Preparation method of methyl ether compound of fatty alcohol

Abstract

The invention belongs to the field of organic chemistry, and particularly relates to a preparation method of a methyl ether compound of fatty alcohol. According to the synthesis method, fatty alcohol is taken as a raw material, an ultra-dry solvent is taken as a solvent, a methoxyl transfer reagent is taken as a methylation reagent, methoxyl active ions are generated in situ, and the methoxyl active ions are subjected to nucleophilic substitution reaction on alcoholic hydroxyl carbon sites, so that the methyl ether compound is synthesized, the method is mild in condition, the raw materials are easy to obtain, the operation is simple, and the product is easy to separate; the product purity is 95% or above, and large-scale preparation can be achieved. The preparation route provided by the invention is beneficial to expanding the application of the compound in the fields of pesticides, medicines, chemical industry, energy sources, materials and the like.

Description

Technical Field

[0001] The invention belongs to the field of organic chemistry, and particularly relates to a method for preparing a methyl ether compound of a fatty alcohol. Background Art

[0002] The alcohol hydroxyl group of fatty alcohol compounds has high polarity, and the oxygen atom on the hydroxyl group easily forms a hydrogen bond with the hydroxyl hydrogen in another alcohol molecule, resulting in a higher boiling point for such compounds than alkanes. As the number of carbon atoms or hydroxyl groups increases, the boiling point increases, and they are generally difficult to volatilize. As fatty alcohol compounds play an important role in people's daily lives, they are often used in pesticides, medicines, disinfectants, flavor enhancers, antifreeze, and are also widely used in the fields of energy and materials. Therefore, the analysis and detection of such compounds is of great significance for understanding the composition and functional properties of alcohol-containing samples.

[0003] In gas chromatography analysis, fatty alcohol compounds often have problems such as low instrument response value and low detection sensitivity. The simplest and most feasible way is to derivatize such substances, reduce their polarity and boiling point, and improve the detection limit. Silylation has been widely used in the conversion of alcohol hydroxyl groups, but the use of silanization agents often accelerates the column loss of gas chromatography and gradually reduces the sensitivity of the detector. Therefore, the development of a new derivatization method is of great value for the analysis of alcohol substances in gas chromatography. The methyl etherification reaction of fatty alcohols not only greatly reduces the boiling point of the derivative products relative to fatty alcohols, but also improves the sensitivity of the detector and the detection limit. However, most of the commonly used methylation reagents are currently hazardous chemicals (such as methyl iodide, dimethyl sulfate, etc.), have high requirements on the qualifications of consumers, and are not easy to obtain. In addition, when using methanol as a methylation reagent, a strong corrosive acid (such as concentrated sulfuric acid, concentrated hydrochloric acid, methanesulfonic acid, trifluoromethanesulfonic acid, etc.) is often required to initiate and catalyze the etherification reaction. The post-treatment of the reaction is dangerous and the operation steps are also cumbersome. When methyl trifluoromethanesulfonate is used as a methylating agent, it is often necessary to use a highly active strong base (such as sodium hydride, potassium hydride, etc.) in advance to convert the alcohol hydroxyl group. In the reaction process, flammable and explosive hydrogen will be produced, which is not suitable for large-scale preparation in an environment with limited air circulation.

[0004] In view of this, developing a direct and simple tandem preparation method that does not require step-by-step processing for the efficient synthesis of methyl ether compounds and rapid analysis of corresponding fatty alcohols, which can be used to obtain a series of important synthetic intermediates and drugs, agrochemicals, and materials, is a technical problem that urgently needs to be solved in this research field. Summary of the invention

[0005] The object of the present invention is to provide a simple and direct method for preparing a methyl ether compound of a fatty alcohol.

[0006] The technical solution adopted by the present invention is as follows:

[0007] A method for preparing a methyl ether compound of a fatty alcohol comprises the following steps:

[0008] S1: under an inert gas atmosphere and stirring conditions at -78°C to 20°C, a methoxy transfer reagent, an organic phosphine and an initiator are added to an ultra-dry solvent; the molar ratio of the methoxy transfer reagent to the starting material fatty alcohol is 1 to 1000; the molar ratio of the organic phosphine to the methoxy transfer reagent is 1 to 100; the molar ratio of the initiator to the methoxy transfer reagent is 0.01 to 0.5; the concentration of the reaction system is a ratio of the molar number of the methoxy transfer reagent to the volume of the ultra-dry solvent of 0.01 to 100 mol / L;

[0009] The methoxy transfer reagent is selected from 1-methoxy-1,2,3-benzoiodine-3,3-thiophene dioxide (MOBI);

[0010] The ultra-dry solvent is selected from any one of dichloromethane (DCM), tetrachloromethane, dichloroethane, acetone, acetonitrile, propionitrile, butyronitrile, hexafluoroisopropanol or dimethyl sulfoxide, or a combination of two or more thereof; the organic phosphine is selected from any one of triphenylphosphine (TPP), tri(pentafluorophenyl)phosphine, tri(p-tolyl)phosphine, tri(cyclohexyl)phosphine, tributylphosphine or triethylphosphine, or a combination of two or more thereof;

[0011] The initiator is selected from any one or a combination of two or more of iodine (I2), azobisisobutyronitrile (AIBN), benzoyl peroxide (BPO), tert-butyl peroxide (TBHP) or meta-chloroperbenzoic acid (mCPBA);

[0012] S2: Adjust the system temperature to -78°C to 70°C, add the starting material fatty alcohol at once under argon atmosphere and stirring, and react until complete;

[0013] The fatty alcohol is selected from alkyl alcohol or alkyl alcohol with substituents; the substituent types include fluorine, chlorine, bromine, iodine, trifluoromethyl, difluoromethyl, trichloromethyl, dichloromethyl, cyano, ester, acyl, sulfonyl, carboxyl, nitro, and aryl, and the number of substituents is not limited;

[0014] S3: After the reaction is completed, zinc chloride and ethanol are added, and after the solid is precipitated, a poor solvent is added and the mixture is shaken and filtered; the molar ratio of zinc chloride to organic phosphine is 1 to 100; the amount of ethanol is 0.01 to 10 mL / mmol zinc chloride; the amount of the poor solvent is 0.1 to 100 mL / mmol zinc chloride;

[0015] The poor solvent is selected from any one or a combination of two or more of n-pentane, n-hexane (Hex), n-heptane, ethyl ether, methyl tert-butyl ether, isopropyl ether, tetrahydrofuran or dioxane;

[0016] S4: After step S3 is completed, impurities in the filtered filtrate are removed to obtain a methyl ether compound of a fatty alcohol.

