JP2019156841A - Azobenzene derivative and manufacturing method therefor - Google Patents

Abstract

To provide an azobenzene derivative useful as an intermediate of 2-substituted 4,4'-diaminoazobenzene used as a manufacturing raw material of a polyimide optical oriented film for liquid crystal display, and an effective manufacturing method therefor.SOLUTION: There is provided an azobenzene derivative represented by the general formula (1). Rrepresents a hydrogen atom, an alkyl group which may be substituted, an acyl group which may be substituted and an alkoxycarbonyl group which may be substituted. Rrepresents a hydrogen atom, an arylmethyl group which may be substituted, an alkali metal oxysulfonyl methyl group or an alkoxycarbonyl group which may be substituted. Ris a nitro group, an arylmethylamino group which may be substituted, an alkali metal oxysulfonyl methylamino group, or an alkoxycarbonyl amino group which may be substituted.SELECTED DRAWING: None

Description

  The present invention relates to an azobenzene derivative useful as a production intermediate of 4,4′-diaminoazobenzenes used as a raw material for producing a polyimide photo-alignment film for liquid crystal displays, and a method for producing the same.

Polyimide photo-alignment films having an azobenzene skeleton in the main chain are attracting attention as alignment films that have high ability to control the orientation of liquid crystal molecules, are stable against heat, light, and chemicals and can be used for high-speed operation. The polyimide photo-alignment film comprises 4,4′-diaminoazobenzene having no substituent on the benzene ring or 4,4′-diaminoazobenzene having various substituents on the benzene ring, and tetracarboxylic dianhydride. The polyamic acid obtained by the reaction is dissolved in an organic solvent, applied to a substrate, irradiated with linearly polarized ultraviolet light, and then thermally imidized (see, for example, Patent Documents 1 to 3).
In the production of 4,4'-diaminoazobenzenes that are the raw materials for such polyimide photo-alignment films, a known reaction is applied, for example, a azobenzene skeleton is constructed by diazo coupling reaction of a benzenediazonium salt and a benzene derivative. (For example, see Patent Documents 4 to 6 and Non-Patent Documents 1 to 6) Furthermore, in order to introduce an amino group or a desired substituent into a desired position of the azobenzene skeleton, a reduction reaction of nitro group to amino group or amino Various reactions such as introduction / elimination reaction of a protecting group to the group are appropriately combined.

JP-A-10-253963 JP 2005-275364 A JP 2011-008218 A US Patent Publication No. 2016 / 122285A1 International Publication No. 2011/024892 International Publication No. 2016/060174

Dyes and Pigments, 82 (3), 347-352; 2009 Journal of Enzyme Inhibition and Medicinal Chemistry, 31 (6), 1162-1169; 2016 Synthetic Metals, 206, 84-91; 2015 Chemical Communications (Cambridge, United Kingdom), 50 (93), 14613-14615; 2014 Journal of the American Chemical Society, 135 (26), 9777-9784; 2013 Bioconjugate Chemistry, 27 (3), 509-514; 2016

As described above, 4,4′-diaminoazobenzenes are composed of an azobenzene skeleton by diazo coupling reaction of a benzenediazonium salt and a benzene derivative, a reduction reaction of a nitro group to an amino group, and a protective group for an amino group. Manufactured by combining introduction and desorption reactions.
However, among the azobenzenes, the synthesis method is being studied because the types and positions of the substituents of the two benzene rings bonded to the 1,2-positions of the azo group (—NH═NH—) are equal. In fact, there are no reported examples of synthetic methods for compounds having a structure and having different types and substitution positions of substituents of two benzene rings (asymmetric azobenzene).

  Under such circumstances, as a raw material of the polyimide photo-alignment film, the present inventors have a hydroxymethyl group, an alkoxymethyl group, an acyloxymethyl group or an alkoxycarbonyloxymethyl group at the 2-position of one benzene ring. Attention was focused on 4′-diaminoazobenzenes (hereinafter collectively referred to as “2-substituted 4,4′-diaminoazobenzenes”). An object is to find an intermediate capable of efficiently producing the compound with high purity by a simple technique, and to provide a production method capable of efficiently producing the intermediate by a simple technique. We proceeded with examination.

  As a result of intensive studies to solve the above problems, the present inventors have a hydroxymethyl group, an alkoxymethyl group, an acyloxymethyl group or an alkoxycarbonyloxymethyl group at the 2-position of one benzene ring, An azobenzene derivative having an amino group or a substituted amino group protected with a specific protecting group at the 4-position and a substituted amino group protected with a nitro group or a specific protecting group at the 4′-position of the other benzene ring As an intermediate, the inventors have found that the desired 2-substituted 4,4′-diaminoazobenzenes can be produced with high purity and high yield by a simple technique. Furthermore, it has also been found that this azobenzene derivative can be efficiently produced by a simple method by performing a diazo coupling reaction between a specific benzenediazonium salt and a specific aniline derivative, and if necessary, a deprotection reaction or a reduction reaction. It was. The present invention has been proposed based on these findings, and specifically has the following configuration.

[1] An azobenzene derivative represented by the following general formula (1).
[In General Formula (1), R ¹ represents a hydrogen atom, an optionally substituted alkyl group, an optionally substituted acyl group, or an optionally substituted alkoxycarbonyl group. R ² represents a hydrogen atom, an optionally substituted arylmethyl group, an alkali metal oxysulfonylmethyl group, or an optionally substituted alkoxycarbonyl group. R ³ represents a nitro group, an optionally substituted arylmethylamino group, an alkali metal oxysulfonylmethylamino group, or an optionally substituted alkoxycarbonylamino group. ]
[2] R ^{1 in the} general formula (1) is a hydrogen atom, an unsubstituted alkyl group having 1 to 6 carbon atoms, an unsubstituted acyl group having 2 to 6 carbon atoms, or an unsubstituted alkoxycarbonyl group having 2 to 6 carbon atoms The azobenzene derivative according to [1], which is a group.
[3] R ^{2 in the} general formula (1) is a hydrogen atom, 4-methoxybenzyl group, 2,4-dimethoxybenzyl group, 3,4-dimethoxybenzyl group, 2-naphthylmethyl group, sodiooxysulfonylmethyl group or The azobenzene derivative according to [1] or [2], which is a tert-butyloxycarbonyl group.
[4] The azobenzene derivative according to any one of [1] to [3], wherein R ^{3 in the} general formula (1) is a nitro group or a tert-butyloxycarbonylamino group.
[5] An azobenzene derivative represented by the following general formula (1a) is produced by reacting a benzenediazonium salt represented by the following general formula (2a) with an aniline derivative represented by the following general formula (3a). A method for producing an azobenzene derivative.
[In the general formula (2a), X ⁻ represents a counter ion. R ³ represents a nitro group, an optionally substituted arylmethylamino group, an alkali metal oxysulfonylmethylamino group, or an optionally substituted alkoxycarbonylamino group. ]
[In General Formula (3a), R ¹ represents a hydrogen atom, an optionally substituted alkyl group, an optionally substituted acyl group, or an optionally substituted alkoxycarbonyl group. R ^2a represents an arylmethyl group which may be substituted, an alkali metal oxysulfonylmethyl group or an alkoxycarbonyl group which may be substituted. ]
[In General Formula (1a), R ¹ represents a hydrogen atom, an optionally substituted alkyl group, an optionally substituted acyl group, or an optionally substituted alkoxycarbonyl group. R ^2a represents an arylmethyl group which may be substituted, an alkali metal oxysulfonylmethyl group or an alkoxycarbonyl group which may be substituted. R ³ represents a nitro group, an optionally substituted arylmethylamino group, an alkali metal oxysulfonylmethylamino group, or an optionally substituted alkoxycarbonylamino group. ]
[6] A method for producing an azobenzene derivative, which comprises deprotecting an amino-protecting group R ^2a in an azobenzene derivative represented by the following general formula (1a) to produce an azobenzene derivative represented by the following general formula (1b).
[In General Formula (1a), R ¹ represents a hydrogen atom, an optionally substituted alkyl group, an optionally substituted acyl group, or an optionally substituted alkoxycarbonyl group. R ^2a represents an arylmethyl group which may be substituted, an alkali metal oxysulfonylmethyl group or an alkoxycarbonyl group which may be substituted. R ³ represents a nitro group, an optionally substituted arylmethylamino group, an alkali metal oxysulfonylmethylamino group, or an optionally substituted alkoxycarbonylamino group. ]
[In General Formula (1b), R ¹ represents a hydrogen atom, an optionally substituted alkyl group, an optionally substituted acyl group, or an optionally substituted alkoxycarbonyl group. R ³ represents a nitro group, an optionally substituted arylmethylamino group, an alkali metal oxysulfonylmethylamino group, or an optionally substituted alkoxycarbonylamino group. ]
[7] After obtaining an azobenzene derivative represented by the following general formula (1a) by reacting a benzenediazonium salt represented by the following general formula (2a) with an aniline derivative represented by the following general formula (3a) A method for producing an azobenzene derivative, wherein the azobenzene derivative represented by the following general formula (1b) is produced by deprotecting the protecting group R ^2a of the amino group in the azobenzene derivative represented by the general formula (1a).
[In the general formula (2a), X ⁻ represents a counter ion. R ³ represents a nitro group, an optionally substituted arylmethylamino group, an alkali metal oxysulfonylmethylamino group, or an optionally substituted alkoxycarbonylamino group. ]
[In General Formula (3a), R ¹ represents a hydrogen atom, an optionally substituted alkyl group, an optionally substituted acyl group, or an optionally substituted alkoxycarbonyl group. R ^2a represents an arylmethyl group which may be substituted, an alkali metal oxysulfonylmethyl group or an alkoxycarbonyl group which may be substituted. ]
[In General Formula (1a), R ¹ represents a hydrogen atom, an optionally substituted alkyl group, an optionally substituted acyl group, or an optionally substituted alkoxycarbonyl group. R ^2a represents an arylmethyl group which may be substituted, an alkali metal oxysulfonylmethyl group or an alkoxycarbonyl group which may be substituted. R ³ represents a nitro group, an optionally substituted arylmethylamino group, an alkali metal oxysulfonylmethylamino group, or an optionally substituted alkoxycarbonylamino group. ]
[In General Formula (1b), R ¹ represents a hydrogen atom, an optionally substituted alkyl group, an optionally substituted acyl group, or an optionally substituted alkoxycarbonyl group. R ³ represents a nitro group, an optionally substituted arylmethylamino group, an alkali metal oxysulfonylmethylamino group, or an optionally substituted alkoxycarbonylamino group. ]
[8] By reacting an azobenzene derivative represented by the following general formula (1ba) with a compound represented by the following general formula (5) in the presence of a base, an azobenzene derivative represented by the following general formula (1bb) is obtained. A method for producing an azobenzene derivative.
[In General Formula (1ba), R ^1a represents a hydrogen atom. R ³ represents a nitro group, an amino group, an arylmethylamino group which may be substituted, an alkali metal oxysulfonylmethylamino group or an alkoxycarbonylamino group which may be substituted. ]
[In General Formula (5), R ^1b represents an optionally substituted alkyl group, an optionally substituted acyl group, or an optionally substituted alkoxycarbonyl group. L represents a leaving group. ]
[In General Formula (1bb), R ^1b represents an optionally substituted alkyl group, an optionally substituted acyl group, or an optionally substituted alkoxycarbonyl group. R ³ represents a nitro group, an amino group, an arylmethylamino group which may be substituted, an alkali metal oxysulfonylmethylamino group or an alkoxycarbonylamino group which may be substituted. ]
[9] The hydrogen atom of the hydroxyl group at the 2-position of the azobenzene derivative represented by the following general formula (1c) is an optionally substituted alkyl group, an optionally substituted acyl group, or an optionally substituted alkoxycarbonyl. A method for producing an azobenzene derivative, wherein an azobenzene derivative represented by the following general formula (1d) is produced by substitution with a group.
[In General Formula (1c), R ^2a represents an optionally substituted arylmethyl group, an alkali metal oxysulfonylmethyl group, or an optionally substituted alkoxycarbonyl group. R ^3a represents an optionally substituted arylmethylamino group, an alkali metal oxysulfonylmethylamino group or an optionally substituted alkoxycarbonylamino group. ]
[In General Formula (1d), R ^1b represents an optionally substituted alkyl group, an optionally substituted acyl group, or an optionally substituted alkoxycarbonyl group. R ^2a represents an arylmethyl group which may be substituted, an alkali metal oxysulfonylmethyl group or an alkoxycarbonyl group which may be substituted. R ^3a represents an optionally substituted arylmethylamino group, an alkali metal oxysulfonylmethylamino group or an optionally substituted alkoxycarbonylamino group. ]
[10] R ^{1b in the} general formula (1d) is an optionally substituted acyl group or an optionally substituted alkoxycarbonyl group, the compound represented by the general formula (1c), and the following general formula (8): The method for producing an azobenzene derivative according to [9], wherein the azobenzene derivative represented by the general formula (1d) is produced by reacting the compound represented by the following general formula (9) or the following general formula (10): .
[In General Formula (8), General Formula (9), and General Formula (10), R ^1ba represents an optionally substituted alkyl group or an optionally substituted alkoxy group. R ^1bb represents an ^optionally substituted alkyl group. ]

  The azobenzene derivative of the present invention is useful as an intermediate for producing 2-substituted 4,4′-diaminoazobenzenes used as a raw material for producing a polyimide photo-alignment film for liquid crystal displays. In addition, the azobenzene derivative of the present invention can be efficiently produced by a simple method by performing a reaction between a specific benzenediazonium salt and a specific aniline derivative and, if necessary, a deprotection reaction or a reduction reaction. it can.

  Hereinafter, the present invention will be described in detail. The description of the constituent elements described below may be made based on representative embodiments and specific examples, but the present invention is not limited to such embodiments. In the present specification, a numerical range expressed using “to” or “from” means a range including numerical values described before and after “to” or “from” as a lower limit value and an upper limit value.

Azobenzene derivative The azobenzene derivative of the present invention has a structure represented by the general formula (1).

In the azobenzene derivative represented by the general formula (1) of the present invention, R ¹ represents a hydrogen atom, an optionally substituted alkyl group, an optionally substituted acyl group, or an optionally substituted alkoxycarbonyl group. To express. Preferably, R ¹ is substituted with a hydrogen atom, a halogen atom such as a fluorine atom or a chlorine atom, an alkyl group which may be substituted with a C 1-4 alkoxy group, or a halogen atom such as a fluorine atom or a chlorine atom. An acyl group which may be substituted or an alkoxycarbonyl group which may be substituted with a halogen atom such as a fluorine atom or a chlorine atom.
The alkyl group in R ¹ may be linear, branched or cyclic. The carbon number of the alkyl group is preferably 1 to 6, more preferably 1 to 4, and further preferably 1 to 3. Specific examples of the alkyl group include methyl group, ethyl group, propyl group, isopropyl group, butyl group, isobutyl group, sec-butyl group, tert-butyl group, pentyl group, isopentyl group, neopentyl group, tert-pentyl group, 1 Examples include -methylbutyl group, 1-ethylpropyl group, hexyl group, isohexyl group, 1-methylpentyl group, 1-ethylbutyl group and the like. The alkyl group in R ¹ may be substituted with a halogen atom. Examples of the halogen atom that can be substituted for the alkyl group include a fluorine atom, a chlorine atom, a bromine atom, and an iodine atom, and a fluorine atom is preferable. Specific examples of the alkyl group substituted with a halogen atom include a 2,2-difluoroethyl group, a 2,2,2-trifluoroethyl group, and a 3-fluoropropyl group. The alkyl group in R ¹ may be substituted with an alkoxy group having 1 to 4 carbon atoms, and the alkoxy group herein may be linear or branched. Specific examples of the alkoxy group include a methoxy group, an ethoxy group, a propoxy group, an isopropoxy group, and a butoxy group. The alkyl group in R ¹ is preferably a methyl group, an ethyl group, a propyl group, or an isopropyl group.
The acyl group for R ¹ may be linear, branched or cyclic. The acyl group here is a concept including both a structure in which an alkyl group is bonded to a carbonyl group and a structure in which an aryl group is bonded to a carbonyl group. The acyl group in R ¹ may be substituted with a halogen atom such as a fluorine atom or a chlorine atom. The acyl group preferably has 2 to 7 carbon atoms, more preferably 2 to 6 carbon atoms, still more preferably 2 to 4, and even more preferably 2 or 3. Specific examples of acyl groups include methanoyl group (formyl group), ethanoyl group (acetyl group), trifluoroacetyl group, trichloroacetyl group, propanoyl group (propionyl group), butanoyl group (butyryl group), isobutanoyl group (isobutyryl group) , Pentanoyl group (valeryl group), isopentanoyl group (isovaleryl group), sec-pentanoyl group (2-methylbutyryl group), tert-pentanoyl group (pivaloyl group), hexanoyl group, isohexanoyl group (4-methylpentanoyl group) Group), 2,2-dimethylbutanoyl group, 3,3-dimethylbutanoyl group, 2-methylpentanoyl group, 2-ethylbutanoyl group, benzoyl group, 2-fluorophenylcarbonyl group, 4-fluorophenylcarbonyl Group 2,4-difluorophenyl carbonate Examples thereof include a bonyl group, a 2,6-difluorophenylcarbonyl group, a 2,4,6-trifluorophenylcarbonyl group, a perfluorophenylcarbonyl group and the like, and an ethanoyl group (acetyl group) and a propanoyl group (propionyl group). Is preferred.
The alkoxycarbonyl group in R ¹ may be linear, branched, or cyclic. The alkoxycarbonyl group in R ¹ may be substituted with a halogen atom such as a fluorine atom or a chlorine atom. The carbon number of the alkoxycarbonyl group is preferably 2-6, more preferably 2-4, and even more preferably 2 or 3. Specific examples of the alkoxycarbonyl group include methoxycarbonyl group, ethoxycarbonyl group, propyloxycarbonyl group, isopropyloxycarbonyl group, butyloxycarbonyl group, isobutyloxycarbonyl group, sec-butyloxycarbonyl group, tert-butyloxycarbonyl group, Pentyloxycarbonyl group, isopentyloxycarbonyl group, neopentyloxycarbonyl group, tert-pentyloxycarbonyl group, 1-methylbutyloxycarbonyl group, 1-ethylpropyloxycarbonyl group, 2,2-ditrifluoroethyloxycarbonyl group , 2,2,2-trifluoroethyloxycarbonyl group, 1,1,2,2-tetrafluoroethyloxycarbonyl group, etc. , Ethoxycarbonyl group is preferred.
R ¹ is preferably a methyl group, an ethyl group, a propyl group, an ethanoyl group (acetyl group), an ethoxycarbonyl group, or a hydrogen atom from the viewpoint that the performance of the finally produced photo-alignment film can be improved.

