Preparation method of (Z)-3-hexene-1-ol

Abstract

The invention discloses a preparation method of leaf alcohol (Z)-3-hexene-1-alcohol. The method comprises the following steps: (1) taking 3-bromine-1-propanol as a raw material, and carrying out aldolization on the 3-bromine-1-propanol and paraformaldehyde to prepare a target fragment bis (3-bromopropoxy) methane shown in a formula (II); (2) preparing a corresponding quaternary phosphonium salt shown as a formula (III) from bis (3-bromopropoxy) methane shown as a formula (II) and triphenylphosphine under certain conditions; (3) taking the quaternary phosphonium salt shown in the formula (III) as a raw material, and carrying out Wittig reaction on the quaternary phosphonium salt and n-propionaldehyde in the presence of alkali to prepare a target fragment bis ((Z)-3-hexene-1-oxy) methane shown in a formula (IV); and (4) carrying out acetal hydrolysis reaction by taking the bis ((Z)-3-hexene-1-oxyl) methane shown in the formula (IV) as a raw material to prepare the (Z)-3-hexene-1-alcohol shown in the formula (I). The method has the advantages of short reaction route, cheap and easily available raw materials, mild reaction conditions, easy amplification, small environmental pollution, and good economic and social values in popularization.

Description

Technical Field

[0001] The invention belongs to the field of chemical synthesis and relates to a method for preparing (Z)-3-hexene-1-ol. Background Art

[0002] (Z)-3-Hexen-1-ol, also known as leaf alcohol, is a colorless liquid with a strong green leaf fragrance. It is used in many aspects: it can be used as a pheromone and sex attractant to control pests; in the latest published GB 2760-2024 "Standards for the Use of Food Additives", it is clearly stipulated that leaf alcohol can be used as a synthetic flavoring for food; at the same time, leaf alcohol is both a precious flavor and an important raw material for synthesizing precious flavors such as jasmone. Leaf alcohol and its derivatives are the symbol of the green revolution in the flavor industry in the 1960s.

[0003] At present, the mainstream methods reported in the world for synthesizing leaf alcohol include the following:

[0004] 1. Catalytic hydrogenation

[0005] This route uses 3-hexyne-1-ol as a synthetic intermediate, and then obtains leaf alcohol through cis hydrogenation under the catalysis of Lindlar catalyst. It includes acetylene method, butyne method, propionaldehyde method, propargyl alcohol method, butadiene method, etc. Through specific catalysts and reaction conditions, stereoselective catalytic hydrogenation is achieved to synthesize leaf alcohol. Taking the butyne method as an example, the synthetic route is as follows:

[0006]

[0007] The disadvantages of this route are: it requires the use of active metals such as lithium or sodium, which is somewhat dangerous; some methods require the use of bromine for addition reaction followed by debromination, which has low atomic utilization and is environmentally unfriendly; in addition, the yields of several currently reported methods using catalytic hydrogenation of 3-hexyn-1-ol as a synthetic intermediate are not high.

[0008] 2. Continuous Restore

[0009] This route prepares leaf alcohol by using unsaturated esters with chemical solvents, metal salt additives and reducing agents in a continuous reactor. Taking the sorbic acid method as an example, the synthesis route is as follows:

[0010]

[0011] The disadvantages of this route are: it requires concentrated sulfuric acid, which has very high requirements for equipment and may cause equipment corrosion; the lithium aluminum hydride used in the reaction is very active, flammable, easy to absorb moisture and decompose, and is highly irritating to the human body. Special conditions are required for transportation and storage, which increases costs.

[0012] 3. Reductive ring opening

[0013] This route achieves the synthesis of leaf alcohol by reductive ring opening, including tetrahydrofuran method, cis-3-hexenoic acid methyl ester method, anisole method, etc. Taking the reductive ring opening of 2-ethyl-3-chlorotetrahydrofuran as an example, the synthesis method is as follows:

[0014]

[0015] The disadvantages of this route are: the materials used are highly sensitive and difficult to industrialize; the ring opening requires the use of metals such as sodium and magnesium, which is somewhat dangerous; and the Grignard reaction to achieve chain growth has high requirements for reaction conditions such as moisture and air.

