EP0117371B1 - Process for the production of aminobenzoic acids from corresponding nitrotoluenes - Google Patents

Description

The present invention relates to a new process for preparing aminobenzoic acids, and in particular para-aminobenzoic acid, by oxidation of nitrotoluenes, followed by electrochemical reduction of the nitrobenzoic acids obtained.

où: n représente un nombre entier égal à 1, 2 ou 3, et la liaison pénétrante dans le cycle benzénique représente une possibilité de substitution de ce dernier en position ortho, méta et/ou para, le cycle benzénique pouvant également porter d'autres substituants demeurant inchangés au cours de la réaction.This process, making it possible to prepare various aminobenzoic acids, can be illustrated by the following reaction scheme:

where: n represents an integer equal to 1, 2 or 3, and the penetrating bond in the benzene cycle represents a possibility of substitution of the latter in ortho, meta and / or para position, the benzene cycle can also carry other substituents remaining unchanged during the reaction.

Aminobenzoic acids, obtained according to the process of the present invention, are chemicals mainly used in the pharmaceutical industry and in the dye industry.

The oxidation of nitrotoluene to nitrobenzoic acid by an oxidizing chemical agent (nitric acid, permanganate, chromic acid, oxygen), then reduction of the nitrobenzoic acid thus obtained to aminobenzoic acid by hydrogen, by metals or by electrolysis constitute a process for the preparation of these compounds well known in the prior art.

The oxidation of nitrotoluenes by sulfochromic solutions has been known for a very long time (see for example: KAMM, MATTHEWS, Org. Syn. 2, 53 (1922); KASTENS, KAPLAN, Ind. Eng. Chem. 42, 402 (1950) ; Vogel's textbook of practical organic chemistry - edited by LONGMAN (1978) p. 819).

However, chromic acid is an expensive and particularly toxic reagent which is preferred to be replaced in industry by oxygen in the presence of a catalyst or by nitric acid.

The electrochemical regeneration of sulfochromic solutions having served for oxidations of organic products is a very old industrial reaction (see for example the German patents n ° 103.860 and American n ° 2.450.858). It avoids the cost and toxicity problems of chromium salts by recycling them entirely.

As for the electrochemical reduction of nitrobenzoic acids, it makes it possible to obtain excellent yields (see for example: N.A. Izgaryshev, M. Ya. Fioshin - Doklady. Akad. Nauk. SSSR, 90, 169-90 (1953);

J. Phillips, A. Lowy, Trans. Electrochem. Soc. 71, 494 (1937); Indian patent 145096 (1976).

• - la réduction par le fer en milieu acide, qui donne un produit mêlé à des oxydes de fer,
• - l'hydrogénation catalytique, qui nécessite des conditions de pH assez précises et donne un produit mêlé avec du catalyseur.

Such electrochemical reduction also has advantages over conventional methods:

• - reduction by iron in an acid medium, which gives a product mixed with iron oxides,
• - catalytic hydrogenation, which requires fairly precise pH conditions and gives a product mixed with catalyst.

Electrochemistry does not have these drawbacks: pure aminobenzoic acid sulfate can be recovered by simple filtration after electrolysis.

The present invention relates to a process for the preparation of aminobenzoic acids, of the type comprising a first step of oxidation of nitrotoluenes to nitrobenzoic acids, followed by a second step of electrochemical reduction of said nitrobenzoic acids, characterized in that the agent oxidant used for the implementation of the first step is a sulfochromic solution which is regenerated at the anode of an electrolyser simultaneously ensuring the electrochemical reduction of the second step, said second electrochemical reduction step being carried out in an electrolyser whose compartments anode and cathode are separated by a membrane.

• - l'investissement dû à l'électrolyse est diminué de moitié (une seule installation au lieu de deux), et
• - l'énergie nécessaire pour conduire les deux réactions est diminuée de plus de la moitié, la tension de J'électrolyse commune étant légèrement inférieure à chacune des tensions d'électrolyses séparées.

