Synthesis method of citral compound

Abstract

The invention provides a synthesis method of a citral compound, which comprises the following steps: taking nerol or geraniol as a raw material, taking a complex formed by TEMPO, imidazole and cuprous salt as a catalyst, taking dichloromethane as a solvent and taking oxygen as an oxidant, and carrying out oxidation reaction under a homogeneous catalysis system to obtain single-configuration citral with high yield. The method has the advantages of high reaction activity, high selectivity, cheap and easily available initial raw materials, cleanness, environmental protection and very high industrial application value.

Description

Technical Field

[0001] This invention belongs to the field of organic synthesis, specifically relating to a method for preparing a single-configuration citral compound by oxidation of nerol or geraniol. Background Technology

[0002] Citral is a very important chemical intermediate, mainly used in chemical materials intermediates, nutritional products, and synthetic fragrances. It is primarily used in the formulation of lemon flavorings and the manufacture of citrus flavorings. It is also used in the synthesis of ionones (a raw material for the synthesis of vitamin A), citrate, methyl ionone, hydroxycitronellol, isoprene, dihydrodamascone, and other compounds. It also possesses antibacterial and pheromone properties.

[0003] Currently, there are two main routes for the production of citral: one is the synthesis of citral by dehydrogenation of nerol under noble metal catalysis [WO2004060844]. This route uses platinum as a noble metal catalyst, resulting in higher production costs. The other route utilizes the rearrangement of dehydrogenated linalool under high temperature conditions [(a)CN105289751.(b)].

[0004] [CN101391942]. The second route involves a rearrangement reaction under high-temperature conditions. This route is carried out under high-temperature conditions. Since this rearrangement reaction is a strongly exothermic reaction with an adiabatic temperature rise of >200℃, if it gets out of control during industrial production, it is extremely easy to cause fire and explosion risks. Summary of the Invention

[0005] The purpose of this invention is to provide a method for synthesizing citral compounds. This method provides a highly efficient oxidation catalytic system that does not use precious metal catalysts, does not require high-temperature conditions, avoids the possibility of danger under high-temperature conditions, and uses oxygen as an oxidant. It is inexpensive, readily available, simple to operate, and has high reactivity, which greatly reduces the reaction cost and has high industrial application value.

[0006] This invention provides a method for synthesizing citral compounds, using nerol or geraniol as raw materials and a complex formed by TEMPO, imidazole, and cuprous salt as a catalyst, to undergo an oxidation reaction under oxygen conditions to almost quantitatively generate citral with a single configuration. The specific steps are as follows:

[0007] Add nerol or geraniol to the solvent, start stirring, and then add TEMPO, imidazole, and cuprous salt sequentially. Introduce oxygen and react at 20-100℃ for 1-24 hours. TLC is used to confirm complete reaction. Post-treatment: Add water, separate the layers, extract the aqueous phase with dichloromethane, combine the organic phases, wash with saturated sodium thiosulfate and saturated brine, dry with anhydrous sodium sulfate, remove the solvent, and distill under reduced pressure to obtain the product.

[0008]

[0009] The reaction medium is at least one selected from toluene, benzene, methanol, ethanol, isopropanol, dichloromethane, dichloroethane, carbon tetrachloride, ethyl acetate, diethyl ether, tetrahydrofuran, dimethyl sulfoxide, or N,N-dimethylformamide. Dichloromethane is preferred.

[0010] The complex formed by TEMPO, imidazole, and cuprous salt serves as a catalyst, wherein TEMPO (2,2,6,6-tetramethylpiperidine oxide) has the following general structural formula:

[0011]

[0012] R1 is selected from H, C1-C 10 Alkyl, C3-C8 cycloalkyl, C1-C 40 One or more of alkoxy, halogen, nitro, hydroxyl, ester, cyano, phenyl, amino, substituted phenyl, benzyl, and substituted benzyl groups are selected, respectively. The substituents on the substituted phenyl and substituted benzyl groups are selected from C1-C40 alkoxy groups (preferably C1-C10 alkoxy groups, such as methoxy, ethoxy, etc., one or more) and C1-C40 alkyl groups (preferably C1-C10 alkyl groups, such as CH4). 3、 CH3CH 2、 (CH3)2CH 、 (CH3)3C, etc., one or more of the following: C1 to C40 alkyl, nitro, cyano, halogen (F, Cl, Br, I), with 1 to 5 substituents.

