CN115448833A - Method for directly chlorinating hydroxyl of polyfunctional aliphatic primary alcohol derivative - Google Patents
Method for directly chlorinating hydroxyl of polyfunctional aliphatic primary alcohol derivative Download PDFInfo
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- CN115448833A CN115448833A CN202211027465.7A CN202211027465A CN115448833A CN 115448833 A CN115448833 A CN 115448833A CN 202211027465 A CN202211027465 A CN 202211027465A CN 115448833 A CN115448833 A CN 115448833A
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- primary alcohol
- aliphatic primary
- alcohol derivative
- reaction
- chlorinating
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- -1 aliphatic primary alcohol Chemical class 0.000 title claims abstract description 25
- 238000000034 method Methods 0.000 title claims abstract description 25
- 125000002887 hydroxy group Chemical group [H]O* 0.000 title claims abstract description 21
- 238000006243 chemical reaction Methods 0.000 claims abstract description 29
- 238000001914 filtration Methods 0.000 claims abstract description 12
- 239000012046 mixed solvent Substances 0.000 claims abstract description 11
- 239000002904 solvent Substances 0.000 claims abstract description 11
- 239000007787 solid Substances 0.000 claims abstract description 10
- 239000003153 chemical reaction reagent Substances 0.000 claims abstract description 8
- 239000000706 filtrate Substances 0.000 claims abstract description 8
- 239000000047 product Substances 0.000 claims abstract description 7
- 238000003756 stirring Methods 0.000 claims abstract description 7
- 238000005660 chlorination reaction Methods 0.000 claims abstract description 6
- 238000001035 drying Methods 0.000 claims abstract description 5
- 238000004537 pulping Methods 0.000 claims abstract description 5
- 230000035484 reaction time Effects 0.000 claims abstract description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 18
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 15
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 9
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 claims description 9
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 6
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 6
- 239000012320 chlorinating reagent Substances 0.000 claims description 6
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 claims description 6
- UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical compound NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 claims description 6
- JRNVZBWKYDBUCA-UHFFFAOYSA-N N-chlorosuccinimide Chemical compound ClN1C(=O)CCC1=O JRNVZBWKYDBUCA-UHFFFAOYSA-N 0.000 claims description 5
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 4
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 claims description 4
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 4
- 239000007791 liquid phase Substances 0.000 claims description 4
- 238000012544 monitoring process Methods 0.000 claims description 4
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 claims description 4
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 claims description 4
- USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 claims description 3
- 239000005695 Ammonium acetate Substances 0.000 claims description 3
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Natural products NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 claims description 3
- 125000003545 alkoxy group Chemical group 0.000 claims description 3
- 229940043376 ammonium acetate Drugs 0.000 claims description 3
- 235000019257 ammonium acetate Nutrition 0.000 claims description 3
- 125000004185 ester group Chemical group 0.000 claims description 3
- UCPYLLCMEDAXFR-UHFFFAOYSA-N triphosgene Chemical compound ClC(Cl)(Cl)OC(=O)OC(Cl)(Cl)Cl UCPYLLCMEDAXFR-UHFFFAOYSA-N 0.000 claims description 3
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 claims description 2
- FUKUFMFMCZIRNT-UHFFFAOYSA-N hydron;methanol;chloride Chemical compound Cl.OC FUKUFMFMCZIRNT-UHFFFAOYSA-N 0.000 claims description 2
- UHZYTMXLRWXGPK-UHFFFAOYSA-N phosphorus pentachloride Chemical compound ClP(Cl)(Cl)(Cl)Cl UHZYTMXLRWXGPK-UHFFFAOYSA-N 0.000 claims description 2
- FAIAAWCVCHQXDN-UHFFFAOYSA-N phosphorus trichloride Chemical compound ClP(Cl)Cl FAIAAWCVCHQXDN-UHFFFAOYSA-N 0.000 claims description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 2
- 239000000243 solution Substances 0.000 claims description 2
- JRMUNVKIHCOMHV-UHFFFAOYSA-M tetrabutylammonium bromide Chemical compound [Br-].CCCC[N+](CCCC)(CCCC)CCCC JRMUNVKIHCOMHV-UHFFFAOYSA-M 0.000 claims description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 2
