A process for the preparation of isomethylionone

Abstract

The present application provides a preparation method of isomethylionone, which comprises the following steps: preparing pseudo-isomethylionone by condensation reaction of citral and butanone, and generating alpha-isomethylionone by cyclization reaction of the pseudo-isomethylionone; wherein, the ratio of geranial and neral isomers contained in the citral is not less than 60:40. The isomethylionone product prepared by the present application maintains the proportion of alpha-isomethylionone at 70-90%, and the aroma quality is excellent.

Description

Technical Field

[0001] This invention relates to a method for preparing high-quality isomethylionone. More specifically, it relates to a synthetic method for preparing isomethylionone from citral and butanone, belonging to the field of organic synthesis technology. Background Technology

[0002] Methyl ionone possesses a beeswax-like and woody aroma, with notes reminiscent of osmanthus and acacia. It can be used to formulate violet and lily-type fragrances and flavorings. Methyl ionone has six isomers, with α-isomethyl ionone exhibiting the best aroma, 2-3 times stronger than α-n-methyl ionone. α-Isomethyl ionone and α-n-methyl ionone are physically similar and difficult to separate; commercially available methyl ionone is sold as a mixture of α-isomethyl ionone and α-n-methyl ionone. Other configurations are rarely seen in the market.

[0003] Patent CN 106748696 reports that methyl ionone is typically prepared by cyclization of citral and butanone. Because butanone has two nucleophilic sites that attack the aldehyde carbonyl group of citral, the condensation reaction produces two isomers: pseudo-n-methyl ionone and pseudo-isomethyl ionone. Pseudo-n-methyl ionone and pseudo-isomethyl ionone undergo cyclization reactions to produce six isomers: α-n-methyl ionone, β-n-methyl ionone, γ-n-methyl ionone, α-isomethyl ionone, β-isomethyl ionone, and γ-isomethyl ionone. To increase the content of α-isomethylionone, PEG was used as a solvent and metal hydroxide as a condensing agent to carry out Aldol condensation reaction to synthesize pseudomethylionone, so that the proportion of pseudoisomethylionone was maintained at 68-79%. Phosphoric acid-n-hexane catalytic cyclization was used to increase the cyclization yield to 92-95%, of which α-isomethylionone was maintained at 60-80%.

[0004] Citral and butanone condense under alkaline conditions to form pseudomethyl ionone. Both citral and pseudomethyl ionone possess multiple double bonds, making them prone to polymerization. Butanone also undergoes aldol condensation under alkaline conditions, leading to complex condensation products and reduced yield. Patent CN 1171842 reports the use of an antioxidant inhibitor, achieving a total yield of over 94% for pseudomethyl ionone and its isomers; however, the proportion of α-isomethyl ionone among the specific isomers was not significantly increased.

[0005] Therefore, it is still necessary to develop a new method for preparing isomethyl ionone, increase the proportion of α-isomethyl ionone isomers, and improve the quality of the product. Summary of the Invention

[0006] To address the aforementioned problems in the prior art, this invention provides a method for preparing isomethyl ionone, wherein pseudoisomethyl ionone is prepared by condensation of citral and butanone, and the pseudoisomethyl ionone undergoes a cyclization reaction to generate α-isomethyl ionone, wherein the proportion of α-isomethyl ionone is maintained at 70-90%.

[0007] Existing citral is typically a mixture of geranialdehyde and nerol, two cis-trans isomers, in an almost 1:1 ratio. This invention has found in experiments that the ratio of geranialdehyde to nerol in citral significantly affects the ratio of pseudoisomethylionone to pseudo-n-methylionone in the condensation reaction product. The condensation of geranialdehyde with butanone more readily yields a high proportion of pseudoisomethylionone. Therefore, controlling the ratio of geranialdehyde to nerol in citral to no less than 60:40 (since they are isomers, the calculation basis for their ratio is not limited and can be based on mass, molar amount, etc.) and increasing the geranialdehyde content can yield a condensation reaction product with a high proportion of pseudoisomethylionone. The pseudoisomethylionone then undergoes a further cyclization reaction to generate α-isomethylionone, with the α-isomethylionone proportion maintained at 70-90%. All proportions mentioned in this invention refer to the proportion within the isomers and are calculated based on the total amount of isomers.

[0008] To achieve the above technical effects, the technical solution adopted by this invention is as follows:

[0009] This invention provides a method for preparing isomethylionone, comprising the following steps:

[0010] Pseudoisomethylionone was prepared by condensation reaction of citral and butanone, and α-isomethylionone was generated by cyclization reaction of pseudoisomethylionone.

[0011] The ratio of geranialdehyde to neraldehyde isomers in citral is not less than 60:40, for example, 60:40, 65:35, 70:30, 75:25, 80:20, 85:15, 90:10, 95:5, 99:1, preferably 60:40-99:1, and more preferably 70:30-99:1.