R ² represents a hydrogen atom, an optionally substituted arylmethyl group, an alkali metal oxysulfonylmethyl group, or an optionally substituted alkoxycarbonyl group. Preferably, R ² is a hydrogen atom, a halogen atom such as a fluorine atom or a chlorine atom, an arylmethyl group which may be substituted with a C 1-4 alkyl group or a C 1-4 alkoxy group, an alkali metal It represents an alkoxycarbonyl group which may be substituted with an oxysulfonylmethyl group or a halogen atom such as a fluorine atom or a chlorine atom.
The aryl moiety of the arylmethyl group in R ² may be a single ring or a condensed ring. The carbon number of the aryl moiety is preferably 6 to 22, more preferably 6 to 14, and still more preferably 6 to 10. Specific examples of the aryl moiety include a phenyl group, a 1-naphthyl group, and a 2-naphthyl group. The arylmethyl group in R ² may be substituted with a halogen atom, and examples of the halogen atom herein include a fluorine atom, a chlorine atom, a bromine atom, and an iodine atom, preferably a fluorine atom and a chlorine atom. . The arylmethyl group in R ² may be substituted with an alkyl group having 1 to 4 carbon atoms, and the alkyl group here may be either linear or branched. Specific examples of the alkyl group include a methyl group, an ethyl group, a propyl group, an isopropyl group, and a butyl group. The arylmethyl group in R ² may be substituted with an alkoxy group having 1 to 4 carbon atoms, and the alkoxy group herein may be either linear or branched. Specific examples of the alkoxy group include a methoxy group, an ethoxy group, a propoxy group, an isopropoxy group, and a butoxy group. Specific examples of the arylmethyl group include 4-methoxybenzyl group, 2,4-dimethoxybenzyl group, 3,4-dimethoxybenzyl group, 2-naphthylmethyl group and the like.
Preferred examples of the alkali metal of the alkali metal oxysulfonylmethyl group that R ² can take include sodium and potassium. Preferred is a sodiooxysulfonylmethyl group.
The alkoxycarbonyl group in R ² may be linear, branched or cyclic, but is preferably branched. The alkoxycarbonyl group in R ² may be substituted with a halogen atom such as a fluorine atom or a chlorine atom. The carbon number of the alkoxycarbonyl group is preferably 2-6, more preferably 4-6, and even more preferably 4 or 5. For specific examples of the alkoxycarbonyl group, specific examples of the alkoxycarbonyl group in R ¹ can be referred to. The alkoxycarbonyl group in R ² is preferably an isopropyloxycarbonyl group, an isobutyloxycarbonyl group, a sec-butyloxycarbonyl group, or a tert-butyloxycarbonyl group, and particularly preferably a tert-butyloxycarbonyl group.
R ³ represents a nitro group, an optionally substituted arylmethylamino group, an alkali metal oxysulfonylmethylamino group, or an optionally substituted alkoxycarbonylamino group. Preferably, R ³ is a nitro group, a halogen atom such as a fluorine atom or a chlorine atom, an arylmethylamino group optionally substituted with a C 1-4 alkyl group or a C 1-4 alkoxy group, an alkali It represents an alkoxycarbonylamino group which may be substituted with a metal oxysulfonylmethylamino group or a halogen atom. For the explanation and preferred ranges and specific examples of the arylmethyl group, alkali metal oxysulfonylmethyl group or alkoxycarbonyl group in the amino group of R ³ , and preferred substituents thereof, see the corresponding description for R ^2. it can.

R ² can take a halogen atom such as a fluorine atom or a chlorine atom, an alkyl group having 1 to 4 carbon atoms, an arylmethyl group optionally substituted with an alkoxy group having 1 to 4 carbon atoms, an alkali metal oxysulfonylmethyl group, and An alkoxycarbonyl group optionally substituted with a halogen atom such as a fluorine atom or a chlorine atom; a halogen atom such as a fluorine atom or a chlorine atom in the amino group of R ³ ; an alkyl group having 1 to 4 carbon atoms; An arylmethyl group, an alkali metal oxysulfonylmethyl group, and an alkoxycarbonyl group optionally substituted with a halogen atom such as a fluorine atom or a chlorine atom, an azobenzene derivative, a diazo cup When synthesizing using a ring reaction or the like, the hydrogen atom of the 2-position hydroxy group is When substituted with a group or an alkoxycarbonyl group, functions as a protective group for protecting the amino group.
In the following description, “optionally substituted arylmethyl group, alkali metal oxysulfonylmethyl group and optionally substituted alkoxycarbonyl group” is referred to as “predetermined protecting group” and “optionally substituted”. The “arylmethylamino group, alkali metal oxysulfonylmethylamino group and optionally substituted alkoxycarbonylamino group” may be referred to as “an amino group protected with a predetermined protective group”.

As a preferred combination of R ^{1 to} R ³ , R ¹ is a hydrogen atom or an optionally substituted alkyl group, and R ² is a hydrogen atom, an optionally substituted arylmethyl group or an alkali metal oxysulfonylmethyl group. A combination in which R ³ is a nitro group, R ¹ is an optionally substituted acyl group or an optionally substituted alkoxycarbonyl group, and R ² is an optionally substituted alkoxycarbonyl group And a combination in which R ³ is an optionally substituted alkoxycarbonylamino group.

Hereinafter, specific examples of the azobenzene derivative represented by the general formula (1) are illustrated. However, the azobenzene derivative represented by the general formula (1) that can be used in the present invention should not be limitedly interpreted by these specific examples.

[Uses of azobenzene derivatives]
By synthesizing 4,4′-diaminoazobenzenes using the azobenzene derivative represented by the general formula (1) as an intermediate, the 2-position is useful as a raw material for a photo-alignment film, and the 2-position is a hydroxymethyl group, an alkoxymethyl group, an acyloxy group 4,4′-diaminoazobenzenes substituted with a methyl group or an alkoxycarbonyloxymethyl group (collectively referred to as “2-substituted 4,4′-diaminoazobenzenes”) with high purity by a simple technique. It can be manufactured efficiently. Therefore, the azobenzene derivative represented by the general formula (1) is useful as an intermediate for producing 2-substituted 4,4′-diaminoazobenzenes.
Specifically, for example, a known reaction is simply applied to construct an azobenzene skeleton, and a combination of a reduction reaction of a nitro group to an amino group and an introduction / elimination reaction of a protecting group to the amino group, and the like. -When trying to synthesize asymmetric azobenzenes such as substituted 4,4'-diaminoazobenzenes, the number of steps increases, and the purity and yield are reduced due to loss of raw materials and products in each step and contamination of impurities. Tend to be lower.
On the other hand, in the present invention, for example, among the azobenzene derivatives represented by the general formula (1),
(I) R ¹ is an optionally substituted alkyl group, R ² is a hydrogen atom, and R ³ is a nitro group (for example, azobenzene derivatives A1 to A5) reduce the nitro group of R ³ Can be converted to 4,4′-diamino-2- (alkoxymethyl) azobenzenes. Also,
(II) In the general formula (1), R ¹ is an optionally substituted alkyl group, R ² is a predetermined protecting group, and R ³ is a nitro group (for example, azobenzene derivatives B1 to B6) The group constituting R ² can be converted to 4,4′-diamino-2- (alkoxymethyl) azobenzenes by reducing (deprotecting) the group constituting R ² and then reducing the nitro group of R ^3. .
(III) In the general formula (1), when R ¹ and R ² are both hydrogen atoms and R ³ is a nitro group (for example, azobenzene derivative C1), the nitro group of R ³ is reduced to an amino group. By conversion, 4,4′-diamino-2- (hydroxymethyl) azobenzenes can be obtained, and by substituting the hydrogen atom of R ¹ with an alkyl group (alkylation of the hydroxyl group), 4,4′- Diamino-2- (alkoxymethyl) azobenzenes can be produced.
(IV) In the general formula (1), R ¹ is a hydrogen atom, R ² is a predetermined protecting group, and R ³ is a nitro group (for example, azobenzene derivatives D1 and D2), a group constituting R ² 4,4′-diamino-2- (hydroxymethyl) azobenzenes can be obtained by converting (deprotecting) to a hydrogen atom, reducing the nitro group constituting R ³ and converting it to an amino group, 4,4′-diamino-2- (alkoxymethyl) azobenzenes can be generated by substituting the hydrogen atom of R ¹ with an alkyl group (alkylation of the hydroxyl group).
(V) In the general formula (1), R ¹ is an optionally substituted acyl group or an optionally substituted alkoxycarbonyl group, R ² is a predetermined protecting group, and R ³ is protected by a predetermined protecting group. In the case of the amino group (for example, azobenzene derivatives E1 and E2), the group constituting R ² is converted to a hydrogen atom (deprotection) and R ³ is deprotected and converted to an amino group. 4,4′-diamino-2- (acyloxymethyl) azobenzenes or 4,4′-diamino-2- (alkoxycarbonyloxymethyl) azobenzenes can be obtained.
Further, in the method described in the above (I) and (II) column, when R ¹ is an optionally substituted acyl group or an optionally substituted alkoxycarbonyl group, By the same operation as described in each column, 4,4′-diamino-2- (acyloxymethyl) azobenzenes or 4,4′-diamino-2- (alkoxycarbonyloxymethyl) azobenzenes can be obtained. .
In addition, when the substituent for replacing the hydrogen atom of R ¹ is changed to an acyl group or an alkoxycarbonyl group by the method described in the above columns (III) and (IV), it is the same as described in each column. By the above operation, 4,4′-diamino-2- (acyloxymethyl) azobenzenes or 4,4′-diamino-2- (alkoxycarbonyloxymethyl) azobenzenes can be obtained.
Further, in the method described in the column (V) above, when R ¹ is an optionally substituted alkyl group, the same operation as described in this column is performed. 4'-diamino-2- (alkoxymethyl) azobenzenes can be obtained.
That is, even when any azobenzene derivative is used as an intermediate, the target 2-substituted 4,4′-diaminoazobenzenes can be produced with a relatively small number of steps, thereby realizing high purity and high yield. can do.
The details of the method for producing 2-substituted 4,4′-diaminoazobenzenes using the azobenzene derivative of the present invention as an intermediate will be described in the column for the method for producing 4,4′-diaminoazobenzenes below. . Here, as a representative, R ^{1 in the} general formula (1) is a hydrogen atom, an optionally substituted alkyl group, an optionally substituted acyl group, or an optionally substituted alkoxycarbonyl group, and R ² is When using a hydrogen atom, an azobenzene derivative in which R ³ is a nitro group, and R ¹ is an optionally substituted alkyl group, an optionally substituted acyl group or an optionally substituted alkoxycarbonyl group, The case where an azobenzene derivative in which R ² is a predetermined protecting group and R ³ is an amino group protected by a predetermined protecting group is used as an example, but other azobenzene derivatives (R ² is a predetermined protecting group, R ³ When an azobenzene derivative having a nitro group is used as an intermediate, the method described in the column for the production method of 4,4′-diaminoazobenzenes and an azobenzene derivative are used. Reference can be made to the descriptions of the deprotection step of the amino group in the first production method of the body (step 1-2).
Further, 2-substituted 4,4′-diaminoazobenzenes produced using the azobenzene derivative of the present invention as an intermediate are useful as a raw material for a photoalignment film. That is, the coating film of the polyamic acid solution produced using 2-substituted 4,4′-diaminoazobenzenes as a raw material is imparted with orientation by irradiation with linearly polarized ultraviolet light, and then heated and baked. The alkoxy group, acyl group, or alkoxycarbonyl group substituted at the 2-position reacts with the azo group to form a cyclic structure, and the photo-alignment film does not contain the azobenzene group. Since the formed photo-alignment film does not contain an azobenzene group, for example, when used for a liquid crystal alignment film of a liquid crystal display element, the voltage holding ratio of the liquid crystal display element is lowered even when exposed to intense light for a long time. Therefore, high display quality can be maintained.
The purity of the azobenzene derivative used for the production of 4,4′-diaminoazobenzenes is that the desired 4,4′-diaminoazobenzenes are obtained with high purity, and from the viewpoint of improving the quality of the finally obtained photoalignment film, Preferably it is 95% or more, More preferably, it is 98% or more, More preferably, it is 99% or more.

Production method of azobenzene derivative Next, the production method (first production method to fourth production method) of the azobenzene derivative of the present invention will be described in detail. The azobenzene derivative represented by the general formula (1) of the present invention can be efficiently produced by a simple method by using the method for producing an azobenzene derivative of the present invention.

[First production method of azobenzene derivative]
In the first production method of the azobenzene derivative, among the azobenzene derivatives represented by the general formula (1) of the present invention, R ² may be an arylmethyl group, an alkali metal oxysulfonylmethyl group or a substituted one. A compound which is a good alkoxycarbonyl group (predetermined protecting group), that is, an azobenzene derivative represented by the following general formula (1a) is produced. Specifically, the benzenediazonium salt represented by the following general formula (2a) and the aniline derivative represented by the following general formula (3a) are reacted (step 1-1), thereby being represented by the general formula (1a). An azobenzene derivative (1a) is produced.

In the benzenediazonium salt represented by the general formula (2a), X ⁻ represents a counter ion. Counter ions represented by X ⁻ include halide ions such as Cl ⁻ and Br ⁻ , hydrogen sulfate ions (HSO ₄ ⁻ ), nitrate ions (NO ₃ ⁻ ), perchlorate ions (ClO ₄ ⁻ ), tetra Examples thereof include fluoroborate ions (BF ₄ ⁻ ) and hexafluorophosphate ions (PF ₆ ⁻ ). X ⁻ is preferably a halide ion such as Cl ⁻ or Br ⁻ or a hydrogen sulfate ion (HSO ₄ ⁻ ) in that the benzenediazonium salt (2a) can be easily prepared.
In the aniline derivative represented by the general formula (3a) and the azobenzene derivative represented by the general formula (1a), R ¹ is a hydrogen atom, an optionally substituted alkyl group, an optionally substituted acyl group or a substituted group. Represents an optionally substituted alkoxycarbonyl group, and R ^2a represents an optionally substituted arylmethyl group, an alkali metal oxysulfonylmethyl group, or an optionally substituted alkoxycarbonyl group.
In the benzenediazonium salt represented by the general formula (2a) and the azobenzene derivative represented by the general formula (1a), R ³ represents a nitro group, an optionally substituted arylmethylamino group, an alkali metal oxysulfonylmethylamino group or It represents an optionally substituted alkoxycarbonylamino group.
Here, description and preferred ranges of the radicals represented by R ^1, for example, the general formula (1) can be referred to the corresponding description of R ^1, the preferred and description of each group represented by R ^2a For the range and specific examples, the corresponding description of R ^{2 in the} general formula (1) can be referred to. For the explanation of each group represented by R ³ and the preferred range and specific examples, the general formula (1) Reference may be made to the corresponding description for R ³ .

The reaction between the benzenediazonium salt represented by the general formula (2a) and the aniline derivative represented by the general formula (3a) (the reaction in the step 1-1) is a diazo coupling reaction, which is a common in diazo coupling reactions. The reaction conditions can be adopted. For example, by carrying out the reaction in the presence of a carboxylate such as sodium acetate or potassium acetate, the azobenzene derivative represented by the general formula (1a) as the target product can be obtained in high yield. Here, it does not restrict | limit in particular in the usage-amount of carboxylate, The usage-amount normally used by a diazo coupling reaction is employable.
The reaction of step 1-1 can be carried out in a solvent. Examples of the solvent include water, alcohol solvents such as methanol and ethanol, aprotic solvents such as N, N-dimethylformamide (DMF), tetrahydrofuran (THF), acetonitrile, acetone, dimethyl sulfoxide (DMSO), or a mixed solvent thereof. Can be used.
The reaction temperature in Step 1-1 can be appropriately selected from the range of 0 to 50 ° C. The reaction time varies depending on other conditions such as the reaction temperature, but 1 to 5 hours is appropriate.

  The azobenzene derivative obtained by the reaction in Step 1-1 may be subjected to the next reaction (for example, the following second production method) without being purified, or may be subjected to the next reaction after being purified. . Examples of purification methods include extraction, column chromatography, and recrystallization.

  Here, the benzenediazonium salt represented by the general formula (2a) used as the raw material in Step 1-1 can be obtained by a general synthesis method of a diazonium salt using the corresponding 4-nitroaniline as a raw material. For the method of synthesizing the diazonium salt, for example, the method described in Journal of Heterocyclic Chemistry, 42, 781-786; 2005 can be referred to. Regarding the method for synthesizing the aniline derivative (3a) represented by the general formula (3a), the following <Method for producing aniline derivative> can be referred to.

[Second production method of azobenzene derivative]
In the second method for producing an azobenzene derivative, among the azobenzene derivatives represented by the general formula (1) of the present invention, a compound in which R ² is a hydrogen atom, that is, an azobenzene derivative represented by the following general formula (1b) is produced. Specifically, by the step (step 1-2) of converting (deprotecting) the protecting group R ^2a of the amino group of the azobenzene derivative represented by the following general formula (1a) into a hydrogen atom, the following general formula (1b) The azobenzene derivative shown is produced.

R ¹ , R ^2a and R ³ in the general formula (1a) have the same meanings as R ¹ , R ^2a and R ³ in the general formula (1a) in the first production method of the azobenzene derivative, respectively. R ¹ and R ³ have the same meanings as R ¹ and R ³ in the general formula (1a) in the first production method, respectively. That is, R ¹ represents a hydrogen atom, an optionally substituted alkyl group, an optionally substituted acyl group, or an optionally substituted alkoxycarbonyl group, and R ^2a represents an optionally substituted aryl. Represents a methyl group, an alkali metal oxysulfonylmethyl group or an optionally substituted alkoxycarbonyl group, and R ³ represents a nitro group, an optionally substituted arylmethylamino group, an alkali metal oxysulfonylmethylamino group or a substituted Represents an optionally substituted alkoxycarbonylamino group. For their explanation, preferred range, and specific examples, the corresponding description of general formula (1a) of the first production method of azobenzene derivatives can be referred to.
The azobenzene derivative represented by the general formula (1a) may be an azobenzene derivative obtained by the above-mentioned first production method or an azobenzene derivative obtained by another method. The obtained azobenzene derivative is preferable.

The reaction in Step 1-2 can produce the target azobenzene derivative represented by the general formula (1b) with high yield by utilizing a deprotection method suitable for the protecting group R ^2a of the amino group.
As the deprotection method, when the protecting group R ^2a of the amino group is an arylmethyl group which may be substituted, an alkali metal oxysulfonylmethyl group or an alkoxycarbonyl group which may be substituted, hydrogenolysis Deprotection with (for example, H ₂ , Pd / C), deprotection under oxidizing conditions, deprotection under strongly acidic conditions, and the like can be mentioned. Among these, deprotection under oxidizing conditions is preferable, and quinone-based oxidizing reagents such as 2,3-dichloro-5,6-dicyano-p-benzoquinone (DDQ), p-chloranil, o-chloranil, and diammonium cerium nitrate (IV Deprotection under mild oxidation conditions using an oxidizing agent such as) is more preferable because it does not harm other substituents of the azobenzene derivative represented by the general formula (1a). Moreover, trifluoroacetic acid (TFA) and hydrochloric acid can be used for deprotection under strongly acidic conditions.
These hydrogenolysis, oxidation conditions, or deprotection reactions under strongly acidic conditions can be carried out in an organic solvent. As the organic solvent, any solvent that does not harm the reaction can be used. Specifically, halogen solvents such as dichloromethane and chloroform, ethers such as dioxane, tetrahydrofuran (THF), diisopropyl ether, and cyclopentyl methyl ether. A system solvent can be illustrated. These organic solvents may be used alone or in combination of two or more.
The reaction temperature in this deprotection reaction can be appropriately selected from the range of room temperature to 60 ° C., whereby the azobenzene derivative represented by the general formula (1b), which is the target product, can be obtained in good yield. The reaction time varies depending on other conditions such as the reaction temperature, but 2 to 48 hours is appropriate.

The protective group R ^2a amino groups in the case of Soviet geo oxysulfonyl methyl group, by hydrolysis in an alkaline aqueous solution, can be deprotected easily protecting group R ^2a. Examples of the alkali used for deprotection include alkali metal hydroxides and alkaline earth metal hydroxides. Among them, it is preferable to use an alkali metal hydroxide such as sodium hydroxide or potassium hydroxide because it is inexpensive and an azobenzene derivative represented by the general formula (1b) can be obtained with good yield.
The deprotection reaction by alkaline hydrolysis can be performed in an aqueous solution, but in a mixed solvent of an organic solvent and an alkaline aqueous solution that is uniformly mixed with water such as methanol, ethanol, and THF, or in toluene, xylene, dichloromethane, or the like. It may be carried out in a two-layer system that does not mix with water.
The reaction temperature in this deprotection reaction can be appropriately selected from the range of room temperature to the solvent reflux temperature, whereby the azobenzene derivative represented by the general formula (1b) as the target product can be obtained in high yield. . The reaction time varies depending on other conditions such as the reaction temperature, but 1 to 3 hours is appropriate.

