JPS6010019B2 - Method for producing 3-amino-4-alkoxytoluene - Google Patents

Description

[Detailed description of the invention]

The present invention relates to an industrial method for producing 3-amino-4-alkoxytoluene with high purity and high yield, which is useful as a dye intermediate, a pharmaceutical intermediate, and an intermediate raw material for various organic compounds. Conventionally, methods for producing 3-amino-4-alkoxytoluenes include, for example, as shown in the following reaction scheme (1): (1) Using P-chlorotoluene as a starting material, the first step is to nitrate this P-chlorotoluene, (2) A second step of separating and purifying 3-nitro-4-chlorotoluene and 2-nitro-4-chlorotoluene produced by the nitration in the first step; and methanol and methanol-potassium solution, neutralized with sulfuric acid, and separated the produced 3-nitro-4-methoxytoluene; A method (IG method, PB 77764) is known in which the target 3-amino-4-methoxytoluene is produced in four steps by reducing iron powder in the presence of water and formic acid. Conventional method - Reaction process formula (1) (Production rate; 70%: 30%) Chlornitrotoluene Separation and purification by fractional distillation and crystallization However, in the conventional method using this P-chlorotoluene as a starting material, 3, in which the 3-position necessary for producing the desired 3-amino-4-alkoxytoluene by the nitration reaction is nitrated.
-Nitro-4-chlorotoluene cannot be selectively produced, and the yield of 3-nitro-4-chlorotoluene produced by nitration of P-chlorotoluene is approximately 30%.
As a result, the desired 3-amino-4-alkoxytoluene cannot be produced in high yield from P-chlorotoluene. After the nitration reaction, 3-nitro-4-chlorotoluene, which is only about 30% produced, must be separated and purified from the large amount of 2-nitro-4-chlorotoluene produced, otherwise the alkoxylation will occur in the next step. Moreover, there is a drawback that the desired 3-amino-4-alkoxytoluene cannot be produced with high purity through the reduction reaction, and this separation and purification step also requires a complicated operation of repeating fractional distillation and crystallization. Therefore, since a separation and purification step is required after the nitration reaction, there is also the drawback that the target 3-amino-4-alkoxytoluene cannot be efficiently produced from the starting material P-chlorotoluene through continuous reaction. Furthermore, in the iron powder reduction reaction in the final step, there is the disadvantage that heavy iron oxide and iron hydroxide are created, which makes the post-treatment after the reaction complicated. Conventionally, as shown in the following reaction process formula (0), (1) a first step in which P-cresol is used as a starting material and the P-cresol is nitrated; - a second step of separating and purifying the cresol; (i) a third step of alkylating the 2-nitro-P-cresol obtained by the separation and purification of the second step; and (ii) a third step of alkylating the 3-nitro-4-alkoxy obtained by the alkylation of the third step. A method for producing the target 3-amino-4-alkoxytoluene in four steps by reducing toluene is also known. Conventional method - Reaction process formula (0) Production rate 3 70%: 30% Nitrocresol However, this conventional method using P-cresol as a starting material has the same drawbacks as the conventional method using P-chlorotoluene as a starting material. That is, the nitration reaction of P-cresol can achieve the desired goal. Since it is not possible to selectively produce the 2-nitro P-cresol required to produce the desired 3-amino-4-alkoxytoluene, the desired 3-amino-4-alkoxytoluene cannot be produced selectively.