[0012] The isomethyl ionone prepared by the method of the present invention has an α-isomethyl ionone content of 70-90%, for example 70%, 75%, 80%, 85%, or 90%.

[0013] In the method described in this invention, pseudo-isomethyl ionone is prepared by a condensation reaction of citral and butanone. Specifically, citral containing a high proportion of geranialdehyde (the ratio of geranialdehyde to nerol isomers is not less than 60:40) and butanone are used as raw materials, and a metal hydroxide is used as a catalyst to carry out the condensation reaction to prepare pseudo-isomethyl ionone.

[0014] In this invention, the molar ratio of citral to butanone is 1:2-20, for example 1:2, 1:5, 1:10, 1:15, 1:20, preferably 1:4-8.

[0015] In this invention, the condensation reaction is carried out under the action of a catalyst, which is a metal hydroxide;

[0016] The metal hydroxide is selected from one or more of LiOH, NaOH, KOH, CsOH, and Ba(OH)2, preferably KOH and / or NaOH;

[0017] The metal hydroxide can be added in solid form or in the form of an aqueous solution to the reaction system; preferably, the metal hydroxide is prepared as an aqueous solution before addition, with a solution concentration of 10-90 wt%, for example, 10 wt%, 30 wt%, 50 wt%, 70 wt%, or 90 wt%.

[0018] The molar ratio of the metal hydroxide to citral is 0.1-2:1, for example, 0.1:1, 0.5:1, 1.0:1, 1.5:1, 2.0:1, preferably 0.5-1:1.

[0019] In this invention, the condensation reaction is carried out at a temperature of 0-80℃, for example, 0℃, 10℃, 20℃, 30℃, 40℃, 50℃, 60℃, 70℃, or 80℃, preferably 10-50℃, and for a reaction time of 0.5-12h, for example, 0.5h, 1h, 3h, 5h, 7h, 9h, 11h, or 12h, preferably 1-8h.

[0020] Preferably, at the start of the condensation reaction, the citral is added continuously, preferably dropwise, at a temperature of 10-50°C (e.g., 10°C, 20°C, 30°C, 40°C, 50°C) and a time of 0.5-4 hours (e.g., 0.5 hours, 1 hour, 2 hours, 3 hours, 4 hours). The time of addition is not included in the condensation reaction time. Of course, the citral can also be added all at once at the start of the reaction using a conventional method.

[0021] Preferably, when adding citral by dropping, in order to slow down the formation of butanone polymerization products, the citral can be mixed with a portion of the butanone raw material, and then the citral and butanone mixture is added dropwise to the reaction system; more preferably, the portion of butanone used to mix with citral accounts for 0-90% of the total butanone feed amount, for example 0 wt%, 10 wt%, 30 wt%, 50 wt%, 70 wt%, 90 wt%, preferably 30-70%.

[0022] In this invention, after the condensation reaction is completed, post-processing processes such as neutralization, washing, and distillation are also included. These are all conventional operations in the field, and this invention does not have any special requirements. For example, in some specific examples, the post-processing method used is as follows: the condensation reaction solution is neutralized, washed, butanone is recovered, and distilled to remove excess weight, to obtain pseudoisomethyl ionone. The proportion of pseudoisomethyl ionone is maintained at 80-95%, for example, 80%, 85%, 90%, and 95%.

[0023] In the method described in this invention, α-isomethylionone is generated by a cyclization reaction of pseudoisomethylionone. Specifically, α-isomethylionone is generated by a cyclization reaction of pseudoisomethylionone under the action of an acid catalyst.

[0024] In this invention, the cyclization reaction is carried out in the presence of a catalyst, which is an acid;

[0025] Preferably, the acid is an inorganic acid, preferably one or more of sulfuric acid, phosphoric acid, hydrochloric acid, and nitric acid, and more preferably phosphoric acid;

[0026] Preferably, the acid is prepared as an aqueous solution before addition, with a concentration of 30-99 wt%, for example, 30 wt%, 50 wt%, 70 wt%, 90 wt%, or 99 wt%.

[0027] Preferably, the amount of acid used is 0.1-1.0 times the molar amount of pseudoisomethylionone, for example, 0.1 times, 0.3 times, 0.5 times, 0.7 times, 0.9 times, 1.0 times, and more preferably 0.2-0.5 times.

[0028] In this invention, the cyclization reaction can be carried out in a non-solvent environment or in an organic solvent environment;

[0029] Preferably, the organic solvent is one or more of alkanes, aromatics, and alcohols, more preferably one or more of C1-C10 alkanes, C1-C15 aromatics, and C1-C10 alcohols, and even more preferably one or more of n-hexane, toluene, and methanol; preferably, the amount of the organic solvent is 0-5 times the mass of pseudoisomethylionone, for example, 0 times, 0.1 times, 0.5 times, 1.0 times, 2.0 times, 3.0 times, 4.0 times, or 5.0 times, and more preferably 0.1-1.5 times.

