CN114591157A - Synthesis process of 5-chloro-2-pentanone - Google Patents
Synthesis process of 5-chloro-2-pentanone Download PDFInfo
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- CN114591157A CN114591157A CN202210359800.7A CN202210359800A CN114591157A CN 114591157 A CN114591157 A CN 114591157A CN 202210359800 A CN202210359800 A CN 202210359800A CN 114591157 A CN114591157 A CN 114591157A
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- XVRIEWDDMODMGA-UHFFFAOYSA-N 5-chloropentan-2-one Chemical compound CC(=O)CCCCl XVRIEWDDMODMGA-UHFFFAOYSA-N 0.000 title claims abstract description 38
- 238000000034 method Methods 0.000 title claims abstract description 26
- 230000015572 biosynthetic process Effects 0.000 title claims abstract description 18
- 238000003786 synthesis reaction Methods 0.000 title claims abstract description 18
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims abstract description 58
- 239000000203 mixture Substances 0.000 claims abstract description 55
- JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 claims abstract description 42
- 239000003054 catalyst Substances 0.000 claims abstract description 29
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims abstract description 29
- 238000001914 filtration Methods 0.000 claims abstract description 25
- 239000002131 composite material Substances 0.000 claims abstract description 24
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims abstract description 22
- 239000011592 zinc chloride Substances 0.000 claims abstract description 21
- 235000005074 zinc chloride Nutrition 0.000 claims abstract description 21
- 238000001035 drying Methods 0.000 claims abstract description 18
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims abstract description 13
- 238000002156 mixing Methods 0.000 claims abstract description 13
- 239000001301 oxygen Substances 0.000 claims abstract description 13
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 13
- 239000012279 sodium borohydride Substances 0.000 claims abstract description 11
- 229910000033 sodium borohydride Inorganic materials 0.000 claims abstract description 11
- JIQXRLOYKOJECL-UHFFFAOYSA-N 1-(2-chloroethoxy)-2-methoxyethane Chemical compound COCCOCCCl JIQXRLOYKOJECL-UHFFFAOYSA-N 0.000 claims abstract description 9
- HNBDRPTVWVGKBR-UHFFFAOYSA-N n-pentanoic acid methyl ester Natural products CCCCC(=O)OC HNBDRPTVWVGKBR-UHFFFAOYSA-N 0.000 claims abstract description 5
- 230000002194 synthesizing effect Effects 0.000 claims abstract 8
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 48
- 238000006243 chemical reaction Methods 0.000 claims description 43
- 238000003756 stirring Methods 0.000 claims description 29
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 27
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 26
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 claims description 24
- 239000008367 deionised water Substances 0.000 claims description 21
- 229910021641 deionized water Inorganic materials 0.000 claims description 21
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 18
- 239000012074 organic phase Substances 0.000 claims description 18
- 239000012018 catalyst precursor Substances 0.000 claims description 17
- 239000000706 filtrate Substances 0.000 claims description 14
- 238000010992 reflux Methods 0.000 claims description 14
- OEFNYQCKZXMGIN-UHFFFAOYSA-N cobalt 4-[10,15,20-tris(4-sulfophenyl)-21,23-dihydroporphyrin-5-yl]benzenesulfonic acid Chemical compound [Co].OS(=O)(=O)c1ccc(cc1)-c1c2ccc(n2)c(-c2ccc(cc2)S(O)(=O)=O)c2ccc([nH]2)c(-c2ccc(cc2)S(O)(=O)=O)c2ccc(n2)c(-c2ccc(cc2)S(O)(=O)=O)c2ccc1[nH]2 OEFNYQCKZXMGIN-UHFFFAOYSA-N 0.000 claims description 12
- 239000000243 solution Substances 0.000 claims description 11
- 239000000047 product Substances 0.000 claims description 10
- 159000000000 sodium salts Chemical class 0.000 claims description 10
- 238000005406 washing Methods 0.000 claims description 10
- 239000011701 zinc Substances 0.000 claims description 10
- CFMZSMGAMPBRBE-UHFFFAOYSA-N 2-hydroxyisoindole-1,3-dione Chemical compound C1=CC=C2C(=O)N(O)C(=O)C2=C1 CFMZSMGAMPBRBE-UHFFFAOYSA-N 0.000 claims description 9
- 239000012266 salt solution Substances 0.000 claims description 9
- ACHJFGYOUCOVQP-UHFFFAOYSA-N methyl 4-hydroxypentanoate Chemical compound COC(=O)CCC(C)O ACHJFGYOUCOVQP-UHFFFAOYSA-N 0.000 claims description 8
- 238000001816 cooling Methods 0.000 claims description 7
- 238000001704 evaporation Methods 0.000 claims description 7
- 238000010791 quenching Methods 0.000 claims description 7