[0016] 4. Using 1-pentene as raw material, leaf alcohol (CN101875599A) was synthesized by Alder Ene reaction. The specific synthesis method is as follows:

[0017]

[0018] The disadvantage of this route is that the reaction products contain two structures, cis and trans, and the ratio of the two is close to 1:1.

[0019] 5. Using silane-Lewis acid as a catalyst to promote the ring opening of methyl pyran to form leaf alcohol (CN106631687A). The specific synthesis method is as follows:

[0020]

[0021] The disadvantages of this route are: the recovery of silane additives requires high temperature and high pressure, and the application of catalysts will lead to a decrease in the yield of leaf alcohol.

[0022] 6. Using 2,4-hexadienal as a synthetic intermediate, catalytic hydrogenation is used to synthesize leaf alcohol (CN116655455A). The specific synthesis method is as follows:

[0023]

[0024] The disadvantages of this route are: the reaction conditions are complex, the pressure of the catalytic hydrogenation step must reach 1.0-5.0 MPa, and the temperature must reach 200°C, which is not conducive to large-scale industrial production. Summary of the invention

[0025] In view of the above technical status, the present invention provides a method for preparing (Z)-3-hexene-1-ol which is safe and reliable, has a short route, generates less waste, has low cost, and has high yield and selectivity.

[0026] The technical solution of the present invention can be summarized as follows:

[0027] A method for preparing (Z)-3-hexen-1-ol, wherein the (Z)-3-hexen-1-ol has a structure shown in formula (I):

[0028] Formula (I):

[0029] The steps include:

[0030] (1) Using 3-bromo-1-propanol as a raw material and polyformaldehyde in the presence of concentrated sulfuric acid as a catalyst, an acetal reaction occurs to obtain the target fragment bis(3-bromopropoxy)methane (II);

[0031] (2) Using bis(3-bromopropoxy)methane (II) as a raw material, reacting with triphenylphosphine to obtain the target fragment quaternary phosphonium salt (III);

[0032] (3) Using quaternary phosphonium salt (III) as raw material, a Wittig reaction is carried out with n-propionaldehyde in the presence of a base to obtain the target fragment bis((Z)-3-hexen-1-oxy)methane (IV);

[0033] (4) Using bis((Z)-3-hexene-1-oxy)methane (IV) as a raw material, an acetal hydrolysis reaction is carried out under acidic conditions to obtain (Z)-3-hexene-1-ol (I).

[0034] According to the present invention, preferably, the bis(3-bromopropoxy)methane in step (1) has a structure shown in formula (II):

[0035] Formula (II):

[0036] According to the present invention, preferably, the reaction in step (1) is carried out in a solvent, and further preferably, the solvent is one or a combination of toluene, xylene, benzene and n-hexane;

[0037] Preferably, in step (1), the molar ratio of 3-bromo-1-propanol to paraformaldehyde is 1:(0.5-3);

[0038] Preferably, the reaction temperature of step (1) is controlled at 60°C to 160°C.

[0039] According to the present invention, preferably, the quaternary phosphonium salt in step (2) has a structure shown in formula (III):

[0040] Formula (III):

[0041] According to the present invention, preferably, the reaction in step (2) is carried out in a solvent, and further preferably, the solvent is one or a combination of N,N-dimethylformamide, N,N-dimethylacetamide, toluene, acetonitrile, and xylene;

[0042] Preferably, the molar ratio of bis(3-bromopropoxy)methane to triphenylphosphine in step (2) is 1:(2-5);

[0043] Preferably, the reaction temperature of step (2) is controlled at 70°C to 150°C.

