Method of producing aminophenol compounds

FIELD: chemistry.

SUBSTANCE: invention relates to a method of producing and aminophenol compound of formula (1) , where each of R1 and R2, which can be identical or different, are a hydrogen atom, C1-C6 alkyl group, which can be substituted with phenyl, or phenyl; R1 and R2 together with the neighbouring nitrogen atom can form a 5- or 6-member heterocyclic group, selected from piperidinyl and piperazinyl; the heterocyclic group can be substituted with one substitute selected from hydroxyl group, C1-C6 alkyl group and phenoxy group, which can have a C1-C6 alkoxy group, substituted with 1-3 halogen atoms. The method involves reacting a cyclohexanedione compound of formula (2) with a amine compound of formula (3) , where R1 and R2 assume values given above, in neutral or basic conditions.

EFFECT: wider range of use of the compound.

8 cl, 4 dwg, 13 ex

 

The technical field

The present invention relates to a method for aminophenolic connections.

Prior art

Aminophenol compounds represented by formula (1), and their salts:

(where each of R1and R2that may be the same or different, represents a hydrogen atom, substituted or unsubstituted lower alkyl group, a substituted or unsubstituted aryl group or a substituted or unsubstituted heterocyclic group; R1and R2together with the adjacent nitrogen atom may form a 5 - or 6-membered heterocycle with or without other intermediate heteroatoms; the heterocycle may be substituted by 1-3 substituents selected from the group consisting of hydroxyl group, substituted or unsubstituted lower alkyl group, a substituted or unsubstituted aryl group, substituted or unsubstituted of alloctype, substituted or unsubstituted heterocyclic group and actigraphy, replaced by a substituted or unsubstituted heterocyclic group; and hydroxyl group in the formula (1) is a Deputy in the second or fourth position of the phenyl ring) are suitable as intermediates for the synthesis of various pharmaceutical agents (preferably protimeter lesnych agents) and agrochemical means.

So far as the method of obtaining aminophenolic compounds are known, for example, the methods shown in the following reaction scheme 1 and reaction scheme 2 (Stephen L. Buchwald et al. Organic Letters, vol. 4, 2885 (2002)).

The reaction scheme-1

The reaction scheme-2

In the above schemes, the group-NR'r R” represents dibutylamino, N-methylaminopropyl, morpholinopropan, 4-methylpiperidino group, 4-hydroxypiperidine group, 4-methylaniline, 4-methoxyaniline and 3,4-dimethoxyaniline, and R represents a protective group of hydroxyl group.

These methods, however, have various disadvantages and are therefore not suitable for industrial production method.

For example, the method shown in reaction scheme-1, requires major or expensive metal catalysts such as palladium-based catalyst, aromatic triflate and copper catalyst. The method shown in reaction scheme-2, requires complex stage of protection of the hydroxyl group of phenol and subsequent removal of the protective group.

Kazuo Haga et al. (Bull. Chem. Soc. Jpn., 57, 1586 (1984) and Bull. Chem. Soc. Jpn., 59, 803-807 (1986)) describe the reaction of 1,4-cyclohexandione and a secondary amine in the presence of an acid catalyst does not aminophenolate connect the tion or if the leads, the output is only from 4 to 12% and the main reaction product is aniline connection.

A. Reiker et al. (Tetrahedron, 23, 3723 (1967)), J. Figueras et al. (J. Org. Chem., 36, 3497 (1971)) and JP-A-62-29557 describe what the reaction of 1,4-benzoquinone and a primary amine in the presence of an acid catalyst leads to hinolonovogo connection and received genomanalyse the connection should be restored to obtain the target aminophenols connection.

Description of the invention

The purpose of the present invention is to provide advantageous from the industrial point of view the method of obtaining aminophenolic compounds represented by formula (1), using a simple and easy-to-do operations with high yield and high purity.

In order to solve the above problems, the authors of the present invention have carried out intensive research aimed at the method of obtaining aminophenolic compounds represented by formula (1), and as a result found that the above problems can be solved by introducing cyclohexandione the compounds of formula (2) reacts with aminoven compound of the formula (3) under neutral or basic conditions. The present invention was completed based on these received data.

The present invention provides a method of receiving the Oia aminophenols connection represented by formula (1)

(where each of R1and R2that may be the same or different, represents a hydrogen atom, substituted or unsubstituted lower alkyl group, a substituted or unsubstituted aryl group or a substituted or unsubstituted heterocyclic group; R1and R2together with the adjacent nitrogen atom may form a 5 - or 6-membered heterocycle with or without other intermediate heteroatoms; the heterocycle may be substituted by 1-3 substituents selected from the group consisting of hydroxyl group, substituted or unsubstituted lower alkyl group, a substituted or unsubstituted aryl group, substituted or unsubstituted of alloctype, substituted or unsubstituted heterocyclic group and actigraphy, replaced by a substituted or unsubstituted heterocyclic group; and hydroxyl group in the formula (1) is a Deputy in the 2 - or 4-position relative to the amino group of the phenyl ring), which includes the introduction of cyclohexadienones connection represented by the formula (2)

in the reaction with aminoven compound represented by the formula (3)

(where R1and R2have the above values), under neutral or basic conditions./p>

The present invention also provides a method according to the above method, where each of R1and R2that may be the same or different, represents a hydrogen atom; a lower alkyl group which may have 1 to 3 substituents selected from the group consisting of halogen atom, hydroxyl group, substituted or unsubstituted aryl groups and substituted or unsubstituted heterocyclic group; aryl group which may have 1 to 3 substituents selected from the group consisting of lower alkyl groups which may have from 1 to 3 substituents selected from the group consisting of a halogen atom and a hydroxyl group, a lower alkoxygroup, which may have 1 to 3 substituents selected from the group consisting of a halogen atom and a hydroxyl group, and halogen atoms; or a heterocyclic group which may have 1 to 3 substituents selected from the group consisting of lower alkyl groups which may have from 1 to 3 substituents selected from the group consisting of a halogen atom and a hydroxyl group, lower alkoxygroup, which may have 1 to 3 substituents selected from the group consisting of a halogen atom and a hydroxyl group, and halogen atoms; R1and R2together with the adjacent nitrogen atom may form a 5 - or 6-is by a heterocycle with or without other intermediate heteroatoms; and the heterocycle may be substituted by 1-3 substituents selected from the group consisting of hydroxyl groups; lower alkyl groups which may have from 1 to 3 substituents selected from the group consisting of halogen atom, hydroxyl group, substituted or unsubstituted aryl groups and substituted or unsubstituted heterocyclic group; aryl group which may have 1 to 3 substituents selected from the group consisting of lower alkyl groups which may have from 1 to 3 substituents selected from the group consisting of a halogen atom and a hydroxyl group, a lower alkoxygroup, which may have from 1 to 3 substituents selected from the group consisting of a halogen atom and a hydroxyl group, and halogen atoms; alloctype, which may have 1 to 3 substituents selected from the group consisting of lower alkyl groups which may have from 1 to 3 substituents selected from the group consisting of a halogen atom and a hydroxyl group, a lower alkoxygroup, which may have 1 to 3 substituents selected from the group consisting of a halogen atom and a hydroxyl group, and halogen atoms; a heterocyclic group which may having from 1 to 3 substituents selected from the group consisting of lower alkyl groups which may have from 1 to 3 substituents selected from the group consisting of a halogen atom and a hydroxyl group, a lower alkoxygroup, which may have 1 to 3 substituents selected from the group consisting of a halogen atom and a hydroxyl group, and halogen atoms; and actigraphy substituted heterocyclic group that may have 1 to 3 substituents selected from the group consisting of lower alkyl groups which may have from 1 to 3 substituents selected from the group consisting of a halogen atom and a hydroxyl group, a lower alkoxygroup, which may have 1 to 3 substituents selected from the group consisting from a halogen atom and a hydroxyl group, and halogen atoms.

The present invention provides a method according to the above method, where each of R1and R2that may be the same or different, represents a hydrogen atom; a lower alkyl group which may have 1 to 3 substituents selected from the group consisting of halogen atom, hydroxyl group, substituted or unsubstituted aryl groups and substituted or unsubstituted heterocyclic group; aryl group which may have 1 to 3 substituents selected from the group consisting of lower alkyl groups which may have from 1 to 3 substituents selected from the group consisting of a halogen atom and a hydroxyl group, nih is her alkoxygroup, which may have from 1 to 3 substituents selected from the group consisting of a halogen atom and a hydroxyl group, and halogen atoms; or a heterocyclic group which may have 1 to 3 substituents selected from the group consisting of lower alkyl groups which may have from 1 to 3 substituents selected from the group consisting of a halogen atom and a hydroxyl group, a lower alkoxygroup, which may have 1 to 3 substituents selected from the group consisting of a halogen atom and a hydroxyl group, and halogen atoms.

The present invention provides a method according to the above method, where R1and R2together with the adjacent nitrogen atom may form a 5 - or 6-membered heterocycle with or without other intermediate heteroatoms and the heterocycle may be substituted by 1-3 substituents selected from the group consisting of hydroxyl groups; lower alkyl groups which may have from 1 to 3 substituents selected from the group consisting of halogen atom, hydroxyl group, substituted or unsubstituted aryl groups and substituted or unsubstituted heterocyclic group; aryl group which may have 1 to 3 substituents selected from the group consisting of lower alkyl groups which may have from 1 to 3 substituents selected from the group consisting of an atom of the halogen and hydroxyl groups, low alkoxygroup, which may have 1 to 3 substituents selected from the group consisting of a halogen atom and a hydroxyl group, and halogen atoms; alloctype, which may have 1 to 3 substituents selected from the group consisting of lower alkyl groups which may have from 1 to 3 substituents selected from the group consisting of a halogen atom and a hydroxyl group, a lower alkoxygroup, which may have 1 to 3 substituents selected from the group consisting of a halogen atom and a hydroxyl group, and halogen atoms; heterocyclic groups which may have from 1 to 3 substituents selected from the group consisting of lower alkyl groups which may have from 1 to 3 substituents selected from the group consisting of a halogen atom and a hydroxyl group, a lower alkoxygroup, which may have 1 to 3 substituents selected from the group consisting of a halogen atom and a hydroxyl group, and halogen atoms; and actigraphy substituted heterocyclic group that may have 1 to 3 substituents selected from the group consisting of lower alkyl groups which may have from 1 to 3 substituents selected from the group consisting of a halogen atom and a hydroxyl group, a lower alkoxygroup, which may have 1 to 3 substituents selected from the group consisting of the atoms of halogen and hydroxyl groups, and halogen atoms.

The present invention provides a method according to the above methods, where the aryl group is a phenyl group or naftalina group; alloctype is fenoxaprop or naphthyloxy; the heterocyclic group is a 5 - or 6-membered saturated or unsaturated heterocyclic group; and oxygraph, a substituted heterocyclic group is oxygraph, substituted 5 - or 6-membered saturated or unsaturated heterocyclic group.

The present invention provides a method according to the above method, where aminophenolate connection is a 1-(4-hydroxyphenyl)-4-(4-triftormetilfosfinov)piperidine, 1-(4-hydroxyphenyl)-4-hydroxypiperidine, 1-(4-hydroxyphenyl)piperidine, 1-(4-hydroxyphenyl)-4-methylpiperazine, N-(4-hydroxyphenyl)-N-methylaniline, N-(4-hydroxyphenyl)aniline or N-(4-hydroxyphenyl)dibenzylamine.

The present invention provides a method according to the above methods, which is carried out in the presence of dehydrogenating agent, where dehydrogenative agent is used in amount of at least 1 wt.% in relation to the number of amine compounds of the formula (3).

The present invention provides a method according to the above methods, which can be done without dehydr generouse agent.

The present invention provides a method according to the above methods, which is carried out under neutral conditions.

The present invention provides a method according to the above methods, which is carried out in the presence of a basic compound, where the compound is used in an amount of from 0.5 to 5 mol per 1 mol of amine compounds of the formula (3).

The present invention provides a method according to the above methods, where the reaction is carried out at a reaction temperature from room temperature to 150°C.

The present invention provides a method according to the above methods, where cyclohexadienone compound of the formula (2) is used in an amount of from equimolar to 10 mol per 1 mol of amine compounds of the formula (3).

More specifically, the groups described in the formula (1)represent the following.

