JP4307108B2 - Method for producing orthobenzidine compounds - Google Patents

Description

[0001]
BACKGROUND OF THE INVENTION
The present invention relates to a method for producing an orthobenzidine compound having a specific structure.
[0002]
The orthobenzidine compound having a specific structure produced by the production method of the present invention includes an intermediate for pharmaceuticals, agricultural chemicals, an intermediate for pigments such as organic dyes and organic pigments, a catalyst for asymmetric synthesis, or an organic electroluminescent material. It is useful as an intermediate for organic photoconductive materials of organic electrophotographic photoreceptors in electrophotography.
[0003]
[Prior art]
As a method for synthesizing a benzidine compound from a hydrazobenzene compound, a method using a benzidine rearrangement (see Non-Patent Document 1) in which a hydrazobenzene compound is rearranged in the presence of a protonic acid such as hydrochloric acid is known.
[0004]
However, in this method, although a parabenzidine compound is obtained, an orthobenzidine compound is not obtained at all, or even if it is obtained, it is a very small amount. Also, benzidine rearrangement using the above-mentioned protonic acid as a catalyst, starting from a hydrazobenzene compound having a substituent introduced at the 4-, 4'-position (para-position of the nitrogen atom), which is the bonding position of the benzidine rearrangement, is performed. Even if it is applied, only a semizine compound in which a C—N bond is newly formed or an azo compound in which a hydrazobenzene compound is decomposed is formed, and an orthobenzidine compound which is the target compound of the present invention cannot be obtained at all.
[0005]
Further, as another method for obtaining an orthobenzidine compound, a method using a Suzuki reaction (Non-patent Document 2) for coupling an arylboronic acid compound and a halogenated aryl compound, or an iodinated aryl compound as a copper catalyst. A method of applying a coupling reaction to obtain a biphenyl compound such as the Ullmann reaction (Non-patent Document 3) heated at high temperature in the presence is also conceivable. However, a benzidine having an amino group in its structure, such as the target compound of the present invention. When synthesizing a compound, an orthobenzidine compound cannot be obtained because an arylamine reacted with an amino group is produced.
[0006]
Furthermore, after applying the above coupling reaction to obtain a nitro compound or phenol compound that can be a precursor compound of an orthobenzidine compound, a method of substituting it with an amino group is also conceivable, but it becomes a raw material for the coupling reaction. It is difficult to synthesize aryl boronic acid compounds and halogenated aryl compounds, and the method cannot be practically applied as a synthesis method.
[0007]
Furthermore, after introducing an iodine atom directly into the ortho position of the biphenyl compound, there is also a method of introducing an amino group using the Ullmann reaction, but the synthesis yield of the iodine compound as a raw material is low, and the Ullmann reaction itself Since the yield was low, the overall yield was extremely low, which was not practical.
[0008]
[Non-Patent Document 1]
Tai Organic Chemistry (Asakura Shoten: 1959 Vol. 16), p. 517-518
[Non-Patent Document 2]
TCL Mail (Tokyo Chemical Industry Co., Ltd .: 2000/1 No. 105), p. 18-22
[Non-Patent Document 3]
Tai Organic Chemistry (Asakura Shoten: 1959 Vol. 16), p. 510-513
[0009]
[Problems to be solved by the invention]
An object of the present invention is to provide a method for producing an orthobenzidine compound, which has been difficult to synthesize by a conventional production method, easily and in a high yield.
[0010]
[Means for Solving the Problems]
In the present invention, a hydrazobenzene compound having a substituent at the 4-, 4′-position of the structure represented by the following formula (1) is rearranged in the presence of a reagent having aprotic Lewis acidity. A method for producing an orthobenzidine compound for synthesizing an orthobenzidine compound having a structure represented by the following formula (2) :
An orthobenzidine compound characterized in that the reactant is aluminum trichloride, aluminum tribromide, phosphorus trichloride, phosphorus tribromide, iron trichloride, iron tribromide, trimethylsilyl chloride or tri-tert-butyltin . It is a manufacturing method.