[0044] According to the present invention, preferably, the bis((Z)-3-hexene-1-oxy)methane in step (3) has a structure shown in formula (IV):

[0045] Formula (IV):

[0046] According to the present invention, preferably, the reaction in step (3) is carried out in a solvent, and further preferably, the solvent is one or a combination of tetrahydrofuran, toluene, N,N-dimethylformamide, and diethyl ether;

[0047] Preferably, the base in step (3) is one or a combination of potassium bis(trimethylsilyl)amide, lithium bis(trimethylsilyl)amide, sodium bis(trimethylsilyl)amide, trityl sodium, sodium amide, potassium tert-butoxide, lithium diisopropylamide, potassium carbonate, potassium hydroxide, and sodium hydroxide;

[0048] Preferably, the molar ratio of the quaternary phosphonium salt to the base in step (3) is 1:(2-3);

[0049] Preferably, the reaction temperature of step (3) is controlled at -40°C to 40°C;

[0050] Preferably, the reaction in step (3) is carried out under a nitrogen atmosphere.

[0051] According to the present invention, preferably, the (Z)-3-hexen-1-ol in step (4) has a structure shown in formula (I):

[0052] Formula (I):

[0053] According to the present invention, preferably, the acid in step (4) is one or a combination of formic acid, acetic acid, trifluoroacetic acid, hydrochloric acid, sulfuric acid, phosphoric acid, and nitric acid;

[0054] Preferably, the reaction temperature of step (4) is controlled at -20°C to 40°C.

[0055] The beneficial effects of the present invention are as follows:

[0056] The invention synthesizes leaf alcohol through four-step reactions, has a short synthesis route, high selectivity, high product yield, mild reaction conditions, low raw material price, little environmental pollution, simple operation, can meet the requirements of industrial large-scale production, and has high economic value and social value. DETAILED DESCRIPTION

[0057] The invention provides a method for preparing (Z)-3-hexene-1-ol which is safe and reliable, generates less waste, has low cost, and has high yield and selectivity.

[0058] According to the present invention, the preparation route of the (Z)-3-hexene-1-ol is as follows:

[0059]

[0060] A method for preparing (Z)-3-hexene-1-ol, wherein the (Z)-3-hexene-1-ol has a structure shown in formula (I):

[0061] Formula (I):

[0062] The steps include:

[0063] (1) 3-bromo-1-propanol as a raw material and polyformaldehyde are used as a catalyst under concentrated sulfuric acid, and an acetal reaction is carried out under solvent and temperature conditions to obtain the target fragment bis(3-bromopropoxy)methane formula (II);

[0064] (2) using the target fragment bis(3-bromopropoxy)methane formula (II) as a raw material and reacting with triphenylphosphine under solvent and temperature conditions to obtain the target fragment quaternary phosphonium salt formula (III);

[0065] (3) using the quaternary phosphonium salt (III) as a raw material and reacting it with n-propionaldehyde in the presence of a base to produce the target fragment bis((Z)-3-hexene-1-oxy)methane (IV);

[0066] (4) Using bis((Z)-3-hexene-1-oxy)methane (IV) as a raw material, an acetal hydrolysis reaction is carried out under acidic conditions to obtain (Z)-3-hexene-1-ol (I).

[0067] According to the present invention, the bis(3-bromopropoxy)methane described in step (1) has a structure shown in formula (II):

[0068] Formula (II):

[0069] The 3-bromo-1-propanol has the following structure:

[0070] In one or more preferred embodiments, the reaction in step (1) is carried out in a solvent, and further preferably, the solvent is one or a combination of toluene, xylene, benzene, and n-hexane;

[0071] Preferably, the molar ratio of 3-bromo-1-propanol to paraformaldehyde in step (1) is 1:(0.5-3);

[0072] Preferably, the reaction temperature of step (1) is controlled at 60°C to 160°C.

