Synthesis method and catalyst of dimethyl 3-(3-oxo-2-pentyl)cyclopentylmalonate

Abstract

The present invention discloses a method and catalyst for the synthesis of dimethyl 3-(3-oxo-2-pentyl)cyclopentylmalonate. [Solution] In the synthesis method, 2-pentyl-2-cyclopentenone and dimethyl malonate are used as raw materials, and are reacted in the presence of a catalyst to prepare and obtain 3-(3-oxo-2-pentyl)cyclopentyl dimethyl malonate, in which the catalyst is an alkaline ionic liquid, the cation moiety of which is formed from a nitrogen-containing heterocyclic compound, and the pH of the alkaline ionic liquid is not less than 10. This synthesis method is environmentally friendly, has a stable reaction, low production costs, and uses the alkaline ionic liquid as a catalyst, so the conversion rate of 2-pentyl-2-cyclopentenone is obviously improved.

Description

Technical Field

[0001] The present invention relates to a method for synthesizing dimethyl 3-(3-oxo-2-pentyl)cyclopentylmalonate and a catalyst therefor.

Background Art

[0002] Methyl 3-oxo-2-pentylcyclopentylacetate, also known as Methyl Dihydrojasmonate (MDJ), belongs to the jasmon compound and is an important synthetic fragrance. MDJ is a transparent liquid with a colorless or light yellow appearance, relatively stable chemical properties, slow volatility, long-lasting fragrance, and does not discolor even when used in flavoring. It is often used in the formulation of oriental fragrances such as jasmine, lily, and tuberose.

[0003] Industrially, methyl dihydrojasmonate is mainly synthesized using cyclopentanone, n-valeraldehyde, and dimethyl malonate as raw materials. The specific process steps are as follows: 1) a step in which cyclopentanone and n-valeraldehyde undergo a condensation dehydration reaction to produce 2-pentylidenecyclopentanone; 2) a step in which 2-pentylidenecyclopentanone undergoes an isomerization reaction to produce 2-pentyl-2-cyclopentenone; 3) a step in which 2-pentyl-2-cyclopentenone and dimethyl malonate undergo a Michael addition reaction to produce dimethyl 3-(3-oxo-2-pentyl)cyclopentylmalonate; and 4) a step in which dimethyl 3-(3-oxo-2-pentyl)cyclopentylmalonate is hydrolyzed and decarboxylated to obtain methyl dihydrojasmonate.

[0004] Regarding the Michael addition reaction of 2-pentyl-2-cyclopentenone and dimethyl malonate to produce dimethyl 3-(3-oxo-2-pentyl)cyclopentylmalonate, currently, sodium methoxide is mainly adopted as a catalyst in the industry. For example, in Chinese Patent CN101429122B, first, 2-pentylcyclopentenone and dimethyl malonate are subjected to addition and decarboxylation with sodium methoxide in a methanol solution as a catalyst to obtain methyl dihydrojasmonate, and a decarboxylation method for synthesizing methyl dihydrojasmonate is disclosed. However, when using sodium methoxide as a catalyst, first, since sodium methoxide cannot be reused, it is necessary to quench the reaction with an acid at the end of the reaction, and it is also necessary to wash the organic phase with a large amount of saturated aqueous sodium bicarbonate solution and brine, generating a large amount of salt-containing wastewater and increasing the environmental load. Second, since sodium methoxide is very sensitive to water during use, even a trace amount of moisture can cause the decomposition of sodium methoxide and lead to reaction instability. Finally, since the viscosity of sodium methoxide is very high, it is necessary to add a large amount of methanol as a solvent during the reaction. However, depending on the addition of the solvent, not only does the energy consumption for separation increase, but there is also a problem of increasing the amount of waste to be treated.

Summary of the Invention

Problems to be Solved by the Invention

[0005] In view of the drawbacks and deficiencies of the prior art, the present invention provides an improved method for synthesizing dimethyl 3-(3-oxo-2-pentyl)cyclopentylmalonate that is environmentally friendly, has a stable reaction, and a low manufacturing cost.

