WO2021249008A1 - 一种利用原位过氧化物制备ε-己内酯的方法 - Google Patents

一种利用原位过氧化物制备ε-己内酯的方法 Download PDF

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WO2021249008A1
WO2021249008A1 PCT/CN2021/087032 CN2021087032W WO2021249008A1 WO 2021249008 A1 WO2021249008 A1 WO 2021249008A1 CN 2021087032 W CN2021087032 W CN 2021087032W WO 2021249008 A1 WO2021249008 A1 WO 2021249008A1
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caprolactone
catalyst
reaction
preparing
cyclohexanone
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PCT/CN2021/087032
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English (en)
French (fr)
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李浩然
杜仁峰
袁浩然
姚加
王钰
李景波
陈斌
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浙江大学
浙江新和成股份有限公司
山东新和成精化科技有限公司
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Priority to DE112021001985.6T priority Critical patent/DE112021001985T5/de
Publication of WO2021249008A1 publication Critical patent/WO2021249008A1/zh

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D313/00—Heterocyclic compounds containing rings of more than six members having one oxygen atom as the only ring hetero atom
    • C07D313/02—Seven-membered rings
    • C07D313/04—Seven-membered rings not condensed with other rings

Definitions

  • the invention belongs to the field of chemistry and relates to a new method for producing ⁇ -caprolactone based on oxygen oxidation.
  • ⁇ -caprolactone monomer is an important chemical intermediate. Its polymer (PCL) is widely used in many fields including medical polymer resins, environmental protection materials, adhesives and coatings due to its excellent properties. Industrially, ⁇ -caprolactone is mainly produced by the Baeyer-Villiger (BV) reaction between cyclohexanone and peroxide containing active oxygen. (In situ) Organic peroxyacids (such as peroxybenzoic acid, peroxyacetic acid, trifluoroperoxyacetic acid, etc.) have excellent reactivity and become the most commonly used oxidant at present (Chem. Lett., 1991, 20, 641; J.
  • the (in-situ) hydrogen peroxide oxidation process still has several significant problems: one is that due to its insufficient reactivity, a higher concentration of hydrogen peroxide is usually required, and there is a safety problem; the other is expensive The hexafluoroisopropanol is the only excellent solvent, which seriously affects the application of this method in chemical production; third, as the substrate conversion rate increases, the yield of ⁇ -caprolactone will decrease significantly; fourth is the reaction The presence of water in the system can easily cause the hydrolysis of ⁇ -caprolactone, thereby reducing the selectivity of ⁇ -caprolactone; fifth, the use efficiency of hydrogen peroxide substances decreases with the progress of the BV reaction.
  • the present invention provides a method for preparing ⁇ -caprolactone using in-situ peroxide, which is safe and simple to operate, and has a high yield of ⁇ -caprolactone.
  • a method for preparing ⁇ -caprolactone using in-situ peroxide In the presence of catalyst, organic solvent and oxygen, the peroxide obtained by the oxidation reaction of sacrificial alcohol reacts with cyclohexanone in situ to obtain cyclohexanone The peroxide intermediate, and then the intermediate undergoes decomposition reaction to obtain the ⁇ -caprolactone product;
  • R 1 and R 2 are independently selected from H, C 1 -C 10 linear or branched alkyl, aryl, or aryl substituted C 1 -C 10 linear or branched alkyl; preferably Preferably, R 1 and R 2 are independently selected from H, C 1 -C 5 linear or branched alkyl, aryl or benzyl.
  • the catalyst used includes a first catalyst and a second catalyst
  • the organic solvent used includes a first organic solvent and a second organic solvent
  • the first step is the preparation process of cyclohexanone peroxide intermediate.
  • the first catalyst, the first organic solvent, the sacrificial alcohol and cyclohexanone are reacted in the presence of oxygen to obtain an intermediate reaction liquid;
  • the second step is the decomposition process of cyclohexanone peroxide.
  • a second catalyst and a second organic solvent are added to the intermediate reaction solution obtained in the first step to continue the reaction to obtain the epsilon-caprolactone product.
  • the principle of the present invention is that under the action of the first catalyst and the first organic solvent, the sacrificial alcohol 1 is oxidized by oxygen, and at the same time, a peroxyhydroxy group or a hydrogen peroxide compound is obtained. These peroxides react with cyclohexanone 2 to obtain a ring
  • the function of the first catalyst is to catalyze the oxygen oxidation reaction of the sacrificial alcohol to prepare peroxides such as peroxyhydroxyl or hydrogen peroxide compounds
  • the first catalyst is an organic nitroxide radical catalyst precursor A mixture with azobisisobutyronitrile; further, the molar ratio of the organic nitroxide radical catalyst precursor to azobisisobutyronitrile is 1:0.4-1.
  • the organic nitroxide radical precursor is selected from the nitrogen-containing cyclic compounds represented by the following formulas (I-1), (I-2), (I-3) or (I-4),
  • R 3 to R 12 are independently selected from hydrogen atom, alkyl group, cycloalkyl group, aromatic group, and heterocyclic ring , Hydroxyl, nitro or halogen,
  • R 3 and R 4 form a ring
  • R 5 and R 6 form a ring
  • R 7 , R 8 , and R 9 form a ring
  • R 10 , R 11 , and R 12 form a ring.