[0017] Preferably, in the steps S1 to S3, the reaction is carried out for 0.01 to 48 hours, and the stirring condition is 100 to 100000 rpm.

[0018] Preferably, in step S1, the methoxy transfer reagent is 1-methoxy-1,2,3-benzoiodine-3,3-dioxide (MOBI), the ultra-dry solvent is dichloromethane (DCM), and the initiator is elemental iodine (I2); in step S3, the poor solvent is Hex.

[0019] Furthermore, the preparation method of the 1-methoxy-1,2,3-benzoiodine-thiolane-3,3-dioxide (MOBI) is as follows:

[0020] Take 5 molar parts of 1-hydroxy-1,2,3-benzoiodine thiolane-3,3-dioxide (HBI), add 2 parts by volume of trimethyl orthoformate (TMOF) and 2 parts by volume of ultra-dry dichloromethane (DCM) at 5-15° C. in an inert gas protection atmosphere, so that the ratio of 1-hydroxy-1,2,3-benzoiodine thiolane-3,3-dioxide (HBI) to trimethyl orthoformate (TMOF) is 1-4 mmol / mL, stir well, slowly raise the reaction temperature to room temperature, continue stirring until the reaction is fully reacted; remove TMOF and DCM, add 8-15 parts by volume of ultra-dry dichloromethane (DCM) to redissolve, filter and remove insoluble matter, and remove DCM to obtain 1-methoxy-1,2,3-benzoiodine thiolane-3,3-dioxide (MOBI).

[0021] Further, the reaction formula is expressed as the following reaction formula I:

[0022]

[0023] Wherein, the compound of formula I represents a fatty alcohol, wherein R represents an alkyl group or a substituted alkyl group; the compound of formula II represents a methyl ether compound of a fatty alcohol;

[0024] The number of carbon atoms of the alkyl or substituted alkyl represented by R is ≥ 1. The substituents include, but are not limited to, fluorine, chlorine, bromine, iodine, trifluoromethyl, difluoromethyl, trichloromethyl, dichloromethyl, cyano, ester, acyl, sulfonyl, carboxyl, nitro, and aryl. The number and position of the substituents are not limited.

[0025] Furthermore, the amount of I2 used is 0.01 to 0.2 equivalents of the starting material fatty alcohol. The method of the present invention preferably uses iodine (I2) as an initiator, and commercial reagents can be used without special treatment.

[0026] Furthermore, the amount of MOBI is 1 to 3 times the equivalent of the starting material fatty alcohol. The method of the present invention preferably uses 1-methoxy-1,2,3-benzoiodine thiophene-3,3-dioxide (MOBI) as a methoxy transfer reagent and is prepared by a known method. Generally, the amount of MOBI is preferably 1 to 3 times the equivalent of the starting material fatty alcohol, but when the fatty alcohol is a secondary alcohol or a tertiary alcohol, the more MOBI is used, the better the reaction effect.

[0027] Furthermore, the amount of triphenylphosphine (TPP) used is 1 to 3 times the equivalent of the fatty alcohol. The method of the present invention requires the addition of triphenylphosphine (TPP), and commercial reagents can be used without special treatment.

[0028] Furthermore, the amount of DCM used is 1-20 mL / mmol of fatty alcohol. The method of the present invention preferably uses dichloromethane (DCM) as an ultra-dry solvent, and commercial reagents can be used without special treatment.

[0029] Furthermore, the amount of n-hexane (Hex) used is 10 to 100 times the volume of DCM, and Hex plays a key role in cleaning the target product.

[0030] The method of the present invention uses fatty alcohol as a reaction substrate and MOBI as a methoxy transfer reagent. Under the action of I2 and TPP, a tandem reaction occurs in ultra-dry DCM to prepare a methyl ether compound through a one-pot method. The reaction conditions are mild, the product is easy to separate, and the method can be widely used in preparing methyl ether compounds of various fatty alcohols.

[0031] Compared with the prior art, the present invention has the positive effect that: a methoxy transfer reagent is directly used as a methylating reagent, a highly active methoxytriphenylphosphonium is first generated in situ, and a methyl ether compound of a fatty alcohol is efficiently, directly and simply prepared through a subsequent Appel-like reaction without separation and purification. The present invention solves the problems in the prior art that most commonly used methylating reagents are limited to hazardous chemicals (such as methyl iodide, dimethyl sulfate, etc.), have high requirements for the qualifications for purchase and use, or require a strong corrosive acid (such as concentrated sulfuric acid, concentrated hydrochloric acid, etc.) to initiate the etherification reaction, and the post-processing is relatively dangerous and cumbersome, or require a highly active strong base (such as sodium hydride, potassium hydride, etc.) to pre-convert the alcohol hydroxyl group, generate flammable and explosive hydrogen, and are not suitable for mass preparation. Specific implementation methods

[0033] The present invention will be further described below in conjunction with specific embodiments. These embodiments should be understood to be only used to illustrate the present invention and not to limit the scope of protection of the present invention. After reading the contents of the present invention, those skilled in the art may make various changes or modifications to the present invention, and these equivalent changes and modifications also fall within the scope defined by the claims of the present invention. However, the scope of the present invention is not limited in any way.

[0034] The synthesis method of 1-methoxy-1,2,3-benzoiodine-thiolane-3,3-dioxide (MOBI) used in the following Examples 1 to 6 is as follows:

[0035] In a 25mL round-bottom flask, add 5mmol 1-hydroxy-1,2,3-benzoiodothiolane-3,3-dioxide (HBI), add 2mL trimethyl orthoformate (TMOF) and 2mL ultra-dry dichloromethane (DCM) at 10°C in an argon atmosphere, stir for 1h, then slowly raise the reaction temperature to room temperature, and continue stirring for 12h. Remove TMOF and DCM by vacuum distillation, add 10mL ultra-dry dichloromethane (DCM) to redissolve and filter to remove insoluble matter, spin dry DCM to obtain 1-methoxy-1,2,3-benzoiodothiolane-3,3-dioxide (MOBI), whose structure is shown below:

[0036]

[0037] The compound is a white solid with a yield of 90%. Its NMR data are as follows:

[0038] 1 H NMR (DMSO-d6, 300MHz): δ = 8.24-7.90 (m, 2H), 7.76-7.64 (m, 2H), 4.26 (s, 3H) ppm.