Means for Solving the Problems

[0006] To achieve the above object, the technical means adopted in the present invention are as follows: A method for synthesizing dimethyl 3-(3-oxo-2-pentyl)cyclopentylmalonate, wherein in the said synthesis method, 2-pentyl-2-cyclopentenone and dimethyl malonate are used as raw materials, and they react in the presence of a catalyst to prepare and obtain the said dimethyl 3-(3-oxo-2-pentyl)cyclopentylmalonate. Front record Catalyst has a pH of 10 or more; the said catalyst is prepared by a method including the step of stirring and mixing a nitrogen-containing heterocyclic compound with an aliphatic carboxylate or a hydroxy aliphatic carboxylate or a fluorophosphate. In some embodiments of the present invention, the molar ratio of the nitrogen-containing heterocyclic compound to the aliphatic carboxylate or hydroxy aliphatic carboxylate or fluorophosphate is 0.5.

[0007] In some embodiments of the present invention, the said aliphatic carboxylate is selected from salts of one or more combinations of R1COOH and HOOCR2COOH, the said hydroxy aliphatic carboxylate is selected from salts of one or more combinations of OHR3COOH, the said fluorophosphate is selected from one or more combinations of trifluorophosphate, tetrafluorophosphate and hexafluorophosphate, R1 is selected from C1-C8 alkyl groups, R2 is selected from a single bond or C1-C7 alkylidene groups, and R3 is selected from C1-C5 alkylidene groups.

[0008] In some embodiments of the present invention, the said Catalyst has a pH of 12-14.

[0009] In some embodiments of the present invention, the said nitrogen-containing heterocyclic compound is 1,8-diazabicyclo[5.4.0]undec-7-ene,

Chemical formula

[0010] 4-dimethylaminopyridine

Chemical formula

[0011] and 1,5-diazabicyclo[4.3.0]nona-5-ene

Chemical formula

[0012] is selected from one or more combinations of the following.

[0013] In some embodiments of the present invention, the aliphatic carboxylate is selected from one or more combinations of acetate, propionate, and oxalate; the hydroxy aliphatic carboxylate is selected from one or more combinations of glycolate, hydroxypropionate, and hydroxybutyrate.

[0014] 2-Pentyl-2-cyclopentenone and dimethyl malonate Catalyst undergo a Michael addition reaction to form dimethyl 3-(3-oxo-2-pentyl)cyclopentylmalonate, and the reaction formula is as follows.

[0015]

Chemical formula

[0016] As a result of research, the inventors discovered that a strong alkali with a pH of 10 or higher formed from a nitrogen-containing heterocyclic compound Catalyst when used as a catalyst for the Michael addition reaction of 2-pentyl-2-cyclopentenone and dimethyl malonate to form dimethyl 3-(3-oxo-2-pentyl)cyclopentylmalonate, this reaction does not require a solvent, is environmentally friendly to this reaction environment, the reaction is stable, and the production cost can be reduced.

[0017] In some embodiments of the present invention, the reaction is carried out in the presence of a monodentate phosphine ligand. Depending on the presence of the monodentate phosphine ligand, the conversion rate of 2-pentyl-2-cyclopentenone can be further improved.

[0018] Furthermore, the monodentate phosphine ligand is selected from one or a combination of more than one of triphenylphosphine, [(4-(N,N-dimethylamino)phenyl]di-tert-butylphosphine, diphenyl-2-pyridylphosphine, and 4-(dimethylamino)phenyl diphenylphosphine.

[0019] Preferably, the molar ratio of the monodentate phosphine ligand to the catalyst is 1:(1 - 50).

[0020] In some embodiments of the present invention, the molar ratio of the 2-pentyl-2-cyclopentenone to dimethyl malonate is 1:(0.5 - 5).

[0021] In some embodiments of the present invention, the mass ratio of the catalyst to dimethyl malonate is 1:(10 - 50).