  • the formed ring is an aromatic ring or an aliphatic ring; further, the formed ring is a five-membered or six-membered aromatic ring, and a five-membered or six-membered aliphatic ring.
  • organic nitroxide radical catalyst precursors include N-hydroxyphthalimide or other organic nitroxide radical catalyst precursors, which can be specifically one of compounds (a) to (i). kind:
  • the function of the second catalyst is to catalyze the decomposition reaction of cyclohexanone peroxide
  • the second catalyst is a diselenide compound
  • the second catalyst is diphenyl diselenide Compounds, the structural formula is as follows:
  • R is one or two trifluoromethyl groups; further, the second catalyst is 1,2-bis(3,5-bis(trifluoromethyl)phenyl)diselenium.
  • One of the innovations of the present invention lies in the development of a catalyst combination based on an organic nitroxide radical catalyst/diselenium compound.
  • the two catalysts are synergistically catalyzed.
  • the organic nitroxide free radical catalyst catalyzes the oxygen oxidation process of the sacrificial alcohol, and the diselenide catalyzes the decomposition reaction of the cyclohexanone peroxide intermediate. Therefore, this method uses oxygen as the oxidant while taking into account ⁇ -High yield of caprolactone product.
  • NHPI and diselenide compound used in the present invention can not only catalyze the generated hydrogen peroxide, but also directly use peroxy hydroxy radicals, which can significantly reduce the production of water and greatly increase the yield of ⁇ -caprolactone. (Formula (C)).
  • the molar ratio of the sacrificial alcohol, cyclohexanone, and the second catalyst is 150-300:100:1-10.
  • the sacrificial alcohol, cyclohexanone, the first catalyst, and the second catalyst are The molar ratio of the catalyst is 150-300:100:1-10:1-10, more preferably 150:100:7.5:3; as another preference, the sacrificial alcohol, cyclohexanone, the first catalyst,
  • the molar ratio of the second catalyst is 150-300:100:5-50:1-10, more preferably 150:100:17:3.
  • the first catalyst is the total amount of N-hydroxyphthalimide or other organic nitroxide radical catalyst precursor and azobisisobutyronitrile.
  • the first organic solvent has a wide selection range, for example, it may be one or more of ester solvents, hydrocarbon solvents, halogenated hydrocarbon solvents, nitrile solvents, and the like.
  • the first organic solvent is preferably one or more of ethyl acetate, chlorobenzene, acetonitrile, benzonitrile, and n-butyl acetate; most preferably ethyl acetate.
  • the second organic solvent is a fluorine-substituted alcohol solvent.
  • the second organic solvent is a fluorine-substituted C 1 to C 6 alcohol solvent.
  • the first The second organic solvent is trifluoroethanol;
  • the mass ratio of the sacrificial alcohol, cyclohexanone, the first organic solvent and the second organic solvent is 2-4:1:1-3:10-50, preferably 2.75:1:3:50.
  • the oxygen is pure oxygen or oxygen in the air or a mixed gas of oxygen and nitrogen in different ratios.
  • the reaction temperature in the first step is 65°C-100°C; preferably 75°C.
  • the reaction temperature in the second step is 25°C to 60°C; preferably 30°C.
  • the reaction temperature in the first step is 6-10 hours; preferably 8 hours.
  • the reaction temperature in the second step is 3-12 hours; preferably 6 hours.
  • the present invention has the following advantages:
  • reaction yield is significantly improved, and the atom economy is high; 2) The reaction system is not sensitive to water, and there is still excellent ⁇ -caprolactone selectivity in the second half of the reaction; 3) The use efficiency of sacrificial alcohol is further improved; 4) The operation is safe and simple; 5) The environment is friendly; 6) The catalyst is cheap and the synthesis is convenient.
  • diphenyl diselenide compounds please refer to the literature (J.Org.Chem., 2001.66.2429; Appl.Organometal.Chem., 2014,28,652; Catal.Sci.Technol.,2016,6,1804), using Grignard
  • the reagent is synthesized by reacting with selenium powder. In the glove box, measure 25mL 0.5mol/L of 3,5-bis(trifluoromethyl)phenylmagnesium bromide THF solution, gradually add 0.95g of selenium powder and stir continuously. After adding it in about 30 minutes, continue the reaction 1 hour.
  • N-hydroxyphthalimide (NHPI, 75mg, 0.45mmol), azobisisobutyronitrile (AIBN, 38mg, 0.23mmol), benzhydrol (1104mg, 6mmol), cyclohexane into the three-necked flask Ketone (392mg, 4mmol) and ethyl acetate (AcOEt, 1.5mL), ventilate (pure oxygen) three times, and react at 75°C for 8 hours.
  • the temperature of the reaction solution was reduced to 30°C, and 1,2-bis(3,5-bis(trifluoromethyl)phenyl)diselenide (Se-Cat1, 70mg, 0.12mmol), trifluoroethanol (TFE, 15mL) were added ), continue the reaction for 6 hours to obtain 3a 99% (using biphenyl as internal standard, gas phase yield), and 4 99% (using biphenyl as internal standard, gas phase yield).
