CN117886681A - Selective oxidation method for benzyl compound and allyl compound - Google Patents
Selective oxidation method for benzyl compound and allyl compound Download PDFInfo
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- 238000000034 method Methods 0.000 title claims abstract description 20
- 230000003647 oxidation Effects 0.000 title claims abstract description 9
- 238000007254 oxidation reaction Methods 0.000 title claims abstract description 9
- -1 benzyl compound Chemical class 0.000 title claims description 17
- 238000006243 chemical reaction Methods 0.000 claims abstract description 31
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims abstract description 18
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims abstract description 11
- 150000001350 alkyl halides Chemical class 0.000 claims abstract description 10
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims abstract description 10
- MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 claims abstract description 7
- 238000005286 illumination Methods 0.000 claims abstract description 7
- 229910001882 dioxygen Inorganic materials 0.000 claims abstract description 6
- 239000003153 chemical reaction reagent Substances 0.000 claims abstract description 5
- 239000002994 raw material Substances 0.000 claims abstract description 5
- 230000003197 catalytic effect Effects 0.000 claims abstract description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 39
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 22
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 12
- 239000003208 petroleum Substances 0.000 claims description 11
- 238000000926 separation method Methods 0.000 claims description 9
- 239000002904 solvent Substances 0.000 claims description 7
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 claims description 6
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 6
- 239000012298 atmosphere Substances 0.000 claims description 6
- 239000012295 chemical reaction liquid Substances 0.000 claims description 6
- 238000000746 purification Methods 0.000 claims description 6
- 230000035484 reaction time Effects 0.000 claims description 6
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 4
- 238000004440 column chromatography Methods 0.000 claims description 4
- 230000003213 activating effect Effects 0.000 claims description 3
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 3
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 2
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 claims description 2
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 2
- 125000000217 alkyl group Chemical group 0.000 claims description 2
- 125000004432 carbon atom Chemical group C* 0.000 claims description 2
- 239000003795 chemical substances by application Substances 0.000 claims description 2
- 239000003480 eluent Substances 0.000 claims description 2
- LYGJENNIWJXYER-UHFFFAOYSA-N nitromethane Chemical compound C[N+]([O-])=O LYGJENNIWJXYER-UHFFFAOYSA-N 0.000 claims description 2
- 238000002390 rotary evaporation Methods 0.000 claims description 2
- XHFLOLLMZOTPSM-UHFFFAOYSA-M sodium;hydrogen carbonate;hydrate Chemical class [OH-].[Na+].OC(O)=O XHFLOLLMZOTPSM-UHFFFAOYSA-M 0.000 claims description 2
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 claims 1
- PAAZPARNPHGIKF-UHFFFAOYSA-N 1,2-dibromoethane Chemical group BrCCBr PAAZPARNPHGIKF-UHFFFAOYSA-N 0.000 claims 1
- FJBFPHVGVWTDIP-UHFFFAOYSA-N dibromomethane Chemical compound BrCBr FJBFPHVGVWTDIP-UHFFFAOYSA-N 0.000 claims 1
- 230000001590 oxidative effect Effects 0.000 claims 1
- YFKBXYGUSOXJGS-UHFFFAOYSA-N 1,3-Diphenyl-2-propanone Chemical class C=1C=CC=CC=1CC(=O)CC1=CC=CC=C1 YFKBXYGUSOXJGS-UHFFFAOYSA-N 0.000 abstract description 7
- 238000011031 large-scale manufacturing process Methods 0.000 abstract description 2
- 239000007810 chemical reaction solvent Substances 0.000 abstract 1
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 17
- 238000005481 NMR spectroscopy Methods 0.000 description 13
- YNQLUTRBYVCPMQ-UHFFFAOYSA-N Ethylbenzene Chemical compound CCC1=CC=CC=C1 YNQLUTRBYVCPMQ-UHFFFAOYSA-N 0.000 description 12
- 238000010898 silica gel chromatography Methods 0.000 description 9