-Alkoxytoluene cannot be produced in high yield, and after the nitration reaction, 2nito-o-
Unless P-cresol and 3-nitro-P-cresol are separated and purified, the desired 3-amino-4-alkoxytoluene cannot be produced with high purity through the alkylation and reduction steps in the next step. Furthermore, similar to the conventional method using P-chlorotoluene as a starting material, this conventional method using P-cresol as a starting material also requires a separation and purification step after the nitration reaction. There is also the drawback that the desired 3-amino-4-alkoxytoluene cannot be efficiently produced by continuous reaction. As mentioned above, in any of the secondary methods, it is not easy to selectively produce the target 3-amino-4-alkoxytoluene with high purity and high yield, and it is difficult to produce it efficiently by continuous reaction. I couldn't. The present inventors have conducted various studies to efficiently produce 3-amino-4-alkoxytoluene in high yield. As a result, they adopted a 4-halogenopenzylamine compound as a starting material and nitrated it to produce 3-amino-4-alkoxytoluene. Nitro-4-halogen/
If a penzylamine compound is selectively obtained in high yield and then the 3-nitro-4-alkoxybenzylamine compound obtained by dehalogenation-alkoxylation is reduced, it will have an adverse effect on the alkoxy group bonded to the 4-position. In one step, the nitro group bonded to the 3-position is reduced to an amino group, and the C- of the -C star-NnoRI\R2 group is
The present invention was completed by discovering that N-bonds can be cleaved and reduced. That is, the present invention is based on the general formula (in which R represents a hydrogen atom, an alkyl group, or a phenyl group, and R2 represents a hydrogen atom or an alkyl group,
X represents a halogen atom. 4-halogenobenzylamine compound represented by ) is nitrated, then dehalogenated-alkoxylated, and further reduced. This is a method for producing amino-4-alkoxytoluene. As shown in the reaction process formula below, the production method of the present invention is as follows:
A 3-nitro-4-halogenobenzylamine compound produced by nitrating the 4-halogenobenzylamine compound represented by and then selectively nitrating the 3-position by a nitration reaction

[0] is dehalogenated and alkoxylated, and the 3- produced by the dehalogenated and alkoxylated
Nitro-4-alkoxybenzylamine compound

[0] is reduced, amination of the nito-O group bonded to the 3-position and -C
This is a method for producing the desired 3-amino-4-alkoxytoluene [W] in three steps by cutting and reducing the C--N bond of H2 in one step. ■Nitration ■Dehalogen-alkoxylation (R, , R2, R3 and x in the formula represent the same atoms or groups as above) As the starting materials of the present invention, R of the general formula [1],
is a hydrogen atom, methyl group, ethyl group, n-propyl group, i
-propyl group, n-butyl group, i-butyl group, n-amyl group, hexyl group, heptyl group, octyl group, nonyl group, decyl group, phenyl group or substituted phenyl group, and R2 is a hydrogen atom, methyl group, ethyl group, etc. group, n-propyl group, n-amyl group, hexyl group, heptyl group, octyl group, menyl group, or decyl group, etc., and X is a chlorine atom, a bromine atom, or a fluorine atom. As starting materials, 4
-chloro- or 4-prom-penzylamine, 1N-methylbenzylamine, 1N-ethylbenzylamine,
1N-n-propylbenzylamine, 1N-propylbenzylamine, 1N-n-butylbenzylamine,
1N-n-amylbenzylamine, 1N-hexylbenzylamine, 1N-n-heptylbenzylamine,
1N-n-octylbenzylamine, 1N-n-nonylbenzylamine, 1N-n-decylbenzylamine, 1N-phenylbenzylamine, 1N,N-dimethylbenzylamine, 1N,N-diethyl Benzylamine, 1N
．． N-di-n-propylbenzylamine, 1N,N-di-i-propylbenzylamine, 1N,N-dibutylbenzylamine, 1N,N-diamylbenzylamine, 1N-methyl-N-phenylbenzylamine , -N-ethyl-N-phenylbenzylamine, and the like. The nitration reaction of the present invention is carried out by a conventional nitration method using a mixed acid of nitric acid and sulfuric acid or concentrated nitric acid as a nitration agent. 1 to 1.5 mol, preferably 1.
Hawkic acid consisting of 1 to 1.3 moles of fuming nitric acid and 2.5 to 5 moles, preferably 3 to 4 moles of concentrated sulfuric acid, was heated at 000 to 50°C.