[0030] In this invention, the cyclization reaction is carried out at a temperature of 30-90℃, for example, 30℃, 40℃, 50℃, 60℃, 70℃, 80℃, or 90℃, preferably 50-70℃, and for a reaction time of 1-12h, for example, 1h, 3h, 5h, 7h, 9h, 11h, or 12h, preferably 2-6h.

[0031] Preferably, at the start of the cyclization reaction, the pseudoisomethyl ionone is added to the reaction system in a continuous feeding manner, preferably by dropwise addition; more preferably, the feeding temperature of the pseudoisomethyl ionone is 10-50℃, for example, 10℃, 20℃, 30℃, 40℃, 50℃, and the feeding time is 0.5-4h, for example, 0.5h, 1h, 2h, 3h, 4h, and the feeding time is not included in the cyclization reaction time; of course, the pseudoisomethyl ionone can also be added in a conventional manner at the start of the reaction.

[0032] In this invention, after the cyclization reaction is completed, post-processing processes such as washing and distillation are also included. These are all conventional operations in the field and are not particularly required by this invention. For example, in some specific examples, the post-processing method used is as follows: the cyclization reaction solution is washed with water, desolventized, and distilled to obtain isomethyl ionone, and the proportion of isomethyl ionone is maintained at 70-90%, for example, 70%, 75%, 80%, 85%, and 90%.

[0033] In the method described in this invention, the ratio of geranialdehyde to neraldehyde isomers in the citral raw material is not less than 60:40. Citral products within this ratio range have been reported in the prior art and can be directly purchased or prepared by any feasible method; this invention does not have special requirements regarding their source. For example, high-proportion geranialdehyde is known in the prior art to be obtained through citral distillation or catalytic conversion. Patent WO2009068444A2 provides a detailed description of a citral distillation separation method, in which citral containing a high proportion of geranialdehyde is obtained at the bottom of the distillation column after efficient distillation to separate neraldehyde. The catalytic conversion of citral refers to the complete or partial conversion of neraldehyde in citral to geranialdehyde through catalysis. Patent CN102458659A discloses that a catalyst composed of a metal support, an optically active cyclic nitrogen-containing compound, and an acid can directly asymmetric hydrogenate citral to prepare optically active citronellol. This report shows that geranialdehyde and neraldehyde can undergo configurational inversion, and by selecting a suitable catalytic system, citral products containing a high proportion of geranialdehyde can be obtained.

[0034] Based on existing research, this invention discovers a preferred method for preparing a high proportion of geranialdehyde. By using chiral prolyl compounds, nerol in citral can be catalytically converted into geranialdehyde, resulting in a citral product with a geranialdehyde to nerol isomer ratio of not less than 60:40.

[0035] In some specific examples, the present invention provides a method for converting nerol in citral to geranialdehyde, which uses citral containing a low proportion of geranialdehyde as raw material and a chiral prolyl-type compound as catalyst to perform an isomerization reaction of nerol in citral to geranialdehyde, thereby obtaining citral with a geranialdehyde to nerol isomer ratio of not less than 60:40.

[0036] In this invention, the citral containing a low proportion of geranialdehyde has a geranialdehyde to nerol ratio of 60:40-50:50, for example 60:40, 58:42, 56:44, 54:46, 52:48, and 50:50.

[0037] In this invention, the chiral prolyl-type compounds include, but are not limited to, (S)-diphenylprolyl, (S)-α,α-bis(3,5-dimethylphenyl)prolyl, (S)-α,α-bis(3,5-dimethylphenyl)prolyl trimethylsilyl ether, (S)-α,α-bis(3,5-ditrifluoromethylphenyl)prolyl, (S)-α,α-bis(3,5-ditrifluoromethylphenyl)prolyl trimethylsilyl ether, and (S)-N-methyldiphenyl One or more of the following: α,α-prolyl, (S)-diphenylprolyl trimethylsilyl ether, (S)-α,α-bis(3,5-dimethylphenyl)prolyl triethylsilyl ether, (S)-α,α-bis(3,5-ditrifluoromethylphenyl)prolyl triethylsilyl ether, (S)-α,α-bis(3,5-ditrifluoromethylphenyl)prolyl tert-butyl dimethylsilyl ether, and (S)-α,α-bis(3,5-dimethylphenyl)prolyl tert-butyl dimethylsilyl ether.

[0038] In this invention, the amount of the chiral prolyl compound used is 0.5-5% of the mass of citral containing a low proportion of geraniol, for example 0.5%, 1%, 2%, 3%, 4%, 5%, preferably 1-3%.

[0039] In this invention, the isomerization reaction is carried out at a temperature of 30-120℃, for example, 30℃, 50℃, 70℃, 90℃, 110℃, 120℃, preferably 60-90℃, and for a reaction time of 1-24h, for example, 1h, 5h, 10h, 15h, 20h, 24h, preferably 6-12h.

