CN116789538B - Method for preparing 1, 1-dichloro pinacolone compound - Google Patents
Method for preparing 1, 1-dichloro pinacolone compound Download PDFInfo
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- CN116789538B CN116789538B CN202310793058.5A CN202310793058A CN116789538B CN 116789538 B CN116789538 B CN 116789538B CN 202310793058 A CN202310793058 A CN 202310793058A CN 116789538 B CN116789538 B CN 116789538B
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- -1 1, 1-dichloro pinacolone compound Chemical class 0.000 title claims abstract description 34
- 238000000034 method Methods 0.000 title claims abstract description 21
- JRNVZBWKYDBUCA-UHFFFAOYSA-N N-chlorosuccinimide Chemical compound ClN1C(=O)CCC1=O JRNVZBWKYDBUCA-UHFFFAOYSA-N 0.000 claims abstract description 32
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims abstract description 19
- 239000002904 solvent Substances 0.000 claims abstract description 11
- AZJPTIGZZTZIDR-UHFFFAOYSA-L rose bengal Chemical compound [K+].[K+].[O-]C(=O)C1=C(Cl)C(Cl)=C(Cl)C(Cl)=C1C1=C2C=C(I)C(=O)C(I)=C2OC2=C(I)C([O-])=C(I)C=C21 AZJPTIGZZTZIDR-UHFFFAOYSA-L 0.000 claims abstract description 10
- 229960003138 rose bengal sodium Drugs 0.000 claims abstract description 10
- 239000003504 photosensitizing agent Substances 0.000 claims abstract description 9
- 239000000758 substrate Substances 0.000 claims abstract description 8
- 238000006243 chemical reaction Methods 0.000 claims description 21
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 20
- 150000001875 compounds Chemical class 0.000 claims description 17
- 239000000460 chlorine Substances 0.000 claims description 15
- PJGSXYOJTGTZAV-UHFFFAOYSA-N pinacolone Chemical compound CC(=O)C(C)(C)C PJGSXYOJTGTZAV-UHFFFAOYSA-N 0.000 claims description 12
- 229910052801 chlorine Inorganic materials 0.000 claims description 11
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 10
- 150000003254 radicals Chemical class 0.000 claims description 10
- 150000001723 carbon free-radicals Chemical class 0.000 claims description 9
- 239000003480 eluent Substances 0.000 claims description 8
- 150000002831 nitrogen free-radicals Chemical class 0.000 claims description 7
- 239000003960 organic solvent Substances 0.000 claims description 6
- 238000006880 cross-coupling reaction Methods 0.000 claims description 5
- 239000003208 petroleum Substances 0.000 claims description 5
- 238000010791 quenching Methods 0.000 claims description 5
- 230000000171 quenching effect Effects 0.000 claims description 5
- 238000000605 extraction Methods 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 claims description 4
- 238000010505 homolytic fission reaction Methods 0.000 claims description 3
- 238000004587 chromatography analysis Methods 0.000 claims description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 2
- 239000012046 mixed solvent Substances 0.000 claims description 2
- 238000002156 mixing Methods 0.000 claims description 2
- 238000005286 illumination Methods 0.000 claims 2
- IVDFJHOHABJVEH-UHFFFAOYSA-N HOCMe2CMe2OH Natural products CC(C)(O)C(C)(C)O IVDFJHOHABJVEH-UHFFFAOYSA-N 0.000 claims 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 abstract description 9
- 238000000926 separation method Methods 0.000 abstract description 8
- 239000000203 mixture Substances 0.000 abstract description 6
- 238000002360 preparation method Methods 0.000 abstract description 5
- 239000002994 raw material Substances 0.000 abstract description 3
- 230000001678 irradiating effect Effects 0.000 abstract 1
- 230000009286 beneficial effect Effects 0.000 description 12
- 239000000543 intermediate Substances 0.000 description 11
- 239000000047 product Substances 0.000 description 11
- UDWZXMQIEHAAQT-UHFFFAOYSA-N 1,1-dichloro-3,3-dimethylbutan-2-one Chemical compound CC(C)(C)C(=O)C(Cl)Cl UDWZXMQIEHAAQT-UHFFFAOYSA-N 0.000 description 8
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 6
- 235000019439 ethyl acetate Nutrition 0.000 description 6
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 5
- 229940125904 compound 1 Drugs 0.000 description 5
- 238000006467 substitution reaction Methods 0.000 description 5
- 238000004809 thin layer chromatography Methods 0.000 description 5
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 4
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 4
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 4
- 239000001257 hydrogen Substances 0.000 description 4
- 229910052739 hydrogen Inorganic materials 0.000 description 4
- 239000000741 silica gel Substances 0.000 description 4