Further, when the protecting group R ^2a of the amino group is an alkoxycarbonyl group, by acid treatment, it can be deprotected easily protecting group R ^2a. Examples of the acid used for deprotection include TFA and hydrochloric acid.
The deprotection reaction by acid treatment can be carried out in an organic solvent. As the organic solvent, any solvent that does not harm the reaction can be used. Specifically, halogen solvents such as dichloromethane and chloroform, ethers such as dioxane, tetrahydrofuran (THF), diisopropyl ether, and cyclopentyl methyl ether. A system solvent can be illustrated. These organic solvents may be used alone or in combination of two or more.
The reaction temperature in this deprotection reaction can be appropriately selected from the range of room temperature to the reflux temperature of the solvent, whereby the target azobenzene derivative represented by the general formula (1b) can be obtained in good yield. Can do. The reaction time varies depending on other conditions such as the reaction temperature, but 2 to 24 hours is appropriate.

[Third production method of azobenzene derivative]
In the third production method of an azobenzene derivative, among the azobenzene derivatives represented by the general formula (1) of the present invention, a compound in which R ¹ is an optionally substituted alkyl group and R ² is a hydrogen atom, that is, An azobenzene derivative represented by the general formula (1bb) is produced. Specifically, by the step of reacting an azobenzene derivative represented by the following general formula (1ba) with a compound represented by the following general formula (5) in the presence of a base (step 2-1), the following general formula ( An azobenzene derivative represented by 1bb) is produced.

R ^{1a in the} general formula (1ba) represents a hydrogen atom.
R ^{1b in} general formula (5) and general formula (1bb) represents an optionally substituted alkyl group, an optionally substituted acyl group, or an optionally substituted alkoxycarbonyl group.
R ^{3 in the} general formula (1ba) and the general formula (1bb) is a nitro group, an amino group, an optionally substituted arylmethylamino group, an alkali metal oxysulfonylmethylamino group or an optionally substituted alkoxycarbonylamino group. Represents.
Here, for the explanation and preferred ranges and specific examples of each group represented by R ^1b , the corresponding description of R ^{1 in the} general formula (1) can be referred to, and explanation and preferred of each group represented by R ^3. For the range and specific examples, the corresponding description of R ^{3 in the} general formula (1) can be referred to.
L in the general formula (5) represents a leaving group. Examples of the leaving group represented by L in the general formula (5) include halogen atoms such as bromine atom and iodine atom, methanesulfonyloxy group, trifluoromethanesulfonyloxy group, benzenesulfonyloxy group, p-toluenesulfonyloxy group and the like. The sulfonyloxy group of can be illustrated.

The reaction of the azobenzene derivative represented by the general formula (1ba) and the compound represented by the general formula (5) (step 2-1) is carried out in the presence of a base. Examples of the base include alkali metal hydroxides such as sodium hydroxide and potassium hydroxide, alkali metal carbonates such as sodium carbonate and potassium carbonate, alkali metal hydrides such as sodium hydride, sodium methoxide and sodium ethoxide. Examples thereof include alkali metal alkoxides and tetrabutylammonium hydroxide. There is no restriction | limiting in particular in the usage-amount of a base, What is necessary is just to use 1-5 mol equivalent with respect to the azobenzene derivative shown by General formula (1ba) as a raw material.
The reaction of step 2-1 can be carried out in a solvent. As the solvent, any solvent that does not harm the reaction can be used. For example, ether solvents such as diethyl ether, diisopropyl ether, cyclopentyl methyl ether, dimethoxyethane, tetrahydrofuran (THF), dioxane, acetonitrile, Nitrile solvents such as pionitrile, aromatic solvents such as benzene, toluene, xylene, chlorobenzene and dichlorobenzene, amide solvents such as N, N-dimethylformamide (DMF) and N, N-dimethylacetamide, dimethyl sulfoxide ( DMSO), water and the like. These solvents may be used alone or in combination of two or more.
The reaction temperature in Step 2-1 can be appropriately selected from the range of the reflux temperature of the solvent used from room temperature. The reaction time varies depending on other conditions such as the reaction temperature, but 1 to 24 hours is appropriate.

[Fourth Production Method of Azobenzene Derivative]
In the fourth production method of an azobenzene derivative, among the azobenzene derivatives represented by the general formula (1) of the present invention, R ¹ is a hydrogen atom, R ² is an optionally substituted arylmethyl group, an alkali metal oxysulfonylmethyl group Alternatively, an optionally substituted alkoxycarbonyl group (predetermined protecting group), an arylmethylamino group on which R ³ may be substituted, an alkali metal oxysulfonylmethylamino group, or an optionally substituted alkoxycarbonylamino group ( An amino group protected with a predetermined protecting group), that is, an azobenzene derivative represented by the following general formula (1c), an alkyl group that R ¹ may be substituted, an acyl group that may be substituted, or substituted it is also good alkoxycarbonyl group, a protected R ² is given protecting group, R ³ is predetermined Compounds in a protected amino group, namely the production of azobenzene derivative represented by the following general formula (1d). Specifically, a predetermined protecting group is introduced into the amino group of 4,4′-diamino-2- (hydroxymethyl) -azobenzene represented by the following formula (4c), and it is represented by the following general formula (1c). And a hydrogen atom of the hydroxymethyl group of the compound represented by the following general formula (1c), an alkyl group which may be substituted, or an acyl group which may be substituted Alternatively, an azobenzene derivative represented by the following general formula (1d) is produced by the step of substitution with an optionally substituted alkoxycarbonyl group (step 7-2).

R ^{1b in the} general formula (1d) represents an optionally substituted alkyl group, an optionally substituted acyl group, or an optionally substituted alkoxycarbonyl group.
R ^{2a in} general formula (1c) and general formula (1d) represents an optionally substituted arylmethyl group, an alkali metal oxysulfonylmethyl group, or an optionally substituted alkoxycarbonyl group.
R ^{3a in} general formula (1c) and general formula (1d) represents an optionally substituted arylmethylamino group, an alkali metal oxysulfonylmethylamino group or an optionally substituted alkoxycarbonylamino group.
Here, for the explanation and preferred ranges and specific examples of each group represented by R ^1b , the corresponding description of R ^{1 in the} general formula (1) can be referred to, and explanations and preferred descriptions of the groups represented by R ^2a are preferable. For the range and specific examples, the corresponding description of R ^{2 in the} general formula (1) can be referred to. For the explanation of each group represented by R ^3a and the preferred range and specific examples, the general formula (1) Reference may be made to the corresponding description for R ³ .
The 4,4′-diamino-2- (hydroxymethyl) -azobenzene represented by the formula (4c) may be an azobenzene derivative obtained by the first production method of 4,4′-diaminoazobenzene described later. Although it may be obtained by other methods, it is preferably obtained by the first production method of 4,4′-diaminoazobenzene described later.

In Step 7-1, for example, an azobenzene derivative in which R ^{2a in the} general formula (1c) is an alkoxycarbonyl group and R ^3a is an alkoxycarbonylamino group is 4,4′-diamino- represented by the following formula (4c). It can be obtained by reacting 2- (hydroxymethyl) -azobenzene with a carbonic acid ester represented by the following general formula (7).

In General Formula (7), R ^23a represents an alkyl group which may be substituted. The alkyl group for R ^23a may be linear, branched or cyclic, but is preferably branched. The carbon number of the alkyl group is preferably 1 to 5, more preferably 3 to 5, and even more preferably 3 or 4. Specific examples of the alkyl group include methyl group, ethyl group, propyl group, isopropyl group, butyl group, isobutyl group, sec-butyl group, tert-butyl group, pentyl group, isopentyl group, neopentyl group, tert-pentyl group, 1 -A methylbutyl group, 1-ethylpropyl group, etc. can be illustrated, An isopropyl group, an isobutyl group, a sec-butyl group, and a tert-butyl group are preferable, and a tert-butyl group is especially preferable.

The reaction (step 7-1) of the azobenzene derivative represented by the general formula (4c) and the compound represented by the general formula (7) is protection of the amino group. There is no restriction | limiting in particular in the usage-amount of the carbonic acid ester shown by General formula (7) used at process 7-1, If it uses 2-5 mol equivalent with respect to the azobenzene derivative shown by General formula (4c) as a raw material. Good.
The reaction in step 7-1 can be carried out in an organic solvent. The organic solvent is not particularly limited as long as it does not harm the reaction, for example, halogen solvents such as dichloromethane and chloroform, ether solvents such as dioxane, THF, diisopropyl ether, cyclopentyl methyl ether, Examples include aromatic organic solvents such as benzene and toluene, and amide solvents such as DMF and N, N-dimethylacetamide. These organic solvents may be used alone or in combination of two or more. Among these, ether solvents such as dioxane, THF, diisopropyl ether, and cyclopentyl methyl ether are preferable in that the azobenzene derivative represented by the general formula (1c) can be obtained with high yield. These organic solvents may be used alone or in combination of two or more.
In addition, the reaction in Step 7-1 can be promoted in the presence of a base. Bases include tertiary amines such as triethylamine, diisopropylethylamine, tributylamine, aromatic amines such as pyridine, N, N-dimethyl-4-aminopyridine (DMAP), and alkali metal waters such as sodium hydroxide and potassium hydroxide. Examples include oxides, alkali metal carbonates such as sodium carbonate and potassium carbonate, alkali metal hydrides such as sodium hydride, alkali metal alkoxides such as sodium methoxide and sodium ethoxide, and tetrabutylammonium hydroxide. . Among these, tertiary amines such as triethylamine, diisopropylethylamine, and tributylamine are preferable in that the azobenzene derivative represented by the general formula (1c) can be obtained with high yield. There is no restriction | limiting in particular in the usage-amount of a base, What is necessary is just to use 1-2 mol equivalent with respect to the azobenzene derivative shown by General formula (4c).
The reaction temperature in step 7-1 can be appropriately selected from the range of the reflux temperature of the solvent used from 0 ° C., and since a high yield is obtained, the reaction is carried out while controlling the temperature to be 40 to 60 ° C. It is preferable to carry out. The reaction time varies depending on other conditions such as the reaction temperature, but 2 to 24 hours is appropriate.

The azobenzene derivative obtained by the reaction in Step 7-1 may be used for the next reaction without purification, or may be used for the next reaction after purification. Examples of purification methods include extraction, column chromatography, and recrystallization.
In Step 7-2, the hydrogen atom of the hydroxyl group at the 2-position of the azobenzene derivative represented by the general formula (1c) is optionally substituted with an alkyl group, optionally substituted acyl group, or optionally substituted. An azobenzene derivative represented by the general formula (1d) is produced by substitution with an alkoxycarbonyl group. The azobenzene derivative in which R ^{1b in the} general formula (1d) is an acyl group includes an azobenzene derivative represented by the general formula (1c) and a carboxylic acid anhydride represented by the following general formula (8) or the following general formula (9). The azobenzene derivative which can be obtained by a reaction with the carboxylic acid chloride shown, wherein R ^{1b in the} general formula (1d) is an alkoxycarbonyl group, includes the azobenzene derivative represented by the general formula (1c) and the following general formula (9) It can obtain by reaction with the chloroformate shown by or carbonic acid ester shown by the following general formula (10).

In General Formula (8), General Formula (9), and General Formula (10), R ^1ba represents an optionally substituted alkyl group or alkoxy group. The alkyl group for R ^1ba may be linear, branched, or cyclic. The carbon number of the alkyl group is preferably 1 to 5, more preferably 1 to 3, and even more preferably 1 or 2. For specific examples of the alkyl group, specific examples of the alkyl group in R ^23a can be referred to. The alkyl group for R ^1ba is preferably a methyl group or an ethyl group. Moreover, about the process 7-2, the description about the process 2-1 in said 3rd manufacturing method of an azobenzene derivative can also be referred. The carbon number of the alkoxy group in R ^1ba is preferably 1 to 5, more preferably 1 to 3, and even more preferably 1 or 2. The alkoxy group for R ^1ba is preferably a methoxy group or an ethoxy group. R ^1bb represents an ^optionally substituted alkyl group. The alkyl group in R ^1bb may be linear, branched, or cyclic. The carbon number of the alkyl group is preferably 1 to 5, more preferably 1 to 3, and even more preferably 1 or 2. For specific examples of the alkyl group, specific examples of the alkyl group in R ^23a can be referred to. The alkyl group for R ^1ba is preferably a methyl group or an ethyl group.

Reaction of the azobenzene derivative represented by general formula (1c) with the compounds represented by general formula (8), general formula (9) and general formula (10) (step 7-2) is acylation and alkoxycarbonylation of the hydroxy group. It is. There is no restriction | limiting in particular in the usage-amount of the carboxylic acid anhydride, carboxylic acid chloride, chloroformate, and carbonic acid ester which are shown by General formula (8), General formula (9), and General formula (10) used at process 7-2. What is necessary is just to use 1-3 mol equivalent with respect to the azobenzene derivative shown by General formula (1c) as a raw material.
The reaction of step 7-2 can be carried out in an organic solvent. The organic solvent is not particularly limited as long as it does not harm the reaction, for example, halogen solvents such as dichloromethane and chloroform, ether solvents such as dioxane, THF, diisopropyl ether, cyclopentyl methyl ether, Examples thereof include aromatic organic solvents such as benzene and toluene, and amide solvents such as DMF and N, N-dimethylacetamide. These organic solvents may be used alone or in combination of two or more. Among these, ether solvents such as dioxane, THF, diisopropyl ether, and cyclopentyl methyl ether are preferable in that the azobenzene derivative represented by the general formula (1d) can be obtained with high yield. These organic solvents may be used alone or in combination of two or more.
In addition, the reaction in Step 7-2 is more preferably performed in the presence of a base. Thereby, reaction can be promoted. Bases include tertiary amines such as triethylamine, diisopropylethylamine, and tributylamine, aromatic amines such as pyridine and DMAP, alkali metal hydroxides such as sodium hydroxide and potassium hydroxide, and alkali metals such as sodium carbonate and potassium carbonate. Examples thereof include carbonates, alkali metal hydrides such as sodium hydride, alkali metal alkoxides such as sodium methoxide and sodium ethoxide, and tetrabutylammonium hydroxide. Among them, it is desirable to use pyridine and DMAP in combination in that the azobenzene derivative represented by the general formula (1d) can be obtained with high yield. There is no restriction | limiting in particular in the usage-amount of a base, What is necessary is just to use 1-3 mol equivalent with respect to the azobenzene derivative shown by General formula (1c).
The reaction temperature in step 7-2 can be appropriately selected from the range of the reflux temperature of the solvent used from 0 ° C., and since a high yield is obtained, the reaction is carried out while controlling the temperature to be 40 to 60 ° C. It is preferable to carry out. The reaction time varies depending on other conditions such as the reaction temperature, but 2 to 12 hours is appropriate.

  The azobenzene derivative obtained by the reaction in Step 7-2 may be used for the next reaction without purification, or may be used for the next reaction after purification. Examples of purification methods include extraction, column chromatography, and recrystallization.

[Purification of azobenzene derivatives]
Since the azobenzene derivatives produced by the above-mentioned first production method to fourth production method have high purity, they may be used for the production of 4,4′-diaminoazobenzenes without purification, but if necessary, they may be further changed. Purification may be performed. For example, it is also preferable to carry out purification in the final stage or in the middle of a series of manufacturing processes in order to eliminate a trace amount of metal contained in the manufactured product of the azobenzene derivative and to reduce coloring of the manufactured product. Examples of the method for removing a trace amount of metal include washing with water, acid or basic water, and it is particularly preferable to use pure water washing, dilute hydrochloric acid washing, dilute sulfuric acid washing, sodium bicarbonate water washing, caustic soda water washing or the like. . Examples of the method for reducing coloring include recrystallization of simple substance or acid salt, column chromatography, activated carbon adsorption treatment and the like. For the chromatography, it is preferable to use an adsorbent such as silica gel, alumina or zeolite. Further, the product finally obtained by the reaction may be purified by a usual method such as silica gel column chromatography, recrystallization, activated carbon treatment or the like.

Next, a method for producing the aniline derivative represented by the general formula (3a) used in the production of the azobenzene derivative represented by the general formula (1a) in the first method for producing the azobenzene derivative will be described.

[First production method of aniline derivative]
In the first production method of an aniline derivative, among the aniline derivatives represented by the general formula (3a), a compound in which R ^2a is an ^optionally substituted arylmethyl group, that is, an aniline derivative represented by the following general formula (3aa) Manufacturing. Specifically, an aniline derivative represented by the following general formula (3b) is synthesized by reacting an aniline derivative represented by the following general formula (3) with an aromatic aldehyde represented by the following general formula (6). The step of performing (Step 3-1) and the step of producing the aniline derivative represented by General Formula (3aa) by reducing the synthesized aniline derivative represented by General Formula (3b) (Step 3-2) are sequentially performed.

Formula (3), in (3b) and (3aa), ^{R 1} has the same meaning as ^{R 1} in the general formula (1a) in the first manufacturing method of the azobenzene derivative. That is, R ¹ represents a hydrogen atom, an alkyl group that may be substituted, an acyl group that may be substituted, or an alkoxycarbonyl group that may be substituted. For the description, preferred range, and specific examples, the corresponding description of the general formula (1a) of the first production method of the azobenzene derivative can be referred to.
In the general formulas (3b), (3aa) and (6), R ^2aa represents an arylmethyl group which may be substituted or an alkoxycarbonyl group which may be substituted.

The reaction in Step 3-1 is a condensation reaction between the aniline derivative represented by the general formula (3) and the aromatic aldehyde represented by the general formula (6). There is no restriction | limiting in particular in the usage-amount of the aromatic aldehyde shown by General formula (6) used at process 3-1, 1-1.5 mol etc. with respect to the aniline derivative shown by General formula (3) as a raw material. The amount may be used.
The reaction in step 3-1 can be carried out in an organic solvent. The organic solvent is not particularly limited as long as it does not harm the reaction, and examples thereof include aromatic organic solvents such as benzene and toluene, alcohol solvents such as methanol, ethanol, and isopropyl alcohol. be able to. Of these, alcohol solvents such as methanol, ethanol and isopropyl alcohol are preferred in that the aniline derivative represented by the general formula (3b) can be obtained with a good yield. These organic solvents may be used alone or in combination of two or more.
Moreover, it is more preferable to perform reaction of the process 3-1 in presence of an acid. Thereby, reaction can be promoted. Examples of the acid include carboxylic acids such as acetic acid, chloroacetic acid, trichloroacetic acid and trifluoroacetic acid, sulfonic acids such as p-toluenesulfonic acid, and mineral acids such as hydrochloric acid and sulfuric acid.
The reaction temperature in step 3-1 can be appropriately selected from the range of the reflux temperature of the solvent used from room temperature, and since a high yield is obtained, the reaction is performed while controlling the temperature so as to be the reflux temperature of the solvent. Preferably it is done. The reaction time varies depending on other conditions such as the reaction temperature, but 2 to 15 hours is appropriate.

  The aniline derivative obtained by the reaction in Step 3-1 may be subjected to the next reaction without being purified, or may be subjected to the next reaction after being purified. Examples of purification methods include extraction, column chromatography, and recrystallization.

The reduction of the aniline derivative represented by the general formula (3b) in Step 3-2 is described in, for example, Journal of Organic Chemistry, 55, 2034-2044; 1990, Journal of Organic Chemistry, 37, 1673-1674; 1972. Thus, it can be carried out using a reducing agent such as sodium borohydride, sodium cyanoborohydride, sodium triacetoxyborohydride, dimethylamine borane, 2-picoline borane, etc., using other known reduction methods Also good. There is no restriction | limiting in particular in the usage-amount of a reducing agent, What is necessary is just to use 1-1.5 molar equivalent with respect to the aniline derivative shown by General formula (3b).
The reaction of step 3-2 can be carried out in an organic solvent. The organic solvent is not particularly limited as long as it does not harm the reaction, and examples thereof include alcohol solvents such as methanol, ethanol, isopropyl alcohol, N, N-dimethylformamide (DMF), tetrahydrofuran (THF). ) And the like. Methanol, ethanol or isopropyl alcohol is preferable in that the desired aniline derivative represented by the general formula (3aa) can be obtained with good yield. These solvents may be used alone or in combination of two or more.
The reaction temperature in step 3-2 can be appropriately selected from the range of the solvent reflux temperature used from room temperature, and since a high yield is obtained, the reaction is performed while controlling the temperature so as to be the solvent reflux temperature. It is preferable. The reaction time varies depending on other conditions such as the reaction temperature, but 1 to 48 hours is appropriate.