  • the ⁇ -caprolactone product was separated. After the mother liquor was distilled under reduced pressure to remove the solvent, 20mL of ether was added to dissolve it, and then extracted with water as the extractant (10mL ⁇ 3). The aqueous phase was dried by rotary evaporation to obtain 419mg (92%). ) ⁇ -caprolactone product with a purity of 97%.
  • N-hydroxyphthalimide (NHPI, 75mg, 0.45mmol), azobisisobutyronitrile (AIBN, 38mg, 0.23mmol), 4,4'-dimethylbenzyl alcohol into the three-necked flask (1272mg, 6mmol), cyclohexanone (392mg, 4mmol) and ethyl acetate (AcOEt, 1.5mL), ventilate (pure oxygen) three times, and react at 75°C for 8 hours.
  • NHPI N-hydroxyphthalimide
  • AIBN azobisisobutyronitrile
  • AcOEt ethyl acetate
  • reaction solution was reduced to 30°C, and 1,2-bis(3,5-bis(trifluoromethyl)phenyl)diselenide (Se-Cat1, 70mg, 0.12mmol), trifluoroethanol (TFE, 15mL) were added ), continue the reaction for 6 hours to obtain 3b 99% (using biphenyl as internal standard, gas-phase yield) and 4 99% (using biphenyl as internal standard, gas-phase yield).
  • N-hydroxyphthalimide (NHPI, 75mg, 0.45mmol), azobisisobutyronitrile (AIBN, 38mg, 0.23mmol), 4,4'-di-n-propyl diphenyl to the three-necked flask Methanol (1608mg, 6mmol), cyclohexanone (392mg, 4mmol) and ethyl acetate (AcOEt, 1.5mL), ventilate (pure oxygen) three times, and react at 75°C for 8 hours.
  • NHPI N-hydroxyphthalimide
  • AIBN azobisisobutyronitrile
  • AcOEt ethyl acetate
  • reaction solution was reduced to 30°C, and 1,2-bis(3,5-bis(trifluoromethyl)phenyl)diselenide (Se-Cat1, 70mg, 0.12mmol), trifluoroethanol (TFE, 15mL) were added ), continue the reaction for 6 hours to obtain 3c 99% (using biphenyl as internal standard, gas-phase yield), 4 99% (using biphenyl as internal standard, gas-phase yield).
  • N-hydroxyphthalimide 75mg, 0.45mmol
  • azobisisobutyronitrile AIBN, 38mg, 0.23mmol
  • 4-n-propyl benzhydrol 1356mg, 6mmol
  • cyclohexanone 392mg, 4mmol
  • ethyl acetate ethyl acetate
  • reaction solution was reduced to 30°C, and 1,2-bis(3,5-bis(trifluoromethyl)phenyl)diselenide (Se-Cat1, 70mg, 0.12mmol), trifluoroethanol (TFE, 15mL) were added ), continue the reaction for 6 hours, and obtain 3d 99% (using biphenyl as internal standard, gas-phase yield), 4 99% (using biphenyl as internal standard, gas-phase yield).
  • the temperature of the reaction solution was lowered to 30°C, and 1,2-bis(3,5-bis(trifluoromethyl)phenyl)diselenide (Se-Cat1, 70mg, 0.12mmol), trifluoroethanol (TFE, 15 mL), continue the reaction for 6 hours, and obtain 3e 99% (using biphenyl as internal standard, gas-phase yield) and 4 99% (using biphenyl as internal standard, gas-phase yield).
  • N-hydroxyphthalimide (NHPI, 75mg, 0.45mmol), azobisisobutyronitrile (AIBN, 38mg, 0.23mmol), benzhydrol (1104mg, 6mmol), cyclohexane into the three-necked flask Ketone (392mg, 4mmol) and ethyl acetate (AcOEt, 1.5mL), ventilate (pure oxygen) three times, and react at 75°C for 8 hours.
  • reaction solution was reduced to 30°C, and 1,2-bis(2,4-bis(trifluoromethyl)phenyl)diselenide (Se-Cat2, 70mg, 0.12mmol), trifluoroethanol (TFE, 15mL) were added ), continue the reaction for 6 hours to obtain 3a 99% (using biphenyl as internal standard, gas phase yield), 446% (using biphenyl as internal standard, gas phase yield).
  • N-hydroxyphthalimide (NHPI, 75mg, 0.45mmol), azobisisobutyronitrile (AIBN, 38mg, 0.23mmol), benzhydrol (1104mg, 6mmol), cyclohexane into the three-necked flask Ketone (392mg, 4mmol) and ethyl acetate (AcOEt, 1.5mL), ventilate (pure oxygen) three times, and react at 75°C for 8 hours.
  • N-hydroxyphthalimide (NHPI, 75mg, 0.45mmol), azobisisobutyronitrile (AIBN, 38mg, 0.23mmol), benzhydrol (1104mg, 6mmol), cyclohexane into the three-necked flask Ketone (392mg, 4mmol) and ethyl acetate (AcOEt, 1.5mL), ventilate (pure oxygen) three times, and react at 75°C for 8 hours.
  • reaction solution was lowered to 30°C, 1,2-bis(2-trifluoromethylphenyl)diselenide (Se-Cat4, 54mg, 0.12mmol), trifluoroethanol (TFE, 15mL) were added, and the reaction was continued 6 Hours, 3a 99% (using biphenyl as internal standard, gas-phase yield), 4 62% (using biphenyl as internal standard, gas-phase yield).
