JPH0655697B2 - Method for producing aminobenzylamine - Google Patents

Description

TECHNICAL FIELD The present invention relates to a novel method for producing aminobenzylamine, and in particular, provides an extremely advantageous method for industrial implementation. .

More specifically, the general formula (I) (In the formula, the nitro group is at the o-position, m-position or p-position) The present invention relates to a method for producing aminobenzylamine, which comprises catalytically reducing nitrobenzylamine in the presence of an acid.

Aminobenzylamine is an important substance as a raw material for epoxy resin curing agents, polyamides, polyimides and agricultural and pharmaceutical intermediates.

(Prior Art) Aminobenzylamine is conventionally known to be typically produced by using nitrobenzaldehyde or nitrobenzonitrile as a starting material. For example, as a method of using the former as a starting material, there are the following methods.

(B) Nitrobenzyl bromide is derived from nitrobenzaldehyde and then reacted with phthalimido potassium to give N-
(Nitrobenzyl) -phthalimide is obtained, which is reduced and hydrolyzed to give m- and p-aminobenzylamine in about 20% yield (N. Kornblum et al., J. Am. Che.
m.Soc., 71 , 2137 (1949)).

(B) m-Nitrobenzaldehyde is reacted with phenylhydrazine to obtain a hydrazone compound, which is catalytically reduced to obtain m-aminobenzylamine in a yield of 60% (A. Siddiqui et al., Synth. Commn. , 7 , 71-78 (1977)).

(C) m-Nitrobenzaldoxime was obtained from m-nitrobenzaldehyde and subjected to high pressure catalytic reduction using Raney nickel catalyst to obtain m-aminobenzylamine in 52% yield (JR Griffith et al., NRL Report, 6439).

On the other hand, as a method using the latter as a starting material, there is the following method.

(D) p-Aminobenzonitrile derived from p-nitrobenzonitrile is reduced with lithium aluminum hydride to obtain p-aminobenzylamine in 37% yield (NC Brown et al., J. of Medicinal Chem. ., 20 , 11
89 (1977)).

(E) m-nitrobenzonitrile was subjected to high-pressure catalytic reduction using Raney nickel catalyst to give m-aminobenzylamine 4
9% yield (JR Griffith et al. NRL Report, 643
9).

As another method, there is a method in which nitrobenzylamine is used as a starting material and is reduced to produce it. For example, (f) m-nitrobenzylamine is reduced with tin and hydrochloric acid to obtain m-aminobenzylamine (S. Gabriel
Ber., 20 , 2869-2870 (1887)).

(To) o-nitrobenzylamine was reduced with red phosphorus and a large amount of hydriodic acid to obtain o-aminobenzylamine (S. Gabriel et al., Ber., 37 , 3643-3645 (190).
Four)).

(Problems to be Solved by the Invention) As described above, in the production of aminobenzylamine by a known method, the method using nitrobenzaldehyde or nitrobenzonitrile as a starting material is the same as in (a) and (b). And relatively expensive compounds such as phenylhydrazine are used in an equivalent amount or more to produce an intermediate, and this is reduced to obtain the desired product. However, these methods require a long reaction step or produce by-products. It is not economical because it requires cost and labor for collection.

The method (d) also has the drawback that the reducing agent is expensive and difficult to handle.

It is obvious that the method of high pressure catalytic reduction in an autoclave using a Nine nickel catalyst as in (c) and (e) is disadvantageous because the apparatus is expensive and the volumetric efficiency is low.

On the other hand, a known method using nitrobenzylamine as a starting material is a reduction using a large amount of tin and hydrochloric acid as shown in (f) to isolate as a tin salt, which is then metathesized to liberate the desired product. However, in this method, it is necessary to take care that the separation operation from the metal compound used for reduction is complicated and that a trace amount of metal does not remain. In addition, there is a problem in that a large amount of heavy metal and waste acid are required to be made pollution-free, or costly and labor is required for recovery or the like.

