Method for preparing omega-chloro straight-chain primary alcohol from alpha, omega-straight-chain diol
The described method addresses the low yield and high cost issues of existing methods by dissolving α,ω-straight-chain diol in hydrochloric acid and purifying the reaction mixture, achieving high yield and purity of ω-chloro straight-chain primary alcohol suitable for large-scale production.
Patent Information
- Application Number
- CN202411075486.5
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2024-08-07
- Publication Date
- 2024-12-13
AI Technical Summary
Existing methods for preparing ω-chloro linear primary alcohol from α,ω-linear diol suffer from low yield, high cost, and environmental unfriendliness, making them unsuitable for large-scale production.
A method involving the dissolution of α,ω-straight-chain diol in a reaction solvent with hydrochloric acid at 86-110°C for 13-25 hours, followed by purification steps to obtain ω-chloro straight-chain primary alcohol, with optional use of solvents like toluene and hydrochloric acid ratios, and cooling to precipitate unreacted diol.
The method achieves a yield of over 60% and purity of over 80%, with a maximum yield of 96% and purity of 95%, providing a high-efficiency, low-cost, and easily operable process.
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Figure CN119118777A_ABST
Abstract
Description
Technical Field
[0001] The invention belongs to the field of synthesis technology, and in particular relates to a method for preparing ω-chloro linear primary alcohol from α,ω-linear diol. Background Art
[0002] Since α,ω-straight-chain diols have two alcohol functional groups with similar reactivity, how to perform monosubstitution on α,ω-straight-chain diols has always been a research difficulty in the field of synthesis.
[0003] European Journal of Medicinal Chemistry (2017), 135, 77-88. The method reported in this paper uses decanediol as a raw material and 0.3 eq of methanesulfonyl chloride to carry out unilateral methanesulfonation and then chlorinate with lithium chloride to achieve monochlorination. However, the yield of this method is too low. In actual experiments, the yield calculated based on decanediol is only 12%, which is too low to be mass-produced:
[0004]
[0005] In addition, Advanced Synthesis & Catalysis (2018), 360(19), 3810-3817. reported the synthesis of ω-halogenated linear primary alcohols by reacting one hydroxyl group of α,ω-linear diols with carbon tetrabromide and triphenylphosphine. This method has poor atom economy, is not environmentally friendly, has high production costs, and is not conducive to large-scale production. Summary of the invention
[0006] In view of the above problems existing in the prior art, the present invention provides a method for preparing ω-chloro linear primary alcohol from α,ω-linear diol to provide a high-efficiency, high-yield and low-cost mono-substitution method for diol.
[0007] The technical solution provided by the present invention is as follows:
[0008] A method for preparing ω-chloro straight-chain primary alcohol from α,ω-straight-chain diol comprises the following steps:
[0009] The α,ω-straight-chain diol is dissolved in a reaction solvent, hydrochloric acid is added, and a substitution reaction is carried out at 86-110° C. for 13-25 hours to obtain a mixture; the mixture is purified to obtain the ω-chloro straight-chain primary alcohol.
[0010] Optionally, the α,ω-linear diol includes 1,8-octanediol, 1,9-nonanediol or 1,10-decanediol.
[0011] Optionally, the purification comprises: cooling the mixture to precipitate unreacted α,ω-straight-chain diol, filtering to obtain a filtrate, allowing the filtrate to stand for separation to obtain an organic phase, and washing the organic phase with an aqueous solution of a second solvent and then concentrating to obtain the ω-chloro-straight-chain primary alcohol. Preferably, the volume fraction of the second solvent in the aqueous solution of the second solvent is 0-30%.
[0012] Preferably, after the filtrate is separated, the aqueous phase is extracted with a first solvent to recover the organic phase, and the first solvent is one or more of toluene, xylene, chlorobenzene, dichloromethane, ethyl acetate and methyl tert-butyl ether.
[0013] Optionally, the mixture is cooled to 0-10°C to precipitate unreacted α,ω-linear diol.
[0014] Optionally, the second solvent is one or more of methanol, ethanol, isopropanol and N,N-dimethylformamide.
[0015] Optionally, the substitution reaction is carried out in a pressure vessel at a reaction temperature of 100 to 110° C. and a reaction time of 20-25 h.
[0016] Optionally, the reaction solvent includes one or more of toluene, xylene, chlorobenzene and methylcyclohexane.
[0017] Optionally, the amount ratio of α,ω-straight-chain diol to hydrochloric acid is 1:(1.5~16).
[0018] Optionally, the mass volume ratio (g / mL) of α,ω-straight-chain diol to the reaction solvent is 1:(3~10).
[0019] Optionally, the purification step further comprises distillation under reduced pressure after the organic phase is concentrated.
