Organic compounds -- part of the class 532-570 series – Organic compounds – Carboxylic acid esters
Reexamination Certificate
2001-07-12
2003-10-07
Barts, Samuel (Department: 1621)
Organic compounds -- part of the class 532-570 series
Organic compounds
Carboxylic acid esters
C560S021000, C560S022000, C560S023000
Reexamination Certificate
active
06630598
ABSTRACT:
FIELD OF THE INVENTION
The present invention relates to a method for producing N-acylnitroaniline derivatives and, more specifically, an N-acylnitroaniline derivative of formula (4) as shown below, which is useful as an intermediate in the production of pharmaceutical or agricultural products.
DESCRIPTION OF RELATED ART
A method for producing an N-acylnitroaniline derivative of formula (4) is known which includes the steps of N-acylation of a nitroaniline compound with an acylating agent, such as di-tert-butyl dicarbonate, in the presence of a base, such as 4-N,N-dimethylaminopyridine or the like, and an N-alkylating reaction of the N-acylated product (Japanese Patent Laid-Open Hei 9-295970 (1997)).
However, the method described above has problems in that the yield is not always satisfactory, and a purification process by crystallization was required in the step of N-acylation since large amounts of impurities are present.
Hence, development of an industrially advantageous production method for producing N-acylnitroaniline derivatives of formulas (1) and (4) has been desired.
SUMMARY OF THE INVENTION
According to the present invention, N-acylation of nitroaniline compounds can be selectively conducted by using an alkali metal compound or an alkaline earth metal compound in an amount of about 1.6 moles or more per mol of a nitroaniline, and further derivatization thereafter can proceed smoothly to give a desired N-substituted N-acylnitroaniline derivative in a good yield.
Thus, the present invention provides
a method for producing an N-acylnitroaniline derivative of formula (1);
wherein X may be the same or different and each denotes
a hydrogen atom; a halogen atom; an alkyl group; a haloalkyl group; an alkoxy group; a phenylalkyl group; a phenylalkoxyl group;
a phenyl group which may be optionally substituted with a halogen, a nitro group, an alkyl group, an N-alkylacylamino group, an N-aralkylacylamino group or an N,N-dialkylamino group;
a benzoyl group which may be optionally substituted with a halogen atom, a nitro group or an alkyl group,
an alkoxycarbonyl group,
an N-alkylacylamino group, an N-aralkylacylamino group, an alkylthio group, an aralkylthio group, an arylthio group, a formyl group, an N,N-dialkylamino group, an optionally substituted alkenyl group, an optionally substituted alkynyl group, or a piperidyl group,
n denotes an integer from 0 to 4, or
Xn, together with the benzene ring to which it is bonded, may form a quinoline, fluorene, or naphthalene group, and
R
1
denotes an alkyl group, an alkenyl group, an aryl group, an aralkyl group, an alkoxy group, an aryloxy group or an aralkyloxy group,
which comprises reacting a nitroaniline compound of formula (2);
wherein X and n are the same as described above, with an acid anhydride of formula (3a) or an acid chloride of formula (3b):
wherein R
1
is the same as defined above and Z denotes a halogen atom, in the presence of an alkali metal compound or an alkaline earth metal compound in an amount of about 1.6 moles or more per mol of a nitroaniline compound of formula (1), and
a method for producing an N-acylnitroaniline derivative of formula (4);
wherein R
1
is the same as defined above and R
2
denotes an optionally substituted alkyl group, an optionally substituted alkenyl group, or an optionally substituted alkynyl group, and X and n denote the same as described above, which comprises reacting the resulting product obtained in the above-described method with a compound of formula (5);
R
2
—Y
wherein R
2
denotes the same as defined above and Y denotes a leaving group.
DETAILED DESCRIPTION OF THE INVENTION
First, a description will be made to the production method of obtaining N-acylnitroaniline derivative of formula (1).
In the compounds disclosed in the present invention, the halogen atoms denoted by X or Z include fluorine, chlorine, bromine and iodine atoms.
The alkyl group in the haloalkyl group, the alkoxy group, the phenylalkyl group, the alkoxycarbonyl group, the phenylalkoxyl group, the N-alkylacylamino group, the N,N-dialkylamino group, and the alkylthio group include an alkyl group of 1 to 10 carbon atoms.
In the N-aralkylacylamino group and the aralkylthio group, the alkyl moiety include an alkyl groups of 1 to 6 carbon atoms such as a methyl group, an ethyl group, n-propyl group, i-propyl group, t-butyl group, n-butyl group, s-butyl group, n-pentyl group, i-pentyl group, n-hexyl group, or the like.