As a method to improve the difficulties related to these metals (G)
The target compound is obtained by reducing with red phosphorus and hydroiodic acid as shown in the above, but it is not realistic because a large amount of expensive hydroiodic acid is used and red phosphorus, which has a high risk of ignition etc., is used. .

As described above, the known method for producing aminobenzylamine has drawbacks such as long process steps, complicated post-treatment, and problems with equipment, and thus is suitable for industrial production methods. Absent.

(Means for Solving the Problem) The present inventors diligently studied a method for producing aminobenzylamine that does not have the above-mentioned drawbacks. As a result, nitrobenzylamine was used as a raw material, which was added in the presence of an acid,
We have found that aminobenzylamine can be produced in high yield by catalytic reduction using a reduction catalyst, and completed the method of the present invention.

That is, the method of the present invention has the general formula (I) (In the formula, the nitro group is in the o-position, m-position or p-position), an amino acid characterized by hydrogenation reduction using a reduction catalyst in the presence of an acid. It is a method for producing benzylamine.

The raw material used in the method of the present invention is o-nitrobenzylamine, m-nitrobenzylamine or p-nitrobenzylamine. These nitrobenzylamines are produced in high yield by the method of reacting the corresponding nitrobenzyl chloride with ammonia or phthalimide (R / Gabriel et al., Ber., 2869 (1887), ELHolm.
es et al., J. Chem. soc., 1800-1821 (1925), HLing et al., J. Ch.
em.Soc., 2348-2351 (1926)).

The acid used in the method of the present invention is a mineral acid, an organic acid or carbonic acid.

The mineral acid is hydrochloric acid, sulfuric acid, nitric acid, boric acid, phosphoric acid, boric anhydride or phosphoric anhydride.

By using these mineral acids, the reaction can proceed selectively to obtain the desired product.

This mineral acid is relatively inexpensive, and since accelerated cost in the reduction reaction is also recognized, it is possible to efficiently and economically produce the desired product.

Furthermore, when the anhydride of mineral acid is used, the water contained in the reaction system and the water produced by the reduction of the nitro group are trapped,
The reduction reaction can be performed in an ideal state of anhydrous system.

That is, unnecessary action such as decomposition by water or side reaction is suppressed, and a reduction reaction with extremely good selectivity can be performed.

As the organic acid, formic acid, acetic acid, propionic acid, oxalic acid, malonic acid, succinic acid, maleic acid and other aliphatic mono- or di-carlevonic acids, benzoic acid, phthalic acid and other aromatic carboxylic acids, p-toluene sulfone Examples thereof include acids, sulfonic acids such as benzenesulfinic acid, and sulfinic acids, and a part of carboxylic acids is also used as an anhydride. Of these organic acids, acetic acid is industrially preferably used. Moreover, a part of the organic acids can also be used as a solvent.

In the reaction using this organic acid, the organic acid is well mixed with the raw material and other solvent, and therefore the reaction proceeds rapidly under mild conditions. Further, since the post-treatment after the reaction is a uniform solution, the catalyst and the solvent can be easily recovered. In addition, this method has a great advantage that the activity of the recovered catalyst is hardly reduced, and thus it can be repeatedly used and is economically advantageous.
Furthermore, depending on the case, it is also possible to recover the organic acid from the liberated organic acid salt of aminobenzylamine by a means such as distillation.
More favorable results are obtained.

Further, by using carbon dioxide as carbonic acid, satisfactory results can be obtained.

That is, carbon dioxide gas becomes carbonic acid by the water in the reaction system or the water produced by the reduction of the nitro group.

This carbon dioxide gas may be used in any form of gas, liquid and solid.

This reaction using carbon dioxide has a great feature that post-treatment after the reaction can be performed relatively easily.

That is, after completion of the reaction, excess carbon dioxide gas is released, the catalyst is removed, and then a base is added as it is for distillation, whereby the solvent can be recovered at a high recovery rate and the target aminobenzylamine can be highly recovered. It can be obtained in yield. Also,
This method has the advantage that the activity of the recovered catalyst does not decrease, so it can be used repeatedly and is economically advantageous.