[0020] At least the following beneficial effects are included:
[0021] The method for preparing the ω-chloro straight-chain primary alcohol comprises dissolving an α,ω-straight-chain diol in a reaction solvent, adding hydrochloric acid, carrying out a substitution reaction at 86-110°C for 13-25 hours to obtain a mixture, and then purifying the mixture to obtain the ω-chloro straight-chain primary alcohol. The reaction yield is above 60%, and can reach up to 96% at the highest. The purity of the ω-chloro straight-chain primary alcohol is above 80A%, and can reach 95A%. The method for preparing the ω-chloro straight-chain primary alcohol has high efficiency and high yield, and has low cost and is easy to operate. BRIEF DESCRIPTION OF THE DRAWINGS
[0022] Figure 1 The NMR spectrum of 8-chloro-1-octanol obtained in Example 2 of the present invention;
[0023] Figure 2This is the NMR spectrum of 10-chloro-1-decanol obtained in Example 4 of the present invention. DETAILED DESCRIPTION
[0024] The present invention is further described below. The following examples are only used to more clearly illustrate the technical solution of the present invention, and are not intended to limit the protection scope of the present invention.
[0025] In the present application, 1,8-octanediol or 1,9-nonanediol or 1,10-decanediol is used as a raw material, and hydrochloric acid is used to carry out a chlorine substitution reaction in a pressure vessel to obtain 8-chloro-1-octanol or 9-chloro-1-nonanediol or 10-chloro-1-decanol, and the synthesis route is as follows:
[0026]
[0027] The present application uses α,ω-straight-chain diol as a raw material, adds hydrochloric acid and toluene into a reaction container, heats the reaction for 20-25 hours to obtain a mixed solution, then controls the temperature of the mixed solution to 0-5°C, stirs for 1-5 hours to allow the unreacted raw material α,ω-straight-chain diol to be fully crystallized, removes the unconverted α,ω-straight-chain diol by suction filtration; allows the filtrate to stand for separation, extracts the aqueous phase once with a first solvent having an equal volume to the aqueous phase, and combines the organic phases; then washes the combined organic phases with an aqueous solution of a second solvent, and concentrates the washed organic phases to remove the solvent to obtain ω-chloro straight-chain primary alcohol.
[0028] Example 1
[0029] This embodiment provides a method for preparing 8-chloro-1-octanol from 1,8-octanediol, comprising the following steps:
[0030] Add 10 g of 1,8-octanediol, 50 mL of toluene, and 40 mL (7 eq.) of hydrochloric acid into a 200 mL high-pressure tank, heat the sealed system to 100-110°C, and stir and react for 20 h to obtain a mixed solution;
[0031] Turn off the heating, control the temperature of the mixed solution to 0 to 5 °C, stir for 2 h, open the can and filter to remove unreacted raw materials, let the filtrate stand to separate, and extract the aqueous phase once with 40 mL of toluene, combine the organic layers, and wash once with 50 mL of water; the washed organic phase is concentrated to remove toluene to obtain 8-chloro-1-octanol.
[0032] The purity of 8-chloro-1-octanol obtained in this example is 81.3 A%, and the yield is 96%.
[0033] Example 2
[0034] This embodiment provides a method for preparing 8-chloro-1-octanol from 1,8-octanediol, comprising the following steps:
[0035] In a 200 mL sealed container, add 10 g of 1,8-octanediol, 50 mL of toluene, and 40 mL of hydrochloric acid (7 eq.), heat the sealed system to 100-110 °C, and stir for 20 h to obtain a mixed solution;
[0036] Turn off the heating, control the temperature of the mixed solution to 0 to 5 °C, stir for 2 h, open the can and filter to remove unreacted raw materials, let the filtrate stand for separation, and extract the aqueous phase once with 40 mL of toluene, combine the organic layers, and wash three times with 50 mL of 10% methanol aqueous solution each time; the washed organic phase is concentrated to remove toluene to obtain 8-chloro-1-octanol.
[0037] The purity of 8-chloro-1-octanol obtained in this example is 92 A%, and the yield is 67%.
[0038] Detection by 1H NMR detection method: 1H NMR (400 MHz, DMSO) δ3.52 (t, J = 8.4 Hz 4H), 3.38 (q, J = 8.4 Hz, 2H), 1.81 (q, J = 8.4 Hz, 2 H), 1.41 (m, 4H) 1.3 (m, 6H).
[0039] Example 3
[0040] This embodiment provides a method for preparing 9-chloro-1-nonanol from 1,9-nonanediol, comprising the following steps:
[0041] In a 200 mL autoclave, 10 g of 1,9-nonanediol, 50 mL of toluene, and 36 mL (7 eq.) of hydrochloric acid were added, and the closed system was heated to 100-110 °C, and stirred for 20 h to obtain a mixed solution;
[0042] Turn off the heating, control the temperature of the mixed solution to 0 to 5 °C, stir for 2 h, open the can and filter to remove unreacted raw materials, let the filtrate stand for separation, and extract the aqueous phase once with 200 mL of toluene, combine the organic layers, and then wash the organic phase with 50 mL of water each time for 3 times; the washed organic phase is concentrated to remove toluene to obtain 9-chloro-1-nonanol.
[0043] The GC purity of 9-chloro-1-nonanol obtained in this example is 80.8 A%, and the yield is 96.3%.