- 239000008096 xylene Substances 0.000 claims description 2
- 239000012295 chemical reaction liquid Substances 0.000 claims 1
- 239000000203 mixture Substances 0.000 claims 1
- 125000001424 substituent group Chemical group 0.000 claims 1
- 238000002360 preparation method Methods 0.000 abstract description 6
- 239000002994 raw material Substances 0.000 abstract description 6
- 238000006677 Appel reaction Methods 0.000 abstract description 5
- 230000001476 alcoholic effect Effects 0.000 abstract description 4
- 239000006227 byproduct Substances 0.000 abstract description 2
- HVLLSGMXQDNUAL-UHFFFAOYSA-N triphenyl phosphite Chemical compound C=1C=CC=CC=1OP(OC=1C=CC=CC=1)OC1=CC=CC=C1 HVLLSGMXQDNUAL-UHFFFAOYSA-N 0.000 abstract 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 12
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 8
- 239000000126 substance Substances 0.000 description 4
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 4
- 238000004128 high performance liquid chromatography Methods 0.000 description 3
- 238000005303 weighing Methods 0.000 description 3
- AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 2
- 125000001309 chloro group Chemical group Cl* 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 239000012847 fine chemical Substances 0.000 description 2
- 125000000524 functional group Chemical group 0.000 description 2
- 230000006872 improvement Effects 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 238000010907 mechanical stirring Methods 0.000 description 2
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 238000004064 recycling Methods 0.000 description 2
- 239000000758 substrate Substances 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- IPLKGJHGWCVSOG-UHFFFAOYSA-N 4-chlorobutanoic acid Chemical compound OC(=O)CCCCl IPLKGJHGWCVSOG-UHFFFAOYSA-N 0.000 description 1
- SJZRECIVHVDYJC-UHFFFAOYSA-N 4-hydroxybutyric acid Chemical compound OCCCC(O)=O SJZRECIVHVDYJC-UHFFFAOYSA-N 0.000 description 1
- 229940006015 4-hydroxybutyric acid Drugs 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- VWMHHTSUCLYIFK-UHFFFAOYSA-N OC1=CC=CC=C1.OC1=CC=CC=C1.OC1=CC=CC=C1.P Chemical compound OC1=CC=CC=C1.OC1=CC=CC=C1.OC1=CC=CC=C1.P VWMHHTSUCLYIFK-UHFFFAOYSA-N 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 238000003889 chemical engineering Methods 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 239000000460 chlorine Substances 0.000 description 1
- FOCAUTSVDIKZOP-UHFFFAOYSA-N chloroacetic acid Chemical compound OC(=O)CCl FOCAUTSVDIKZOP-UHFFFAOYSA-N 0.000 description 1
- 229940106681 chloroacetic acid Drugs 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 150000002148 esters Chemical group 0.000 description 1
- 238000007306 functionalization reaction Methods 0.000 description 1
- 230000026030 halogenation Effects 0.000 description 1
- 238000005658 halogenation reaction Methods 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- QDMZCBABQCORRW-BYPYZUCNSA-N methyl (2s)-2-amino-4-hydroxybutanoate Chemical compound COC(=O)[C@@H](N)CCO QDMZCBABQCORRW-BYPYZUCNSA-N 0.000 description 1
- QPOGJYQAKMZQQO-UHFFFAOYSA-N methyl 2-amino-4-chlorobutanoate Chemical compound COC(=O)C(N)CCCl QPOGJYQAKMZQQO-UHFFFAOYSA-N 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 238000006396 nitration reaction Methods 0.000 description 1
- 238000010534 nucleophilic substitution reaction Methods 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 150000003138 primary alcohols Chemical class 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- QOWQDMIPYOKNHP-UHFFFAOYSA-N triphenoxy phosphate Chemical compound C=1C=CC=CC=1OOP(OOC=1C=CC=CC=1)(=O)OOC1=CC=CC=C1 QOWQDMIPYOKNHP-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
- C07C51/347—Preparation of carboxylic acids or their salts, halides or anhydrides by reactions not involving formation of carboxyl groups
- C07C51/363—Preparation of carboxylic acids or their salts, halides or anhydrides by reactions not involving formation of carboxyl groups by introduction of halogen; by substitution of halogen atoms by other halogen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C227/00—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton
- C07C227/14—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton from compounds containing already amino and carboxyl groups or derivatives thereof
- C07C227/16—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton from compounds containing already amino and carboxyl groups or derivatives thereof by reactions not involving the amino or carboxyl groups