- 229910002027 silica gel Inorganic materials 0.000 description 4
- BKOOMYPCSUNDGP-UHFFFAOYSA-N 2-methylbut-2-ene Chemical group CC=C(C)C BKOOMYPCSUNDGP-UHFFFAOYSA-N 0.000 description 3
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 3
- 238000011161 development Methods 0.000 description 3
- 230000000977 initiatory effect Effects 0.000 description 3
- 239000007858 starting material Substances 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 229910004298 SiO 2 Inorganic materials 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 238000006555 catalytic reaction Methods 0.000 description 2
- 239000013064 chemical raw material Substances 0.000 description 2
- 229940126214 compound 3 Drugs 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 238000003818 flash chromatography Methods 0.000 description 2
- 230000007246 mechanism Effects 0.000 description 2
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen(.) Chemical compound [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 2
- 239000011941 photocatalyst Substances 0.000 description 2
- 229920006395 saturated elastomer Polymers 0.000 description 2
- RLGGOWVSISCWMB-UHFFFAOYSA-N 1,1,1-trichloro-3,3-dimethylbutan-2-one Chemical compound CC(C)(C)C(=O)C(Cl)(Cl)Cl RLGGOWVSISCWMB-UHFFFAOYSA-N 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- ULSAJQMHTGKPIY-UHFFFAOYSA-N 1-chloro-3,3-dimethylbutan-2-one Chemical compound CC(C)(C)C(=O)CCl ULSAJQMHTGKPIY-UHFFFAOYSA-N 0.000 description 1
- VZSRBBMJRBPUNF-UHFFFAOYSA-N 2-(2,3-dihydro-1H-inden-2-ylamino)-N-[3-oxo-3-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)propyl]pyrimidine-5-carboxamide Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)C(=O)NCCC(N1CC2=C(CC1)NN=N2)=O VZSRBBMJRBPUNF-UHFFFAOYSA-N 0.000 description 1
- 101100293720 Caenorhabditis elegans ncs-2 gene Proteins 0.000 description 1
- KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 description 1
- 241000235648 Pichia Species 0.000 description 1
- DHXVGJBLRPWPCS-UHFFFAOYSA-N Tetrahydropyran Chemical compound C1CCOCC1 DHXVGJBLRPWPCS-UHFFFAOYSA-N 0.000 description 1
- 238000007259 addition reaction Methods 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- ZPUCINDJVBIVPJ-LJISPDSOSA-N cocaine Chemical compound O([C@H]1C[C@@H]2CC[C@@H](N2C)[C@H]1C(=O)OC)C(=O)C1=CC=CC=C1 ZPUCINDJVBIVPJ-LJISPDSOSA-N 0.000 description 1
- 238000006482 condensation reaction Methods 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 230000032798 delamination Effects 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 229920001971 elastomer Polymers 0.000 description 1
- SEACYXSIPDVVMV-UHFFFAOYSA-L eosin Y Chemical compound [Na+].[Na+].[O-]C(=O)C1=CC=CC=C1C1=C2C=C(Br)C(=O)C(Br)=C2OC2=C(Br)C([O-])=C(Br)C=C21 SEACYXSIPDVVMV-UHFFFAOYSA-L 0.000 description 1
- 230000005281 excited state Effects 0.000 description 1
- 238000004880 explosion Methods 0.000 description 1
- 239000000835 fiber Substances 0.000 description 1
- 239000004519 grease Substances 0.000 description 1
- 230000005283 ground state Effects 0.000 description 1
- 239000010985 leather Substances 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
- 239000003973 paint Substances 0.000 description 1
- 238000007146 photocatalysis Methods 0.000 description 1
- 230000001699 photocatalysis Effects 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 1
- 238000007347 radical substitution reaction Methods 0.000 description 1
- 239000005060 rubber Substances 0.000 description 1
- 150000003839 salts Chemical group 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 238000005507 spraying Methods 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
Classifications
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- 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
- C07C45/61—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups
- C07C45/63—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O 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
- C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
- C07C45/78—Separation; Purification; Stabilisation; Use of additives
-
- 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
- C07C45/78—Separation; Purification; Stabilisation; Use of additives
- C07C45/79—Separation; Purification; Stabilisation; Use of additives by solid-liquid treatment; by chemisorption
-
- 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
- C07C45/78—Separation; Purification; Stabilisation; Use of additives
- C07C45/80—Separation; Purification; Stabilisation; Use of additives by liquid-liquid treatment
