US3413334A

US3413334A - Process for the preparation of esters of aromatic n, n-dialkylaminocarboxylic acids

Info

Publication number: US3413334A
Application number: US505196A
Authority: US
Inventors: Burkhardt Rudolf; Wulff Helmut
Original assignee: Chemische Werke Witten GmbH
Current assignee: Chemische Werke Witten GmbH
Priority date: 1964-12-09
Filing date: 1965-10-25
Publication date: 1968-11-26
Anticipated expiration: 1985-11-26
Also published as: NL6512080A; BE673447A; FR1456442A; DE1493544A1; GB1052610A

Description

United States Patent 3,413,334 PROCESS FOR THE PREPARATION OF ESTERS OF AROMATIC N,N-DIALKYLAMINOCARBOXYLIC ACIDS Rudolf Burkhardt and Helmut Wulif, Witten (Ruhr), Germany, assignors to Chemische Werke Witten G.m.b.H., Witten (Ruhr), Germany No Drawing. Filed Oct. 25, 1965, Ser. No. 505,196 Claims priority, application Ester-many, Dec. 9, 1964,

8 Claims. of. 260471) ABSTRACT OF THE DISCLOSURE This invention relates to the preparation of esters. More particularly, it relates to a process for the preparation of eters of aromatic dicarboxylic acids. Even more particularly, the invention relates to a process for the preparation of esters of aromatic N,N-dialkylaminocarboxylic acids.

Aromatic N,N-dialkylaminocarboxylic acids, wherein both the dialkylamino groups and the carboxylic groups are linked directly to the aromatic residue, may be prepared by the oxidation of aromatic N,N-dialkylaminoaldehydes or aromatic N,N-dialkylamines having one or more methyl groups substituted in the aromatic nucleus thereof, by the carboxylation of aromatic N,N-dialkylamines with phosgene or carbon dioxide and Grignard compounds, or by the alkylation of the amino group of aromatic aminocarboxylic acids. Of greatest significance among these various methods of preparation is the lastmentioned N-alkylation which is carried out under reducing conditions either with the use of conventional alkylation agents or with aliphatic aldehydes.

It is known in the prior art to prepare p-dialkylaminobenzoic acid alkyl esters by the reductive alkylation of p-aminobenzoic acid esters with aliphatic aldehydes. This reduction is carried out with hydrogen in the presence of hydrogenation catalysts and, if desired, other supplementary catalysts, or with zinc and acetic acid. Yields of 30 to 60% have been obtained with this process.

More general applicability has been attained with the N-alkylation process wherein known alkylation agents were employed. Exemplary of such are the reactive alkyl halides, particularly alkyl iodides, dialkyl sulfates and the alkyl esters of benzenesulfonic acid and p-toluenesulfonic acid. The reaction of these compounds with amino acids or the esters thereof produces both monoand dialkylated products. It is necessary to use a more or less significant excess of alkylation agents in order to increase the yield of dialkylamino compounds. However, this may, in turn, lead to the formation of undesirable trialkyl ammonium salts and/or betaine. While alkyl iodides and alkyl esters of aromatic sulfonic acids are of great importance in preparing such compounds, they have been found to be unsuitable on a commercial or technical basis because of reasons of economics. Furthermore, the alkyl bromides can only be used to a limited extent because of their low reactivity. Hence, dialkyl sulfates have chiefly been employed for such alkylations on a large or technical scale.

The aliphatic alcohols which are utilized to a large extent for the alkylation of ammonia and amines must also be considered as alkylation agents. Very little has been done in the prior art With regard to using the processes conventional With such alkylation agents in connection withthe alkylation of the aromatic aminocarboxylic acids and the esters thereof, since these compounds are sensitive to high temperatures and acid catalysts. For example, when paminobenzoicacid is alkylated with ethanol in the presence of Raney nickel, only the monoethylated compound, while very little or no p-diethylaminobenzoic acid, is obtained.

One of the objects of the present invention is to provide an improved process for the preparation of esters of aromatic N,N-dialkylaminocarboxylic acids which overcomes the disadvantages and deficiencies of the prior art methods.

Another object of the present invention is to provide a process for the preparation of esters of aromatic N,N- dialkylaminocarboxylic acids which may be carried out in an efficacious and simple manner.