[0013] The general structural formula of imidazole is as follows:

[0014]

[0015] R1, R2, and R3 are selected from H, C1-C 10 Alkyl, C3-C8 cycloalkyl, C1-C 40 One or more of alkoxy, halogen, nitro, hydroxyl, ester, cyano, phenyl, amino, substituted phenyl, benzyl, and substituted benzyl groups are selected, respectively. The substituents on the substituted phenyl and substituted benzyl groups are selected from C1-C40 alkoxy groups (preferably C1-C10 alkoxy groups, such as methoxy, ethoxy, etc., one or more) and C1-C40 alkyl groups (preferably C1-C10 alkyl groups, such as CH4). 3、 CH3CH 2、 (CH3)2CH 、 (CH3)3C, etc., one or more of the following: C1 to C40 alkyl, nitro, cyano, halogen (F, Cl, Br, I), with 1 to 5 substituents.

[0016] The method for synthesizing citral according to claim 1 is characterized in that: the copper salt is selected from one or more cuprous salts such as CuCl, CuBr, CuI, Cu2S, CH3COOCu, Cu2O, and CuCN. Preferably, CuCN is selected.

[0017] The molar ratio of alcohol substrate: imidazole compound: cuprous salt: TEMPO is 10000-10:2-4:1:1-6, preferably 700-10:2:1:2-4, and more preferably 500-10:2:1:3-4.

[0018] The catalytic reaction conditions are as follows:

[0019] Temperature: 20-100℃, preferably 30℃;

[0020] Time: 1-24 hours, preferably 12 hours.

[0021] The present invention has the following advantages:

[0022] 1. Starting materials are readily available.

[0023] 2. It has high reactivity, mild reaction conditions, high yield, and high selectivity.

[0024] 3. Compared with traditional methods, this method greatly reduces reaction costs and simplifies the process.

[0025] 4. The single configuration of citral can be quantitatively obtained, which is clean and environmentally friendly and has high industrial application value. Attached Figure Description

[0026] Figure 1 The 1H NMR spectrum of Z-citral prepared in Example 1;

[0027] Figure 2 The carbon NMR spectrum of Z-citral prepared in Example 1.

[0028] Figure 3 The 1H NMR spectrum of E-citral prepared in Example 2;

[0029] Figure 4 The carbon NMR spectrum of E-citral prepared in Example 2. Detailed Implementation

[0030] The following examples will further illustrate the invention, but are not intended to limit the invention. Nuclear magnetic resonance (NMR) measurements were performed using a Bruker 400 NMR spectrometer.

[0031] Example 1

[0032] The structural formula of 4-OH-TEMPO is as follows:

[0033]

[0034] The structural formula of imidazole is as follows:

[0035]

[0036] 18.5 g (120 mmol) of nerol was added to a reaction flask, followed by 100 mL of dichloromethane. The flask was placed in an oil bath and stirred. Then, 0.689 g (4 mmol) of 4-OH-TEMPO, 0.3126 g (2 mmol) of imidazole, and 89.56 mg (1 mmol) of cuprous cyanide were added. The reaction flask was incubated with an oxygen bulb at 30 °C for 12 h. The reaction was then monitored by TLC until complete. 100 mL of water was added for hydration. The aqueous phase was extracted with dichloromethane. The organic phases were combined, washed with saturated sodium thiosulfate and saturated brine, dried over anhydrous sodium sulfate, and the concentrated solvent was distilled under reduced pressure to obtain 18.15 g of Z-citral.

[0037] 1 H NMR (400MHz, CDCl3) δ9.99 (d, J=8.1Hz, 1H), 5.88 (dd, J=8.1, 1.0Hz, 1H), 5.13-4 .99(m,1H),2.24-2.19(m,4H),2.17(d,J=1.1Hz,3H),1.69(s,3H),1.61(s,3H).

[0038] 13 C NMR (400MHz, CDCl3) δ17.55,17.69,25.62,25.71,40.58,122.56,127.39,132.87,163.81,191.25.

[0039] Example 2

[0040] The process and conditions were the same as in Example 1, except that nerol, the raw material in Example 1, was replaced with an equimolar amount of geraniol, while the rest remained the same as in Example 1. Vacuum distillation yielded 18.10 g of E-citral.

[0041] 1 H NMR(400MHz, CDCl3) δ9.99(d,J=8.1Hz,1H),5.88(d,J=7.4Hz,1H),5.08(d,J=6 .4Hz,1H),2.24-2.19(m,4H),2.17(d,J=1.0Hz,3H),1.69(s,3H),1.61(s,3H).

[0042] 13C NMR (400MHz, CDCl3) δ17.63,17.76,25.69,25.77,40.65,122.60,127.45,132.95,163.89,191.36

[0043] Example 3

[0044] The process and conditions were the same as in Example 1, except that the 4-OH-TEMPO in Example 1 was replaced with an equimolar amount of 4-H-TEMPO, and the rest were the same as in Example 1. Reduced pressure distillation yielded 18.05 g of product.