[0039] 13 C NMR (DMSO-d6, 75MHz): δ = 137.1, 134.2, 133.1, 132.9, 127.0, 120.3, 64.1ppm.

[0040] Example 1

[0041] Synthesis of 2-(Phenyl)ethyl Methyl Ether

[0042] In a 25mL round-bottom flask, add 1mmol 1-methoxy-1,2,3-benzoiodothiolane-3,3-dioxide (MOBI), 1mmol triphenylphosphine (TPP), 0.1mmol iodine (I2) and 10mL ultra-dry dichloromethane (DCM). In an argon atmosphere, stir at 10°C for 10min, then raise the temperature of the reaction flask to room temperature and continue stirring for 30min. Under argon protection, add 1mmol 2-phenylethanol to the reaction system and continue stirring for 1h. After the reaction is completed, add 6mmol zinc chloride and 5mL ethanol. After the solid is precipitated, add 5mL n-hexane and shake and filter. The organic solvent in the filtrate is spin-dried to obtain a crude product, and finally column chromatography is used to separate pure 2-phenylethyl methyl ether.

[0043]

[0044] The compound is a colorless liquid with a yield of 31%. Its NMR data are as follows:

[0045] 1 H NMR (CDCl3, 300MHz): δ = 7.37-7.24 (m, 5H), 3.65 (t, J = 7.1Hz, 2H), 3.40 (s, 3H), 2.93 (t, J = 7.1Hz, 2H) ppm.

[0046] Example 2

[0047] Synthesis of 2-(Phenyl)ethyl Methyl Ether

[0048] In a 25mL round-bottom flask, add 2mmol 1-methoxy-1,2,3-benzoiodothiolane-3,3-dioxide (MOBI), 2mmol triphenylphosphine (TPP), 0.1mmol iodine (I2) and 10mL ultra-dry dichloromethane (DCM). In an argon atmosphere, stir at 0°C for 10min, then raise the temperature of the reaction flask to room temperature and continue stirring for 5min. Under argon protection, add 1mmol 2-phenylethanol to the reaction system and continue stirring for 1h. After the reaction is completed, add 6mmol zinc chloride and 5mL ethanol. After the solid is precipitated, add 5mL n-hexane and shake and filter. The organic solvent in the filtrate is spin-dried to obtain a crude product, and finally separated by column chromatography to obtain pure 2-phenylethyl methyl ether.

[0049]

[0050] The compound is a colorless liquid with a yield of 88%. Its NMR data are as follows:

[0051] 1H NMR (CDCl3, 300MHz): δ = 7.37-7.24 (m, 5H), 3.65 (t, J = 7.1Hz, 2H), 3.40 (s, 3H), 2.93 (t, J = 7.1Hz, 2H) ppm.

[0052] Example 3

[0053] Synthesis of 2-(Phenyl)ethyl Methyl Ether

[0054] In a 25mL round-bottom flask, add 2mmol 1-methoxy-1,2,3-benzoiodothiolane-3,3-dioxide (MOBI), 2mmol triphenylphosphine (TPP), 0.1mmol AIBN and 10mL ultra-dry dichloromethane (DCM). In an argon atmosphere, stir at 10°C for 10min, then raise the temperature of the reaction flask to room temperature and continue stirring for 30min. Under argon protection, add 1mmol 2-phenylethanol to the reaction system and continue stirring for 1h. After the reaction is completed, add 6mmol zinc chloride and 5mL ethanol. After the solid is precipitated, add 5mL n-hexane and shake and filter. The organic solvent in the filtrate is spin-dried to obtain a crude product, and finally separated by column chromatography to obtain pure 2-phenylethyl methyl ether.

[0055]

[0056] The compound is a colorless liquid with a yield of 7%. Its NMR data are as follows:

[0057] 1 H NMR (CDCl3, 300MHz): δ = 7.37-7.24 (m, 5H), 3.65 (t, J = 7.1Hz, 2H), 3.40 (s, 3H), 2.93 (t, J = 7.1Hz, 2H) ppm.

[0058] Example 4

[0059] Synthesis of 2-(Phenyl)ethyl Methyl Ether

[0060] In a 25mL round-bottom flask, add 2mmol 1-methoxy-1,2,3-benzoiodothiolane-3,3-dioxide (MOBI), 2mmol triphenylphosphine (TPP), 0.1mmol BPO and 10mL ultra-dry dichloromethane (DCM). In an argon atmosphere, stir at 10°C for 10min, then raise the temperature of the reaction flask to room temperature and continue stirring for 30min. Under argon protection, add 1mmol 2-phenylethanol to the reaction system and continue stirring for 1h. After the reaction is completed, add 6mmol zinc chloride and 5mL ethanol. After the solid is precipitated, add 5mL n-hexane and shake and filter. The organic solvent in the filtrate is spin-dried to obtain a crude product, and finally separated by column chromatography to obtain pure 2-phenylethyl methyl ether.

[0061]

[0062] The compound is a colorless liquid with a yield of 5%. Its NMR data are as follows:

[0063] 1 H NMR (CDCl3, 300MHz): δ = 7.37-7.24 (m, 5H), 3.65 (t, J = 7.1Hz, 2H), 3.40 (s, 3H), 2.93 (t, J = 7.1Hz, 2H) ppm.

[0064] Example 5

[0065] Synthesis of 2-(Phenyl)ethyl Methyl Ether

[0066] In a 25mL round-bottom flask, add 2mmol 1-methoxy-1,2,3-benzoiodothiolane-3,3-dioxide (MOBI), 2mmol triphenylphosphine (TPP), 0.1mmol TBHP and 10mL ultra-dry dichloromethane (DCM). In an argon atmosphere, stir at 10°C for 10min, then raise the temperature of the reaction flask to room temperature and continue stirring for 30min. Under argon protection, add 1mmol 2-phenylethanol to the reaction system and continue stirring for 1h. After the reaction is completed, add 6mmol zinc chloride and 5mL ethanol. After the solid is precipitated, add 5mL n-hexane and shake and filter. The organic solvent in the filtrate is spin-dried to obtain a crude product, and finally separated by column chromatography to obtain pure 2-phenylethyl methyl ether.