- 150000001875 compounds Chemical class 0.000 description 7
- 239000007788 liquid Substances 0.000 description 6
- 239000007787 solid Substances 0.000 description 5
- PBZROIMXDZTJDF-UHFFFAOYSA-N hepta-1,6-dien-4-one Chemical class C=CCC(=O)CC=C PBZROIMXDZTJDF-UHFFFAOYSA-N 0.000 description 4
- 239000012074 organic phase Substances 0.000 description 4
- 229920006395 saturated elastomer Polymers 0.000 description 4
- KUJFKFWQVGCSAR-UHFFFAOYSA-M sodium;ethyl acetate;hydrogen carbonate Chemical compound [Na+].OC([O-])=O.CCOC(C)=O KUJFKFWQVGCSAR-UHFFFAOYSA-M 0.000 description 4
- 238000001308 synthesis method Methods 0.000 description 4
- 238000003786 synthesis reaction Methods 0.000 description 4
- APQIUTYORBAGEZ-UHFFFAOYSA-N 1,1-dibromoethane Chemical compound CC(Br)Br APQIUTYORBAGEZ-UHFFFAOYSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 239000003054 catalyst Substances 0.000 description 3
- 238000006555 catalytic reaction Methods 0.000 description 3
- 229910052751 metal Inorganic materials 0.000 description 3
- 239000002184 metal Substances 0.000 description 3
- 231100000331 toxic Toxicity 0.000 description 3
- 230000002588 toxic effect Effects 0.000 description 3
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
- RJKFOVLPORLFTN-LEKSSAKUSA-N Progesterone Chemical compound C1CC2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H](C(=O)C)[C@@]1(C)CC2 RJKFOVLPORLFTN-LEKSSAKUSA-N 0.000 description 2
- 150000001728 carbonyl compounds Chemical class 0.000 description 2
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 2
- 239000011651 chromium Substances 0.000 description 2
- HGCIXCUEYOPUTN-UHFFFAOYSA-N cyclohexene Chemical compound C1CCC=CC1 HGCIXCUEYOPUTN-UHFFFAOYSA-N 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 150000002978 peroxides Chemical class 0.000 description 2
- 239000000758 substrate Substances 0.000 description 2
- MCODLPJUFHPVQP-GFCCVEGCSA-N (2r)-2-[(2-methylpropan-2-yl)oxycarbonylamino]-4-phenylbutanoic acid Chemical compound CC(C)(C)OC(=O)N[C@@H](C(O)=O)CCC1=CC=CC=C1 MCODLPJUFHPVQP-GFCCVEGCSA-N 0.000 description 1
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 1
- 238000005160 1H NMR spectroscopy Methods 0.000 description 1
- WMPPDTMATNBGJN-UHFFFAOYSA-N 2-phenylethylbromide Chemical compound BrCCC1=CC=CC=C1 WMPPDTMATNBGJN-UHFFFAOYSA-N 0.000 description 1
- ICMVGKQFVMTRLB-UHFFFAOYSA-N 4-phenylbutanenitrile Chemical compound N#CCCCC1=CC=CC=C1 ICMVGKQFVMTRLB-UHFFFAOYSA-N 0.000 description 1
- OBKXEAXTFZPCHS-UHFFFAOYSA-N 4-phenylbutyric acid Chemical compound OC(=O)CCCC1=CC=CC=C1 OBKXEAXTFZPCHS-UHFFFAOYSA-N 0.000 description 1
- VYZAMTAEIAYCRO-UHFFFAOYSA-N Chromium Chemical compound [Cr] VYZAMTAEIAYCRO-UHFFFAOYSA-N 0.000 description 1
- 238000005727 Friedel-Crafts reaction Methods 0.000 description 1
- BUGBHKTXTAQXES-UHFFFAOYSA-N Selenium Chemical compound [Se] BUGBHKTXTAQXES-UHFFFAOYSA-N 0.000 description 1
- WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 1
- 239000012346 acetyl chloride Substances 0.000 description 1
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 235000012000 cholesterol Nutrition 0.000 description 1
- 229910052804 chromium Inorganic materials 0.000 description 1
- 229940125904 compound 1 Drugs 0.000 description 1
- CZZYITDELCSZES-UHFFFAOYSA-N diphenylmethane Chemical compound C=1C=CC=CC=1CC1=CC=CC=C1 CZZYITDELCSZES-UHFFFAOYSA-N 0.000 description 1
- 229910001385 heavy metal Inorganic materials 0.000 description 1
- 238000009776 industrial production Methods 0.000 description 1
- 239000002808 molecular sieve Substances 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 239000010815 organic waste Substances 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- 229960003387 progesterone Drugs 0.000 description 1
- 239000000186 progesterone Substances 0.000 description 1
- 238000004064 recycling Methods 0.000 description 1
- 229910052703 rhodium Inorganic materials 0.000 description 1
- 239000010948 rhodium Substances 0.000 description 1
- MHOVAHRLVXNVSD-UHFFFAOYSA-N rhodium atom Chemical compound [Rh] MHOVAHRLVXNVSD-UHFFFAOYSA-N 0.000 description 1
- 229910052711 selenium Inorganic materials 0.000 description 1