-
- 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
- C07C45/78—Separation; Purification; Stabilisation; Use of additives
- C07C45/81—Separation; Purification; Stabilisation; Use of additives by change in the physical state, e.g. crystallisation
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Crystallography & Structural Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention relates to a method for preparing a 1, 1-dichloro pinacolone compound, which comprises the following steps: the method comprises the steps of using a pinacolone compound and N-chlorosuccinimide (NCS) as substrates, using Acid Red 94 as a photosensitizer and using Tetrahydrofuran (THF) as a solvent, and irradiating the mixture for 12 hours under the condition of 30W blue LED (455-460 nm) at the temperature of 20-25 ℃ in an air atmosphere, so as to obtain the 1, 1-dichloro pinacolone compound with high yield. The method has the advantages of simple and easily obtained raw materials, green and economic steps, amplified preparation of products, high separation yield, simple subsequent separation and the like.
Description
Technical Field
The invention belongs to the technical field of chemical preparation, and particularly relates to a method for preparing a 1, 1-dichloro-pinacolone compound, which is an effective method for preparing the 1, 1-dichloro-pinacolone compound through a substitution reaction initiated by free radicals.
Background
1, 1-dichloro pinacolone is used as an important chemical raw material and can be used in industries such as plastics, rubber, fiber, leather making, grease, paint spraying and the like. At present, isoamylene is generally used as a starting material at home and abroad, and the pinacolone is produced by the addition reaction of the isoamylene and hydrochloric acid and the condensation reaction of the isoamylene and formaldehyde. Next, the synthesized pinacolone is substituted with an excess of chlorine to produce 1, 1-dichloroppinacolone. However, the introduction of excessive chlorine gas can cause the generation of more byproduct trichloropinacolone, affect the yield of 1, 1-dichloro pinacolone, and cause the defects of low purity, difficult subsequent separation and the like. Therefore, it is necessary to develop a novel method for synthesizing 1, 1-dichloroppinacolone compound simply and efficiently.
Organic radicals have gradually attracted considerable attention due to their unique reactive nature and great potential for development. The development of a chemical bond conversion strategy based on free radical initiation participates in the breaking and reconstruction of chemical bonds in a controllable and efficient manner, and even is applied to complex molecular synthesis, thereby having great significance to the development of free radical chemistry. Up to now, no method for preparing 1, 1-dichloroppinacolone compounds using a controlled substitution of visible free radicals has been reported.
Disclosure of Invention
In view of the problems of the prior art, the present invention provides a process for preparing 1, 1-dichloroppinacolone compounds by a visible light-induced free radical controlled substitution.
The technical scheme for solving the technical problems is as follows:
the invention provides a method for preparing a 1, 1-dichloro pinacolone compound, which comprises the following steps: and taking the pinacolone compound as a substrate, performing NCS homolytic cleavage under photochemical drive to generate a Cl free radical and a nitrogen free radical intermediate, selectively and stepwise capturing hydrogen atoms in the pinacolone by the nitrogen free radical intermediate to generate a carbon free radical intermediate, and finally performing cross coupling reaction on the carbon free radical and the chlorine free radical to generate the 1, 1-dichloro pinacolone compound.
The beneficial effects of adopting the technical scheme include: the invention efficiently prepares the 1, 1-dichloro pinacolone product by photocatalysis controllable chlorine free radical initiation substitution reaction. 1, 1-dichloro pinacolone is used as an important chemical raw material and a synthetic intermediate, and is widely applied to a plurality of fields such as biology, medicine, dye and the like. The method is easy to amplify and is beneficial to preparing other valuable molecules. The method has the advantages of green and economical steps, simple and easily obtained raw materials, wide substrate range, amplified preparation of products and the like.