Examples of substituted or unsubstituted lower alkyl group include linear or branched alkyl group containing from 1 to 6 carbon atoms which may have from 1 to 3 substituents selected from the group consisting of halogen atom, hydroxyl group, substituted or unsubstituted aryl groups and substituted or unsubstituted heterocyclic group, such as methyl, ethyl, propyl, n-butyl, sec-butyl, tert-butyl, n-pentyl, n-hexyl, hydroxymethyl, 2-Ki is axetil, 1-hydroxyethyl, 3-hydroxypropyl, 2,3-dihydroxypropyl, 4-hydroxybutyl, 1,1-dimethyl-2-hydroxyethyl, 5,5,4-trihydroxyphenyl, 5-hydroxyphenyl, 6-hydroxyhexyl, 1-hydroxyisopropyl, 2-methyl-3-hydroxypropyl, trifluoromethyl, trichloromethyl, chloromethyl, methyl bromide, vermeil, iodomethyl, deformity, dibromomethyl, 2-chloroethyl, 2,2,2-triptorelin, 2,2,2-trichloroethyl, 3-chloropropyl, 2,3-dichloropropyl, 4,4,4-trichloroethyl, 4-terbutyl, 5-chloropentyl, 3-chloro-2-methylpropyl, 5-bromohexyl, 5,6-diclohexal, 3-hydroxy-2-chloropropyl, benzyl, 2-phenylethyl, 1-phenylethyl, 3-phenylpropyl, 4-phenylbutyl, 5-fenilpentil, 6-phenylhexa, 1,1-dimethyl-2-phenylethyl, 2-methyl-3-phenylpropyl, α-naphthylmethyl, β-naphthylmethyl, 2-(α-naphthyl)ethyl, 1-(β-naphthyl)ethyl, 3-(α-naphthyl)propyl, 4-(β-naphthyl)butyl, 5-(α-naphthyl)pentyl, 6-(β-naphthyl)hexyl, 1,1-dimethyl-2-(α-naphthyl)ethyl, 2-methyl-3-(β-naphthyl)propyl, 3-furylmethyl, (4 morpholino)methyl, (1-piperazinil)methyl, (1-pyrrolidinyl)methyl, (1-piperidinyl)methyl, (3-pyridyl)methyl, 2-(2-thienyl)ethyl, 1-(3-pyrrolyl)ethyl, 3-(2-oxazolyl)propyl, 4-(2-thiazolyl)butyl, 5-(2-imidazolyl)pentyl, 6-(2-pyridyl)hexyl, 1,1-dimethyl-2-(2-pyrimidyl)ethyl and 2-methyl-3-(3-pyridil)propyl.

Examples of substituted or unsubstituted aryl groups include phenyl groups which may have from 1 to 3 substituents, and raftiline group that may have 1 to 3 substituents. Examples of the substituent aryl group VK is ucaut linear or branched alkyl group, containing from 1 to 6 carbon atoms which may have from 1 to 3 substituents selected from the group consisting of a halogen atom and a hydroxyl group, such as methyl, ethyl, propyl, n-butyl, sec-butyl, tert-butyl, n-pentyl, n-hexyl, hydroxymethyl, 2-hydroxyethyl, 1-hydroxyethyl, 3-hydroxypropyl, 2,3-dihydroxypropyl, 4-hydroxybutyl, 1,1-dimethyl-2-hydroxyethyl, 5,5,4-trihydroxyphenyl, 5-hydroxyphenyl, 6-hydroxyhexyl, 1-hydroxyisopropyl, 2-methyl-3-hydroxypropyl, trifluoromethyl, trichloromethyl, chloromethyl, methyl bromide, vermeil, iodomethyl, deformity, dibromomethyl, 2-chloroethyl, 2,2,2-triptorelin, 2,2,2-trichloroethyl, 3-chloropropyl, 2,3-dichloropropyl, 4,4,4-trichloroethyl, 4-terbutyl, 5-chloropentyl, 3-chloro-2-methylpropyl, 5-bromohexyl, 5,6-diclohexal, 3-hydroxy-2-chloropropyl and the like; linear or branched alkoxygroup containing from 1 to 6 carbon atoms, which may having from 1 to 3 substituents selected from the group consisting of a halogen atom and a hydroxyl group, such as methoxy, ethoxy, propoxy, n-butoxy, sec-butoxy, tert-butoxy, n-pentyloxy, n-hexyloxy, hydroxyethoxy, 2-hydroxyethoxy, 1 hydroxyethoxy, 3 hydroxypropoxy, 2,3-dihydroxypropane, 4-hydroxybutane, 1,1-dimethyl-2-hydroxyethoxy, 5,5,4-trihydroxyanthracene, 5-hydroxyethyloxy, 6-hydroxyhexyloxy, 1 hydroxyisopropyl, 2-methyl-3-hydroxypropoxy t is aftermatket, trichlormethane, chloromethoxy, bromoethoxy, formatosi, admetox, deformedarse, dibromoethane, 2-chloroethoxy, 2,2,2-triptoreline, 2,2,2-trichloroethane, 3 chloropropoxy, 2,3-dichloropropene, 4,4,4-trichlorobutane, 4-forbooks, 5-chloropentane, 3-chloro-2-methylpropoxy, 5-Bromhexine, 5,6-dichlorohexane, 3-hydroxy-2-chloropropoxy and the like; or halogen atoms such as fluorine atom, bromine atom, chlorine atom and iodine atom. If there are two or more substituents, these substituents may be the same or different.

Examples of the substituted or unsubstituted heterocyclic group include aromatic heterocyclic groups which may have from 1 to 3 substituents. Examples of heterocyclic groups include 5 - or 6-membered saturated or unsaturated heterocyclic groups such as furyl, thienyl, pyrrolyl 2N-pyrrolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolin, imidazolyl, pyrazolyl, furutani, pyranyl, pyridyl, pyridil, pyrimidyl, Persil, piperidyl, piperazin, pyrrolidine, morpholine and the like, examples of the substituent of the heterocyclic group include linear or branched alkyl group containing from 1 to 6 carbon atoms which may have from 1 to 3 substituents selected from the group consisting of a halogen atom and a hydroxyl group such as methyl, ethyl, propyl, n-butyl, sec-butyl, tert-butyl, n-pentyl n-hexyl, hydroxymethyl, 2-hydroxyethyl, 1-hydroxyethyl, 3-hydroxypropyl, 2,3-dihydroxypropyl, 4-hydroxybutyl, 1,1-dimethyl-2-hydroxyethyl, 5,5,4-trihydroxyphenyl, 5-hydroxyphenyl, 6-hydroxyhexyl, 1-hydroxyisopropyl, 2-methyl-3-hydroxypropyl, trifluoromethyl, trichloromethyl, chloromethyl, methyl bromide, vermeil, iodomethyl, deformity, dibromomethyl, 2-chloroethyl, 2,2,2-triptorelin, 2,2,2-trichloroethyl, 3-chloropropyl, 2,3-dichloropropyl, 4,4,4-trichloroethyl, 4-terbutyl, 5-chloropentyl, 3-chloro-2-methylpropyl, 5-bromohexyl, 5,6-diclohexal, 3-hydroxy-2-chloropropyl and the like; linear or branched alkoxygroup containing from 1 to 6 carbon atoms which may have from 1 to 3 substituents selected from the group consisting of a halogen atom and a hydroxyl group, such as methoxy, ethoxy, propoxy, n-butoxy, sec-butoxy, tert-butoxy, n-pentyloxy, n-hexyloxy, hydroxyethoxy, 2-hydroxyethoxy, 1 hydroxyethoxy, 3 hydroxypropoxy, 2,3-dihydroxypropane, 4-hydroxybutane, 1,1-dimethyl-2-hydroxyethoxy, 5,5,4-trihydroxyanthracene, 5-hydroxyethyloxy, 6-hydroxyhexyloxy, 1 hydroxyisopropyl, 2-methyl-3-hydroxypropoxy, triptoreline, trichlormethane, chloromethoxy, bromoethoxy, formatosi, admetox, deformedarse, dibromoethane, 2-chloroethoxy, 2,2,2-triptoreline, 2,2,2-trichloroethane, 3 chloropropoxy, 2,3-dichloropropene, 4,4,4-trichlorobutane, 4-forbooks,5-chloropentane, 3-chloro-2-methylpropoxy, 5-Bromhexine, 5,6-dichlorohexane, 3-hydroxy-2-chloropropoxy and the like; or halogen atoms such as fluorine atom, bromine atom, chlorine atom and iodine atom. If there are two or more substituents, these substituents may be the same or different.

Examples of substituted or unsubstituted of alloctype include fenoxaprop, which may have 1 to 3 substituents, and naphthyloxy, which may have 1 to 3 substituents. Examples of the substituent aryl groups include linear or branched alkyl group containing from 1 to 6 carbon atoms which may have from 1 to 3 substituents selected from the group consisting of a halogen atom and a hydroxyl group, such as methyl, ethyl, propyl, n-butyl, sec-butyl, tert-butyl, n-pentyl, n-hexyl, hydroxymethyl, 2-hydroxyethyl, 1-hydroxyethyl, 3-hydroxypropyl, 2,3-dihydroxypropyl, 4-hydroxybutyl, 1,1-dimethyl-2-hydroxyethyl, 5,5,4-trihydroxyphenyl, 5-hydroxyphenyl, 6-hydroxyhexyl, 1-hydroxyisopropyl, 2-methyl-3-hydroxypropyl, trifluoromethyl, trichloromethyl, chloromethyl, methyl bromide, vermeil, iodomethyl, deformity, dibromomethyl, 2-chloroethyl, 2,2,2-triptorelin, 2,2,2-trichloroethyl, 3-chloropropyl, 2,3-dichloropropyl, 4,4,4-trichloroethyl, 4-terbutyl, 5-chloropentyl, 3-chloro-2-methylpropyl, 5-bromohexyl, 5,6-diclohexal, 3-hydroxy-2-chloropropyl and the like; linear mud is branched alkoxygroup, containing from 1 to 6 carbon atoms which may have from 1 to 3 substituents selected from the group consisting of a halogen atom and a hydroxyl group, such as methoxy, ethoxy, propoxy, n-butoxy, sec-butoxy, tert-butoxy, n-pentyloxy, n-hexyloxy, hydroxyethoxy, 2-hydroxyethoxy, 1 hydroxyethoxy, 3 hydroxypropoxy, 2,3-dihydroxypropane, 4-hydroxybutane, 1,1-dimethyl-2-hydroxyethoxy, 5,5,4-trihydroxyanthracene, 5-hydroxyethyloxy, 6-hydroxyhexyloxy, 1-hydroxyisopropyl, 2-methyl-3-hydroxypropoxy, triptoreline, trichlormethane, chloromethoxy, bromoethoxy, formatosi, admetox, deformedarse, dibromoethane, 2-chloroethoxy, 2,2,2-triptoreline, 2,2,2-trichloroethane, 3 chloropropoxy, 2,3-dichloropropene, 4,4,4-trichlorobutane. 4 forbooks, 5-chloropentane, 3-chloro-2-methylpropoxy, 5-Bromhexine, 5,6-dichlorohexane, 3-hydroxy-2-chloropropoxy and the like; or halogen atoms such as fluorine atom, bromine atom, chlorine atom and iodine atom. If there are two or more substituents, these substituents may be the same or different.