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention discloses a method for directly chlorinating hydroxyl of a polyfunctional aliphatic primary alcohol derivative, which comprises the following steps: stirring and reacting polyfunctional aliphatic primary alcohol derivative, chlorinated reagent and cocatalyst in a solvent at 25-100 ℃ for 1-10 hours, filtering filtrate, distilling the filtrate under reduced pressure to remove the solvent, pulping solid residues by using a mixed solvent, filtering and drying to obtain a direct chlorinated product; the invention optimizes the whole flow of the key preparation process and the parameter conditions of each reaction step, including the proportion of reaction raw materials, the type of chlorinated reagent, the reaction temperature, the reaction time and the like, and has the advantages of good route economy, high reaction selectivity, high industrial application value and the like compared with the traditional Appel reaction, thereby avoiding the triphenyl oxyphosphorus byproduct which is generated by the traditional alcoholic hydroxyl chlorination and is difficult to remove in the system.
Description
Technical Field
The invention belongs to the technical field of fine chemical preparation, and particularly relates to a method for directly chlorinating hydroxyl of a polyfunctional aliphatic primary alcohol derivative
Background
The alcoholic hydroxyl functional group is an important organic functional group and has a large number of application examples in the fields of natural product chemistry, pharmaceutical chemistry and fine chemical engineering. Due to the particularity and high reactivity of the hydroxyl group, when the hydroxyl group is further derivatized, the alcoholic hydroxyl group is often converted into chlorine, bromine or iodine, so that nucleophilic substitution, coupling and other reactions further occur. However, when active groups such as alkoxy, ester, amino and carboxyl are present in the system, these active functional groups are often incompatible, for example, when phosphorus oxychloride is used as a chlorinating agent, the selectivity of chlorination is greatly reduced if the active groups such as carboxyl are present in the substrate. Although the Appel reaction can solve the problem well, the reaction system generates a phosphorus triphenoxide byproduct which is difficult to remove due to the participation of triphenylphosphine. Therefore, the method is particularly urgent by adding a proper cocatalyst into the system, so that active groups such as amino, carboxyl, alkoxy and the like can be compatible under the halogenation condition, and meanwhile, the method for directly chlorinating alcoholic hydroxyl groups which are difficult to remove impurities such as triphenoxy phosphate and the like is not generated in the system. Based on this, a direct hydroxyl chlorination synthetic route of aliphatic primary alcohol with low production cost, simple synthetic method and high target product selectivity is urgently needed in the current industry.
Disclosure of Invention
In view of the above defects or improvement needs of the prior art, the present invention aims to provide a method for directly chlorinating hydroxyl groups of polyfunctional aliphatic primary alcohol derivatives, wherein by optimizing and improving the overall process of the key preparation process and the parameter conditions of each reaction step (including the ratio of reaction raw materials, the types of chlorinating reagents and cocatalysts, the reaction temperature and time, etc.), compared with the traditional Appel synthesis method, substrates with active groups of amino groups, carboxyl groups and ester groups can be compatible, and the method has the advantages of high reaction selectivity, low cost, simple operation, high industrial application value, etc.
In order to achieve the above object, according to the present invention, there is provided a method for directly chlorinating a hydroxyl group of a polyfunctional aliphatic primary alcohol derivative, comprising the steps of:
stirring and reacting aliphatic primary alcohol, a chlorinated reagent and a cocatalyst in a solvent at 25-100 ℃ for 1-10 hours, filtering, distilling the filtrate under reduced pressure to remove the solvent, pulping the solid residue by using a mixed solvent, filtering and drying to obtain a direct chlorinated product, and weighing to calculate the yield.
In a further preferred embodiment of the present invention, in the step, the chlorinating reagent is any one of HCl methanol solution, NCS, thionyl chloride, oxalyl chloride, triphosgene, carbon tetrachloride, phosphorus trichloride, and phosphorus pentachloride.