[0067]

[0068] The compound is a colorless liquid with a yield of 3%. Its NMR data are as follows:

[0069] 1H NMR (CDCl3, 300MHz): δ = 7.37-7.24 (m, 5H), 3.65 (t, J = 7.1Hz, 2H), 3.40 (s, 3H), 2.93 (t, J = 7.1Hz, 2H) ppm.

[0070] Example 6

[0071] Synthesis of 2-(Phenyl)ethyl Methyl Ether

[0072] In a 25mL round-bottom flask, add 2mmol 1-methoxy-1,2,3-benzoiodothiolane-3,3-dioxide (MOBI), 2mmol triphenylphosphine (TPP), 0.03mmol mCPBA and 10mL ultra-dry dichloromethane (DCM). In an argon atmosphere, stir at 10°C for 10min, then raise the temperature of the reaction flask to room temperature and continue stirring for 30min. Under argon protection, add 1mmol 2-phenylethanol to the reaction system and continue stirring for 1h. After the reaction is completed, add 6mmol zinc chloride and 5mL ethanol. After the solid is precipitated, add 5mL n-hexane and shake and filter. The organic solvent in the filtrate is spin-dried to obtain a crude product, and finally separated by column chromatography to obtain pure 2-phenylethyl methyl ether.

[0073]

[0074] The compound is a colorless liquid with a yield of 7%. Its NMR data are as follows:

[0075] 1 H NMR (CDCl3, 300MHz): δ = 7.37-7.24 (m, 5H), 3.65 (t, J = 7.1Hz, 2H), 3.40 (s, 3H), 2.93 (t, J = 7.1Hz, 2H) ppm.

[0076] Example 7

[0077] Synthesis of 2-(Phenyl)ethyl Methyl Ether

[0078] In a 25mL round-bottom flask, add 2mmol 1-methoxy-1,2,3-benzoiodothiolane-3,3-dioxide (MOBI), 2mmol tri(cyclohexyl)phosphine, 0.1mmol iodine (I2) and 10mL ultra-dry dichloromethane (DCM). In an argon atmosphere, stir at 10°C for 10min, then raise the temperature of the reaction flask to room temperature and continue stirring for 30min. Under argon protection, add 1mmol 2-phenylethanol to the reaction system and continue stirring for 1h. After the reaction is completed, add 6mmol zinc chloride and 5mL ethanol. After the solid is precipitated, add 5mL n-hexane and shake and filter. The organic solvent in the filtrate is spin-dried to obtain a crude product, and finally column chromatography is used to separate pure 2-phenylethyl methyl ether.

[0079]

[0080] The compound is a colorless liquid with a yield of 9%. Its NMR data are as follows:

[0081] 1 H NMR (CDCl3, 300MHz): δ = 7.37-7.24 (m, 5H), 3.65 (t, J = 7.1Hz, 2H), 3.40 (s, 3H), 2.93 (t, J = 7.1Hz, 2H) ppm.

[0082] Example 8

[0083] Synthesis of 2-(Phenyl)ethyl Methyl Ether

[0084] In a 25mL round-bottom flask, add 2mmol 1-methoxy-1,2,3-benzoiodothiolane-3,3-dioxide (MOBI), 2mmol tri(p-tolyl)phosphine, 0.1mmol iodine (I2) and 10mL ultra-dry dichloromethane (DCM). In an argon atmosphere, stir at 10°C for 10min, then raise the temperature of the reaction flask to room temperature and continue stirring for 30min. Under argon protection, add 1mmol 2-phenylethanol to the reaction system and continue stirring for 1h. After the reaction is completed, add 6mmol zinc chloride and 5mL ethanol. After the solid is precipitated, add 5mL n-hexane and shake and filter. The organic solvent in the filtrate is spin-dried to obtain a crude product, and finally separated by column chromatography to obtain pure 2-phenylethyl methyl ether.

[0085]

[0086] The compound is a colorless liquid with a yield of 11%. Its NMR data are as follows:

[0087] 1H NMR (CDCl3, 300MHz): δ = 7.37-7.24 (m, 5H), 3.65 (t, J = 7.1Hz, 2H), 3.40 (s, 3H), 2.93 (t, J = 7.1Hz, 2H) ppm.

[0088] Example 9

[0089] Synthesis of 2-(Phenyl)ethyl Methyl Ether

[0090] In a 25mL round-bottom flask, add 2mmol 1-methoxy-1,2,3-benzoiodothiolane-3,3-dioxide (MOBI), 2mmol triphenylphosphine (TPP), 0.1mmol iodine (I2) and 10mL ultra-dry dichloroethane. In an argon atmosphere, stir at 10°C for 10min, then raise the temperature of the reaction flask to room temperature and continue stirring for 30min. Under argon protection, add 1mmol 2-phenylethanol to the reaction system and continue stirring for 1h. After the reaction is completed, add 6mmol zinc chloride and 5mL ethanol. After the solid is precipitated, add 5mL n-hexane and shake and filter. The organic solvent in the filtrate is spin-dried to obtain a crude product, and finally separated by column chromatography to obtain pure 2-phenylethyl methyl ether.

[0091]

[0092] The compound is a colorless liquid with a yield of 83%. Its NMR data are as follows:

[0093] 1 H NMR (CDCl3, 300MHz): δ = 7.37-7.24 (m, 5H), 3.65 (t, J = 7.1Hz, 2H), 3.40 (s, 3H), 2.93 (t, J = 7.1Hz, 2H) ppm.

[0094] Example 10

[0095] Synthesis of 2-(Phenyl)ethyl Methyl Ether

[0096] In a 25mL round-bottom flask, add 2mmol 1-methoxy-1,2,3-benzoiodothiolane-3,3-dioxide (MOBI), 2mmol triphenylphosphine (TPP), 0.1mmol iodine (I2) and 10mL ultra-dry carbon tetrachloride. In an argon atmosphere, stir at 10°C for 10min, then raise the temperature of the reaction flask to room temperature and continue stirring for 30min. Under argon protection, add 1mmol 2-phenylethanol to the reaction system and continue stirring for 1h. After the reaction is completed, add 6mmol zinc chloride and 5mL ethanol. After the solid is precipitated, add 5mL n-hexane and shake and filter. The organic solvent in the filtrate is spin-dried to obtain a crude product, and finally separated by column chromatography to obtain pure 2-phenylethyl methyl ether.

