DE2349056C3 - Process for the preparation of 4-aminomethylcyclohexanecarboxylic acid (I) - Google Patents

Description

kg / cm ² , characterized in that io is hydrogenated, see Japanese patent specification 70'32258.

one the reaction in the presence of at least one disadvantage is the application of a great

one of the alkali hydroxides sodium, potassium and an amount of ruthenium catalyst. As in your

and calcium hydroxide is found in an amount of 1 to Japanese Patent Publication No. 7032258

10g equivalent per mole of starting material is a continuous production of 4-aminomethyl leads, and the amount of ruthenium metal in the cata- 15 cyclohexanecarboxylic acids) from p-aminomethylben-

lysator per reaction 0.025 to 0.25 weight zoic acid in yields of more than 90% only possible

percent, based on p-aminomethylbenzoic acid, Hch, if more than 30 percent by weight of catalyst,

amounts to. based on the p-aminomethyl) benzoic acid, ven-

2. The method as claimed in claim 1, thereby de- ting. This is characterized by the use of a gro, that the reaction in the presence of 20 ßen kaialysator required economic after-2 The equivalent of sodium hydroxide, but potassium hydroxide is unavoidable, so it is practical droxyd and or calcium hydroxide carried out is impossible, the procedure for the large-scale production will. to use. Ruthenium catalysts are used

3. The method according to claims 1 and 2, known to be relatively rare in the course of a reaction characterized by being poisoned at a temperature of this type. In certain cases, however, occurs

rature of 155 ^:
cm ² hydrogenated.

C and a pressure of 100 kg

poisoning of the catalyst, and by certain kinds of raw materials to be used poisoning is increased. In such a case, the consequence of using a large amount of regenerated catalyst that has been used during the reaction. the

economic disadvantage is exacerbated. This

Process is therefore out of the question for large-scale production.

It is a prerequisite for an industrially feasible and economically advantageous process for the production of 4-aminomethylcyclo-

For the synthesis of 4-aminomethylcyclohexane-hexanecarboxylic acid- (l) directly from p-aminomethylcarboxylic acid- (l) is among other things a Großteehnisches benzoic acid, reducing the activity of the Process known in which to prevent the benzene ring of 40 catalyst and the required p-aminomethylbenzoic acid or its derivatives to reduce the amount of catalyst and thereby the is hydrogenated. In process of making process by the possibility of the catalyst 4-aminomethylcyclohexanecarboxylic acid- (l) by Hy- to use repeatedly, to make it economical, dration of the benzene ring of p-aminomethylbenzoe- the subject of the invention is a process

acid or its derivatives are the starting material for the production of 4-aminomethylcyclohexanecarrial and the economic viability of carrying out the process bonsäure- (l) by hydrogenation of p-aminomethyl technically important. Accordingly, a new verbenzoic acid in the presence of ruthenium catalysis would be which override the known processes and in an alkaline solution at one temperature is of great technical importance. from 90 to 200 ° C and under a pressure of 50 to

In this context, a brief overview of 50 200 kg cm ² , which is characterized in that the reaction in the presence of at least one of the 4-aminomethylcyclohexanecarboxylic acid (l) is given via the known processes for the preparation of. Alkali hydroxides sodium, potassium and calcium from Japanese patent 57/9073 isi a hydroxyd in an amount of 1 to 10 g-equivalent process is known in which cyanobenzoic acid performs in per mole of starting material, and the presence of Ru of a catalyst, the an amount of platinum compound in the catalyst per reaction or a platinum compound and a rhodium of 0.025 to 0.25 percent by weight, based on the compound, is hydrogenated. This process is p-aminomethylbenzoic acid, but has disadvantages, for example due to the fact that the process according to the invention is d:; e

secondary reactions, low selectivity, and hydrogen concentration at least 3 moles per mole of p-amine appear of the reaction product and use 60 normal benzoic acid and the hydrogen pressure 50

expensive catalysts. This method is therefore economically disadvantageous and has accordingly been used for large-scale production not applied.

Furthermore, in Japanese Patent 68.3 101, a method for hydrogenating the aromatic Ring of aminomethylbenzoic acid-N-acetate in the presence of a nickel catalyst at increased Temperature and under high pressure for heating

up to 200 kg cm- ', preferably 80 to 150 kg cm ² . the
Reaction temperature is 90 to 200 ° C.

The starting material for the procedure according to
p-aminomethylbenzoic acid used in the invention
can ν οι partly by hydrogenation of the p-Cyanobenzocsäureincthylcstcrs under alkaline conditions,
for example, by the method described in Japanese Patent Publication 7195243. her-

be asked. The p-cyanobenzoic acid methvIestei can be selectively obtained by distillation of the molten reaction product of terephthalic acid nitrile, dimethyl terephthalate and terephthalic acid.