The amount of the mineral acid, organic acid, carbon dioxide gas or the like to be used is 0.5 equivalent or more, preferably 1 to 3 equivalents, relative to the raw material nitrobenzylamine.

These acids may be used alone or in combination of two or more kinds.

As the solvent used in the method of the present invention, water, methanol, ethanol, isopropyl alcohol, n-butyl alcohol, esc-butyl alcohol, methyl cellosolve, ethyl cellosolve, ethylene glycol, propylene glycol, diglyme, tetraglyme, dioxane, tetrahydrofuran. Alcohols such as alcohol, glacols, ethers are preferably used, and in some cases, hexane, cyclohexane, benzene, toluene, ethyl acetate, butyl acetate, dichloromethane, chloroform, 1,
Aliphatic hydrocarbons such as 1,2-trichloroethane, aromatic hydrocarbons, esters and halogenated hydrocarbons can also be used.

These solvents may be used alone or in combination of two or more. The amount of the solvent used is not particularly limited, but usually 1 to 15 times the weight of the raw material is sufficient.

In the method of the present invention, in the hydrogenation reduction, a commonly used reduction catalyst such as nickel, palladium, platinum, rhodium, ruthenium, cobalt or copper can be used as the reduction catalyst.

These catalysts can be used even in a metal state, but usually they are used by adhering them to the surface of a carrier such as carbon, barium sulfate, silica gel and alumina, and nickel, cobalt and copper are also used as Raney catalysts. Used.

It is industrially preferable to use a palladium catalyst.

The amount of the catalyst used is in the range of 0.01 to 30% by weight as a metal with respect to nitrobenzylamine as a raw material, usually 2 to 20% by weight when used as a Raney catalyst, and 0.05 to 5% when attached to a carrier. It is in the range of% by weight.

The reaction temperature is not particularly limited and is generally in the range of 0 to 150 ° C, preferably 10 to 80 ° C.

The reaction pressure is usually from atmospheric pressure to 50 kg / cm ² · G.

As a general embodiment of the method of the present invention, when a mineral acid or an organic acid is used, reduction is carried out by adding a catalyst in a state in which a raw material and an acid are dissolved or suspended in a solvent.

When carbon dioxide gas is used, the catalyst is added while the raw materials are dissolved or suspended in a solvent, and then a predetermined amount of carbon dioxide gas is added in advance, or reduction is carried out while appropriately introducing it.

In any case, the process is performed at a predetermined temperature until the absorption of hydrogen stops. After the completion of the reaction, in the case of being in a dissolved state, the catalyst can be removed by passing over, neutralized with caustic soda, caustic potash, ammonia, triethylamine, etc., and then distilled to obtain the desired product. When it is in a precipitated state, the acid salt can be isolated and purified by passing it through, followed by neutralization to obtain the desired product.

(Operation and Effect) In the method of the present invention, nitrobenzylamine is reduced in a solvent in the presence of a mineral acid, an organic acid or carbonic acid. Therefore, the intermediate product exists in a stable form as the acid salt of aminobenzylamine.

That is, by stabilizing the aminomethyl group of nitrobenzylamine as a mineral acid salt, organic acid salt or carbonate during reduction, decomposition and side reactions are suppressed, and as a result, reduction of the nitro group to an amino group is achieved. Progresses promptly,
The desired product, aminobenzylamine, can be selectively produced.

After the reaction is completed, aminobenzylamine can be easily isolated by separating and purifying it as a mineral acid salt, an organic acid salt or a carbonate salt, or by distilling and purifying it by a simple neutralization treatment, which is extremely industrially advantageous. Is.

(Example) Hereinafter, the method of the present invention will be specifically described with reference to Examples.