[0097]

[0098] The compound is a colorless liquid with a yield of 77%. Its NMR data are as follows:

[0099] 1 H NMR (CDCl3, 300MHz): δ = 7.37-7.24 (m, 5H), 3.65 (t, J = 7.1Hz, 2H), 3.40 (s, 3H), 2.93 (t, J = 7.1Hz, 2H) ppm.

[0100] Embodiment 11

[0101] Synthesis of 2-(Phenyl)ethyl Methyl Ether

[0102] In a 25mL round-bottom flask, add 2mmol 1-methoxy-1,2,3-benzoiodothiolane-3,3-dioxide (MOBI), 2mmol triphenylphosphine (TPP), 0.1mmol iodine (I2) and 10mL ultra-dry acetonitrile. In an argon atmosphere, stir at 10°C for 10min, then raise the temperature of the reaction flask to room temperature and continue stirring for 30min. Under argon protection, add 1mmol 2-phenylethanol to the reaction system and continue stirring for 1h. After the reaction is completed, add 6mmol zinc chloride and 5mL ethanol. After the solid is precipitated, add 5mL n-hexane and shake and filter. The organic solvent in the filtrate is spin-dried to obtain a crude product, and finally separated by column chromatography to obtain pure 2-phenylethyl methyl ether.

[0103]

[0104] The compound is a colorless liquid with a yield of 6%. Its NMR data are as follows:

[0105] 1H NMR (CDCl3, 300MHz): δ = 7.37-7.24 (m, 5H), 3.65 (t, J = 7.1Hz, 2H), 3.40 (s, 3H), 2.93 (t, J = 7.1Hz, 2H) ppm.

[0106] Example 12

[0107] Synthesis of 2-(Phenyl)ethyl Methyl Ether

[0108] In a 25mL round-bottom flask, add 2mmol 1-methoxy-1,2,3-benzoiodothiolane-3,3-dioxide (MOBI), 2mmol triphenylphosphine (TPP), 0.1mmol iodine (I2) and 10mL ultra-dry acetone. In an argon atmosphere, stir at 10°C for 10min, then raise the temperature of the reaction flask to room temperature and continue stirring for 30min. Under argon protection, add 1mmol 2-phenylethanol to the reaction system and continue stirring for 1h. After the reaction is completed, add 6mmol zinc chloride and 5mL ethanol. After the solid is precipitated, add 5mL n-hexane and shake and filter. The organic solvent in the filtrate is spin-dried to obtain a crude product, and finally separated by column chromatography to obtain pure 2-phenylethyl methyl ether.

[0109]

[0110] The compound is a colorless liquid with a yield of 14%. Its NMR data are as follows:

[0111] 1 H NMR (CDCl3, 300MHz): δ = 7.37-7.24 (m, 5H), 3.65 (t, J = 7.1Hz, 2H), 3.40 (s, 3H), 2.93 (t, J = 7.1Hz, 2H) ppm.

[0112] Embodiment 13

[0113] Synthesis of 2-(Phenyl)ethyl Methyl Ether

[0114] In a 25mL round-bottom flask, add 2mmol 1-methoxy-1,2,3-benzoiodothiolane-3,3-dioxide (MOBI), 2mmol triphenylphosphine (TPP), 0.1mmol iodine (I2) and 10mL hexafluoroisopropanol. In an argon atmosphere, stir at 10°C for 10min, then raise the temperature of the reaction flask to room temperature and continue stirring for 30min. Under argon protection, add 1mmol 2-phenylethanol to the reaction system and continue stirring for 1h. After the reaction is completed, add 6mmol zinc chloride and 5mL ethanol. After the solid is precipitated, add 5mL n-hexane and shake and filter. The organic solvent in the filtrate is spin-dried to obtain a crude product, and finally separated by column chromatography to obtain pure 2-phenylethyl methyl ether.

[0115]

[0116] The compound is a colorless liquid with a yield of 6%. Its NMR data are as follows:

[0117] 1 H NMR (CDCl3, 300MHz): δ = 7.37-7.24 (m, 5H), 3.65 (t, J = 7.1Hz, 2H), 3.40 (s, 3H), 2.93 (t, J = 7.1Hz, 2H) ppm.

[0118] Embodiment 14

[0119] Synthesis of 2-(Phenyl)ethyl Methyl Ether

[0120] In a 25mL round-bottom flask, add 2mmol 1-methoxy-1,2,3-benzoiodothiolane-3,3-dioxide (MOBI), 2mmol triphenylphosphine (TPP), 0.1mmol iodine (I2) and 10mL ultra-dry dimethyl sulfoxide. In an argon atmosphere, stir at 10°C for 10min, then raise the temperature of the reaction flask to room temperature and continue stirring for 30min. Under argon protection, add 1mmol 2-phenylethanol to the reaction system and continue stirring for 1h. After the reaction is completed, add 6mmol zinc chloride and 5mL ethanol. After the solid is precipitated, add 5mL n-hexane and shake and filter. The organic solvent in the filtrate is spin-dried to obtain a crude product, and finally separated by column chromatography to obtain pure 2-phenylethyl methyl ether.

[0121]

[0122] The compound is a colorless liquid with a yield of 3%. Its NMR data are as follows:

[0123] 1H NMR (CDCl3, 300MHz): δ = 7.37-7.24 (m, 5H), 3.65 (t, J = 7.1Hz, 2H), 3.40 (s, 3H), 2.93 (t, J = 7.1Hz, 2H) ppm.

[0124] Embodiment 15

[0125] Synthesis of 2-(Phenyl)ethyl Methyl Ether

[0126] In a 25mL round-bottom flask, add 2mmol 1-methoxy-1,2,3-benzoiodothiolane-3,3-dioxide (MOBI), 2mmol triphenylphosphine (TPP), 0.1mmol iodine (I2) and 10mL ultra-dry dichloromethane (DCM), and stir at room temperature for 30min in an argon atmosphere. Under argon protection, add 1mmol 2-phenylethanol to the reaction system and continue stirring for 1h. After the reaction is completed, add 6mmol zinc chloride and 5mL ethanol. After the solid is precipitated, add 5mL n-hexane and shake and filter. The organic solvent in the filtrate is spin-dried to obtain a crude product, and finally separated by column chromatography to obtain pure 2-phenylethyl methyl ether.