  The aniline derivative obtained by the reaction in Step 3-2 may be subjected to the next reaction (first production method of an azobenzene derivative) without being purified, or may be subjected to the next reaction after being purified. Examples of purification methods include extraction, column chromatography, and recrystallization.

[Second production method of aniline derivative]
In the second method for producing an aniline derivative, among the aniline derivatives represented by the general formula (3a), a compound in which R ^2a is an alkali metal oxysulfonylmethyl group, that is, an aniline derivative represented by the following general formula (3ab) is produced. . Specifically, an aniline derivative represented by the following general formula (3ab) is produced by a step of reacting an aniline derivative represented by the following general formula (3) with formaldehyde and an alkali metal hydrogen sulfite (step 4-1).

In the general formula (3) and (3ab), ^{R 1} has the same meaning as ^{R 1} in the general formula (1a) in the first manufacturing method of the azobenzene derivative. That is, R ¹ represents a hydrogen atom, an alkyl group that may be substituted, an acyl group that may be substituted, or an alkoxycarbonyl group that may be substituted. For the description, preferred range, and specific examples, the corresponding description of the general formula (1a) of the first production method of the azobenzene derivative can be referred to. M represents an alkali metal such as sodium or potassium.
In formula ^{(3ab), R 2ab} represents an alkali metal oxysulfonyl methyl group.

The reaction in Step 4-1 is a reaction in which an alkali metal oxysulfonylmethyl group is added to an aniline derivative. For example, Journal of Photochemistry and Photobiology A: Chemistry, 185, 338-344; 2007 and Journal of the American Chemical Society, 135 9777-9784; 2013 and the like, and the method for adding an alkali metal oxysulfonylmethyl group to aniline or an aniline derivative can be referred to.
In Step 4-1, trioxane or paraformaldehyde in which a plurality of formaldehydes are polymerized can be used instead of formaldehyde. Further, an aqueous solution of formaldehyde, so-called formalin may be used. The concentration of formalin is not particularly limited, and commercially available 37% formalin is preferable because it is easily available and easy to handle. There is no restriction | limiting in particular in the usage-amount of formaldehyde, For example, what is necessary is just to use 1-1.5 mol equivalence with respect to the aniline derivative shown by General formula (3) used as a raw material.
Examples of the alkali metal bisulfite used in Step 4-1 include sodium bisulfite and potassium bisulfite. For example, commercially available sodium bisulfite or the like may be used as it is, or may be used as an aqueous solution. There is no restriction | limiting in particular in the usage-amount of an alkali metal hydrogensulfite, What is necessary is just to use 1-2 mol equivalent with respect to the aniline derivative (3) shown by General formula (3) used as a raw material.
In addition, instead of formaldehyde and alkali metal bisulfite used in Step 4-1, a commercially available alkali metal hydroxymethanesulfonate may be used. From the viewpoint of reducing manufacturing costs, formaldehyde and alkali metal bisulfite are combined. It is preferable to use it. There is no restriction | limiting in particular in the usage-amount of an alkali metal hydroxymethanesulfonate, What is necessary is just to use 1-1.5 mol equivalent with respect to the aniline derivative (3) shown by General formula (3) used as a raw material.
The reaction in Step 4-1 can be performed in an aqueous solution.
The reaction temperature can be appropriately selected within the range of room temperature to 100 ° C. The reaction time varies depending on other conditions such as the reaction temperature, but 1 to 3 hours is appropriate.

  The aniline derivative obtained by the reaction in Step 4-1 may be used for the next reaction (first method for producing an azobenzene derivative) without purification, or may be used for the next reaction after purification. Examples of purification methods include extraction, column chromatography, and recrystallization.

Method for Producing 4,4′-Diaminoazobenzene Next, a method for producing 4,4′-diaminoazobenzene using the azobenzene derivative represented by the general formula (1) as an intermediate is represented by the general formula (1b) or the general formula. The case where the azobenzene derivative represented by (1d) is used as an intermediate will be described as an example.

[First production method of 4,4′-diaminoazobenzenes]
In the first production method of 4,4′-diaminoazobenzenes, a step of converting a nitro group of an azobenzene derivative represented by the following general formula (1b), which is an intermediate, into an amino group by a reduction reaction (step 5-1) To produce 4,4′-diaminoazobenzenes represented by the following general formula (4).

^{R 1} in the general formula (1b) and (4) has the same meaning as ^{R 1} in the general formula (1b) in the second manufacturing method of the azobenzene derivative. That is, R ¹ represents a hydrogen atom, an alkyl group that may be substituted, an acyl group that may be substituted, or an alkoxycarbonyl group that may be substituted. For the explanation, preferred range, and specific examples, the corresponding description about the general formula (1b) of the second production method of the azobenzene derivative can be referred to.

The reduction of the nitro group carried out in step 5-1 includes reduction with a reagent using a sulfide such as sodium sulfide or an inorganic salt such as sodium dithionite as a reducing agent, a Pd / C catalyst, Raney nickel in a hydrogen gas atmosphere. A variety of reduction methods can be used, such as catalytic reduction that reduces using metal, metal reduction that uses iron, zinc, or tin chloride in the presence of acids such as hydrochloric acid and acetic acid. Since it is possible to reduce the nitro group while suppressing the above, it is preferable to use a reducing agent such as sulfide to reduce by a reagent. Regarding specific conditions for the reduction with the reagent, for example, descriptions in JP2014-12218A, JP2014055123A, and the like can be referred to.
The sulfide as the reducing agent is not particularly limited, and any of hydrosulfide, sulfide, disulfide and polysulfide can be used. Specific examples of the hydrosulfide include sodium hydrosulfide, potassium hydrosulfide, and ammonium bisulfide. Examples of the sulfide include sodium sulfide, potassium sulfide, and ammonium sulfide. These may be anhydrous or contain water of crystallization. Examples of disulfides include sodium disulfide, potassium disulfide, and ammonium disulfide. Examples of polysulfides include sodium trisulfide, potassium trisulfide, ammonium trisulfide, sodium tetrasulfide, potassium tetrasulfide, and tetrasulfide. Ammonium etc. are mentioned. Commercially available disulfides and polysulfides may be used, but those prepared from sulfides and sulfur may be used. These sulfides may be used alone or in combination of two or more.
The amount of sulfide used as the reducing agent is not particularly limited, but is preferably 2.5 to 10 molar equivalents in terms of sulfur atom, based on the azobenzene derivative represented by the general formula (1b) as a raw material, 2.5-5 molar equivalents are more preferred. The sulfide is preferably used as an aqueous solution, and the concentration of the aqueous sulfide solution is preferably 10% to 40%, more preferably 18% to 28%.
The reaction in Step 5-1 can also be carried out in an organic solvent that does not harm the reaction. Examples of organic solvents include alcohol solvents such as methanol, ethanol, propyl alcohol, isopropyl alcohol, butyl alcohol, isobutyl alcohol, sec-butyl alcohol, tert-butyl alcohol, and ethylene glycol; aromatic hydrocarbons such as benzene, toluene, and xylene System solvents; halogenated aromatic hydrocarbon solvents such as chlorobenzene and o-dichlorobenzene; ether solvents such as diethyl ether, diisopropyl ether and dibutyl ether. These organic solvents may be used alone or in combination of two or more.
The reaction temperature in Step 5-1 can be appropriately selected from the range of 50 ° C to 150 ° C, and is preferably selected from the range of 90 ° C to 110 ° C. The reaction time varies depending on other conditions such as the reaction temperature, but is suitably in the range of 0.5 to 2 hours, for example.

  It is also preferable to purify the 4,4′-diaminoazobenzenes represented by the general formula (4) obtained by the first production method. For example, 4,4'-diaminoazobenzenes can be efficiently isolated by removing excess sulfide and the like by conventional post-treatment methods such as extraction and washing. Moreover, it can also refine | purify by normal methods, such as silica gel column chromatography, recrystallization, activated carbon treatment.

[Second production method of 4,4′-diaminoazobenzenes]
In the second production method of 4,4′-diaminoazobenzenes, among the 4,4′-diaminoazobenzenes obtained by the first production method, the hydroxyl group of the compound in which R ¹ is a hydrogen atom is converted to an alkoxy group. 4,4′-Diaminoazobenzenes having an alkoxymethyl group at the 2-position are produced. Specifically, a step of reacting 4,4′-diaminoazobenzenes represented by the following general formula (4a) with a compound represented by the following general formula (5) in the presence of a base (step 6-1) To produce 4,4′-diaminoazobenzenes represented by the following general formula (4b).

R ^{1a in the} general formula (4a) represents a hydrogen atom.
R ^{1b in the} general formulas (4b) and (5) represents an optionally substituted alkyl group, an optionally substituted acyl group, or an optionally substituted alkoxycarbonyl group. For the explanation of each group represented by R ^1b and preferred ranges and specific examples, the corresponding description of R ^{1 in the} general formula (1) can be referred to.
L in the general formula (5) represents a leaving group. Examples of the leaving group represented by L include halogen atoms such as bromine atom and iodine atom, and sulfonyloxy groups such as methanesulfonyloxy group, trifluoromethanesulfonyloxy group, benzenesulfonyloxy group and p-toluenesulfonyloxy group. can do.
The reaction of step 6-1 is carried out in the presence of a base. Bases include alkali metal hydroxides such as sodium hydroxide and potassium hydroxide, alkali metal carbonates such as sodium carbonate and potassium carbonate, alkali metal hydrides such as sodium hydride, sodium methoxide and sodium ethoxide. Examples thereof include alkali metal alkoxides and tetrabutylammonium hydroxide. There is no restriction | limiting in particular in the usage-amount of a base, What is necessary is just to use 1-5 mol equivalent with respect to the azobenzene derivative shown by the general formula (4a) which is a raw material.
The reaction in step 6-1 can be carried out in a solvent. As the solvent, any solvent that does not harm the reaction can be used. For example, ether solvents such as diethyl ether, diisopropyl ether, cyclopentyl methyl ether, dimethoxyethane, tetrahydrofuran (THF), dioxane, acetonitrile, Nitrile solvents such as pionitrile, aromatic solvents such as benzene, toluene, xylene, chlorobenzene and dichlorobenzene, amide solvents such as N, N-dimethylformamide (DMF) and N, N-dimethylacetamide, dimethyl sulfoxide ( DMSO), water and the like. These solvents may be used alone or in combination of two or more.
The reaction temperature in step 6-1 can be appropriately selected from the range of room temperature to the reflux temperature of the solvent used, and since a high yield is obtained, the reaction is carried out while controlling the temperature to reach the solvent reflux temperature. It is preferable. The reaction time varies depending on other conditions such as the reaction temperature, but 1 to 24 hours is appropriate.

  It is also preferable to purify the 4,4′-diaminoazobenzenes represented by the general formula (4b) obtained by the second production method. The 4,4'-diaminoazobenzenes can be purified by usual methods such as silica gel column chromatography, recrystallization, activated carbon treatment and the like.

[Third production method of 4,4′-diaminoazobenzenes]
In the third production method of 4,4′-diaminoazobenzenes, the step of deprotecting the protecting group of the azobenzene derivative represented by the following general formula (1d), which is an intermediate, (step 8-1), The 4,4-diaminoazobenzenes shown in 4b) are produced.

R ^{1b in} general formula (1d) and general formula (4b) represents an optionally substituted alkyl group, an optionally substituted acyl group, or an optionally substituted alkoxycarbonyl group.
R ^{2a in} formula (1d) represents an optionally substituted arylmethyl group, an alkali metal oxysulfonylmethyl group, or an optionally substituted alkoxycarbonyl group.
R ^{3a in} formula (1d) represents an optionally substituted arylmethylamino group, an alkali metal oxysulfonylmethylamino group, or an optionally substituted alkoxycarbonylamino group.
Here, for the explanation and preferred ranges and specific examples of each group represented by R ^1b , the corresponding description of R ^{1 in the} general formula (1) can be referred to, and explanations and preferred descriptions of the groups represented by R ^2a are preferable. For the range and specific examples, the corresponding description of R ^{2 in the} general formula (1) can be referred to. For the explanation of each group represented by R ^3a and the preferred range and specific examples, the general formula (1) Reference may be made to the corresponding description for R ³ .

  For the deprotection method performed in Step 8-1, the description of Step 1-2 in the [Second production method of azobenzene derivative] column can be referred to.

  EXAMPLES Hereinafter, although an Example, a reference example, and a comparative example are given and this invention is demonstrated concretely, this invention is limited to these Examples and is not interpreted. For example, materials, amounts used, ratios, processing contents, processing procedures, and the like shown in the following examples can be changed as appropriate without departing from the spirit of the present invention.

[1] Production example 1 of azobenzene derivative
In Examples 1 and 2 below, the azobenzene derivative B1 was produced by protecting the amino group (Example 1), and the azobenzene derivative A1 was produced by deprotecting the amino protecting group of the azobenzene derivative B1 ( Example 2).
In Example 3, the azobenzene derivative B4 was produced by protecting the amino group, and the azobenzene derivative A1 was produced by deprotecting the protecting group of the amino group of the azobenzene derivative B4.

Synthesis of Aniline Derivative 1 Here, in Example 1, the aniline derivative 1 used as a raw material for the azobenzene derivative B1 was synthesized.

Under an argon atmosphere, trinitroamine (49.5 g, 489 mmol) and methanesulfonyl chloride (41.1 g, 359) were added to a solution of 3-nitrobenzyl alcohol (50.0 g, 326 mmol) in dichloromethane (1 L) under ice cooling (ice bath). mmol) and stirred for 1 hour, followed by addition of saturated aqueous ammonium chloride solution. This reaction solution was extracted three times with ethyl acetate (150 mL), and the combined organic layer was washed with saturated brine. The organic layer was dried over magnesium sulfate and concentrated to obtain a crude product of 3-nitrobenzyl methanesulfonate.
Ethanol (500 mL) was added to the obtained crude product of 3-nitrobenzyl methanesulfonate, and a solution of sodium ethoxide (18.5 g, 342 mmol) in ethanol (200 mL) was added dropwise at room temperature, followed by heating for 20 hours. Refluxed. After completion of the reaction, the reaction solution was cooled to room temperature and a saturated aqueous ammonium chloride solution was added. The precipitated insoluble material was removed by filtration, and then the mother liquor was concentrated under reduced pressure. The resulting concentrate was extracted three times with ethyl acetate (150 mL), and the combined organic layer was washed with saturated brine. The organic layer was dried over anhydrous sodium sulfate and then concentrated to obtain a crude product. The crude product was purified by silica gel column chromatography using a solvent of hexane: ethyl acetate = 100: 0 to 83:17 (hexane alone or a mixed solvent of hexane and ethyl acetate) as an eluent, and ethyl (3 A pale yellow oily substance of (nitrobenzyl) ether was obtained in a yield of 56.4 g, yield 94%.
¹ H-NMR (400MHz, CDCl ₃ ): δ 8.22 (m, 1H), 8.14 (m, 1H), 7.68 (m, 1H), 7.52 (m, 1H), 4.59 (s, 2H), 3.60 (q , J = 7.0Hz, 2H), 1.29 (t, J = 7.0Hz, 3H).

Under an argon atmosphere, a solution of ethyl (3-nitrobenzyl) ether (36.2 g, 200 mmol) in methanol (200 mL), ammonium chloride (53.5 g, 1.00 mol) in water (460 mL) and reduced iron (33.5 mL) g, 600 mmol), and the mixture was stirred in an oil bath at 90 ° C. for 4 and a half hours. After completion of the reaction, the reaction solution was cooled to room temperature, and insoluble matters were removed by Celite filtration. After concentrating the mother liquor, extraction was performed three times with ethyl acetate (300 mL), and the combined organic layer was washed with saturated brine. The organic layer was dried over anhydrous sodium sulfate and then concentrated under reduced pressure to obtain a crude product. The crude product was purified by column chromatography using a mixed solvent of hexane: ethyl acetate = 95: 5 to 60:40 as an eluent to obtain 25.2 g of 3- (ethoxymethyl) aniline. Obtained at a rate of 83%.
¹ H-NMR (400MHz, CDCl ₃ ): δ 7.12 (m, 1H), 6.73-6.61 (m, 2H), 6.60 (m, 1H), 4.42 (s, 2H), 3.65 (brs, 2H), 3.53 (q, J = 7.0Hz, 2H), 1.24 (t, J = 7.0Hz, 3H).

Add chloroacetic acid (374 mg, 3.96 mmol) and 4-methoxybenzaldehyde (25.3 mL, 208 mmol) to a solution of 3- (ethoxymethyl) aniline (30.0 g, 198 mmol) in isopropyl alcohol (300 mL) under an argon atmosphere. The mixture was heated to reflux with stirring for 14 hours, chloroacetic acid (1.50 g, 15.8 mmol) was added, and the mixture was further heated to reflux with stirring for 2 hours. After completion of the reaction, the reaction solution was cooled to room temperature and concentrated under reduced pressure to obtain a crude product of 3- (ethoxymethyl) -N- (4-methoxybenzylidene) aniline.
The obtained crude product of 3- (ethoxymethyl) -N- (4-methoxybenzylidene) aniline was dissolved in ethanol (200 mL), the solution was ice-cooled, and sodium borohydride (7.49 g, 198). mmol) was added in small portions. The reaction solution was stirred at room temperature for 3 hours and then heated to reflux for an additional 12 hours. After completion of the reaction, the reaction solution was ice-cooled, water (200 mL) was slowly added, and the mixture was concentrated under reduced pressure. The resulting reaction solution was extracted three times with chloroform (250 mL), and the combined organic layer was washed with water and saturated brine. The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The resulting crude product was subjected to column chromatography using a mixed solvent of hexane: ethyl acetate = 94: 6 to 73:27 as an eluent. Purified. Through the above steps, a yellow oily substance of 3- (ethoxymethyl) -N- (4-methoxybenzyl) aniline (aniline derivative 1) was obtained in a yield of 45.6 mg, yield: 85%.
¹ H-NMR (400MHz, CDCl ₃ ): δ 7.29 (d, J = 8.7Hz, 2H), 7.14 (m, 1H), 6.88 (d, J = 8.7Hz, 2H), 6.71-6.63 (m, 2H ), 6.55 (m, 1H), 4.43 (s, 2H), 4.26 (s, 2H), 3.95 (brs, 1H), 3.80 (s, 2H), 3.51 (q, J = 7.0Hz, 2H), 1.22 (t, J = 7.0Hz, 3H).

(Example 1) Production of azobenzene derivative B1 In this example, azobenzene derivative B1 was produced by reacting benzenediazonium salt 1 produced from 4-nitroaniline with synthesized aniline derivative 1.

To a mixed solution of 4-nitroaniline (15.1 g, 109 mmol), acetic acid (140 mL) and propionic acid (72 mL), sulfuric acid (20 mL) was added under ice cooling (ice bath). Then, a solution of sodium nitrite (9.04 g, 131 mmol) in water (24 mL) was slowly added to this solution under ice cooling (ice bath), stirred for 5 minutes, and then urea (2.16 g, 36.0 mmol). ) And further stirred for 5 minutes to prepare an aqueous solution of 4-nitrobenzenediazonium sulfate (benzenediazonium salt 1).
An aqueous solution of the obtained 4-nitrobenzenediazonium sulfate was added to ice-cooled 3- (ethoxymethyl) -N- (4-methoxybenzyl) aniline (aniline derivative 1: 29.7 g, 109 mmol) in ethanol (200 mL). Slowly added to the solution with stirring. The reaction solution was stirred for 3 hours under ice cooling (ice bath), and then a solution of sodium hydroxide (40 g) in water (200 mL) was added. The reaction mixture was concentrated under reduced pressure, extracted three times with ethyl acetate (300 mL), and the combined organic layer was washed with water and saturated brine. The organic layer was dried over anhydrous sodium sulfate and then concentrated under reduced pressure to give crude 2- (ethoxymethyl) -4- (4-methoxybenzylamino) -4′-nitroazobenzene (azobenzene derivative B1) as a purple solid. Was obtained in a yield of 42.9 g. The obtained 2- (ethoxymethyl) -4- (4-methoxybenzylamino) -4′-nitroazobenzene can be used in the next reaction without purification.
¹ H-NMR (400MHz, CDCl ₃ ): δ 8.33 (d, J = 9.1Hz, 2H), 7.89 (d, J = 9.1Hz, 2H), 7.79 (m, 1H), 7.32-7.27 (m, 2H ), 6.93-6.88 (m, 3H), 6.57 (m, 1H), 5.08 (s, 2H), 4.68 (brs, 1H), 4.40 (s, 2H), 3.82 (s, 3H), 3.66 (q, J = 7.0Hz, 2H), 1.28 (t, J = 7.0Hz, 3H).