- 239000011669 selenium Substances 0.000 description 1
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 1
- 239000007790 solid phase Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- CIHOLLKRGTVIJN-UHFFFAOYSA-N tert‐butyl hydroperoxide Chemical compound CC(C)(C)OO CIHOLLKRGTVIJN-UHFFFAOYSA-N 0.000 description 1
- 231100000701 toxic element Toxicity 0.000 description 1
- 239000002699 waste material Substances 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
- C07C45/33—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 CHx-moieties
- C07C45/34—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 CHx-moieties in unsaturated compounds
- C07C45/36—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 CHx-moieties in unsaturated compounds in compounds containing six-membered aromatic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B41/00—Formation or introduction of functional groups containing oxygen
- C07B41/06—Formation or introduction of functional groups containing oxygen of carbonyl groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C201/00—Preparation of esters of nitric or nitrous acid or of compounds containing nitro or nitroso groups bound to a carbon skeleton
- C07C201/06—Preparation of nitro compounds
- C07C201/12—Preparation of nitro compounds by reactions not involving the formation of nitro groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C253/00—Preparation of carboxylic acid nitriles
- C07C253/30—Preparation of carboxylic acid nitriles by reactions not involving the formation of cyano groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C269/00—Preparation of derivatives of carbamic acid, i.e. compounds containing any of the groups, the nitrogen atom not being part of nitro or nitroso groups
- C07C269/06—Preparation of derivatives of carbamic acid, i.e. compounds containing any of the groups, the nitrogen atom not being part of nitro or nitroso groups by reactions not involving the formation of carbamate groups
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- 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
- C07C51/373—Preparation of carboxylic acids or their salts, halides or anhydrides by reactions not involving formation of carboxyl groups by introduction of functional groups containing oxygen only in doubly bound form
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J7/00—Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of two carbon atoms
- C07J7/0005—Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of two carbon atoms not substituted in position 21
- C07J7/001—Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of two carbon atoms not substituted in position 21 substituted in position 20 by a keto group
- C07J7/0015—Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of two carbon atoms not substituted in position 21 substituted in position 20 by a keto group not substituted in position 17 alfa
- C07J7/002—Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of two carbon atoms not substituted in position 21 substituted in position 20 by a keto group not substituted in position 17 alfa not substituted in position 16
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J9/00—Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of more than two carbon atoms, e.g. cholane, cholestane, coprostane
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/12—Systems containing only non-condensed rings with a six-membered ring
- C07C2601/16—Systems containing only non-condensed rings with a six-membered ring the ring being unsaturated
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention discloses a selective oxidation method of benzyl compounds and allyl compounds, which takes benzyl compounds and allyl compounds as raw materials, haloalkane as a catalytic reagent, acetonitrile as a reaction solvent, air as a molecular oxygen source and reacts under the condition of illumination, and benzyl ketone compounds and allyl compounds are generated by selective oxidation. The method has the advantages of high reaction efficiency, mild reaction conditions, convenient operation, economy, green property and the like, and is suitable for large-scale production.