Preferably, the reaction is carried out under the ocean for 2 to 5 hours at a temperature range of 100 to 40 oC, or 1 to 4 mol, preferably 2 to 3 mol of concentrated sulfuric acid is added per 1 mol of the 4-halogenobenzylamine compound at 0°C. ~4000 preferably 15℃
After mixing at ~30:00 to form a sulfate of the 4-halogenobenzylamine compound, 1 to 1.5 mol, preferably 1.1 to 1.5 mol, per 1 mol of the 4-halogenobenzylamine compound used. 3 moles of fuming nitric acid and 0.5 to 5 moles, preferably 1 to 3 moles of concentrated sulfuric acid (however, the total amount of concentrated sulfuric acid is 4
- 1.5 to 1 mole of halogenobenzylamine compound
9 mol (preferably 3 to 6 mol) of deer acid consisting of 000
1 in the temperature range of ~5 pi0 preferably looo~40qo
React under light for ~4 hours. After the nitration reaction, ammonia, potassium hydroxide,
By neutralizing with an alkali such as sodium hydroxide or sodium carbonate and washing with water, a 3-nitro-4-halogenobenzylamine compound with a purity of 98% or more can be obtained in high yield. In the post-treatment after the completion of the reaction, there is no problem even if an inert solvent such as benzene, xylene, toluene, etc. is added to extract the target product, followed by neutralization and washing with water. In the present invention, 2
Since by-products such as 2-nitro-4-halogenobenzylamine compounds that are nitrated at positions are hardly produced, the 3-nitro-4-halogenobenzylamine compounds obtained by the nitration reaction can be used in the following steps without isolating and purifying them. A dehalogen-alkoxylation reaction can also be carried out subsequently. Although the nitration reaction of the present invention can be carried out by any of the above-mentioned methods, the purity and yield can be improved by employing methods 1 to 2. Next, in the dehalogen-alkoxylation reaction of the present invention, the 3-nitro-4-halogenobenzylamine compound obtained by the nitration reaction is treated under normal pressure or under pressure in the presence of an alkali metal hydroxide. Formula R3-OH
[V] (In the formula, R3 represents the same group as above.) or -
(2) The reaction is carried out by reacting with a metal alcoholate represented by the general formula R30-M [W] (M in the formula represents an alkali metal atom and R3 represents the same group as above) in an alcoholic solvent. When dehalogen-alkoxylation is carried out by the above-mentioned method 1 - 1, sodium hydroxide, potassium hydroxide, etc. can be used as the alkali metal hydroxide, and this alkali metal hydroxide is 3-nitro-4-halogenobenzyl. The amount used is 1.05 to 1.40 mol, preferably 1.2 to 1.3 mol, per mol of the amine compound. Examples of the alcohol represented by the general formula [V] include methyl alcohol, ethyl alcohol, n-propyl alcohol, lso-propyl alcohol, n-butyl alcohol, lso-butyl alcohol, and amyl alcohol. [V] also serves as a reaction solvent, and is preferably 7 to 15 moles per mole of the 3-nitro-4-halogenobenzylamine compound, preferably 10 to 15 moles.
Use 13 moles. On the other hand, dehydration was carried out by the above method (■-■). When carrying out gene-alkoxylation, lower alcohols such as methyl alcohol, ethyl alcohol, and propyl alcohol are used as the reaction solvent, and the metal alcoholates represented by the general formula [W] include sodium, potassium,
Alkali metal alcoholates such as calcium are used,
Specific examples include sodium methylate, potassium methylate, sodium ethylate, potassium ethylate, sodium proparate, etc., and this metal alcoholate [W] is equivalent to 1 mole of the 3-nitro-4-halogenobenzylamine compound. , 1.0 to 1.30 mol, preferably 1.05 to 1.1 mol. In any of the above methods ■-■ and ■-■, when the reaction is carried out under normal pressure, the alcohol of 30 to 15,000 is preferably used in the reaction as represented by the general formula [V] or the alcohol used as the reaction solvent. When the reaction is carried out at a reducing temperature and under pressure, the reaction time is 90 to 150 oo, preferably 100 oo to 120 q, in a pressure-resistant container such as an autoclave.
In addition, in both the above methods ■-■ and ■-■, the reaction is carried out in an oxygen atmosphere or with an oxidizing agent such as oxidized steel, manganese dioxide, lead oxide, zinc oxide, calcium oxide, etc. The yield can be improved by carrying out the reaction in the presence of 3-nitro-4-halogenobenzylamine compound, and when the reaction is carried out in an oxygen atmosphere, oxygen is preferably 0.01 to 0.03 mol per mol of the 3-nitro-4-halogenobenzylamine compound. is 0.
015 to 0.025 mol is used, and when an oxidizing agent is used, 2.0 to 5.0 mol is used per 3-nitro-4-halogenobenzylamine compound. The weight percent of preferably 3.0 to 4.