[0040] Preferably, the isomerization reaction is carried out in a protective gas atmosphere, which is selected from nitrogen and argon.

[0041] In this invention, after the isomerization reaction is completed, conventional post-processing operations such as vacuum distillation to separate the fractions are also included to obtain citral with a high proportion of geranialdehyde.

[0042] It should be noted that the methods disclosed in this invention are merely illustrative examples of one catalytic conversion method used to achieve the high-proportion geranyl citral of this invention. The source of the high-proportion geranyl citral raw material described in this invention should not be limited by the steps and parameters in the above methods. Similarly, the method for preparing isomethyl ionone described in this invention should not be limited by the examples above.

[0043] Compared with the prior art, the positive effects of the technical solution of this invention are as follows:

[0044] This invention obtains a condensation reaction product with a high proportion of pseudoisomethyl ionone by controlling the ratio of geranialdehyde and nerol isomers in citral, a raw material for pseudoisomethyl ionone. Then, the pseudoisomethyl ionone undergoes a cyclization reaction to generate α-isomethyl ionone. The obtained α-isomethyl ionone content is as high as 70-90%, and the product has excellent aroma quality. Detailed Implementation

[0045] The following embodiments will further illustrate the method provided by the present invention, but the present invention is not limited to the listed embodiments and should also include any other known modifications within the scope of the claims of the present invention.

[0046] The main raw material sources in the embodiments and comparative examples of this invention are as follows; unless otherwise specified, all other raw materials were obtained through ordinary commercial channels:

[0047] Citral: Beijing Innocare Technology Co., Ltd.;

[0048] (S)-α,α-bis(3,5-dimethylphenyl)proline: Daicel Pharmaceutical Chiral Technology (Shanghai) Co., Ltd.;

[0049] (S)-α,α-bis(3,5-ditrifluoromethylphenyl)proline: Daicel Pharmaceutical Chiral Technology (Shanghai) Co., Ltd.

[0050] The main analytical methods used in the embodiments and comparative examples of this invention are as follows:

[0051] Gas chromatography: Agilent 7890, column DB-5, injection port temperature: 300℃; split ratio 50:1; carrier gas flow rate: 52.8 ml / min; temperature program: hold at 95℃ for 40 min, increase to 180℃ at a rate of 10℃ / min, hold for 40 min; detector temperature: 280℃.

[0052] Aroma Evaluation: Six experienced smellers were selected. Each smeller smelled the sample four times. Data was selected based on the simultaneous detection by at least half of the smellers. The evaluation indicators included four aspects: aroma quality, aroma quantity, off-odors, and transparency. Each of the four indicators was scored from 0 to 10. The average score given by the smellers was recorded, with higher scores indicating better performance in that aspect.

[0053] The proportions of pseudo-isomethyl ionone isomers and α-isomethyl ionone isomers mentioned in the following examples and comparative examples are calculated based on pure substances (i.e., the total amount of each isomer contained therein).

[0054] Example 1

[0055] 1) Preparation of citral with a high proportion of geranialdehyde:

[0056] Neraldehyde was separated using distillation. The distillation column had 75 theoretical plates. Citral (geranialdehyde to neraldehyde in a ratio of 53:47) was fed from plate 50. The bottom temperature was 130°C, the top vacuum was 200 PaA, and the reflux ratio was 10:1. Neraldehyde was collected at the top of the column, and the molar ratio of geranialdehyde to neraldehyde in the top product was 0.5:99.5. The remaining product was collected from the bottom of the column after citral separation, and the molar ratio of geranialdehyde to neraldehyde in the remaining product was 75:25.

[0057] 2) Preparation of isomethylionone:

[0058] (1) Add 78.5 g (0.7 mol) of 50 wt% KOH aqueous solution to a glass multi-necked flask, and add 200.0 g (2.77 mol) of butanone. Place the multi-necked flask in a constant temperature water bath. Then add 152.2 g (1 mol) of citral (geranialdehyde and nerol molar ratio of 75:25) and 232.6 g (3.22 mol) of butanone to a dropping funnel. While stirring, add the citral and butanone mixture dropwise to the reaction system over 1 hour at a temperature of 10°C. After the addition is complete, raise the temperature to 20°C and continue the condensation reaction for 4 hours. After the reaction is complete, neutralize, wash with water, and separate the liquids. First, recover most of the butanone under normal pressure, and then recover the butanone under reduced pressure. Continue vacuum distillation to collect the fraction at 140 PaA / 115-118℃ to obtain a pseudomethyl ionone product with a purity of 99.3%, of which the pseudo isomethyl ionone isomer accounted for 82.1%.

