Claims:1. A process for preparing dimethyl succinyl succinate, the process comprising reacting dimethyl succinate and sodium methoxide in a solvent mixture comprising N-methyl pyrrolidone and dimethyl sulfoxide in a ratio in the range of 70:30 to 95:5, at a temperature in the range of 135-200°C to obtain dimethyl succinyl succinate.

2. The process as claimed in claim 1, wherein sodium methoxide is in a powder form.

3. The process as claimed in claim 1, wherein the solvent mixture comprises N-methyl pyrrolidone and dimethyl sulfoxide in a ratio of 80:20.

4. The process as claimed in claim 1, wherein the temperature is in the range of 150-160 °C.

5. The process as claimed in claim 1, wherein the process is carried out under a nitrogen atmosphere.

6. The process as claimed in claim 1, wherein the reaction is carried out for 3-4 hours.

7. The process as claimed in claim 1, wherein 1-1.2 moles of sodium methoxide is reacted with a mole of dimethyl succinate.

8. The process as claimed in claim 1, wherein the ratio of sodium methoxide, dimethyl succinate, and the solvent mixture is in the range of 3.5:9:30 to 4.5:12:70.

9. The process as claimed in claim 1, wherein the solvent mixture is recycled.

10. The process as claimed in claim 1 wherein the reacting comprises:
preparing a reaction mixture by adding sodium methoxide and dimethyl succinate into the solvent mixture, wherein sodium methoxide is added in the range of 1 to 1.2 moles per mole of dimethyl succinate;
maintaining the reaction mixture at a temperature in the range of 150-160°C for 3-4 hours while constantly stirring;
cooling and filtering the reaction mixture to obtain sodium salt of dimethyl succinyl succinate;
dissolving the sodium salt of dimethyl succinyl succinate in water to obtain a solution; and
adding sulfuric acid to the solution till the pH of the solution is in the range of 6-7 to obtain a precipitate of dimethyl succinyl succinate.

11. The process as claimed in any of claims 1-10, wherein sodium methoxide and dimethyl succinate are added under continuous stirring.

12. The process as claimed in claim 10, wherein the preparing a reaction mixture comprises:
adding sodium methoxide into the solvent mixture at room temperature;
heating the sodium methoxide and the solvent mixture at a temperature in the range of 50-55°C to obtain a sodium methoxide solvent solution; and
adding dimethyl succinate to the sodium methoxide solvent solution to obtain the reaction mixture.

13. The process as claimed in claim 10, wherein prior to the dissolving in water the sodium salt of dimethyl succinyl succinate is washed with methanol till dimethyl succinate is completely removed.

14. The process of claim 10, wherein sulfuric acid is added to the solution under continuous vigorous stirring.

15. The process as claimed in claim 10 further comprising filtering, washing, and drying the precipitated dimethyl succinyl succinate.

16. The process as claimed in claim 15, wherein the washing is carried out with water till the ¬¬¬¬¬¬total dissolved solids in filtrate are less than 400 ppm.
17. The process as claimed in claim 15, wherein the drying is carried out till the moisture of the precipitated dimethyl succinyl succinate is less than 1% as detected by loss in weight method at 120 °C.
, Description:TECHNICAL FIELD

The present invention relates to a process for preparing dimethyl succinyl succinate.

BACKGROUND

Dimethyl succinyl succinate is used as an intermediate for the manufacture of high-performance quinacridone dyes. For use as an intermediate in the manufacture of quinacridone dyes, high purity of dimethyl succinyl succinate is required. Several processes for preparing dimethyl succinyl succinate are known in the art.

JP4005256A discloses a process of preparation of dimethyl succinyl succinate by condensing dimethyl succinate at 80-180°C in a solvent containing xylene and toluene in the presence of sodium methoxide and dimethyl sulfoxide. The precipitated dimethyl succinyl succinate metal salt so obtained is neutralized with acid and then subjected to washing and drying to obtain dimethyl succinyl succinate.

JP8268960A discloses a process that involves heating a mixture of xylene, dimethyl sulfoxide, dimethyl succinate at 130°C, and adding sodium methylate dropwise. The mixture is aged at 130°C for 1 hr and then cooled to 25°C. Sulfuric acid is then added to neutralize the mixture. The mixture is then heated to 90°C and cooled to obtain dimethyl succinyl succinate.