- 239000012153 distilled water Substances 0.000 claims description 5
- JLDSOYXADOWAKB-UHFFFAOYSA-N aluminium nitrate Chemical compound [Al+3].[O-][N+]([O-])=O.[O-][N+]([O-])=O.[O-][N+]([O-])=O JLDSOYXADOWAKB-UHFFFAOYSA-N 0.000 claims description 4
- ONDPHDOFVYQSGI-UHFFFAOYSA-N zinc nitrate Inorganic materials [Zn+2].[O-][N+]([O-])=O.[O-][N+]([O-])=O ONDPHDOFVYQSGI-UHFFFAOYSA-N 0.000 claims description 2
- 238000007711 solidification Methods 0.000 claims 1
- 230000008023 solidification Effects 0.000 claims 1
- 239000002994 raw material Substances 0.000 abstract description 13
- 125000002887 hydroxy group Chemical group [H]O* 0.000 abstract description 10
- 238000005660 chlorination reaction Methods 0.000 abstract description 5
- 239000003814 drug Substances 0.000 abstract description 4
- 230000003647 oxidation Effects 0.000 abstract description 4
- 238000007254 oxidation reaction Methods 0.000 abstract description 4
- 125000004185 ester group Chemical group 0.000 abstract description 3
- 150000001875 compounds Chemical class 0.000 abstract description 2
- 238000010511 deprotection reaction Methods 0.000 abstract description 2
- 238000005580 one pot reaction Methods 0.000 abstract description 2
- 230000000052 comparative effect Effects 0.000 description 14
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 6
- 238000009776 industrial production Methods 0.000 description 5
- 229910052725 zinc Inorganic materials 0.000 description 5
- -1 5-chloropentylene Chemical group 0.000 description 3
- 239000000543 intermediate Substances 0.000 description 3
- 230000001590 oxidative effect Effects 0.000 description 3
- 238000001308 synthesis method Methods 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 2
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 2
- YIKMRTHKLRXOBU-UHFFFAOYSA-N bromomethane;triphenylphosphane Chemical compound BrC.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 YIKMRTHKLRXOBU-UHFFFAOYSA-N 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 238000000975 co-precipitation Methods 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 150000002576 ketones Chemical class 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 239000007800 oxidant agent Substances 0.000 description 2
- XKJCHHZQLQNZHY-UHFFFAOYSA-N phthalimide Chemical compound C1=CC=C2C(=O)NC(=O)C2=C1 XKJCHHZQLQNZHY-UHFFFAOYSA-N 0.000 description 2
- HDKKRASBPHFULQ-UHFFFAOYSA-N 3-Hydroxy-2-pentanone Chemical compound CCC(O)C(C)=O HDKKRASBPHFULQ-UHFFFAOYSA-N 0.000 description 1
- CDIIZULDSLKBKV-UHFFFAOYSA-N 4-chlorobutanoyl chloride Chemical compound ClCCCC(Cl)=O CDIIZULDSLKBKV-UHFFFAOYSA-N 0.000 description 1
- AEUAEICGCMSYCQ-UHFFFAOYSA-N 4-n-(7-chloroquinolin-1-ium-4-yl)-1-n,1-n-diethylpentane-1,4-diamine;dihydrogen phosphate Chemical compound OP(O)(O)=O.ClC1=CC=C2C(NC(C)CCCN(CC)CC)=CC=NC2=C1 AEUAEICGCMSYCQ-UHFFFAOYSA-N 0.000 description 1
- GRGNJBKJCVOFEO-UHFFFAOYSA-N 5-(diethylamino)pentan-2-one Chemical compound CCN(CC)CCCC(C)=O GRGNJBKJCVOFEO-UHFFFAOYSA-N 0.000 description 1
- HTJDQJBWANPRPF-UHFFFAOYSA-N Cyclopropylamine Chemical compound NC1CC1 HTJDQJBWANPRPF-UHFFFAOYSA-N 0.000 description 1
- 229910021578 Iron(III) chloride Inorganic materials 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 238000007792 addition Methods 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 150000001450 anions Chemical class 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- PBHVCRIXMXQXPD-UHFFFAOYSA-N chembl2369102 Chemical compound C1=CC(S(=O)(=O)O)=CC=C1C(C1=CC=C(N1)C(C=1C=CC(=CC=1)S(O)(=O)=O)=C1C=CC(=N1)C(C=1C=CC(=CC=1)S(O)(=O)=O)=C1C=CC(N1)=C1C=2C=CC(=CC=2)S(O)(=O)=O)=C2N=C1C=C2 PBHVCRIXMXQXPD-UHFFFAOYSA-N 0.000 description 1
- 239000003638 chemical reducing agent Substances 0.000 description 1
- 229960002328 chloroquine phosphate Drugs 0.000 description 1
- 229910017052 cobalt Inorganic materials 0.000 description 1
- 239000010941 cobalt Substances 0.000 description 1
- GUTLYIVDDKVIGB-UHFFFAOYSA-N cobalt atom Chemical compound [Co] GUTLYIVDDKVIGB-UHFFFAOYSA-N 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 1
- 239000010931 gold Substances 0.000 description 1
- 229910052737 gold Inorganic materials 0.000 description 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
- 239000011229 interlayer Substances 0.000 description 1
- RBTARNINKXHZNM-UHFFFAOYSA-K iron trichloride Chemical compound Cl[Fe](Cl)Cl RBTARNINKXHZNM-UHFFFAOYSA-K 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- LISFMEBWQUVKPJ-UHFFFAOYSA-N quinolin-2-ol Chemical compound C1=CC=C2NC(=O)C=CC2=C1 LISFMEBWQUVKPJ-UHFFFAOYSA-N 0.000 description 1