In a further preferred embodiment of the present invention, in the step, the cocatalyst is any one of thiourea, N-bromosuccinimide, tetrabutylammonium bromide, potassium iodide, and ammonium acetate.
In a further preferred embodiment of the present invention, in the step, the solvent is any one of toluene, xylene, dichloromethane, chloroform, acetonitrile, water, methanol, ethanol, and acetic acid, or a mixed solvent of any two of them.
In a further preferred embodiment of the present invention, in the step, the molar ratio of the aliphatic primary alcohol to the chlorinating reagent is 1:3 to 3:1, the reaction temperature is 80 ℃, and the reaction time is 8 hours.
Compared with the traditional Appel synthetic route, the technical scheme disclosed by the invention provides a new method for directly chlorinating primary alcohol. The method does not relate to triphenylphosphine in an Appel method, active groups such as amino, carboxyl, ester group and the like can be compatible, and a cheap and easily obtained chlorinated reagent is directly used as a raw material. Therefore, the preparation method provided by the invention is simple to operate, the raw materials are cheap and easy to obtain, and the reaction selectivity is good and the yield of chlorinated products is high by optimizing the reaction conditions (especially aiming at the material ratio of reactants, the types of chlorinated reagents and cocatalysts, the reaction temperature and time and the like).
The invention takes polyfunctional aliphatic primary alcohol as raw material, directly carries out chloro functionalization to prepare chloro product, and has the characteristics of high synthesis efficiency, lower cost and simple operation compared with the prior art. The preparation method of the invention firstly takes polyfunctional group aliphatic primary alcohol derivative and chlorinated reagent as raw materials to react in a single or mixed solvent to prepare chlorinated product. The main reactions involved are as follows:
the synthesis reaction can ensure higher yield, only needs one step, and does not relate to dangerous processes such as oxidation, nitration and the like. In conclusion, compared with the traditional direct chlorination of primary hydroxyl, the method has the advantages of high reaction selectivity, lower cost, simple operation, high industrial application value and the like.
Detailed Description
In order to make the objects, technical solutions and advantages of the present invention more apparent, the present invention is further described in detail with reference to the following embodiments. It should be understood that the specific embodiments described herein are merely illustrative of the invention and do not limit the invention. In addition, the technical features involved in the embodiments of the present invention described below may be combined with each other as long as they do not conflict with each other.
The preparation method of the hydroxyl direct chlorination of the polyfunctional aliphatic primary alcohol derivative is mainly realized by the following steps:
sequentially adding a polyfunctional group aliphatic primary alcohol derivative, a halogenated reagent, a cocatalyst and a solvent into a reactor with mechanical stirring, mixing the materials, and stirring and reacting at 25-100 ℃ for 1-8 hours; cooling and filtering to remove insoluble substances after the reaction is finished, distilling the filtrate under reduced pressure, recycling the solvent, pulping the residual solid residue by using a mixed solvent of n-hexane and ethyl acetate, filtering and drying, and weighing to calculate the yield.
The above scheme is described in detail below with different reaction conditions.
Example 1
The method comprises the following steps: a mixed solvent of methanol and acetonitrile (150mL, V) in which 7.6g (0.1 mol) of glycolic acid was dissolved was taken (150mL Methanol ：V H2O = 1:1), 13.3g (0.2 mol) of NCS and 3.8g (0.05 mol) of thiourea were added in portions with stirring at room temperature, and the above reaction solution was reacted with stirring at 60 ℃ for 4 hours in a reactor equipped with a mechanical stirrer. After the liquid phase monitoring reaction is finished, cooling the reaction system to room temperature, filtering to remove insoluble substances, distilling the filtrate under reduced pressure, recycling the solvent, pulping the residual solid residue by using a mixed solvent of n-hexane and ethyl acetate, filtering and drying, measuring the purity of chloroacetic acid by using a high performance liquid chromatography to be 98.2%, weighing and calculating the yield to obtain 7.4g of white solid, wherein the yield is 76.8%.