US3045040 discloses a process for the preparation of 2, 5-diarylamino-3, 6-dihydroterephthalic acid esters. In the disclosed process, first, a di-alkali metal salt of succinylosuccinic acid ester is prepared by condensation of succinic acid ester (dimethyl succinate, or diethyl succinate) with alkali metal alcoholate (sodium methylate, potassium methylate) in an organic solvent (N-methyl-2pyrrolidone) at a temperature of 150°C, preferably to 110-120°C for 7-8 hrs. The di-alkali metal salt of the succinylosuccinic acid ester is then further condensed in the presence of an acid-reacting substance with an arylamino compound to form the corresponding 2, 5 diarylamino-3,6-dihydroterephthalic acid ester.

EP0166214B1 discloses a process of preparing dialkyl succinylosuccinates by adding sodium methylate in methanol to dimethyl succinate and heating the mixture so obtained to 100-130°C. According to the disclosure, dimethyl succinate acts as both a reaction component and as a solvent for the reaction.

The processes known in the art involve reacting dimethyl succinate with sodium methoxide in different solvents like methanol, N-methyl-2-pyrrolidone, dimethylformamide, xylene-dimethyl sulfoxide, methanol-dioxane while maintaining specific reaction parameters like temperature, reaction time, etc. The known processes generally give a low yield of about 65-80 % and require long reaction time. Some of the conventional processes also require recrystallization of the final product to get the desired purity.

SUMMARY

The present disclosure relates to a process for preparing dimethyl succinyl succinate, the process comprising reacting dimethyl succinate and sodium methoxide in a solvent mixture comprising N-methyl pyrrolidone and dimethyl sulfoxide in a ratio in the range of 70:30 to 95:5, at a temperature in the range of 135-200°C to obtain dimethyl succinyl succinate.

BRIEF DESCRIPTION OF DRAWINGS

FIG. 1 depicts the effect of reaction temperature on the yield of dimethyl succinyl succinate in accordance with an embodiment of the present disclosure.

FIG. 2 depicts the effect of reaction time on the yield of dimethyl succinyl succinate in accordance with an embodiment of the present disclosure.

FIG. 3 depicts the synergistic effect of a combination of N-methyl pyrrolidone and dimethyl sulfoxide in a solvent mixture on the yield of dimethyl succinyl succinate and reaction time in accordance with an embodiment of the present disclosure.
DETAILED DESCRIPTION

For the purpose of promoting an understanding of the principles of the disclosure, reference will now be made to embodiments and specific language will be used to describe the same. It will nevertheless be understood that no limitation of the scope of the disclosure is thereby intended, such alterations and further modifications in the disclosed composition and method, and such further applications of the principles of the disclosure therein being contemplated as would normally occur to one skilled in the art to which the disclosure relates.

It will be understood by those skilled in the art that the foregoing general description and the following detailed description are exemplary and explanatory of the disclosure and are not intended to be restrictive thereof.

Reference throughout this specification to “one embodiment”, “an embodiment” or similar language means that a particular feature, structure, or characteristic described in connection with the embodiment is included in at least one embodiment of the present disclosure. Thus, appearances of the phrase “in one embodiment”, “in an embodiment” and similar language throughout this specification may, but do not necessarily, all refer to the same embodiment.

The present disclosure relates to a process for preparing dimethyl succinyl succinate. The process comprises reacting dimethyl succinate and sodium methoxide in a solvent mixture comprising N-methyl pyrrolidone and dimethyl sulfoxide in a ratio in the range of 70:30 to 95:5, at a temperature in the range of 135-200°C to obtain dimethyl succinyl succinate.

In the disclosed process, 1-1.2 moles of sodium methoxide is reacted with a mole of dimethyl succinate. In accordance with an embodiment, 1.1 moles of sodium methoxide is reacted with a mole of dimethyl succinate. Sodium methoxide may be used in a form of an alcoholic solution or as a powder. In accordance with an embodiment, sodium methoxide used is in a powder form.

The solvent mixture may be taken in an amount sufficient to dissolve sodium methoxide and dimethyl succinate. In accordance with an embodiment, the ratio of sodium methoxide, dimethyl succinate, and the solvent mixture is in the range of 3.5:9:30 to 4.5:12:70. In accordance with an embodiment, the ratio is ¬¬¬ 4.2:10:40.

In accordance with an embodiment, the solvent mixture comprises N-methyl pyrrolidone and dimethyl sulfoxide in a ratio of 80:20. In accordance with an embodiment, the solvent mixture is recycled. In an aspect, the solvent mixture is recycled 10 times. In another aspect, the solvent mixture is recycled 5 times.