[0073] In one or more preferred embodiments, in step (1), 3-bromo-1-propanol and a solvent are mixed and stirred, and then paraformaldehyde and concentrated sulfuric acid are added. After controlling the temperature to react for a period of time, a reaction solution is obtained, and a saturated sodium carbonate solution is added dropwise to the reaction solution, and the pH is adjusted to 9, and the phases are separated, and the organic phase is dried over anhydrous sodium sulfate, and the solvent is removed by rotary evaporation to obtain bis(3-bromopropoxy)methane (II).

[0074] According to the present invention, the synthetic route of step (1) is as follows:

[0075]

[0076] According to the present invention, the quaternary phosphonium salt in step (2) has a structure shown in formula (III):

[0077] Formula (III):

[0078] In one or more preferred embodiments, the reaction in step (2) is carried out in a solvent, and further preferably, the solvent is one or a combination of N,N-dimethylformamide, N,N-dimethylacetamide, toluene, acetonitrile, and xylene;

[0079] Preferably, the molar ratio of bis(3-bromopropoxy)methane to triphenylphosphine in step (2) is 1:(2-5);

[0080] Preferably, the reaction temperature of step (2) is controlled at 70°C to 150°C.

[0081] In one or more preferred embodiments, in step (2), bis(3-bromopropoxy)methane and a solvent are mixed and stirred, and then triphenylphosphine is added. After controlling the temperature to react for a period of time, a reaction solution is obtained, and after cooling treatment, a solid is obtained, which is filtered, washed with ethyl acetate, pulped and then spin-dried to obtain a quaternary phosphonium salt of formula (III).

[0082] According to the present invention, the synthetic route of step (2) is as follows:

[0083]

[0084] According to the present invention, the bis((Z)-3-hexene-1-oxy)methane in step (3) has a structure shown in formula (IV):

[0085] Formula (IV):

[0086] In one or more preferred embodiments, the reaction in step (3) is carried out in a solvent, and further preferably, the solvent is one or a combination of tetrahydrofuran, toluene, N,N-dimethylformamide, and diethyl ether;

[0087] Preferably, the base in step (3) is one or a combination of potassium bis(trimethylsilyl)amide, lithium bis(trimethylsilyl)amide, sodium bis(trimethylsilyl)amide, trityl sodium, sodium amide, potassium tert-butoxide, lithium diisopropylamide, potassium carbonate, potassium hydroxide, and sodium hydroxide;

[0088] Preferably, the molar ratio of the quaternary phosphonium salt to the base in step (3) is 1:(2-3);

[0089] Preferably, the reaction temperature of step (3) is controlled at -40°C to 40°C;

[0090] Preferably, the reaction in step (3) is carried out under a nitrogen atmosphere.

[0091] In one or more preferred embodiments, in step (3), a quaternary phosphonium salt and a solvent are added to a reaction flask, the system temperature is controlled, a base is added in batches, a vacuum is drawn, and the mixture of n-propanal and the solvent is slowly added dropwise under controlled temperature, and after the addition is completed, the mixture is maintained for a certain period of time to obtain a reaction solution containing bis((Z)-3-hexene-1-oxy)methane of formula (IV).

[0092] According to the present invention, the synthetic route of step (3) is as follows:

[0093]

[0094] According to the present invention, the (Z)-3-hexen-1-ol in step (4) has a structure shown in formula (I):

[0095] Formula (I):

[0096] In one or more preferred embodiments, the acid in step (4) is one or a combination of formic acid, acetic acid, trifluoroacetic acid, hydrochloric acid, sulfuric acid, phosphoric acid, and nitric acid;

[0097] Preferably, the reaction temperature of step (4) is controlled at -20°C to 40°C.

[0098] In one or more preferred embodiments, in step (4), acid and water are added to the reaction solution of the previous step, and the reaction is controlled at a certain temperature for a period of time to obtain a reaction solution. Water is added dropwise to the reaction solution, and then dichloromethane is added for extraction, and the organic phase is dried and concentrated by rotary evaporation to obtain (Z)-3-hexene-1-ol of formula (I).