- 229910001415 sodium ion Inorganic materials 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
- C07C45/27—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by oxidation
- C07C45/32—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by oxidation with molecular oxygen
- C07C45/37—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by oxidation with molecular oxygen of >C—O—functional groups to >C=O groups
- C07C45/38—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by oxidation with molecular oxygen of >C—O—functional groups to >C=O groups being a primary hydroxyl group
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C29/00—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring
- C07C29/09—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring by hydrolysis
- C07C29/10—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring by hydrolysis of ethers, including cyclic ethers, e.g. oxiranes
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C41/00—Preparation of ethers; Preparation of compounds having groups, groups or groups
- C07C41/01—Preparation of ethers
- C07C41/18—Preparation of ethers by reactions not forming ether-oxygen bonds
- C07C41/26—Preparation of ethers by reactions not forming ether-oxygen bonds by introduction of hydroxy or O-metal groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C67/00—Preparation of carboxylic acid esters
- C07C67/30—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group
- C07C67/31—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by introduction of functional groups containing oxygen only in singly bound form
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Catalysts (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention relates to a synthesis process of 5-chloro-2-pentanone, belonging to the technical field of medicine synthesis and comprising the following steps: s1, dissolving 4-hydroxy methyl valerate in tetrahydrofuran, and adding 1- (2-chloroethoxy) -2-methoxyethane to obtain a composition A; s2, dissolving the composition A in tetrahydrofuran, adding zinc chloride, and adding sodium borohydride to obtain a composition B; s3, mixing the composition B with concentrated hydrochloric acid, and adding anhydrous zinc chloride to obtain a composition C; s4, dissolving the composition C in tetrahydrofuran, adding a composite catalyst, introducing oxygen, filtering, extracting, drying and distilling to obtain the 5-chloro-2-pentanone. In the technical scheme of the invention, 4-hydroxy methyl valerate is used as an initial raw material for synthesizing 5 chloro-2-pentanone, and a target compound is prepared by 5 steps of hydroxyl protection, ester group one-pot deprotection, chlorination and hydroxyl oxidation.
Description
Technical Field
The invention belongs to the technical field of medicine synthesis, and particularly relates to a synthesis process of 5-chloro-2-pentanone.
Background
The 5-chloro-2-pentanone is an important medical and chemical intermediate, can be used for preparing important drug intermediates such as 5-diethylamino-2-pentanone, cyclopropylamine and the like, and is used for producing chloroquine phosphate and quinolone drugs. In recent years, the demand of the product is increased sharply, and the research on the synthesis process is carried out to improve the production capacity and the process level of the product, thereby having important significance.
4 synthetic routes to 5-chloro-2-pentanone are reported in the prior art: 1) 5-chloropentylene is used as a raw material, gold is used as a catalyst, and a target product is obtained by reaction under an acidic condition, so that the yield is low, and the price of the used raw material is high; 2) 4-chlorobutyryl chloride is used as an initial raw material, an intermediate amide is prepared firstly and then reacts with triphenylphosphine methyl bromide to obtain 5-chloro-2-pentanone, the method uses butyl lithium, triphenylphosphine methyl bromide and other raw materials, the reaction conditions are harsh, and the method is not suitable for industrial production; 3) acetyl-n-propanol is used as a starting material, and a target product is prepared through chlorination, but the price of the raw material is higher. Therefore, the existing 5-chloro-2-pentanone synthesis method is not suitable for large-scale industrial production due to the limitations of raw material sources, reaction conditions, low conversion rate and the like.