% by weight of oxidizing agent is used. After the dehalogen-alkoxylation reaction is completed, 3-nitro-3 with a purity of 98% or higher is neutralized with mineral acids such as sulfuric acid and hydrochloric acid, and washed with filtered water.
The 4-alkoxybenzylamine compound can be obtained in high yield, and the reduction reaction, which is the next and final step, can be carried out without isolating and purifying the obtained 3-nitro-4-alkoxyberzylamine compound. . In the post-treatment after the completion of the reaction, there is no problem even if an inert solvent such as benzene, xylene, toluene, etc. is added to extract the target product, followed by neutralization and washing with water. Next, for the reduction reaction which is the final step of the present invention, a catalytic reduction reaction using hydrogen can be applied in a pressure-resistant vessel such as an autoclave in the presence of a reduction catalyst.
Catalysts such as palladium can be used. Although the catalyst can be used as a metal, it is usually supported on the surface of a carrier such as carbon black or activated carbon, and the amount used is 0.1% of the metal per 3nitro-4-alkoxybenzylamine compound. ~0.4% by weight
Preferably 0.2-0. Use box weight%. Hydrogen is 70
~110k9/ground, preferably 90~110k9/evenly filled, 100~150oo preferably <120~130ko○
Perform the Hajikushita reaction. The reduction reaction of the present invention proceeds only under hydrogen pressure, but a key acid such as hydrochloric acid, sulfuric acid, or nitric acid is added per mole of the 3-nitro-4-alkoxybenzylamine compound,
．． The reduction reaction can be promoted by co-presence of 5 to 1.2 moles, preferably 0.7 to 1.0 moles. Although the reaction can be carried out either in the presence or absence of an inert solvent, it is preferable to carry out the reaction in a solvent that is inert to the reaction in order to ensure that the reaction proceeds smoothly. For example, alcohols such as methanol, ethanol, propanol, and phthanol are preferably used, and the amount used is 3 to 6 times, preferably 4 to 5 times by weight, based on the 3-nitro-4-alkoxybenzylamine compound.
Use twice the weight. After the reduction reaction is completed, 3-amino-4-alkoxytoluene with a purity of 99% or more is converted to 3-amino-4-alkoxytoluene with a purity of 93% or more based on the 3-nitro-4-alkoxybenzylamine compound (4-halogenobenzylamine compound as the starting material) by processing in a conventional manner. It can be produced with a yield of 84 to 86%), and at the same time is useful as a raw material for various industrial products. ) can be efficiently co-produced and recovered. For example, after the completion of the reduction reaction, the used catalyst is separated by a three-passage method or the like, and when chlorine acid is added in the reduction reaction, the amine can be obtained by a distillation separation method after neutralization. Next, to explain the features and advantages of the method of the present invention, firstly, by employing a 4-halogenobenzylamine compound as a starting material, by nitrating it, selective 4-halogenobenzylamine can be obtained. Compound 3
A highly purified 3-nitro-4-halogenobenzylamine compound is obtained in high yield by nitration at the position, and 3-nitro-4-halogenobenzylamine compound is further obtained in high yield by dehalogen-alkoxylation reaction of the 3-nitro-4-halogenobenzylamine compound. If a nitro 4-alkoxybenzylamine compound is reduced, 4