[0099] According to the present invention, the synthetic route of step (4) is as follows:

[0100]

[0101] In order to enable those skilled in the art to better understand the technical solution of the present invention, the present invention is further described in detail below in conjunction with specific implementation methods.

[0102] Example 1

[0103] The preparation method of (Z)-3-hexene-1-ol comprises the following steps:

[0104] (1) Preparation of bis(3-bromopropoxy)methane (II):

[0105] Add 3-bromo-1-propanol (82.2 g, 0.59 mol) to a 500 ml reaction bottle, then add 200 ml toluene and start stirring. Add paraformaldehyde (12 g, 0.4 mol) and 0.2 g of concentrated sulfuric acid, add a water separator to the system, control the temperature to 115 ° C, and maintain it for 5 hours. Cool down, add saturated sodium carbonate solution to the system, adjust the pH to 9, separate the phases, dry the organic phase with anhydrous sodium sulfate, and concentrate by rotary evaporation to remove the solvent to obtain bis(3-bromopropoxy)methane (II), a colorless liquid with a yield of 92.0%.

[0106] (2) Preparation of quaternary phosphonium salt (III):

[0107] Add bis(3-bromopropoxy)methane (80 g, 0.28 mol) to a 1 L reaction bottle, then add 500 ml of N,N-dimethylformamide and start stirring. Add triphenylphosphine (157 g, 0.6 mol), control the temperature to 90 ° C, and maintain for 15 hours. After cooling, the solvent is removed by rotary evaporation, and the remaining material is washed with ethyl acetate, pulped, filtered, and then rotary evaporated and dried to obtain quaternary phosphonium salt (III), off-white solid (207 g), with a yield of 90.0%.

[0108] (3) Preparation of bis((Z)-3-hexene-1-oxy)methane (IV):

[0109] Add quaternary phosphonium salt (207g, 0.25mol) to a 2L reaction bottle, then add 500ml of tetrahydrofuran and start stirring. Control the temperature to 5℃, replace with nitrogen and protect the system. Add potassium tert-butoxide (78g, 0.7mol) to the system in 3 portions, then raise the temperature to 30℃ and keep for 1h. Then cool the system to -20℃, slowly drop a mixture of n-propanal (35g, 0.6mol) and 75ml of tetrahydrofuran, and keep for 30min after the addition is complete to generate bis((Z)-3-hexene-1-oxy)methane (IV).

[0110] (4) Preparation of (Z)-3-hexen-1-ol (I):

[0111] To the reaction solution of step (3), 30 g of water and formic acid (51 g, 1.1 mol) were added dropwise, and the temperature was controlled at 15°C and maintained for 7 h. Water and dichloromethane were added dropwise for extraction, and the organic phase was dried over anhydrous sodium sulfate, concentrated by rotary evaporation, and then (Z)-3-hexene-1-ol (I) was distilled off under reduced pressure to obtain 45.6 g of colorless liquid. The yield of the two-step reaction was 90%, and the purity was 98.1%. 1 H NMRδppm: 5.5(2H); 3.5(2H); 3.2(1H); 2.3(4H); 1.0(3H).

[0112] Example 2

[0113] The preparation method of (Z)-3-hexene-1-ol comprises the following steps:

[0114] (1) Preparation of bis(3-bromopropoxy)methane (II):

[0115] Add 3-bromo-1-propanol (80.8 g, 0.58 mol) to a 500 ml reaction bottle, then add 200 ml of xylene and start stirring. Add paraformaldehyde (24 g, 0.8 mol) and 0.2 g of concentrated sulfuric acid, and add a water separator filled with xylene to the system at the same time, control the temperature to 150 ° C, and maintain it for 2 hours. Cool down, add saturated sodium carbonate solution to the system, adjust the pH to 9, separate the phases, dry the organic phase with anhydrous sodium sulfate, and concentrate by rotary evaporation to remove the solvent to obtain bis(3-bromopropoxy)methane (II), a colorless liquid with a yield of 94%.