[0022] In some embodiments of the present invention, the synthesis method includes the steps of mixing dimethyl malonate and a catalyst, or mixing dimethyl malonate, a catalyst, and a monodentate phosphine ligand to obtain a mixture, dropping 2-pentyl-2-cyclopentenone into the mixture, and continuing to react by stirring at a certain temperature after the dropping is completed.

[0023] Furthermore, the temperature of the mixture during the dropping is -10 to 30°C, and the dropping time is 1 to 10 hours.

[0024] Furthermore, the certain temperature is -10 to 50°C, and the time at the certain temperature is 1 to 30 hours.

[0025] Preferably, after the dropping is completed, the reaction system is cooled to -5°C and stirred at this temperature to continue the reaction.

[0026] In some embodiments of the present invention, the synthesis method further includes the step of adding water to the reaction system after the reaction is completed, standing still, and separating the layers.

[0027] After standing still and undergoing layer separation, the upper layer is the organic layer and the lower layer is the aqueous layer. When the water in the aqueous layer is removed by distillation, the alkali catalyst can be recovered and obtained.

[0028] The present invention further provides the above-mentioned catalyst.

[0029] The present invention includes a step of stirring and mixing a nitrogen-containing heterocyclic compound with an aliphatic carboxylate or a hydroxyaliphatic carboxylate or a fluorophosphate. The aliphatic carboxylate is selected from salts of one or more combinations of R1COOH and HOOCR2COOH. The hydroxyaliphatic carboxylate is selected from salts of one or more combinations of OHR3COOH. The fluorophosphate is selected from one or more combinations of trifluorophosphate, tetrafluorophosphate, and hexafluorophosphate. R1 is selected from C1-C8 alkyl groups, R2 is selected from a single bond or C1-C7 alkylidene groups, and R3 is selected from C1-C5 alkylidene groups. The present invention further provides a method for preparing the above-mentioned catalyst.

[0030] Preferably, the temperature in the mixing is 20-80°C, and the mixing time is 4-24 hours.

[0031] The above-mentioned catalyst is a pale yellow transparent liquid.

[0032] Compared with the prior art, the present invention has the following advantages.

[0033] Mixing a nitrogen-containing heterocyclic compound with an aliphatic carboxylate or a hydroxyaliphatic carboxylate or a fluorophosphate to form a strong alkali with a pH of 10 or more. Catalyst When used as the catalyst for the synthesis method, this synthesis method does not require a solvent, the reaction conditions are mild, and the conversion rate of 2-pentyl-2-cyclopentenone can be improved.

[0034] The catalyst of the present invention is easy to prepare, easy to recover and reuse, and after multiple reuses, the activity of the catalyst does not change significantly, and the catalyst has good stability.

[0035] The synthesis method of the present invention does not require a solvent and only uses water for catalyst recovery, resulting in less waste, lower costs, and environmental friendliness.

[0036] In the present invention, the conversion rate of 2-pentyl-2-cyclopentenone can be further improved by adding a monodentate phosphine ligand to the reaction system, and the conversion rate can reach 99%. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0037] The present invention will be further described below with reference to examples. However, the present invention is not limited to the following examples. The implementation conditions adopted in the examples can be further adjusted according to different requirements of specific use, and the implementation conditions not specified are general conditions in the industry. The technical features according to various embodiments of the present invention can be combined with each other as long as they are not contradictory to each other.

[0038] Example 1 1) Alkaline Catalyst Preparation of Weigh out 0.5 mol of 1,8-diazabicyclo[5.4.0]undec-7-ene and 1 mol of sodium acetate, place them in a beaker, and stir at a constant temperature of 30°C for 6 hours to obtain the required amount. Catalyst is obtained, the pH of which is 13.2.

[0039] 2) Preparation of dimethyl 3-(3-oxo-2-pentyl)cyclopentylmalonate Above 2g Catalyst Weigh out 50g of dimethyl malonate and place it in a 100mL three-neck flask, place the three-neck flask in a thermostat sink at 25℃, then slowly add 56g of 2-pentyl-2-cyclopentenone dropwise, controlling the addition time to 6 hours. After the addition is complete, lower the temperature of the water bath to -5℃ and stir at a constant temperature for 6 hours.