[0127]

[0128] The compound is a colorless liquid with a yield of 73%. Its NMR data are as follows:

[0129] 1 H NMR (CDCl3, 300MHz): δ = 7.37-7.24 (m, 5H), 3.65 (t, J = 7.1Hz, 2H), 3.40 (s, 3H), 2.93 (t, J = 7.1Hz, 2H) ppm.

[0130] Example 16

[0131] Synthesis of 2-(Phenyl)ethyl Methyl Ether

[0132] In a 25mL round-bottom flask, add 2mmol 1-methoxy-1,2,3-benzoiodothiolane-3,3-dioxide (MOBI), 2mmol triphenylphosphine (TPP), 0.1mmol iodine (I2) and 10mL ultra-dry dichloroethane. In an argon atmosphere, stir at 10°C for 10min, then raise the temperature of the reaction flask to 70°C and continue stirring for 30min. Under argon protection, add 1mmol 2-phenylethanol to the reaction system and continue stirring for 1h. After the reaction is completed, add 6mmol zinc chloride and 5mL ethanol. After the solid is precipitated, add 5mL n-hexane and shake and filter. The organic solvent in the filtrate is spin-dried to obtain a crude product, and finally separated by column chromatography to obtain pure 2-phenylethyl methyl ether.

[0133]

[0134] The compound is a colorless liquid with a yield of 31%. Its NMR data are as follows:

[0135] 1 H NMR (CDCl3, 300MHz): δ = 7.37-7.24 (m, 5H), 3.65 (t, J = 7.1Hz, 2H), 3.40 (s, 3H), 2.93 (t, J = 7.1Hz, 2H) ppm.

[0136] Embodiment 17

[0137] Synthesis of 2-(Phenyl)ethyl Methyl Ether

[0138] In a 25mL round-bottom flask, add 2mmol 1-methoxy-1,2,3-benzoiodothiolane-3,3-dioxide (MOBI), 2mmol triphenylphosphine (TPP), 0.1mmol iodine (I2) and 10mL ultra-dry dichloromethane (DCM). In an argon atmosphere, stir at -20°C for 10min, then raise the temperature of the reaction flask to room temperature and continue stirring for 30min. Under argon protection, add 1mmol 2-phenylethanol to the reaction system and continue stirring for 1h. After the reaction is completed, add 6mmol zinc chloride and 5mL ethanol. After the solid is precipitated, add 5mL n-hexane and shake and filter. The organic solvent in the filtrate is spin-dried to obtain a crude product, and finally separated by column chromatography to obtain pure 2-phenylethyl methyl ether.

[0139]

[0140] The compound is a colorless liquid with a yield of 87%. Its NMR data are as follows:

[0141] 1H NMR (CDCl3, 300MHz): δ = 7.37-7.24 (m, 5H), 3.65 (t, J = 7.1Hz, 2H), 3.40 (s, 3H), 2.93 (t, J = 7.1Hz, 2H) ppm.

[0142] Embodiment 18

[0143] Synthesis of 2-(Phenyl)ethyl Methyl Ether

[0144] In a 25mL round-bottom flask, add 2mmol 1-methoxy-1,2,3-benzoiodothiolane-3,3-dioxide (MOBI), 2mmol triphenylphosphine (TPP), 0.1mmol iodine (I2) and 10mL ultra-dry dichloromethane (DCM). In an argon atmosphere, stir at -40°C for 10min, then raise the temperature of the reaction flask to room temperature and continue stirring for 30min. Under argon protection, add 1mmol 2-phenylethanol to the reaction system and continue stirring for 1h. After the reaction is completed, add 6mmol zinc chloride and 5mL ethanol. After the solid is precipitated, add 5mL n-hexane and shake and filter. The organic solvent in the filtrate is spin-dried to obtain a crude product, and finally column chromatography is used to separate pure 2-phenylethyl methyl ether.

[0145]

[0146] The compound is a colorless liquid with a yield of 85%. Its NMR data are as follows:

[0147] 1 H NMR (CDCl3, 300MHz): δ = 7.37-7.24 (m, 5H), 3.65 (t, J = 7.1Hz, 2H), 3.40 (s, 3H), 2.93 (t, J = 7.1Hz, 2H) ppm.

[0148] Embodiment 19

[0149] Synthesis of 2-(Phenyl)ethyl Methyl Ether

[0150] In a 25mL round-bottom flask, add 2mmol 1-methoxy-1,2,3-benzoiodothiolane-3,3-dioxide (MOBI), 2mmol triphenylphosphine (TPP), 0.1mmol iodine (I2) and 10mL ultra-dry dichloromethane (DCM). In an argon atmosphere, stir at 10°C for 10min, then raise the temperature of the reaction flask to room temperature and continue stirring for 5min. Under argon protection, add 1mmol 2-phenylethanol to the reaction system and continue stirring for 1h. After the reaction is completed, add 6mmol zinc chloride and 5mL ethanol. After the solid is precipitated, add 5mL n-hexane and shake and filter. The organic solvent in the filtrate is spin-dried to obtain a crude product, and finally separated by column chromatography to obtain pure 2-phenylethyl methyl ether.

[0151]

[0152] The compound is a colorless liquid with a yield of 90%. Its NMR data are as follows:

[0153] 1 H NMR (CDCl3, 300MHz): δ = 7.37-7.24 (m, 5H), 3.65 (t, J = 7.1Hz, 2H), 3.40 (s, 3H), 2.93 (t, J = 7.1Hz, 2H) ppm.