Oxygraph, replaced by a substituted or unsubstituted heterocyclic group means, for example, oxygraph substituted heterocyclic group that may have 1 to 3 substituents. Examples of actigraphy substituted heterocyclic group include exigrep is, substituted 5 - or 6-membered saturated or unsaturated heterocyclic group, such as forelocks, titilate, pyrrolidone 2N-pyrrolidone, oxazolidone, isoxazolidine, thiazolidine, isothiazolinone, imidazolinone, pyrazolinone, furazolidone, pyranyloxy, pyridyloxy, pyridazinone, pyrimidinone, pyrazolone, piperidinyloxy, piperazinone, pyrrolidinyloxy, morpholine and the like, examples of the substituent of the heterocyclic group include linear or branched alkyl group containing from 1 to 6 carbon atoms which may have from 1 to 3 substituents selected from the group consisting of a halogen atom and a hydroxyl group, such as methyl, ethyl, propyl, n-butyl, sec-butyl, tert-butyl, n-pentyl, n-hexyl, hydroxymethyl, 2-hydroxyethyl, 1-hydroxyethyl, 3-hydroxypropyl, 2,3-dihydroxypropyl, 4-hydroxybutyl, 1,1-dimethyl-2-hydroxyethyl, 5,5,4-trihydroxyphenyl, 5-hydroxyphenyl, 6-hydroxyhexyl, 1-hydroxyisopropyl, 2-methyl-3-hydroxypropyl, trifluoromethyl, trichloromethyl, chloromethyl, methyl bromide, vermeil, iodomethyl, deformity, dibromomethyl, 2-chloroethyl, 2,2,2-triptorelin, 2,2,2-trichloroethyl, 3-chloropropyl, 2,3-dichloropropyl, 4,4,4-trichloroethyl, 4-terbutyl, 5-chloropentyl, 3-chloro-2-methylpropyl, 5-bromohexyl, 5,6-diclohexal, 3-hydroxy-2-chloropropyl and the like; linear or branched alkoxygroup containing from 1 to carbon atoms, which may have from 1 to 3 substituents selected from the group consisting of a halogen atom and a hydroxyl group, such as methoxy, ethoxy, propoxy, n-butoxy, sec-butoxy, tert-butoxy, n-pentyloxy, n-hexyloxy, hydroxyethoxy, 2-hydroxyethoxy, 1 hydroxyethoxy, 3 hydroxypropoxy, 2,3-dihydroxypropane, 4-hydroxybutane, 1,1-dimethyl-2-hydroxyethoxy, 5,5,4-trihydroxyanthracene, 5-hydroxyethyloxy, 6-hydroxyhexyloxy, 1 hydroxyisopropyl, 2-methyl-3-hydroxypropoxy, triptoreline, trichlormethane, chloromethoxy, bromoethoxy, formatosi, admetox, deformedarse, dibromoethane, 2-chloroethoxy, 2,2,2-triptoreline, 2,2,2-trichloroethane, 3 chloropropoxy, 2,3-dichloropropene, 4,4,4-trichlorobutane, 4-forbooks, 5-chloropentane, 3-chloro-2-methylpropoxy, 5-Bromhexine, 5,6-dichlorohexane, 3-hydroxy-2-chloropropoxy and the like; or halogen atoms such as fluorine atom, bromine atom, chlorine atom and iodine atom. If there are two or more substituents, these substituents may be the same or different.

Examples of 5 - or 6-membered heterocyclic group formed by R1and R2together with the neighboring nitrogen atom with or without other intermediate heteroatoms include pyrrolidinyl, piperidinyl, piperazinil, morpholino and thiomorpholine. Heterocyclic group may be substituted by 1-3 substituents, selected the data from the group consisting of hydroxyl group, the above substituted or unsubstituted lower alkyl group, the above substituted or unsubstituted aryl group, the above substituted or unsubstituted of alloctype, the above substituted or unsubstituted heterocyclic group, and the above actigraphy, replaced by a substituted or unsubstituted heterocyclic group. If there are two or more substituents, these substituents may be the same or different.

The method of obtaining aminophenols the compounds of formula (1) according to the present invention are described below.

Aminophenolate the compounds of formula (1) according to the present invention is produced by introducing cyclohexadienone compounds represented by formula (2), reaction with aminoven compound represented by the formula (3), under neutral or basic conditions.

The reaction cyclohexadienone compounds represented by formula (2), and amine compounds represented by the formula (3), is carried out in a suitable solvent in the presence or in the absence of dehydrogenating agent with or without the primary connection.

Examples of the solvent include halogenated hydrocarbons such as dichloromethane, chloroform and carbon tetrachloride, lower alcohols such as methanol, ethanol and isopropanol, ketones, t is such as acetone and methyl ethyl ketone, ethers, such as diethyl ether, dioxane, tetrahydrofuran, onomatology ether of ethylene glycol and dimethyl ether of ethylene glycol, aromatic hydrocarbons such as benzene, toluene and xylene, esters such as ethyl acetate and methyl acetate, acetonitrile, pyridine, 2,4,6-kallidin, dimethylsulfoxide, dimethylformamide, triamide hexamethylphosphoric acid and a mixed solvent of these.

Examples dehydrogenating agent include metal catalysts such as palladium, platinum, iridium, rhodium, manganese, ruthenium and Nickel. The metal catalyst may be a catalyst in which the above metal deposited on an inert carrier such as activated carbon, alumina, barium sulfate and calcium carbonate, as palladium on carbon.

Dehydrogenative agent is used alone or in mixture of two or more kinds.

The number dehydrogenating agent is usually at least 1 wt.%, preferably about 1 to 200 wt.% in relation to the number of amine compounds of the formula (3).

As the basic compounds can be used a large number of organic bases and inorganic bases.

Examples of organic bases include triethylamine, trimethylamine, pyridine, dimethylaniline, N-ethyldiethanolamine, dimethylaminopyridine, N-IU Immortalis,

1,5-diazabicyclo[4.3.0]nonan-5 (DBN),

1,8-diazabicyclo[5.4.0]undecene-7 (DBU),

1,4-diazabicyclo[2.2.2]octane (DABCO), and

1,8-bis(dimethylamino)naphthalene.

Examples of inorganic bases include carbonates such as sodium carbonate, potassium carbonate, cesium carbonate, sodium bicarbonate and potassium bicarbonate; metal hydroxides such as sodium hydroxide, potassium hydroxide, calcium hydroxide and cesium hydroxide; phosphate, such as tribalistic, declivities, trisodium phosphate and intrigejosa; potassium hydride, sodium hydride, potassium, sodium, and sodium amide.

The primary connection using one or a mixture of two or more kinds.

The amount of basic compound is usually from 0.5 to 5 mol, preferably from 0.5 to 2 mol per 1 mol of amine compounds of the formula (3).

The number cyclohexandione the compounds of formula (2) is usually from equimolar to about 10 mol, preferably from equimolar to about 2 mol per 1 mol of amine compounds of the formula (3).

The reaction is usually progressing at a temperature of from about room temperature up to about 150°C, preferably from about room temperature up to about 100°C. the Reaction is generally complete within about 1 to 15 hours.

The reaction can be carried out in the presence or in the absence of dehydrogenating agent, what about the reaction proceeds even in an open system (in contact with air) or by bubbling air or oxygen into the system.

Cyclohexadienone compound represented by the formula (2), which is used as the starting material is readily available known connection.

Some amine compounds of the formula (3) are new compounds and can be obtained, for example, by the method shown in the following reaction scheme-3.

The reaction scheme-3

In the formulas, R3represents a substituted or unsubstituted aryl group; R1Aand R2Atogether with the adjacent nitrogen atom may form a 5 - or 6-membered heterocycle with or without other intermediate heteroatoms (where the heterocycle is substituted by at least one group X and may be further substituted by 1-2 substituents selected from the group consisting of hydroxyl group, substituted or unsubstituted lower alkyl group, a substituted or unsubstituted aryl group, substituted or unsubstituted of alloctype, substituted or unsubstituted heterocyclic group and actigraphy, replaced by a substituted or unsubstituted heterocyclic group); R1band R2btogether with the adjacent nitrogen atom may form a 5 - or 6-membered heterocycle with or without other intermediate heteroatoms (where the heterocycle is substituted by at least one group-OR3and can be additional is but substituted by 1-2 substituents, selected from the group consisting of hydroxyl group, substituted or unsubstituted lower alkyl group, a substituted or unsubstituted aryl group, substituted or unsubstituted of alloctype, substituted or unsubstituted heterocyclic group and actigraphy, replaced by a substituted or unsubstituted heterocyclic group); R4represents a protective group aminogroup; and X represents a lower alkylsulfonates, phenylsulfonylacetate, phenyl ring which may be substituted by a lower alkyl group or a halogen atom.

Examples of the protective group of the amino group include lower alkoxycarbonyl group, aryloxyalkyl group, and aryl-substituted lower alkyl group.

Examples of the lower alkoxycarbonyl groups include linear or branched alkoxycarbonyl group having from 1 to 6 carbon atoms, such as methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, butoxycarbonyl, tert-butoxycarbonyl, ventilatsiooniga and hexyloxymethyl group.

Examples aryloxyalkyl groups include phenoxycarbonyl group that may have 1 to 3 substituents, and naphthalocyanine group that may have 1 to 3 substituents. Examples of the substituent aryl groups include Lin is inie or branched alkyl group, containing from 1 to 6 carbon atoms which may have from 1 to 3 substituents selected from the group consisting of a halogen atom and a hydroxyl group, such as methyl, ethyl, propyl, n-butyl, sec-butyl, tert-butyl, n-pentyl, n-hexyl, hydroxymethyl, 2-hydroxyethyl, 1-hydroxyethyl, 3-hydroxypropyl, 2,3-dihydroxypropyl, 4-hydroxybutyl, 1,1-dimethyl-2-hydroxyethyl, 5,5,4-trihydroxyphenyl, 5-hydroxyphenyl, 6-hydroxyhexyl, 1-hydroxyisopropyl, 2-methyl-3-hydroxypropyl, trifluoromethyl, trichloromethyl, chloromethyl, methyl bromide, vermeil, iodomethyl, deformity, dibromomethyl, 2-chloroethyl, 2,2,2-triptorelin, 2,2,2-trichloroethyl, 3-chloropropyl, 2,3-dichloropropyl, 4,4,4-trichloroethyl, 4-terbutyl, 5-chloropentyl, 3-chloro-2-methylpropyl, 5-bromohexyl, 5,6-diclohexal, 3-hydroxy-2-chloropropyl and the like; linear or branched alkoxygroup containing from 1 to 6 carbon atoms, which may having from 1 to 3 substituents selected from the group consisting of a halogen atom and a hydroxyl group, such as methoxy, ethoxy, propoxy, n-butoxy, sec-butoxy, tert-butoxy, n-pentyloxy, n-hexyloxy, hydroxyethoxy, 2-hydroxyethoxy, 1 hydroxyethoxy, 3 hydroxypropoxy, 2,3-dihydroxypropane, 4-hydroxybutane, 1,1-dimethyl-2-hydroxyethoxy, 5,5,4-trihydroxyanthracene, 5-hydroxyethyloxy, 6-hydroxyhexyloxy, 1 hydroxyisopropyl, 2-methyl-3-hydroxypropoxy t is aftermatket, trichlormethane, chloromethoxy, bromoethoxy, formatosi, admetox, deformedarse, dibromoethane, 2-chloroethoxy, 2,2,2-triptoreline, 2,2,2-trichloroethane, 3 chloropropoxy, 2,3-dichloropropene, 4,4,4-trichlorobutane, 4-forbooks, 5-chloropentane, 3-chloro-2-methylpropoxy, 5-Bromhexine, 5,6-dichlorohexane, 3-hydroxy-2-chloropropoxy and the like; or halogen atoms such as fluorine atom, bromine atom, chlorine atom and iodine atom. If there are two or more substituents, these substituents may be the same or different.

Examples of aryl-substituted lower alkyl group include phenyl-substituted linear or branched alkyl group containing from 1 to 6 carbon atoms which may have from 1 to 3 substituents, and naphthyl-substituted linear or branched alkyl group containing from 1 to 6 carbon atoms which may have from 1 to 3 substituents, such as benzyl, 2-phenylethyl, 1-phenylethyl, 3-phenylpropyl, 4-phenylbutyl, 5-fenilpentil, 6-phenylhexa, 1,1-dimethyl-2-phenylethyl, 2-methyl-3-phenylpropyl, α-naphthylmethyl, β-naphthylmethyl, 2-(α-naphthyl)ethyl, 1-(β-naphthyl)ethyl, 3-(α-naphthyl)propyl, 4-(β-naphthyl)butyl, 5-(α-naphthyl)pentyl, 6-(β-naphthyl)hexyl, 1,1-dimethyl-2-(α-naphthyl)ethyl and 2-methyl-3-(β-naphthyl)propyl. Examples of the substituent aryl groups include linear or branched alkyl group containing from 1 to 6 carbon atoms, to which e can have from 1 to 3 substituents, selected from the group consisting of a halogen atom and a hydroxyl group, such as methyl, ethyl, propyl, n-butyl, sec-butyl, tert-butyl, n-pentyl, n-hexyl, hydroxymethyl, 2-hydroxyethyl, 1-hydroxyethyl, 3-hydroxypropyl, 2,3-dihydroxypropyl, 4-hydroxybutyl, 1,1-dimethyl-2-hydroxyethyl, 5,5,4-trihydroxyphenyl, 5-hydroxyphenyl, 6-hydroxyhexyl, 1-hydroxyisopropyl, 2-methyl-3-hydroxypropyl, trifluoromethyl, trichloromethyl, chloromethyl, methyl bromide, vermeil, iodomethyl, deformity, dibromomethyl, 2-chloroethyl, 2,2,2-triptorelin, 2,2,2-trichloroethyl, 3-chloropropyl, 2,3-dichloropropyl, 4,4,4-trichloroethyl, 4-terbutyl, 5-chloropentyl, 3-chloro-2-methylpropyl, 5-bromohexyl, 5,6-diclohexal, 3-hydroxy-2-chloropropyl and the like; linear or branched alkoxygroup containing from 1 to 6 carbon atoms which may have from 1 to 3 substituents selected from the group consisting of a halogen atom and a hydroxyl groups such as methoxy, ethoxy, propoxy, n-butoxy, sec-butoxy, tert-butoxy, n-pentyloxy, n-hexyloxy, hydroxyethoxy, 2-hydroxyethoxy, 1 hydroxyethoxy, 3 hydroxypropoxy, 2,3-dihydroxypropane, 4-hydroxybutane, 1,1-dimethyl-2-hydroxyethoxy, 5,5,4-trihydroxyanthracene, 5-hydroxyethyloxy, 6-hydroxyhexyloxy, 1 hydroxyisopropyl, 2-methyl-3-hydroxypropoxy, triptoreline, trichlormethane, chloromethoxy, bromoethoxy, formatosi, yogmata the si, deformedarse, dibromoethane, 2-chloroethoxy, 2,2,2-triptoreline, 2,2,2-trichloroethane, 3 chloropropoxy, 2,3-dichloropropene, 4,4,4-trichlorobutane, 4-forbooks, 5-chloropentane, 3-chloro-2-methylpropoxy, 5-Bromhexine, 5,6-dichlorohexane, 3-hydroxy-2-chloropropoxy and the like; or halogen atoms such as fluorine atom, bromine atom, chlorine atom and iodine atom. If there are two or more substituents, these substituents may be the same or different.