[0045] The structural formula of 4-H-TEMPO is as follows:

[0046]

[0047] Example 4

[0048] The process and conditions were the same as in Example 1, except that the imidazole in Example 1 was replaced with an equimolar amount of 2-methylimidazolium, and the rest were the same as in Example 1. Vacuum distillation yielded 15.32 g of product.

[0049] The structural formula of 2-methylimidazole is as follows:

[0050]

[0051] Example 5

[0052] The process and conditions were the same as in Example 1, except that the imidazole in Example 1 was replaced with an equimolar amount of 2-ethylimidazole, and the rest were the same as in Example 1. Vacuum distillation yielded 13.49 g of product.

[0053] The structural formula of 2-ethylimidazole is as follows:

[0054]

[0055] Example 6

[0056] The process and conditions were the same as in Example 1, except that the imidazole in Example 1 was replaced with an equimolar amount of 2-imidazolium formaldehyde, and the rest were the same as in Example 1. Vacuum distillation yielded 5.67 g of product.

[0057] The structural formula of 2-imidazolium formaldehyde is as follows:

[0058]

[0059] Example 7

[0060] The process and conditions were the same as in Example 1, except that the imidazole in Example 1 was replaced with an equimolar amount of 2-aminoimidazole, and the rest were the same as in Example 1. Vacuum distillation yielded 14.79 g of product.

[0061] The structural formula of 2-aminoimidazole is as follows:

[0062]

[0063] Example 8

[0064] The process and conditions were the same as in Example 1, except that the imidazole in Example 1 was replaced with an equimolar amount of 4-methylimidazolium, and the rest were the same as in Example 1. Vacuum distillation yielded 16.15 g of product.

[0065] The structural formula of 4-methylimidazole is as follows:

[0066]

[0067] Example 9

[0068] The process and conditions were the same as in Example 1, except that cuprous cyanide in Example 1 was replaced with an equimolar amount of cuprous chloride, and the rest were the same as in Example 1. Vacuum distillation yielded 11.95 g of product.

[0069] Example 10

[0070] The process and conditions were the same as in Example 1, except that cuprous cyanide in Example 1 was replaced with an equimolar amount of cuprous bromide, and the rest were the same as in Example 1. Vacuum distillation yielded 13.42 g of product.

[0071] Example 11

[0072] The process and conditions were the same as in Example 1, except that cuprous cyanide in Example 1 was replaced with an equimolar amount of cuprous iodide, and the rest were the same as in Example 1. Vacuum distillation yielded 15.36 g of product.

[0073] Example 12

[0074] The process and conditions were the same as in Example 1, except that cuprous cyanide in Example 1 was replaced with an equimolar amount of cuprous acetate, and the rest were the same as in Example 1. Vacuum distillation yielded 10.78 g of product.

[0075] Example 13

[0076] The process and conditions were the same as in Example 1, except that the solvent dichloromethane in Example 1 was replaced with an equal volume of methanol, and the rest remained the same as in Example 1. Reduced pressure distillation yielded 3.26 g of product.

[0077] Example 14

[0078] The process and conditions were the same as in Example 1, except that the solvent dichloromethane in Example 1 was replaced with an equal volume of ethyl acetate, and the rest remained the same as in Example 1. Vacuum distillation yielded 16.28 g of product.

[0079] Example 15

[0080] The process and conditions were the same as in Example 1, except that the solvent dichloromethane in Example 1 was replaced with an equal volume of 1,2-dichloroethane, and the rest remained the same as in Example 1. Vacuum distillation yielded 17.36 g of product.

[0081] Example 16

[0082] The process and conditions were the same as in Example 1, except that the solvent dichloromethane in Example 1 was replaced with an equal volume of acetonitrile, and the rest remained the same as in Example 1. Reduced pressure distillation yielded 13.75 g of product.

[0083] Example 17

[0084] The process and conditions were the same as in Example 1, except that the solvent dichloromethane in Example 1 was replaced with an equal volume of tetrahydrofuran, and the rest were the same as in Example 1. Vacuum distillation yielded 11.25 g of product.

[0085] Example 18

[0086] The process and conditions were the same as in Example 1, except that the solvent dichloromethane in Example 1 was replaced with an equal volume of DMSO, and the rest remained the same as in Example 1. Vacuum distillation yielded 6.58 g of product.