Disclosure of Invention
The invention aims to provide a synthesis process of 5-chloro-2-pentanone, which is characterized in that 4-hydroxy methyl valerate serving as a raw material and a high-efficiency composite catalyst are adopted, high conversion of 5-chloro-2-pentanone is realized, reaction conditions are mild, and the synthesis process is suitable for industrial production.
The technical problems to be solved by the invention are as follows: the existing 5-chloro-2-pentanone synthesis method is not suitable for industrial production due to the limitations of raw material sources, reaction conditions, low conversion rate and the like.
The purpose of the invention can be realized by the following technical scheme:
a synthesis process of 5-chloro-2-pentanone comprises the following steps:
s1, dissolving 4-hydroxy valeric acid methyl ester in tetrahydrofuran, adding 1- (2-chloroethoxy) -2-methoxyethane, stirring and reacting for 1h at 0 ℃, separating out an organic phase, washing with deionized water for 2-3 times, drying with anhydrous sodium sulfate, filtering to remove the anhydrous sodium sulfate, concentrating and solidifying under reduced pressure to obtain a composition A, wherein the dosage ratio of the 4-hydroxy valeric acid methyl ester to the toluene to the 1- (2-chloroethoxy) -2-methoxyethane is 0.08-0.12 mol: 98-102 mL: 0.18-0.22 mol;
the reaction process comprises the following steps:
s2, dissolving the composition A in tetrahydrofuran, adding zinc chloride, adding sodium borohydride at room temperature, performing reflux reaction for 4 hours, adding deionized water to quench the reaction, continuing stirring for 1 hour, and performing reduced pressure concentration to recover tetrahydrofuran to obtain a composition B, wherein the dosage ratio of the composition A to the tetrahydrofuran to the zinc chloride to the sodium borohydride to the deionized water is 14-28 g: 95-105 mL: 0.01-0.03 mol:18-22mL of 0.17-0.22 mol;
the reaction process comprises the following steps:
s3, uniformly mixing the composition B and concentrated hydrochloric acid, adding anhydrous zinc chloride after the reaction is finished, performing reflux reaction for 4 hours, cooling to room temperature, and filtering to obtain a composition C, wherein the dosage ratio of the anhydrous zinc chloride to the concentrated hydrochloric acid to the composition B is 10.8-11.2 g: 14.5-30 g: 0.07-0.15 mol;
the reaction process comprises the following steps:
s4, dissolving the composition C in tetrahydrofuran, adding a composite catalyst, introducing oxygen, stirring for reaction for 15min, filtering to obtain a filtrate, extracting the filtrate with dichloromethane, combining organic phases, drying the organic phases with anhydrous sodium sulfate, removing the anhydrous sodium sulfate, evaporating dichloromethane, and carrying out reduced pressure distillation to obtain 5-chloro-2-pentanone, wherein the dosage ratio of the composition C, the tetrahydrofuran, the composite catalyst, the oxygen and the dichloromethane is 6-12 g: 150-220 mL: 5-10 mg: 0.01-0.02 g: 90-110 mL.
The reaction process comprises the following steps:
further, the composite catalyst is prepared by the following steps:
D1、Zn(NO3)2·6H2o and Al (NO)3)3·9H2Dissolving the mixture of O in deionized water, wherein the solution contains sodium salt of cobalt tetrakis (4-sulfophenyl) porphyrin, continuously dropwise adding 0.1mol/L NaOH solution to maintain the pH value at 8.5, stirring at 80 ℃ for 24h, filtering the product, washing with 80 ℃ distilled water, and finally drying at room temperature to obtain the catalyst precursor, wherein Zn (NO) is Zn (NO)3)2·6H2O、Al(NO3)3·9H2The mass ratio of O, deionized water, the sodium salt solution of cobalt tetra (4-sulfophenyl) porphyrin and the NaOH solution is 1.57-1.72: 0.95-1.15: 45-55: 10.3-12.5: 18-25;
d2, stirring and uniformly mixing the N-hydroxyphthalimide and the catalyst precursor to obtain the composite catalyst, wherein the dosage ratio of the N-hydroxyphthalimide to the catalyst precursor is 0.55-0.64 mmol: 28-32 mg.