[0059] (2) Add 34.6 g (0.3 mol) of 85 wt% phosphoric acid aqueous solution and 50.0 g of n-hexane to a glass multi-necked flask, and place the flask in a constant temperature water bath. Under stirring, add the product from step (1) containing 206.3 g (1 mol) of pseudo-isomethyl ionone dropwise to the reaction system over 1 hour at a temperature of 50°C. After the addition is complete, raise the temperature to 60°C and continue the cyclization reaction for 4 hours. After the reaction is complete, wash with water and separate the liquid. Distill off the solvent and then distill under reduced pressure to collect the fraction at 110 PaA / 95-98°C to obtain a methyl ionone product with a purity of 99.1%, of which the α-isomethyl ionone isomer accounts for 81.5%.

[0060] Aroma sensory evaluation results: aroma quality 9 points, aroma quantity 9 points, off-odors 8 points, permeability 9.5 points.

[0061] Example 2

[0062] 1) Preparation of citral with a high proportion of geranialdehyde:

[0063] Neraldehyde was separated by distillation. The distillation column had 85 theoretical plates. Citral (geranialdehyde to neraldehyde in a ratio of 52:48) was fed from the middle. The ratio of the rectification section to the stripping section was 1:1. The bottom temperature was 140℃, the top vacuum was 200 PaA, and the reflux ratio was 9:1. Neraldehyde was collected at the top of the column, with a molar ratio of geranialdehyde to neraldehyde of 1:99. Citral with a high proportion of geranialdehyde was collected at the bottom of the column, with a molar ratio of geranialdehyde to neraldehyde of 95:5.

[0064] 2) Preparation of isomethylionone:

[0065] (1) 168.3 g (0.6 mol) of 20 wt% KOH aqueous solution and 144.2 g (2 mol) of butanone were added to a glass multi-necked flask, and the flask was placed in a constant temperature water bath. Then, 152.2 g (1 mol) of citral (geranialdehyde and nerol molar ratio of 95:5) and 144.2 g (2 mol) of butanone were added to the reaction system dropwise with stirring over a period of 0.5 hours at a temperature of 30°C. After the addition was complete, the temperature was raised to 40°C and the condensation reaction was continued for 3 hours. After the reaction was completed, the mixture was neutralized, washed with water, and separated. Most of the butanone was recovered under normal pressure, and then under reduced pressure. The fraction collected under reduced pressure at 140 PaA / 115-118°C was obtained to yield a pseudomethyl ionone product with a purity of 99.5%, of which the pseudo-isomethyl ionone isomer accounted for 93.7%.

[0066] (2) Add 23.1 g (0.2 mol) of 85 wt% phosphoric acid aqueous solution and 210.0 g of n-hexane to a glass multi-necked flask, and place the flask in a constant temperature water bath. Under stirring, add the product from step (1) containing 206.3 g (1 mol) of pseudo-isomethyl ionone dropwise to the reaction system over 2 hours at a temperature of 40°C. After the addition is complete, raise the temperature to 50°C and continue the cyclization reaction for 6 hours. After the reaction is complete, wash with water and separate the liquid. Distill off the solvent and then distill under reduced pressure to collect the fraction at 110 PaA / 95-98°C to obtain a methyl ionone product with a purity of 99.3%, of which the α-isomethyl ionone isomer accounts for 89.7%.

[0067] Aroma sensory evaluation results: aroma quality 9.5 points, aroma quantity 9 points, off-odors 8.5 points, permeability 9.5 points.

[0068] Example 3

[0069] 1) Preparation of citral with a high proportion of geranialdehyde:

[0070] Neraldehyde was separated by distillation. The distillation column had 65 theoretical plates. Citral (geranialdehyde to neraldehyde in a 50:50 ratio) was fed from the middle. The ratio of the rectification section to the stripping section was 1:1. The bottom temperature was 140℃, the top vacuum was 200 PaA, and the reflux ratio was 8:1. Neraldehyde was collected at the top of the column, with a geranialdehyde to neraldehyde molar ratio of 2:98. Citral with a high geranialdehyde content was collected at the bottom of the column, with a geranialdehyde to neraldehyde molar ratio of 68:32.

[0071] 2) Preparation of isomethylionone:

[0072] (1) Add 12.0 g (0.5 mol) of solid LiOH and 180.2 g (2.5 mol) of butanone to a glass multi-necked flask and place the flask in a constant temperature water bath. Then add 152.2 g (1 mol) of citral (geranialdehyde and nerol molar ratio of 68:32) and 180.2 g (2.5 mol) of butanone to a dropping funnel. While stirring, add the citral and butanone mixture dropwise to the reaction system over 3 hours at a temperature of 10°C. After the addition is complete, continue the condensation reaction at 10°C for 8 hours. After the reaction is complete, neutralize, wash with water, and separate the liquid. First, recover most of the butanone under normal pressure, and then recover the butanone under reduced pressure. Continue to distill under reduced pressure to collect the fraction at 140 PaA / 115-118°C to obtain a pseudomethyl ionone product with a purity of 96.2%, of which the pseudoisomethyl ionone isomer accounts for 78.1%.