[0116] (2) Preparation of quaternary phosphonium salt (III):

[0117] Add bis(3-bromopropoxy)methane (82g, 0.28mol) to a 1L reaction bottle, then add 500ml of toluene and start stirring. Add triphenylphosphine (157g, 0.6mol), control the temperature to 110°C, and maintain for 20h. Cool down to precipitate solid, wash the solid with ethyl acetate, pulp, filter, and then rotary evaporate to dryness to obtain quaternary phosphonium salt (III), off-white solid (200.6g), yield 88%.

[0118] (3) Preparation of bis((Z)-3-hexene-1-oxy)methane (IV):

[0119] Add quaternary phosphonium salt (200g, 0.25mol) to a 2L reaction bottle, then add 500ml of tetrahydrofuran and start stirring. Control the temperature to 5℃, replace with nitrogen and protect the system with nitrogen. Add bis(trimethylsilyl)potassium amide (120g, 0.6mol) to the system in 3 times, then raise the temperature to 30℃ and keep it for 1h. Then cool the system to -30℃, slowly drop a mixture of n-propanal (29g, 0.5mol) and 70ml of tetrahydrofuran, and keep it for 30min after the addition is completed to generate bis((Z)-3-hexene-1-oxy)methane (IV).

[0120] (4) Preparation of (Z)-3-hexen-1-ol (I):

[0121] To the reaction solution of step (3), 30 g of water and 60 g of acetic acid (1 mol) were added dropwise, and the temperature was controlled at 25°C for 4 h. Dichloromethane was added for extraction, and the organic phase was dried over anhydrous sodium sulfate, concentrated by rotary evaporation, and then (Z)-3-hexene-1-ol (I) was distilled off under reduced pressure to obtain 44.7 g of colorless liquid. The yield of the two-step reaction was 91% and the purity was 98.2%. 1 H NMRδppm: 5.5(2H); 3.5(2H); 3.2(1H); 2.3(4H); 1.0(3H).

[0122] Example 3

[0123] The preparation method of (Z)-3-hexene-1-ol comprises the following steps:

[0124] (1) Preparation of bis(3-bromopropoxy)methane (II):

[0125] Add 3-bromo-1-propanol (83.4 g, 0.6 mol) to a 500 ml reaction bottle, then add 200 ml of n-hexane and start stirring. Add paraformaldehyde (12 g, 0.4 mol) and 0.2 g of concentrated sulfuric acid, add a water separator to the system, control the temperature to 75 ° C, and maintain it for 8 hours. Cool down, add saturated sodium carbonate solution to the system, adjust the pH to 9, separate the phases, dry the organic phase with anhydrous sodium sulfate, and concentrate by rotary evaporation to remove the solvent to obtain bis(3-bromopropoxy)methane (II), a colorless liquid with a yield of 92.4%.

[0126] (2) Preparation of quaternary phosphonium salt (III):

[0127] Add bis(3-bromopropoxy)methane (80 g, 0.28 mol) to a 1 L reaction bottle, then add acetonitrile 500 ml and start stirring. Add triphenylphosphine (157 g, 0.6 mol), control the temperature to 90 ° C, and maintain for 22 hours. After cooling, the solvent is removed by rotary evaporation, and the remaining material is washed with ethyl acetate, pulped, filtered, and then rotary evaporated and dried to obtain quaternary phosphonium salt (III), off-white solid (209.5 g), with a yield of 91.6%.

[0128] (3) Preparation of bis((Z)-3-hexene-1-oxy)methane (IV):

[0129] Add quaternary phosphonium salt (209.5g, 0.25mol) to a 2L reaction bottle, then add 500ml of tetrahydrofuran and start stirring. Control the temperature to 0℃, replace with nitrogen and protect the system. Add potassium tert-butoxide (78g, 0.7mol) to the system in 3 times, then raise the temperature to 30℃ and keep it for 1h. Then cool the system to -20℃, slowly drop a mixture of n-propanal (35g, 0.6mol) and 75ml of tetrahydrofuran, and keep it for 30min after the addition is completed to generate bis((Z)-3-hexene-1-oxy)methane (IV).