In the reaction process, in the step D1, the pH value is maintained at 8.5 by using a NaOH solution, so that the layered double hydroxide composed of Zn and Al is prepared by coprecipitation at a constant pH, the sodium salt solution of cobalt tetra (4-sulfophenyl) porphyrin is obtained by chelating cobalt with tetra (4-sulfophenyl) porphyrin first to form cobalt tetra (4-sulfophenyl) porphyrin and then reacting with sodium ions, and the anion of cobalt tetra (4-sulfophenyl) porphyrin in the sodium salt solution of cobalt tetra (4-sulfophenyl) porphyrin is embedded into the layered double hydroxide composed of Zn and Al, so that the synthesis of a catalyst precursor is realized, and the catalyst precursor has the capability of catalyzing the oxidation of oxygen; in step D2, N-hydroxyphthalimide is oxidized in the presence of oxygen and a catalyst precursor to produce phthalimide N-oxyl radicals, which, in catalytic oxidation, are capable of extracting a hydrogen atom from an alcohol to accelerate the conversion of the alcohol to a ketone.
The invention has the beneficial effects that:
1. in the technical scheme of the invention, 4-hydroxy methyl valerate is used for synthesisPreparing an initial raw material of 5-chloro-2-pentanone, carrying out hydroxyl protection, ester group one-pot deprotection, chlorination and hydroxyl oxidation on the initial raw material to obtain a target compound, wherein 1- (2-chloroethoxy) -2-methoxyethane reacts with hydroxyl to realize the protection of the hydroxyl, sodium borohydride is used as a reducing agent, zinc chloride is used as a catalyst to reduce the ester group into the hydroxyl, the chlorination of the terminal hydroxyl is realized in a hydrochloric acid system, and after the chlorination, ZnCl is subjected to reaction2The protected hydroxyl group is deprotected under the action, the deprotected hydroxyl group is oxidized into carbonyl under the action of the composite catalyst, the total yield is up to 75.6 percent, the product purity reaches 99.2 percent, and the synthesis method of 5-chloro-2-pentanone, which has the advantages of cheap and easily obtained raw materials, high yield, simple and convenient operation and suitability for industrial production, is established;
2. in the technical scheme of the invention, the pH value is kept at 8.5 by NaOH solution, the layered double hydroxide consisting of Zn and Al is prepared by coprecipitation under constant pH, the tetra (4-sulfophenyl) porphyrin cobalt anion in the sodium salt solution of the tetra (4-sulfophenyl) porphyrin cobalt is embedded into the layered double hydroxide consisting of Zn and Al, the synthesis of a catalyst precursor is realized, the layered double hydroxide consisting of Zn and Al embedded with the tetra (4-sulfophenyl) porphyrin cobalt anion has larger interlayer distance compared with the traditional layered double hydroxide, so that more alkaline active sites are exposed, the rate of generating phthalimide N-oxyl free radicals by oxidizing N-hydroxyphthalimide under the condition of the existence of oxygen and the catalyst precursor is accelerated, and the catalyst can be oxidized more quickly, More efficient conversion of alcohols to ketones.
Detailed Description
The technical solutions in the embodiments of the present invention will be clearly and completely described below with reference to the embodiments of the present invention, and it is obvious that the described embodiments are only a part of the embodiments of the present invention, and not all of the embodiments. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.
Example 1
The composite catalyst is prepared by the following steps:
d1, 1.57 to 1.57gZn (NO)3)2·6H2O and 0.95gAl (NO)3)3·9H2Dissolving the mixture of O in 45g of deionized water, adding 10.3g of sodium salt solution of cobalt tetrakis (4-sulfophenyl) porphyrin, continuously dropwise adding 18g of 0.1mol/L NaOH solution to keep the pH value at 8.5, stirring at 80 ℃ for 24h, filtering the product, washing with 80 ℃ distilled water, and finally drying at room temperature to obtain a catalyst precursor;
d2, stirring and mixing 0.55mmol of N-hydroxyphthalimide and 28mg of catalyst precursor uniformly to obtain the composite catalyst.
Example 2
The composite catalyst is prepared by the following steps:
d1, 1.67g Zn (NO)3)2·6H2O and 1.05g Al (NO)3)3·9H2Dissolving the mixture of O in 50g of deionized water, adding 11.2g of sodium salt solution of cobalt tetrakis (4-sulfophenyl) porphyrin, continuously dropwise adding 21g of 0.1mol/L NaOH solution to keep the pH value at 8.5, stirring for 24 hours at 80 ℃, filtering the product, washing with 80 ℃ distilled water, and finally drying at room temperature to obtain a catalyst precursor;
d2, stirring and mixing 0.61mmol of N-hydroxyphthalimide and 30mg of catalyst precursor uniformly to obtain the composite catalyst.