Description
Technical Field
The invention relates to a selective oxidation method of benzyl compounds and allyl compounds, which enables the benzyl compounds and the allyl compounds to be selectively oxidized into benzyl ketone compounds and allyl ketone compounds by activating molecular oxygen through haloalkane light, and belongs to the field of organic synthesis.
Background
Carbonyl compounds are widely used in various natural products and chemical products, among which benzyl ketone compounds and allyl ketone compounds are the most widely used carbonyl compounds. Has extremely high application value in industrial production, synthesis of drug molecules and reconversion as an intermediate.
The most common method for synthesizing benzyl ketone by benzyl compound is Friedel-Crafts reaction, namely benzene reacts with acetyl chloride, acetic anhydride or acetic acid under the catalysis of stoichiometric anhydrous aluminum trichloride. The synthesis method generates a large amount of toxic organic waste liquid which is difficult to treat and has high cost, and simultaneously has the problems of large catalyst consumption, difficult product separation and the like. In the gas-solid phase catalytic reaction system, the requirements on the catalyst and the reaction device are high, the reaction temperature is high, and a large amount of non-renewable energy sources are required to be consumed. The current industry uses metal complexes to oxidize and prepare at homogeneous phase high temperature, and the yield is lower. Synthesis of allylketones also often requires highly toxic reagents (based on toxic elements such as chromium, selenium) or expensive catalysts (such as palladium, rhodium), which are conflicting with the concept of green chemistry.
In recent years, metal complexes and metal molecular sieves such as Cr and the like are blended with peroxides such as H 2 O 2 Benzyl ketones and TBHP and the like can be prepared by light irradiationAllylketones, which require the consumption of large amounts of peroxides, present a high cost and safety problem.
Disclosure of Invention
In view of the shortcomings of the prior art, the invention provides a selective oxidation method of benzyl compounds and allyl compounds. The method has the advantages of high reaction efficiency, mild reaction conditions, convenient operation, economy, green property and the like, and is suitable for large-scale production.
The invention relates to a selective oxidation method of benzyl compounds and allyl compounds, which is characterized in that benzyl compounds or allyl compounds are used as raw materials, haloalkane is used as a catalytic agent, air is used as a molecular oxygen source, the reaction is carried out under the condition of illumination, and benzyl ketone compounds or allyl ketone compounds are obtained after separation and purification.
Specifically, benzyl compounds or allyl compounds are dissolved in a solvent under the air atmosphere, haloalkane is added as an activating reagent of molecular oxygen, the reaction is carried out under the illumination condition, and after the reaction is finished, benzyl ketone compounds or allyl ketone compounds are obtained through separation and purification.
The structure of the benzyl compound is shown as follows:
the structure of the allyl compound is as follows:
wherein R is 3 、R 4 Is long-chain alkyl, and the total number of carbon atoms is 6-32.
The haloalkane is selected from compounds of the following structure:
the addition amount of the alkyl halide is 5-20eq, calculated by taking a substrate as a reference.
The solvent is selected from acetonitrile, acetone, dimethyl sulfoxide, N-dimethylformamide, N-dimethylacetamide, 1, 4-dioxane, toluene, nitromethane or tetrahydrofuran.
The reaction temperature is 25-35 ℃, preferably 30 ℃ and the reaction time is 3-24h.
The illumination wavelength is 365nm-455nm.
The separation and purification are to add saturated sodium bicarbonate water solution into the reaction liquid, then extract the reaction liquid with ethyl acetate for three times, dry the reaction liquid with anhydrous sodium sulfate, remove the solvent by rotary evaporation and then carry out column chromatography separation. The eluent in the column chromatography separation and purification is petroleum ether: ethyl acetate=20:1 to 1:1, v/v.
The reaction route of the invention is schematically shown as follows:
the beneficial effects of the invention are as follows:
1. the synthesis method has the characteristics of green and high efficiency, high yield and wide substrate range.