Examples of the aryl groups in the aralkyl, (C6-C10)aryl group, arylthio and the following aroyl groups include a phenyl group, a naphthyl group and the like. Examples of the arylthio group include a phenylthio group, a naphthylthio group and the like.
Examples of the acyl group of the N-alkylacylamino group and N-aralkylacylamino group include a (C1-C6)alkanoyl or (C6-C10)aroyl group, which may be substituted, for example, with a halogen atom. Specific examples of the acyl group include a formyl group, an acetyl group, a pivaloyl group, a trifluoroacetyl group, a trichloroacetyl group, a benzoyl group, a 2-chlorobenzoyl group, 1- or 2-naphthoyl group and the like. Other examples of acyl groups of N-aralkylacylaminxo group will be apparent to one skilled in the art.
Examples of the optionally substituted alkenyl group include chain, branched or cyclic alkenyl groups of 2 to 10 carbon atoms, which may be substituted with a halogen atom, an alkoxyl group of 1 to 6 carbon atoms, or a halogenoaryl group of 6 to 10 carbon atoms. The halogenoaryl group of 6 to 10 carbon atoms include a phenyl or naphthyl group which is substituted with at least one halogen atom. Specific examples of the halogenoaryl group include a chlorophenyl, dichlorophenyl, bromophenyl, fluorophenyl, difluorophenyl, or iodophenyl group and the like.
Specific examples of the optionally substituted alkenyl group include a vinyl group, a 2,2-dimethylvinyl group, a 1-propenyl group, a 1-butenyl group, a cyclohexenyl group and the like.
Examples of the optionally substituted alkynyl group include an alkynyl group of 2 to 10 carbon atoms, which may be substituted with a halogen atom, an alkoxy group of 1 to 6 carbon atoms, an aryl group of 6 to 10 carbon atoms, a halogenoaryl of 6 to 10 carbon atoms, a trialkyl(C1-C4)silyl group and the like.
Specific examples of the optionally substituted alkynyl group include a trimethylsilylethynyl group, a 1-propynyl group, a 1-butynyl group and the like. The nitroaniline compounds of formula (2) are commercially available or can be produced by known methods.
Specific examples of the nitroaniline compound (2) include
2-nitroaniline, 2-bromo-4,6-dinitroaniline, 6-chloro-2,4-dinitroaniline,
2,4-dinitroaniline, 2,6-dinitroaniline, 2,4-dinitro-5-fluoroaniline,
4-methoxy-2-nitroaniline, 4-ethoxy-2-nitroaniline,
4-amino-3-nitrobenzophenone, 4-amino-3-nitrobenzofluoride
2,6-dinitro-4-methylaniline, 2,4-dichloro-6-nitroaniline,
4,6-dimethyl-2-nitroaniline, 2-methyl-6-nitroaniline,
4,5-dichloro-2-nitroaniline, 5-chloro-2-nitroaniline,
4,5-dimethyl-2-nitroaniline, 5-methyl-2-nitroaniline,
4-fluoro-2-nitroaniline, 4-chloro-2-nitroaniline, 4-methyl-2-nitroaniline,
4,5-difluoro-2-nitroaniline, 2,4-dibromo-6-nitroaniline,
4-amino-3-nitrobenzonitrile,
methyl 4-amino-3-nitrobenzoate, 2-amino-3-nitro-9-fluorenone,
4-benzyloxy-2-nitroaniline, 3,3′-dinitrobenzidine,
2,4-dimethyl-3,6 -dinitroaniline, 2,4-dinitro-6-phenylaniline,
4-methoxy-3-methyl-6-nitroaniline, 3-bromo-4-methoxy-6-nitroaniline,
3-amino-2-nitrofluorene, 5-ethoxy-4-fluoro-2-nitroaniline,
2,4-difluoro-6-nitroaniline, 5-chloro-4-methyl-2-nitroaniline,
4-ethyl-2-nitroaniline, 4-nitroaniline, 2 -bromo-4,6-dinitroaniline,
6-chloro-2,4-dinitroaniline, 2,5-dimethoxy-4-nitroaniline,
2-cyano-4-nitroaniline, 2-methoxy-4-nitroaniline,
2-amino-5-nitrobenzophenone, 2-amino-5-nitrobenzotrifluoride,
2,6-dibromo-4-nitroaniline, 2-chloro-4-nitroaniline,
2,6-dichloro-4-nitroaniline, 2methyl-4-nitroaniline,
5-methoxy-2-methyl-4-nitroaniline, 5-amino-2-nitrobenzotrifluoride,
2-bromo-6-chloro-4-nitroaniline, 2-ethoxy-4-nitroaniline,
2-bromo-4-nit
Barts Samuel
Sumitomo Chemical Company Limited
Zucker Paul A.
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