The advantage of combining the two reactions, regeneration of chromic acid and reduction of nitrobenzoic acid in the same electrolyser is perfectly clear. Indeed, compared to these reactions carried out in two separate electrolysers:

• - the investment due to electrolysis is halved (one installation instead of two), and
• the energy required to conduct the two reactions is reduced by more than half, the voltage of the common electrolysis being slightly lower than each of the separate electrolysis voltages.

Other characteristics and advantages of the process which is the subject of the present invention will appear on reading the detailed description given below, in particular with reference to the appended figure, representing the block diagram of said process.

• 1) le nitrotoluène est maintenu en émulsion ou en suspension dans la solution sulfochromique provenant de l'électrolyse par une agitation violente. La réaction est d'autant plus rapide que la température est plus élevée et que la solution est plus concentrée en acide sulfurique et en acide chromique.

The chemical reaction of oxidation of nitrotoluene by sulfochromic acid can be carried out in two ways, depending on the reactivity of nitrotoluene:

• 1) the nitrotoluene is maintained in emulsion or in suspension in the sulfochromic solution coming from the electrolysis by a violent agitation. The reaction is faster the higher the temperature and the more concentrated the sulfuric acid and chromic acid.

The nitrobenzoic acid, optionally containing unprocessed nitrotoluene is recovered by filtration after cooling.

2) If the nitrotoluene is too reactive, it is necessary to concentrate the sulfochromic solution by evaporation, before bringing it into the presence of the nitrotoluene. After reaction, the reaction medium is extended with ice water to a chromium concentration of less than 2.5 atomograms per liter and a sulfuric acid concentration of less than 50% by weight, then filtered.

The sulfochromic solution used to ensure the oxidation of nitrotoluenes can, for example, advantageously consist of an aqueous solution of 3 to 20% by weight of chromic oxide and 10 to 95% by weight of sulfuric acid which may contain chromium sulfate, and possibly other additives.

After optional separation of the residual nitrotoluene, the nitrobenzoic acid is introduced into the cathode compartment 19 of the electrolyser in the form of a suspension in sulfuric acid of concentration 5 to 40% by weight (optionally containing metal salts serving as catalysts) , while the "used" sulfochromic solution is introduced into the anode compartment ^s .

The electrochemical process can for example be advantageously implemented in an electrolysis cell whose electrodes are lead plates, and the diaphragm which separates them, a cation exchange membrane. This membrane is chosen as a function of its chemical resistance and of its selectivity: it must resist the corrosive action of the sulfochromic mixture and be allowed to pass, under the action of an electric current, only by hydrogen ions.

A circulation of the anodic and cathodic solutions between the electrodes and the diaphragm makes it possible to create sufficient agitation in the vicinity of the electrodes for the good progress of the electrochemical reactions. The temperature is maintained between 20 and 100 ° C and preferably between 50 and 80 ° C, the current density between 3 and 15 A / dm2. The electrolysis voltage is generally between 3 and 5 V.

The amount of current theoretically necessary to reduce one mole of mono-nitrated product at the cathode makes it possible to manufacture, at the anode, a quantity of chromic acid corresponding to the oxidation of one mole of nitrotoluene (6 electrons are required for reduce a nitrated function and 6 electrons to oxidize a 'methyl function).

• - dans le cas d'un mono-nitrotoluène, on fabriquera pendant l'électrolyse trois moles d'hydrogène par mole d'acide mono-nitrobenzoique,
• - dans le cas d'un poly-nitrotoluène, on fabriquera très peu d'hydrogène pendant la réaction, mais on fabriquera de l'oxygène à l'anode.

However, the yield of the anodic reaction is close to 50%, and therefore:

• - in the case of a mono-nitrotoluene, three moles of hydrogen will be produced during the electrolysis per mole of mono-nitrobenzoic acid,
• - In the case of a poly-nitrotoluene, very little hydrogen will be produced during the reaction, but oxygen will be produced at the anode.