[0044] Example 4
[0045] This embodiment provides a method for preparing 10-chloro-1-decanol from 1,10-decanediol, comprising the following steps:
[0046] In a 1000 mL autoclave, 50 g of 1,10-decanediol, 250 mL of toluene, and 195 mL (8 eq.) of hydrochloric acid were added. The closed system was heated to 100-110°C, and the mixture was stirred and reacted for 22 h to obtain a mixed solution.
[0047] Turn off the heating, control the temperature of the mixed solution to 0 to 5 °C, stir for 2 h, open the can and filter to remove unreacted raw materials, let the filtrate stand for separation, and extract the aqueous phase once with 200 mL of toluene, combine the organic layers, and then wash the organic phase with 250 mL of 30% methanol aqueous solution for 5 times; the washed organic phase is concentrated to remove toluene to obtain 10-chloro-1-decanol.
[0048] The purity of 10-chloro-1-decanol obtained in this example is 95.0 A%, and the yield is 62.7%.
[0049] Detection by 1H NMR detection method: 1H NMR (400 MHz, CDCl3) δ3.61 (q, J = 8.4 Hz, 4H), 3.52 (q, J = 8.4 Hz, 2H), 2.13 (s, 1H), 1.77 (m, 2 H), 1.56 (m, 2 H), 1.28-1.45 (m, 12H).
[0050] Example 5
[0051] This embodiment provides a method for preparing 10-chloro-1-decanol from 1,10-decanediol, comprising the following steps:
[0052] In a 2000 mL autoclave, 100 g of 1,10-decanediol, 500 mL of toluene, and 390 mL (8 eq.) of hydrochloric acid were added, and the closed system was heated to 100-110°C, and stirred for 22.5 h to obtain a mixed solution;
[0053] Turn off the heating, control the temperature of the mixed solution to 0 to 5 °C, stir for 2 h, open the can and filter to remove unreacted raw materials, let the filtrate stand for separation, and extract the aqueous phase once with 400 mL of toluene, combine the organic phases, and then wash the organic phases with 500 mL of 30% methanol aqueous solution for 3 times; the washed organic phase is concentrated to remove toluene to obtain 10-chloro-1-decanol.
[0054] The purity of 10-chloro-1-decanol obtained in this example is 91 A%, and the yield is 72.1%.
[0055] The above is only a preferred embodiment of the present invention. It should be pointed out that for ordinary technicians in this technical field, several improvements and modifications can be made without departing from the technical principles of the present invention. These improvements and modifications should also be regarded as the scope of protection of the present invention.
Claims
1. A method for preparing ω-chloro linear primary alcohol from α,ω-linear diol, characterized in that: The following steps are involved: The α,ω-straight-chain diol is dissolved in a reaction solvent, hydrochloric acid is added, and a substitution reaction is carried out at 86-110° C. for 13-25 h to obtain a mixture; the mixture is purified to obtain the ω-chloro straight-chain primary alcohol.
2. The method for preparing ω-chloro linear primary alcohol from α,ω-linear diol according to claim 1, characterized in that: The α,ω-straight-chain diol includes 1,8-octanediol, 1,9-nonanediol or 1,10-decanediol.
3. The method for preparing ω-chloro linear primary alcohol from α,ω-linear diol according to claim 1, characterized in that: The purification comprises: cooling the mixture to precipitate unreacted α,ω-straight-chain diol, filtering to obtain a filtrate, allowing the filtrate to stand for separation to obtain an organic phase, washing the organic phase with an aqueous solution of a second solvent and then concentrating to obtain the ω-chloro straight-chain primary alcohol.
4. The method for preparing ω-chloro linear primary alcohol from α,ω-linear diol according to claim 3, characterized in that: The mixture was cooled to 0-10°C to precipitate unreacted α,ω-linear diol.
5. The method for preparing ω-chloro linear primary alcohol from α,ω-linear diol according to claim 3, characterized in that: The second solvent is one or more of methanol, ethanol, isopropanol and N,N-dimethylformamide.
6. The method for preparing ω-chloro linear primary alcohol from α,ω-linear diol according to claim 1, characterized in that: The substitution reaction is carried out in a pressure vessel at a reaction temperature of 100 to 110° C. and a reaction time of 20 to 25 h.
7. The method for preparing ω-chloro linear primary alcohol from α,ω-linear diol according to claim 1, characterized in that: The reaction solvent includes one or more of toluene, xylene, chlorobenzene and methylcyclohexane.
8. The method for preparing ω-chloro linear primary alcohol from α,ω-linear diol according to claim 1, characterized in that: The molar ratio of α,ω-straight-chain diol to hydrochloric acid is 1:(1.5~16).
9. The method for preparing ω-chloro linear primary alcohol from α,ω-linear diol according to claim 1, characterized in that: The mass volume ratio (g / mL) of α,ω-straight-chain diol to reaction solvent is 1:(3~10).
10. The method for preparing ω-chloro linear primary alcohol from α,ω-linear diol according to claim 3, characterized in that: The purification step further comprises distillation under reduced pressure after the organic phase is concentrated.