[0073] (2) Add 245.2 g (1.0 mol) of 40 wt% sulfuric acid aqueous solution and 200.0 g of n-hexane to a glass multi-necked flask and place the flask in a constant temperature water bath. Add the product from step (1) containing 206.3 g (1 mol) of pseudo-isomethyl ionone dropwise to the reaction system with stirring. The dropwise addition time is 3 hours and the dropwise addition temperature is 30℃. After the dropwise addition is completed, raise the temperature to 90℃ and continue the cyclization reaction for 5 hours. After the reaction is completed, wash with water and separate the liquid. After distilling to remove the solvent, distill under reduced pressure and collect the fraction at 110 PaA / 95-98℃ to obtain methyl ionone product with a purity of 95.2%, of which the α-isomethyl ionone isomer accounts for 71.2%.

[0074] Aroma sensory evaluation results: aroma quality 8 points, aroma quantity 8 points, off-odors 7.5 points, permeability 8.5 points.

[0075] Example 4

[0076] 1) Preparation of citral with a high proportion of geranialdehyde:

[0077] Under nitrogen protection, 200.0 g of citral (geranialdehyde to neraldehyde in a 50:50 ratio) and 2.0 g of (S)-α,α-bis(3,5-dimethylphenyl)proline were added to a glass multi-necked flask. The flask was placed in a constant temperature water bath and the isomerization reaction was carried out at 60 °C for 8 hours. After the reaction was completed, the fraction collected under reduced pressure at 140 Pa / 106-109 °C was collected to obtain citral with a high geranialdehyde content, neraldehyde conversion rate of 80%, yield of 91.3%, and geranialdehyde to neraldehyde molar ratio of 65:35.

[0078] 2) Preparation of isomethylionone:

[0079] (1) Add 84.15 g (0.9 mol) of 60 wt% KOH aqueous solution to a glass multi-necked flask, and add 300.0 g (4.16 mol) of butanone. Place the multi-necked flask in a constant temperature water bath. Then add 124.4 g (1 mol) of citral (geranialdehyde and nerol molar ratio of 65:35) and 276.8 g (3.84 mol) of butanone to a dropping funnel. While stirring, add the citral and butanone mixture dropwise to the reaction system over 4 hours at a temperature of 20°C. After the addition is complete, raise the temperature to 30°C and continue the condensation reaction for 6 hours. After the reaction is complete, neutralize, wash with water, and separate the liquids. First, recover most of the butanone under normal pressure, and then recover the butanone under reduced pressure. Continue vacuum distillation to collect the fraction at 140 PaA / 115-118℃ to obtain a pseudomethyl ionone product with a purity of 97.3%, of which the pseudo isomethyl ionone isomer accounted for 81.1%.

[0080] (2) Add 61.2 g (0.5 mol) of 80 wt% phosphoric acid aqueous solution and 300.0 g of toluene to a glass multi-necked flask and place the flask in a constant temperature water bath. Add the product from step (1) containing 206.3 g (1 mol) of pseudo-isomethyl ionone dropwise to the reaction system with stirring. The dropwise addition time is 4 hours and the dropwise addition temperature is 10℃. After the dropwise addition is completed, raise the temperature to 70℃ and continue the cyclization reaction for 2 hours. After the reaction is completed, wash with water and separate the liquid. After distilling to remove the solvent, distill under reduced pressure and collect the fraction at 110 PaA / 95-98℃ to obtain methyl ionone product with a purity of 96.7%, of which the α-isomethyl ionone isomer accounts for 76.3%.

[0081] The sensory evaluation results for odor are as follows: aroma quality 9 points, aroma quantity 8.5 points, off-odors 8 points, and permeability 9.0 points.

[0082] Example 5

[0083] 1) Preparation of citral with a high proportion of geranialdehyde:

[0084] Under nitrogen protection, 200.0 g of citral (geranialdehyde to neraldehyde ratio of 51:49) and 6.0 g of (S)-α,α-bis(3,5-difluoromethylphenyl)proline were added to a glass multi-necked flask. The flask was placed in a constant temperature water bath and the reaction was maintained at 60℃ for 8 hours. After the reaction was completed, the fraction collected under reduced pressure at 140 PaA / 106-109℃ was collected to obtain citral with a high geranialdehyde content, neraldehyde conversion rate of 80%, yield of 91.3%, and geranialdehyde to neraldehyde molar ratio of 70:30.