  • N-hydroxyphthalimide (NHPI, 150mg, 0.9mmol), azobisisobutyronitrile (AIBN, 75mg, 0.45mmol), benzhydrol (2208mg, 12mmol), cyclohexane into the three-necked flask Ketone (392mg, 4mmol) and ethyl acetate (AcOEt, 1.5mL), ventilate (pure oxygen) three times, and react at 75°C for 8 hours.
  • NHPI N-hydroxyphthalimide
  • AIBN azobisisobutyronitrile
  • benzhydrol (2208mg, 12mmol)
  • cyclohexane into the three-necked flask Ketone (392mg, 4mmol) and ethyl acetate (AcOEt, 1.5mL), ventilate (pure oxygen) three times, and react at 75°C for 8 hours.
  • N-hydroxyphthalimide (NHPI, 49mg, 0.3mmol), azobisisobutyronitrile (AIBN, 25mg, 0.15mmol), benzhydrol (1104mg, 6mmol), cyclohexane into the three-necked flask Ketone (392mg, 4mmol) and ethyl acetate (AcOEt, 1.5mL), ventilate (pure oxygen) three times, and react at 75°C for 8 hours.
  • NHPI N-hydroxyphthalimide
  • AIBN azobisisobutyronitrile
  • benzhydrol (1104mg, 6mmol)
  • cyclohexane into the three-necked flask Ketone (392mg, 4mmol) and ethyl acetate (AcOEt, 1.5mL)
  • ventilate pure oxygen
  • reaction solution was reduced to 30°C, and 1,2-bis(3,5-bis(trifluoromethyl)phenyl)diselenide (Se-Cat1, 70mg, 0.12mmol), trifluoroethanol (TFE, 15mL) were added ), continue the reaction for 6 hours, and obtain 3a 92% (using biphenyl as internal standard, gas-phase yield), 4 91% (using biphenyl as internal standard, gas-phase yield).
  • N-hydroxyphthalimide (NHPI, 33mg, 0.2mmol), azobisisobutyronitrile (AIBN, 16mg, 0.1mmol), benzhydrol (1104mg, 6mmol), cyclohexane into a three-necked flask Ketone (392mg, 4mmol) and ethyl acetate (AcOEt, 1.5mL), ventilate (pure oxygen) three times, and react at 75°C for 8 hours.
  • NHPI N-hydroxyphthalimide
  • AIBN azobisisobutyronitrile
  • benzhydrol (1104mg, 6mmol)
  • cyclohexane into a three-necked flask Ketone (392mg, 4mmol) and ethyl acetate (AcOEt, 1.5mL)
  • ventilate pure oxygen
  • reaction solution was reduced to 30°C, and 1,2-bis(3,5-bis(trifluoromethyl)phenyl)diselenide (Se-Cat1, 70mg, 0.12mmol), trifluoroethanol (TFE, 15mL) were added ), continue the reaction for 6 hours, and obtain 3a 82% (using biphenyl as internal standard, gas-phase yield), 4 75% (using biphenyl as internal standard, gas-phase yield).
  • N-hydroxyphthalimide 16mg, 0.1mmol
  • AIBN azobisisobutyronitrile
  • benzhydrol (1104mg, 6mmol)
  • cyclohexane into the three-necked flask Ketone (392mg, 4mmol) and ethyl acetate (AcOEt, 1.5mL), ventilate (pure oxygen) three times, and react at 75°C for 8 hours.
  • reaction solution was reduced to 30°C, and 1,2-bis(3,5-bis(trifluoromethyl)phenyl)diselenide (Se-Cat1, 70mg, 0.12mmol), trifluoroethanol (TFE, 15mL) were added ), continue the reaction for 6 hours, and obtain 3a 60% (using biphenyl as internal standard, gas-phase yield) and 4 51% (using biphenyl as internal standard, gas-phase yield).
  • reaction solution was reduced to 30°C, and 1,2-bis(3,5-bis(trifluoromethyl)phenyl)diselenide (Se-Cat1, 70mg, 0.12mmol), trifluoroethanol (TFE, 15mL) were added ), continue the reaction for 6 hours to obtain 3a 99% (using biphenyl as internal standard, gas phase yield), 4 90% (using biphenyl as internal standard, gas phase yield).
  • reaction solution was reduced to 30°C, and 1,2-bis(3,5-bis(trifluoromethyl)phenyl)diselenide (Se-Cat1, 70mg, 0.12mmol), trifluoroethanol (TFE, 15mL) were added ), continue the reaction for 6 hours to obtain 3a 99% (using biphenyl as internal standard, gas-phase yield), 4 96% (using biphenyl as internal standard, gas-phase yield).
  • N-hydroxyphthalimide (NHPI, 75mg, 0.45mmol), azobisisobutyronitrile (AIBN, 38mg, 0.23mmol), benzhydrol (1104mg, 6mmol), cyclohexane into the three-necked flask Ketone (392mg, 4mmol) and ethyl acetate (AcOEt, 1.5mL), ventilate (pure oxygen) three times, and react at 75°C for 8 hours.