The preparation method of the invention is used for preparing the 1, 1-dichloro pinacolone compound, the separation yield is good, the separation purity can reach more than 93 percent, the subsequent treatment and separation are not difficult to operate, and the target product can be obtained with good yield and high purity only by conventional reaction operation.
Further, the method comprises the following steps: mixing pinacolone compound, NCS, photosensitizer and solvent, and reacting under light.
The beneficial effects of adopting the technical scheme include: the reaction condition is green and mild, the substrate is cheap and easy to obtain, the reaction has no explosion risk, no metal salt residue and easy to amplify operation.
Further, the molar ratio of pinacolone compound to NCS is 1:2.3.
further, the molar ratio of the pinacolone compound to the photosensitizer is 1:0.04.
further, the molar volume ratio of the pinacolone compound to the solvent was 0.3mmol:3mL.
The beneficial effects of adopting the technical scheme include: the adoption of the proportion is beneficial to the reaction and improves the yield.
Further, the conditions of the photoreaction include: the air atmosphere, visible light, preferably 30W,455-460nm blue light is chosen.
The beneficial effects of adopting the technical scheme include: the invention efficiently prepares the 1, 1-dichloro pinacolone product by visible light catalysis and controllable chlorine free radical initiation substitution reaction. The yield can be further improved by using 30W,455-460nm blue light irradiation.
Further, the photosensitizer is Acid Red 94; and/or the solvent is THF.
The beneficial effects of adopting the technical scheme include: under the condition of visible light irradiation, the Acid Red 94 is converted into an excited state from a ground state; NCS absorbs energy and homolytic breaks into nitrogen and chlorine radical intermediates; the nitrogen free radical performs hydrogen capture and chlorine free radical substitution on the substrate pinacolone in a step-by-step manner to obtain the final 1, 1-dichloro pinacolone product. The selection of Acid Red 94 as photosensitizer and THF as solvent is beneficial to improving the yield (yield) of the target product.
During the experiment, the inventors originally conceived that the target product could be obtained in good yield even in sunlight, but the experimental results did not reach expectations, and the relevant experimental data are shown in example 2, and blue light (455-460 nm) is preferred as the optimal light source in combination with the reaction data.
Further, the method also comprises the following steps: reacting under light until the pinacolone compound is completely consumed; quenching and extracting; concentrating the organic solvent; purifying, eluting with eluent to obtain the compound containing 1, 1-dichloroppinacolone.
Further, naHCO is adopted 3 Quenching and extraction with EA; concentrating the organic solvent in vacuum; the residue was purified by chromatography using a mixed solvent of ethyl acetate and petroleum ether as an eluent to give the 1, 1-dichloroppinacolone compound.
The beneficial effects of adopting the technical scheme include: with NaHCO 3 Quenching is beneficial to reducing the solubility of the product, extraction with EA is beneficial to delamination and thorough extraction of the product, and removal of the eluent is beneficial with ethyl acetate and petroleum ether as the eluent.
Further, the structural formula of the 1, 1-dichloroppinacolone compound is as follows:
drawings
FIG. 1 is a diagram of Compound 3 in example 1 1 H NMR spectrum.
Detailed Description
The principles and features of the present invention are described below with reference to the drawings, the examples are illustrated for the purpose of illustrating the invention and are not to be construed as limiting the scope of the invention.
Unless specifically stated, the reagents used in the present invention are all conventional in the art and are commercially available, wherein NCS, eosin Y, acid Red 94 are purchased from Ann Ji, ru (bpy) 3 Cl 2 ·6H 2 O、Ru(bpz) 3 Cl 2 PF 6 From Pichia, acetonitrile (MeCN), dichloromethane (DCM), ethyl acetate (EtOAc), tetrahydrofuran (THF), dichloroethane (DCE), oxacyclohexane (Dioxane), dimethylformamide (DMF) were all purchased from the national drug group. Can be used without further treatment. All reactions were carried out in air without any precautions to exclude moisture.