Example 3
The composite catalyst is prepared by the following steps:
d1, 1.72g Zn (NO)3)2·6H2O and 1.15g Al (NO)3)3·9H2Dissolving the mixture of O in 55g of deionized water, adding 12.5g of sodium salt solution of cobalt tetrakis (4-sulfophenyl) porphyrin, continuously dropwise adding 25g of 0.1mol/L NaOH solution to keep the pH value at 8.5, stirring for 24 hours at 80 ℃, filtering the product, washing with 80 ℃ distilled water, and finally drying at room temperature to obtain a catalyst precursor;
d2, stirring and mixing 0.64mmol of N-hydroxyphthalimide and 32mg of catalyst precursor uniformly to obtain the composite catalyst.
Comparative example 1
The catalyst of the comparative example is the existing hydrogen peroxide.
Comparative example 2
The catalyst of this comparative example is an existing FeCl3。
Example 4
A synthesis process of 5-chloro-2-pentanone comprises the following steps:
s1, dissolving 0.08mol of 4-hydroxypentanoic acid methyl ester (synthesized according to the method disclosed in the patent publication No. CN 101591246B) in 98mL of toluene, adding 0.18mol of 1- (2-chloroethoxy) -2-methoxyethane, stirring and reacting at 0 ℃ for 1h, separating out an organic phase, washing with 100mL of deionized water for 2-3 times, drying with anhydrous sodium sulfate, filtering out the anhydrous sodium sulfate, and then concentrating and solidifying under reduced pressure to obtain a composition A;
s2, dissolving 14g of the composition A in 95mL of tetrahydrofuran, adding 0.01mol of zinc chloride, adding 0.17mol of sodium borohydride at room temperature, carrying out reflux reaction for 4 hours, adding 18mL of deionized water to quench the reaction, continuing stirring for 1 hour, and carrying out reduced pressure concentration to recover tetrahydrofuran to obtain a composition B;
s3, uniformly mixing 10.8g of anhydrous zinc chloride and 0.06mol of concentrated hydrochloric acid, adding 10.8g of composition B, carrying out reflux reaction for 4 hours, cooling to room temperature, and filtering to obtain a composition C;
s4, dissolving 6g of composition C in 150mL of tetrahydrofuran, adding 5mg of the composite catalyst prepared in example 1, introducing 0.01g of oxygen, stirring for reaction for 15min, filtering to obtain a filtrate, extracting the filtrate with 90mL of dichloromethane, combining organic phases, drying with anhydrous sodium sulfate, removing the anhydrous sodium sulfate, evaporating dichloromethane, and distilling under reduced pressure to obtain 5-chloro-2-pentanone.
Example 5
A synthesis process of 5-chloro-2-pentanone comprises the following steps:
s1, dissolving 0.1mol of methyl 4-hydroxypentanoate in 100mL of toluene, adding 0.2mol of 1- (2-chloroethoxy) -2-methoxyethane, stirring and reacting at 0 ℃ for 1h, separating an organic phase, washing the organic phase for 2-3 times by using 100mL of deionized water, drying the organic phase by using anhydrous sodium sulfate, and filtering the anhydrous sodium sulfate to obtain a composition A;
s2, dissolving 21g of the composition A in 100mL of tetrahydrofuran, adding 0.02mol of zinc chloride, adding 0.2mol of sodium borohydride at room temperature, carrying out reflux reaction for 4 hours, adding 20mL of deionized water to quench the reaction, continuing stirring for 1 hour, and carrying out reduced pressure concentration to recover tetrahydrofuran to obtain a composition B;
s3, uniformly mixing 11g of anhydrous zinc chloride and 0.1mol of concentrated hydrochloric acid, adding 11g of the composition B, carrying out reflux reaction for 4 hours, cooling to room temperature, and filtering to obtain a composition C;
s4, dissolving 10g of composition C in 200mL of tetrahydrofuran, adding 8mg of the composite catalyst prepared in example 2, introducing 0.015g of oxygen, stirring for reacting for 15min, filtering to obtain a filtrate, extracting the filtrate with 100mL of dichloromethane, combining organic phases, drying with anhydrous sodium sulfate, removing the anhydrous sodium sulfate, evaporating dichloromethane, and distilling under reduced pressure to obtain 5-chloro-2-pentanone.