A further object of the present invention is to provide an improved process for the preparation of esters of aromatic N,N-dialkylaminocarboxylic acids which may be carried out on an industrial scale.

A still further object of the invention is to provide a process for the preparation of esters of aromatic N,N- dialkylaminocarboxylic acids which may be carried out economically and effectively on a large scale.

These and other objects of the present invention Will become apparent to those skilled in the art from a reading of the following specification and claims.

In accordance with the present invention, it has been found that alkyl esters of aromatic N,N-dialky1aminocarboxylic acids having the general formula wherein Ar is either a monoor polynuclear or, if desired, an alkyl-substituted aromatic residue, R is an alkyl residue having 1 to 3 carbon atoms, R is an alkyl residue which may be the same or different from R, and n is a whole number from 1 to 3 may be obtained from the corresponding aminocarboxylic acid esters by heating the same with aliphatic alcohols containing from 1 to 3 carbon atoms in the molecule in the presence of catalytic quantities of iodine or low molecular Weight alkyl iodides. The reaction is carried out effectively under pressure at a temperature of from about to 250 C. Further treatment of the reaction mixture is carried out in a conventional manner.

The process according to the present invention renders the preparation of N,N-dialkylaminocarboxylic acid esters possible with the use of aliphatic alcohols. Therefore, the process may be carried out considerably more economically than alkylation processes using other alkylation agents, including compounds mentioned hereinabove such as the dialkyl sulfates and aliphatic aldehydes. Hence, it is possible to carry out the process of the preent invention easily on a large technical scale. For example, as compared to reductive alkylation with aldehyde, the process of the present invention has the advantage that reducing agents are not required in order to carry out the process.

Any of the suitable alkyl esters of aromatic aminocarboxylic acids may be used as a starting material in the process of the present invention. These may be obtained, for example, by reduction of the corresponding nitro-compounds. Exemplary of such starting materials are compounds such as the methyl esters of 3-aminobenzoic acid and of S-aminoisophthalic acid. These compounds are easily obtained by the nitration of the benzoic and, respectively, the isophthalic acid methyl esters and by the subsequent catalytic reduction thereof. Aromatic aminocarboxylic alkyl esters substituted with one or more than one alkyl group in the aromatic nucleus may also be employed. Alkyl herein is meant to refer to at least lower alkyl, defined hereinbelow, but is not to be limited thereto, i.e., when suitable, higher alkyl homologs are included.

Methanol is the preferred aliphatic alcohol to be employed in the process of the present invention, since it is often preferred to introduce methyl groups during the alkylation reaction. However, other aliphatic alcohols may be employed as the alkylation agents herein, for example, ethanol and l-propanol. These three alcohols are especially suitable for the N-alkylation process of the present invention, and while higher alcohols also act in an alkylating manner, they tend to lead to the formation of monoalkylated products because of steric considerations arising from their overall bulkiness.

Suitable cataylsts to be employed in the process of the present invention include elemental iodine and lower alkyl iodides. By lower alkyl is means herein alkyl groups containing from 1 to 4 carbon atoms, i.e., methyl, ethyl, n-propyl, i-propyl, n-butyl, s-butyl, i-butyl and t-butyl. These catalysts may be employed in amounts of from about 0.005 to 0.05 mole per mole of aminocarboxylic acid ester.

The reaction takes place effectively with a temperature range of from about 150 to 250 C. The preferred reaction temperature range is :from about 180 to 230 C. The particular choice of the reaction temperature depends upon the thermal stability of the aminocarboxylic acid esters and can be easily adjusted in accordance therewith by one skilled in the art.

Aromatic dialkylaminocarboxylic acid-s and the esters thereof are compounds having known utilities in the prior art. For example, they may be used for modifying polycondensation products. The methyl esters are particularly useful in this regard and may be used as component parts of the molecular chains in linear polyesters in order to improve the dyeability and the electrostatic properties thereof. As components of unsaturated polyester resins, these compounds accelerate the hardening thereof and, therefore, make it possible to cold-harden these resins. In addition, the aromatic esters produced by the process of the present invention may be used to prepare valuable chemical substances such as drugs and dyestuffs. Their properties of luminescence and of absorbing ultraviolet rays may also 'be used to advantage.

The following examples are .given merely as illustrative of the present invention and are not be be considered as limiting thereof.