[0011]
[Outside 3]
[0012]
[Outside 4]
[0013]
(In the formulas (1) and (2), R ¹ and R ² are each independently an alkyl group having a substituent (provided that the substituent of the alkyl group having the substituent is an alkyl group, an alkoxy group, a nitro group) Group, a cyano group, or a halogen atom.) Or an unsubstituted alkyl group or an alkoxy group having a substituent (provided that the substituent of the alkoxy group having the substituent includes an alkyl group, an alkoxy group, a nitro group, A cyano group or a halogen atom.) Or an unsubstituted alkoxy group, or an aralkyl group having a substituent (however, the substituent of the aralkyl group having the substituent is an alkyl group, an alkoxy group, a nitro group, or a cyano group. , or a halogen atom.) or unsubstituted aralkyl group, an aryl group having a substituent (provided that location aryl groups having the substituent Group is an alkyl group, an alkoxy group, a nitro group, a cyano group, or a halogen atom.) Or unsubstituted aryl group, or a halogen atom, R ³ and R ⁴ are each indicates hydrogen atom It is.)
According to the present invention, an orthobenzidine compound having a substituent at the para-position of a nitrogen atom can be obtained with high selectivity and high yield. Although the reaction mechanism is not clear, 2 of the hydrazobenzene compound having the structure represented by the above formula (1) is attached to the central atom (metal atom, phosphorus atom, silicon atom, etc.) of the aprotic Lewis acid reactive agent. After the formation of an intermediate containing a highly distorted three-membered ring structure coordinated by a lone pair of nitrogen atoms, a rearrangement reaction was performed to form a more stable structure, and an ortho-bond formed It is believed that a benzidine compound is formed.
[0014]
DETAILED DESCRIPTION OF THE INVENTION
In the above formulas (1) and (2), examples of the alkyl group represented by R ¹ and R ² include a methyl group, an ethyl group, an n-propyl group, and a t-butyl group. Examples of the alkoxy group include a methoxy group and an ethoxy group. Groups, propoxy groups, etc., aralkyl groups include benzyl groups, phenethyl groups, etc., aryl groups include phenyl groups, naphthyl groups, etc., halogen atoms include fluorine atoms, chlorine atoms, A bromine atom etc. are mentioned.
[0015]
In addition, the substituents that each of the above groups may have include alkyl groups such as methyl and ethyl groups, alkoxy groups such as methoxy and ethoxy, nitro groups, cyano groups, fluorine atoms, chlorine atoms, bromine And halogen atoms such as atoms.
[0016]
Specific examples of the hydrazobenzene compound having a substituent at the 4-, 4′-position of the structure represented by the above formula (1) are shown below, but the present invention is not limited to these specific examples ( However, the hydrazobenzene compound having a structure represented by the following formula (1-11) is a specific example of a hydrazobenzene compound having a substituent at the 4-, 4′-position of the structure represented by the above formula (1). No.)
[0017]
[Outside 5]
[0018]
[Outside 6]
[0019]
Next, specific examples of the orthobenzidine compound having the structure represented by the above formula (2) will be shown, but the present invention is not limited to these specific examples (however, the structure represented by the following formula (2-11)). The hydrazobenzene compound is not a specific example of an orthobenzidine compound having a structure represented by the above formula (2) .
[0020]
[Outside 7]
[0021]
[Outside 8]
[0022]
The reactant used in the production method of the present invention is not particularly limited as long as it exhibits aprotic Lewis acidity. In particular, a reactant containing a metal atom, phosphorus atom or silicon atom in its structure is preferred. Examples of such a reactive agent include aluminum trichloride, aluminum tribromide, phosphorus trichloride, phosphorus tribromide, iron trichloride, iron tribromide, trimethylsilyl chloride, tri-tert-butyltin and the like.
[0023]
In addition, the amount of the aprotic Lewis acid-reactive agent used is relative to the hydrazobenzene compound having a substituent at the 4-, 4′-position of the structure represented by the above formula (1) as the starting material. 0.01 to 10 equivalents, more preferably 0.05 to 5 equivalents, and even more preferably 0.1 to 2 equivalents.
[0024]
Although there is no limitation in particular about the solvent used for the manufacturing method of this invention, Aprotic solvents, such as toluene, hexane, acetonitrile, dimethylformamide, dimethyl sulfoxide, dichloromethane, chloroform, are preferable.