[0085] 2) Preparation of isomethylionone:

[0086] (1) Add 110g (1.1mol) of 40% NaOH solution and 150.0g (2.08mol) of butanone to a glass multi-necked flask, and place the flask in a constant temperature water bath. Then add 124.4g (1mol) of citral (geranialdehyde and nerol molar ratio of 70:30) and 354.77g (4.92mol) of butanone to a dropping funnel. While stirring, add the citral and butanone mixture dropwise to the reaction system over 2 hours at a temperature of 50°C. After the addition is complete, continue the condensation reaction at 50°C for 1 hour. After the reaction, neutralize, wash with water, and separate the liquid. First, recover most of the butanone under normal pressure, and then recover the butanone under reduced pressure. Continue to distill under reduced pressure to collect the fraction at 140PaA / 115-118°C, obtaining a pseudomethyl ionone product with a purity of 97.6%, of which the pseudoisomethyl ionone isomer accounts for 81.4%.

[0087] (2) Add 52.3 g (0.4 mol) of 75 wt% phosphoric acid aqueous solution and 100.0 g of toluene to a glass multi-necked flask and place the flask in a constant temperature water bath. Under stirring, add the product from step (1) containing 206.3 g (1 mol) of pseudo-isomethyl ionone dropwise to the reaction system over 0.5 hours at a temperature of 20°C. After the addition is complete, raise the temperature to 30°C and continue the cyclization reaction for 3 hours. After the reaction is complete, wash with water and separate the liquid. Distill off the solvent and then distill under reduced pressure to collect the fraction at 110 PaA / 95-98°C to obtain a methyl ionone product with a purity of 97.1%, of which the α-isomethyl ionone isomer accounts for 75.7%.

[0088] The sensory evaluation results for odor are as follows: aroma quality 8.5 points, aroma quantity 9 points, off-odors 7.5 points, and permeability 9.5 points.

[0089] Comparative Example 1

[0090] Isomethylionone was prepared according to step 2) of Example 1, except that the citral raw material was replaced with a ratio of 53:47 of geranialdehyde to neraldehyde instead of 75:25. Other operations and parameters remained unchanged, and methylionone product with a purity of 94.1% was obtained, of which the α-isomethylionone isomer accounted for 65.1%.

[0091] The sensory evaluation results for odor are as follows: aroma quality 8 points, aroma quantity 7.5 points, off-odors 7 points, and permeability 7 points.

Claims

1. A method for preparing isomethylionone, characterized in that the steps include... include: Pseudoisomethylionone was prepared by condensation reaction of citral and butanone, and α-isomethylionone was generated by cyclization reaction of pseudoisomethylionone. Among them, the ratio of geranialdehyde to neraldehyde isomers in citral is not less than 60:

40.

2. The preparation method according to claim 1, characterized in that, Citral contains geranialdehyde and neraldehyde isomers in a ratio of 60:40 to 99:

1.

3. The preparation method according to claim 2, characterized in that, Citral contains geranialdehyde and neraldehyde isomers in a ratio of 70:30 to 99:

1.

4. The preparation method according to claim 1, characterized in that, The isomethyl ionone prepared by the method comprises 70-90% α-isomethyl ionone.

5. The preparation method according to claim 1, characterized in that, The molar ratio of citral to butanone is 1:2-20.

6. The preparation method according to claim 5, characterized in that, The molar ratio of citral to butanone is 1:4-8.

7. The preparation method according to claim 1, characterized in that, The condensation reaction is carried out in the presence of a catalyst, which is a metal hydroxide.

8. The preparation method according to claim 7, characterized in that, The metal hydroxide is selected from one or more of LiOH, NaOH, KOH, CsOH, and Ba(OH)2.

9. The preparation method according to claim 8, characterized in that, The metal hydroxide is added to the reaction system in solid form or in the form of an aqueous solution.

10. The preparation method according to claim 9, characterized in that, The metal hydroxide is prepared as an aqueous solution with a concentration of 10-90 wt% before being added.

11. The preparation method according to claim 8, characterized in that, The molar ratio of the metal hydroxide to citral is 0.1-2:

1.

12. The preparation method according to claim 11, characterized in that, The molar ratio of the metal hydroxide to citral is 0.5-1:

1.

13. The preparation method according to claim 1, characterized in that, The condensation reaction is carried out at a temperature of 0-80℃ for a time of 0.5-12h.

14. The preparation method according to claim 13, characterized in that, The condensation reaction is carried out at a temperature of 10-50℃ for 1-8 hours.

15. The preparation method according to claim 1, characterized in that, At the start of the condensation reaction, the citral is fed continuously.

16. The preparation method according to claim 1, characterized in that, At the start of the condensation reaction, the citral is added to the reaction system dropwise.

17. The preparation method according to claim 1, characterized in that, The citral feeding temperature is 10-50℃, and the feeding time is 0.5-4h. The feeding time is not included in the condensation reaction time.

18. The preparation method according to claim 16, characterized in that, When adding citral by dropping, the citral is mixed with a portion of the butanone raw material and then added dropwise to the reaction system.

19. The preparation method according to claim 18, characterized in that, The portion of methyl ethyl ketone used for mixing with citral accounts for 0-90% of the total methyl ethyl ketone feed.