[0040] 3) Product analysis After the reaction is completed, 10 g of deionized water is added, stirred well, and then allowed to stand for layer separation. The upper layer is the organic phase, and the lower layer is Catalyst an aqueous solution of. The product is analyzed by an Agilent 7890 gas chromatograph, with the chromatographic column being HP-INNOWax and the detector being a TCD detector. The conversion rate and selectivity are calculated by the normalization method.

[0041] Example 2 It is almost the same as Example 1, but the difference is that 4-dimethylaminopyridine is used instead of 1,8-diazabicyclo[5.4.0]undec-7-ene, Catalyst and only the pH of is 11.7.

[0042] Example 3 It is almost the same as Example 1, but the difference is that 1,5-diazabicyclo[4.3.0]nona-5-ene is used instead of 1,8-diazabicyclo[5.4.0]undec-7-ene, Catalyst and only the pH of is 13.4.

[0043] For Examples 1-3, the results of the conversion rate of 2-pentyl-2-cyclopentenone and the selectivity of dimethyl 3-(3-oxo-2-pentyl)cyclopentylmalonate are shown in Table 1 below.

[0044]

Table 1

[0045] As can be seen from Table 1, different nitrogen heterocyclic basicities Catalyst all have excellent activities, with the conversion rate of 2-pentyl-2-cyclopentenone ≥ 90% and the selectivity of dimethyl 3-(3-oxo-2-pentyl)cyclopentylmalonate > 95%.

[0046] Example 4 It is almost the same as Example 1, but the difference is that potassium acetate is used instead of sodium acetate, Catalyst and only the pH of

[0047] Example 5 It is almost the same as Example 1, but the difference is that lithium acetate is used instead of sodium acetate, Catalyst and only the pH of

[0048] For Examples 1, 4 to 5, the conversion rate of 2-pentyl-2-cyclopentenone and the selectivity results of dimethyl 3-(3-oxo-2-pentyl)cyclopentylmalonate are shown in Table 2 below.

[0049]

Table 2

[0050] As can be seen from Table 2, the three cations of sodium, potassium, and lithium do not have a great impact on the activity of the nitrogen-containing heterocyclic base Catalyst , the conversion rate of 2-pentyl-2-cyclopentenone > 90%, and the selectivity of dimethyl 3-(3-oxo-2-pentyl)cyclopentylmalonate > 95%.

[0051] Examples 6 to 13 It is almost the same as Example 1, but the difference is that only an aliphatic carboxylate or a hydroxy fatty carboxylate or a fluorophosphate in Table 3 is used instead of sodium acetate. The conversion rate of 2-pentyl-2-cyclopentenone and the selectivity results of dimethyl 3-(3-oxo-2-pentyl)cyclopentylmalonate for Examples 6 - 13 are shown in Table 3 below.

[0052]

Table 3

[0053] As can be seen from Table 3, the alkalis prepared with different anions in the selected range Catalyst all exhibit excellent catalytic activity, with the conversion rate of 2-pentyl-2-cyclopentenone > 88% and the selectivity of dimethyl 3-(3-oxo-2-pentyl)cyclopentylmalonate > 90%.

[0054] Example 14 In Example 1 Catalyst Perform rotary evaporation on the aqueous solution of, remove water, Catalyst can be reused, and the reuse method is the same as that in Example 1. The reuse results are shown in Table 4 below.

[0055]

Table 4

[0056] As can be seen from Table 4, after 5 times of reuse, the activity of the catalyst does not change much, indicating that the performance of the prepared alkali Catalyst is stable.

[0057] Example 15 1) Preparation of alkali Catalyst The preparation method is the same as that in Example 1.