In the process according to the invention the catalyst plays a very important role. As ruthenium catalysts can according to the invention Ruiheniumoxide, Rutheniumhydroxyd and ruthenium, which on an inert carrier is applied, can be used. Suitable carriers for the purposes of the invention are for example carbon carriers, calcium carbonate, rare earth oxides, for example from cerium, praseodymium or lanthanum, rare earth carbonates, for example of cerium, praseodymium or lanthanum, mixed Rare earth oxide carbonates, aluminum oxide, barium sulfate, kieselguhr, pumice stone, diaspore, Bauxite, periclase, zircon, titanium dioxide. Diatomaceous earth! Calcium sulfate, calcium oxide, barium oxide. Barium carbonate, strontium carbonate, strontium oxide, sirontium sulfate, Silica, Silica-Alumina, Etched Nickel, Nickel Chrome, and Inconel Wire.

These compounds become aluminum oxide. Kieselguhr, carbon carrier, barium sulfate and calcium carbonate = 5, in particular carbon carrier, particularly preferred. Supported ruthenium catalysts are particularly preferred as catalysts. The ruthenium content in the catalyst is 1 to 10 percent by weight, preferably 4 to 6 percent by weight. By adding at least one of the alkali hydroxides sodium hydroxide, potassium hydroxide and calcium hydroxide in an amount of 1 to 35 g equivalents, preferably 1 to 10 g equivalents, per mole of p-aminomethylbenzoic acid, the amount of ruthenium metal used per reaction in the catalyst can be reduced to 0.025 to 0 , 25 percent by weight, based on p-aminomethylbenzoic acid, can be reduced. The result of the reaction is comparable in yield to the result of a reaction in which, based on p-aminomethylbenzoic acid. 30 ⁰ Zo activated charcoal is used as a catalyst to which 5 percent by weight of ruthenium metal is applied (the amount of ruthenium based on p-amiomeihyibenzoic acid being 1.5 percent by weight). Furthermore, the reaction can be brought to completion in an economically acceptable time. When using the ruthenium catalyst, the amount of catalyst used per reaction should be reduced as much as possible in order to enable the process to be carried out on an industrial scale. In the process according to the invention, the objective of the reaction is achieved with certainty without starting material remaining in the reaction liquid, so that the process is extremely advantageous economically. In the above-mentioned known process, hydrogenation of p-aminobenzoic acid in aqueous ammonia using activated carbon to which 5 percent by weight of ruthenium metal is applied. obtained as a catalyst in an amount of 30 ⁰ O, based on p-aminomethylbenzoic acid, 4-aminomethylcyclohexanecarboxylic acid- (l) in yields of up to over 90 °. In certain cases, however, the catalyst used under the conditions of the reaction according to the invention can not be reused more than three times without regeneration. As Table 1 below shows, the reaction is essentially brought to a standstill by reducing the amount of catalyst used per reaction to below 8 ''.

30 (1.5) *)

20 (1.0)

100 100 97 97 97 97 0 0

8 (0.4)

80
98
78
19th

5 (0.25)

58
96
56
42

Table 1

Amount of catalyst per reaction
in ° / o of B

Conversion of B to A, ° / o
Yield A from B, ⁰ zo
Total yield,%

In the liquid reaction mixture
remaining starting material, «.Ό

Reaction conditions
Initial Ho pressure, kg / cm ²
Temperature, ° C
Time, hours

*) The numbers in brackets are the catalytic converters calculated as Ruthcniummi'tall in (icwkhl%) on p-aminomethylbenzoic acid.

Remarks:

Λ denotes 4-AminomeÜiylcyclohexancarbonsämc-n) (denote in the following tables in the same way.

B means p-aminomethylbenzoic acid.

Catalyst: 5% ruthenium on carbon.

Starting material: 10 g B.

Solvent: 70 ml of 5% aqueous ammonia.

Reaction vessel: 300 ml stainless steel autoclave.

100 100 100 100 150 150 150 150 3 3 3 16

The Austen this type of the appear Ungen currency ^ ^ Trae _"to £ £

The reaction can in the core case, η purchase Vernnge g _{maintenance of the high Ak} fj.

are taken, and any procedure in which and for | _{the addition of} , _w

These phenomena occur, is for the greatness of the Katay p-Aminomethylbenzoe

position unusable. Furthermore, st em procedure, be. 5 Aqun ^ nt \ ~ ^g _{ejnes dcr} alkali hydroxides Na.ri

to which a large amount of the expensive and acidic catalyst; at least, _c ^} _{a] c} : .. ^ _hvn '

d Khhydroxydnd CaI «« ^

_so-called equal F ^ \ ejnes the alkali

to which a large amount of the expensive and acidic catalyst; at least ,

the regeneration of the used catalyst after umhydroxyd Kahumhydroxydnd

every reaction is necessary, economically most unpredictable «tD« E.nfl ^ ^dies ^ ^ ^sat

Decent and therefore illustrated by the values in Table 2 for large-scale production.

j,

lousy and therefore suitable for large-scale production

Not insertable.