[0154] Embodiment 20

[0155] Synthesis of 2-(4-bromophenyl)ethyl methyl ether

[0156] In a 25mL round-bottom flask, add 2mmol 1-methoxy-1,2,3-benzoiodothiolane-3,3-dioxide (MOBI), 2mmol triphenylphosphine (TPP), 0.1mmol iodine (I2) and 10mL ultra-dry dichloromethane (DCM). In an argon atmosphere, stir at 10°C for 10min, then raise the temperature of the reaction flask to room temperature and continue stirring for 5min. Under argon protection, add 1mmol 2-(4-bromophenyl)ethanol to the reaction system and continue stirring for 1h. After the reaction is completed, add 6mmol zinc chloride and 5mL ethanol. After the solid is precipitated, add 5mL n-hexane and shake and filter. The organic solvent in the filtrate is spin-dried to obtain a crude product. Finally, column chromatography is used to separate pure 2-(4-bromophenyl)ethyl methyl ether.

[0157]

[0158] The compound is a colorless liquid with a yield of 88%. Its NMR data are as follows:

[0159] 1H NMR (CDCl3, 300MHz): δ = 7.43 (d, J = 8.4Hz, 2H), 7.12 (d, J = 8.4Hz, 2H), 3.60 (t, J = 7.0Hz, 2H), 3.36 (s, 3H), 2.85 (t, J = 7.0Hz, 2H) ppm.

[0160] Embodiment 21

[0161] Synthesis of 2-(4-methylphenyl)ethyl methyl ether

[0162] In a 25mL round-bottom flask, add 2mmol 1-methoxy-1,2,3-benzoiodothiolane-3,3-dioxide (MOBI), 2mmol triphenylphosphine (TPP), 0.1mmol iodine (I2) and 10mL ultra-dry dichloromethane (DCM). In an argon atmosphere, stir at 10°C for 10min, then raise the temperature of the reaction flask to room temperature and continue stirring for 5min. Under argon protection, add 1mmol 2-(4-methylphenyl)ethanol to the reaction system and continue stirring for 1h. After the reaction is completed, add 6mmol zinc chloride and 5mL ethanol. After the solid is precipitated, add 5mL n-hexane and shake and filter. The organic solvent in the filtrate is spin-dried to obtain a crude product. Finally, column chromatography is used to separate pure 2-(4-methylphenyl)ethyl methyl ether.

[0163]

[0164] The compound is a colorless liquid with a yield of 85%. Its NMR data are as follows:

[0165] 1 H NMR (CDCl3, 300MHz): δ = 7.13 (s, 4H), 3.60 (t, J = 7.2Hz, 2H), 3.38 (s, 3H), 2.87 (t, J = 7.2Hz, 2H), 2.34 (s, 3H) ppm.

[0166] Embodiment 22

[0167] Synthesis of 3-(4-methoxyphenyl)-1-propyl methyl ether

[0168] In a 25mL round-bottom flask, add 2mmol 1-methoxy-1,2,3-benzoiodothiolane-3,3-dioxide (MOBI), 2mmol triphenylphosphine (TPP), 0.1mmol iodine (I2) and 10mL ultra-dry dichloromethane (DCM). In an argon atmosphere, stir at 10°C for 10min, then raise the temperature of the reaction flask to room temperature and continue stirring for 5min. Under argon protection, add 1mmol 3-(4-methoxyphenyl)-1-propanol to the reaction system and continue stirring for 1h. After the reaction is completed, add 6mmol zinc chloride and 5mL ethanol. After the solid is precipitated, add 5mL n-hexane and shake and filter. The organic solvent in the filtrate is spin-dried to obtain a crude product. Finally, column chromatography is used to separate pure 3-(4-methoxyphenyl)-1-propyl methyl ether.

[0169]

[0170] The compound is a colorless liquid with a yield of 85%. Its NMR data are as follows:

[0171] 1 H NMR (CDCl3, 300MHz): δ = 7.11 (d, J = 8.8Hz, 2H), 6.84 (d, J = 8.8Hz, 2H), 3.80 (s, 3H), 3. 39(t,J=6.4Hz,2H),3.35(s,3H),2.64(dd,J=7.3,8.1Hz,2H),1.82-1.92(m,2H)ppm.

[0172] Embodiment 23

[0173] Synthesis of 2-(2-methoxyethyl)naphthalene

[0174] In a 25mL round-bottom flask, add 2mmol 1-methoxy-1,2,3-benzoiodothiolane-3,3-dioxide (MOBI), 2mmol triphenylphosphine (TPP), 0.1mmol iodine (I2) and 10mL ultra-dry dichloromethane (DCM). In an argon atmosphere, stir at 10°C for 10min, then raise the temperature of the reaction flask to room temperature and continue stirring for 5min. Under argon protection, add 1mmol 2-naphthylethanol to the reaction system and continue stirring for 1h. After the reaction is completed, add 6mmol zinc chloride and 5mL ethanol. After the solid is precipitated, add 5mL n-hexane and shake and filter. The organic solvent in the filtrate is spin-dried to obtain a crude product, and finally separated by column chromatography to obtain pure 2-(2-methoxyethyl)naphthalene.

[0175]

[0176] The compound is a colorless liquid with a yield of 79%. Its NMR data are as follows:

[0177] 1 H NMR (CDCl3, 300MHz): δ = 7.83-7.76 (m, 3H), 6.84 (d, J = 8.8Hz, 2H), 3.80 (s, 3H), 3.3 9(t,J=6.4Hz,2H),3.35(s,3H),2.64(dd,J=7.3,8.1Hz,2H),1.82-1.92(m,2H)ppm.

[0178] Embodiment 24

[0179] Synthesis of 4-Methylbenzyl ether

[0180] In a 25mL round-bottom flask, add 2mmol 1-methoxy-1,2,3-benzoiodothiolane-3,3-dioxide (MOBI), 2mmol triphenylphosphine (TPP), 0.1mmol iodine (I2) and 10mL ultra-dry dichloromethane (DCM). In an argon atmosphere, stir at 10°C for 10min, then raise the temperature of the reaction flask to room temperature and continue stirring for 5min. Under argon protection, add 1mmol 4-methylbenzyl alcohol to the reaction system and continue stirring for 1h. After the reaction is completed, add 6mmol zinc chloride and 5mL ethanol. After the solid is precipitated, add 5mL n-hexane and shake and filter. The organic solvent in the filtrate is spin-dried to obtain a crude product, and finally separated by column chromatography to obtain pure 4-methylbenzyl methyl ether.

