CN118666658B - Preparation method of Fenmei sandalwood intermediate - Google Patents

Abstract

The invention belongs to the technical field of organic synthesis, and discloses a preparation method of a Fenmei sandalwood intermediate, which comprises the steps of dispersing campholenic aldehyde in a solvent, and carrying out addition reaction with N, N-dimethyl chloroeneimine to obtain a reaction solution containing 1- (N, N-dimethyl) -2- (2, 3-trimethyl-3-cyclopentene-1-yl) -2-propanal; adjusting the reaction liquid to an alkaline condition to remove dimethylamine from 1- (N, N-dimethyl) -2- (2, 3-trimethyl-3-cyclopenten-1-yl) -2-propanal in the reaction liquid to obtain a Fenmei sandalwood intermediate; wherein the mass ratio of campholenic aldehyde to N, N-dimethyl chloroeneimine is 1 (0.66-1.64); the alkaline condition is pH 7.5-10. The total yield of the synthetic route is 85-90%, the product purity is high, the preparation efficiency is greatly improved, and the product quality of the Fenmei sandalwood intermediate is improved.

Description

A preparation method of fenmei sandalwood intermediate

Technical Field

The invention belongs to the technical field of organic synthesis and relates to a preparation method of a fenmei sandalwood intermediate.

Background Art

The information disclosed in this background technology section is only intended to enhance the understanding of the overall background of the invention, and should not necessarily be regarded as an admission or any form of suggestion that the information constitutes the prior art already known to a person skilled in the art.

Fenmei Sandalwood has a strong and natural sandalwood scent. Adding it to fragrance can provide a sandalwood scent, so that the formula can obtain a natural sandalwood aroma, and the fragrance lasting time is further improved. Therefore, Fenmei Sandalwood has a wide market demand and has great application prospects.

The existing preparation of fenmei sandalwood is often based on chemical synthesis, and camphoraldehyde derivatives are used as intermediates in the sandalwood production process. Camphoraldehyde derivatives are one of the indispensable raw materials for producing sandalwood products. Patent US4610813 provides a class of camphoraldehyde derivatives with sandalwood odor, and discloses a preparation method of the derivatives, wherein the intermediate α, β-unsaturated aldehyde is obtained by aldol condensation of camphoraldehyde and formalin under alkaline conditions. However, in this route, the reaction yield of the intermediate α, β-unsaturated aldehyde obtained by the aldol condensation reaction of camphoraldehyde and formalin is only 60%, which seriously restricts the preparation efficiency and quality of the final product camphoraldehyde derivatives, is not conducive to industrial production, and highly polluting and highly toxic formalin is used in the preparation process, which generates a large amount of industrial wastewater, causes serious pollution to the environment, and is seriously harmful to the human body and easily induces cancer.

Therefore, the preparation efficiency of the fenmei sandalwood intermediate is low and the problem of serious pollution in the preparation process needs to be solved urgently.

Summary of the invention

In order to solve the deficiencies of the prior art, the object of the present invention is to provide a method for preparing a fenmei sandalwood intermediate. The object of the present invention is to solve the problem of low preparation efficiency in the preparation process of the fenmei sandalwood intermediate.

In order to achieve the above object, the present invention provides a method for preparing a fenmei sandalwood intermediate, comprising:

Dispersing camphorene aldehyde in a solvent, and performing an addition reaction with N,N-dimethylchlorobenzene imine to obtain a reaction solution containing 1-(N,N-dimethyl)-2-(2,2,3-trimethyl-3-cyclopenten-1-yl)-2-propanal;

The reaction solution is adjusted to alkaline conditions to remove dimethylamine from 1-(N,N-dimethyl)-2-(2,2,3-trimethyl-3-cyclopenten-1-yl)-2-propanal in the reaction solution to obtain a fenmei sandalwood intermediate;

The mass ratio of camphoraldehyde to N,N-dimethylchlorobenzeneimide is 1:(0.66-1.64); the alkaline condition is pH 7.5-10.

Preferably, the alkaline condition is 7.5-9, more preferably 8.

Preferably, the solvent is one of dichloromethane, chloroform or dichloroethane; more preferably dichloromethane.

Preferably, camphoraldehyde is dissolved in dichloromethane, and then N,N-dimethylchlorobenzeneimide is added to react.

Preferably, the reaction solution is added to a saturated sodium bicarbonate aqueous solution for sufficient reaction to obtain a fenmei sandalwood intermediate; further preferably, the volume ratio of the reaction solution to the saturated sodium bicarbonate aqueous solution is (1-2): 1. The reaction solution is added to a saturated sodium bicarbonate aqueous solution for quenching the reaction, and the volume ratio of the reaction solution to the saturated sodium bicarbonate aqueous solution is set to further ensure that the system after quenching is alkaline.