Table 2 Blocked connection
comparison
none NH ₄ OH invention
NaOH KOH 8th 25th 100 100 Conversion from B to A,% 90 94 97 96 Yield of A from B,% 7th 23.5 97 96 Total yield,% 90 75 0 0 In the reaction liquid
remaining starting material, B% Reaction conditions 100
190 100
180 100
150 100
150 H ₂ initial pressure, kg / cm ²
Temperature, ° C 16 8th 1.5 1.5 Time, hours

Remarks:

Based on 1 mol of starting material, 1.5 g equivalent of NH ₄ OH, NaOH and KOH were used.

Type and amount of the catalyst: 5% ruthenium on carbon in an amount of 3 percent by weight, based on the Aus

gang material ß. (Amount of ruthenium metal 0.15 percent by weight, based on p-aminomethylbenzoic acid.)

Starting material: 10 g B.

Solvent: 70 ml of 5% aqueous ammonia or 70 ml of water.

Reaction vessel: 300 ml stainless steel autoclave.

As the values in Table 3 show, the residual economic burden of the subsequent post-treatment

Liche amount of p-aminomethylbenzoic acid in the liquid stage. For example, if you use a

Igen reaction mixture is considerably enriched if ion exchange resin is used for the isolation of the p-

the added amount of the compound under 1 equi-aminomethylbenzoic acid by using a

valentine lies. Residual p-aminomethylbenzoic acid is too large a quantity of additives to be used

undesirable because in the purification stage the p-amide amount of the ion exchange resin

nomethylbenzoic acid and 4-aminomethylcyclo-6c increased avoidably. Because of this undesirable

hexanecarboxylic acid- (l) -like properties at an economic expense, e.g. B. by the size

so that it becomes impossible to use 4-aminomethylation of the amount of liquid for post-treatment,

Cyclohexanecarboxylic acids 1) to get in high purity the plant costs, the energy consumption and

win. Residual p-aminomethylbenzoic acid increased in other costs.

an amount of more than 12 per cent in the reaction product 65 The results of experiments with various

can even after 5 recrystallizations from boiling amounts of additives are listed below in Ta-

Water cannot be removed. The addition of one to belle 3 put together,
large amount of the additive results in too strong

Table 3

Blocked connection
(g equivalent per MoT
0.5 0.9 92 Source material)
1.0 2.0 5.0 10.0 Conversion of B to A, ° / o 70 98 100 100 100 100 Yield,% 98 90 96 98 97 98 Total yield, ° / o 68.7 8th 96 98 97 98 Im liquid reaction
mixture remaining
Starting material B, ° / o 31 0 0 0 0

Reaction conditions

H ₂ initial pressure, kg / cm ² 100

Temperature, ° C 180

Time, hrs. 12

100 100 100 100 100 170 155 155 155 155 8th 3 1.5 1.5 1.5

Remarks:

Added compound: NaOH.
Catalyst: 50 / _o ruthenium on carbon.

Amount of catalyst: 3 percent by weight, based on the starting material B (amount of lithium metal 0.15 percent by weight, based on p-aminomethylbenzocic acid).
Solvent: 70 ml of water.

Reaction vessel: 300 ml stainless steel autoclave. Starting material: 10gB.

As alkali hydroxides are for the purposes of the invention Sodium hydroxide, potassium hydroxide and calcium hydroxide are effective. This becomes sodium hydroxide and potassium hydroxide are particularly preferred. The influence of adding each of these alkali hydroxides is illustrated by the values in Table 4.

Table 4

Alkali hydroxide KOH Ca (OH) ₂ NaOH 100 100 Turnover from B to A, ⁰ zo 100 97 93 Yield,% 98 97 93 Total yield,% 98 0 0 Remaining exit 0 material B in the liquid Reaction mixture, ° / o Reaction conditions 100 100 H ₂ initial pressure, kg / cm ² 100 155 155 Temperature, ° C 155 1.5 1.5 Time, hours 1.5

to 170 ^r 'C, and at a pressure of 50 to 200 kg / cm ² , preferably 80 to 150 kg / cm ² .

The process according to the invention can be carried out in any other conventional conditions will. The order of addition of starting material. Catalyst, alkali hydroxide and Solvent is irrelevant. Preferably the reactants are at the start of the reaction stirred, but further stirring is not absolutely necessary until the reaction has ended.