The nitro group bonded to the 3-position is reduced to an amino group in one step without adversely affecting the alkoxy group bonded to the 3-position, and the C1N bond of the Z group is cleaved and reduced. As a result, 4- 3-Amino-4-alkoxytoluene can be selectively produced from a halogenobenzylamine compound without going through long reaction steps, with high purity and high yield. Second, according to the present invention, the nitration of the 4-halogenobenzylamine compound, followed by dehalogenation-alkoxylation, and further reduction reaction can be carried out continuously without isolating each intermediate product. , 3-amino-4-alkoxytoluene can be efficiently produced from a 4-halogenobenzylamine compound. Thirdly, the 4-halogenobenzylamiso compound used as the starting material of the present invention can be easily obtained by reacting 4-halogenobenzyl halide with an amine, and furthermore, according to the present invention, the desired 3-amino/-4 -Amine can be efficiently recovered from rice cake production together with alkoxytoluene, so this amine can be reused. Next, in order to further clarify the content of the present invention, examples will be shown and specifically explained. Example
1 [Nitration/■] Charge 75.6 moles (1.2 moles) of fuming nitric acid and 370 moles (3.7 moles) of 98% concentrated sulfuric acid into a 500-liter flask, and add while cooling to below 20°C. Azusa Azusa, 4-Kroll-N
, N-diethylbenzylamine (197.6 (1.0 mol)) was added dropwise. After the dropping was completed, the reaction was continued for 3 hours at 300° to 35°. After the reaction was completed, the reaction solution was neutralized with a 24% aqueous sodium monohydroxide solution, and the upper organic layer was collected and washed with water. After washing with water, the obtained organic layer was analyzed by gas chromatography to determine the purity of 3nitro-4-chloro-N,N-jethylbenzylamine. As a result of the analysis, 8.23% of unreacted 4-chloro-N,N-jethylbenzylamine, 0.23% of unknown substances,
3-nitro-4-chloro-N,N- of the desired intermediate
Diethylbenzylamine was 90.65%. Next, the organic layer was distilled under reduced pressure, and one batch of 3-nitro-4-chloro-N,N-jethylbenzylamine (purity 98.5%) with a boiling point of 138 to 14000/5 was added. 9/(yield 80.36%) was obtained. [Nitration/■] 98.0 to 500 private flask. %-concentrated sulfuric acid 300 min (3.
4-chloro-N,N-diethylbenzylamine 197.6 mol), 25 pm C to 30 ℃ under rope Azusa, 4-chloro-N,N-diethylbenzylamine 197.6 pm
．． After adding dropwise 75.8 mol of fuming nitric acid (1.2 mol) and 9 ml of fuming nitric acid while cooling to below 20 ml,
A mixed acid consisting of 8% concentrated sulfuric acid and 1 mole of concentrated sulfuric acid was added dropwise. After completion of the dropping, the solution was allowed to react at 30 qo to 35 qo for 3 hours. After the reaction was completed, the same treatment as above [Nitration-■] was performed to obtain 3-nitro-4-chloro-N,N-jethylbenzylamine (purity 98.6%) for 238.2 hours (yield 96.2%).
8%). [Dechloromethoxylation-■] 3 nitro-4-chloro-N in a 500 kite customer flask,
121.3 moles (0.5 moles) of N-diethylbenzylamine, 160 moles (5.0 moles) of methyl alcohol, and 3.97 moles (0.05 moles) of copper oxide were charged, and the mixture was heated under normal pressure for 5 mols.
35% potassium hydroxide aqueous solution 99.2 at 5℃~60qo
A mixed solution of 0.62 mol of alcohol and 48 mol of methyl alcohol was added dropwise. After completion of the dropping, the mixture was further heated at 55° C. to 60 qo for 7 hours to react. After the reaction was completed, the reaction solution was neutralized by adding sulfuric acid, dried, and concentrated under reduced pressure to remove methanol. Next, 110 parts of toluene was added to the obtained concentrate, and the mixture was thoroughly stirred. Furthermore, 100 parts of water was added and the mixture was stirred, and the toluene solution layer was separated and collected. Next, the toluene solution was concentrated under reduced pressure to remove the toluene, and then rectified under reduced pressure to obtain 3-nitro-4-methoxy N,N-diethylbenzylamine (purity 98.2%) with a boiling point of 144-146°C/4 days. 103.3 hours (yield: 85%) was obtained. [Dechloromethoxylation - ■] In an autoclave with an internal volume of 500, 121.3 mols of 3-nitro-4-chloro-N,N-diethylbenzylamine (0.5 mol) and 34.8 mols of potassium hydroxide ( 0.62
mol) and methyl alcohol 208 mol (6.5 mol)
was prepared and stirred at 100 to 120 qo for 5 hours to react. The pressure inside the autoclave during the reaction was 3.0 to 4.0 kg/
