A method for preparing pseudoionone

Abstract

The invention provides a method for preparing pseudoionone, the method comprising: under nitrogen protection conditions, using citral and acetoacetate compounds as raw materials, using secondary amine organic bases as condensation catalysts, and preparing intermediate 2-acetyl-5,9-dimethyl-dew-2,4,8-trienoic acid ester compounds; intermediate 2-acetyl-5,9-dimethyl-dew-2,4,8-trienoic acid ester compounds and dilute sodium bicarbonate aqueous solution are subjected to hydrolysis and decarboxylation reaction to prepare pseudoionone. The preparation method of the present invention has high yield, simple operation, less wastewater and environmental protection, and the catalyst is easily recovered, and the yield of the obtained pseudoionone is more than 97%, and its purity is more than 97%.

Description

Technical Field

[0001] The invention belongs to the technical field of chemical synthesis and relates to a method for preparing pseudoionone. Background Art

[0002] Pseudoionone is an important intermediate for synthesizing flavors and fragrances such as vitamin A, vitamin E, ionone and carotene. It was prepared by Tiemann in 1893 by condensing citral with acetone under alkaline conditions. Now, most industries still use this method to synthesize pseudoionone. Commonly used condensation catalysts are strong alkaline aqueous solutions such as potassium hydroxide, sodium hydroxide, and lithium hydroxide. Due to the excessive alkalinity of the catalyst system, the raw material citral is prone to self-polymerization, deep condensation and other side reactions, resulting in low product yields. The highest yield of this method is mostly around 85%. In addition, the reactant acetone in this method is excessive, and there is a problem of high energy consumption for acetone recovery. After the reaction, the alkaline catalyst is difficult to separate from the reactants, resulting in complex post-processing of this method, generating a large amount of waste alkaline water, corroding equipment, and polluting the environment.

[0003] Domestic and foreign scholars have been committed to the research on the synthesis of pseudoionone, but most of them are still based on the condensation reaction of citral and acetone. Solid bases and alkaline ionic liquids have appeared as catalysts to replace liquid bases. For example, U.S. Patent No. 4,874,900 (1987) describes a method for preparing pseudoionone by condensing citral and acetone with lithium hydroxide as a solid base. The method performs the condensation reaction intermittently or continuously at -20 to 200° C. The method has the problem that the solid base catalyst is difficult to filter and separate, and has the disadvantages of long reaction time, low yield, and poor catalyst application effect.

[0004] Tomek, B. et al. (Tomek B., Cvrtnvk J. Czech. [J], 1961, 100648.) used strong alkaline anion exchange resin (such as Amberlite IRA-400, 401 Zerolite FFP and Duolite A-40, etc.) instead of strong alkaline solution as catalyst, and reacted under the condition of continuous separation of water. The yield of pseudoionone was 73% to 84.6% and the purity was 95% to 97%. Due to the slow reaction speed and long reaction time, it is not suitable for industrial production.

[0005] Therefore, according to the above-mentioned deficiencies in the existing technology for preparing pseudoionone by condensation of citral and acetone, it is necessary to develop a new process route for the preparation of pseudoionone. Summary of the invention

[0006] The present invention aims to provide a novel method for preparing pseudoionone. In order to achieve the above object, the preparation method of the present invention comprises the following steps: (1) using citral as shown in formula (a) and acetoacetate compounds as shown in formula (b) as raw materials, wherein the acetoacetate compounds are methyl acetoacetate, ethyl acetoacetate or isopropyl acetoacetate, using secondary amine as catalyst, wherein the secondary amine is piperidine, morpholine, diethylamine or dipropylamine, and controlling the reaction temperature to 10 to 30° C. under nitrogen atmosphere for condensation reaction to obtain the intermediate 2-acetyl-5,9-dimethyl-2,4,8-trienoate compounds as shown in formula (c), and the reaction equation is as follows:

[0007]

[0008] 2) The intermediate 2-acetyl-5,9-dimethyl-2,4,8-trienoic acid ester compound as shown in formula (c) is mixed with a dilute aqueous sodium bicarbonate solution, and the reaction temperature is controlled at 35 to 50° C. to perform a hydrolysis and decarboxylation reaction to obtain a pseudoionone as shown in formula (d). The reaction equation is as follows:

[0009]

[0010] In the preferred technical scheme of the preparation method of the present invention, preferably, in step (1), the molar ratio of citral, the acetoacetate compound and the secondary amine is 1:1-1.5:0.002-0.005.