All reactions were monitored by TLC using fume-table GF254 silica gel coated plates. Separating column layer with 200-300 mesh silica gel under normal pressure. Unless specifically stated, the experimental methods employed in the present invention are all conventional in the art.
The invention provides an effective method for preparing 1, 1-dichloro pinacolone, namely preparing the 1, 1-dichloro pinacolone compound by selectively and stepwise capturing hydrogen in pinacolone through a controllable nitrogen free radical intermediate under visible light catalysis and then preparing the 1, 1-dichloro pinacolone through a cross coupling reaction process of chlorine free radicals and carbon free radicals.
The method for cross-coupling reaction of visible light induced chlorine free carbon radical based 1, 1-dichloroppinacolone compounds is as follows:
to the reaction tube were successively added pinacolone compound 1 (0.3 mmol), NCS (2.3 equiv,0.69 mmol), acid Red 94 (4 mol%,0.012 mmol) and THF (3 mL) at room temperature (generally 25 ℃ C.). The mixture was irradiated under 30W (455-460 nm) blue light until the starting material 1 (i.e. pinacolone compound 1) was completely consumed as monitored by TLC analysis by thin layer chromatography. After completion of the reaction, the mixture was treated with saturated NaHCO 3 (i.e., saturated sodium bicarbonate solution at room temperature, sat. Aq.15 mL) was quenched and extracted with EA (3X 5 mL). The organic solvent was then concentrated in vacuo. Residue on SiO 2 (silica gel 200-300 mesh) flash column chromatography, eluting with eluent (ethyl acetate/petroleum ether=20:1, volume ratio) to obtain 1, 1-dichloroppinacolone compound.
The reaction mechanism of the invention:
PC (Acid Red 94) is converted into an excited PC under irradiation of visible light * ，PC * Energy transfer (ENT) with N-chlorosuccinimide (NCS) to promote homolytic cleavage of NCS from a chloro radical and nitrogen radical intermediate a; a, selectively capturing hydrogen in the pinacolone 1 to generate a nitrogen free radical intermediate B and a carbon free radical intermediate C; c and chlorine radicals are cross-coupled to obtain a 1-chloropinacolone intermediate D; then, the nitrogen radical intermediate A again selectively grabs hydrogen in D to generate carbon radicals E and B; finally, E is cross-coupled with chlorine free radicals again to obtain the target product 1, 1-dichloro pinacolone compound.
The reaction mechanism is as follows:
the following is presented by way of specific examples.
Example 1
In this example, the method for preparing 1, 1-dichloroppinacolone compound by cross-coupling reaction of visible light induced chlorine radicals and carbon radicals is as follows:
to the reaction tube were successively added pinacolone compound 1 (0.3 mmol), NCS (2.3 equiv,0.69 mmol), acid Red 94 (4 mol%,0.012 mmol) and THF (3 mL) at room temperature (generally 25 ℃ C.). The mixture was irradiated under 30W (455-460 nm) blue light until the starting material 1 (i.e. pinacolone compound 1) was completely consumed as monitored by TLC analysis by thin layer chromatography. After completion of the reaction, the mixture was treated with saturated NaHCO 3 (i.e., saturated sodium bicarbonate solution at room temperature, sat. Aq.15 mL) was quenched and extracted with EA (3X 5 mL). The organic solvent was then concentrated in vacuo. Residue on SiO 2 (silica gel 200-300 mesh) flash column chromatography, eluting with eluent (ethyl acetate/petroleum ether=20:1, volume ratio) to obtain 1, 1-dichloro pinacolone compound, with separation yield 80%, and separation purity above 93%.
According to compound 3 1 The structure of the compound was known from H NMR spectrum (FIG. 1). Specifically: 1 H NMR(500MHz,CDCl 3 )δ＝6.35(s,1H),1.27(s,9H).
example 2
The type of photocatalyst, the type of solvent, and the photoreaction conditions were respectively adjusted on the basis of example 1 to screen the optimal reaction system for the reaction, and the reaction system and experimental results are shown in table 1.
TABLE 1 screening results for different reaction systems
Reaction conditions: pinacolone compound 1 (0.3 mmol), NCS 2 (0.69 mmol), photocatalysts (4 mol%), solvent (3 mL), a 30W LED strip under airat rt for 12h. b Isolated yield.