After the reaction, the liquid reaction mixture is drawn off, whereupon the 4-aminomethylcyclohexanecarboxylic acid (l) either adsorbed directly to an ion exchange resin of the H ^ type and is dissolved in aqueous ammonium, or the liquid reaction mixture is first neutralized and concentrated, whereupon by recrystallization 4-aminomethylcyclohexanecarboxylic acid (l) is isolated of high purity in high yield.

The 4-aminomethylcyclohexanecarboxylic acid (l) prepared in this way is suitable as a starting material for the production of polymers or drugs.

55

Remarks:

Alkalihydroxydmcngc: 2 g-equivalent per mole of the used Catalyst.

Kalal> satot: 5 ° ο ruthenium on charcoal. Amount of catalyst: 3 percent by weight, based on the starting material B (amount of ruthenium metal 0.15 percent by weight, based on p-aminomethylbenzoic acid). Starting material: 10 g B.
Solvent: 70 ml of water.
Reaction vessel: 300 ml stainless steel autoclave.

The process of the invention is carried out at a reaction temperature of 90 to 200 ° C, preferably 140

example 1

10 g of p-aminomethylbenzoic acid were placed in a 300 ml stainless steel autoclave equipped with a stirrer. 3.0 g sodium hydroxide. 70 ml of water and 0.3 g of activated carbon to which 5 weight percent ruthenium were applied given, whereupon hydrogen at normal temperature to a pressure of 100 kg'cm ² was pressed, and the reaction C for 1.5 hours at 155 ⁰ carried

was leading. The catalyst was filtered off from the liquid reaction mixture. The filtrate was passed through a column of 400 ml of H "-type ion exchange resin (" Ambeilitc 200 "). The resin

609 630/247

was washed with 1 l of water. Then 300 ml of aqueous 1η ammonia were passed through the column. The solution was concentrated and the concentrate dried, leaving 10.3 g of a white solid obtained by NMR and infrared analysis as 4-aminomethylcyclohexanecarboxylic acid- (l) was identified. By quantitative analysis by titration of the amino group and by Gas chromatography found that the in

10

4-aminomethylcyclohexanecarboxylic acid (l) obtained in this way had a purity of 98.5%.

Examples 2 to 9

The reaction was carried out in the manner described in Example 1 with various amounts of catalyst and various types and amounts of the specified alkali hydrolysis are carried out. The results are summarized in Table 5 below.

Table 5

at Catalyst, ° / o Alkali hydroxide g / equi
valentine /
Mole B Reaction conditions Tempe
rature time yield on A off total
out
prey Rest
crowd
from B game (based on Art H ₂ -An-
catching
pressure ⁰ C Hours. sales volume Out
prey Vo o / o 1.0 kg``cm ^! 155 6th "Vo "Vo 96 0.5 2 1.0 (0.05) *) NaOH 10 100 155 4th 99 97 98 0 3 1.0 (0.05) NaOH 10 100 155 3 100 98 95 0 4th 1.5 (0.075) NaOH 10 100 155 1.5 100 95 98 0 5 3.0 (0.15) NaOH 1.0 100 155 1.5 100 98 98 0 6th 5.0 (0.25) NaOH 2.0 100 155 1.5 100 98 97 0 7th 2.0 (0.1) KOH 2.0 100 155 1.5 100 97 97 0 8th 3.0 (0.15) Ca (OH) ₂ 1.5 100 160 1.5 100 97 96 0 9 5.0 (0.25) Ca (OH), 100 100 96

*) The numbers in brackets mean ruthenium metal in ⁰ O, based on material B.

Type and amount of the catalyst: 5 ⁰ Zo ruthenium on carbon in an amount of 3 percent by weight, based on starting material B (amount of the ruthenium metal 0.15 percent by weight, based on p-aminomethylbenzoic acid).

Claims (1)

Claims: position of N-AcetyM-aminomethylcycIohexan carboxylic acid ^ 1) described, which is then ι 4-aminomethylcyclohexanecarboxylic acid (l) hydrolyzed. In addition, as an improvement of this 5 process for the preparation of 4-aminomethylcycIo hexancarlxmsüure- (l) a process has become known in which the aromatic ring in the presence of a ruthenium catalyst directly without protection of the amino group in the p-aminomethylbenzoic acid 1. Procedure to. Production of 4-aminoniethylcyclohexanecarboxylic acid ( 1) by hydrogenation of p-aminomethylbenzoic acid in the presence of ruthenium catalysts and in alkaline Solution at a temperature of 90 to 200 ° C and under a pressure of 50 to