Lowest alkylsulfonates consists of alkyl groups having from 1 to 6 carbon atoms, and sulfonyloxy, and their examples include methanesulfonamido, econsultancy, propanesulfonate, butanesulfonate, pentanesulfonate and hexanesulfonate.

Examples of phenylsulfonylacetate, phenyl ring which may be substituted by lower alkyl groups include benzolsulfonate, which can be substituted by 1-3 linear or branched alkyl groups having from 1 to 6 carbon atoms, such as benzolsulfonate, toluensulfonate, m-toluensulfonate group, p-toluensulfonate, 2-ativanalcoholrape,

3-ativanalcoholrape,

4-ativanalcoholrape,

2-propylbenzenesulfonyl,

3-propelle solarponics.com,

4-propylbenzenesulfonyl,

2,3-dimethylbenzenesulfonamide,

2,4-dimethylbenzenesulfonamide and

2,4,6-trimethylbenzenesulfonamide.

The reaction of the compound of formula (4) and the compounds of formula (5) is usually carried out in a suitable inert solvent in the presence of a phase transfer catalyst with or without the primary connection.

Examples of the solvent include water, aromatic hydrocarbons such as benzene, toluene and xylene; ethers such as diethyl ether, tetrahydrofuran, dioxane, monoglyme and diglyme; halogenated hydrocarbons such as dichloromethane, dichloroethane, chloroform and carbon tetrachloride; lower alcohols such as methanol, ethanol, isopropanol, butanol, tert-butanol and ethylene glycol; esters such as ethyl acetate and methyl acetate; ketones such as acetone and methyl ethyl ketone; pyridine, such as pyridine and 2,6-lutidine; acetonitrile; amides such as N,N-dimethylformamide, N,N-dimethylacetamide and N-organic; dimethylsulfoxide, triamide hexamethylphosphoric acid and a mixed solvent of these.

Examples of the phase transfer catalyst include Quaternary ammonium salts, postname salts and pyridinium salts.

Examples of Quaternary ammonium salts include Quaternary ammonium salts, substituted by a group selected from the group, with Toyama from linear or branched alkyl group, having from 1 to 18 carbon atoms, phenyl-substituted linear or branched alkyl group having from 1 to 6 carbon atoms, and phenyl groups, such as tetrabutylammonium,

tetrabutylammonium, tetrabutylammonium,

tetrabutylammonium, tetrabutylammonium,

tetrabutylammonium, tributyltinchloride,

tributylammonium, Tetramethylammonium,

Tetramethylammonium, tetradecylammonium,

benzyldimethylammonium, methyltrioctylammonium,

benzyldimethylammonium,

methyltrichlorosilane, benzyltrimethylammonium,

benzyltriethylammonium, phenyltrimethylammonium,

tetraethylammonium and Tetramethylammonium.

Examples of postnasal salts include postname salts, substituted linear or branched alkyl group having from 1 to 18 carbon atoms, or a substituted amino group, such as tetrabutylphosphonium and tetrakis(Tris(dimethylamino)phosphorylcholine)phosphonylated.

Examples of pyridinium salts include pyridinium salts, substituted linear or branched alkyl group having from 1 to 18 carbon atoms, such as 1-dodecylpyridinium.

Interphase catalyst is used alone or with the art of two or more types.

The number of interphase catalyst is usually from 0.1 to 1 mol, preferably from 0.1 to 0.5 mol per 1 mol of compound (4).

As the primary connection, you can use a wide range of organic bases and inorganic bases.

Examples of organic bases include metal alcoholate such as sodium methylate, sodium ethylate, n-piperonyl sodium, pyridine, imidazole, N-ethyldiethanolamine, dimethylaminopyridine, triethylamine, trimethylamine, dimethylaniline, N-methylmorpholine, 1,5-diazabicyclo[4.3.0]nonan-5 (DBN), 1,8-diazabicyclo[5.4.0]undecene-7 (DBU), 1,4-diazabicyclo[2.2.2]octane (DABCO) and 1,8-bis(dimethylamino)naphthalene.

Examples of inorganic bases include carbonates such as sodium carbonate, potassium carbonate, sodium bicarbonate, potassium bicarbonate, and cesium carbonate; hydroxides such as sodium hydroxide, potassium hydroxide, cesium hydroxide and calcium hydroxide; hydrides such as sodium hydride and potassium hydride; phosphates, such as tribalistic, declivities, trisodium phosphate and intrigejosa; and alkali metals such as sodium and potassium. The inorganic base includes amides of sodium.

The primary connection using one or a mixture of two or more kinds.

The amount of basic compound is usually at least equimolar, predpochtitel is from about equimolar to 5 mol per 1 mol of compound (4).

The amount of compound (5) is usually at least equimolar, preferably equimolar to 3 mol per 1 mol of compound (4).

The reaction of the compound of formula (4) and the compounds of formula (5) successfully proceeds usually at a temperature from about 0°C to about 200°C, preferably from approximately 0°C to about 150°C. the Reaction is usually completed within a period from about 5 minutes to 10 hours.

The reaction of obtaining compound (3A) from compound (6) is carried out in a suitable solvent or without solvent in the presence of acid or basic compound.

Examples of the solvent include water, lower alcohols such as methanol, ethanol, isopropanol and tert-butanol, ketones, such as acetone and methyl ethyl ketone, ethers such as diethyl ether, dioxane, tetrahydrofuran, monoglyme and diglyme, aliphatic acids such as acetic acid and formic acid, esters such as methyl acetate and ethyl acetate; halogenated hydrocarbons such as chloroform, dichloromethane, dichloroethane and carbon tetrachloride, amides such as N,N-dimethylformamide, N,N-dimethylacetamide and N-organic, dimethylsulfoxide, triamide hexamethylphosphoric acid and a mixed solvent of these.

Examples of the acid include mineral acids such as hydrochloric acid, sulfuric sour is a and Hydrobromic acid, and organic acids such as formic acid, acetic acid, triperoxonane acid, and sulfonic acids such as p-toluensulfonate acid. Examples of basic compounds include carbonates such as sodium carbonate, potassium carbonate, cesium carbonate, sodium bicarbonate and potassium bicarbonate, and metal hydroxides such as sodium hydroxide, potassium hydroxide, calcium hydroxide, cesium hydroxide and lithium hydroxide.

The number of acid and basic compound are usually at least 1 mol, preferably from 1 to 10 mol per 1 mol of compound (6).

The reaction was progressing normally at a temperature of from about 0°C to about 200°C, preferably from approximately 0°C to about 150°C, and usually ends with a period approximately from 10 minutes to 30 hours.

If R4represents an aryl-substituted lower alkyl group, the compound (3A) can also be obtained by reduction of compound (6).

Response recovery can be performed, for example, by catalytic hydrogenation in the presence of a catalyst in a suitable solvent. Examples of the solvent include water, acetic acid, alcohols such as methanol, ethanol and isopropanol, hydrocarbons such as n-hexane and cyclohexane, ethers such as dioxane, tetrahydrofuran, diethyl EPE and dimethyl ether of ethylene glycol, esters, such as ethyl acetate and methyl acetate, aprotic polar solvents such as dimethylformamide and mixed solvents of these. Examples of the catalyst include palladium, palladium black, palladium-carbon, platinum, platinum oxide, copper chromite, Raney Nickel and the mixture. The amount of catalyst is usually from 0.02 to single by weight relative to the amount of the compound (6). The reaction temperature is usually from -20°C to about 100°C, preferably from approximately 0°to approximately 80°C and the hydrogen pressure is usually about 1 to 10 ATM. The reaction is usually completed within from about 0.5 to 20 hours.

2,3-Dihydro-6-nitroimidazo[2,1-b]oxazole compound represented by the formula (9), which is suitable as a drug, can be obtained from aminophenols the compounds of formula (1) according to the present invention by the method described in the following reaction scheme-4.

The reaction scheme-4

In formulas X1represents a halogen atom or a nitro-group; R5represents a hydrogen atom or a C1-6alkyl group; each of R1cand R2cthat may be the same or different, represents a hydrogen atom, a lower alkyl group, a phenyl-lower lilou group (where the phenyl ring may be substituted by at least one group, selected from the group consisting of a halogen atom, halogen-substituted or unsubstituted lower alkyl group and halogen-substituted or unsubstituted lower alkoxygroup), phenyl group (where the phenyl ring may be substituted by at least one group selected from the group consisting of a halogen atom, halogen-substituted or unsubstituted lower alkyl group and halogen-substituted or unsubstituted lower alkoxygroup) or pyridyloxy group (where the pyridine ring may be substituted by at least one halogen atom); R1cand R2ccan also together form piperidinyl group with the neighboring nitrogen atom with or without another heteroatom; the fourth position piperidinyl group may be substituted by at least 1-2 groups selected from the group consisting of hydroxyl group, fenoxaprop (where the phenyl ring may be substituted by at least one group selected from the group consisting of a halogen atom, halogen-substituted or unsubstituted lower alkyl group and halogen-substituted or unsubstituted lower alkoxygroup), phenyl-lower alkyl group (where the phenyl ring may be substituted by at least one group selected from the group consisting of a halogen atom, halogen-substituted or unsubstituted lower alkyl group and halogen-C is displaced or unsubstituted lower alkoxygroup), phenyl group (where the phenyl ring may be substituted by at least one group selected from the group consisting of a halogen atom, halogen-substituted or unsubstituted lower alkyl group and halogen-substituted or unsubstituted lower alkoxygroup), naphthyloxy (where the naphthalene ring may be substituted by at least one lower alkyl group) and pyridyloxy; or R1cand R2ccan also together form a piperazinilnom group with the neighboring nitrogen atom with or without another heteroatom; the fourth position piperazinilnom group may be substituted with one group selected from the group consisting of lower alkyl groups, phenyl-lower alkyl group (where the phenyl ring may be substituted by at least one group selected from the group consisting of a halogen atom, halogen-substituted or unsubstituted lower alkyl group and halogen-substituted or unsubstituted lower alkoxygroup), naphthyl-substituted lower alkyl group, a pyridyl-substituted lower alkyl group (where the pyridine ring can be substituted by at least one halogen atom), furyl-substituted lower alkyl group, thienyl-substituted lower alkyl group (where the thiophene ring may be substituted by at least one halogen atom), thiazolyl-substituted bottom of what she alkyl group (where the thiazole ring may be substituted by at least one niche alkyl group) and isoxazolyl-substituted C 1-6alkyl groups (where isoxazoline ring may be substituted by at least one lower alkyl group) and phenyl group (where the phenyl ring may be substituted by at least one group selected from the group consisting of a halogen atom, halogen-substituted or unsubstituted lower alkyl group and halogen-substituted or unsubstituted lower alkoxygroup).

According to reaction scheme 4, the compound of formula (9) is obtained by introducing the compound represented by the formula (7), in the reaction with the compound represented by formula (1A), or its salt, in the presence or in the absence of a basic compound to obtain the compound represented by the formula (8), and then by cyclization of the obtained compound represented by the formula (8), in the presence of a basic compound.

With regard to the proportion of the compound (1A) and compound (7), usually use the latter to the first, equal to from 0.5 to 5-fold moles, preferably from 0.5 to two times in moles.

The reaction of the compound (7) and the compound (1A) is carried out in the presence or in the absence of an acidic compound or basic compound in a suitable solvent or without solvent.