[0130] (4) Preparation of (Z)-3-hexen-1-ol (I):

[0131] 400 g of 10% sulfuric acid was added dropwise to the reaction solution of step (3), and the temperature was controlled at 10°C for 7 h. Dichloromethane was added for extraction, and the organic phase was dried over anhydrous sodium sulfate, concentrated by rotary evaporation, and then (Z)-3-hexene-1-ol (I) was distilled off under reduced pressure to obtain 46.7 g of colorless liquid. The yield of the two-step reaction was 92.2% and the purity was 98.4%. 1 H NMRδppm: 5.5(2H); 3.5(2H); 3.2(1H); 2.3(4H); 1.0(3H).

[0132] Example 4

[0133] The preparation method of (Z)-3-hexene-1-ol comprises the following steps:

[0134] (1) Preparation of bis(3-bromopropoxy)methane (II):

[0135] Add 3-bromo-1-propanol (83.4 g, 0.6 mol) to a 500 ml reaction bottle, then add 200 ml of benzene and start stirring. Add paraformaldehyde (18 g, 0.6 mol) and 0.2 g of concentrated sulfuric acid, add a water separator to the system, control the temperature to 90 ° C, and maintain it for 6 hours. Cool down, add saturated sodium carbonate solution to the system, adjust the pH to 9, separate the phases, dry the organic phase with anhydrous sodium sulfate, and concentrate by rotary evaporation to remove the solvent to obtain bis(3-bromopropoxy)methane (II), a colorless liquid with a yield of 93.1%.

[0136] (2) Preparation of quaternary phosphonium salt (III):

[0137] Add bis(3-bromopropoxy)methane (82.9 g, 0.29 mol) to a 1 L reaction bottle, then add acetonitrile 500 ml and start stirring. Add triphenylphosphine (209.3 g, 0.8 mol), control the temperature to 90 ° C, and maintain for 22 hours. After cooling, the solvent is removed by rotary evaporation, and the remaining material is washed with ethyl acetate, pulped, filtered, and then the solid is rotary evaporated and dried to obtain quaternary phosphonium salt (III), off-white solid (211.1 g), with a yield of 91.8%.

[0138] (3) Preparation of bis((Z)-3-hexene-1-oxy)methane (IV):

[0139] Add quaternary phosphonium salt (211.1g, 0.25mol) to a 2L reaction bottle, then add 500ml of tetrahydrofuran and start stirring. Control the temperature to 5℃, replace with nitrogen and replace and protect the system with nitrogen. Add trityl sodium (186.4g, 0.7mol) to the system in 5 times, then raise the temperature to 25℃ and keep it for 1h. Then cool the system to -20℃, slowly add a mixture of n-propanal (35g, 0.6mol) and 75ml of tetrahydrofuran, and keep it for 30min after the addition is completed to generate bis((Z)-3-hexene-1-oxy)methane (IV).

[0140] (4) Preparation of (Z)-3-hexen-1-ol (I):

[0141] 400 g of 10% hydrochloric acid was added dropwise to the reaction solution of step (3), and the temperature was controlled at 20°C for 5 h. Water and dichloromethane were added dropwise for extraction, and the organic phase was dried over anhydrous sodium sulfate, concentrated by rotary evaporation, and then (Z)-3-hexene-1-ol (I) was distilled off under reduced pressure to obtain 47.2 g of colorless liquid. The yield of the two-step reaction was 93% and the purity was 97.4%. 1 H NMRδppm: 5.5(2H); 3.5(2H); 3.2(1H); 2.3(4H); 1.0(3H).

[0142] The above description is only the preferred embodiment of the present invention, and does not limit the patent scope of the present invention. For those skilled in the art, the present invention may have various changes and modifications. Any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the present invention and directly or indirectly applied to other related technical fields shall be included in the protection scope of the present invention.