In accordance with an embodiment, the temperature is in the range of 150-160°C. In an embodiment, the process is carried out under a nitrogen atmosphere. In an embodiment, the reaction is carried out for 3-4 hours.
In accordance with an embodiment, the reacting comprises preparing a reaction mixture by adding sodium methoxide and dimethyl succinate into the solvent mixture wherein sodium methoxide is added in the range of 1 to 1.2 moles per mole of dimethyl succinate, maintaining the reaction mixture at a temperature in the range of 150-160°C for 3-4 hours while constantly stirring, cooling and filtering the reaction mixture to obtain sodium salt of dimethyl succinyl succinate, dissolving the sodium salt of dimethyl succinyl succinate in water to obtain a solution, and adding sulfuric acid to the solution till the pH of the solution is in the range of 6-7 to obtain a precipitate of dimethyl succinyl succinate.

Sodium methoxide and dimethyl succinate can be added simultaneously or sequentially in any order. In accordance with an embodiment, the reaction mixture is prepared by adding sodium methoxide into the solvent mixture at room temperature, heating the sodium methoxide and the solvent mixture at a temperature in the range of 50-55°C to obtain a sodium methoxide solvent solution, and adding dimethyl succinate to the sodium methoxide solvent solution to obtain the reaction mixture. In accordance with an embodiment, sodium methoxide and dimethyl succinate are added under continuous stirring.

In accordance with an embodiment, the sodium salt of dimethyl succinyl succinate is washed using methanol till dimethyl succinate is completely removed before it is dissolved in water. In accordance with an embodiment, 99% methanol is used for washing the sodium salt of dimethyl succinyl succinate.
In an embodiment, ¬¬¬¬15-30% sulfuric acid solution is added to the solution. In accordance with an embodiment sulfuric acid is added under continuous vigorous stirring.

The precipitated dimethyl succinyl succinate is filtered and then subjected to further processing according to conventional methods or techniques. In accordance with an embodiment, the filtered precipitate of dimethyl succinyl succinate is subjected to washing and drying. The precipitated dimethyl succinyl succinate is washed to remove the traces of sodium sulfate. In accordance with an embodiment, the washing is carried out with water until the ¬¬¬¬¬¬total dissolved solids in filtrate are less than 400 ppm, preferably less than 200 ppm. In accordance with an embodiment, the drying is carried out till the moisture of the precipitated dimethyl succinyl succinate is less than 1% as detected by the loss in weight method at 120°C.

EXAMPLES

Example 1: Synthesis of dimethyl succinyl succinate: 400 ml of a solvent mixture containing N-methyl pyrrolidone and dimethyl sulfoxide in a ratio of 80:20 ratio was taken in a reaction vessel. The reaction vessel was set at a temperature of 30±5 oC and stirred at a stirring rate of ~200±10 rpm. The reaction vessel was fitted with an appropriate condenser cooled with water circulation. An arrangement was made for the blanketing of the reaction vessel with nitrogen gas. 42 g of sodium methoxide powder was separately weighed and slowly added into the solvent mixture. The temperature of the reaction vessel was then slowly raised. Once the temperature reached 50±5oC, the addition of 100 g of dimethyl succinate into the reaction vessel was started at a flow rate of 3.33 ml/min to obtain a reaction mixture. After the addition of dimethyl succinate was complete, the temperature of the reaction vessel was set at 150oC. Once the temperature reached 150oC, the reaction mixture was maintained for the next 3.5 hours under constant stirring. After 3.5 hours, the reaction vessel was cooled to 45 oC. Thereafter, the reaction mixture was filtered. The filter cake containing sodium salt of dimethyl succinyl succinate was washed with methanol multiple times till dimethyl succinate was removed from the filtrate as shown by thin-layer chromatography. Thereafter, 1 liter of water was taken in a beaker and stirred at 200 rpm. The washed sodium salt of dimethyl succinyl succinate was added to water while continuing the stirring. Once the sodium salt of dimethyl succinyl succinate was completely dissolved, 20% sulfuric acid was added slowly under continuous vigorous stirring till the pH of the solution reached 6-7. The dimethyl succinyl succinate was precipitated. The precipitate of dimethyl succinyl succinate was separated by filtration and washed with water for removal of traces of sodium sulfate till the total dissolved solids in the filtrate were less than 200 ppm. The washed dimethyl succinyl succinate precipitate was dried in an air circulated oven maintained at a temperature of 100°C till the moisture of dimethyl succinyl succinate was less than 1% as detected by loss in weight method at 120°C. Characterization of synthesized dimethyl succinyl succinate was carried out.