[0181]

[0182] The compound is a colorless liquid with a yield of 85%. Its NMR data are as follows:

[0183] 1 H NMR (CDCl3, 300MHz): δ = 7.21 (d, J = 8.0Hz, 2H), 7.16 (d, J = 7.9Hz, 2H), 4.42 (s, 2H), 3.35 (s, 3H), 2.34 (s, 3H) ppm.

Claims

1. A method for preparing a methyl ether compound of a fatty alcohol, characterized in that: The specific steps include: S1: under an inert gas atmosphere and stirring conditions at -78°C to 20°C, a methoxy transfer reagent, an organic phosphine and an initiator are added to an ultra-dry solvent; the molar ratio of the methoxy transfer reagent to the starting material fatty alcohol is 1 to 1000; the molar ratio of the organic phosphine to the methoxy transfer reagent is 1 to 100; the molar ratio of the initiator to the methoxy transfer reagent is 0.01 to 0.5; the concentration of the reaction system is a ratio of the molar number of the methoxy transfer reagent to the volume of the ultra-dry solvent of 0.01 to 100 mol / L; The methoxy transfer reagent is 1-methoxy-1,2,3-benzoiodine-3,3-thiophene dioxide (MOBI); The ultra-dry solvent is selected from any one of dichloromethane (DCM), tetrachloromethane, dichloroethane, acetone, acetonitrile, propionitrile, butyronitrile, hexafluoroisopropanol or dimethyl sulfoxide, or a combination of two or more thereof; the organic phosphine is selected from any one of triphenylphosphine (TPP), tri(pentafluorophenyl)phosphine, tri(p-tolyl)phosphine, tri(cyclohexyl)phosphine, tributylphosphine or triethylphosphine, or a combination of two or more thereof; The initiator is selected from any one or a combination of two or more of iodine (I2), azobisisobutyronitrile (AIBN), benzoyl peroxide (BPO), tert-butyl peroxide (TBHP) or meta-chloroperbenzoic acid (mCPBA); S2: Adjust the system temperature to -78°C to 70°C, add the starting material fatty alcohol at once under argon atmosphere and stirring, and react until complete; The fatty alcohol is selected from alkyl alcohol or alkyl alcohol with substituents; the substituent types include fluorine, chlorine, bromine, iodine, trifluoromethyl, difluoromethyl, trichloromethyl, dichloromethyl, cyano, ester, acyl, sulfonyl, carboxyl, nitro, and aryl, and the number of substituents is not limited; S3: After the reaction is completed, zinc chloride and ethanol are added, and after the solid is precipitated, a poor solvent is added and the mixture is shaken and filtered; the molar ratio of zinc chloride to organic phosphine is 1 to 100; the amount of ethanol is 0.01 to 10 mL / mmol zinc chloride; the amount of the poor solvent is 0.1 to 100 mL / mmol zinc chloride; The poor solvent is selected from any one or a combination of two or more of n-pentane, n-hexane (Hex), n-heptane, ethyl ether, methyl tert-butyl ether, isopropyl ether, tetrahydrofuran or dioxane; S4: After step S3 is completed, impurities in the filtered filtrate are removed to obtain a methyl ether compound of a fatty alcohol.

2. The method for preparing the methyl ether compound of fatty alcohol according to claim 1, characterized in that: In the steps S1 to S3, the reaction is carried out for 0.01 to 48 hours, and the stirring condition is 100 to 100000 rpm.

3. The method for preparing the methyl ether compound of fatty alcohol according to claim 1, characterized in that: The preparation method of the 1-methoxy-1,2,3-benzoiodine thiolane-3,3-dioxide (MOBI) is as follows: Take 5 molar parts of 1-hydroxy-1,2,3-benzoiodine thiolane-3,3-dioxide (HBI), add 2 parts by volume of trimethyl orthoformate (TMOF) and 2 parts by volume of ultra-dry dichloromethane (DCM) at 5-15° C. in an inert gas protection atmosphere, so that the ratio of 1-hydroxy-1,2,3-benzoiodine thiolane-3,3-dioxide (HBI) to trimethyl orthoformate (TMOF) is 1-4 mmol / mL, stir well, raise the reaction temperature to room temperature, continue stirring until the reaction is fully reacted; remove TMOF and DCM, add 8-15 parts by volume of ultra-dry dichloromethane (DCM) to redissolve, filter and remove insoluble matter, and remove DCM to obtain 1-methoxy-1,2,3-benzoiodine thiolane-3,3-dioxide (MOBI).

4. The method for preparing the methyl ether compound of fatty alcohol according to claim 1, characterized in that: In the step S1, the methoxy transfer reagent is 1-methoxy-1,2,3-benzoiodothiolane-3,3-dioxide (MOBI), the ultra-dry solvent is dichloromethane (DCM), and the initiator is elemental iodine (I2); in the step S3, the poor solvent is Hex.

5. The method for preparing the methyl ether compound of fatty alcohol according to claim 4, characterized in that: The reaction formula is expressed as the following reaction formula I: Wherein, the compound of formula I represents a fatty alcohol, wherein R represents an alkyl group or a substituted alkyl group; the compound of formula II represents a methyl ether compound of a fatty alcohol; In the alkyl or substituted alkyl represented by R: the number of carbon atoms of the alkyl or substituted alkyl is ≥ 1; the types of substituents include fluorine, chlorine, bromine, iodine, trifluoromethyl, difluoromethyl, trichloromethyl, dichloromethyl, cyano, ester, acyl, sulfonyl, carboxyl, nitro, and aryl; the number of substituents is not limited.

6. The method for preparing the methyl ether compound of fatty alcohol according to claim 5, characterized in that: The amount of I2 used is 0.01 to 0.2 equivalents of the starting material fatty alcohol.

7. The method for preparing the methyl ether compound of fatty alcohol according to claim 6, characterized in that: The amount of MOBI used is 1 to 3 times the equivalent of the starting material fatty alcohol.

8. The method for preparing the methyl ether compound of fatty alcohol according to claim 7, characterized in that: The amount of triphenylphosphine (TPP) used is 1 to 3 times the equivalent of the fatty alcohol.

9. The method for preparing the methyl ether compound of fatty alcohol according to claim 8, characterized in that: The amount of DCM used is 1-20 mL / mmol of fatty alcohol.

10. The method for preparing the methyl ether compound of fatty alcohol according to claim 9, characterized in that: The amount of n-hexane (Hex) used is 10 to 100 times the volume of DCM.

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