Preferably, the reaction temperature of the addition reaction is 20-30°C. If the temperature is too low, the reaction will proceed slowly, and if the temperature is too high, side reactions may occur and the yield may be reduced.

Preferably, the reaction solution is added to a sodium bicarbonate aqueous solution for sufficient reaction, and then separated, washed, dried and filtered in sequence. The filtrate is concentrated under reduced pressure to remove dichloromethane to obtain a crude product of the fenmei sandalwood intermediate, and more preferably a saturated sodium bicarbonate aqueous solution.

Preferably, the crude product of the fenmei sandalwood intermediate is subjected to desolventization and distillation purification to obtain the fenmei sandalwood intermediate.

Preferably, camphorene aldehyde and N,N-dimethylchlorobenzene imine are reacted for 10-20 h.

The beneficial effects of the present invention are:

1. The preparation method of the fenmei sandalwood intermediate provided by the present invention has an overall yield of 85-90% and a high product purity, which greatly improves the preparation efficiency and the product quality of the fenmei sandalwood intermediate.

2. The route of the present invention adopts low-toxic N,N-dimethylchlorobenzene imine for reaction, avoiding the use of highly polluting and highly toxic formalin, reducing the generation of wastewater, and avoiding environmental pollution and harm to the human body.

3. In the preparation process of the present invention, the reaction is carried out at room temperature, the process conditions are mild, energy consumption is saved, and it is suitable for industrial production.

BRIEF DESCRIPTION OF THE DRAWINGS

The accompanying drawings in the specification, which constitute a part of the present invention, are used to provide a further understanding of the present invention. The exemplary embodiments of the present invention and their descriptions are used to explain the present invention and do not constitute improper limitations on the present invention.

FIG1 is a GC-MS chromatogram of compound Ⅰ in Example 1 of the present invention;

FIG2 is a GC-MS mass spectrum of compound Ⅰ in Example 1 of the present invention;

FIG3 is a GC spectrum of compound I in Example 1 of the present invention.

DETAILED DESCRIPTION

To further illustrate the present invention, the preparation method of the fenmei sandalwood intermediate provided by the present invention is described in detail below with reference to the examples. Unless otherwise specified, all technical and scientific terms used in the present invention have the same meanings as those commonly understood by ordinary technicians in the technical field to which the present invention belongs.

In view of the existing preparation methods of the fenmei sandalwood intermediate, there are problems such as low preparation efficiency, serious environmental pollution caused by the use of formaldehyde, and low product quality, the present invention proposes a preparation method of the fenmei sandalwood intermediate, and the preparation route is as follows:

Among them, formula III is camphoraldehyde, whose Chinese alias is 2-(2,2,3-trimethyl-3-cyclopenten-1-yl)acetaldehyde, formula II is 1-(N,N-dimethyl)-2-(2,2,3-trimethyl-3-cyclopenten-1-yl)-2-propanal, and formula I is 2-(2,2,3-trimethyl-3-cyclopenten-1-yl)-2-propenal.

That is, camphoraldehyde first undergoes an addition reaction with N,N-dimethylchlorobenzene imine, and then the dimethylamine is removed under alkaline conditions to obtain the fenmei sandalwood intermediate. This synthetic route is carried out at room temperature, the reaction conditions are mild, and the preparation efficiency is high, and the product purity is higher.

In the following examples, dichloromethane is selected as the solvent. It should be noted that chloroform or dichloroethane also have the same or similar effects. In the examples of the present invention, the raw materials, instruments, etc. used are all commercially available.

Example 1

Take a clean 3 L four-necked bottle and install the stirrer and thermometer in it;

Add 304.4 g of borneol aldehyde and 1.5 L of dichloromethane to a four-necked bottle, stir evenly, then add 376 g of N,N-dimethylchlorobenzene imine to the four-necked bottle, react at 25°C for 15 hours, monitor the reaction using a gas chromatograph GC, and stop the reaction when the raw material borneol aldehyde accounts for <1%;

After the reaction is completed, the reaction solution is poured into 1 L of saturated sodium bicarbonate aqueous solution for quenching, the quenched mixed liquid is separated, the organic phase is taken, 500 mL of saturated brine is added to the organic phase for washing once, the liquids are separated, anhydrous sodium sulfate is added to the organic phase for drying, the insoluble matter is filtered, and the filtrate is concentrated under reduced pressure to remove dichloromethane to obtain a crude product of the fenmei sandalwood intermediate, and then the crude product obtained above is purified by distillation, and 289 g of compound I is collected at an internal temperature of about 70°C (-0.1 MPa, air temperature <45°C) to obtain the fenmei sandalwood intermediate.