  • reaction solution was reduced to 30°C, and 1,2-bis(3,5-bis(trifluoromethyl)phenyl)diselenide (Se-Cat1, 35mg, 0.06mmol), trifluoroethanol (TFE, 15mL) were added ), continue the reaction for 6 hours to obtain 3a 99% (using biphenyl as internal standard, gas phase yield) and 4 81% (using biphenyl as internal standard, gas phase yield).
  • N-hydroxyphthalimide (NHPI, 73mg, 0.45mmol), azobisisobutyronitrile (AIBN, 38mg, 0.23mmol), benzhydrol (1104mg, 6mmol), cyclohexane into a three-necked flask Ketone (392mg, 4mmol) and ethyl acetate (AcOEt, 1.5mL), ventilate (pure oxygen) three times, and react at 75°C for 8 hours.
  • NHPI N-hydroxyphthalimide
  • AIBN azobisisobutyronitrile
  • benzhydrol (1104mg, 6mmol)
  • cyclohexane into a three-necked flask Ketone (392mg, 4mmol) and ethyl acetate (AcOEt, 1.5mL), ventilate (pure oxygen) three times, and react at 75°C for 8 hours.
  • reaction solution was lowered to 30°C, and 1,2-bis(3,5-bis(trifluoromethyl)phenyl)diselenide (Se-Cat1, 140mg, 0.24mmol), trifluoroethanol (TFE, 15mL) were added ), continue the reaction for 6 hours to obtain 3a 99% (using biphenyl as internal standard, gas phase yield), and 4 99% (using biphenyl as internal standard, gas phase yield).
  • N-hydroxyphthalimide (NHPI, 75mg, 0.45mmol), azobisisobutyronitrile (AIBN, 38mg, 0.23mmol), benzhydrol (1104mg, 6mmol), cyclohexane into the three-necked flask Ketone (392mg, 4mmol) and acetonitrile (MeCN, 1.5mL), ventilate (pure oxygen) three times, and react at 75°C for 8 hours.
  • NHPI N-hydroxyphthalimide
  • AIBN azobisisobutyronitrile
  • MeCN acetonitrile
  • reaction solution was reduced to 30°C, and 1,2-bis(3,5-bis(trifluoromethyl)phenyl)diselenide (Se-Cat1, 75mg, 0.12mmol), trifluoroethanol (TFE, 15mL) were added ), continue the reaction for 6 hours, and obtain 3a 99% (using biphenyl as internal standard, gas-phase yield), 4 85% (using biphenyl as internal standard, gas-phase yield).
  • N-hydroxyphthalimide (NHPI, 75mg, 0.45mmol), azobisisobutyronitrile (AIBN, 38mg, 0.23mmol), benzhydrol (1104mg, 6mmol), cyclohexane into the three-necked flask Ketone (392mg, 4mmol) and chlorobenzene (PhCl, 1.5mL), ventilate (pure oxygen) three times, and react at 75°C for 8 hours.
  • NHPI N-hydroxyphthalimide
  • AIBN azobisisobutyronitrile
  • reaction solution was reduced to 30°C, and 1,2-bis(3,5-bis(trifluoromethyl)phenyl)diselenide (Se-Cat1, 75mg, 0.12mmol), trifluoroethanol (TFE, 15mL) were added ), and continue the reaction for 6 hours to obtain 3a 99% (using biphenyl as internal standard, gas-phase yield) and 4 95% (using biphenyl as internal standard, gas-phase yield).
  • N-hydroxyphthalimide (NHPI, 75mg, 0.45mmol), azobisisobutyronitrile (AIBN, 38mg, 0.23mmol), benzhydrol (1104mg, 6mmol), cyclohexane into the three-necked flask Ketone (392mg, 4mmol) and n-butyl acetate (AcOBu n , 1.5mL), ventilate (pure oxygen) three times, and react at 75°C for 8 hours.
  • NHPI N-hydroxyphthalimide
  • AIBN azobisisobutyronitrile
  • benzhydrol (1104mg, 6mmol)
  • cyclohexane into the three-necked flask Ketone
  • AcOBu n n-butyl acetate
  • reaction solution was reduced to 30°C, and 1,2-bis(3,5-bis(trifluoromethyl)phenyl)diselenide (Se-Cat1, 75mg, 0.12mmol), trifluoroethanol (TFE, 15mL) were added ), the reaction was continued for 6 hours to obtain 3a 99% (using biphenyl as internal standard, gas phase yield), and 4 98% (using biphenyl as internal standard, gas phase yield).
  • N-hydroxyphthalimide (NHPI, 73mg, 0.45mmol), azobisisobutyronitrile (AIBN, 38mg, 0.23mmol), benzhydrol (1104mg, 6mmol), cyclohexane into a three-necked flask Ketone (392mg, 4mmol) and n-propyl acetate (AcOPr n , 1.5mL), ventilate (pure oxygen) three times, and react at 75°C for 8 hours.
  • NHPI N-hydroxyphthalimide
  • AIBN azobisisobutyronitrile
  • benzhydrol (1104mg, 6mmol)
  • cyclohexane into a three-necked flask Ketone (392mg, 4mmol) and n-propyl acetate (AcOPr n , 1.5mL), ventilate (pure oxygen) three times, and react at 75°C for 8 hours.