[0011] In the preferred technical scheme of the preparation method of the present invention, preferably, in step (1), the reaction time is 1 to 3 hours.

[0012] In the preferred technical scheme of the preparation method of the present invention, preferably, in step (1), when the citral content in GC analysis is less than 1.0wt.%, distillation is performed to recover the intermediate 2-acetyl-5,9-dimethyl-2,4,8-trienoic acid ester compound.

[0013] In the preferred technical solution of the preparation method of the present invention, preferably, in step (2), the mass concentration of the dilute sodium bicarbonate aqueous solution is 1 to 1.5 wt.%.

[0014] In the preferred technical solution of the preparation method of the present invention, preferably, in step (2), the reaction time is 1 to 3 hours.

[0015] In the preferred technical scheme of the preparation method of the present invention, preferably, in step (2), when the GC analysis shows that the content of the intermediate 2-acetyl-5,9-dimethyl-2,4,8-trienoic acid ester compound is less than 1.0wt.%, the layers are separated, the oil layer is washed with a small amount of deionized water to a neutral pH, and the pseudo-ionone content is obtained by distillation to reach more than 97.5%.

[0016] The method of the present invention uses citral and acetoacetate compounds to carry out condensation reaction under the catalyst of secondary amine organic base compounds to obtain intermediate 2-acetyl-5,9-dimethyl-kuei-2,4,8-trienoate compounds; then the 2-acetyl-5,9-dimethyl-kuei-2,4,8-trienoate compounds are subjected to decarboxylation reaction under dilute sodium bicarbonate aqueous solution to obtain pseudoionone. The method of the present invention has a higher yield than the traditional inorganic strong base catalyzed condensation of citral and acetone to prepare pseudoionone. The main reason is that the activation energy of the methyl groups on both sides of the carbonyl group is significantly lower than that of the methylene group, so under the catalytic conditions of organic base, only one position can participate in the reaction; while under the catalysis of inorganic strong base, the α hydrogen positions on both sides of the acetone carbonyl group are equivalent, which will react deeply on the one hand, and it is also difficult to activate. Therefore, this method not only has a high yield, but also has the advantages of high efficiency, less wastewater, and easy separation and recovery of the catalyst.

[0017] Compared with the methods of the prior art, the method of the present invention has the following beneficial effects: since pseudoionone is prepared by condensing acetoacetate compounds with citral, the method has the advantages of high reaction efficiency, high atom utilization, high selectivity, easy catalyst recovery and reuse, no environmental pollution, etc. The yield of the prepared pseudoionone is more than 97%, and the purity thereof reaches more than 97%, and the yield is better than that reported in existing data. BRIEF DESCRIPTION OF THE DRAWINGS

[0018] Figure 1 HNMR spectrum of condensation intermediate C

[0019] Figure 1A HNMR local enlargement of condensation intermediate C Figure 1 ;

[0020] Figure 1B HNMR local enlargement of condensation intermediate C Figure 2 ;

[0021] Figure 2 is the CNMR diagram of condensation intermediate C;

[0022] Figure 2A A partial enlargement of the CNMR of the condensation intermediate C Figure 1 ;

[0023] Figure 2BA partial enlargement of the CNMR of the condensation intermediate C Figure 2 ;

[0024] Figure 3 DEPT135NMR diagram of condensation intermediate C;

[0025] Figure 4 is the HNMR spectrum of the product pseudoionone D;

[0026] Figure 4A This is a partial enlargement of the HNMR of the product pseudoionone D Figure 1 ;

[0027] Figure 4B This is a partial enlargement of the HNMR of the product pseudoionone D Figure 2 ;

[0028] Figure 5 is the CNMR diagram of the product pseudoionone D;

[0029] Figure 5A This is a partial enlargement of the CNMR of the product pseudoionone D Figure 1 ;

[0030] Figure 5B This is a partial enlargement of the CNMR of the product pseudoionone D Figure 2 ;

[0031] Figure 6 This is the DEPT135 NMR spectrum of the product pseudoionone D. DETAILED DESCRIPTION

[0032] The present invention will be further described below by way of examples, but are not limited thereto.