Example I 124 grams (0.75 mole) of ethyl p-aminobenzoate together with 500 ml. of ethanol and 3 grams of ethyl iodide are maintained in an autoclave for five hours at ZOO-205 C. The reaction mixture is stirred for 15 minutes with the addition of 300 ml. of benzene and 5 grams of anhydrous sodium carbonate and filtered. Benzene, excess ethanol and water formed during the reaction are distilled out of the filtrate. The liquid brown residue is distilled under vacuum. After distilling off a small preliminary run consisting mainly of diethylaniline, there is obtained, at 1.2 torr and at a temperature of 132 to 138 C., 125 grams of ethyl p-(N,N-diethylamino)-benzoate. This corresponds to a yield of 75.3%. The product solidifies while cooling to crystals having a melting point of 43 C.

Example II 419 grams (2 moles) of methyl S-aminoisophthalate, 2 liters of methanol and 8 grams of iodine are heated in an autoclave to 205-210 C. for five hours. The brownish crystals obtained are suctioned out of the reaction product and recrystallized from 3 liters of methanol with the addition of activated carbon thereto. Obtained is 300 grams of almost colorless crystals having a melting point of C. By mixing the mother liquors back with the crystals and recrystallizing, another 92 grams of product having a melting point of 124.5 C. is obtained. The total yield of 392 grams of dimethyl 5-(N,N- dimethylamino)-isophthalate corresponds to a yield of 82.6%.

Example III The reaction mixture obtained by heating 100 grams of 2-methyl5-aminonaphthoate, 500 ml. of methanol and 2 grams of iodine to 200 C. for five hours is treated as described in Example I. During the distillation thereof, 79.5 grams of 2-methyl-5-(N,N-dimethyl'amino)-naphthoate is obtained as the main fraction. This product passes over as a faintly brownish oil at to C. under a pressure of 0.1 torr. This amount of product represents a 66.5% theoretical yield.

The invention being thus described, it will be obvious that the same may be varied in many ways. Such variations are not to be regarded as a departure from the spirit and scope of the invention and all such modifications are intended to be included within the scope of the following claims.

We claim:

1. A process for the preparation of alkyl esters of aromatic N,N-dialkylaminocarboxylic acids having the formula (R) NAr(COOR') wherein Ar is a mononuclear aromatic nucleus, a polynuclear aromatic nucleus, an alkyl-substituted mononuclear aromatic nucleus or an alkyl-substituted polynuclear aromatic nucleus, R and R are alkyl groups and n is a whole number from 1 to 3, which comprises reacting the corresponding aromatic aminocarboxylic acid ester with an alkanol having from 1 to 3 carbon atoms in the presence of a catalytic amount of iodine or a lower alkyl iodide at a temperature of from about 150 to 250 C.

2. The process of claim 1, wherein said alkanol is methanol.

3. The process of claim 1, wherein the reaction is carried out under pressure.

4. The process of claim 1, wherein the reaction is carried out at a temperature of from about 180 to 230 C.

5. The process of claim 1, wherein said iodine or lower alkyl iodide is employed in amounts of from about 0.005 to 0.05 mole per mole of aminocarboxylic acid ester.

6. A process for the preparation of alkyl esters of aromatic N,N-dialkylaminocarboxylic acids having the formula (R) NAr(COOR) wherein Ar is a mononuclear aromatic nucleus, a polynuclear aromatic nucleus, an alkyl-substituted mononuclear aromatic nucleus or an alkyl-substituted polynuclear aromatic nucleus, R is an alkyl group having from 1 to 3 carbon atoms, R is an alkyl group and n is a whole number from 1 to 3, which comprises reacting the corresponding aromatic aminocarboxylic acid ester with an alkanol having from 1 to 3 carbon atoms at a temperature of from about 150 to 250 C. in the presence of from about 0.005 to 0.05 mole per mole of aminocarboxylic acid ester of iodine or a lower alkyl iodide.

7. The process of claim 6, wherein said alkanol is methanol.

8. The process of claim 6, wherein the reaction is carried out under pressure.

References Cited Advanced Organic Chemistry, by Royals (Prentice Hall) 1956, pp. 467 and 468 recited.

LORRAINE A. WEINBERGER, Primary Examiner.

A. THAXTON, Assistant Examiner.