[0058] 2) Preparation of dimethyl 3-(3-oxo-2-pentyl)cyclopentylmalonate Weigh 2 g of the above Catalyst , 0.3 g of [(4-(N,N-dimethylamino)phenyl]di-tert-butylphosphine and 50 g of dimethyl malonate, place them in a 100 mL three-necked flask, place the three-necked flask in a thermostatic sink at 25 °C, and then slowly add 56 g of 2-pentyl-2-cyclopentenone dropwise, controlling the dropping time to 6 hours. After the dropping is completed, lower the temperature of the water bath to -5 °C and stir at a constant temperature for 6 hours.

[0059] 3) Product analysis The analysis method is the same as that in Example 1.

[0060] Examples 16 - 18 Examples 16 - 18 are almost the same as Example 15. The difference is that triphenylphosphine, diphenyl-2-pyridylphosphine, and 4-(dimethylamino)phenyl diphenylphosphine are used respectively instead of [(4-(N,N-dimethylamino)phenyl]di-tert-butylphosphine. The catalytic performances of Examples 15 - 18 are shown in Table 5 below.

[0061]

Table 5

[0062] As can be seen from Table 5, the addition of a monodentate phosphine ligand can improve the conversion rate of 2-pentyl-2-cyclopentenone, with the conversion rate of 2-pentyl-2-cyclopentenone > 95% and the selectivity of dimethyl 3-(3-oxo-2-pentyl)cyclopentylmalonate > 95%.

[0063] Comparative Example 1 Comparative Example 1 is almost the same as Example 1. The difference is that N-methylimidazole is used instead of 1,8-diazabicyclo[5.4.0]undec-7-ene, Catalyst and the only difference is that the pH of

[0064] As a result, the conversion rate of 2-pentyl-2-cyclopentenone is 41%, and the selectivity of dimethyl 3-(3-oxo-2-pentyl)cyclopentylmalonate is 81%.

[0065] Comparative Example 2 1) Weigh 2 g of 1,8-diazabicyclo[5.4.0]undec-7-ene and 50 g of dimethyl malonate and place them in a 100 mL three-necked flask. Place the three-necked flask in a thermostatic sink at 25 °C. Then, slowly add 56 g of 2-pentyl-2-cyclopentenone dropwise, controlling the dropping time to 6 hours. After the dropping is completed, lower the temperature of the water bath to -5 °C and stir at a constant temperature for 6 hours.

[0066] 2) After the reaction is completed, 10 g of deionized water is added, stirred well, and then allowed to stand for layer separation. The upper layer is the organic phase, and the product is analyzed by gas chromatography.

[0067] Comparative Examples 3 - 4 It is almost the same as Comparative Example 2. The difference is that instead of 1,8 - diazabicyclo[5.4.0]undec - 7 - ene, 4 - dimethylaminopyridine and 1,5 - diazabicyclo[4.3.0]nona - 5 - ene are used respectively. The results of the catalytic activities of Comparative Examples 2 - 4 are shown in Table 6 below.

[0068]

Table 6

[0069] As can be seen from Table 6, a single nitrogen - containing heterocyclic compound can catalyze the reaction between dimethyl malonate and 2 - pentyl - 2 - cyclopentenone, but the conversion rate of 2 - pentyl - 2 - cyclopentenone is significantly decreased. It is shown that after a nitrogen - containing heterocyclic compound and an aliphatic carboxylate or a hydroxy - aliphatic carboxylate or a fluorophosphate Catalyst are formed, the conversion rate of 2 - pentyl - 2 - cyclopentenone can be improved.

[0070] Comparative Example 5 1) Weigh 2 g of sodium acetate, 0.3 g of [(4 - (N,N - dimethylamino)phenyl]di - tert - butylphosphine and 50 g of dimethyl malonate and place them in a 100 mL three - necked flask. Place the three - necked flask in a thermostatic sink at 25 °C. Then, slowly add 56 g of 2 - pentyl - 2 - cyclopentenone, control the dropping time to 6 hours. After the dropping is completed, lower the temperature of the water bath to - 5 °C and stir at a constant temperature for 6 hours.

[0071] 2) After the reaction is completed, 10 g of deionized water is added, stirred well, and then allowed to stand for layer separation. The upper layer is the organic phase. As can be seen from the analysis, dimethyl 3-(3-oxo-2-pentyl)cyclopentylmalonate has not been detected in the reaction product. The above results indicate that the nitrogen-containing heterocyclic compound is the main active site of the reaction.