20. The preparation method according to claim 19, characterized in that, The portion of methyl ethyl ketone used for mixing with citral accounts for 30-70% of the total methyl ethyl ketone feed.

21. The preparation method according to claim 1, characterized in that, The cyclization reaction is carried out in the presence of a catalyst, which is an acid.

22. The preparation method according to claim 21, characterized in that, The acid is an inorganic acid.

23. The preparation method according to claim 22, characterized in that, The acid is one or more of sulfuric acid, phosphoric acid, hydrochloric acid, and nitric acid.

24. The preparation method according to claim 21, characterized in that, The acid is prepared as an aqueous solution before being added, with a concentration of 30-99 wt%.

25. The preparation method according to claim 21, characterized in that, The amount of acid used is 0.1-1.0 times the molar amount of pseudoisomethyl ionone.

26. The preparation method according to claim 21, characterized in that, The amount of acid used is 0.2-0.5 times the molar amount of pseudoisomethyl ionone.

27. The preparation method according to claim 1, characterized in that, The cyclization reaction is carried out in a non-solvent environment or in an organic solvent environment.

28. The preparation method according to claim 27, characterized in that, The organic solvent is one or more of alkanes, aromatics, and alcohols.

29. The preparation method according to claim 28, characterized in that, The organic solvent is one or more of C1-C10 alkanes, C1-C15 aromatics, and C1-C10 alcohols.

30. The preparation method according to claim 29, characterized in that, The organic solvent is one or more of n-hexane, toluene, and methanol.

31. The preparation method according to claim 27, characterized in that, The amount of organic solvent used is 0-5 times the mass of pseudoisomethyl ionone.

32. The preparation method according to claim 31, characterized in that, The amount of organic solvent used is 0.1-1.5 times the mass of pseudoisomethylionone.

33. The preparation method according to claim 1, characterized in that, The cyclization reaction is carried out at a temperature of 30-90℃ for 1-12 hours.

34. The preparation method according to claim 33, characterized in that, The cyclization reaction is carried out at a temperature of 50-70℃ for 2-6 hours.

35. The preparation method according to claim 1, characterized in that, At the start of the cyclization reaction, the pseudoisomethyl ionone is fed continuously.

36. The preparation method according to claim 1, characterized in that, At the start of the cyclization reaction, the pseudoisomethylionone was added to the reaction system dropwise.

37. The preparation method according to claim 1, characterized in that, The addition temperature of the pseudoisomethyl ionone is 10-50℃, and the addition time is 0.5-4h. The addition time is not included in the cyclization reaction time.

38. The preparation method according to claim 1, characterized in that, Using citral containing a low proportion of geranialdehyde as raw material and a chiral prolyl-type compound as catalyst, the isomerization reaction of nerol in citral is carried out to produce geranialdehyde, thereby obtaining citral raw material with a ratio of geranialdehyde to nerol isomers of not less than 60:

40.

39. The preparation method according to claim 38, characterized in that, The citral containing a low proportion of geranialdehyde, wherein the ratio of geranialdehyde to neraldehyde is 55:45-50:50; and / or The chiral prolyl compounds are selected from (S)-diphenylprolyl, (S)-α,α-bis(3,5-dimethylphenyl)prolyl, (S)-α,α-bis(3,5-dimethylphenyl)prolyl trimethylsilyl ether, (S)-α,α-bis(3,5-difluoromethylphenyl)prolyl, (S)-α,α-bis(3,5-difluoromethylphenyl)prolyl trimethylsilyl ether, (S)-N-methyldiphenylprolyl, ( One or more of the following: (S)-diphenylprolyl trimethylsilyl ether, (S)-α,α-bis(3,5-dimethylphenyl)prolyl triethylsilyl ether, (S)-α,α-bis(3,5-ditrifluoromethylphenyl)prolyl triethylsilyl ether, (S)-α,α-bis(3,5-ditrifluoromethylphenyl)prolyl tert-butyl dimethylsilyl ether, and (S)-α,α-bis(3,5-dimethylphenyl)prolyl tert-butyl dimethylsilyl ether; and / or The amount of the chiral prolyl compound used is 0.5-5% of the mass of citral containing a low proportion of geraniol; and / or The isomerization reaction is carried out at a temperature of 30-120℃ for a time of 1-24 hours.

40. The preparation method according to claim 39, characterized in that, The amount of the chiral prolyl compound used is 1-3% of the mass of citral containing a low proportion of geraniol.

41. The preparation method according to claim 39, characterized in that, The isomerization reaction is carried out at a temperature of 60-90℃ for a time of 6-12 hours.

42. The preparation method according to claim 38, characterized in that, The isomerization reaction is carried out in a protective gas atmosphere.

43. The preparation method according to claim 42, characterized in that, The protective gas atmosphere is selected from nitrogen and argon.