[0025]
Regarding reaction temperature, it is preferable to carry out in the range of -100-150 degreeC, and it is more preferable to react in the range of 10-50 degreeC from the point of handling.
[0026]
The production method of the present invention is a method that can be produced in air at normal pressure, but the production may be carried out under inert gasification such as nitrogen or argon.
[0027]
After completion of the reaction, the desired compound can be obtained by treating in a conventional manner.
[0028]
The hydrazobenzene compound having a substituent at the 4-, 4′-position of the structure represented by the above formula (1) is, for example, a nitrobenzene derivative having a desired substituent at the para-position as a raw material in an ethanol solvent, By reacting in the presence of a catalyst such as sodium hydroxide aqueous solution, potassium hydroxide aqueous solution, zinc or aluminum, it can be obtained in good yield.
[0029]
A synthesis example of a hydrazobenzene compound having a substituent at the 4-, 4′-position of the structure represented by the above formula (1) is shown below.
[0030]
(Synthesis Example 1)
Synthesis of hydrazobenzene compound (hydrazotoluene) having the structure represented by the above formula (1-1) 4-Nitrotoluene (13.0 g / 94.8 mmol) was dissolved in ethanol (100 ml) in a 300 ml flask, and An aqueous sodium hydroxide solution (16.6 g of sodium hydroxide and 40 ml of water) was added and stirred. Then, zinc (15.2 g / 0.22 mol) was added and deaerated by ultrasonic waves. Then, it refluxed for 4 hours, applying an ultrasonic wave. Thereafter, the mixture was cooled to room temperature, zinc (25.0 g / 0.36 mol), ethanol (90 ml) and an aqueous sodium hydroxide solution (16.6 g of sodium hydroxide and 40 ml of water) were added, and the mixture was again subjected to ultrasonic waves for 2 hours. Refluxed.
[0031]
The reaction solution was subjected to suction filtration, and hydrazotoluene contained in the filtrate was extracted with hot benzene. Benzene was removed to obtain hydrazotoluene (6.23 g / 29.4 mmol).
[0032]
・ Hydrazotoluene
¹ H-NMR (CDCl _{3 /} TMS) δ = 1.26 (2H, s), 2.42 (6H, s), 7.30 (4H, d, J = 8.9 Hz), 7.81 (4H , D, J = 8.9 Hz)
IR: (KBr) ν = 3334, 3049, 3021, 2958, 2869, 1603, 1505, 749 cm ⁻¹
m. p. : 123.0-126.7 ° C
Yield: 65%
(Synthesis Example 2)
Synthesis of hydrazobenzene compound (hydrazoanisole) having the structure represented by the above formula (1-3) Hydrazobenzene compound having a structure represented by the above formula (1-6) (4,4′-dibromohydrazo Synthesis of benzene) Synthesis of hydrazobenzene compound (4-methoxy-4′-bromohydrazobenzene) having the structure represented by the above formula (1-7) 4-nitroanisole (8.0 g / 0.52 mmol) and 4-Bromonitrobenzene (10.6 g / 0.52 mmol) was dissolved in ethanol (100 ml) in a 300 ml flask, and further an aqueous sodium hydroxide solution (16.6 g of sodium hydroxide and 40 ml of water) was added and stirred. Thereafter, aluminum (15.2 g 0.22 mol) was added and deaerated by ultrasonic waves. Then, it refluxed for 4 hours, applying an ultrasonic wave. Thereafter, the mixture was cooled to room temperature, and aluminum (25.0 g / 0.36 mol), ethanol (90 ml) and an aqueous sodium hydroxide solution (16.6 g of sodium hydroxide and 40 ml of water) were added, and the mixture was again subjected to ultrasonic waves for 2 hours. Refluxed.
[0033]
The reaction solution was subjected to suction filtration, and hydrazotoluene contained in the filtrate was extracted with hot benzene. Benzene was removed by column chromatography _(SiO 2, 100-fold, hexane: ethyl acetate = 9: 1) to give hydrazo anisole, 4,4'-dibromo hydrazobenzene, 4-methoxy-4'-bromo Hydrazobenzene was obtained in a ratio of 1: 1: 2.