Example 6
A synthesis process of 5-chloro-2-pentanone comprises the following steps:
s1, dissolving 0.12mol of methyl 4-hydroxypentanoate in 102mL of toluene, adding 0.22mol of 1- (2-chloroethoxy) -2-methoxyethane, stirring and reacting at 0 ℃ for 1h, separating an organic phase, washing the organic phase for 2-3 times by using 100mL of deionized water, drying the organic phase by using anhydrous sodium sulfate, and filtering the anhydrous sodium sulfate to obtain a composition A;
s2, dissolving 28g of the composition A in 105mL of tetrahydrofuran, adding 0.03mol of zinc chloride, adding 0.22mol of sodium borohydride at room temperature, carrying out reflux reaction for 4 hours, adding 22mL of deionized water to quench the reaction, continuing stirring for 1 hour, and carrying out reduced pressure concentration to recover tetrahydrofuran to obtain a composition B;
s3, uniformly mixing 11.2g of anhydrous zinc chloride and 0.12mol of concentrated hydrochloric acid, adding 11.2g of the composition B, carrying out reflux reaction for 4 hours, cooling to room temperature, and filtering to obtain a composition C;
s4, dissolving 12g of the composition C in 220mL of tetrahydrofuran, adding 10mg of the composite catalyst prepared in the embodiment 3, introducing 0.02g of oxygen, stirring and reacting for 15min, filtering to obtain a filtrate, extracting the filtrate with 110mL of dichloromethane, combining organic phases, drying the organic phases with anhydrous sodium sulfate, removing the anhydrous sodium sulfate, evaporating the dichloromethane, and distilling under reduced pressure to obtain the 5-chloro-2-pentanone.
Comparative example 3
A synthesis process of 5-chloro-2-pentanone comprises the following steps:
s1, dissolving 0.08mol of methyl 4-hydroxypentanoate in 98mL of tetrahydrofuran, adding 0.01mol of zinc chloride, adding 0.17mol of sodium borohydride at room temperature, carrying out reflux reaction for 4 hours, adding 18mL of deionized water to quench the reaction, continuing stirring for 1 hour, and carrying out reduced pressure concentration to recover tetrahydrofuran to obtain a composition B;
s2, uniformly mixing 10.8g of anhydrous zinc chloride and 0.06mol of concentrated hydrochloric acid, adding 10.8g of composition B, carrying out reflux reaction for 4 hours, cooling to room temperature, and filtering to obtain a composition C;
s3, dissolving 6g of composition C in 150mL of tetrahydrofuran, adding 5mg of the composite catalyst prepared in example 1, introducing 0.015g of oxygen, stirring for reaction for 15min, filtering to obtain a filtrate, extracting the filtrate with 90mL of dichloromethane, combining organic phases, drying with anhydrous sodium sulfate, removing the anhydrous sodium sulfate, evaporating dichloromethane, and distilling under reduced pressure to obtain 5-chloro-2-pentanone.
Comparative example 4
A synthesis process of 5-chloro-2-pentanone comprises the following steps:
s1, dissolving 0.1mol of methyl 4-hydroxypentanoate in 100mL of tetrahydrofuran, adding 0.02mol of zinc chloride, adding 0.2mol of sodium borohydride at room temperature, carrying out reflux reaction for 4 hours, adding 20mL of deionized water to quench the reaction, continuously stirring for 1 hour, and carrying out reduced pressure concentration to recover tetrahydrofuran to obtain a composition B;
s2, uniformly mixing 11g of anhydrous zinc chloride and 0.1mol of concentrated hydrochloric acid, adding 11g of the composition B, carrying out reflux reaction for 4 hours, cooling to room temperature, and filtering to obtain a composition C;
s3, dissolving 10g of composition C in 200mL of tetrahydrofuran, adding 8mg of the composite catalyst prepared in example 2, introducing 0.02g of oxygen, stirring for reacting for 15min, filtering to obtain a filtrate, extracting the filtrate with 100mL of dichloromethane, combining organic phases, drying with anhydrous sodium sulfate, removing the anhydrous sodium sulfate, evaporating dichloromethane, and distilling under reduced pressure to obtain 5-chloro-2-pentanone.
Comparative example 5
This comparative example replaces the composite catalyst prepared in example 2 in step S4 of example 5 with the oxidant in comparative example 1, and the other steps and reagents are the same as in example 5.
Comparative example 6
This comparative example replaces the composite catalyst prepared in example 3 in step S4 of example 6 with the oxidant in comparative example 2, and the other steps and reagents are the same as in example 6.
The yields and purities of 5-chloro-2-pentanone prepared in examples 4-6 and comparative examples 3-6 were now tested and the results are shown in table 1 below:
TABLE 1
As can be seen from table 1 above, the 5-chloro-2-pentanone prepared in the examples of the present invention has higher yield and purity, and higher raw material utilization rate, compared with the comparative examples, and is suitable for industrial mass production.