[0033] Example 1

[0034] Weigh 100.0 g (0.658 mol) of citral, 80.1 g (0.691 mol) of methyl acetoacetate and 0.120 g (1.40 mmol) of piperidine in a 500 ml three-necked flask, replace with nitrogen, control the internal temperature at 10-20 ° C, react for 1.5 h under nitrogen protection, take samples for GC analysis, and when the citral content is less than 0.5%, stop the reaction, and recover by vacuum distillation to obtain 165 g of the intermediate 2-acetyl-5,9-dimethyl-kui-2,4,8-trienoic acid methyl ester, which is a mixture of the following two structures, with a yield of 98.8%, a GC content of 98.5%, and a structural analysis of the intermediate. Figure 1 , Figure 1A , Figure 1B , Figure 2 , Figure 2A , Figure 2B , Figure 3 .

[0035]

[0036] NMR C1 (cis-trans mixture, taking the main component as an example):

[0037] 1 H NMR(400MHz, CDCl3)δ7.595(d,1H,J=12.4),6.298(d,1H,J=12.4),5.064(m,1H),4.264(q,2H ,J=7.2),2.393(s,3H),2.106-201(m,4H),1.940(s,3H),1.587(s,6H),1.290(t,3H,J=7.2).

[0038] 13 C NMR (100MHz, CDCl3) δ201.43,165.65,156.02,139.97,132.42,130.22,123.07,120.51,60.98,40.84,31.29,26.26,25.18,17.70,17.51,14.21.

[0039] DEPT135 NMR (100MHz, CDCl3) δ140.01,123.10,120.53,60.98(D),40.87(D),31.32,26.29(D),25.18,17.73,17.54,14.23.

[0040] NMR C2:

[0041] 1 HNMR (400MHz, CDCl3) δ6.357(d,1H,J=10.0),5.090(d,1H,J=10.0),5.043(m,1H),4.177(q,2H,J= 7.2),2.270(s,3H),1.980-2.060(m,2H),1.669(s,6H),1.511-1.758(m,2H),1.314(t,3H,J=7.2).

[0042] 13 C NMR (100MHz, CDCl3) δ166.56,166.03,131.79,123.86,120.31,119.67,102.52,80.56,59.72,40.99,26.44,25.65,22.55,20.18,17.58,14.38.

[0043] DEPT135 NMR (100MHz, CDCl3) δ123.86,120.31,119.67,59.75(D),41.01(D),26.47,25.69,22.58(D),20.21,17.61,14.41.

[0044] Weigh 160g of the intermediate 2-acetyl-5,9-dimethyl-2,4,8-trienoic acid methyl ester obtained in the previous step and 20g of 1wt.% sodium bicarbonate aqueous solution in a 500ml three-necked flask, control the internal temperature at 35-45°C, and perform hydrolysis and decarboxylation reaction for 1h. When the content of the intermediate 2-acetyl-5,9-dimethyl-2,4,8-trienoic acid methyl ester is less than 0.5%, stop the reaction, cool and separate the layers, wash the oil layer with a small amount of deionized water until the pH is neutral, and obtain pseudoionone by distillation, with a total yield of 97% and a GC content of 98.0%. For the structural analysis of pseudoionone (cis-trans mixture, taking the main component as an example), see Figure 4 , Figure 4A , Figure 4B , Figure 5 , Figure 5A , Figure 5B , Figure 6 .

[0045] 1 H NMR (400MHz, CDCl3) δ7.417(t,1H,J=12.0),6.052(t,1H,J=12.8),5.993(d,1H,J=9.2),5.059-5.120(m, 1H),2.263(s,3H),2.296-2.326(m,1H),2.125-2.156(m,3H),1.902(s,3H),1.673(s,3H),1.598(s,3H).

[0046] 13 C NMR (100MHz, CDCl3) δ198.80,151.18,139.59,132.28,128.39,123.67,123.19,40.44,27.51,26.86,25.69,17.71,17.53.

[0047] DEPT135 NMR (100MHz, CDCl3) δ139.59, 128.39, 123.67, 123.19, 40.44 (D), 27.51, 26.86 (D), 25.69, 17.71, 17.53.

[0048] Example 2

[0049] Weigh 100.0g (0.658mol) of citral, 102.6 (0.789mol) of ethyl acetoacetate and 0.150g (1.74mmol) of piperidine in a 500ml three-necked flask, replace with nitrogen, control the internal temperature at 10-20°C, react for 2h under nitrogen protection, sample GC analysis and when the citral content is less than 0.5%, stop the reaction, and recover by vacuum distillation to obtain 172g of intermediate 2-acetyl-5,9-dimethyl-kui-2,4,8-trienoic acid ethyl ester, with a yield of 98.1% and a GC content of 99.1%. The product NMR spectrum and data are consistent with those in Example 1.