It was. After the reaction was completed, the reaction solution in the autoclave was taken out and treated in the same manner as above [Dechloromethoxylation-■] to obtain 3-nitro-4-methoxy-N,N-jethylbenzylamine (purity 98.3%). 109.2 evening (
Yield: 90.1%). [Dechloromethoxylation-■] 3-nitro-4- in an autoclave with an internal volume of 500
121.3 moles (0.5 mol) of chloro-N,N-diethylbenzylamine, 4.8 moles (0.62 mol) of potassium hydroxide, and 208 moles (6.5 mol) of methyl alcohol were charged, and 1 mol of oxygen gas was added. .0k9/enemy filling 100~
The mixture was allowed to react at 120 oo for 5 hours. The pressure inside the autoclave during the reaction was 3.5 to 4.5k9/
It was a pleasure. After the reaction, the reaction solution in the autoclave was taken out and treated in the same manner as above [Dechloromethoxylation-■] to obtain 3-nitro-4-methoxy N,N-jethylbenzylamine (purity 98.8% ) to 114.2 evening (
Yield: 94.9%). [Dechloromethoxylation - ■] In an autoclave with an internal volume of 500, 121.3 mols of 3-nitro-4-chloro-N,N-diethylbenzylamine (0.5 mol) and 34.8 mols of potassium hydroxide were added. (0.62
208 moles), methyl alcohol 208 moles (6.5 moles) and oxidized steel 3.97 moles (0.05 moles) were charged, and then 1.0 kg/oxygen gas was charged and heated at 100 to 120 o'clock for 5 hours. and reacted. The pressure inside the autoclave during the reaction was 3.5 to 4.5k9/
It was a pleasure. After the reaction, the reaction solution in the autoclave was taken out and treated in the same manner as above [Dechloromethoxylation-■] to obtain 3nitro-4-methoxy N,N-jethylbenzylamine (purity pseudo.6%). was obtained in 114.5 days (yield 94.6%). [Dechloromethoxylation-■] 3-nitro-4-chloro-N,
Prepare 121.3 moles (0.5 mol) of N-diethylbenzylamine and 136 moles of methyl alcohol, and add 50 q of N-diethylbenzylamine under normal pressure.
100.3 molar (0.52 mol) of a 28% methyl alcohol solution of methyl alcoholate was added dropwise at 0 to 60 CO. After the addition of the bottle, the mixture was stirred for 7 hours at 5000 to 6000 to react. After the reaction was completed, the same treatment as above [Dechloromethoxylation - 88.0%). 0 [Dechloromethoxylation - ■] 3-nitro-4- in an autoclave with an internal volume of 500
121.3 parts (0.5 mol) of chloro-N,N-diethylbenzylamine, 136 parts of methyl alcohol, and 5 parts of a 28% solution of methyl alcoholate in methyl alcohol.
0.3 mol (0.52 mol) was charged, and 1.0 k9 mol of oxygen gas was charged, and the reaction was carried out at 100° C. to 120° C. for 5 hours. The pressure inside the autoclave during the reaction was 4.5k9/m. After the reaction was completed, the reaction solution in the autoclave was taken out and treated in the same manner as above [Dechlorination-methoxylation-■] to obtain 3-nitro-4-methoxy N,N-diethylbenzylamine (purity: .6%). 114.9 evenings (yield 95
．． 1%) obtained. [Reduction reaction-■] In an autoclave with an internal volume of 500, 71.58 mols of 3-nitro-4-methoxy N,N-diethylbenzylamine (0.3 mol) were added.
322 parts of methyl alcohol and 1 part of 10% Pd-C
．． After charging 95k9 (0.0016 mol as Pd) and purging the inside of the autoclave with nitrogen, hydrogen gas was added at 95k9/
The mixture was filled with lumps and reacted at 120:00 to 130:00 for 5:00. After the reaction was completed, the reaction solution in the autoclave was taken out and filtered to separate and remove the catalyst, and concentrated under reduced pressure to remove ethyl alcohol and diethylamine. Next, 40 g of benzene was added to the obtained concentrate, and it was thoroughly simmered, and then 1 g of water was added.
After adding 0.00 g of [200 g] and stirring, the benzene solution and the aqueous layer were separated. The collected benzene solution was concentrated under reduced pressure to remove benzene, and then further distilled under reduced pressure to achieve a boiling point of 100 to
1020/1 product 3-amino-4-methoxytoluene (purity 99.2%) was prepared at 38.6% (yield 93.20%).
%)Obtained. [Reduction reaction-■] In an autoclave with an internal volume of 500 ml, 71.58 nitro-4-methoxy N,N-diethylbenzylamine (0.3 mol), 322 ml of ethyl alcohol, and 352 ml of ethyl alcohol were added.