Example 1 13.6 g of m-nitrobenzylamine (0.
1 mol), 90% isopropanol aqueous solution 200 ml, 35%
21 g (0.2 mol) of hydrochloric acid and 0.4 g of 5% pb-C catalyst were charged, and hydrogen was introduced with vigorous stirring.

When the reaction temperature was kept at 25 to 35 ° C for 3 hours, 6.68 hydrogen was absorbed. Since no further absorption was observed, the process was terminated.

Next, the reaction solution was heated to 70 ° C. and then passed through to remove the catalyst.

When the liquid was allowed to cool, white needle-like crystals of m-aminobenzylamine hydrochloride were precipitated. This was separated, washed with isopropanol and dried to obtain 15.8 g (yield 81%).
The melting point was 274 to 277 ° C, and the results of elemental analysis were as follows.

Example 2 13.6 g of m-nitrobenzylamine in a glass closed container.
(0.1 mol), 100 ml of water, 20 g (0.2 mol) of phosphoric acid and 0.4 g of 5% Pd-C catalyst were charged, and hydrogen was introduced to carry out the reaction as in Example 1. After the completion of the reaction, the Pd-C catalyst was filtered off, the solution was concentrated to about 1/3 and allowed to cool, whereby white needle-like crystals of m-aminobenzylamine phosphate were precipitated. This was separated, washed with methanol and dried to obtain 20.4 g (yield 77.3%). Melting point 209
The results of elemental analysis were as follows at ~ 213 ° C.

Example 3 Reaction was carried out in the same manner as in Example 1 except that 50 ml of methanol, 3.5 g (0.05 mol) of boric anhydride and 0.27 g of 5% Pd-C were used per 13.6 g (0.1 mol) of m-nitrobenzylamine. Natsuta.

After completion of the reaction, the reaction solution was filtered to remove the catalyst, and then concentrated under reduced pressure to distill off methanol, whereby a yellow viscous liquid was obtained.

When this yellow viscous liquid was neutralized with a 35% aqueous sodium hydroxide solution, a brown oily crude m-aminobenzylamine was liberated in the upper layer.

This brown oil was vacuum distilled at a pressure of 6 mmHg and the distillation temperature was
11.6 g of a fraction of 131 to 132 ° C was obtained (yield 94.9%).

This was crystallized when left to stand overnight. Melting point 40
The results of elemental analysis at ~ 41 ° C are as follows.

Example 4 13.6 g (0.1 mol) of p-nitrobenzylamine, 50 ml of methanol, 14.2 g (0.1 mol) of phosphorus oxide and 5% P
The reaction and post-treatment were carried out in the same manner as in Example 3 except that 0.27 g of d-C catalyst was used.

Vacuum distillation yielded 11.4 g of a distillate fraction of 129.5 to 130 ° C / 5 to 6 mmHg (yield 93.3%).

This was a colorless and transparent oily substance, and the results of elemental analysis are as follows.

Example 5 13.6 g of p-nitrobenzylamine in a glass closed container.
(0.1 mole), water 75 ml, 60% nitric acid 10.5 g (0.1 mole)
Then, 0.27 g of a 5% Pd-C catalyst was charged, and hydrogen was introduced with vigorous stirring.

The reaction was completed for 3 hours while maintaining the reaction temperature at 20 to 30 ° C.

Next, the reaction solution was heated to 60 ° C. and then passed through to remove the catalyst. 32 g of flaky caustic soda (0.8
Mol) was added and neutralized to release crude oily brown p-aminobenzylamine in the upper layer. The brown oil was vacuum distilled to give 10.4 g of p-aminobenzylamine (yield 85.1).
%).

Example 6 13.6 g (0.
1 mol), 50 ml of methanol, 6.2 g (0.1 mol) of boric acid and 1 g of Raney nickel were charged, and hydrogen was charged with vigorous stirring to keep the pressure at 20 to 30 kg / cm ² · G. The reaction temperature was 70 to 80 ° C for 90 minutes to complete the reaction.