In summary, the invention uses pinacolone compound and NCS as substrates, acid Red 94 as photosensitizer and THF as solvent, and irradiates the mixture for 12 hours under the condition of 30W blue LED (455-460 nm) in the air atmosphere of 25 ℃, thus obtaining 1, 1-dichloro pinacolone compound with high yield. The method has the advantages of green and economical steps, simple and easily obtained raw materials, wide substrate range, amplified preparation of products and the like.
The foregoing description of the preferred embodiments of the invention is not intended to limit the invention to the precise form disclosed, and any such modifications, equivalents, and alternatives falling within the spirit and scope of the invention are intended to be included within the scope of the invention.
Claims (5)
1. A process for preparing a 1, 1-dichloroppinacolone compound comprising the steps of: taking a pinacolone compound as a substrate, performing homolytic cleavage on N-chlorosuccinimide under photochemical drive to generate a Cl free radical and a nitrogen free radical intermediate, selectively and stepwise capturing hydrogen atoms in the pinacolone by the nitrogen free radical intermediate to generate a carbon free radical intermediate, and finally performing cross-coupling reaction on the carbon free radical and the chlorine free radical to generate a 1, 1-dichloro pinacolone compound;
mixing a pinacolone compound, N-chlorosuccinimide, a photosensitizer and a solvent, carrying out an illumination reaction, and waiting for the illumination reaction until the pinacolone compound is completely consumed; quenching and extracting; concentrating the organic solvent; purifying, eluting with eluent to obtain a compound containing 1, 1-dichloroppinacolone;
the photosensitizer is Acid Red 94, and the solvent is THF;
the condition of the photoreaction is air atmosphere, and blue light of 30W,455-460nm is irradiated.
2. The method for preparing a 1, 1-dichloroppinacol compound according to claim 1, wherein the molar ratio of pinacol compound to N-chlorosuccinimide is 1:2.3.
3. the method for preparing a 1, 1-dichloroppinacolone compound according to claim 1, wherein the molar ratio of pinacolone compound to photosensitizer is 1:0.04.
4. the method for producing a 1, 1-dichloroppinacolone compound according to claim 1, wherein the molar volume ratio of the pinacolone compound to the solvent is 0.3mmol:3mL.
5. The process for preparing 1, 1-dichloroppinacolone compound according to claim 1, wherein NaHCO is employed 3 Quenching and extraction with EA; concentrating the organic solvent in vacuum; the residue was purified by chromatography using a mixed solvent of ethyl acetate and petroleum ether as an eluent to give the 1, 1-dichloroppinacolone compound.
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| CN107628935A (en) * | 2017-09-27 | 2018-01-26 | 南通利奥化工科技有限公司 | A kind of production method of dichloro pinacoline |
| CN109574816A (en) * | 2018-12-11 | 2019-04-05 | 南通鸿富达利化工有限公司 | A kind of dichloro pinacoline production technology |
| CN111484401A (en) * | 2020-04-07 | 2020-08-04 | 南通利奥化工科技有限公司 | Production process for improving conversion rate of dichloropinacolone |
| CN112047825A (en) * | 2020-09-16 | 2020-12-08 | 南通鸿富达利化工有限公司 | Production process of dichloro pinacolone |
| CN112961043A (en) * | 2021-03-12 | 2021-06-15 | 重庆医科大学 | Preparation of alpha, alpha-dichloroketone under solvent-free condition |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN107628935A (en) * | 2017-09-27 | 2018-01-26 | 南通利奥化工科技有限公司 | A kind of production method of dichloro pinacoline |
| CN109574816A (en) * | 2018-12-11 | 2019-04-05 | 南通鸿富达利化工有限公司 | A kind of dichloro pinacoline production technology |
| CN111484401A (en) * | 2020-04-07 | 2020-08-04 | 南通利奥化工科技有限公司 | Production process for improving conversion rate of dichloropinacolone |
| CN112047825A (en) * | 2020-09-16 | 2020-12-08 | 南通鸿富达利化工有限公司 | Production process of dichloro pinacolone |
| CN112961043A (en) * | 2021-03-12 | 2021-06-15 | 重庆医科大学 | Preparation of alpha, alpha-dichloroketone under solvent-free condition |
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