2. The synthesis method is simple, the synthesis time is short, the reaction can be carried out at normal temperature and normal pressure, the operation is easy, the product selectivity is good, and the yield is high.
3. The synthesis method is suitable for the site-selective oxidation of benzyl and allyl groups in drug molecules.
4. The alkyl halide used for catalysis is redistilled for recycling, and the residue of heavy metal or the post-treatment of toxic reagent waste liquid in the previous reaction are avoided, so that the harm to the environment is reduced, and the reaction cost is reduced.
Detailed Description
To further illustrate the features and advantages of the present invention, the following describes the technical aspects of the present invention in connection with specific embodiments. The following examples are provided to further illustrate the invention and are not intended to limit the invention.
Example 1:
to a 25mL clear Schlenk tube equipped with a magnetic stirrer was added ethyl benzene 1a (0.2 mmol), dibromoethane 1mmol, and 2mL of anhydrous acetonitrile was added under an air atmosphere. After 5h reaction at room temperature with the light wavelength set at 395nm, saturated aqueous sodium bicarbonate ethyl acetate was added to extract 3 times, the organic phases were combined, dried over anhydrous sodium sulfate, and then concentrated in vacuo, and the product was purified by silica gel column chromatography (petroleum ether: ethyl acetate=5:1) to give colorless transparent liquid 1b (23 mg, 96%). The nuclear magnetic data of the compound are: 1 H NMR(600MHz,Chloroform-d)δ7.94(d,J=7.9Hz,2H),7.54(t,J=7.3Hz,1H),7.44(t,J=7.7Hz,2H),2.59(s,3H). 13 C NMR(151MHz,Chloroform-d)δ198.11,137.08,133.08,128.54,128.27,126.59.
example 2:
diphenylmethane 2a was used in place of ethylbenzene 1a for a reaction time of 6h, otherwise identical to example 1. The product was purified by silica gel column chromatography (petroleum ether: ethyl acetate=10:1) to give 2b (34.6 mg, 95%) as a white solid. The nuclear magnetic data of the compound are: 1 HNMR(600MHz,Chloroform-d)δ7.81(d,J=7.3Hz,2H),7.58(t,J=7.4Hz,1H),7.47(t,J=7.7Hz,2H).
13 C NMR(151MHz,Chloroform-d)δ196.71,137.57,132.43,130.05,128.28.
example 3:
with 4-nitro-compoundThe reaction time was 24 hours in place of ethylbenzene 1a by phenethyl bromide 3a, and the procedure was as in example 1. The product was purified by silica gel column chromatography (petroleum ether: ethyl acetate=5:1) to give 3b (39.7 mg, 82%) as a pale yellow solid, whose nuclear magnetic data were: 1 H NMR(600MHz,Chloroform-d)δ8.34(d,J=8.9Hz,2H),8.15(d,J=9.0Hz,2H),4.46(s,2H). 13 C NMR(151MHz,Chloroform-d)δ190.03,150.83,138.49,130.22,124.18,30.26.
example 4:
phenylbutyric acid 4a was used in place of ethylbenzene 1a for a reaction time of 24h, otherwise identical to example 1. The product was purified by silica gel column chromatography (petroleum ether: ethyl acetate=1:1) to give 4b (26.4 mg, 74%) as a white solid, which had nuclear magnetic data of: 1 HNMR(600MHz,Chloroform-d)δ7.98(dd,J=8.4,1.3Hz,2H),7.57(t,J=7.4Hz,1H),7.47(t,J=7.7Hz,2H),3.31(t,J=6.6Hz,2H),2.81(t,J=6.6Hz,2H). 13 C NMR(151MHz,Chloroform-d)δ
197.97,179.04,136.48,133.46,128.77,128.17,33.28,28.18.