  • reaction solution was reduced to 30°C, and 1,2-bis(3,5-bis(trifluoromethyl)phenyl)diselenide (Se-Cat1, 70mg, 0.12mmol), trifluoroethanol (TFE, 15mL) were added ), continue the reaction for 6 hours to obtain 3a 99% (using biphenyl as internal standard, gas phase yield), and 4 99% (using biphenyl as internal standard, gas phase yield).
  • N-hydroxyphthalimide (NHPI, 73mg, 0.45mmol), azobisisobutyronitrile (AIBN, 38mg, 0.23mmol), benzhydrol (1104mg, 6mmol), cyclohexane into a three-necked flask Ketone (392mg, 4mmol) and isobutyl acetate (AcOBu i , 1.5mL) were ventilated (pure oxygen) three times and reacted at 75°C for 8 hours.
  • reaction solution was reduced to 30°C, and 1,2-bis(3,5-bis(trifluoromethyl)phenyl)diselenide (Se-Cat1, 70mg, 0.12mmol), trifluoroethanol (TFE, 15mL) were added ), the reaction was continued for 6 hours to obtain 3a 99% (using biphenyl as internal standard, gas phase yield), and 4 98% (using biphenyl as internal standard, gas phase yield).
  • N-hydroxyphthalimide (NHPI, 73mg, 0.45mmol), azobisisobutyronitrile (AIBN, 38mg, 0.23mmol), benzhydrol (1104mg, 6mmol), cyclohexane into a three-necked flask Ketone (392mg, 4mmol) and ethyl acetate (AcOEt, 1.5mL), ventilate (pure oxygen) three times, and react at 75°C for 8 hours.
  • NHPI N-hydroxyphthalimide
  • AIBN azobisisobutyronitrile
  • benzhydrol (1104mg, 6mmol)
  • cyclohexane into a three-necked flask Ketone (392mg, 4mmol) and ethyl acetate (AcOEt, 1.5mL), ventilate (pure oxygen) three times, and react at 75°C for 8 hours.
  • N-hydroxyphthalimide (NHPI, 73mg, 0.45mmol), azobisisobutyronitrile (AIBN, 38mg, 0.23mmol), benzhydrol (1104mg, 6mmol), cyclohexane into a three-necked flask Ketone (392mg, 4mmol) and ethyl acetate (AcOEt, 1.5mL), ventilate (pure oxygen) three times, and react at 75°C for 8 hours.
  • NHPI N-hydroxyphthalimide
  • AIBN azobisisobutyronitrile
  • benzhydrol (1104mg, 6mmol)
  • cyclohexane into a three-necked flask Ketone (392mg, 4mmol) and ethyl acetate (AcOEt, 1.5mL), ventilate (pure oxygen) three times, and react at 75°C for 8 hours.
  • the temperature of the reaction solution was lowered to 30°C, and 1,2-bis(3,5-bis(trifluoromethyl)phenyl)diselenide (Se-Cat1, 70mg, 0.12mmol), hexafluoroisopropanol (HFIP) were added , 15mL), continue the reaction for 6 hours, and get 3a 99% (using biphenyl as internal standard, gas-phase yield), 4 99% (using biphenyl as internal standard, gas-phase yield).
  • Si-Cat1 1,2-bis(3,5-bis(trifluoromethyl)phenyl)diselenide
  • HFIP hexafluoroisopropanol
  • N-hydroxyphthalimide (NHPI, 73mg, 0.45mmol), azobisisobutyronitrile (AIBN, 38mg, 0.23mmol), benzhydrol (1104mg, 6mmol), cyclohexane into a three-necked flask Ketone (392mg, 4mmol) and ethyl acetate (AcOEt, 1.5mL), ventilate (pure oxygen) three times, and react at 75°C for 8 hours.
  • NHPI N-hydroxyphthalimide
  • AIBN azobisisobutyronitrile
  • benzhydrol (1104mg, 6mmol)
  • cyclohexane into a three-necked flask Ketone (392mg, 4mmol) and ethyl acetate (AcOEt, 1.5mL), ventilate (pure oxygen) three times, and react at 75°C for 8 hours.
  • reaction solution was lowered to 30°C, and 1,2-bis(3,5-bis(trifluoromethyl)phenyl)diselenide (Se-Cat1, 70mg, 0.12mmol), trichloroethanol (TCE, 15mL) were added ), continue the reaction for 6 hours to obtain 3a 99% (using biphenyl as internal standard, gas-phase yield), 4 38% (using biphenyl as internal standard, gas-phase yield).
  • N-hydroxyphthalimide (NHPI, 75mg, 0.45mmol), azobisisobutyronitrile (AIBN, 38mg, 0.23mmol), benzhydrol (1104mg, 6mmol), cyclohexane into the three-necked flask Ketone (392mg, 4mmol) and ethyl acetate (AcOEt, 1.5mL) were pumped (standard air) three times and reacted at 75°C for 8 hours.
  • NHPI N-hydroxyphthalimide
  • AIBN azobisisobutyronitrile
  • benzhydrol (1104mg, 6mmol)
  • cyclohexane (1104mg, 6mmol)
  • AcOEt ethyl acetate
  • reaction solution was reduced to 30°C, and 1,2-bis(3,5-bis(trifluoromethyl)phenyl)diselenide (Se-Cat1, 75mg, 0.12mmol), trifluoroethanol (TFE, 15mL) were added ), the reaction was continued for 6 hours to obtain 3a 79% (using biphenyl as internal standard, gas-phase yield), 4 63% (using biphenyl as internal standard, gas-phase yield).