The finally obtained fenmei sandalwood intermediate was analyzed by gas chromatography-mass spectrometry GC-MS and gas chromatograph GC, and the GC-MS spectrum of compound I was shown in Figures 1 and 2, and the GC spectrum was shown in Figure 3. The separation of the compounds in the GC spectrum in Figure 3 is shown in Table 1. Combining Figures 1-3 and Table 1, it can be seen that compound I is the fenmei sandalwood intermediate of this embodiment - 2-(2,2,3-trimethyl-3-cyclopentene-1-yl)-2-propenal, and the remaining embodiments are the same as this embodiment. Compound I is a fenmei sandalwood intermediate (2-(2,2,3-trimethyl-3-cyclopentene-1-yl)-2-propenal).

Through analysis and calculation, it was found that the content of 2-(2,2,3-trimethyl-3-cyclopenten-1-yl)-2-propenal was 92%, the yield was 88%, and MS (ES ⁺ ): M/Z = 164 (M ⁺ ).

Table 1 GC spectrum data of Fenmei sandalwood intermediates

Example 2

Take a clean 3 L four-necked bottle and install the stirrer and thermometer in it;

Add 304.4 g of borneol aldehyde and 1.5 L of dichloromethane to a four-necked bottle, stir evenly, then add 202 g of N,N-dimethylchlorobenzene imine to the four-necked bottle, react at 30°C for 10 hours, and monitor the reaction using a gas chromatograph GC; stop the reaction when the raw material borneol aldehyde accounts for less than 1%;

After the reaction is completed, the reaction solution is poured into 1 L of saturated sodium bicarbonate aqueous solution for quenching, the quenched mixed liquid is separated, the organic phase is taken, 500 mL of saturated brine is added to the organic phase for washing once, the liquids are separated, anhydrous sodium sulfate is added to the organic phase for drying, the insoluble matter is filtered, and the filtrate is concentrated under reduced pressure to remove dichloromethane to obtain a crude product of the fenmei sandalwood intermediate, and then the crude product obtained above is purified by distillation, and 296 g of compound I is collected at an internal temperature of about 70°C (-0.1 MPa, air temperature <45°C) to obtain the fenmei sandalwood intermediate.

The final obtained fenmei sandalwood intermediate was analyzed by gas chromatography-mass spectrometry GC-MS and gas chromatography GC, and it was found that compound I was a fenmei sandalwood intermediate (2-(2,2,3-trimethyl-3-cyclopenten-1-yl)-2-propenal), and the content of 2-(2,2,3-trimethyl-3-cyclopenten-1-yl)-2-propenal was 92%, the yield was 90%, MS (ES ⁺ ): M/Z = 164 (M ⁺ ).

Example 3

Take a clean 3 L four-necked bottle and install the stirrer and thermometer in it;

Add 304.4 g of borneol aldehyde and 1.5 L of dichloromethane to a four-necked bottle, stir evenly, then add 506 g of N,N-dimethylchlorobenzene imine to the four-necked bottle, react at 20°C for 20 hours, and monitor the reaction using a gas chromatograph GC; stop the reaction when the raw material borneol aldehyde accounts for <1%;

After the reaction is completed, the reaction solution is poured into 1 L of saturated sodium bicarbonate aqueous solution for quenching, the quenched mixed liquid is separated, the organic phase is taken, 500 mL of saturated brine is added to the organic phase for washing once, the liquids are separated, anhydrous sodium sulfate is added to the organic phase for drying, the insoluble matter is filtered, and the filtrate is concentrated under reduced pressure to remove dichloromethane to obtain a crude product of the fenmei sandalwood intermediate, and then the crude product obtained above is purified by distillation, and 282 g of compound I is collected at an internal temperature of about 70°C (-0.1 MPa, air temperature <45°C) to obtain the fenmei sandalwood intermediate.

The final obtained fenmei sandalwood intermediate was analyzed by gas chromatography-mass spectrometry GC-MS and gas chromatography GC, and it was found that compound I was a fenmei sandalwood intermediate (2-(2,2,3-trimethyl-3-cyclopenten-1-yl)-2-propenal), and the content of 2-(2,2,3-trimethyl-3-cyclopenten-1-yl)-2-propenal was 92%, the yield was 86%, MS (ES ⁺ ): M/Z = 164 (M ⁺ ).