[0034]
・ Hydrazoanisole
¹ H-NMR (CDCl _{3 /} TMS) δ = 1.18 (2H, s), 3.80 (6H, s), 6.92 (4H, d, J = 8.9 Hz), 7.80 (4H , D, J = 8.9 Hz)
IR: (KBr) ν = 3301, 3084, 3034, 3014, 2952, 2835, 1608, 1503, 1236, 1031, 806 cm ⁻¹
m. p. 199.5-202.6 ° C
Yield: 22%
・ 4,4'-dibromohydrazobenzene
¹ H-NMR (CDCl _{3 /} TMS) δ = 4.84 (2H, s), 6.72 (4H, d, J = 8.9 Hz), 7.34 (4H, d, J = 8.9 Hz)
IR: (KBr) ν = 3241, 3070, 1591, 1069, 823, 809 cm ⁻¹
Yield: 23%
4-methoxy-4′-bromohydrazobenzene
¹ H-NMR (CDCl _{3 /} TMS) δ = 3.77 (3H, s), 4.66 (2H, bs) 6.7 to 6.8 (6H, m,), 7.33 (2H, m )
IR: (KBr) ν = 3330, 2954, 2835, 1588, 1230, 1070, 1033, 824 cm ⁻¹
m. p. 225.2-228.1C
Yield: 46%
Other hydrazobenzene compounds having a substituent at the 4-, 4′-position of the structure represented by the above formula (1) can be synthesized in the same manner as in Synthesis Examples 1 and 2.
[0035]
【Example】
Examples of synthesizing an orthobenzidine compound having the structure represented by the above formula (2) from a hydrazobenzene compound having a substituent at the 4-, 4′-position of the structure represented by the above formula (1) are shown below. However, the present invention is not limited to these examples.
[0036]
Example 1
Synthesis of orthobenzidine compound (4,4′-dimethylorthobenzidine) having the structure represented by the above formula (2-1) Hydrazobenzene compound (hydrazotoluene) 2 having the structure represented by the above formula (1-1) 0.0 g (9.42 mmol) was substituted with argon in a 100 ml flask, dissolved in 50 ml of hexane (solvent), and stirred. There, _PBr 3 as a reactant showing an aprotic Lewis acid: was added dropwise (3.77 mmol / ml 0.4 eq) and stirred for 1 day. Thereafter, the solvent was removed, quenched with an aqueous sodium hydrogen carbonate solution, and extracted with diethyl ether. Thereafter, the extraction solvent was removed, the column was purified by column chromatography (SiO ₂ , 100 times, hexane: ethyl acetate = 9: 1), and the orthobenzidine compound (4, 4) having the structure represented by the above formula (2-1) was obtained. '-Dimethylorthobenzidine) was obtained.
¹ H-NMR (CDCl _{3 /} TMS) δ = 1.25 (2H, s), 2.64 (6H, s), 7.66 (2H, d, J = 8.9 Hz), 7.97 (2H , S), 8.11 (2H, d, J = 8.9 Hz)
IR: (KBr) ν = 3435,3051,924,2853,1638,1514,1356,803 cm ⁻¹
m. p. : 242.1-245.9 ° C
Yield: 71%
(Examples 2 to 10 and Reference Example 11)
In Example 1, the orthobenzidine compound shown in Table 1 was synthesized in the same manner as in Example 1 except that the starting material was changed to the hydrazobenzene compound shown in Table 1.
[0037]
(Examples 12 to 16)
In Example 1, the orthobenzidine compound shown in Table 1 was changed in the same manner as in Example 1 except that the type and amount of the aprotic Lewis acid-reactive agent and the solvent were changed as shown in Table 1. Synthesized.
[0038]
Table 1 shows the results of Examples 1 to 10, Reference Example 11 and Examples 12 to 16.
[0039]
[Table 1]
[0040]
(Comparative Example 1)
In Example 1, the PBr ₃ is a reactant showing an aprotic Lewis acid, except for changing the hydrochloride protic acid were reacted in the same manner as in Example 1. However, an orthobenzidine compound (4,4′-dimethylorthobenzidine) having a structure represented by the above formula (2-1) as the target compound was not obtained at all.