[0072] The above examples are only for explaining the technical idea and features of the present invention. For the purpose of this, those who know this technology can understand the content of the present invention and implement it accordingly, but the protection scope of the present invention cannot be limited thereby. According to the idea of the present invention, any equivalent changes or modifications that are substantially made should be included in the protection scope of the present invention.

[0073] Neither the endpoints nor any value in the ranges disclosed in this specification should be limited to the exact range or value, and these ranges or values should be understood to include values close to these ranges or values. For numerical ranges, between the endpoint values of each range, between the endpoint value of each range and a single point value, and between single point values, one or more numerical ranges can be obtained by combining them with each other, and these numerical ranges should be regarded as specifically disclosed in this specification.

Claims

1. A method for synthesizing dimethyl 3-(3-oxo-2-pentyl)cyclopentylmalonate, which uses 2-pentyl-2-cyclopentenone and dimethyl malonate as raw materials, reacts in the presence of a catalyst and a monodentate phosphine ligand, and prepares and obtains dimethyl 3-(3-oxo-2-pentyl)cyclopentylmalonate, comprising: The catalyst is prepared by a method including a step of stirring and mixing a nitrogen-containing heterocyclic compound with an aliphatic carboxylate or a hydroxy aliphatic carboxylate or a fluorophosphate, and the molar ratio of the nitrogen-containing heterocyclic compound to the aliphatic carboxylate or the hydroxy aliphatic carboxylate or the fluorophosphate is 0.5; The aliphatic carboxylate or the hydroxy aliphatic carboxylate or the fluorophosphate is selected from one or a combination of more than one of sodium acetate, potassium acetate, lithium acetate, sodium propionate, sodium oxalate, sodium glycolate, sodium hydroxypropionate, sodium hydroxybutyrate, sodium trifluorophosphate, sodium tetrafluorophosphate and sodium hexafluorophosphate; The nitrogen-containing heterocyclic compound is selected from one or a combination of more than one of 1,8-diazabicyclo[5.4.0]undec-7-ene, 4-dimethylaminopyridine and 1,5-diazabicyclo[4.3.0]nona-5-ene; A method for synthesizing dimethyl 3-(3-oxo-2-pentyl)cyclopentylmalonate, characterized by the above.

2. The synthesis method according to Claim 1, characterized in that the temperature in the mixing is 20 to 80°C and the time of the mixing is 4 to 24 hours.

3. The monodentate phosphine ligand is selected from one or a combination of more than one of triphenylphosphine, [(4-(N,N-dimethylamino)phenyl]di-tert-butylphosphine, diphenyl-2-pyridylphosphine and 4-(dimethylamino)phenyl diphenylphosphine, A synthesis method according to Claim 1, characterized by the above.

4. The synthesis method according to Claim 1, characterized in that the molar ratio of the monodentate phosphine ligand to the catalyst is 1:(1 to 50).

5. The molar ratio of the 2-pentyl-2-cyclopentenone to dimethyl malonate is 1:(0.5 to 5), and / or the mass ratio of the catalyst to dimethyl malonate is 1:(10 to 50). The synthesis method according to claim 1, characterized in that.

6. The synthesis method includes a step of mixing dimethyl malonate, the catalyst, and the monodentate phosphine ligand to obtain a mixture, dropping 2-pentyl-2-cyclopentenone into the mixture, and continuing to react by stirring at a certain temperature after the dropping is completed. The synthesis method according to claim 1, characterized in that.

7. The temperature of the mixture during the dropping is -10 to 30 °C, the dropping time is 1 to 10 hours, and / or the certain temperature is -10 to 50 °C, and the time at the certain temperature is 1 to 30 hours. The synthesis method according to claim 6, characterized in that.

8. The synthesis method further includes a step of adding water to the reaction system after the reaction is completed, standing still, and separating the layers. The synthesis method according to claim 6, characterized in that.

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