Example 2
The method comprises the following steps: homoserine methyl ester 13.3g (0.1 mol), carbon tetrachloride 18.4g (0.12 mol) and potassium iodide 8.3g (0.05 mol) were sequentially dissolved in a mixed solvent of methanol and toluene (150mL Methanol ：V Toluene = 1:2) the reaction solution was stirred in a reactor equipped with mechanical stirring at 80 ℃ for 8 hours. After the completion of the liquid-phase monitoring reaction, the reaction system was cooled to room temperature, insoluble substances were removed by filtration, the filtrate was distilled under reduced pressure, the remaining solid residue was slurried with an n-hexane/ethyl acetate mixed solvent, filtered and dried, the purity of 2-amino-4-chloro-butyric acid methyl ester was 94.2% by high performance liquid chromatography, 13.9g of a white solid was weighed, and the yield was 86.7%.
Example 3
The method comprises the following steps: 10.4g (0.1 mol) of 4-hydroxybutyric acid and 44.5g (0.15 mol) of triphosgene were dissolved in toluene (200), and after stirring at room temperature for 30 minutes, 7.7g (0.1 mol) of ammonium acetate was added, and the above reaction mixture was stirred in a reactor equipped with a mechanical stirrer at 100 ℃ for 2 hours. After the completion of the liquid phase monitoring reaction, the reaction system was cooled to room temperature, insoluble substances were removed by filtration, the filtrate was distilled under reduced pressure, the remaining solid residue was slurried with a mixed solvent of n-hexane/ethyl acetate, filtered and dried, the purity of 4-chloro-butyric acid was 97.1% by high performance liquid chromatography, and 8.9g of a white solid was weighed, and the yield was 70.8%.
It will be understood by those skilled in the art that the foregoing is only a preferred embodiment of the present invention, and is not intended to limit the invention, and that any modification, equivalent replacement, or improvement made within the spirit and principle of the present invention should be included in the scope of the present invention.
Claims (7)
1. A multifunctional group aliphatic primary alcohol derivative has a structural formula as follows:
wherein, the R substituent group comprises one or two of alkoxy, ester group, carboxyl and amino.
2. A method for directly chlorinating hydroxyl of a multifunctional aliphatic primary alcohol derivative is characterized by comprising the following steps:
(1) Stirring and reacting an aliphatic primary alcohol derivative, a chlorinated reagent and a cocatalyst in a solvent at 25-100 ℃ for 1-8 hours, and monitoring a reaction solution by a liquid phase until the reaction is finished;
(2) And (2) filtering the reaction liquid in the step (1), distilling the filtrate under reduced pressure to remove the solvent, pulping the solid residue by using the mixed solvent, filtering and drying to obtain the direct chlorination product.
3. The method for directly chlorinating the hydroxyl group of a polyfunctional aliphatic primary alcohol derivative according to claim 1, wherein in the step (1), the chlorinating agent is any one of HCl-methanol solution, NCS, thionyl chloride, oxalyl chloride, triphosgene, carbon tetrachloride, phosphorus trichloride, and phosphorus pentachloride.
4. The method for directly chlorinating the hydroxyl group of a polyfunctional aliphatic primary alcohol derivative according to claim 1, wherein in the step (1), the cocatalyst is any one of thiourea, N-bromosuccinimide, tetrabutylammonium bromide, potassium iodide and ammonium acetate.
5. The method for directly chlorinating the hydroxyl group of a polyfunctional aliphatic primary alcohol derivative according to claim 1, wherein the solvent in step (1) is any one or a mixture of any two of toluene, xylene, methylene chloride, chloroform, acetonitrile, water, methanol, ethanol and acetic acid.
6. The method for directly chlorinating the hydroxyl group of a polyfunctional aliphatic primary alcohol derivative according to claim 1, wherein the molar ratio of the aliphatic primary alcohol to the chlorinating reagent in step (1) is 1:3 to 3:1.
7. The method for directly chlorinating the hydroxyl group of a polyfunctional aliphatic primary alcohol derivative according to claim 1, wherein the reaction temperature in the step (1) is 80 ℃ and the reaction time is 8 hours.
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2022
- 2022-08-25 CN CN202211027465.7A patent/CN115448833B/en active Active
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