Example 2 Production of Azobenzene Derivative A1 In this example, the amino protecting group of the azobenzene derivative B1 produced in Example 1 was deprotected to produce an azobenzene derivative A1.

To a solution of 2- (ethoxymethyl) -4- (4-methoxybenzylamino) -4′-nitroazobenzene (azobenzene derivative B1: 42.9 g, 102 mmol) in dichloromethane (600 mL) was added water (380 mL) and DDQ (23.6 g, 104 mmol) was added, and the mixture was stirred at room temperature for 3.5 hours. After completion of the reaction, chloroform (200 mL) was added to the reaction mixture, followed by Celite filtration to remove insoluble matters. A saturated aqueous sodium hydrogen carbonate solution was added to the mother liquor, and the organic layer and the aqueous layer were separated. The aqueous layer was extracted three times with chloroform (200 mL), and the combined organic layer was washed successively with saturated aqueous sodium hydrogen carbonate solution, water and saturated brine. The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure to obtain a purple solid of 4-amino-2- (ethoxymethyl) -4′-nitroazobenzene (azobenzene derivative A1) in a yield of 30.6 g. The obtained 4-amino-2- (ethoxymethyl) -4′-nitroazobenzene can be used for the next reaction without purification.
¹ H-NMR (400MHz, CDCl ₃ ): δ 8.34 (d, J = 9.1Hz, 2H), 7.90 (d, J = 9.1Hz, 2H), 7.76 (d, J = 8.8Hz, 1H), 6.94 ( d, J = 2.6Hz, 1H), 6.61 (dd, J = 8.8 and 2.6Hz, 1H), 5.07 (s, 2H), 4.25 (brs, 2H), 3.69 (q, J = 7.0Hz, 2H), 1.31 (t, J = 7.0Hz, 3H).

(Example 3) Production of azobenzene derivative B4, production by other steps of A1 In this example, benzenediazonium salt 2 produced from 4-nitroaniline and 3 prepared by the method described in the synthesis column of aniline derivative 1 were used. The azobenzene derivative B4 was obtained by reacting with the aniline derivative 7 synthesized from-(ethoxymethyl) aniline, and then the protective group of the amino group of the azobenzene derivative B4 was deprotected to produce the azobenzene derivative A1.

Concentrated hydrochloric acid (24 mL) was added to a suspension of 4-nitroaniline (13.8 g, 100 mmol) in water (100 mL) with stirring at room temperature, and the mixture was cooled in an ice bath at 0 ° C. Next, while cooling in an ice bath, a solution of sodium nitrite (6.90 g, 100 mmol) in water (33 mL) was added dropwise to the reaction solution, followed by stirring at 0 ° C. for 30 minutes, whereby 4-nitrobenzenediazonium chloride ( An aqueous solution of benzenediazonium salt 2) was obtained. The entire amount of this aqueous solution was used for the next reaction.
To a 1 L separable flask equipped with a mechanical stirrer was added 3- (ethoxymethyl) aniline (15.1 g, 100 mmol), sodium formaldehyde bisulfite (13.8 g, 100 mmol), and water (23.5 mL). The aniline derivative 7 was synthesized by vigorous stirring and cooled in an ice bath at 0 ° C. After cooling, water (150 mL) was added, and the previously prepared aqueous solution of 4-nitrobenzenediazonium chloride (benzenediazonium salt 2) was added dropwise at 0 ° C. over 5 minutes. The reaction mixture was stirred for 3 hours while gradually warming to room temperature.
The resulting reaction solution containing the azobenzene derivative B4 was cooled in an ice bath at 0 ° C, toluene (150 mL) and 48% aqueous sodium hydroxide (55.2 mL, 1.00 mol) were added, and the temperature was raised to 70 ° C. And stirred for 2 hours. After completion of the reaction, the reaction mixture was cooled to room temperature, distilled water (600 mL) was added, and the mixture was extracted with ethyl acetate (600 mL). The organic layer was washed with water (300 mL), dried over anhydrous sodium sulfate, and concentrated under reduced pressure using an evaporator to obtain crude 4-amino-2- (ethoxymethyl) -4′-nitroazobenzene (azobenzene derivative A1). A purple solid was obtained in a yield of 26.4 g. The NMR spectrum is as described in Example 2.

[2] Production example 2 of azobenzene derivative
In the following Examples 4 and 5, the azobenzene derivative B3 was produced by protecting the amino group (Example 4), and the azobenzene derivative A3 was produced by deprotecting the amino protecting group of the azobenzene derivative B3 ( Example 5).
In Example 6, azobenzene derivatives B3 and A3 were produced in the same manner as in Examples 4 and 5 except that the amount of sodium hydroxide used for deprotecting the amino group was changed.

Synthesis of aniline derivative 2 Here, in Example 4, aniline derivative 2 used as a raw material for azobenzene derivative B3 was synthesized.

Under an argon atmosphere, 55% oily sodium hydride (5.59 g, 128 mmol) was washed with hexane, propyl alcohol (200 mL) was slowly added under ice cooling (ice bath), and the mixture was stirred for 20 minutes. Next, 3-nitrobenzyl bromide (25.0 g, 116 mmol) was added to the mixture, and the mixture was stirred for 3 hours while gradually warming to room temperature. After completion of the reaction, the reaction solution was ice-cooled (ice bath), and a saturated aqueous ammonium chloride solution (200 mL) was added. The precipitated insoluble material was removed by filtration, the mother liquor was concentrated under reduced pressure, and extracted three times with ethyl acetate (150 mL). The combined organic layer was washed successively with water (150 mL) and saturated brine (150 mL), dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure to give 3-nitrobenzyl (propyl). A pale yellow oil of ether was obtained in a yield of 22.6 g.
¹ H-NMR (400MHz, CDCl ₃ ): δ 8.22 (m, 1H), 8.14 (m, 1H), 7.68 (m, 1H), 7.52 (m, 1H), 4.59 (s, 2H), 3.49 (t , J = 6.7Hz, 2H), 1.68 (qt, J = 7.4 and 6.7Hz, 2H), 0.97 (t, J = 7.4Hz, 3H).

Under an argon atmosphere, reduced iron (19.4 g, 348 mmol) and 2M hydrochloric acid (50 mL) were added to a solution of 3-nitrobenzyl (propyl) ether (22.6 g, 116 mmol) in ethanol (200 mL) at 90 ° C ( (Oil bath) and stirred for 2 hours. After completion of the reaction, the reaction mixture was cooled to room temperature, and a solution of potassium carbonate (16 g) in water (75 mL) was added. The obtained reaction solution was filtered through Celite, and then the mother liquor was concentrated under reduced pressure. The resulting mixture was extracted three times with ethyl acetate (100 mL), and the combined organic layer was washed with water (100 mL) and saturated brine (100 mL). The organic layer was dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure to obtain a brown oily product of 3- (propyloxymethyl) aniline (aniline derivative 2) in a yield of 19.2 g.
¹ H-NMR (400MHz, CDCl ₃ ): δ 7.12 (m, 1H), 6.73-6.61 (m, 2H), 6.60 (m, 1H), 4.42 (s, 2H), 3.65 (brs, 2H), 3.42 (t, J = 6.7Hz, 2H), 1.64 (qt, J = 7.4 and 6.7Hz, 2H), 0.94 (t, J = 7.4Hz, 3H).

(Example 4) Production of azobenzene derivative B3 In this example, an azobenzene derivative B3 was produced by reacting a benzenediazonium salt 2 produced from 4-nitroaniline with an aniline derivative 3 produced from aniline derivative 2. .

Concentrated hydrochloric acid (3 mL) was added to a suspension of 4-nitroaniline (1.67 g, 12.1 mmol) in water (12 mL) with stirring at room temperature, and the mixture was cooled in an ice bath at 0 ° C. . Next, while cooling in an ice bath, a solution of sodium nitrite (0.835 g, 12.1 mmol) in water (4 mL) was added dropwise to the reaction solution, followed by stirring at 0 ° C. for 30 minutes to give 4-nitrobenzenediazonium chloride ( An aqueous solution of benzenediazonium salt 2) was obtained. This aqueous solution was directly used for the next reaction.
A solution of sodium bisulfite (1.75 g, 16.8 mmol) and 37% formalin (1.13 ml, 15.1 mmol) in water (2 mL) was stirred in an oil bath at 50 ° C. for 30 minutes. To this solution, an ethanol solution of 3- (propyloxymethyl) aniline (aniline derivative 2: 2.00 g, 12.1 mmol) and ethanol (1 mL) was added in an oil bath at 70 ° C., and the mixture was stirred for 1.5 hours. The mixture was allowed to stand for 10 minutes under ice cooling. A solution of sodium acetate (8 g) in water (40 mL) was added to the reaction mixture to obtain a suspension of sodium [{3- (propyloxymethyl) phenyl} amino] methylsulfonate (aniline derivative 3).
An aqueous solution of 4-nitrobenzenediazonium chloride (benzenediazonium salt 2) separately prepared was added to a suspension of the obtained sodium [{3- (propyloxymethyl) phenyl} amino] methylsulfonate under ice cooling (ice bath). For 10 minutes. The reaction mixture was stirred for 3 hours while gradually warming to room temperature, and the precipitated solid was collected by filtration. The solid was washed with distilled water and dried under reduced pressure to give a brown solid of crude 2- (propyloxymethyl) -4- (sodiooxysulfonylmethylamino) -4′-nitroazobenzene (azobenzene derivative B3). Yield 5.21 g.
¹ H-NMR (400MHz, DMSO-d ₆ ): δ 8.35 (d, J = 9.1Hz, 2H), 7.91 (d, J = 9.1Hz, 2H), 7.68 (d, J = 9.1Hz, 1H), 7.67 (t, J = 6.9Hz, 1H), 6.96 (d, J = 2.5Hz, 1H), 6.79 (dd, J = 9.1 and 2.5Hz, 1H), 4.95 (s, 2H), 4.03 (d, J = 6.9Hz, 2H), 3.50 (t, J = 6.5Hz, 2H), 1.60 (qt, J = 7.4 and 6.5Hz, 2H), 0.91 (t, J = 7.4Hz, 3H).

(Example 5) Production of azobenzene derivative A3 In this example, the amino protecting group of azobenzene derivative B3 was deprotected to produce azobenzene derivative A3.

2- (propyloxymethyl) -4- (sodiooxysulfonylmethylamino) -4′-nitroazobenzene (azobenzene derivative B3: 5.21 g, 12.1 mmol) was added to sodium hydroxide (1.09 g, 27.2 mmol) in water ( 15 mL) solution was added at room temperature and then stirred in an oil bath at 80 ° C. for 2 hours. After completion of the reaction, the reaction mixture was cooled to room temperature, water (100 mL) was added, and the precipitated solid was collected by filtration. The obtained solid was washed with water (100 mL) and then dissolved in ethyl acetate (200 mL). The obtained ethyl acetate solution was washed with water (50 mL) and saturated brine (100 mL), dried over anhydrous sodium sulfate, and concentrated under reduced pressure to give 4-amino-2- (propyloxymethyl)- A brown solid of 4′-nitroazobenzene (azobenzene derivative A3) was obtained in a yield of 2.46 g and a yield of 65%.
¹ H-NMR (400MHz, CDCl ₃ ): δ 8.34 (d, J = 9.1Hz, 2H), 7.90 (d, J = 9.1Hz, 2H), 7.76 (d, J = 8.8Hz, 1H), 6.94 ( d, J = 2.6Hz, 1H), 6.61 (dd, J = 8.8 and 2.6Hz, 1H), 5.07 (s, 2H), 4.26 (brs, 2H), 3.58 (t, J = 6.7Hz, 2H), 1.71 (qt, J = 7.4 and 6.7Hz, 2H), 0.98 (t, J = 7.4Hz, 3H).

(Example 6) Production by other steps of azobenzene derivative A3 In this example, an azobenzene derivative B3 was produced in the same manner as in Example 4, and the protecting group of the amino group of the azobenzene derivative B3 was deprotected to produce an azobenzene derivative. A3 was produced.

In the same manner as in Example 4, an aqueous solution of 2- (propyloxymethyl) -4- (sodiooxysulfonylmethylamino) -4′-nitroazobenzene (azobenzene derivative B3) was obtained.
To a solution of the obtained 2- (propyloxymethyl) -4- (sodiooxysulfonylmethylamino) -4′-nitroazobenzene, a solution of sodium hydroxide (2.42 g, 60.5 mmol) in water (20 mL) at room temperature was added. And then stirred in an oil bath at 80 ° C. for 2 hours. After completion of the reaction, the reaction mixture was cooled to room temperature, water (100 mL) was added, and the precipitated solid was collected by filtration. The obtained solid was washed with water (100 mL) and then dissolved in ethyl acetate (200 mL). The obtained ethyl acetate solution was washed with water (50 mL) and saturated brine (100 mL), dried over anhydrous sodium sulfate, and concentrated under reduced pressure to give 4-amino-2- (propyloxymethyl)- A brown solid (azobenzene derivative A3) of 4′-nitroazobenzene was obtained in a yield of 3.25 g and a yield of 86%.
¹ H-NMR (400MHz, CDCl ₃ ): δ 8.34 (d, J = 9.1Hz, 2H), 7.90 (d, J = 9.1Hz, 2H), 7.76 (d, J = 8.8Hz, 1H), 6.94 ( d, J = 2.6Hz, 1H), 6.61 (dd, J = 8.8 and 2.6Hz, 1H), 5.07 (s, 2H), 4.26 (brs, 2H), 3.58 (t, J = 6.7Hz, 2H), 1.71 (qt, J = 7.4 and 6.7Hz, 2H), 0.98 (t, J = 7.4Hz, 3H).

[3] Production example 3 of azobenzene derivative
In Examples 7 and 8 below, the azobenzene derivative B2 was produced by protecting the amino group (Example 7), and the azobenzene derivative A2 was produced by deprotecting the amino protecting group of the azobenzene derivative B2 ( Example 8).

Synthesis of aniline derivative 4 Here, in Example 7, the aniline derivative 4 used as a raw material for the azobenzene derivative B2 was synthesized.

Under an argon atmosphere, 55% oily sodium hydride (5.59 g, 128 mmol) was washed with hexane, and then isopropyl alcohol (200 mL) was slowly added under ice cooling (ice bath), followed by stirring for 20 minutes. Subsequently, 3-nitrobenzyl bromide (25.0 g, 116 mmol) was added, and the mixture was stirred for 3 hours while gradually warming to room temperature. After completion of the reaction, the reaction solution was ice-cooled (ice bath), and a saturated aqueous ammonium chloride solution (200 mL) was added. The precipitated insoluble material was removed by filtration, the mother liquor was concentrated under reduced pressure, and extracted three times with ethyl acetate (100 mL). The combined organic layer was washed with water (200 mL) and saturated brine (200 mL), then dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure to obtain isopropyl (3-nitrobenzyl) ether. Was obtained in a yield of 22.6 g.
¹ H-NMR (400MHz, CDCl ₃ ): δ 8.22 (m, 1H), 8.13 (m, 1H), 7.68 (m, 1H), 7.51 (m, 1H), 4.59 (s, 2H), 3.73 (sep , J = 6.1Hz, 1H), 1.25 (d, J = 6.1Hz, 6H).

Under an argon atmosphere, reduced iron (32.7 g, 585 mmol) and 2N hydrochloric acid (100 mL) were added to an ethanol solution of isopropyl (3-nitrobenzyl) ether (44.2 g, 216 mmol) and ethanol (200 mL). Stir in an oil bath at 0 ° C. for 3 hours. After completion of the reaction, the reaction mixture was cooled to room temperature, and an aqueous solution of potassium carbonate (32 g) and water (150 mL) was added. The obtained reaction solution was filtered through Celite, and then the mother liquor was concentrated under reduced pressure. The resulting mixture was extracted three times with ethyl acetate (100 mL), and the combined organic layer was washed with water (100 mL) and saturated brine (100 mL). The organic layer was dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure. Purification by column chromatography gave a brown oily product of 3- (isopropyloxymethyl) aniline in a yield of 31.5 g, yield: 88%.
¹ H-NMR (400MHz, CDCl ₃ ): δ 7.11 (m, 1H), 6.74-6.68 (m, 2H), 6.59 (m, 1H), 4.43 (s, 2H), 3.67 (sep, J = 6.1Hz , 1H), 3.65 (brs, 2H), 1.21 (d, J = 6.1Hz, 6H).

Under an argon atmosphere, chloroacetic acid (1.80 g, 19.1 mmol) and 4-methoxybenzaldehyde (24.4 mL, 201 mmol) were added to a solution of 3- (isopropyloxy) aniline (31.5 g, 191 mmol) and isopropyl alcohol (190 mL). In addition, the mixture was heated to reflux with stirring for 13 hours, and then concentrated under reduced pressure to obtain a crude product of 3- (isopropyloxymethyl) -N- (4-methoxybenzylidene) aniline.
The obtained crude product of 3- (isopropyloxymethyl) -N- (4-methoxybenzylidene) aniline was dissolved in ethanol (200 mL), the solution was ice-cooled, and sodium borohydride (7.23 g, 191 mmol) was added in small portions. The reaction solution was stirred at room temperature for 4 hours. After completion of the reaction, the reaction solution was ice-cooled, saturated aqueous ammonium chloride solution (150 mL) was slowly added, and the mixture was concentrated under reduced pressure. The resulting concentrate was extracted three times with ethyl acetate (150 mL), and the combined organic layer was washed with water and saturated brine. The organic layer was dried over anhydrous sodium sulfate and then concentrated under reduced pressure, and the resulting crude product was mixed with hexane: ethyl acetate = 100: 0 to 90:10 solvent (hexane alone or a mixture of hexane and ethyl acetate). The solvent was used as an eluent and purified by column chromatography to obtain the desired yellow oily product of 3- (isopropyloxymethyl) -N- (4-methoxybenzyl) aniline (aniline derivative 4) in a yield of 50 4. g, Yield: 92%.
¹ H-NMR (400MHz, CDCl ₃ ): δ 7.39 (d, J = 8.7Hz, 2H), 7.13 (m, 1H), 6.88 (d, J = 8.7Hz, 2H), 6.70-6.64 (m, 2H ), 6.54 (m, 1H), 4.44 (s, 2H), 4.25 (s, 2H), 3.95 (brs, 2H), 3.80 (s, 3H), 3.66 (sep, J = 6.1Hz, 2H), 1.19 (d, J = 6.1Hz, 6H).

(Example 7) Production of azobenzene derivative B2 In this example, an azobenzene derivative B2 was produced by reacting the benzenediazonium salt 1 produced from 4-nitroaniline with the synthesized aniline derivative 4.