% hydrochloric acid (0.3 mol), and 10% Pd-
After charging 1.8 moles of C (0.0016 mol as Pd) and replacing the inside of the autoclave with nitrogen, 70 moles of hydrogen gas was charged.
The reactor was loaded at 120 oz to 130 qo for 5 hours to react. After the reaction is complete, remove the reaction solution from the autoclave and
After neutralizing by adding 40% aqueous sodium hydroxide solution (0.3 mol), the same treatment as above [Reduction reaction-■] was performed to obtain 3-amino-4-methoxytoluene (purity 99.3%)
) is spotted. It was obtained in 5 days (yield 93.0%). Example 2 ■ 98%-concentrated sulfuric acid (300 ml) was added to a 500' customer flask.
After adding 197.6 mol of 4-chloro-N,N-diethylbenzylamine (1.0 mol) dropwise at 2 to 30 q○, the flies were further cooled to below 20 q0. Azusa, fuming nitric acid 75.8 m (1.2 mol)
A mixed acid consisting of 1 mole of 98% concentrated sulfuric acid and 1 mole of concentrated sulfuric acid was added dropwise. After completion of the addition, reaction was allowed to occur for 3 hours at 30 qo to 35 qo. After the reaction was completed, the reaction solution was neutralized with a 24% aqueous sodium hydroxide solution, and the upper organic layer was collected and washed with water. ■ The total amount of the organic layer obtained by the nitration reaction in (■) above, 70.13 moles (1.25 moles) of potassium hydroxide, and 416 moles (13 moles) of methyl alcohol were mixed into an inner volume of 100
0' autoclave, and add oxygen gas to 1
．． The mixture was charged at an even rate of 0k9 and reacted at 100 to 120 qo for 5 hours. After the reaction was completed, the reaction solution in the autoclave was taken out, sulfuric acid was added thereto to neutralize it, and the reaction solution was filtered through an oven to obtain a reaction solution. ■ The total amount of the reaction solution obtained by dehalogenation-methoxylation in (■), 35% hydrochloric acid (1.0 mol) and 10% Pd-C was added to 5.9 mol (o.oo56 mol as Pd).
mol) into an autoclave with an internal volume of 500,
After replacing the inside of the autoclave with nitrogen, replace hydrogen gas with 95k
It was charged at 120° C. to 13,000° C. for an hour to react. After the reaction is complete, remove the reaction solution from the autoclave and
After neutralizing by adding a 40% aqueous sodium hydroxide solution, the resulting reaction solution was concentrated under reduced pressure to remove methyl alcohol and diethylamine. Next, the obtained concentrate was dissolved in benzene 137 and washed with water, and the obtained benzene solution was concentrated under reduced pressure to remove the benzene, and then further reduced under reduced pressure to obtain a solution with a boiling point of 100 to 10.
3-amino-4-methoxytoluene (purity 99.1%) from 1 day ago was prepared at 128.5 days (theoretical yield based on the starting material 4-chloro-N,N-jethylbenzylamiso). 85%). Example 3 Using the same machine as Example 2, various 4-chlorobenzylamine compounds were used as starting materials to obtain 3-amino-4-methoxytoluene. The results are shown in Table 1. The yields in Table 1 are all based on the theoretical yield of 3-amino-4-methoxytoluene [W] based on the starting material 4-chlorobenzylamine compound. Table-1 Example 4 Various 4-c. Using G/penzylamine compound [1] as a starting material, it was 1) nitrated in the same manner as in Example 2, then reacted with alcohol [V] in the presence of potassium hydroxide, 1) dehalogenated and alkoxylated, and 3) subjected to a reduction reaction. The corresponding 3-amino-4-alkoxytoluene [W] was obtained.

Claims (1)

[Claims] 1. General formula ▲ Numerical formula, chemical formula, table, etc. ▼ (In the formula, R_1 represents a hydrogen atom, an alkyl group, or a phenyl group, R_2 represents a hydrogen atom or an alkyl group, and ▲There are mathematical formulas, chemical formulas, tables, etc.▼ (R_3 in the formula represents a lower alkyl group.) A method for producing 3-amino-4-alkoxytoluene.