example 5:
4-phenylbutyronitrile 5a was used instead of ethylbenzene 1a, and the reaction time was 12h, otherwise identical to example 1. The product was purified by silica gel column chromatography (petroleum ether: ethyl acetate=10:1) to give clear oily liquid 5b (28.1 mg, 89%) as a nuclear magnetic data of the compound: 1 H NMR(600MHz,Chloroform-d)δ7.94(d,J=7.2Hz,2H),7.61(t,J=7.4Hz,1H),7.49(t,J=7.8Hz,2H),3.38-3.36(m,2H),2.76(t,J=7.2Hz,2H). 13 C NMR(151MHz,Chloroform-d)δ195.45,135.67,133.97,128.95,128.09,119.34,34.33,11.87.
example 6:
Boc-D-homophenylalanine 6a was used in place of ethylbenzene 1a for 24h with the procedure of example 1. The product was purified by silica gel column chromatography (petroleum ether: ethyl acetate=2:1) to give a clear oily liquid 6b (49.7 mg, 81%), the nuclear magnetic data of which were: 1 H NMR(600MHz,Chloroform-d)δ7.94(d,J=7.3Hz,2H),7.58(t,J=7.4Hz,1H),7.47(t,J=7.8Hz,2H),5.62(d,J=8.5Hz,1H),4.69(dt,J=8.3,3.9Hz,2H),3.74(s,3H),3.72(d,J=4.0Hz,1H),3.53(dd,J=18.1,4.0Hz,1H),1.43(s,9H). 13 C NMR(151MHz,Chloroform-d)δ197.78,172.02,155.56,136.01,133.70,128.71,128.13,80.00,52.64,49.53,40.94,28.29.
example 7:
to a 25mL clear Schlenk tube equipped with a magnetic stirrer was added raw material progesterone 7a (0.2 mmol), dibromoethane 2mmol, and 2mL anhydrous acetonitrile was added under an air atmosphere. After 3.5h reaction at room temperature with the light wavelength set to 395nm, saturated aqueous sodium bicarbonate ethyl acetate was added to extract 3 times, the organic phases were combined, dried over anhydrous sodium sulfate, and then concentrated in vacuo, and the product was purified by silica gel column chromatography (petroleum ether: ethyl acetate=2:1) to give 7b (41.9 mg, 49%) as a pale yellow solid. The nuclear magnetic data of the compound are: 1 H NMR(400MHz,Chloroform-d)δ6.16(s,1H),2.68(dd,J=16.0,4.0Hz,2H),2.58-2.46(m,2H),2.14(s,2H),2.08-2.00(m,1H),1.92(dd,J=12.3,4.1Hz,3H),1.77-1.69(m,5H),1.50(d,J=8.3Hz,3H),1.41(d,J=7.9Hz,1H),1.27(dd,J=17.2,11.0Hz,2H),1.15(s,5H),0.66(s,4H). 13 C NMR(101MHz,Chloroform-d)δ209.04,201.81,199.48,160.61,125.78,63.21,56.58,50.77,46.59,43.97,39.77,38.21,35.59,34.08,34.02,31.60.
example 8:
to a 25mL clear Schlenk tube equipped with a magnetic stirrer was added cyclohexene 8a (0.2 mmol), dichloroethane 2mmol, and 2mL of anhydrous acetonitrile under an air atmosphere. After 12h reaction at room temperature with the light wavelength set at 395nm, saturated aqueous sodium bicarbonate ethyl acetate was added to extract 3 times, the organic phases were combined, dried over anhydrous sodium sulfate, and then concentrated in vacuo, and the product was purified by silica gel column chromatography (petroleum ether: ethyl acetate=5:1) to give colorless liquid 8b (16.3 mg, 85%). The nuclear magnetic data of the compound are: 1 H NMR(400MHz,Chloroform-d)δ6.95-6.90(m,1H),5.94-5.91(m,1H),2.36-2.33(m,2H),2.29-2.26(m,2H),1.96-1.91(m,2H).13C NMR(101MHz,Chloroform-d)δ199.7,150.7,129.8,38.0,25.6,22.7
example 9:
to a 25mL clear Schlenk tube equipped with a magnetic stirrer was added raw material cholesterol 9a (0.2 mmol), dibromoethane 2mmol, and 2mL of anhydrous acetone was added under an air atmosphere. After 5h reaction at room temperature with the light wavelength set to 395nm, saturated aqueous sodium bicarbonate ethyl acetate was added to extract 3 times, the organic phases were combined, dried over anhydrous sodium sulfate, and then concentrated in vacuo, and the product was purified by silica gel column chromatography (petroleum ether: ethyl acetate=2:1) to give 9b (49.6 mg, 62%) as a white solid. The nuclear magnetic data of the compound are: 1H NMR (400 MHz, chloroform-d) delta 5.69 (s, 1H), 3.69-3.64 (m, 1H), 2.53-2.49 (m, 1H), 2.43-2.37 (m, 2H), 2.27-2.21 (m, 1H), 2.05-1.86 (m, 5H), 1.67-1.48 (m, 8H), 1.34-1.07 (m, 13H), 0.93-0.85 (m, 8H), 0.68 (s, 3H); 13C NMR (101 MHz, chloride-d). Delta. 202.5,165.3,126.2,70.6,54.8,53.5,50.0,49.9,45.5,43.2,39.6,38.7,38.4,36.4,36.3,35.8,31.2,28.6,28.1,26.4,23.9,22.9,22.6,21.3,18.9,17.4,12.1.