After electrolysis, that is to say when the catholyte no longer contains nitrated product and when the chromic solution has reached the desired concentration, the catholyte is cooled and filtered. The precipitate is aminobenzoic acid in the form of sulfate. The filtrate is re-acidified with concentrated sulfuric acid to compensate for the departure of acid bound to the amine. He can again serve as a catholyte.

The anode solution will be used for further oxidation of nitrotoluene.

These different elementary steps of the method of the invention are clearly illustrated in the block diagram appended to this description.

Some non-limiting examples of implementation of the method according to the invention will be mentioned below.

Example 1 Chemical oxidation:

24 g of a chromic solution originating from the electrochemical regeneration of the residual waters of a previous experiment, and containing 30% of sulfuric acid, 7.9% of chromium trioxide and 3% of chromium sulfate, are added 24 g of paranitrotoluene.

The solution is stirred at 80 ° C for 46 hours. After cooling, the organic products are filtered. The filtrate is dosed and contains 31% sulfuric acid, 2% chromium trioxide and 11.3% chromium sulphate.

Product separation:

The solid is suspended in 500 ml of water which is basified to pH 13 by progressive addition of sodium hydroxide. The mixture is filtered.

The precipitate, containing 8.5 g of unprocessed nitrotoluene and 1.7 g of chromium hydroxide (from insufficient filtration) will be recycled in the following experiment.

The filtrate containing the sodium salt of nitrobenzoic acid is acidified to pH 1 and then filtered. 16.2 g of para-nitrobenzoic acid are thus recovered, which corresponds to a yield of 85% relative to the para-nitrotoluene consumed and 82% relative to the chromic acid consumed.

• La réaction est menée dans un électrolyseur constitué de deux feuilles de plomb parallèles séparées par une membrane échangeuse de cations. Une pompe permet la circulation des électrolytes entre chacune des électrodes et la membrane.

Electrolysis:

• The reaction is carried out in an electrolyser consisting of two parallel lead sheets separated by a cation exchange membrane. A pump allows the circulation of electrolytes between each of the electrodes and the membrane.

In the anode compartment circulates the sulfochromic solution used to oxidize the nitrotoluene.

The cathode solution is a suspension of the 16.2 g of nitrobenzoic acid previously obtained in 500 g of a solution which had already served as a catholyte in a previous experiment and containing 125 g of sulfuric acid and 15 g of titanyl sulfate .

The temperature is maintained at 60 ° C, the current density at 10 A / dm2. The electrolysis voltage is close to 4 V.

When twice the amount of electricity necessary for the reduction of nitrobenzoic acid has passed through the electrolyzer, the catholyte is cooled before filtering it.

14.8 g of para-aminobenzoic acid sulfate are thus obtained (mass yield 82%). Para-aminobenzoic acid can be recovered by basifying an aqueous suspension of the sulfate at pH 4.

The titanium salt solution will be reused in subsequent reductions after adding 4 g of concentrated sulfuric acid.

The anodic solution contains 6.7% chromic acid and can be used for other oxidations (current efficiency 48%).

Example 2 Chemical oxidation:

The procedure is the same as in Example 1. The chromic solution used is the regenerated solution in Example 1. 13 g of para-nitrotoluene are added thereto and the mixture of nitrotoluene and chromous hydroxide recovered at the end of the chemical reaction of Example 1.

12.7 g of nitrobenzoic acid are obtained, which represents a yield of 80% relative to the nitrotoluene consumed and 81% relative to the chromic acid consumed.

• Le mode opératoire est le même que dans l'exemple 1.

Electrolysis:

• The procedure is the same as in Example 1.

2.5 times the amount of electricity needed to reduce nitrobenzoic acid is used.

The concentration of the chromic solution goes from 2.01% to 5.81%, ie a current yield of 40%.

12 g of para-aminobenzoic acid sulfate are obtained, ie a yield of 85% relative to nitrobenzoic acid.

Example 3 Chemical oxidation:

1000 g of a chromic solution containing 4.6% chromic acid and 25% sulfuric acid from a previous regeneration are evaporated to a weight of 500 g.