To a mixed solution of 4-nitroaniline (2.71 g, 19.6 mmol), acetic acid (25 mL) and propionic acid (13 mL), sulfuric acid (3.6 mL) was added under ice cooling (ice bath). Then, a solution of sodium nitrite (1.62 g, 23.5 mmol) in water (4 mL) was slowly added to this solution under ice cooling (ice bath), stirred for 5 minutes, and then urea (466 mg, 7.76 mmol). And stirred for 5 minutes to obtain a solution of 4-nitrobenzenediazonium sulfate (benzenediazonium salt 1).
The obtained 4-nitrobenzenediazonium sulfate solution was cooled with ice-cooled 3- (isopropyloxymethyl) -N- (4-methoxybenzyl) aniline (aniline derivative 4: 5.58 g, 19.6 mmol) in ethanol (40 mL). Slowly added to the solution with stirring. The reaction solution was stirred for 3 hours under ice cooling (ice bath), distilled water (200 mL) was added, and the solid in the reaction system was collected by filtration. The solid was washed successively with water (500 mL), ethanol (50 mL), hexane (100 mL), and dried under reduced pressure to give crude 2- (isopropyloxymethyl) -4- (4-methoxybenzylamino). ) -4'-nitroazobenzene (azobenzene derivative B2) was obtained in a yield of 7.86 g. The obtained 2- (isopropyloxymethyl) -4- (4-methoxybenzylamino) -4′-nitroazobenzene can be used in the next reaction without purification.
¹ H-NMR (400MHz, CDCl ₃ ): δ 8.33 (d, J = 9.1Hz, 2H), 7.89 (d, J = 9.1Hz, 2H), 7.79 (m, 1H), 7.32-7.27 (m, 2H ), 6.93-6.87 (m, 3H), 6.56 (m, 1H), 5.07 (s, 2H), 4.68 (brs, 1H), 4.40 (s, 2H), 3.82 (s, 3H), 3.78 (sep, J = 6.1Hz, 1H), 1.25 (d, J = 6.1Hz, 3H).

Example 8 Production of Azobenzene Derivative A2 In this example, the amino protecting group of the azobenzene derivative B2 produced in Example 7 was deprotected to produce an azobenzene derivative A2.

To a solution of 2- (isopropyloxymethyl) -4- (4-methoxybenzylamino) -4′-nitroazobenzene (azobenzene derivative B2: 7.00 g, 16.1 mmol) in dichloromethane (100 mL) was added water (50 mL) and DDQ ( 3.70 g, 16.3 mmol) was added, and the mixture was stirred at room temperature for 3 hours. After completion of the reaction, chloroform (300 mL) was added to the reaction mixture, followed by Celite filtration to remove insoluble matters. A saturated aqueous sodium hydrogen carbonate solution was added to the mother liquor, and the organic layer and the aqueous layer were separated. The organic layer was washed successively with saturated aqueous sodium hydrogen carbonate solution, water and saturated brine. The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure to obtain a crude 4-amino-2- (isopropyloxymethyl) -4′-nitroazobenzene (azobenzene derivative A2) purple solid in a yield of 5.06 g. It was. The obtained 4-amino-2- (isopropyloxymethyl) -4′-nitroazobenzene can be used in the next reaction without purification.
¹ H-NMR (400MHz, CDCl ₃ ): δ 8.34 (d, J = 9.1Hz, 2H), 7.90 (d, J = 9.1Hz, 2H), 7.75 (d, J = 8.8Hz, 1H), 6.96 ( d, J = 2.6Hz, 1H), 6.60 (dd, J = 8.8 and 2.6Hz, 1H), 5.07 (s, 2H), 4.26 (brs, 2H), 3.81 (sep, J = 6.1Hz, 1H), 1.28 (d, J = 6.1Hz, 3H).

[4] Production example 4 of azobenzene derivative
In Example 9 below, the azobenzene derivative B5 was produced by protecting the amino group, and the azobenzene derivative A4 was produced by deprotecting the protecting group of the amino group of the azobenzene derivative B5.

Synthesis of aniline derivative 8 Here, in Example 9, the aniline derivative 8 used as a raw material of the azobenzene derivative B5 was synthesized.

Under an argon atmosphere, 55% oily sodium hydride (7.77 g, 178 mmol) was washed with hexane, and then isobutyl alcohol (290 mL) was slowly added under ice cooling (ice bath), followed by stirring for 15 minutes. Subsequently, 3-nitrobenzyl bromide (35.0 g, 162 mmol) was added to the mixture, and the mixture was stirred for 3 hours and a half while gradually warming to room temperature. After completion of the reaction, the reaction solution was ice-cooled (ice bath), and a saturated aqueous ammonium chloride solution (300 mL) was added. The precipitated insoluble material was removed by filtration, the mother liquor was concentrated under reduced pressure, and extracted three times with ethyl acetate (150 mL). The combined organic layer was washed successively with water (150 mL) and saturated brine (150 mL), then dried over anhydrous sodium sulfate, and the solvent was removed under reduced pressure to give isobutyl (3-nitrobenzyl). A pale yellow oil of ether was obtained in a yield of 33.8 g.
¹ H-NMR (400MHz, CDCl ₃ ): δ 8.21 (m, 1H), 8.14 (m, 1H), 7.68 (m, 1H), 7.52 (m, 1H), 4.59 (s, 2H), 3.29 (d , J = 6.6Hz, 2H), 1.94 (m, 1H), 0.95 (d, J = 6.7Hz, 6H).

Under an argon atmosphere, reduced iron (27.1 g, 486 mmol) and 2M hydrochloric acid (90 mL) were added to a solution of isobutyl (3-nitrobenzyl) ether (33.8 g, 162 mmol) in ethanol (130 mL) at 90 ° C. (Oil bath) and stirred for 2 hours. After completion of the reaction, the reaction mixture was cooled to room temperature, and a solution of potassium carbonate (29 g) in water (125 mL) was added. The obtained reaction solution was filtered through Celite, and then the mother liquor was concentrated under reduced pressure. The resulting mixture was extracted three times with ethyl acetate (150 mL), and the combined organic layer was washed with water (100 mL) and saturated brine (50 mL). The organic layer was dried over anhydrous sodium sulfate and the solvent was distilled off under reduced pressure to obtain a brown oily product of 3- (isobutyloxymethyl) aniline (aniline derivative 8) in a yield of 28.3 g and a yield of 98%. .
¹ H-NMR (400MHz, CDCl ₃ ): δ 7.12 (m, 1H), 6.72 (m, 1H), 6.69 (m, 1H), 6.60 (m, 1H), 4.42 (s, 2H), 3.65 (brs , 2H), 3.22 (t, J = 6.7Hz, 2H), 1.91 (m, 1H), 0.92 (d, J = 6.7Hz, 6H).

(Example 9) Production of azobenzene derivatives B5 and A4 In this example, benzenediazonium salt 2 produced from 4-nitroaniline and aniline derivative 9 synthesized from aniline derivative 8 were reacted to produce azobenzene derivative B5. Then, the amino protecting group of azobenzene derivative B5 was deprotected to produce azobenzene derivative A4.

Concentrated hydrochloric acid (46 mL) was added to a suspension of 4-nitroaniline (25.6 g, 185 mmol) in water (180 mL) with stirring at room temperature, and the mixture was cooled in an ice bath at 0 ° C. Next, while cooling in an ice bath, a solution of sodium nitrite (12.8 g, 185 mmol) in water (60 mL) was added dropwise to the reaction solution, followed by stirring at 0 ° C. for 30 minutes to give 4-nitrobenzenediazonium chloride. An aqueous solution of (benzenediazonium salt 2) was obtained. This aqueous solution was directly used for the next reaction.
A solution of sodium bisulfite (26.7 g, 257 mmol) and 37% formalin (17.1 mL, 216 mmol) in water (30 mL) was stirred in an oil bath at 50 ° C. for 30 minutes. To this solution, a solution of 3- (isobutyloxymethyl) aniline (aniline derivative 8: 33.1 g, 185 mmol) in ethanol (15 mL) was added in a 70 ° C. oil bath, stirred for 1 hour and a half, and then cooled on ice. A solution of sodium acetate (120 g) in water (600 mL) was added thereto to obtain a suspension of aniline derivative 9. A separately prepared aqueous solution of 4-nitrobenzenediazonium chloride (benzenediazonium salt 2) was added dropwise to the resulting suspension of aniline derivative 9 under ice cooling (ice bath) over 10 minutes. The reaction mixture was stirred for 3.5 hours while gradually warming to room temperature.
To the reaction solution containing the obtained azobenzene derivative B5, a solution of sodium hydroxide (37.0 g, 925 mmol) in water (300 mL) was added at room temperature, and then stirred in an oil bath at 80 ° C. for 2 hours. After completion of the reaction, the reaction mixture was cooled to room temperature, water (1 L) was added, and the precipitated solid was collected by filtration. The obtained solid was washed with water (1 L) and dried under reduced pressure to obtain a brown solid of crude 4-amino-2- (isobutyloxymethyl) -4′-nitroazobenzene (azobenzene derivative A4) in a yield of 60.7 g. Got in.
¹ H-NMR (400MHz, CDCl ₃ ): δ 8.34 (d, J = 9.1Hz, 2H), 7.91 (d, J = 9.1Hz, 2H), 7.80 (d, J = 8.9Hz, 1H), 6.94 ( d, J = 2.5Hz, 1H), 6.64 (dd, J = 8.9 and 2.5Hz, 1H), 5.09 (s, 2H), 3.39 (d, J = 6.7Hz, 2H), 1.98 (m, 1H), 0.96 (d, J = 6.7Hz, 6H).

[5] Production example 5 of azobenzene derivative
In Example 10 below, the azobenzene derivative B6 was produced by protecting the amino group, and the azobenzene derivative A5 was produced by deprotecting the amino protecting group of the azobenzene derivative B6.

Synthesis of Aniline Derivative 10 Here, in Example 10, the aniline derivative 10 used as a raw material for the azobenzene derivative B6 was synthesized.

Under an argon atmosphere, 55% oily sodium hydride (5.59 g, 128 mmol) was washed with hexane, suspended in THF (150 mL), and then 2,2,2-trimethylated under ice cooling (ice bath). Fluoroethanol (29.0 g, 290 mmol) was slowly added and stirred for 10 minutes. Subsequently, 3-nitrobenzyl bromide (25.0 g, 116 mmol) was added to the mixture, and the mixture was stirred overnight while gradually warming to room temperature. After completion of the reaction, the reaction solution was ice-cooled (ice bath), and a saturated aqueous ammonium chloride solution (100 mL) was added. The precipitated insoluble material was removed by filtration, the mother liquor was concentrated under reduced pressure, and extracted three times with ethyl acetate (150 mL). The combined organic layer was washed successively with water (50 mL) and saturated brine (50 mL), dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure to give 3-nitrobenzyl (2, A pale yellow oily substance of 2,2-trifluoroethyl) ether (aniline derivative 10) was obtained in a yield of 27.3 g.
¹ H-NMR (400MHz, CDCl ₃ ): δ 8.25-8.15 (m, 2H), 7.70 (m, 1H), 7.57 (m, 1H), 4.78 (s, 2H), 3.93 (q, J = 8.6Hz , 2H); ¹⁹ F-NMR (376 MHz, CDCl ₃ ): -73.9 (s).

Under an argon atmosphere, a solution of 3-nitrobenzyl (2,2,2-trifluoroethyl) ether (27.3 g, 116 mmol) in ethanol (100 mL) was added reduced iron (19.4 g, 348 mmol) and 2M hydrochloric acid (65 mL) was added, and the mixture was stirred at 90 ° C. (oil bath) for 2.5 hours. After completion of the reaction, the reaction mixture was cooled to room temperature, and a solution of potassium carbonate (20 g) in water (100 mL) was added. The obtained reaction solution was filtered through Celite, and then the mother liquor was concentrated under reduced pressure. The resulting mixture was extracted three times with ethyl acetate (100 mL), and the combined organic layer was washed with water (100 mL) and saturated brine (100 mL). The organic layer was dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure to obtain a brown oily product of 3-[(2,2,2-trifluoroethyloxy) methyl] aniline in a yield of 22.4 g. Obtained at 94%.
¹ H-NMR (400MHz, CDCl ₃ ): δ 7.14 (m, 1H), 6.73-6.62 (m, 3H), 4.59 (s, 2H), 3.80 (q, J = 8.7Hz, 2H), 3.69 (brs , 2H); ¹⁹ F-NMR (376 MHz, CDCl ₃ ): -73.9 (s).

(Example 10) Production of azobenzene derivatives B6 and A5 In this example, benzenediazonium salt 2 produced from 4-nitroaniline and aniline derivative 11 synthesized from aniline derivative 10 were reacted to produce azobenzene derivative B6. Then, the amino protecting group of azobenzene derivative B6 was deprotected to produce azobenzene derivative A5.

Concentrated hydrochloric acid (27 mL) was added to a suspension of 4-nitroaniline (15.1 g, 109 mmol) in water (100 mL) with stirring at room temperature, and the mixture was cooled in an ice bath at 0 ° C. Next, while cooling in an ice bath, a solution of sodium nitrite (7.59 g, 110 mmol) in water (30 mL) was added dropwise to the reaction solution, followed by stirring at 0 ° C. for 30 minutes to give 4-nitrobenzenediazonium chloride ( An aqueous solution of benzenediazonium salt 2) was obtained. This aqueous solution was directly used for the next reaction.
A solution of sodium bisulfite (15.8 g, 152 mmol) and 37% formalin (9.72 mL, 128 mmol) in water (20 mL) was stirred in an oil bath at 50 ° C. for 30 minutes. To this solution was added a solution of 3-[(2,2,2-trifluoroethyloxy) methyl] aniline (22.4 g, 109 mmol) in ethanol (10 mL) in an oil bath at 70 ° C. for 1 hour and a half. After stirring, a solution of sodium acetate (70 g) in water (350 mL) was added under ice cooling, and an aqueous solution of 4-nitrobenzenediazonium chloride prepared separately was added to the resulting suspension under ice cooling (ice bath). For 10 minutes. The reaction mixture was stirred for 3.5 hours while gradually warming to room temperature.
To a reaction solution containing the obtained azobenzene derivative B6, a solution of sodium hydroxide (22.0 g, 550 mmol) in water (150 mL) was added at room temperature, and then stirred in an oil bath at 80 ° C. for 1 hour. After completion of the reaction, the reaction mixture was cooled to room temperature, water (1 L) was added, and the precipitated solid was collected by filtration. The obtained solid was washed with water (1 L) and dried under reduced pressure to give crude 4-amino-2-[(2,2,2-trifluoroethyloxy) methyl] -4′-nitroazobenzene (azobenzene). A brown solid of derivative A5) was obtained with a yield of 38.6 g.
¹ H-NMR (400MHz, CDCl ₃ ): δ 8.34 (d, J = 9.1Hz, 2H), 7.89 (d, J = 9.1Hz, 2H), 7.79 (d, J = 8.8Hz, 1H), 6.90 ( d, J = 2.6Hz, 1H), 6.65 (dd, J = 8.8 and 2.6Hz, 1H), 5.25 (s, 2H), 3.98 (d, J = 8.7Hz, 2H); ¹⁹ F-NMR (376MHz, CDCl ₃ ): -73.9 (s).

[6] Production example 6 of azobenzene derivative
In the following Examples 11 and 12, the azobenzene derivative D1 was produced by protecting the amino group (Example 11), and the azobenzene derivative C1 was produced by deprotecting the amino-protecting group of the azobenzene derivative D1 ( Example 12).

Synthesis of aniline derivative 5 Here, the aniline derivative 5 used as a raw material of the azobenzene derivative D1 in Example 11 was synthesized.

Under an argon atmosphere, chloroacetic acid (767 mg, 8.12 mmol) and 4-methoxybenzaldehyde (10.4 mL, 85.3 mmol) were added to a solution of 3-aminobenzyl alcohol (10.0 g, 81.2 mmol) and isopropyl alcohol (120 mL). The mixture was heated to reflux with stirring for 14 hours. After the reaction, the reaction solution was returned to room temperature and concentrated under reduced pressure to obtain a crude product of 3- (hydroxymethyl) -N- (4-methoxybenzylidene) aniline.
The obtained crude product of 3- (hydroxymethyl) -N- (4-methoxybenzylidene) aniline in ethanol (120 mL) was ice-cooled, and then sodium borohydride (3.07 g, 81.2 mmol) was added little by little. The mixture was further stirred at room temperature for 2 days. After completion of the reaction, the reaction solution was ice-cooled, water (100 mL) was slowly added, and the mixture was concentrated under reduced pressure. The resulting reaction solution was extracted three times with chloroform (100 mL), and the combined organic layer was washed with water and saturated brine. The organic layer was dried over sodium sulfate, concentrated under reduced pressure, and purified by column chromatography using a mixed solvent of hexane: ethyl acetate = 94: 6 to 73:27 as an eluent to give 3- (hydroxy A yellow oily product of methyl) -N- (4-methoxybenzyl) aniline (aniline derivative 5) was obtained in a yield of 18.6 g and a yield of 94%.
¹ H-NMR (400MHz, CDCl ₃ ): δ 7.28 (d, J = 8.7Hz, 2H), 7.16 (m, 1H), 6.88 (d, J = 8.7Hz, 2H), 6.70 (m, 1H), 6.66 (m, 1H), 6.56 (m, 1H), 4.60 (s, 2H), 4.26 (s, 2H), 3.99 (brs, 1H), 3.80 (s, 3H).

(Example 11) Production of azobenzene derivative D1 In this example, azobenzene derivative D1 was produced by reacting benzenediazonium salt 1 produced from 4-nitroaniline with synthesized aniline derivative 5.

A mixture of 4-nitroaniline (10.6 g, 76.4 mmol), acetic acid (93 mL) and propionic acid (46 mL) was ice-cooled, and sulfuric acid (14 mL) was added. To this solution was slowly added a solution of sodium nitrite (6.33 g, 91.7 mmol) in water (14 mL), followed by stirring for 5 minutes under ice cooling (ice bath), and then urea (1.51 g, 25.2 mmol) was added. The mixture was further stirred for 5 minutes to obtain an aqueous solution of 4-nitrobenzenediazonium sulfate (benzenediazonium salt 1).
The obtained aqueous solution of 4-nitrobenzenediazonium sulfate was mixed with ice-cooled N- (3-hydroxymethyl) -N- (4-methoxybenzyl) aniline (aniline derivative 5: 18.6 g, 76.4 mmol) in ethanol (150 mL). ) Slowly added to the solution and stirred for 3 hours under ice cooling (ice bath). After the reaction, the resulting solid was collected by filtration, washed with water (2 L), ethanol (100 mL) and hexane (500 mL), and dried under reduced pressure. Ethyl acetate (200 mL) and hexane (300 mL) were added to the resulting crude solid, and the precipitated solid was collected by filtration to give crude 2- (hydroxymethyl) -4- (4-methoxybenzylamino). ) -4′-nitroazobenzene (azobenzene derivative D1) was obtained in a yield of 25.9 g. The obtained 2- (hydroxymethyl) -4- (4-methoxybenzylamino) -4′-nitroazobenzene can be used for the next reaction without purification.
¹ H-NMR (400MHz, DMSO-d ₆ ): δ 8.34 (d, J = 8.6Hz, 2H), 7.88 (d, J = 8.6Hz, 2H), 7.67 (m, 1H), 7.29 (d, J = 8.6Hz, 2H), 6.95 (m, 1H), 6.91 (d, J = 8.6Hz, 2H), 6.62 (m, 1H), 5.00 (s, 2H), 4.37 (s, 2H), 3.73 (s , 3H).

(Example 12) Production of azobenzene derivative C1 In this example, the amino protecting group of the azobenzene derivative D1 produced in Example 11 was deprotected to produce an azobenzene derivative C1.