Examples of acidic compounds include solid acid and a Lewis acid. Specific examples of solid acids include silica gel and zeolite. Examples of the slot Lewis include triflate metal, such as triflate scandium, triplet yttrium complex of boron TRIFLUORIDE-simple ether and titanium tetrachloride.

As the primary connection, you can use a wide number of well-known inorganic basic compounds and organic basic compounds.

Examples of the inorganic basic compounds include metal hydrides, hydroxides, carbonates, bicarbonates, phosphates and fluorides of metals.

Specific examples of the metal hydride include sodium hydride and potassium hydride. Specific examples of the hydroxide include sodium hydroxide, cesium hydroxide and potassium hydroxide. Specific examples of the carbonate include sodium carbonate, cesium carbonate and potassium carbonate. Specific examples of the carbonate include sodium bicarbonate and potassium bicarbonate. Specific examples of the phosphate include tribalistic, declivities, trisodium phosphate and intrigejosa. Specific examples of the metal fluoride include sodium fluoride, potassium fluoride, cesium fluoride and mixtures thereof with a carrier, such as alumina.

In addition to the above inorganic basic compounds include sodium amide.

Examples of the organic basic compound include a metal alcoholate and acetates. Specific examples of the anion of the metal include sodium methoxide, ethoxide sodium tert-piperonyl potassium tert-piperonyl intothree is, tert-pentoxide and potassium tert-pentoxide sodium. Specific examples include acetate sodium acetate and potassium acetate.

The primary connection using one or a mixture of two or more kinds.

The amount of basic compound is usually a catalytic amount, preferably from 0.1 to 3 mol, more preferably from 0.1 to 2 mol per 1 mol of the compounds of formula (1A).

While the reaction is not inhibited, as a solvent, you can use a wide range of known solvents. Examples of such solvents include amides such as N,N-dimethylformamide (DMF), N,N-dimethylacetamide and N is an organic, aprotic polar solvents such as dimethylsulfoxide (DMSO) and acetonitrile, ketone solvents such as acetone and methyl ethyl ketone, hydrocarbon solvents such as benzene, toluene, xylene, tetralin and liquid paraffin, alcohol solvents such as methanol, ethanol, isopropanol, n-butanol and tert-butanol, based solvents ethers, such as tetrahydrofuran (THF), dioxane, dipropionyl ether, diethyl ether, monoglyme and diglyme, solvent-based esters, such as ethyl acetate, methyl acetate, propyl, n-butyl acetate, tert-butyl acetate, pentalateral, methylpropionate, ethylpropane, propylphosphonate, n-butylphosphonate and tert-butylphosphonate and a mixed solvent of these. These solvents may contain water.

Instead of using the compounds (1A) and the primary connection, you can use the salt of the compound (1A). Examples of such salt include salts of alkaline metal compounds (1A), such as sodium salt and potassium salt.

The reaction of the compound of formula (7) and compounds of formula (1A) is conducted usually at a temperature from room temperature up to 150°C, preferably from room temperature to 120°C. the reaction Time is usually from 10 minutes to 48 hours, preferably from 10 minutes to 24 hours, more preferably from 10 minutes to 10 hours.

The compound represented by the formula (9), according to the present invention receives, subjecting the compound represented by the formula (8), the cyclization reaction. The cyclization reaction is conducted, for example, by dissolving the compound represented by the formula (8), obtained above, in the reaction solvent by addition of a basic compound and stirring the mixture at a predetermined temperature.

As the reaction solvent and the basic compound can be used as the reaction solvent and the basic compound used in the reaction of compounds of formula (7) and compounds of formula (1A).

The amount of basic compound is usually in moles from equimolar to excess, preferably from equimolar the th to 5 mol, more preferably equimolar to 2 mol per 1 mol of the compounds of formula (8).

The reaction temperature for the cyclization reaction is usually from -20 to 120°C, preferably from -10 to 120°C, more preferably from -10 to 100°C. the reaction Time is usually from 10 minutes to 48 hours, preferably from 10 minutes to 24 hours, more preferably from 20 minutes to 4 hours.

In the present invention, the reaction mixture can be subjected to further cyclization without isolating the compounds of formula (8)obtained by reaction of compounds of formula (7) and compounds of formula (1A), through which can be obtained target compound represented by the formula (9).

If the reaction is carried out using a basic compound in an amount of from equimolar to excess in moles per 1 mol of compound (1A) at a temperature of from 50 to 100°C, the compound of formula (9) can be obtained without isolating the intermediate compound (8). The same approach is used when using a salt of an alkali metal (e.g. sodium salt, potassium salt) of the compound (1A).

Compounds represented by formula (1) (final products), and intermediate compound obtained above in reaction schemes in the present invention include stereoisomers and optical isomers.

Compounds according to the present invention include the pharmaceutical is viable salt. Examples of such salt include salts of inorganic acids such as hydrochloride, Hydrobromic, nitrate, sulfate and phosphate, and salts of organic acids, such as methanesulfonate, p-toluensulfonate, acetate, citrate, tartrate, maleate, fumarate, malate and lactate.

The target compounds obtained by the method according to the present invention, can be isolated from the reaction system using conventional methods of isolation and can be further purified. As the method of isolation and purification, for example, can be used distillation, recrystallization, column chromatography, ion exchange chromatography, gel chromatography, affinity chromatography, preparative thin-layer chromatography and solvent extraction.

According to the method of the present invention the target aminophenol compound of formula (1) can be obtained with high yield and high purity without the use of expensive catalysts, such as bases and metals, and moreover, without any complicated steps.

Thus, the method according to the present invention is particularly advantageous in industry.

EXAMPLES

Further, the present invention is described in more detail with reference to examples.

Example comparison 1

Obtain 1-tert-butoxycarbonyl-4-methyloxirane

To 300 ml of ethyl acetate, soda is out of 30.00 g of N-tert-butoxycarbonyl-4-hydroxypiperidine and 41.6 ml of triethylamine, was added dropwise to 17.3 ml methylchloride at -10°C for 10 minutes. The temperature rose to 5°C due to heat. After stirring under cooling in an ice bath for 10 minutes to the reaction mixture was carefully added dropwise 90 ml of water. The temperature was raised from 0°C to 6°C due to heat. After stirring for 10 minutes, the mixture was separated and the organic phase was washed in order with water (90 ml × 2), saturated brine (90 ml), water (90 ml) and saturated brine (90 ml). After drying over anhydrous magnesium sulfate were concentrated under reduced pressure and got 40,74 g of 1-tert-butoxycarbonyl-4-methyloxirane.

1H-NMR (300 MHz, DCl3) δ ppm: of 1.46 (9H, s), 1,48-1,90 (2H, m), 1,90-2,04 (2H, m), 3.04 from (3H, s), 3,32 is 3.40 (2H, m), 3,61-3,81 (2H, m), 4,88 (1H, DDD, J=11,5 Hz, J=7,Hz, J= 3,GC).

Example 2 comparison

Getting 4-(4-triftormetilfosfinov)piperidine

40,74 g of 1-tert-butoxycarbonyl-4-methyloxirane obtained in example comparison 1 above, 14,43 g of 4-cryptomaterial and 4.50 g of Tetra-n-butylammonium suspended in 72 ml of water. Then after adding to the suspension 33,59 g of potassium carbonate, the suspension is boiled under reflux for 8 hours (internal temperature 101°C). After keeping the suspension at room temperature over night to it was added 216 ml nhexane and was stirred for 5 minutes. To the specified solution was added 72 ml of 10% aqueous sodium hydroxide solution and after mixing, the mixture was separated. After washing with water (72 ml × 2) and the organic phase was dried over anhydrous magnesium sulfate, concentrated under reduced pressure and got 39,02 g of a mixture of 1-tert-butoxycarbonyl-4-(4-triftormetilfosfinov)piperidine and 1-tert-butoxycarbonyl-3,4-dihydropyridine.

According to the1H-NMR (DCl3analysis of the mixture contains 28,48 g of 1-tert-butoxycarbonyl-4-(4-triftormetilfosfinov)of piperidine and 10,54 g of 1-tert-butoxy-3,4-dihydropyridine.

The above mixture was dissolved in 117 ml of ethyl acetate was added thereto dropwise at room temperature within 10 minutes 51 ml of 4N-hydrogen chloride-ethyl acetate. After stirring the mixture at room temperature for one hour analysis of thin-layer chromatography showed that the original substance is not fully consumed and, thus, to the mixture was further added 51 ml of 4N-hydrogen chloride-ethyl acetate. The mixture was additionally stirred at room temperature for 3 hours and left at room temperature over night. The reaction solution was cooled on ice and gently poured 163 ml of 10% aqueous sodium hydroxide solution. The temperature rose to 23°C due to heat. The mixture was divided and an ethyl acetate phase p is washed with saturated brine (80 ml) and water (80 ml), and then was dried over anhydrous magnesium sulfate. The solvent was concentrated under reduced pressure and got 19,45 g light yellow solid of 4-(4-triftormetilfosfinov)piperidine.

1H-NMR (300 MHz, DCl3) δ ppm: 1,54 (1H, USS), 1,58-of 1.73 (2H, m), 1,94 e 2.06 (2H, m), of 2.72 (2H, DDD, J=12,5 Hz, J=9,4 Hz, J=3,1 Hz), 3,14 (2H, DDD, J=12,5 Hz, J=4,8gts, J=4,8gts), to 4.33 (1H, DDD, J=12,3 Hz, J=8,4 Hz, J=4,0 Hz), 6.89 in (2H, d, J=9,1 Hz), 7,12 (2H, d, J=9,1 Hz).

Data for comparison

1-tert-butoxycarbonyl-4-(4-triftormetilfosfinov)piperidine:

1H-NMR (300 MHz, DCl3) δ ppm: to 1.47 (9H, s), 1,68-to 1.82 (2H, m), 1,82 is 2.00 (2H, m), 3,29 is 3.40 (2H, m), 3,63-of 3.78 (2H, m), 4,39-of 4.49 (1H, m), of 6.90 (2H, d, J=8,Hz), 7,13 (2H, d, J=8,Hz).

1-tert-butoxycarbonyl-3,4-dihydropyrimidin:

1H-NMR (300 MHz, DCl3) δ ppm: of 1.46 (9H, s)to 2.13 (2H, USS), 3,49 (2H, t, J=5,GC), 3,88 (2H, OST, J=2,5Hz), 5,58-5,74 (1H, m), 5,74-5,91 (1H, m).

Example 3 comparison

Obtain (2R)-2-methyl-6-nitro-2-{4-[4-(4-triftormetilfosfinov)piperidine-1-yl]phenoxymethyl}-2,3-dihydroimidazo[2,1-b]oxazole

1-(4-Hydroxyphenyl)-4-(4-triftormetilfosfinov)piperidine (2034 g) and 2-chloro-1-[(2R)-2-methyl-2,3-epoxypropyl]-4-nitroimidazol (1388) was heated with stirring for 8 hours at about 100°C and obtained crude 1-{4-[(2R)-3-(2-chloro-4-nitroimidazol-1-yl)-2-hydroxy-2-methylpropoxy]phenyl}-4-(4-triftormetilfosfinov)piperidine. At the time of cooling the obtained substances to 88°C was added dimethylformamide (,5 l) and carried out the dissolution. After keeping the mixture at room temperature for 13 hours was additionally added dimethylformamide (15,8 l) and the mixture was cooled to -9°C. To the mixture was slowly added tert-piperonyl sodium (715 g) and the temperature was maintained at a value not higher than 0°C for 3.5 hours. After stirring for an additional 15 minutes, the reaction mixture was poured into a mixture of water (41,2 l) and ethyl acetate (2.1 liters) at room temperature. After stirring for one hour at 30°C the precipitate was filtered. The crystals were washed with water (9.2 liters)and then with ethyl acetate (8.2 liters) boiling under reflux. After cooling to 5°C the precipitate was filtered. The precipitate was washed with ethyl acetate (2.2 l) and was dried by blowing with compressed air at 60°C for 18 hours, receiving (2R)-2-methyl-6-nitro-2-{4-[4-(4-triftormetilfosfinov)piperidine-1-yl]phenoxymethyl}-2,3-chromides[2,1-b]oxazol (1548; yield 50%).

1H-NMR (300 MHz, DCl3) δ ppm: 1,76 (3H, s), 1,88-2,04 (2H, m), 2,04-of 2.21 (2H, m), 2,93-is 3.08 (2H, m), 3,30 is-3.45 (2H, m), a 4.03 (1H, d, J=10,2 Hz), Android 4.04 (1H, d, J=10,2 Hz), 4,18 (1H, d, J=10,2 Hz), 4,35-4,47 (1H, m), 4,50 (1H, d, J=10,2 Hz), 6,78 (2H, d, J=8,Hz), 6,86-6,97 (4H, m), 7,14 (2H, d, J=8,Hz), 7,55 (1H, s).