[0050] Weigh 170g of the intermediate 2-acetyl-5,9-dimethyl-kuei-2,4,8-trienoic acid ethyl ester obtained in the previous step, 20g of 1wt.% sodium bicarbonate aqueous solution in a 500ml three-necked flask, control the internal temperature at 35-45°C, hydrolyze and decarboxylate for 1.5h, sample and analyze the intermediate 2-acetyl-5,9-dimethyl-kuei-2,4,8-trienoic acid ethyl ester content when it is less than 0.5%, stop the reaction, cool and stratify, wash the oil layer with a small amount of deionized water to neutral pH, and obtain pseudoionone by distillation, with a total yield of 97.3% and a GC content of 98.4%. The product NMR spectrum and data are consistent with those in Example 1.

[0051] Example 3

[0052] Weigh 250g (1.645mol) of citral, 210g (1.810mol) of methyl acetoacetate and 0.300g (4.11mmol) of diethylamine in a 1000ml three-necked flask, replace with nitrogen, control the internal temperature at 20-30°C, react for 1.5h under nitrogen protection, sample GC analysis and when the citral content is less than 0.5%, stop the reaction, and recover by vacuum distillation to obtain 408g of intermediate 2-acetyl-5,9-dimethyl-kui-2,4,8-trienoic acid methyl ester, with a yield of 98.6% and a GC content of 99.4%. The product NMR spectrum and data are consistent with those in Example 1.

[0053] Weigh 400g of the intermediate 2-acetyl-5,9-dimethyl-kuei-2,4,8-trienoic acid methyl ester obtained in the previous step, 50g of 1.5wt.% sodium bicarbonate aqueous solution in a 1000ml three-necked flask, control the internal temperature at 40-50°C, decarboxylation reaction for 1.5h, sample GC analysis of the intermediate 2-acetyl-5,9-dimethyl-kuei-2,4,8-trienoic acid methyl ester content is less than 0.5%, stop the reaction, cool and stratify, wash the oil layer with a small amount of deionized water to neutral pH, and obtain pseudoionone by distillation, with a total yield of 98% and a GC content of 98.2%. The product NMR spectrum and data are consistent with those in Example 1.

[0054] Example 4

[0055] Weigh 250g (1.645mol) of citral, 210g (1.810mol) of methyl acetoacetate and 0.300g (3.45mmol) of morpholine in a 1000ml three-necked flask, replace with nitrogen, control the internal temperature at 20-30°C, react for 2.5h under nitrogen protection, sample GC analysis and when the citral content is less than 0.5%, stop the reaction, and recover by vacuum distillation to obtain 409g of intermediate 2-acetyl-5,9-dimethyl-kui-2,4,8-trienoic acid methyl ester, with a yield of 98.3% and a GC content of 98.8%. The product NMR spectrum and data are consistent with those in Example 1.

[0056] Weigh 405g of the intermediate 2-acetyl-5,9-dimethyl-kuei-2,4,8-trienoic acid methyl ester obtained in the previous step, 50g of 1.5wt.% sodium bicarbonate aqueous solution in a 1000ml three-necked flask, control the internal temperature at 40-50°C, decarboxylation reaction for 2h, sample GC analysis of the intermediate 2-acetyl-5,9-dimethyl-kuei-2,4,8-trienoic acid methyl ester content is less than 0.5%, stop the reaction, cool and stratify, wash the oil layer with a small amount of deionized water until the pH is neutral, and obtain pseudoionone by distillation, with a total yield of 97% and a GC content of 97.5%. The product NMR spectrum and data are consistent with those in Example 1.

[0057] Example 5

[0058] Weigh 200g (1.316mol) of citral, 180g (1.385mol) of ethyl acetoacetate and 0.300g (3.45mmol) of morpholine in a 1000ml three-necked flask, replace with nitrogen, control the internal temperature at 20-30°C, react for 2h under nitrogen protection, sample GC analysis and when the citral content is less than 0.5%, stop the reaction, and recover by vacuum distillation to obtain 345g of intermediate 2-acetyl-5,9-dimethyl-kui-2,4,8-trienoic acid ethyl ester, with a yield of 98.1% and a GC content of 98.8%. The product NMR spectrum and data are consistent with those in Example 1.