Example 10:
reference standard for reaction conditions with compound 1 a:
conditions (conditions) | Reaction parameters | Yield of 2a (%) |
1 | Standard conditions (air, normal temperature 25 ℃, 395nm wavelength.) | 96 |
2 | Reaction under nitrogen | 0 |
3 | Reaction under dark conditions | 0 |
4 | Replaced by 365nm/455nm light sources | 56/23 |
5 | Reaction under pure oxygen condition | 82 |
6 | Reaction at 0 DEG C | 0 |
7 | Reaction at 30 DEG C | 96 |
8 | Reaction at 50 DEG C | 90 |
9 | Reaction at 70 DEG C | 83 |
10 | Solvent exchange to acetone/dichloromethane/tetrahydrofuran | 89/0/76 |
Claims (9)
1. A process for the selective oxidation of benzyl and allyl compounds characterized by:
using benzyl compound or allyl compound as raw material, using haloalkane as catalytic agent, using air as molecular oxygen source, making reaction under the condition of illumination, and selectively oxidizing to obtain benzyl ketone compound or allyl ketone compound;
the structure of the benzyl compound is shown as follows:
the structure of the allyl compound is as follows:
wherein R is 3 、R 4 Is long-chain alkyl, and the total number of carbon atoms is 6-32.
2. The method according to claim 1, characterized in that:
dissolving a benzyl compound or an allyl compound in a solvent under an air atmosphere, adding haloalkane as an activating reagent of molecular oxygen, reacting under the condition of illumination, and separating and purifying after the reaction is finished to obtain the benzyl ketone compound or the allyl ketone compound.
3. The method according to claim 1, characterized in that:
the alkyl halide is selected from 1,2 dibromoethane, dibromomethane or 1,2 dichloroethane, and the addition amount is 5-20 equivalents.
4. The method according to claim 2, characterized in that:
the illumination wavelength is 365nm-455nm.
5. The method according to claim 2, characterized in that:
the solvent is selected from acetonitrile, acetone, dimethyl sulfoxide, N-dimethylformamide, N-dimethylacetamide, 1, 4-dioxane, toluene, nitromethane or tetrahydrofuran.
6. The method according to claim 2, characterized in that:
the reaction temperature is 25-35 ℃ and the reaction time is 3-24h.
7. The method according to claim 2, characterized in that:
the reaction temperature is normal temperature.
8. The method according to claim 2, characterized in that:
the separation and purification are to add saturated sodium bicarbonate water solution into the reaction liquid, then extract the reaction liquid with ethyl acetate, dry the reaction liquid with anhydrous sodium sulfate, remove the solvent by rotary evaporation and then carry out column chromatography separation.
9. The method according to claim 8, wherein:
the eluent used in the column chromatography separation and purification is petroleum ether: ethyl acetate=20:1 to 1:1, v/v.
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