NMR spectral data for 1-{4-[(2R)-3-(2-chloro-4-nitroimidazol-1-yl)-2-hydroxy-2-methylpropoxy]phenyl}-4-(4-triftormetilfosfinov)of piperidine are as follows.

1H-NMR (300 MHz, DCl3) δ ppm: 1,33 (3H, s), 1,88-2,02 (2H, m), 2,03-2,19 (2H, m), 2.95 and-is 3.08 (2H, m), 3,30-3,44 (2H, m), 3,81(1H, d, J=9,4 Hz), 3,85 (1H, d, J=9,4 Hz), 4,15 (1H, d, J=14,3 Hz), 4,28 (1H, d, J=14,3 Hz), 4,37-4,48 (1H, m), for 6.81 (2H, d, J=8,Hz), 6,87-6,97 (4H, m), 7,14 (2H, d, J=8,Hz), 8,01 (1H, s).

Example 1

Obtaining 1-(4-hydroxyphenyl)-4-(4-triftormetilfosfinov)piperidine

(1) 261 mg of 4-(4-triftormetilfosfinov)of piperidine and 224 mg of 1,4-cyclohexanedione was heated at the boiling point under reflux in 5 ml of ethanol and the reaction was performed for 7 hours. After concentrating the reaction mixture under reduced pressure, the obtained product was divided by column chromatography on silica gel (n-hexane:ethyl acetate=3:1) and received 154,9 mg of 1-(4-hydroxyphenyl)-4-(4-triftormetilfosfinov)piperidine (output 43,8%).

1H-NMR (300 MHz, DCl3) δ ppm: 1,91 is 2.01 (2H, m), 2,07-of 2.15 (2H, m), 2,94-to 3.02 (m, 2H), 3,32-3,39 (2H, m), 4,37 is 4.45 (1H, m), 4,7 (1H, ush.), 6,74-6,79 (2H, m), 6.87 in-6,94 (4H, m), 7,11-7,17 (2H, m).

(2) 261 mg of 4-(4-triftormetilfosfinov)piperidine, 224 mg of 1,4-cyclohexanedione and 4 mg of 10% palladium on carbon was heated in ethanol and carried out the reaction at a temperature from 70°C to 80°C for 9 hours. After completion of the reaction, the obtained product was divided by column chromatography on silica gel (n-hexane:ethyl acetate=3:1) and received 315 mg of 1-(4-hydroxyphenyl)-4-(4-triftormetilfosfinov)piperidine (yield 89%).

1H-NMR (300 MHz, DCl3) δ ppm: 1,91 is 2.01 (2H, m), 2,07-of 2.15 (2H, m), 2,94-to 3.02 (m, 2H), 3,32-3,39 (2H, m), 4,37 is 4.45 (1H, m), 4,7 (1H, ush.), 6,74-6,79 (2H, m), 6.87 in-6,94 (4H, m), 7,11-7,17 (2H, m).

(3) 100 mg of 4-(4-triftormetilfosfinov)piperidine, 64 mg of 1,4-cyclohexandione and 0.02 ml of triethylamine was heated in 15 ml of ethanol and carried out the reaction at a temperature from 50°C to 60°C for 6 hours. After completion of the reaction, the reaction mixture was concentrated under reduced pressure and to the resulting product was added ethyl acetate to obtain an ethyl acetate solution, to which was added p-toluensulfonate acid. After keeping at room temperature for 30 minutes the precipitate was filtered and washed with ethyl acetate. The obtained crystals were dried by air and received 139 mg p-toluensulfonate 1-(4-hydroxyphenyl)-4-(4-triftormetilfosfinov)piperidine.

TPL 218,9-219,6°C

1H-NMR (300 MHz, DMSO-d6) δ ppm: 1,9-2,2 (2H, ush.), of 2.27 (3H, s), 2,2-2,4 (2H, ush.), 3,62 (2H, ush.), of 4.77 (1H, ush.), make 6.90 (2H, d, J=8,Hz), 7,11 (2H, d, J=7,8gts), 7,1-7,2 (2H, m), 7,32 (2H, d, J=8,Hz), 7,45-of 7.55 (2H, m), 7,49 (2H, d, J=7,GC).

(4) 4.0 g of 4-(4-triftormetilfosfinov)piperidine, 2,575 g of 1,4-cyclohexandione and 2.16 ml of triethylamine was heated in 60 ml of ethanol and carried out the reaction at a temperature from 50°C to 60°C for 6 hours. After completion of the reaction, the reaction mixture was concentrated under reduced pressure and to the resulting product was added ethyl acetate to obtain an ethyl acetate solution, to which was added monohydrate p-toluensulfonate acid. After keeping at room temperature for 30 minutes the precipitate was filtered, promyslitelnym, dried air and received 5,116 g p-toluensulfonate 1-(4-hydroxyphenyl)-4-(4-triftormetilfosfinov)piperidine (output 63,75%).

TPL 218,9-219,6°C

1H-NMR (300 MHz, DMSO-d6) δ ppm: 1,9-2,2 (2H, ush.), of 2.27 (3H, s), 2,2-2,4 (2H, ush.), 3,62 (2H, ush.), of 4.77 (1H, ush.), make 6.90 (2H, d, J, 8,GC), 7,11 (2H, d, J=7,8gts), 7,1-7,2 (2H, m), 7,32 (2H, d, J=8,Hz), 7,45-of 7.55 (2H, m), 7,49 (2H, d, J=7,GC).

(5) and 1.00 g of p-toluensulfonate 1-(4-hydroxyphenyl)-4-(4-triftormetilfosfinov)of piperidine was recrystallized from a mixture of 4.2 ml of ethanol and 2.8 ml of water. The precipitate was filtered and washed with 60% ethanol. The obtained crystals were dried by air and received 0,7636 g p-toluensulfonate 1-(4-hydroxyphenyl)-4-(4-triftormetilfosfinov)piperidine (yield of 76.3%)

TPL 218,9-219,6°C

1H-NMR (300 MHz, DMSO-d6) δ ppm: 1,9-2,2 (2H, ush.), of 2.27 (3H, s), 2,2-2,4 (2H, ush.), 3,62 (2H, ush.), of 4.77 (1H, ush.), make 6.90 (2H, d, J=8,Hz), 7,11 (2H, d, J=7,8gts), 7,1-7,2 (2H, m), 7,32 (2H, d, J=8,Hz), 7,45-of 7.55 (2H, m) 7,49 (2H, d, J=7,GC).

Example 2

Obtaining 1-(4-hydroxyphenyl)-4-hydroxypiperidine

202 mg of 4-hydroxypiperidine and 448 mg of 1,4-cyclohexanedione was heated at boiling under reflux in 10 ml ethanol and the reaction was performed for 9 hours when the air supply pump. During the reaction, if necessary, was added ethanol. After completion of the reaction the mixture was divided by column chromatography on silica gel (n-hexane:ethyl acetate=2:1) and received 0,218 g of 1-(4-hydroxyphenyl)-4-hydroxyprop Regina (output 56,48%).

1H-NMR (300 MHz, CDCl3) δ ppm: 1,66-of 1.78 (2H, m), 1,98-of 2.05 (2H, m), 2.77-to of 2.86 (2H, m), 3,35-of 3.42 (2H, m), 3,78-of 3.85 (1H, m), 4,5 (1H, ush.), 6.73 x-is 6.78 (2H, m), 6,84-of 6.90 (2H, m).

Example 3

Obtaining 1-(4-hydroxyphenyl)piperidine

0.85 grams of piperidine and 2.24 g of 1,4-cyclohexanedione was heated with stirring in 15 ml of ethanol at a temperature from 50°C to 60°C and the reaction was performed in air for 8 hours. During the reaction, if necessary, was added ethanol. After completion of the reaction, the reaction mixture was concentrated under reduced pressure, the resulting mixture was divided by column chromatography on silica gel (n-hexane:ethyl acetate=2:1) and obtained 0.95 g of 1-(4-hydroxyphenyl)piperidine (yield of 53.7%).

1H-NMR (300 MHz, CDCl3) δ ppm: 1,45 is 1.58 (2H, m), by 1.68 to 1.76 (4H, m), 3,01 (4H, t-like, J=5,3 Hz, J=5,4 Hz), 6,74 (2H, d, J=8,Hz), 6,87 (2H, d, J=8,Hz).

Example 4

Obtaining 1-(4-hydroxyphenyl)piperidine

0,85 g of piperidine, 1.68 g of 1,4-cyclohexandione and 40 mg of 10% palladium on carbon was heated with stirring in 40 ml of ethanol at a temperature from 50°C to 60°C and reaction was performed for 8 hours while bubbling air. During the reaction, if necessary, was added ethanol. After completion of the reaction the catalyst was separated by filtration and the filtrate was concentrated under reduced pressure. The obtained product was purified column chromatography on silica gel (n-hexane:ethyl acetate=4:), again was purified column chromatography on silica gel and got 0,668 g of 1-(4-hydroxyphenyl)piperidine (yield of 43.4%).

1H-NMR (300 MHz, CDCl3) δ ppm: 1,50 is 1.58 (2H, m), 1,67 to 1.76 (4H, m), 3,01 (4H, t-like, J=5,3 Hz, J=5,GC), 6,74 (2H, d, J=9,0 Hz), 6.87 in (2H, d, J=9,0 Hz).

Example 5

Obtaining 1-(4-hydroxyphenyl)-4-methylpiperazine

to 1.00 g of 1-methylpiperazine and 2.24 g of 1,4-cyclohexanedione was heated with stirring in 15 ml of ethanol at a temperature from 50°C to 60°C and the reaction was performed in air for 8 hours. During the reaction, if necessary, was added ethanol. After completion of the reaction, the reaction mixture was concentrated under reduced pressure, the resulting mixture was divided by column chromatography on silica gel (ethyl acetate:methanol=3:1) and was obtained 0.65 g of 1-(4-hydroxyphenyl)-4-methylpiperazine (output 33,9%).

1H-NMR (300 MHz, CDCl3) δ ppm: is 2.37 (3H, s), 2.63 in (4H, t-like, J=5,1 Hz, J=4,Hz), 3,10 (4H, t-like, J=5,1 Hz, J=4,Hz), 6,74 (2H, d, J=8,Hz), at 6.84 (2H, d, J=9,0 Hz).

Example 6

Obtaining 1-(4-hydroxyphenyl)-4-methylpiperazine

to 1.00 g of 1-methylpiperazine, 1.68 g of 1,4-cyclohexandione and 40 mg of 10% palladium on carbon was heated with stirring in 40 ml of ethanol at a temperature from 50°C to 60°C and reaction was performed for 8 hours while bubbling air. During the reaction, if necessary, was added ethanol. After completion of the reaction the catalyst was removed filter is a W and the filtrate was concentrated under reduced pressure. The resulting substance was purified column chromatography on silica gel (ethyl acetate:methanol=3:1) and obtained 1.26 g of 1-(4-hydroxyphenyl)-4-methylpiperazine (output 65,5%).

1H-NMR (300 MHz, CDCl3) δ ppm: is 2.37 (3H, s)of 2.64 (4H, t-like, J=5,1 Hz, J=4,8gts), 3,10 (4H, t-like, J=5,1 Hz, J=4,GC), is 6.78 (2H, d, J=9,0 Hz), at 6.84 (2H, d, J=9,0 Hz).

Example 7

Obtain N-(4-hydroxyphenyl)-N-methylaniline

1.07 g of N-methylaniline, 2.24 g of 1,4-cyclohexandione and 1.4 ml of triethylamine was heated with stirring in 15 ml of ethanol at a temperature from 50°C to 60°C and the reaction was performed in air for 8 hours. During the reaction, if necessary, was added ethanol. After completion of the reaction, the reaction mixture was concentrated under reduced pressure, the resulting mixture was divided by column chromatography on silica gel (n-hexane:ethyl acetate=3:1) and was obtained 0.64 g of N-(4-hydroxyphenyl)-N-methylaniline (32.1%).

1H-NMR (300 MHz, CDCl3) δ ppm: 3,25 (3H, s), 5,1 (1H, ush.), 6,76-6,85 (3H, m), 6,83 (2H, d, J=8,Hz),? 7.04 baby mortality (2H, d, J=8,Hz), 7,16-of 7.23 (2H, m).