Example 4

Take a clean 3 L four-necked bottle and install the stirrer and thermometer in it;

Add 304.4 g of borneol aldehyde and 1.5 L of dichloromethane to a four-necked bottle, stir evenly, then add 400 g of N,N-dimethylchlorobenzene imine to the four-necked bottle, react at 23°C for 10 hours, and monitor the reaction using a gas chromatograph GC; stop the reaction when the raw material borneol aldehyde accounts for <1%;

After the reaction is completed, the reaction solution is poured into 1 L of saturated sodium bicarbonate aqueous solution for quenching, the quenched mixed liquid is separated, the organic phase is taken, 500 mL of saturated brine is added to the organic phase for washing once, the liquids are separated, anhydrous sodium sulfate is added to the organic phase for drying, the insoluble matter is filtered, and the filtrate is concentrated under reduced pressure to remove dichloromethane to obtain a crude product of the fenmei sandalwood intermediate, and then the crude product obtained above is purified by distillation, and 279 g of compound I is collected at an internal temperature of about 70°C (-0.1 MPa, air temperature <45°C) to obtain the fenmei sandalwood intermediate.

The final obtained fenmei sandalwood intermediate was analyzed by gas chromatography-mass spectrometry GC-MS and gas chromatography GC, and it was found that compound I was a fenmei sandalwood intermediate (2-(2,2,3-trimethyl-3-cyclopenten-1-yl)-2-propenal), and the content of 2-(2,2,3-trimethyl-3-cyclopenten-1-yl)-2-propenal was 92%, the yield was 85%, MS (ES ⁺ ): M/Z = 164 (M ⁺ ).

The invention uses borneol aldehyde and N, N-dimethylchlorobenzene imine to carry out addition reaction to generate intermediate 1-(N, N-dimethyl)-2-(2,2,3-trimethyl-3-cyclopenten-1-yl)-2-propanal, and then easily removes dimethylamine under alkaline conditions to obtain a fenmei sandalwood intermediate. This scheme does not cause aldol condensation side reaction, the overall yield of the synthetic route is high, which can reach 85-90%, the product purity is high, the preparation efficiency is greatly improved, and the product quality of the fenmei sandalwood intermediate is improved.

The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. For those skilled in the art, the present invention may have various modifications and variations. Any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the present invention shall be included in the protection scope of the present invention.

Claims (10)

1. A method for preparing a fenmei sandalwood intermediate, characterized by comprising: Dispersing camphorene aldehyde in a solvent, and performing an addition reaction with N,N-dimethylchlorobenzene imine to obtain a reaction solution containing 1-(N,N-dimethyl)-2-(2,2,3-trimethyl-3-cyclopenten-1-yl)-2-propanal; The reaction solution is adjusted to alkaline conditions to remove dimethylamine from 1-(N,N-dimethyl)-2-(2,2,3-trimethyl-3-cyclopenten-1-yl)-2-propanal in the reaction solution to obtain a fenmei sandalwood intermediate; The mass ratio of camphoraldehyde to N,N-dimethylchlorobenzeneimide is 1:(0.66-1.64); the alkaline condition is pH 7.5-10. 2. The method for preparing a fenmei sandalwood intermediate according to claim 1, wherein the solvent is one of dichloromethane, chloroform or dichloroethane. 3. The method for preparing the fenmei sandalwood intermediate according to claim 2, characterized in that borneol aldehyde is dissolved in dichloromethane, and then N, N-dimethylchlorobenzene imine is added to react. 4. The method for preparing a fenmei sandalwood intermediate according to claim 1, wherein the alkaline condition is a pH of 7.5-9. 5. The method for preparing a fenmei sandalwood intermediate according to claim 1, wherein the alkaline condition is a pH of 8. 6. The method for preparing the fenmei sandalwood intermediate according to claim 1, characterized in that the reaction solution is added to a saturated sodium bicarbonate aqueous solution for sufficient reaction to obtain the fenmei sandalwood intermediate, and the volume ratio of the reaction solution to the saturated sodium bicarbonate aqueous solution is (1-2):1. 7. The method for preparing the fenmei sandalwood intermediate according to claim 1, characterized in that the reaction temperature of the addition reaction is set to 20-30°C. 8. The method for preparing the fenmei sandalwood intermediate according to claim 6, characterized in that the reaction solution is added to a saturated sodium bicarbonate aqueous solution for sufficient reaction, and then liquid separation, washing, drying and filtering are carried out in sequence, and the filtrate is concentrated under reduced pressure to remove dichloromethane to obtain a crude product of the fenmei sandalwood intermediate. 9. The method for preparing the fenmei sandalwood intermediate according to claim 8, characterized in that the crude product of the fenmei sandalwood intermediate is subjected to desolventization and rectification and purification to obtain the fenmei sandalwood intermediate. 10. The method for preparing a fenmei sandalwood intermediate according to claim 1, characterized in that borneol aldehyde and N,N-dimethylchlorobenzene imine are reacted for 10-20 h.