The effect of various types of solvents, reaction time, and reaction temperature on the yield of dimethyl succinyl succinate prepared by reacting dimethyl succinate and sodium methoxide was studied. The results and observations are provided below.

A. The effect of solvents on the yield of dimethyl succuny succinate: Table 1 shows the effect of different solvents on the yield of dimethyl succinyl succinate.

Table 1: Effect of Different Solvents

S. No. Solvent Temperature (°C) Time (Hr) Yield (%)
1a N-methyl pyrrolidone 150-160 7 97
1b N-methyl pyrrolidone 150-160 3.5 73
1c N-methyl pyrrolidone 120 7 59
2a Dimethyl sulfoxide 150-160 3.5 NR
2b Dimethyl sulfoxide
200 3.5 NR
3a Xylene and dimethyl sulfoxide 120 7 71
3b Xylene and dimethyl sulfoxide 150 7 79
4a Xylene, Toluene, and dimethyl sulfoxide 150 7 74
5a N-methyl pyrrolidone and dimethyl sulfoxide 150-160 3.5 97
5b N-methyl pyrrolidone and dimethyl sulfoxide 150-160 3.5 95.8
5c N-methyl pyrrolidone and dimethyl sulfoxide 120 7 65

Observations: The process using only N-methyl pyrrolidone as a solvent (1a-1c), requires higher reaction time and temperature to provide a good yield. The process using dimethyl sulfoxide (2a-2b) alone does not provide the desired product (degradation of material observed). The process using N-methyl pyrrolidone and dimethyl sulfoxide (5a-5b) provides higher yield in less reaction time at a temperature of 150-160°C. However, a lower temperature of 120°C does not provide a high yield (5c). Dimethyl sulfoxide does not give the same synergistic effect with xylene (3a-3b) or with xylene and toluene (4a) as with N-methyl pyrrolidone.

B. Effect of reaction temperature on the yield of dimethyl succinyl succinate: Table 2 and FIG. 1 show the effect of temperature on the yield of dimethyl succinyl succinate prepared in accordance with the present disclosure.

TABLE: 2: Effect of reaction temperature on the yield of dimethyl succinyl succinate
S. No. Temperature (°C) Time (Hr) Yield (%)

1 150-160 7 97
2 120 7 65
3 100 7 44

Observations: As the temperature increases from 100 oC to 150-160 °C the yield of dimethyl succinyl succinate increases.

C. Effect of reaction time on the yield of dimethyl succinyl succinate: Table 3 and FIG. 2 show the effect of reaction time on the yield of dimethyl succinyl succinate prepared in accordance with the present disclosure.

Table 3: Effect of reaction time on the dimethyl succinyl succinate yield

S. No. Temperature (°C)
Time (Hr) Yield (%)

1 150 1.5 71
2 150 3.5 97
3 150 7 97

Observations: As the reaction time increases, yield increases. The reaction completes in 3.5 hr (97% yield) and thereafter, there is no further increase in the yield.

Effect of a solvent on the yield of dimethyl succinyl succinate: Table 4 and FIG. 3 show the synergistic effect of a combination of N-methyl pyrrolidone and dimethyl sulfoxide in a solvent mixture on the yield of dimethyl succinyl succinate and reaction time in accordance with an embodiment of the present disclosure.

TABLE: 4: Effect of a solvent on dimethyl succinyl succinate yield

S. No. Solvent
Temperature (°C)
Time (Hr) Yield (%)
1 N-methyl pyrrolidone and dimethyl sulfoxide 150 3.5 97
2 N-methyl pyrrolidone 150 3.5 73
3 N-methyl pyrrolidone 150 7 97
4 Xylene and dimethyl sulfoxide 150 7 79

Observations: Dimethyl sulfoxide gives a good synergistic effect with N-methyl pyrrolidone and helps in improving yield and reducing reaction time. Dimethyl sulfoxide does not give the same synergistic effect with xylene.
INDUSTRIAL APPLICABILITY

The present disclosure provides an efficient, safe, fast, highly productive, and environmently friendly process for the preparation of highly pure dimethyl succinyl succinate. The disclosed process provides more than 95% yield. The process is completed in a shorter period. The solvent mixture used in the disclosed process can be recycled and reused many times without affecting the quality of dimethyl succinyl succinate. The disclosed process allows one to avoid the use of methanol in the reactants, which results in ease of handling and transportation, allows achieving higher reaction temperatures, elimination of separation, and distillation steps.