After completion of the reaction, the reaction mixture was cooled and post-treated in the same manner as in Example 3 to obtain 9.8 g of o-aminobenzylamine.

Yield 80.2%, boiling point 91 ~ 93 ° C / 1mmHg, melting point 59 ~ 6
The results of elemental analysis at 1 ° C are as follows.

Example 7 13.6 g of m-nitrobenzylamine in a glass closed container.
(0.1 mol), glacial acetic acid 6 g (0.1 mol), 5% Pd / C0.3
g and 50 ml of isopropanol were charged, and the mixture was vigorously stirred while introducing hydrogen. When the temperature was maintained at 30 to 40 ° C for 5 hours, 6.9 hydrogen was absorbed. Since no more absorption was observed, the test was terminated.

After the completion of the reaction, the catalyst was removed by passing, and the mixture was concentrated under reduced pressure to distill off most of isopropanol to obtain a yellow viscous liquid. I left it and it crystallized, so I passed
After washing with isopropanol, it was dried to give m-
13.3 g of aminobenzylamine acetate was obtained.

Yield 73.2%, melting point 129-131 ° C, elemental analysis results are as follows.

Example 8 13.6 g of p-nitrobenzylamine in a glass closed container.
(0.1 mol), propionic acid 7.4 g (0.1 mol), 5% Pt /
Example 7 was charged with 0.4 g of C catalyst and 50 ml of methanol.
The reaction was performed in the same manner as in. After completion of the reaction, the catalyst was removed in excess and most of the methanol was recovered.
35 g of a% caustic soda solution was added. After stirring, the mixture was allowed to stand and separated into two layers, so the lower layer was removed and the upper layer was distilled to obtain colorless transparent oily p-aminobenzylamine 11.3.
g was obtained. The yield is 92.5% and the boiling point is 129 to 131 ° C / 6 mmHg.

Example 9 13.6 g (0.1 mol) of o-nitrobenzylamine as a raw material,
5% Pd / C 0.6g as catalyst, acid and acetic acid 5 as solvent
The same procedure as in Example 8 was carried out using 0 ml to obtain 10.6 g of o-aminobenzylamine. Yield 86.7%, melting point 60-6
The boiling point is 1 ° C and the boiling point is 91 to 93 ° C / 1 mmHg.

Example 10 13.6 g of p-nitrobenzylamine (0.
1 mol), 13.2 g (0.3 mol) of solid carbon dioxide, 1 g of Raney nickel catalyst and 75 ml of methanol were charged, and hydrogen was introduced to maintain the pressure at 30 to 35 kg / cm ² · G. The reaction was terminated at 20-40 ° C for 5 hours with vigorous stirring.

Next, after the reaction solution was passed to remove the catalyst, 4 g of caustic soda was added and distilled to obtain 11.0 g of p-aminobenzylamine having a purity of 99.9% by gas chromatography.
Was obtained (yield 90%).

The results of elemental analysis are as follows.

Example 11 Example 1 except that 13.6 g (0.1 mol) of m-nitrobenzylamine was used as the raw material and 50 ml of tetrahydrofuran was used as the solvent.
Reaction was performed in the same manner as 0. After the reaction was completed, the precipitated crystals were filtered out and recrystallized from isopropanol to obtain 6.7 g of pure white needle crystals of m-aminobenzylamine carbonate. The results of elemental analysis are as follows, with a yield of 43.1% and a melting point of 115-117 ° C.

Claims (4)

[Claims] 1. A nitrobenzylamine represented by the general formula (I): (In the formula, the nitro group is at the o-position, m-position or p-position) A method for producing aminobenzylamine, which comprises hydrogenating and reducing using a reducing catalyst in the presence of an acid. 2. The method for producing aminobenzylamine according to claim 1, wherein the acid is a mineral acid and / or an anhydride thereof. 3. The method for producing aminobenzylamine according to claim 1, wherein the acid is an organic acid. 4. The method for producing aminobenzylamine according to claim 1, wherein carbon dioxide gas is present as the acid.