[0059] Weigh 340g of the intermediate 2-acetyl-5,9-dimethyl-kuei-2,4,8-trienoic acid ethyl ester obtained in the previous step, 45g of 1.3wt.% sodium bicarbonate aqueous solution in a 1000ml three-necked flask, control the internal temperature at 40-50°C, decarboxylation reaction for 2h, sample GC analysis of the intermediate 2-acetyl-5,9-dimethyl-kuei-2,4,8-trienoic acid ethyl ester content is less than 0.5%, stop the reaction, cool and stratify, wash the oil layer with a small amount of deionized water until the pH is neutral, and obtain pseudoionone by distillation, with a total yield of 97.2% and a GC content of 97.5%. The product NMR spectrum and data are consistent with those in Example 1.

[0060] Example 6

[0061] Weigh 200g (1.316mol) of citral, 227g (1.576mol) of isopropyl acetoacetate and 0.300g (2.97mmol) of dipropylamine in a 1000ml three-necked flask, replace with nitrogen, control the internal temperature at 20-30°C, react for 2.5h under nitrogen protection, sample GC analysis and when the citral content is less than 0.5%, stop the reaction, and recover by vacuum distillation to obtain 364g of intermediate 2-acetyl-5,9-dimethyl-sunflower-2,4,8-trienoic acid isopropyl ester, with a yield of 97.6% and a GC content of 98.1%. The product NMR spectrum and data are consistent with those in Example 1.

[0062] Weigh 360g of the intermediate 2-acetyl-5,9-dimethyl-2,4,8-trienoic acid isopropyl ester obtained in the previous step, 50g of 1.5wt.% sodium bicarbonate aqueous solution in a 1000ml three-necked flask, control the internal temperature at 40-50°C, decarboxylation reaction for 3h, sample GC analysis of the intermediate 2-acetyl-5,9-dimethyl-2,4,8-trienoic acid isopropyl ester content is less than 0.5%, stop the reaction, cool and stratify, wash the oil layer with a small amount of deionized water to neutral pH, and obtain pseudoionone by distillation, with a total yield of 96.8% and a GC content of 98.5%. The product NMR spectrum and data are consistent with those in Example 1.

[0063] The above has been described in detail with general descriptions and specific embodiments of the present invention, but it is obvious to those skilled in the art that some modifications or improvements can be made on the basis of the present invention. Therefore, these modifications or improvements made on the basis of not departing from the present invention all belong to the scope of protection claimed in the present invention.

Claims

1. A method for preparing pseudoionone, characterized in that: The method comprises the following steps: (1) Using citral as shown in formula (a) and an acetoacetate compound as shown in formula (b) as raw materials, wherein the acetoacetate compound is methyl acetoacetate, ethyl acetoacetate or isopropyl acetoacetate, and using a secondary amine as a catalyst, wherein the secondary amine is piperidine, morpholine, diethylamine or dipropylamine, a condensation reaction is carried out under a nitrogen atmosphere at a temperature of 10 to 30° C. to obtain an intermediate 2-acetyl-5,9-dimethyl-2,4,8-trienoate compound as shown in formula (c), and the reaction equation is as follows: (2) The intermediate 2-acetyl-5,9-dimethyl-2,4,8-trienoic acid ester compound shown in formula (c) is mixed with a dilute aqueous sodium bicarbonate solution, and the reaction temperature is controlled at 35 to 50° C. to perform a hydrolysis and decarboxylation reaction to obtain a pseudoionone shown in formula (d). The reaction equation is as follows:

2. The method according to claim 1, characterized in that: In step (1), the molar ratio of citral, the acetoacetate compound and the secondary amine is 1:1-1.5:0.002-0.

005.

3. The method according to claim 1, characterized in that In step (1), the reaction time is 1 to 3 hours.

4. The method according to claim 1, characterized in that In step (1), when the citral content is less than 1.0 wt.% according to GC analysis, distillation is performed to recover the intermediate 2-acetyl-5,9-dimethyl-2,4,8-trienoic acid ester compound.

5. The method according to claim 1, characterized in that In step (2), the mass concentration of the dilute sodium bicarbonate aqueous solution is 1 to 1.5 wt.%.

6. The method according to claim 1, characterized in that In step (2), the reaction time is 1 to 3 hours.

7. The method according to claim 1, characterized in that In step (2), when the GC analysis shows that the content of the intermediate 2-acetyl-5,9-dimethyl-2,4,8-trienoic acid ester compound is less than 1.0wt.%, the layers are separated, and the oil layer is washed with a small amount of deionized water to a neutral pH. The pseudo-ionone content is obtained by distillation to reach more than 97.5%.

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