Example 8

Obtain N-(4-hydroxyphenyl)aniline

of 0.93 g of aniline, 2.24 g of 1,4-cyclohexandione and 1.4 ml of triethylamine was heated with stirring in 15 ml of ethanol at a temperature from 50°C to 60°C and the reaction was performed in air for 8 hours. During the reaction, if necessary, was added ethanol. After concentrating the reaction mixture under reduced pressure, the AI resulting substance was purified column chromatography on silica gel (n-hexane:ethyl acetate=3:1) and was obtained 0.50 g of N-(4-hydroxyphenyl)aniline (yield 27.4 per cent).

1H-NMR (300 MHz, CDCl3) δ ppm: 4,70 (1H, ush.), of 5.48 (1H, ush.), 6,76-6,87 (1H, m), 6,79 (2H, d, J=9,0 Hz), 6,88-6,92 (2H, m), 7,00-7,06 (1H, m), 7,03 (2H, d, J=8,Hz), 7,18-7,28 (3H, m).

Example 9

Obtain N-(4-hydroxyphenyl)dibenzylamine

1,97 g dibenzylamine, 1.68 g of 1,4-cyclohexandione and 40 mg of 10% palladium on carbon was heated with stirring in 40 ml of ethanol at a temperature from 50°C to 60°C and reaction was performed for 8 hours while bubbling air. During the reaction, if necessary, was added ethanol. After completion of the reaction the catalyst was removed by filtration and the filtrate was concentrated under reduced pressure. The resulting substance was purified column chromatography on silica gel (n-hexane:ethyl acetate=30:1), optionally separated column chromatography on silica gel (n-hexane:ethyl acetate=10:1) and received a rate of 1.67 g of N-(4-hydroxyphenyl)dibenzylamine (yield 57%).

1H-NMR (300 MHz, CDCl3) δ ppm: 1,5-2,5 (1H, ush.), a 3.83 (4H, s), 6,84-6,90 (10H, m).

Example 10

Obtaining 1-(4-hydroxyphenyl)-4-(4-triftormetilfosfinov)piperidine

Suspension in 4 ml of 90% ethanol containing 100 mg of 4-(4-triftormetilfosfinov)piperidine, 86 mg of 1,4-cyclohexandione and 100 mg of 5% palladium on carbon (containing 54% water)was heated with stirring in a stream of argon at a temperature of from 70 to 80°C for 10 hours. After cooling the reaction mixture to room temperature rolled the ATOR was removed by filtration. To the stock solution was added 201 mg of the monohydrate of p-toluensulfonate acid and the mixture was concentrated under reduced pressure. To the residue was added 8 ml of ethyl acetate and the mixture was concentrated under reduced pressure. To the residue was additionally added 8 ml of ethyl acetate and washing the dispersion was carried out at 70°C. After cooling on ice, the precipitated crystals were filtered, dried in vacuum at room temperature and received 123 mg p-toluensulfonate 1-(4-hydroxyphenyl)-4-(4-triftormetilfosfinov)piperidine (yield of 61.2%).

So pl.: 218,9-219,6°C

1H-NMR (300 MHz, DMSO-d6) δ ppm: 1,9-2,2 (2H, ush.), of 2.27 (3H, s), 2,2-2,4 (2H, ush.), 3,62 (2H, ush.), of 4.77 (1H, ush.), make 6.90 (2H, d, J=8,Hz), 7,11 (2H, d, J=7,8gts), 7,1-7,2 (2H, m), 7,32 (2H, d, J=8,Hz), 7,45-of 7.55 (2H, m), 7,49 (2H, d, J=7,GC).

1. The method of obtaining aminophenolic compounds represented by formula (1)

(where each of R1and R2that may be the same or different, represents a hydrogen atom, a C1-C6alkyl group which may be substituted by phenyl, or phenyl, R1and R2together with the adjacent nitrogen atom may form a 5 - or 6-membered heterocyclic group selected from the group comprising piperidinyl and piperazinil; heterocyclic group may be substituted by 1 Deputy selected from the group consisting of a hydroxyl group is s, C1-C6alkyl groups and fenoxaprop, which may have a C1-C6alkoxygroup substituted by 1 to 3 halogen atoms), which includes the introduction of cyclohexadienone compounds represented by formula (2)

in the reaction with aminoven compound represented by the formula (3)

(where R1and R2have the above values), under neutral or basic conditions.

2. The method according to claim 1, where R1and R2together with the adjacent nitrogen atom may form piperidinyl group which may be substituted by 1 Deputy selected from the group consisting of a hydroxyl group of C1-C6alkyl groups; and fenoxaprop, substituted trihalogen-substituted C1-C6alkoxygroup.

3. The method according to claim 1, where aminophenolate connection is a 1-(4-hydroxyphenyl)-4-(4-triftormetilfosfinov)piperidine, 1-(4-hydroxyphenyl)-4-hydroxypiperidine, 1-(4-hydroxyphenyl)piperidine, 1-(4-hydroxyphenyl)-4-methylpiperazine, N-(4-hydroxyphenyl)-N-methylaniline, N-(4-hydroxyphenyl)aniline or N-(4-hydroxyphenyl)dibenzylamine.

4. The method according to claim 1, which is carried out in the presence of dehydrogenating agent, where dehydrogenative agent is used in amount of at least 1 wt.% in relation to the number of amine compounds is Oia formula (3).

5. The method according to claim 1, which is carried out under neutral conditions.

6. The method according to claim 1, which is carried out in the presence of a basic compound, where the compound is used in an amount of from 0.5 to 5 mol per 1 mol of amine compounds of the formula (3).

7. The method according to claim 1, where the reaction is carried out at a reaction temperature from room temperature to 150°C.

8. The method according to claim 1, where cyclohexadienone compound of the formula (2) is used in an amount of equimolar quantities of up to 10 mol per 1 mol of amine compounds of the formula (3).



 

Same patents:

FIELD: chemistry.

SUBSTANCE: in derivatives of 1,2-di(cyclo)substituted benzole of general formula I, their salts and hydrates , R10 is 5-10 member cycloalkyl, optionally substituted, or 5-10 member cycloalkenyl, optionally substituted, n=0, 1 or 2; XI is CH or nitrogen.

EFFECT: inhibiting activity with respect to cell adhesion or cell infiltration and application as therapeutic or preventive agent for inflammatory and autoimmune diseases, connected with adhesion and infiltration of leucocytes.

22 cl, 3 tbl, 118 ex

FIELD: chemistry.

SUBSTANCE: invention pertains to quaternary ammonium salts, with formula (I) where R1 represents alkyl with a straight or branched chain, with between 1 and 4 carbon atoms, R2 represents methyl or ethyl and X represents a fluorine containing anion. The invention also relates to electrolytes, electrolytic solutions and electrochemical devices.

EFFECT: invention provides for electrochemical devices, used under high voltages, with high discharge capacity and capable of discharging by large current; the invention provides for electrolytic solutions, with high stability under voltage and high electrolytic conductance.

151 cl, 77 ex, 47 tbl, 10 dwg

FIELD: medicine; pharmacology.

SUBSTANCE: composition is intended for treatment or prevention of insulin resistance of susceptible warm-blooded animals, including humans, and contains selective modulator of estrogen receptor EM-652-HC1, taken in amount determined by therapeutic efficiency.

EFFECT: effective treatment of prevention of insulin resistance development for warm-blooded mammals.

5 cl, 20 ex, 12 tbl, 8 dwg

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to novel substituted derivatives of 5-amino-1-pentene-3-ol of the general formula (I)

as a free form or as their physiologically compatible salts possessing the analgesic effect. In general formula (I) each R1 and R2 means independently of one another (C1-C6)-alkyl that can be branched or unbranched, saturated or unsaturated, unsubstituted or mono- or multi-substituted; or R1 and R2 form in common -(CH2)2-9-mono- or bicyclic ring; each R3 and R4 means independently of one another (C1-C6)-alkyl, or R3 and R4 form in common a ring and mean the group -CH2CH2NR22CH2CH2 wherein R22 represents (C1-C10)-alkyl; R5 means (C1-C10)-alkyl that is saturated or unsaturated, branched or unbranched, mono- or multi-substituted or unsubstituted, (C3-C9)-cycloalkyl that is saturated or means phenyl, heteroaryl that can be condensed with benzene ring and chosen from 5-membered heteroaryl with sulfur or oxygen atom as a heteroatom bound through saturated (C1-C3)-alkyl, phenyl bound through saturated (C1-C3)-alkyl-(C3-C10)-cycloalkyl wherein each among all these alkyl, phenyl, heteroaryl and cycloalkyl residues and independently of others can be unsubstituted or mono- or multi-substituted residues chosen independently of one another from the group comprising atoms F, Cl, Br, J, groups -OR18, (C1-C3)-alkyl) that is saturated or branched or unbranched, mono- or multi-substituted halide, or unsubstituted and wherein R18 represents hydrogen atom (H), (C1-C10)-alkyl that is saturated, branched or unbranched; R6 means (C1-C10)-alkyl that is saturated or unsaturated, branched or unbranched and unsubstituted, phenyl or heteroaryl that is chosen from 5-membered heteroaryl with oxygen atom as a heteroatom wherein each of them is unsubstituted or mono- or multi-substituted as indicated above; R7 means H. Also, invention relates to a medicinal agent based on proposed compounds and to a method for their synthesis.

EFFECT: improved method of synthesis, valuable medicinal properties of compounds.

10 cl, 493 ex

FIELD: organic chemistry, chemical technology.

SUBSTANCE: invention relates to novel [(heterylonio)-methylcarbonyloxypoly(alkyleneoxy)]-[(ammonio)methylcarbonyloxypoly(alkyleneoxy)]propane trichlorides of the general formula: wherein: at X+ = Y+ means X+ means -N+R1R2R3 wherein R1 = R2 means hydrogen atom (H); R3 means aliphatic hydrocarbon radical comprising 10-16 carbon atoms; a + c + e (total degree of oxypropylation) = 49; b + d + f (total degree of oxyethylation) = 9; at X+ = Y+ means Z+ means -N+R1R2R3 wherein R1 = R2 means H; R3 means aliphatic hydrocarbon radical comprising 10-16 carbon atoms; a + c + e = 55; b + d + f = 10; at X+ means Y+ = Z+ means -N+R1R2R wherein R1 = R2 means H; R3 means aliphatic hydrocarbon radical comprising 10-16 carbon atoms; a + c + e = 49; b + d + f = 9; at X+ means Y+ = Z+ means -N+R1R2R3 wherein R1 = R2 means H; R3 means aliphatic hydrocarbon radical comprising 10-16 carbon atoms; a + c + e = 55; b + d + f = 10; at X+ means Y+ = Z+ means -N+R1R2R3 wherein R1 = R2 means H; R3 means aliphatic hydrocarbon radical comprising 10-16 carbon atoms; a + c + e = 49; b + d + f = 0; at X+ means Y+ = Z+ means -N+R1R2R3 wherein R1 = R2 means H; R3 means aliphatic hydrocarbon radical comprising 10-16 carbon atoms; a + c + e = 55; b + d + f = 0; at X+ = Y+ means Z+ means -N+R1R2R3 wherein R1 = R2 means H; R3 means aliphatic hydrocarbon radical comprising 10-16 carbon atoms; a + c + e = 49; b + d + f = 0; at X+ = Y+ means Z+ means -N+R1R2R3 wherein R1 = R2 means H; R3 means aliphatic hydrocarbon radical comprising 10-16 carbon atoms; a + c + e = 55; b + d + f = 0, and to a method for their synthesis. Method involves interaction of 1,2,3-tris-[hydroxypoly(alkyleneoxy)]propane of the formula: wherein a + c + e = 55; b + d + f = 0-10 with monochloroacetic acid in the presence of acid catalysts, in organic solvent medium and with azeotropic removal of formed water and the following treatment at heating of the synthesized reaction productwith a mixture of morpholine and aliphatic amine in the molar ratio of reagents - hydroxyl derivative of propane: monochloroacetic acid : morpholine : aliphatic amine = 1:(3.0-3.2):(1.0-2.1):(1.0-2.1), respectively and wherein the total amount of morpholine and aliphatic amine is 3.0-3.2 mole. Novel compounds possess emulsifying properties for aqueous-bitumen and aqueous-mazut emulsions.

EFFECT: improved method of synthesis, valuable properties of compounds.

6 cl, 2 tbl, 8 ex

FIELD: organic chemistry, chemical technology.