[0041]
(Comparative Example 2)
3.6 g (19.8 mmol) of 3,3′-dimethylbiphenyl, 4.0 g (31.6 mmol) of iodine, 1.8 g (7.9 mmol) of periodic acid, 20 ml of glacial acetic acid and 5 ml of water were added to a Dimroth condenser tube. Into a 100 ml three-necked flask equipped with a thermometer and a stirrer, the mixture was heated and stirred at 80 ° C. for 2 hours.
[0042]
After completion of the reaction, the product was extracted with toluene, and the organic layer was washed with a 10% sodium thiosulfate aqueous solution, a 10% sodium hydrogen carbonate aqueous solution and water in this order.
[0043]
Thereafter, toluene was distilled off and purification was performed using column chromatography to obtain 1.2 g (yield 14.0%) of 3,3′-dimethyl-6,6′-iodobiphenyl.
[0044]
Then, 3,3′-dimethyl-6,6′-iodobiphenyl 1.2 g (2.76 mmol), acetamide 0.33 g (5.52 mmol), copper powder 0.88 g (13.8 mmol), potassium carbonate 0 .76 g (5.52 mmol) and 10 ml of orthodichlorobenzene were added and heated under reflux in an oil bath for 8 hours (Ullmann reaction).
[0045]
After allowing to cool, 20 ml of toluene was added, and the catalyst was removed by filtration.
[0046]
Furthermore, sodium methoxide was added to the obtained crude reaction product, and the mixture was heated under reflux for 2 hours. The reaction solution was poured into water, extracted with toluene, and the organic layer was washed with water. Thereafter, the organic layer is separated, and toluene is concentrated, and then the target product is separated using column chromatography, and the orthobenzidine compound (4,4′-) having the structure represented by the above formula (2-1) is obtained. 0.1 g of dimethylorthobenzidine was obtained (yield 17.1%).
[0047]
In any case, the orthobenzidine compound having the structure represented by the above formula (2) is obtained in good yield in any case, but the conventional method (Comparative Example 1: benzidine rearrangement method, Comparative Example 2: Ullmann reaction) When the synthesis method) was used, the target product was not obtained at all, or the yield was extremely low.
[0048]
From the above, the usefulness of the present invention is clear.
[0049]
【The invention's effect】
According to the present invention, an orthobenzidine compound, which has been difficult to synthesize by a conventional production method, can be produced easily and with a high yield.

Claims (1)

A hydrazobenzene compound having a substituent at the 4-, 4′-position of the structure represented by the following formula (1) is subjected to a rearrangement reaction in the presence of a reagent having aprotic Lewis acidity. A method for producing an orthobenzidine compound for synthesizing an orthobenzidine compound having the structure represented by (2),
An orthobenzidine compound characterized in that the reactant is aluminum trichloride, aluminum tribromide, phosphorus trichloride, phosphorus tribromide, iron trichloride, iron tribromide, trimethylsilyl chloride or tri-tert-butyltin. Manufacturing method.
[Outside 1]
[Outside 2]
(In the formulas (1) and (2), R ¹ and R ² are each independently an alkyl group having a substituent (however, the substituent of the alkyl group having the substituent is an alkyl group, an alkoxy group, a nitro group) Group, a cyano group, or a halogen atom) or an unsubstituted alkyl group or a substituted alkoxy group (provided that the substituent of the alkoxy group having a substituent includes an alkyl group, an alkoxy group, a nitro group, A cyano group or a halogen atom) or an unsubstituted alkoxy group or an aralkyl group having a substituent (however, the substituent of the aralkyl group having the substituent is an alkyl group, an alkoxy group, a nitro group or a cyano group) , or a halogen atom.) or unsubstituted aralkyl group, an aryl group having a substituent (provided that location aryl groups having the substituent Group is an alkyl group, an alkoxy group, a nitro group, a cyano group, or a halogen atom.) Or unsubstituted aryl group, or a halogen atom, R ³ and R ⁴ are each indicates hydrogen atom It is.)