To a solution of 2- (hydroxymethyl) -4- (4-methoxybenzylamino) -4′-nitroazobenzene (azobenzene derivative D1: 5.00 g, 12.7 mmol) and dichloromethane (80 mL) was added water (50 mL) and DDQ ( 2.95 g, 13.0 mmol) was added, and the mixture was stirred at room temperature for 2 days. After completion of the reaction, chloroform (200 mL) was added to the reaction mixture, and the solid was collected by filtration. The obtained solid was dissolved in ethyl acetate (300 mL), and washed successively with saturated aqueous sodium hydrogen carbonate solution, water and saturated brine. The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure to obtain a crude 4-amino-2- (hydroxymethyl) -4′-nitroazobenzene (azobenzene derivative C1) purple solid in a yield of 2.51 g. . The obtained 4-amino-2- (hydroxymethyl) -4′-nitroazobenzene can be used in the next reaction without purification.
¹ H-NMR (400MHz, DMSO-d ₆ ): δ 8.34 (d, J = 9.1Hz, 2H), 7.88 (d, J = 9.1Hz, 2H), 7.65 (m, 1H), 6.89 (m, 1H ), 6.56 (brs, 2H), 6.54 (m, 1H), 5.23 (m, 1H), 5.01-4.98 (m, 2H).

[7] Production example 7 of azobenzene derivative
In Example 13 below, an azobenzene derivative D2 was produced by protecting the amino group, and an azobenzene derivative C1 was produced by deprotecting the amino protecting group of the azobenzene derivative D2. In Example 14, the azobenzene derivative A1 was produced by converting the hydroxyl group at the 2-position of the azobenzene derivative C1 to an ethoxy group.

(Example 13) Production of azobenzene derivatives D2 and C1 In this example, an azobenzene derivative was prepared by reacting benzenediazonium salt 2 produced from 4-nitroaniline with aniline derivative 6 produced from 3-aminobenzyl alcohol. D2 was produced, and further the azobenzene derivative C1 was produced by deprotecting the protecting group of the amino group of the azobenzene derivative D2.

Concentrated hydrochloric acid (3 mL) was added to a suspension of 4-nitroaniline (1.67 g, 12.1 mmol) in water (12 mL) with stirring at room temperature. Next, while cooling in an ice bath, a solution of sodium nitrite (835 mg, 12.1 mmol) in water (4 mL) was added dropwise to the reaction solution, and then the mixture was stirred for 30 minutes under ice cooling (ice bath). An aqueous solution of nitrobenzenediazonium chloride (benzenediazonium salt 2) was obtained. The entire amount of this aqueous solution was used for the next reaction.
A solution obtained by mixing sodium bisulfite (1.75 g, 16.8 mmol), 37% formalin (1.13 mL, 15.1 mmol) and water (2 mL) was stirred at 50 ° C. (oil bath) for 30 minutes. To this solution was added a solution of 3-aminobenzyl alcohol (1.49 g, 12.1 mmol) in ethanol (1 mL) in an oil bath at 70 ° C., and the mixture was stirred for 1.5 hours and then allowed to stand for 10 minutes under ice cooling. . A solution of sodium acetate (8 g) in water (40 mL) was added to the reaction mixture to obtain a suspension of sodium [{3- (hydroxymethyl) phenyl} amino] methylsulfonate (aniline derivative 6).
To the obtained suspension of [{3- (hydroxymethyl) phenyl} amino] methylsulfonate, an aqueous solution of 4-nitrobenzenediazonium chloride (benzenediazonium salt 2) separately prepared was ice-cooled (ice bath). It was added dropwise over 10 minutes. The reaction mixture was stirred for 3 hours while gradually warming to room temperature to obtain an aqueous solution of 2- (hydroxymethyl) -4- (sodiooxysulfonylmethylamino) -4′-nitroazobenzene (azobenzene derivative D2).
To a solution of the obtained 2- (hydroxymethyl) -4- (sodiooxysulfonylmethylamino) -4′-nitroazobenzene, a solution of sodium hydroxide (2.42 g, 60.5 mmol) in water (20 mL) at room temperature. The mixture was then stirred in an oil bath at 80 ° C. for 1.5 hours. After completion of the reaction, the reaction mixture was cooled to room temperature, water (100 mL) was added, and the precipitated solid was collected by filtration. The obtained solid was washed with water (100 mL) and dried under reduced pressure to obtain a yield of 2.48 g of a brown solid of 4-amino-2- (hydroxymethyl) -4′-nitroazobenzene (azobenzene derivative C1). Rate: Obtained at 75%.
¹ H-NMR (400MHz, DMSO-d ₆ ): δ 8.34 (d, J = 9.1Hz, 2H), 7.88 (d, J = 9.1Hz, 2H), 7.65 (m, 1H), 6.89 (m, 1H ), 6.56 (brs, 2H), 6.54 (m, 1H), 5.23 (m, 1H), 5.01-4.98 (m, 2H).

(Example 14) Production of azobenzene derivative A1 In this example, the azobenzene derivative A1 was produced by converting the hydroxyl group of the azobenzene derivative C1 produced in Example 13 to an ethoxy group.

Under an argon atmosphere, 55% oily sodium hydride (64.1 mg, 1.47 mmol) obtained by washing away mineral oil with hexane was suspended in DMF (2 mL) under cooling (ice bath), and 4- A solution of amino-2- (hydroxymethyl) -4′-nitroazobenzene (azobenzene derivative C1: 100 mg, 0.367 mmol) in DMF (2 mL) was slowly added. Then, iodoethane (60 mg, 0.385 mmol) was added, and the mixture was warmed to room temperature and stirred for 24 hours. After completion of the reaction, the reaction mixture was cooled (ice bath) and water (50 mL) was added. The resulting mixture was extracted three times with ethyl acetate (50 mL), and the combined organic layer was washed with distilled water and saturated brine. The organic layer was dried over anhydrous sodium sulfate and then concentrated under reduced pressure, and the crude product obtained was subjected to silica gel column chromatography using a mixed solvent of hexane: ethyl acetate = 64: 36 to 43:57 as an eluent. By purifying with 4-amino-2- (ethoxymethyl) -4′-nitroazobenzene (azobenzene derivative A1), a reddish brown solid was obtained in a yield of 42.5 mg and a yield of 37%.
¹ H-NMR (400MHz, CDCl ₃ ): δ 8.34 (d, J = 9.1Hz, 2H), 7.90 (d, J = 9.1Hz, 2H), 7.76 (d, J = 8.8Hz, 1H), 6.94 ( d, J = 2.6Hz, 1H), 6.61 (dd, J = 8.8 and 2.6Hz, 1H), 5.07 (s, 2H), 4.25 (brs, 2H), 3.69 (q, J = 7.0Hz, 2H), 1.31 (t, J = 7.0Hz, 3H).

[8] Production example 8 of azobenzene derivative
In Example 15 below, an azobenzene derivative F1 in which an amino group was protected was produced, and an azobenzene derivative E1 was produced by converting the hydroxyl group of the azobenzene derivative F1 to an acetyloxy group. In Example 16, the azobenzene derivative E2 was produced by converting the hydroxyl group of the azobenzene derivative F1 to an ethoxycarbonyloxy group.

(Example 15) Production of azobenzene derivatives F1 and E1 In this example, azobenzene derivatives F1 and E1 were produced using 4,4′-diamino-2- (hydroxymethyl) azobenzene as a raw material.

Under an argon atmosphere, a solution of 4,4′-diamino-2- (hydroxymethyl) azobenzene (15.0 g, 61.9 mmol) in THF (300 mL) was ice-cooled, and then di-tert-butyl dicarbonate (40.6 g, 186 mmol). ) Was added. The reaction system was stirred at 55 ° C. for 12 hours and then concentrated under reduced pressure, and the resulting residue was washed with hexane to give 4,4′-bis (tert-butyloxycarbonylamino) -2- (hydroxymethyl). A yellow solid of azobenzene (azobenzene derivative F1) was obtained in a yield of 24.4 g and a yield of 89%.
¹ H-NMR (400MHz, DMSO-d ₆ ): δ 9.72 (brs, 1H), 9.69 (brs, 1H), 7.87 (d, J = 2.2Hz, 1H), 7.77 (d, J = 9.0Hz, 2H ), 7.64 (d, J = 9.0Hz, 2H), 7.55 (d, J = 8.8Hz, 1H), 7.43 (dd, J = 8.9 and 2.3Hz, 1H), 5.21 (t, J = 5.6Hz, 1H ), 5.02 (d, J = 5.5Hz, 2H), 1.50 (s, 18H).

Under an argon atmosphere, a solution of 4,4′-bis (tert-butyloxycarbonylamino) -2- (hydroxymethyl) azobenzene (azobenzene derivative F1: 24.0 g, 54.2 mmol) in THF (300 mL) was ice-cooled, Acetic anhydride (5.81 g, 56.9 mmol), pyridine (8.54 g, 108 mmol), and 4-dimethylaminopyridine (66 mg, 0.54 mmol) were sequentially added. The reaction system was stirred at 50 ° C. for 4 hours, then concentrated under reduced pressure, and the residue was dissolved in ethyl acetate (500 mL). The organic layer was washed with water (200 mL) and saturated brine (100 mL), dried over anhydrous sodium sulfate, and concentrated under reduced pressure to give 4,4′-bis (tert-butyloxycarbonylamino)- A yellow solid of 2- (acetyloxymethyl) azobenzene (azobenzene derivative E1) was obtained in a yield of 23.5 g and a yield of 89%.
¹ H-NMR (400MHz, DMSO-d ₆ ): δ 9.77 (brs, 1H), 9.76 (brs, 1H), 7.79 (d, J = 9.0Hz, 2H), 7.69 (d, J = 2.2Hz, 1H ), 7.66 (d, J = 9.0Hz, 2H), 7.65 (d, J = 8.9Hz, 1H), 7.58 (dd, J = 8.9 and 2.2Hz, 1H), 5.59 (s, 2H), 2.09 (s , 3H), 1.50 (s, 18H).

(Example 16) Production of azobenzene derivative E2 In this example, the azobenzene derivative E2 was produced using the azobenzene derivative F1 synthesized in Example 15 as a raw material.

In an argon atmosphere, a solution of the azobenzene derivative F1 (19.0 g, 42.9 mmol) in THF (150 mL) was ice-cooled, and then pyridine (8.46 g, 107 mmol), 4-dimethylaminopyridine (524 mg, 4.29 mmol), chloro Ethyl formate (7.91 g, 72.9 mmol) was added sequentially. The reaction system was stirred for 1.5 hours while warming to room temperature, then concentrated under reduced pressure, and the residue was dissolved in ethyl acetate (500 mL). The organic layer was washed with water (200 mL), dried over anhydrous sodium sulfate, and concentrated under reduced pressure to give 4,4′-bis (tert-butyloxycarbonylamino) -2- (ethoxycarbonyloxymethyl). A yellow solid of azobenzene (azobenzene derivative E2) was obtained in a yield of 20.9 g and a yield of 95%.
¹ H-NMR (400MHz, CDCl ₃ ): δ 7.86 (m, 2H), 7.76 (m, 1H), 7.55 (m, 1H), 7.52-7.45 (m, 3H), 6.65 (brs, 2H), 5.74 (s, 2H), 4.23 (q, J = 7.1Hz, 2H), 1.55 (s, 9H), 1.54 (s, 9H), 1.31 (t, J = 7.1Hz, 3H).

[9] Production Example of 4,4′- Diaminoazobenzenes In the following Examples 17 to 25, 4,4′-diaminoazobenzenes 1 to 8 using azobenzene derivatives A1 to A5, C1, E1, and E2 as raw materials. Manufactured.

(Example 17) Production of 4,4'-diaminoazobenzenes 1 In this example, 4,4'-diaminoazobenzenes 1 were produced using azobenzene derivative A1 as a raw material.

4-Amino-2- (ethoxymethyl) -4'-nitroazobenzene (azobenzene derivative A1: 30.6 g, 102 mmol) in ethanol (500 mL) solution in water (50 mL) and sodium sulfide (23.9 g, 306 mmol) And heated to reflux for 30 minutes. After completion of the reaction, the reaction solution was cooled to room temperature, water (100 mL) was added, the mixture was concentrated under reduced pressure, and extracted with ethyl acetate (300 mL). The combined organic layer was washed with water and saturated brine. The organic layer was dried over anhydrous sodium sulfate and then concentrated under reduced pressure to obtain a crude product of 4,4′-diamino-2- (ethoxymethyl) azobenzene.
Toluene (70 mL) was added and dissolved in the resulting crude product, hexane (100 mL) was added, and the precipitated solid was collected by filtration. The obtained solid was purified by column chromatography using a mixed solvent of hexane: ethyl acetate = 70: 30 to 25:75 as an eluent, dissolved in methanol (200 mL), and activated carbon (10 g). And stirred in an oil bath at 50 ° C. for 10 minutes. The activated carbon was filtered off, and the solvent was distilled off from the mother liquor under reduced pressure to yield a yellow solid of 4,4′-diamino-2- (ethoxymethyl) azobenzene (4,4′-diaminoazobenzenes 1) in a yield of 9.93. g, yield 36%.
¹ H-NMR (400MHz, CDCl ₃ ): δ 7.71 (d, J = 8.7Hz, 2H), 7.63 (m, 1H), 6.90 (m, 1H), 6.72 (d, J = 8.7Hz, 2H), 6.59 (m, 1H), 5.05 (s, 2H), 3.95 (brs, 4H), 3.65 (q, J = 7.0Hz, 2H), 1.29 (t, J = 7.0Hz, 3H).

(Example 18) Production of 4,4'-diaminoazobenzenes 2 In this example, 4,4'-diaminoazobenzenes 2 were produced using azobenzene derivative A3 as a raw material.

To a solution of 4-amino-2- (propyloxymethyl) -4′-nitroazobenzene (azobenzene derivative A3: 3.00 g, 9.54 mmol) in ethanol (48 mL), water (4.8 mL) and sodium sulfide (2.23 g, 28.6 mmol) was added and heated to reflux for 30 minutes. The reaction mixture was cooled to room temperature and concentrated under reduced pressure, water (50 mL) was added, and the mixture was extracted 3 times with ethyl acetate (50 mL). The combined organic layer was washed with water (50 mL) and saturated brine (50 mL), dried over anhydrous sodium sulfate, and then concentrated under reduced pressure to give 4,4′-diamino-2- (propyloxy). A crude product of methyl) azobenzene was obtained.
The resulting crude product of 4,4′-diamino-2- (propyloxymethyl) azobenzene was purified by silica gel column chromatography using a mixed solvent of hexane: ethyl acetate = 60: 40 as an eluent. The polar component was removed. Next, the obtained crude product was dissolved in toluene (5 mL), hexane (10 mL) was added, and the precipitated solid was collected by filtration to obtain a crude solid (2.2 g). The obtained crude solid (2.2 g) was dissolved in methanol (44 mL). Activated carbon (2.2 g) was added to this methanol solution, and the mixture was stirred in an oil bath at 50 ° C. for 10 minutes. Methanol (44 mL) was further added, and activated carbon was removed by Celite filtration. The mother liquor obtained was concentrated under reduced pressure and then dried under reduced pressure to yield a yellow solid of 4,4′-diamino-2- (propyloxymethyl) azobenzene (4,4′-diaminoazobenzenes 2) in a yield of 1.87 g. The yield was 69%.
¹ H-NMR (400MHz, CDCl ₃ ): δ 7.72 (d, J = 8.8Hz, 2H), 7.63 (d, J = 8.7Hz, 1H), 6.91 (s, 1H), 6.73 (d, J = 8.8 Hz, 2H), 6.60 (dd, J = 8.7 and 2.6Hz, 1H), 5.05 (s, 2H), 3.95 (brs, 4H), 3.55 (t, J = 6.71Hz, 2H), 1.67 (qt, J = 7.4 and 6.7Hz, 2H), 0.97 (t, J = 7.4Hz, 3H).

Example 19 Production of 4,4′-diaminoazobenzenes 3 In this example, 4,4′-diaminoazobenzenes 3 were produced using azobenzene derivative A2 as a raw material.

To a solution of 4-amino-2- (isopropyloxymethyl) -4′-nitroazobenzene (azobenzene derivative A2: 5.06 g, 16.1 mmol) in ethanol (80 mL), water (8 mL) and sodium sulfide (3.77 g, 48.3 mmol) was added and heated to reflux for 30 minutes. The reaction mixture was cooled to room temperature and concentrated under reduced pressure, water (30 mL) was added, and the mixture was extracted 4 times with ethyl acetate (100 mL). The combined organic layer was washed with water (150 mL) and saturated brine (150 mL), dried over anhydrous sodium sulfate, and then concentrated under reduced pressure to give 4,4′-diamino-2- (propyloxy). A crude product of methyl) azobenzene was obtained.
The obtained crude product of 4,4′-diamino-2- (propyloxymethyl) azobenzene was subjected to silica gel column chromatography using a mixed solvent of hexane: ethyl acetate = 70: 30 to 25:75 as an eluent. Purified to remove high polar components. Subsequently, the obtained crude product was dissolved in toluene (5 mL), hexane (10 mL) was added, and the precipitated solid was collected by filtration to obtain a crude solid (2.4 g). The obtained crude solid (2.4 g) was dissolved in methanol (48 mL). Activated carbon (2.4 g) was added to this methanol solution, and the mixture was stirred at 50 ° C. (oil bath) for 10 minutes. Methanol (48 mL) was further added, and activated carbon was removed by Celite filtration. The obtained mother liquor was concentrated under reduced pressure and then dried under reduced pressure to yield a yellow solid of 4,4′-diamino-2- (isopropyloxymethyl) azobenzene (4,4′-diaminoazobenzenes 3) in a yield of 1.63 g, Obtained in a yield of 36%.
¹ H-NMR (400MHz, CDCl ₃ ): δ 7.72 (d, J = 8.8Hz, 2H), 7.62 (d, J = 8.7Hz, 1H), 6.93 (d, J = 2.6Hz, 1H), 6.73 ( d, J = 8.8Hz, 2H), 6.60 (dd, J = 8.7 and 2.6Hz, 1H), 5.05 (s, 2H), 3.95 (brs, 4H), 3.78 (t, J = 6.1Hz, 1H), 1.26 (d, J = 6.1Hz, 6H).

(Example 20) Production of 4,4'-diaminoazobenzenes 4 In this example, 4,4'-diaminoazobenzenes 4 were produced using azobenzene derivative C1 as a raw material.

To a solution of 4-amino-2- (hydroxymethyl) -4′-nitroazobenzene (azobenzene derivative C1: 132 mg, 0.485 mmol) in ethanol (25 mL) was added water (2.5 mL) and sodium sulfide (114 mg, 1.46 mmol). ) And heated to reflux for 30 minutes. After completion of the reaction, the reaction solution was cooled to room temperature, water (100 mL) was added, and the mixture was concentrated under reduced pressure. The obtained reaction solution was extracted three times with ethyl acetate (100 mL), and the combined organic layer was washed with water and saturated brine. The organic layer was dried over anhydrous sodium sulfate and then concentrated under reduced pressure to obtain a crude product of 4,4′-diamino-2- (hydroxymethyl) azobenzene.
The resulting crude product of 4,4′-diamino-2- (hydroxymethyl) azobenzene was purified by silica gel column chromatography using ethyl acetate as an eluent to remove highly polar components. Next, toluene (5 mL) and hexane (10 mL) were added to the obtained crude product, and the precipitated solid was collected by filtration to obtain a crude solid (0.1 g). The obtained crude solid (0.1 g) was dissolved in methanol (10 mL). Activated carbon (0.1 g) was added to this methanol solution, and the mixture was stirred at 50 ° C. (oil bath) for 10 minutes. Methanol (10 mL) was further added, and activated carbon was removed by Celite filtration. The obtained mother liquor was concentrated under reduced pressure and then dried under reduced pressure to obtain a yellow solid of 4,4′-diamino-2- (hydroxymethyl) azobenzene (yield 67 mg, yield: 58%).
¹ H-NMR (400MHz, DMSO-d ₆ ): δ 7.50 (d, J = 8.8Hz, 2H), 7.42 (m, 1H), 6.81 (m, 1H), 6.62 (d, J = 8.8Hz, 2H ), 6.46 (m, 1H), 5.72 (brs, 2H), 5.71 (brs, 2H), 5.00 (m, 1H), 4.93-4.90 (m, 2H).