SUBSTANCE: invention relates to novel 1,2,3-tris-[(ammonio)methylcarbonyloxypoly(alkyleneoxy)]-propane trichlorides of the general formula:

wherein at -X+ as -N+R1RR, R1 = R2 mean hydrogen atom (H), R3 means aliphatic hydrocarbon radical comprising 10-16 carbon atoms, a + c + e (the general degree of oxypropylation) = 49,b + d + f (the general degree of oxyethylation) = 0; at -X+ as -N+R1R2R3, R1 = R2 mean H, R3 means aliphatic hydrocarbon radical comprising 10-16 carbon atoms, a + c + e = 55, b + d + f = 0; at -X+ as -N+R1R2R3, R1 = R2 mean H, R3 means aliphatic hydrocarbon radical comprising 10-16 carbon atoms, a + c + e = 80, b + d + f = 24; at -X+ as -N+R1R2R3, R1 = R2 mean H, R3 means aliphatic hydrocarbon radical comprising 10-16 carbon atoms, a + c + e = 90, b + d + f = 27; at -X+ as -N+R1R2R3, R1 = R2 means H, R3 means phenyl, a + c + e = 80, b + d + f = 24; at -X+ as -N+R1R2R3, R1 = R2 mean H, R3 means phenyl, a + c + e = 90, b + d + f = 27; at -X+ as , a + c + e = 80, b + d + f = 24; at -X+ as , a + c + e = 90, b + d + f =27. Also, invention relates to a method for synthesis of these compounds. Method involves interaction of 1,2,3-tris-[hydroxypoly(alkyleneoxy)]-propane of the formula:

wherein a + c + e = 49-90, b + d + f = 0-27 with monochloroacetic acid in the presence of acidic catalyst, in boiling organic solvent medium with azeotropic removal of water formed and the following treatment of synthesized reaction product in polar solvent medium at heating with amino-compounds of the formula: NR1R2R3 wherein R1 = R2 mean H, R3 means aliphatic hydrocarbon radical comprising 10-16 carbon atoms, phenyl, or morpholine of the formula:

in the following mole ratios of reagents - propane hydroxyl derivative : monochloroacetic acid : amino-compound or morpholine = 1:(3.0-3.2):(3.0-3.2), respectively. New compounds show the bactericidal and fungicide activity and properties of demulsifying agents for petroleum emulsions.

EFFECT: improved method of synthesis, valuable properties of compounds.

7 cl, 3 tbl, 8 ex

FIELD: organic chemistry, medicine.

SUBSTANCE: invention relates to novel retinoid compounds of the structural formula (I) or their pharmaceutically acceptable salts and pharmaceutical compositions possessing agonistic activity with respect to retinoid receptors and comprising indicated compounds wherein n = 1; d = 0 or 1; B means -CR7=CR8-, -CH2O- wherein R7 and R8 each means independently hydrogen atom; X means phenyl optionally substituted with halogen atom, or 5-membered heteroaryl comprising sulfur atom (S) as a heteroatom; R1 means -C(=O)-R9 wherein R9 means alkyl, hydroxyl, amino-, heteroaryloxy-group comprising oxygen atom (O) or 6-membered heterocyclyl comprising nitrogen atom (N) as a heteroatom; R2 means: (a) -(CR10R11)m-Yp-R12; m means a whole number from 1 to 10; p means 0 or 1; R10 and R11 mean hydrogen atom; Y means -O-, -S- or -NR13-; R13 means hydrogen atom; R12 means hydrogen atom, alkyl, cycloalkyl, phenyl, 5- or 6-membered heteroaryl comprising atoms N, S, O as a heteroatom, 5- or 6-membered heteroarylalkyl comprising atoms N, S, O as a heteroatom, heteroalkyl comprising atoms N, S, O as a heteroatom, 5- or 6-membered heterocyclyl comprising atoms N, S, O as a heteroatom, or 5- or 6-membered heterocyclylalkyl comprising atoms N, S, O as a heteroatom under condition that when p means 0 then R12 doesn't mean hydrogen atom or alkyl; (b) 5- or 6-membered heteroaryl comprising atoms N, S, O as a heteroatom; (c) -Z-L wherein Z means -CR14=CR15-, -C≡C-, -C(=O) or -S-; R14 and R15 mean hydrogen atom; L means 5- or 6-membered heteroaryl comprising atoms N, S, O as a heteroatom; (d) -CR14=CR15-L1 wherein L1 means -S(O)2R17 or -SO2NR18R19 wherein R17 means alkyl; R18 and R19 mean hydrogen atom; each R3 means independently hydrogen atom, hydroxyl or oxo-group; t means 1 or 2.

EFFECT: valuable medicinal properties of compounds and compositions.

59 cl, 10 tbl, 54 ex

FIELD: organic chemistry, chemical technology.

SUBSTANCE: invention relates to a method for purifying racemic cis-6-phenyl-5-[4-(2-pyrrolidine-1-ylethoxy)phenyl]-5,6,7,8-tetrahydronaphthalene-2-ol that involves the following stages: (a) suspending racemic cis-6-phenyl-5-[4-(2-pyrrolidine-1-ylethoxy)phenyl]-5,6,7,8-tetrahydronaphthalene-2-ol in ethanol and tetrahydrofuran mixture to form suspension wherein indicated mixture of ethanol and tetrahydrofuran has the volume ratio from 4:1 to 1:1; (b) stirring and heating the indicated suspension; (c) cooling the indicated suspension from the stage (b), and (d) collection of solid purified racemic cis-6-phenyl-5-[4-(2-pyrrolidine-1-ylethocy)phenyl]-5,6,7,8-tetrahydronaphthalene-2-ol. Method provides preparing the end product containing less 0.1% of impurities.

EFFECT: improved purifying method.

11 cl, 11 tbl, 11 ex

FIELD: organic chemistry, medicine, endocrinology, pharmacy.

SUBSTANCE: invention relates to new derivatives of acylphenylurea of the formula (I) and to their physiologically acceptable salts possessing property of glycogen phosphorylase inhibitors. In compound of the formula (I) A means phenyl and phenyl residue can be substituted three times with fluorine (F), chlorine (Cl), bromine (Br) atoms, -CF3, -NO2, -O-(C1-C6)-alkyl, -SO2-(C1-C6)-alkyl, (C1-C6)-alkyl, -COOH; R1 means hydrogen atom (H), (C1-C6)-alkyl; R2 means H, (C1-C6(-alkyl, -CO-(C1-C6)-alkyl; 3, R4, R5 and R6 mean independently of one another H, F, Cl, Br, -O(C1-C6)-alkyl, (C1-C6)-alkyl, (C3-C7)-cycloalkyl, -COOH, -COO-(C1-C6)-alkyl; X means oxygen (O), sulfur (S) atom; R7 means (C1-C10)-alkylene-COOH, (C1-C10)-alkylene-COO-(C1-C6)-alkyl, (C1-C10)-alkylene-NH2, (C1-C10)-alkylene-NH-(C1-C6)-alkyl, (C1-C10)-alkylene-N-[(C1-C6)-alkyl]2, (C1-C10)-alkylene-B wherein B means piperidinyl or furyl. Also, invention relates to a pharmaceutical composition and a method for preparing the pharmaceutical composition. Proposed compounds can be used for preparing pharmaceutical composition useful for declining level of blood glucose and for treatment of diabetes mellitus type II.

EFFECT: improved preparing method, valuable medicinal properties of compounds and composition.

7 cl, 2 sch, 2 tbl, 1 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to derivatives of nitrogen-containing heterocyclic compounds of the general formula (I'):

wherein R represents the group:

m = 0-3; R1 represents halogen atom, cyano-group and others; X represents oxygen or sulfur atom, or the group -CH2 and others; Z1 and Z2 represents the group -CH2 and others; Q represents oxygen or sulfur atom, or the group -CH2 or -NH; R2 represents substituted phenyl; n = 0-2; R3 represents (C1-C6)-alkyl, (C1-C6)-alkoxycarbonyl group and others; R4, R5, R6 and R7 represent hydrogen atom or (C1-C6)-alkyl and others; R8 represents hydrogen atom, (C1-C6)-alkyl. Compounds of the formula (I') possess of activity modulating activity of chemokine MIP-1α receptors and can be used in medicine in treatment of inflammatory diseases and respiratory ways diseases.

EFFECT: improved preparing method, improved methods for treatment, valuable medicinal properties of compounds and composition.

20 cl, 283 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to derivatives of nitrogen-containing heterocyclic compounds of the general formula (I'):

wherein R represents the group:

m = 0-3; R1 represents halogen atom, cyano-group and others; X represents oxygen or sulfur atom, or the group -CH2 and others; Z1 and Z2 represents the group -CH2 and others; Q represents oxygen or sulfur atom, or the group -CH2 or -NH; R2 represents substituted phenyl; n = 0-2; R3 represents (C1-C6)-alkyl, (C1-C6)-alkoxycarbonyl group and others; R4, R5, R6 and R7 represent hydrogen atom or (C1-C6)-alkyl and others; R8 represents hydrogen atom, (C1-C6)-alkyl. Compounds of the formula (I') possess of activity modulating activity of chemokine MIP-1α receptors and can be used in medicine in treatment of inflammatory diseases and respiratory ways diseases.

EFFECT: improved preparing method, improved methods for treatment, valuable medicinal properties of compounds and composition.

20 cl, 283 ex

The invention relates to an anhydrous crystalline form of the hydrochloride R(-)-M-(4,4-di(3-methyltin-2-yl)but-3-enyl)-nicotinebuy acid, free from associated organic solvent (1), which is nephroscopes and thermally stable under normal storage conditions

The invention relates to the chemistry of fluorine-containing nitrogenous heterocycles, namely to a new connection, 2-trifluoromethyl-3-heptafluoroisopropyl-4,4-bystreptomyces-dalidio-2 formula (THBI)

with growth stimulating activity against pathogenic fungi Verticillium dahlia, Fusarium oxysporium, Thialaviopsis basicola, Risoctonia solani, and ergotaminum strain of ergot, which can find application in biotechnology

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention describes compound of the formula (I):

as a free form or salt wherein Ar means group of the formula (II):

wherein R1 means hydrogen atom or hydroxy-group; R2 and R3 each means independently of one another hydrogen atom or (C1-C4)-alkyl; R4, R5, R6 and R7 each means independently of one another hydrogen atom, (C1-C4)-alkoxy-group, (C1-C4)-alkyl or (C1-C4)-alkyl substituted with (C1-C4)-alkoxy-group; or R5 and R6 in common with carbon atoms to which they are joined mean 6-membered cycloaliphatic ring or 6-membered heterocyclic ring comprising two oxygen atoms; R8 means -NHR13 wherein R13 means hydrogen atom, (C1-C4)-alkyl or -COR14 wherein R14 means hydrogen atom; or R13 means -SO2R17 wherein R17 means (C1-C4)-alkyl; R9 means hydrogen atom; or R8 means -NHR18 wherein -NHR18 and R9 in common with carbon atoms to which they are joined mean 6-membered heterocycle; R10 means -OH; X means (C1-C4)-alkyl; Y means carbon atom; n = 1 or 2; p = 1; q = 1; r = 0 or 1. Also, invention describes pharmaceutical composition based on compound of the formula (I), a method for preparing compound of the formula (I) and intermediate compound that is used in the method for preparing. Compounds elicit the positive stimulating effect of β2-adrenoceptor.

EFFECT: improved preparing method, valuable medicinal properties of compounds.

13 cl, 3 tbl, 35 ex

The invention relates to new derivatives of 2- (iminomethyl) aminobenzoyl General formula (I) where a represents either a radical represented by the formula of the invention in which R1and R2denote, independently, a hydrogen atom, a group HE, a linear or branched alkyl or alkoxy having from 1 to 6 carbon atoms, R3means a hydrogen atom, a linear or branched alkyl with 1-6 carbon atoms or the radical COR4, R4means a linear or branched alkyl with 1-6 carbon atoms, or radicals represented by the formula of the invention, R5means a hydrogen atom, a group HE or linear or branched alkyl or alkoxy with 1-6 carbon atoms, means thienyl, X means Z1-, -Z1-CO-, -Z1-NR3-CO, -CH=CH-CO - or a simple bond, Y represents a radical chosen from the radicals Z2-Q, piperazinil, homopiperazine, -NR3-CO-Z2-Q-, -NR3-O-Z2-, -O-Z2Q-in which Q means a simple bond, -O-Z3and-N(R3)-Z3-, Z1, Z2and Z3means independently a simple link or a linear or branched alkylene with 1-6 carbon atoms, preferably Z1, Z2and Z3means -(CH2)m-, and m is an integer, R

The invention relates to organic chemistry, in particular to a technology for production of aromatic amines
The invention relates to the synthesis of intermediates for dyes, namely, the method of production of 4 - and 6-nitro-2-aminophenol
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