[0087] Example 19

[0088] The process and conditions were the same as in Example 1, except that the 0.689 g (4 mmol) 4-OH-TEMPO in Example 1 was replaced with 0.517 g (3 mmol) 4-OH-TEMPO, otherwise the same as in Example 1. Reduced pressure distillation yielded 18.12 g of product.

[0089] The above-described embodiments are merely examples of implementation methods of the present invention, but should not be construed as limiting the scope of the present invention. It should be noted that those skilled in the art can make various modifications and improvements without departing from the concept of the present invention, and these modifications and improvements are all within the scope of protection of the present invention.

Claims

1. A method for synthesizing a citral compound, characterized in that: Using nerol and / or geraniol as raw materials, and utilizing a complex formed by TEMPO, imidazole compounds and cuprous salts as a catalyst, a single configuration of citral is generated through an oxidation reaction under oxygen conditions.

2. The synthesis method according to claim 1, characterized in that: The nerol and geraniol compounds each have the following structures:

3. The synthesis method according to claim 1, characterized in that: The single-configuration citral compounds each have the following structures:

4. The synthesis method according to claim 1, characterized in that: The general structural formula of TEMPO (2,2,6,6-tetramethylpiperidine oxide) is as follows: R1 is selected from H, C1-C 10 Alkyl, C3-C8 cycloalkyl, C1-C 40 Alkoxy, halogen, nitro, hydroxyl, C1-C 10 One or more of ester, cyano, phenyl, substituted phenyl, benzyl, and substituted benzyl groups, wherein the substituents on the substituted phenyl and substituted benzyl groups are respectively selected from one or more of C1-C40 alkoxy groups (preferably C1-C10 alkoxy groups, such as methoxy, ethoxy, etc.) and C1-C40 alkyl groups (preferably C1-C10 alkyl groups, such as CH4). 3、 CH3CH 2、 (CH3)2CH 、 (CH3)3C, etc., one or more of the following: C1 to C40 alkyl, nitro, cyano, halogen (F, Cl, Br, I), with 1 to 5 substituents.

5. The synthesis method according to claim 1, characterized in that: The imidazole compounds described herein have the following general structural formula: R1, R2, and R3 are H, C1-C, and C1-C, respectively. 10 Alkyl, C3-C8 cycloalkyl, C1-C 40 Alkoxy, hydroxyl, C1-C 10 Aldehyde, halogen, nitro, C1-C 10 One or more of ester, cyano, phenyl, amino, substituted phenyl, benzyl, and substituted benzyl groups are selected, respectively. The substituents on the substituted phenyl and substituted benzyl groups are selected from one or more of C1-C40 alkoxy groups (preferably C1-C10 alkoxy groups, such as methoxy, ethoxy, etc.) and C1-C40 alkyl groups (preferably C1-C10 alkyl groups, such as CH4). 3、 CH3CH 2、 (CH3)2CH 、 (CH3)3C, etc., one or more of the following: nitro, cyano, halogen (F, Cl, Br, I), with 1-5 substituents.

6. The synthesis method according to claim 1, characterized in that: The cuprous salt is selected from one or more of the cuprous salts such as CuCl, CuBr, CuI, Cu2S, CH3COOCu, Cu2O, and CuCN, with CuCN being preferred.

7. The synthesis method according to claim 1, characterized in that: The reaction medium (solvent) is at least one or more of toluene, benzene, methanol, ethanol, isopropanol, dichloromethane, dichloroethane, carbon tetrachloride, ethyl acetate, diethyl ether, tetrahydrofuran, dimethyl sulfoxide or N,N-dimethylformamide, preferably dichloromethane.

8. The synthesis method according to claim 1, characterized in that: The molar ratio of the alcohol (nerol and / or geraniol): imidazole compound: cuprous salt: TEMPO is 10000-10:2-4:1:1-6, preferably 700-10:2:1:2-4, more preferably 500-10:2:1:3-4; The concentration of the alcohol in the solvent is 0.1 mol. The solvent used for the alcohol is 50-200 mL, preferably 70-120 mL.

9. The synthesis method according to any one of claims 1-8, characterized in that: The specific process is as follows: Add nerol and / or geraniol to the solvent, stir, then add TEMPO, imidazole, and cuprous salt; introduce oxygen and react at 20-100℃ for 1-24 hours.

10. The synthesis method according to claim 9, characterized in that: The specific process is as follows: Post-reaction treatment: Water was added to the reaction system, and the mixture was separated. The aqueous phase was extracted with dichloromethane, and the organic phases were combined. The mixture was then washed with saturated sodium thiosulfate and saturated brine, dried with anhydrous sodium sulfate, and the solvent was removed. The product was then obtained by vacuum distillation.

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