Claims

1. A method for preparing (Z)-3-hexen-1-ol, wherein the (Z)-3-hexen-1-ol has a structure shown in formula (I): The steps include: (1) Using 3-bromo-1-propanol as a raw material and polyformaldehyde in the presence of concentrated sulfuric acid as a catalyst, an acetal reaction occurs to obtain the target fragment bis(3-bromopropoxy)methane (II); (2) Using bis(3-bromopropoxy)methane (II) as a raw material, reacting with triphenylphosphine to obtain the target fragment quaternary phosphonium salt (III); (3) Using quaternary phosphonium salt (III) as raw material, a Wittig reaction is carried out with n-propionaldehyde in the presence of a base to obtain the target fragment bis((Z)-3-hexen-1-oxy)methane (IV); (4) Using bis((Z)-3-hexene-1-oxy)methane (IV) as a raw material, an acetal hydrolysis reaction is carried out under acidic conditions to obtain (Z)-3-hexene-1-ol (I).

2. The method for preparing (Z)-3-hexene-1-ol according to claim 1, characterized in that: The bis(3-bromopropoxy)methane described in step (1) has a structure shown in formula (II): The reaction in step (1) is carried out in a solvent. Preferably, the solvent is one or a combination of toluene, xylene, benzene and n-hexane.

3. The method for preparing (Z)-3-hexene-1-ol according to claim 1, characterized in that: In step (1), the molar ratio of 3-bromo-1-propanol to paraformaldehyde is 1:(0.5-3); Preferably, the reaction temperature of step (1) is controlled at 60°C to 160°C.

4. The method for preparing (Z)-3-hexene-1-ol according to claim 1, characterized in that: The quaternary phosphonium salt described in step (2) has a structure shown in formula (III): Preferably, the reaction in step (2) is carried out in a solvent, and further preferably, the solvent is one or a combination of N,N-dimethylformamide, N,N-dimethylacetamide, toluene, acetonitrile and xylene.

5. The method for preparing (Z)-3-hexen-1-ol according to claim 1, characterized in that: The molar ratio of bis(3-bromopropoxy)methane to triphenylphosphine in step (2) is 1:(2-5); Preferably, the reaction temperature of step (2) is controlled at 70°C to 150°C.

6. The method for preparing (Z)-3-hexene-1-ol according to claim 1, characterized in that: The bis((Z)-3-hexene-1-oxy)methane described in step (3) has a structure shown in formula (IV): Preferably, the reaction in step (3) is carried out in a solvent, and further preferably, the solvent is one or a combination of tetrahydrofuran, toluene, N,N-dimethylformamide, and diethyl ether.

7. The method for preparing (Z)-3-hexen-1-ol according to claim 1, characterized in that: The base in step (3) is one or a combination of potassium bis(trimethylsilyl)amide, lithium bis(trimethylsilyl)amide, sodium bis(trimethylsilyl)amide, trityl sodium, sodium amide, potassium tert-butoxide, lithium diisopropylamide, potassium carbonate, potassium hydroxide, and sodium hydroxide.

8. The method for preparing (Z)-3-hexen-1-ol according to claim 1, characterized in that: The molar ratio of the quaternary phosphonium salt formula to the base in step (3) is 1:(2-3); Preferably, the reaction temperature of step (3) is controlled at -40°C to 40°C; Preferably, the reaction in step (3) is carried out under a nitrogen atmosphere.

9. The method for preparing (Z)-3-hexen-1-ol according to claim 1, characterized in that: The (Z)-3-hexen-1-ol described in step (4) has the structure shown in formula (I): Preferably, the acid in step (4) is one or a combination of formic acid, acetic acid, trifluoroacetic acid, hydrochloric acid, sulfuric acid, phosphoric acid and nitric acid.

10. The method for preparing (Z)-3-hexen-1-ol according to claim 1, characterized in that: The reaction temperature of step (4) is controlled at -20°C to 40°C.

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