After reaction with 30.1 g of para-nitrotoluene for 10 hours at 95 ° C, the reaction medium is extended with 380 g of water and then filtered.

The procedure is then identical to that of Example 1.

35 g of nitrobenzoic acid are obtained and 0.5 g of unprocessed nitrotoluene is recovered.

The chromic solution contains 0.3% chromic acid.

The yield is therefore 97% compared to nitrotoluene and 96% compared to chromic acid.

• Le mode opératoire est identique à celui de l'exemple 1. Au catholyte est ajouté 0,5 % de sulfate de cuivre, ce qui a pour effet d'abaisser la tension d'électrolyse à 3,3 V.

Electrolysis:

• The procedure is identical to that of Example 1. To the catholyte is added 0.5% copper sulphate, which has the effect of lowering the electrolysis voltage to 3.3 V.

Twice the amount of electricity needed to reduce nitrobenzoic acid is used.

The concentration of the chromic solution goes from 0.3% to 5.3%, giving a current yield of 49%.

32.7 g of para-aminobenzoic acid sulfate are obtained, ie a yield of 84% relative to the nitrobenzoic acid.

Claims (12)

1. Process for the preperation of aminobenzoic acids, of the type comprising a first stage of oxidation of the nitrotoluenes into nitrobenzoic acids, followed by a second stege of electro-chemical reduction of said nitrobenzoic acids, characterised in that the oxidising agent used for carrying out the first stage is a sulphochromic solution which is regenerated at the anode of an electrolyser simulteneously providing the electro-chemical reduction of the second stage, said second stage of electro-chemical reduction being conducted in an electrolyser in which the anodic and cathodic compartments are separated by a membrane.

2. Process according to claim 1, characterised in that said sulphochromic solution is a aqueous solution of 3 - 20 weight % of chromic oxide and of 10 - 95 weight % sulphuric acid able to contain some sulphate of chrome and possibly other additives.

3. Process according to one of claim 1 or 2, characterised in that the nitrobenzoic acid, produced by the oxidation of the first stage, is separated from the sulphochromic solution, after reaction, by:

- dilution possibly up to a concentration of chrome less than 2.5 gramme-atoms per litre and a concentration of sulphuric acid less than 50 weight %, then

- filtration providing the separation of solid nitrobenzoic acid and the sulphochromic solution to regenerate.

4. Process according to one of claims 1 to 3, characterised in that said membrane is a cation exchange membrane.

5. Process according to one of claims 1 to 4, characterised in that the electrode of the anodic compartment of the electrolyser is an anode of lead or of lead oxide.

6. Process according to one of claims 1 to 5, characterised in that the electrolysis is conducted in said electrolyser at a temperature between 20 and 100°C, preferably between 50 and 80°C.

7. Process according to one of claims 1 to 6, characterised in that the liquid introduced into the cathodic compartment of the electrolyser is a suspension of nitrobenzoic acid obtained as a result of the first stage, in a aqueous solution of sulphuric acid able to contain some aminobenzoic acid and possibly other additives.

8. Process according to one of claims 1 to 7, characterised in that the catholyte, electrolyte bathing the cathod of the electrolyser, contains from 5 to 40 weight % of sulphuric acid.

9. Process according to one of claims 3 to 8, characterised in that the liquid introduced into the anodic compartment of the electrolyser is a sulphochromic solution which results from the separation operation according to claim 3.

10. Process according to one of claims 1 to 9, characterised in that the anolyte, electrolyte bathing the anode, is concentrated after electrolysis, in order to be used in a new oxidation stage of nitrotoluene.

11. Process according to one of claims 1 to 10, characterised in that the aminobenzoic acid is extracted from the catholyte, in the form of sulphate of aminobenzoic acid by filtration.

12. Process according to claim 11, characterised in that the filtrate, resulting from the extraction of the aminobenzoic acid from the catholyte, is recharged in sulphuric acid and in nitrobenzoic acid in order to serve afresh as catholyte supplying the cathodic compartment of the electrolyser.

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