. 3,825,594 discloses a production method for aryl halide having two trifluoromethyl groups in an aryl ring, in which 2,6- or 2,4-bis(trifluoromethyl) benzoic acids are formed into acid chlorides which are subjected to amidation with primary amines. Additionally, a literature (Chemical Abstracts, Vol. 79: 42101, Zh. Org. Khim. 1973, 9(5), 1019-24 (Russ)) discloses that 2,6-bis(carboxytrifluoro methyl) benzene is reacted with SF
4
to produce 2,6-bis(trifluoromethyl) benzoylfluoride which is then reached with ammonia thereby to form 2,6-bistrifluoromethyl benzoic amides. Further, a literature (J. Org. Chem., Vol. 39, No. 23, 1974, 3327-3331) discloses that aryl halides, carbon monoxide and primary or secondary amine are reacted in the presence of a catalytic amount of triphenylphosphine-palladium salt complex thereby to produce corresponding secondary and tertiary amides.
As discussed above, trifluoromethyl benzamides can be produced from acid chloride or acid fluoride of bistrifluoromethyl benzoic acid. However, difficulties have been encountered in the above conventional techniques. That is, the conventional techniques require to prepare the acid chloride or the acid fluoride as a precursor. As a result, a production process of the trifluoromethyl benzamides requires multi-state reaction steps.
SUMMARY OF THE INVENTION
It is an object of the present invention to provide an improved production method of benzamides, which can effectively overcome difficulties encountered in conventional production methods for benzamides.
Another object of the present invention is to provide an improved production method of benzamides, which can provide benzamides at a single reaction step from aromatic compounds which are readily available.
A further object of the present invention is to provide an improved production method of benzamides, which can provide bis(trifluoromethyl) benzamides at a single reaction step from aromatic halides which are readily available.
A still further object of the present invention is to provide an improved production method of benzamides, which can provide benzamides at a single reaction step from aromatic compounds, while largely reducing an amount of expensive noble metal catalysts such as palladium to be consumed in reaction of the production method.
A first aspect of the present invention resides in a method of producing benzamides represented by the following general formula (1):
where R is trifluoromethyl group, trifluoromethyloxy group, halogen (fluorine, chlorine, bromine or iodine), nitro group, acetyl group, cyano group, alkyl group having 1 to 4 carbon atoms, alkoxy group having 1 to 4 carbon atoms, or a alkoxycarbonyl group having 2 to 5 carbon atoms; and n is 0 or an integer ranging from 1 to 3.
The method comprises the step of allowing an aromatic compound represented by the following general formula (2) to react with carbon monoxide and ammonia in the presence of a metal of the group VIII of the periodic table and phosphine:
where X is halogen (fluorine, chlorine, bromine or iodine), trifluoromethanesulfonate group, alkylsulfonate group having 1 to 4 carbon atoms, or substituted or unsubstituted arylsulfonate group; R is trifluoromethyl group, trifluoromethyloxy group, halogen (fluorine, chlorine, bromine or iodine), nitro group, acetyl group, cyano group, alkyl group having 1 to 4 carbon atoms, alkoxy group having 1 to 4 carbon atoms, or alkoxycarbonyl group having 2 to 5 carbon atoms; and n is 0 or an integer ranging from 1 to 3.
According to the first aspect, the benzamides can be produced at a single reaction from aromatic compound (preferably aromatic halide) having bis(trifluoromethyl) group, carbon monoxide and ammonia, thereby simplifying the process of production of the benzamides.
A second aspect of the present invention resides in a method of producing benzamides, comprising the following steps:
(a) allowing an aromatic compound represented by the following general formula (2) to react with carbon monoxide and ammonia in the presence of palladium and phosphine in a reaction system:
where X is halogen (fluorine, chlorine, bromine or iodine), trifluoromethanesulfonate group, alkylsulfonate group having 1 to 4 carbon atoms, or substituted or unsubstituted arylsulfonate group; R is trifluoromethyl group, trifluoromethyloxy group, halogen (fluorine, chlorine, bromine or iodine), nitro group, acetyl group, cyano group, alkyl group having 1 to 4 carbon atoms, alkoxy group having 1 to 4 carbon atoms, or a alkoxycarbonyl group having 2 to 5 carbon atoms; and n is 0 or an integer ranging from 1 to 3,
(b) separating at least benzamide represented by the following general formula (1):
where R is trifluoromethyl group, trifluoromethyloxy group, halogen (fluorine, chlorine, bromine or iodine), nitro group, acetyl group, cyano group, alkyl group having 1 to 4 carbon atoms, alkoxy group having 1 to 4 carbon atoms, or a alkoxycarbonyl group having 2 to 5 carbon atoms; and n is 0 or an integer ranging from 1 to 3; and
(c) adding the aromatic compound represented by the general formula (2), ammonia and carbon monoxide into the reaction system from which at least the benzamide is separated, so as to accomplish reaction in the reaction system.
According to the second aspect, the benzamides can be produced at a single reaction from aromatic compound (preferably aromatic halide) having bis(trifluoromethyl) group, carbon monoxide and ammonia, while sharply reducing the amount of expensive catalyst to be used in the reaction.
A third aspect of the present invention resides in a method of producing benzamides, comprising the following steps:
(a) allowing an aromatic compound represented by the following general formula (2) to react with carbon monoxide and ammonia in the presence of palladium and phosphine in a reaction system:
where X is halogen (fluorine, chlorine, bromine or iodine), trifluoromethanesulfonate group, alkylsulfonate group having 1 to 4 carbon atoms, or substituted or unsubstituted arylsulfonate group; R is trifluoromethyl group, trifluoromethyloxy group, halogen (fluorine, chlorine, bromine or iodine), nitro group, acetyl group, cyano group, alkyl group having 1 to 4 carbon atoms, alkoxy group having 1 to 4 carbon atoms, or a alkoxycarbonyl group having 2 to 5 carbon atoms; and n is 0 or an integer ranging from 1 to 3,
(b) separating at least benzamide represented by the following general formula (1):
where R is trifluoromethyl group, trifluoromethyloxy group, halogen (fluorine, chlorine, bromine or iodine), nitro group, acetyl group, cyano group, alkyl group having 1 to 4 carbon atoms, alkoxy group having 1 to 4 carbon atoms, or a alkoxycarbonyl group having 2 to 5 carbon atoms; and n is 0 or an integer ranging from 1 to 3; and
(d) recovering palladium-phosphine complex compound from the reaction system; and
(e) using the palladium-phosphine complex compound recovered in the step (d) as a catalyst.
Other aspects of the present invention will become apparent from the description made hereinafter.
DETAILED DESCRIPTION OF THE INVENTION
According to an aspect of the present invention, a method of producing benzamides represented by the following general formula (1) is provided:
where R is trifluoromethyl group, trifluoromethyloxy group, halogen (fluorine, chlorine, bromine or iodine), nitro group, acetyl group, cyano group, alkyl group having 1 to 4 carbon atoms, alkoxy group having 1 to 4 carbon atoms, or a alkoxycarbonyl group having 2 to 5 carbon atoms; and n is 0 or an integer ranging from 1 to 3.
The method comprises the step of allowing an aromatic compound represented by the following general formula (2) to react with carbon monoxide and
Ishida Michio
Koide Makoto
Kume Takashi
Morino Yuzuru
Narizuka Satoru
Central Glass Company Limited
Crowell & Moring LLP
Padmanabhan Sreeni
Parsa J.
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