Under an argon atmosphere, 55% oily sodium hydride (54.1 mg, 1.24 mmol) washed with hexane and washed with hexane was suspended in THF (6 mL). A solution of 4′-diamino-2- (hydroxymethyl) azobenzene (300 mg, 1.24 mmol) in THF (6 mL) was slowly added. Next, iodomethane (176 mg, 1.24 mmol) was added, the temperature was raised to room temperature, and the mixture was stirred for 22 hours. After completion of the reaction, the reaction mixture was cooled (ice bath) and water (50 mL) was added. The resulting mixture was extracted three times with ethyl acetate (30 mL), and the combined organic layer was washed with distilled water and saturated brine. The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure, and the crude product was purified by silica gel column chromatography using a mixed solvent of hexane: ethyl acetate = 57: 43 to 36:64 as an eluent. The yellow solid of 4,4′-diamino-2- (methoxymethyl) azobenzene (4,4′-diaminoazobenzenes 4) was obtained in a yield of 135 mg and a yield of 42%.
¹ H-NMR (400MHz, CDCl ₃ ): δ 7.72 (d, J = 8.8Hz, 2H), 7.64 (d, J = 8.7Hz, 1H), 6.88 (d, J = 2.6Hz, 1H), 6.73 ( d, J = 8.8Hz, 2H), 6.61 (dd, J = 8.8 and 2.6Hz, 1H), 5.01 (s, 2H), 3.95 (brs, 4H), 3.49 (s, 3H).

(Example 21) Production of 4,4'-diaminoazobenzenes 1 by other steps 4,4'-diamino-2- (hydroxymethyl) was conducted in the same manner as in Example 20 except that iodoethane was used instead of iodomethane. ) 4,4′-Diamino-2- (ethoxymethyl) azobenzene (4,4′-diaminoazobenzenes 1) was synthesized using azobenzene as a raw material.

Under an argon atmosphere, 55% oily sodium hydride (54.1 mg, 1.24 mmol) washed with hexane and washed with hexane was suspended in DMF (6 mL) under cooling (ice bath). A solution of 4′-diamino-2- (hydroxymethyl) azobenzene (300 mg, 1.24 mmol) and DMF (6 mL) was added slowly. Then, iodoethane (193 mg, 1.24 mmol) was added, and the mixture was warmed to room temperature and stirred for 22 hours. After completion of the reaction, the reaction mixture was cooled (ice bath) and water (50 mL) was added. The resulting mixture was extracted three times with ethyl acetate (50 mL), and the combined organic layer was washed with distilled water and saturated brine. The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The crude product obtained was subjected to silica gel column chromatography using a mixed solvent of hexane: ethyl acetate = 57: 43 to 36:64 as an eluent. By purification, a yellow solid of 4,4′-diamino-2- (ethoxymethyl) azobenzene (4,4′-diaminoazobenzenes 1) was obtained in a yield of 132 mg and a yield of 39%.
¹ H-NMR (400MHz, CDCl ₃ ): δ 7.71 (d, J = 8.7Hz, 2H), 7.63 (m, 1H), 6.90 (m, 1H), 6.72 (d, J = 8.7Hz, 2H), 6.59 (m, 1H), 5.05 (s, 2H), 3.95 (brs, 4H), 3.65 (q, J = 7.0Hz, 2H), 1.29 (t, J = 7.0Hz, 3H).

(Example 22) Production of 4,4'-diaminoazobenzenes 5 In this example, 4,4'-diaminoazobenzenes 5 were produced using azobenzene derivative A4 as a raw material.

To a solution of 4-amino-2- (isobutyloxymethyl) -4′-nitroazobenzene (azobenzene derivative A4: 58.8 g, 179 mmol) in ethanol (880 mL), water (60 mL) and sodium sulfide (42.0 g, 538 mmol) was added and heated to reflux for 30 minutes. The reaction mixture was cooled to room temperature and concentrated under reduced pressure, water (300 mL) was added, and the mixture was extracted 3 times with ethyl acetate (300 mL). The combined organic layer was washed with water (300 mL) and saturated brine (300 mL), dried over anhydrous sodium sulfate, and then concentrated under reduced pressure to give 4,4′-diamino-2- (isobutyloxy). A crude product of methyl) azobenzene was obtained.
The obtained crude product of 4,4′-diamino-2- (isobutyloxymethyl) azobenzene was purified by silica gel column chromatography using a mixed solvent of hexane: ethyl acetate = 60: 40 as an eluent. The polar component was removed. Next, the obtained crude product was dissolved in toluene (50 mL), hexane (200 mL) was added, and the precipitated solid was collected by filtration to obtain a crude solid. Dissolve the resulting crude solid (15 g) in methanol (600 mL), add activated carbon (15 g), stir in an oil bath at 50 ° C for 5 min, add methanol (300 mL), and filter through Celite. The activated carbon was removed. The obtained mother liquor was concentrated under reduced pressure and then dried under reduced pressure to yield 12.4 g of a yellow solid of 4,4′-diamino-2- (isobutyloxymethyl) azobenzene (4,4′-diaminoazobenzenes 5), The yield was 23%.
¹ H-NMR (400MHz, CDCl ₃ ): δ 7.72 (d, J = 8.8Hz, 2H), 7.62 (d, J = 8.6Hz, 1H), 6.92 (d, J = 2.6Hz, 1H), 6.73 ( d, J = 8.8Hz, 2H), 6.60 (dd, J = 8.6 and 2.6Hz, 1H), 5.04 (s, 2H), 3.95 (brs, 4H), 3.35 (d, J = 6.7Hz, 2H), 1.97 (m, 1H), 0.96 (d, J = 6.7Hz, 6H).

(Example 23) Production of 4,4'-diaminoazobenzenes 6 In this example, 4,4'-diaminoazobenzenes 6 were produced using azobenzene derivative A5 as a raw material.

To a solution of 4-amino-2-[(2,2,2-trifluoroethyloxy) methyl] -4′-nitroazobenzene (azobenzene derivative A5: 38.6 g, 109 mmol) in ethanol (550 mL) was added water (45 mL) and sodium sulfide (25.5 g, 327 mmol) were added, and the mixture was heated to reflux for 30 minutes. The reaction mixture was cooled to room temperature and concentrated under reduced pressure, water (100 mL) was added, and the mixture was extracted 3 times with ethyl acetate (100 mL). The combined organic layer was washed with water (150 mL) and saturated brine (150 mL), dried over anhydrous sodium sulfate, and then concentrated under reduced pressure to give 4,4′-diamino-2-[(2 , 2,2-trifluoroethyloxy) methyl] azobenzene was obtained.
The obtained crude product of 4,4′-diamino-2-[(2,2,2-trifluoroethyloxy) methyl] azobenzene was used as an eluent with a mixed solvent of hexane: ethyl acetate = 60: 40. And purified by silica gel column chromatography to remove highly polar components. Next, the obtained crude product was dissolved in toluene (10 mL), hexane (200 mL) was added, and the precipitated solid was collected by filtration to obtain a crude solid (12.7 g). The obtained crude solid (12.7 g) was dissolved in methanol (260 mL), activated carbon (13 g) was added, and the mixture was stirred in an oil bath at 50 ° C. for 5 minutes. Methanol (260 mL) was further added, and the mixture was filtered through Celite. The activated carbon was removed. The obtained mother liquor was concentrated under reduced pressure and then dried under reduced pressure to obtain 4,4′-diamino-2-[(2,2,2-trifluoroethyloxy) methyl] azobenzene (4,4′-diaminoazobenzenes). The yellow solid of 6) was obtained in a yield of 9.53 g and a yield of 27%.
¹ H-NMR (400MHz, CDCl ₃ ): δ 7.71 (d, J = 8.7Hz, 2H), 7.66 (d, J = 8.7Hz, 1H), 6.86 (d, J = 2.6Hz, 1H), 6.73 ( d, J = 8.7Hz, 2H), 6.65 (dd, J = 8.7 and 2.6Hz, 1H), 5.22 (s, 2H), 3.99 (brs, 4H), 3.94 (t, J = 8.8Hz, 2H); ¹⁹ F-NMR (376 MHz, CDCl ₃ ): -74.0 (s).

(Example 24) Production of 4,4-diaminoazobenzenes 7 In this example, 4,4-diaminoazobenzenes 7 were produced using azobenzene derivative E1 as a raw material.

In an argon atmosphere, a solution of 4,4′-bis (tert-butyloxycarbonylamino) -2- (acetyloxymethyl) azobenzene (azobenzene derivative E1: 23.4 g, 48.3 mmol) in dichloromethane (450 mL) was ice-cooled. , TFA (55.1 g, 483 mmol) was added. The reaction system was stirred for 13 hours while gradually warming to room temperature, and then concentrated under reduced pressure. Ethyl acetate (500 mL) was added to the residue, and then saturated aqueous sodium carbonate solution (200 mL) was added and stirred. The organic layer was washed with water (200 mL) and saturated brine (200 mL), dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The resulting crude product was purified by silica gel column chromatography using a mixed solvent of hexane: ethyl acetate = 60: 40 as an eluent to remove highly polar components. Subsequently, the obtained crude product was dissolved in toluene (20 mL), hexane (200 mL) was added, and the precipitated solid was collected by filtration to obtain a crude solid (10.9 g). The obtained crude solid (10.9 g) was dissolved in methanol (600 mL), activated carbon (10 g) was added, and the mixture was stirred in an oil bath at 50 ° C. for 5 min. Methanol (600 mL) was further added, and the mixture was filtered through Celite. The activated carbon was removed. The obtained mother liquor was concentrated under reduced pressure, and then dried under reduced pressure to yield a yellow solid of 4,4′-diamino-2- (acetyloxymethyl) azobenzene (4,4′-diaminoazobenzenes 7) in a yield of 8.59 g, Yield was 63%.
¹ H-NMR (400MHz, CDCl ₃ ): δ 7.73 (d, J = 8.8Hz, 2H), 7.67 (d, J = 8.7Hz, 1H), 6.78 (d, J = 2.6Hz, 1H), 6.72 ( d, J = 8.8Hz, 2H), 6.66 (dd, J = 8.7 and 2.6Hz, 1H), 5.66 (s, 2H), 3.97 (brs, 4H), 2.12 (s, 3H).

(Example 25) Production of 4,4-diaminoazobenzenes 8 In this example, 4,4-diaminoazobenzenes 8 were produced using azobenzene derivative E2 as a raw material.

Under an argon atmosphere, a solution of 4,4′-bis (tert-butyloxycarbonylamino) -2- (ethoxycarbonyloxymethyl) azobenzene (azobenzene derivative E2: 81.9 mg, 0.159 mmol) in dichloromethane (1 mL) was ice-cooled. Later, TFA (181 mg, 1.59 mmol) was added. The reaction system was stirred for 21 hours while gradually warming to room temperature, and then concentrated under reduced pressure. Ethyl acetate (10 mL) was added to the residue, and then saturated aqueous sodium carbonate solution (10 mL) was added and stirred. The organic layer was washed with water (50 mL), dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The resulting residue was purified by column chromatography to obtain a yellow solid of 4,4′-diamino-2- (ethoxycarbonyloxymethyl) azobenzene (4,4′-diaminoazobenzenes 8) in a yield of 3.66 mg, The yield was 7%.
¹ H-NMR (400MHz, CDCl ₃ ): δ 7.73 (d, J = 8.8Hz, 2H), 7.67 (d, J = 8.7Hz, 1H), 6.82 (d, J = 2.6Hz, 1H), 6.72 ( d, J = 8.8Hz, 2H), 6.65 (dd, J = 8.7 and 2.6Hz, 1H), 5.72 (s, 2H), 4.24 (q, J = 7.1Hz, 2H), 3.97 (brs, 4H), 1.32 (t, J = 7.1Hz, 3H).

  By using the azobenzene derivative of the present invention as an intermediate, 4,4′-diaminoazobenzenes, which are raw materials for producing polyimide photoalignment films for liquid crystal displays, can be efficiently produced with high purity by a simple technique. Therefore, the azobenzene derivative of the present invention has high industrial applicability.

Claims (10)

An azobenzene derivative represented by the following general formula (1).
[In General Formula (1), R ¹ represents a hydrogen atom, an optionally substituted alkyl group, an optionally substituted acyl group, or an optionally substituted alkoxycarbonyl group. R ² represents a hydrogen atom, an optionally substituted arylmethyl group, an alkali metal oxysulfonylmethyl group, or an optionally substituted alkoxycarbonyl group. R ³ represents a nitro group, an optionally substituted arylmethylamino group, an alkali metal oxysulfonylmethylamino group, or an optionally substituted alkoxycarbonylamino group. ] R ^{1 in the} general formula (1) is a hydrogen atom, an unsubstituted alkyl group having 1 to 6 carbon atoms, an unsubstituted acyl group having 2 to 6 carbon atoms, or an unsubstituted alkoxycarbonyl group having 2 to 6 carbon atoms. The azobenzene derivative according to claim 1. R ^{2 in} the general formula (1) according to claim 1 is a hydrogen atom, 4-methoxybenzyl group, 2,4-dimethoxybenzyl group, 3,4-dimethoxybenzyl group, 2-naphthylmethyl group, sodiooxysulfonyl The azobenzene derivative according to claim 1 or 2, which is a methyl group or a tert-butyloxycarbonyl group. The azobenzene derivative according to any one of claims 1 to 3, wherein R ^{3 in} the general formula (1) according to claim 1 is a nitro group or a tert-butyloxycarbonylamino group. An azobenzene derivative that produces an azobenzene derivative represented by the following general formula (1a) by reacting a benzenediazonium salt represented by the following general formula (2a) with an aniline derivative represented by the following general formula (3a): Production method.
[In the general formula (2a), X ⁻ represents a counter ion. R ³ represents a nitro group, an optionally substituted arylmethylamino group, an alkali metal oxysulfonylmethylamino group, or an optionally substituted alkoxycarbonylamino group. ]
[In General Formula (3a), R ¹ represents a hydrogen atom, an optionally substituted alkyl group, an optionally substituted acyl group, or an optionally substituted alkoxycarbonyl group. R ^2a represents an arylmethyl group which may be substituted, an alkali metal oxysulfonylmethyl group or an alkoxycarbonyl group which may be substituted. ]
[In General Formula (1a), R ¹ represents a hydrogen atom, an optionally substituted alkyl group, an optionally substituted acyl group, or an optionally substituted alkoxycarbonyl group. R ^2a represents an arylmethyl group which may be substituted, an alkali metal oxysulfonylmethyl group or an alkoxycarbonyl group which may be substituted. R ³ represents a nitro group, an optionally substituted arylmethylamino group, an alkali metal oxysulfonylmethylamino group, or an optionally substituted alkoxycarbonylamino group. ] The protecting group R ^2a of the amino group in the azobenzene derivative represented by the following general formula (1a) is deprotected to produce the azobenzene derivative represented by the following general formula (1b), the manufacturing method of the azobenzene derivative.
[In General Formula (1a), R ¹ represents a hydrogen atom, an optionally substituted alkyl group, an optionally substituted acyl group, or an optionally substituted alkoxycarbonyl group. R ^2a represents an arylmethyl group which may be substituted, an alkali metal oxysulfonylmethyl group or an alkoxycarbonyl group which may be substituted. R ³ represents a nitro group, an optionally substituted arylmethylamino group, an alkali metal oxysulfonylmethylamino group, or an optionally substituted alkoxycarbonylamino group. ]
[In General Formula (1b), R ¹ represents a hydrogen atom, an optionally substituted alkyl group, an optionally substituted acyl group, or an optionally substituted alkoxycarbonyl group. R ³ represents a nitro group, an optionally substituted arylmethylamino group, an alkali metal oxysulfonylmethylamino group, or an optionally substituted alkoxycarbonylamino group. ] After obtaining the azobenzene derivative represented by the following general formula (1a) by reacting the benzenediazonium salt represented by the following general formula (2a) with the aniline derivative represented by the following general formula (3a), A method for producing an azobenzene derivative, comprising deprotecting an amino-protecting group R ^2a in an azobenzene derivative represented by the formula (1a) to produce an azobenzene derivative represented by the following general formula (1b).
[In the general formula (2a), X ⁻ represents a counter ion. R ³ represents a nitro group, an optionally substituted arylmethylamino group, an alkali metal oxysulfonylmethylamino group, or an optionally substituted alkoxycarbonylamino group. ]
[In General Formula (3a), R ¹ represents a hydrogen atom, an optionally substituted alkyl group, an optionally substituted acyl group, or an optionally substituted alkoxycarbonyl group. R ^2a represents an arylmethyl group which may be substituted, an alkali metal oxysulfonylmethyl group or an alkoxycarbonyl group which may be substituted. ]
[In General Formula (1a), R ¹ represents a hydrogen atom, an optionally substituted alkyl group, an optionally substituted acyl group, or an optionally substituted alkoxycarbonyl group. R ^2a represents an arylmethyl group which may be substituted, an alkali metal oxysulfonylmethyl group or an alkoxycarbonyl group which may be substituted. R ³ represents a nitro group, an optionally substituted arylmethylamino group, an alkali metal oxysulfonylmethylamino group, or an optionally substituted alkoxycarbonylamino group. ]
[In General Formula (1b), R ¹ represents a hydrogen atom, an optionally substituted alkyl group, an optionally substituted acyl group, or an optionally substituted alkoxycarbonyl group. R ³ represents a nitro group, an optionally substituted arylmethylamino group, an alkali metal oxysulfonylmethylamino group, or an optionally substituted alkoxycarbonylamino group. ] An azobenzene derivative represented by the following general formula (1bb) is produced by reacting an azobenzene derivative represented by the following general formula (1ba) with a compound represented by the following general formula (5) in the presence of a base. A method for producing an azobenzene derivative.
[In General Formula (1ba), R ^1a represents a hydrogen atom. R ³ represents a nitro group, an amino group, an arylmethylamino group which may be substituted, an alkali metal oxysulfonylmethylamino group or an alkoxycarbonylamino group which may be substituted. ]
[In General Formula (5), R ^1b represents an optionally substituted alkyl group, an optionally substituted acyl group, or an optionally substituted alkoxycarbonyl group. L represents a leaving group. ]
[In General Formula (1bb), R ^1b represents an optionally substituted alkyl group, an optionally substituted acyl group, or an optionally substituted alkoxycarbonyl group. R ³ represents a nitro group, an amino group, an arylmethylamino group which may be substituted, an alkali metal oxysulfonylmethylamino group or an alkoxycarbonylamino group which may be substituted. ] The hydrogen atom of the hydroxyl group at the 2-position of the azobenzene derivative represented by the following general formula (1c) is substituted with an optionally substituted alkyl group, an optionally substituted acyl group or an optionally substituted alkoxycarbonyl group. By doing this, the manufacturing method of an azobenzene derivative which manufactures the azobenzene derivative shown by the following general formula (1d).
[In General Formula (1c), R ^2a represents an optionally substituted arylmethyl group, an alkali metal oxysulfonylmethyl group, or an optionally substituted alkoxycarbonyl group. R ^3a represents an optionally substituted arylmethylamino group, an alkali metal oxysulfonylmethylamino group or an optionally substituted alkoxycarbonylamino group. ]
[In General Formula (1d), R ^1b represents an optionally substituted alkyl group, an optionally substituted acyl group, or an optionally substituted alkoxycarbonyl group. R ^2a represents an arylmethyl group which may be substituted, an alkali metal oxysulfonylmethyl group or an alkoxycarbonyl group which may be substituted. R ^3a represents an optionally substituted arylmethylamino group, an alkali metal oxysulfonylmethylamino group or an optionally substituted alkoxycarbonylamino group. ] R ^{1b in the} general formula (1d) is an optionally substituted acyl group or an optionally substituted alkoxycarbonyl group, the compound represented by the general formula (1c), the following general formula (8), and the following general formula The method for producing an azobenzene derivative according to claim 9, wherein the azobenzene derivative represented by the general formula (1d) is produced by reacting the compound represented by the formula (9) or the following general formula (10).
[In General Formula (8), General Formula (9), and General Formula (10), R ^1ba represents an optionally substituted alkyl group or an optionally substituted alkoxy group. R ^1bb represents an ^optionally substituted alkyl group. ]