  • N-hydroxyphthalimide (NHPI, 75mg, 0.45mmol), azobisisobutyronitrile (AIBN, 38mg, 0.23mmol), benzhydrol (1104mg, 6mmol), cyclohexane into the three-necked flask Ketone (392mg, 4mmol) and ethyl acetate (AcOEt, 1.5mL), ventilate (pure oxygen) three times, and react at 65°C for 8 hours.
  • reaction solution was reduced to 30°C, and 1,2-bis(3,5-bis(trifluoromethyl)phenyl)diselenide (Se-Cat1, 75mg, 0.12mmol), trifluoroethanol (TFE, 15mL) were added ), continue the reaction for 6 hours, and obtain 3a 83% (using biphenyl as internal standard, gas-phase yield) and 4 88% (using biphenyl as internal standard, gas-phase yield).
  • N-hydroxyphthalimide (NHPI, 75mg, 0.45mmol), azobisisobutyronitrile (AIBN, 38mg, 0.23mmol), benzhydrol (1104mg, 6mmol), cyclohexane into the three-necked flask Ketone (392mg, 4mmol) and ethyl acetate (AcOEt, 1.5mL), ventilate (pure oxygen) three times, and react at 75°C for 8 hours.
  • reaction solution was lowered to 45°C, and 1,2-bis(3,5-bis(trifluoromethyl)phenyl)diselenide (Se-Cat1, 75mg, 0.12mmol), trifluoroethanol (TFE, 15mL) were added ), continue the reaction for 6 hours, and obtain 3a 99% (using biphenyl as internal standard, gas-phase yield), 4 92% (using biphenyl as internal standard, gas-phase yield).
  • N-hydroxyphthalimide (NHPI, 75mg, 0.45mmol), azobisisobutyronitrile (AIBN, 38mg, 0.23mmol), benzhydrol (1104mg, 6mmol), cyclohexane into the three-necked flask Ketone (392mg, 4mmol) and ethyl acetate (AcOEt, 1.5mL), ventilate (pure oxygen) three times, and react at 75°C for 10 hours.
  • NHPI N-hydroxyphthalimide
  • AIBN azobisisobutyronitrile
  • benzhydrol (1104mg, 6mmol)
  • cyclohexane into the three-necked flask Ketone (392mg, 4mmol) and ethyl acetate (AcOEt, 1.5mL)
  • ventilate pure oxygen
  • reaction solution was reduced to 30°C, and 1,2-bis(3,5-bis(trifluoromethyl)phenyl)diselenide (Se-Cat1, 75mg, 0.12mmol), trifluoroethanol (TFE, 15mL) were added ), continue the reaction for 6 hours, and obtain 3a 99% (using biphenyl as internal standard, gas-phase yield), 4 78% (using biphenyl as internal standard, gas-phase yield).
  • N-hydroxyphthalimide (NHPI, 75mg, 0.45mmol), azobisisobutyronitrile (AIBN, 38mg, 0.23mmol), benzhydrol (1104mg, 6mmol), cyclohexane into the three-necked flask Ketone (392mg, 4mmol) and ethyl acetate (AcOEt, 1.5mL), ventilate (pure oxygen) three times, and react at 75°C for 8 hours.
  • reaction solution was reduced to 30°C, and 1,2-bis(3,5-bis(trifluoromethyl)phenyl)diselenide (Se-Cat1, 75mg, 0.12mmol), trifluoroethanol (TFE, 15mL) were added ), continue the reaction for 3 hours to obtain 3a 99% (using biphenyl as internal standard, gas phase yield), 4 90% (using biphenyl as internal standard, gas phase yield).
  • N-hydroxyphthalimide (NHPI, 75mg, 0.45mmol), azobisisobutyronitrile (AIBN, 38mg, 0.23mmol), benzhydrol (1104mg, 6mmol), cyclohexane into the three-necked flask Ketone (392mg, 4mmol) and ethyl acetate (AcOEt, 1.5mL), ventilate (pure oxygen) three times, and react at 75°C for 8 hours.
  • reaction solution was lowered to 30°C, and 1,2-bis(3,5-bis(trifluoromethyl)phenyl)diselenide (Se-Cat1, 75mg, 0.12mmol), trifluoroethanol (TFE, 15mL) were added ), continue the reaction for 8 hours, and obtain 3a 99% (using biphenyl as internal standard, gas-phase yield) and 4 95% (using biphenyl as internal standard, gas-phase yield).
  • N-hydroxyphthalimide (NHPI, 75mg, 0.45mmol), azobisisobutyronitrile (AIBN, 38mg, 0.23mmol), benzhydrol (1104mg, 6mmol), cyclohexane into the three-necked flask Ketone (392mg, 4mmol) and ethyl acetate (AcOEt, 1.5mL), ventilate (pure oxygen) three times, and react at 75°C for 8 hours.
  • reaction solution was lowered to 30°C, and 1,2-bis(3,5-bis(trifluoromethyl)phenyl)diselenide (Se-Cat1, 75mg, 0.12mmol), trifluoroethanol (TFE, 11.25) were added mL), continue the reaction for 6 hours, and obtain 3a 99% (using biphenyl as internal standard, gas-phase yield), 4 89% (using biphenyl as internal standard, gas-phase yield).