In the description herein, references to the description of "one embodiment," "an example," "a specific example" or the like are intended to mean that a particular feature, structure, material, or characteristic described in connection with the embodiment or example is included in at least one embodiment or example of the invention. In this specification, the schematic representations of the terms used above do not necessarily refer to the same embodiment or example. Furthermore, the particular features, structures, materials, or characteristics described may be combined in any suitable manner in any one or more embodiments or examples.
The foregoing is illustrative and explanatory only and is not intended to be exhaustive or to limit the invention to the precise embodiments described, and various modifications, additions, and substitutions may be made by those skilled in the art without departing from the scope of the invention or exceeding the scope of the claims.
Claims (8)
1. A synthesis process of 5-chloro-2-pentanone is characterized by comprising the following steps: the method comprises the following steps:
s1, dissolving 4-hydroxy methyl valerate in toluene, adding 1- (2-chloroethoxy) -2-methoxyethane, stirring and reacting for 1h at 0 ℃, separating out an organic phase, washing with deionized water for 2-3 times, drying with anhydrous sodium sulfate, filtering to remove the anhydrous sodium sulfate, and then carrying out reduced pressure concentration and solidification to obtain a composition A;
s2, dissolving the composition A in tetrahydrofuran, adding zinc chloride, adding sodium borohydride at room temperature, performing reflux reaction for 4 hours, adding deionized water to quench the reaction, continuing stirring for 1 hour, and performing reduced pressure concentration to recover tetrahydrofuran to obtain a composition B;
s3, uniformly mixing the composition B with concentrated hydrochloric acid, adding anhydrous zinc chloride after complete reaction, performing reflux reaction for 4 hours, cooling to room temperature, and filtering to obtain a composition C;
s4, dissolving the composition C in tetrahydrofuran, adding the composite catalyst, introducing oxygen, stirring for reaction for 15min, filtering to obtain a filtrate, extracting the filtrate with dichloromethane, combining organic phases, drying with anhydrous sodium sulfate, removing the anhydrous sodium sulfate, evaporating dichloromethane, and distilling under reduced pressure to obtain 5-chloro-2-pentanone.
2. The process for synthesizing 5-chloro-2-pentanone according to claim 1, wherein: in step S1, the ratio of the amount of methyl 4-hydroxypentanoate to the amount of toluene to the amount of 1- (2-chloroethoxy) -2-methoxyethane is 0.08 to 0.12 mol: 98-102 mL: 0.18-0.22 mol.
3. The process for synthesizing 5-chloro-2-pentanone according to claim 1, wherein: in step S2, the amount ratio of the composition a, tetrahydrofuran, zinc chloride, sodium borohydride and deionized water is 14-28 g: 95-105 mL: 0.01-0.03 mol:18-22mL of 0.17-0.22 mol.
4. The process for synthesizing 5-chloro-2-pentanone according to claim 1, characterized in that: in step S3, the dosage ratio of the anhydrous zinc chloride, the concentrated hydrochloric acid and the composition B is 10.8-11.2 g: 0.06-0.12 mol: 0.07-0.15 mol.
5. The process for synthesizing 5-chloro-2-pentanone according to claim 1, wherein: in step S4, the composition C, tetrahydrofuran, the composite catalyst, oxygen, and dichloromethane are used in an amount ratio of 6 to 12 g: 150-220 mL: 5-10 mg: 0.01-0.02 g: 90-110 mL.
6. The process for synthesizing 5-chloro-2-pentanone according to claim 1, wherein: the composite catalyst is prepared by the following steps:
D1、Zn(NO3)2·6H2o and Al (NO)3)3·9H2Dissolving the mixture of O in deionized water, adding a sodium salt solution of cobalt tetra (4-sulfophenyl) porphyrin, continuously dropwise adding 0.1mol/L NaOH solution to keep the pH value at 8.5, stirring at 80 ℃ for 24 hours, filtering a product, washing with 80 ℃ distilled water, and finally drying at room temperature to obtain a catalyst precursor;
d2, stirring and mixing the N-hydroxyphthalimide and the catalyst precursor uniformly to obtain the composite catalyst.
7. The process for synthesizing 5-chloro-2-pentanone according to claim 6, wherein: in step D1, Zn (NO)3)2·6H2O、Al(NO3)3·9H2The mass ratio of O, deionized water, the sodium salt solution of cobalt tetra (4-sulfophenyl) porphyrin and the NaOH solution is 1.57-1.72: 0.95-1.15: 45-55: 10.3-12.5:18-25.
8. The process for synthesizing 5-chloro-2-pentanone according to claim 6, wherein: in step D2, the ratio of the amount of N-hydroxyphthalimide to the amount of catalyst precursor used was 0.55 to 0.64 mmol: 28-32 mg.
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