  • N-hydroxyphthalimide (NHPI, 75mg, 0.45mmol), azobisisobutyronitrile (AIBN, 38mg, 0.23mmol), benzhydrol (1104mg, 6mmol), cyclohexane into the three-necked flask Ketone (392mg, 4mmol) and ethyl acetate (AcOEt, 1.5mL), ventilate (pure oxygen) three times, and react at 75°C for 8 hours.
  • reaction solution was lowered to 30°C, and 1,2-bis(3,5-bis(trifluoromethyl)phenyl)diselenide (Se-Cat1, 75mg, 0.12mmol) and trifluoroethanol (TFE, 18.75) were added. mL), continue the reaction for 6 hours, and obtain 3a 99% (using biphenyl as internal standard, gas-phase yield) and 4 99% (using biphenyl as internal standard, gas-phase yield).
  • Se-Cat1 1,2-bis(3,5-bis(trifluoromethyl)phenyl)diselenide
  • TFE trifluoroethanol
  • N-hydroxysuccinimide (NHS, 52mg, 0.45mmol), azobisisobutyronitrile (AIBN, 38mg, 0.23mmol), benzhydrol (1104mg, 6mmol), cyclohexanone (392mg) to the three-necked flask , 4mmol) and ethyl acetate (AcOEt, 1.5mL), ventilate (pure oxygen) three times, and react at 75°C for 8 hours.
  • reaction solution was reduced to 30°C, and 1,2-bis(3,5-bis(trifluoromethyl)phenyl)diselenide (Se-Cat1, 70mg, 0.12mmol), trifluoroethanol (TFE, 15mL) were added ), continue the reaction for 6 hours, and obtain 3a 99% (using biphenyl as internal standard, gas-phase yield), 4 85% (using biphenyl as internal standard, gas-phase yield).
  • reaction solution was reduced to 30°C, and 1,2-bis(3,5-bis(trifluoromethyl)phenyl)diselenide (Se-Cat1, 70mg, 0.12mmol), trifluoroethanol (TFE, 15mL) were added ), continue the reaction for 6 hours, and obtain 3a 99% (using biphenyl as internal standard, gas-phase yield), 4 92% (using biphenyl as internal standard, gas-phase yield).
  • reaction solution was reduced to 30°C, and 1,2-bis(3,5-bis(trifluoromethyl)phenyl)diselenide (Se-Cat1, 70mg, 0.12mmol), trifluoroethanol (TFE, 15mL) were added ), continue the reaction for 6 hours to obtain 3a 99% (using biphenyl as internal standard, gas phase yield), 4 90% (using biphenyl as internal standard, gas phase yield).
  • reaction solution was reduced to 30°C, and 1,2-bis(3,5-bis(trifluoromethyl)phenyl)diselenide (Se-Cat1, 70mg, 0.12mmol), trifluoroethanol (TFE, 15mL) were added ), continue the reaction for 6 hours, and obtain 3a 99% (using biphenyl as internal standard, gas-phase yield) and 4 93% (using biphenyl as internal standard, gas-phase yield).

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Abstract

本发明公开了一种利用原位过氧化物制备ε-己内酯的方法，该方法高效利用氧气氧化醇的过程中得到的原位过氧化物将环己酮氧化为ε-己内酯，即在催化剂催化下，在将醇氧化成相应的酮的同时充分利用该过程产生的过氧羟基或过氧化氢等物质，实现了环己酮到ε-己内酯的Baeyer-Villiger氧化反应。相较于以前的ε-己内酯合成方法，本方法产物收率显著提高，醇的使用效率进一步提高，同时本方法原料和试剂廉价易得，操作简单，反应条件温和，清洁环保。

Description

一种利用原位过氧化物制备ε-己内酯的方法 技术领域
本发明属于化学领域，涉及一种基于氧气氧化的ε-己内酯生产的新方法。
背景技术
ε-己内酯单体是一种重要的化工中间体，其聚合物(PCL)由于具有优异的性能而被广泛应用于包括医用高分子树脂、环保材料、胶黏剂和涂料等众多领域。工业上主要通过环己酮与含有活性氧的过氧化物之间的Baeyer-Villiger(BV)反应来生产ε-己内酯。(原位)有机过氧酸(如过氧苯甲酸、过氧乙酸、三氟过氧乙酸等)具有优良的反应性成为目前最常用的氧化剂(Chem.Lett.,1991,20,641；J.Am.Chem.Soc.,1958,80,4079；J.Mol.Catal.A:Chem.,2004,212,237；Angew.Chem.Int.Ed.,2015,54,11848)，但是由于其不稳定性、苛刻的操作条件、较高的成本等缺点而逐渐被取代。(原位)过氧化氢氧化法与过酸氧化法相比更为安全、经济、环保，近些年来成为BV反应的研究热点(Org.Lett.,2000,2,2861；Nature,2001,412,423；Tetrahedron Lett.,2001,42,3479；Angew.Chem.Int.Ed.,2002,41,4481；Angew.Chem.Int.Ed.,2012,51,11736；J.Catal.,2017,352,1；Green Chem.,2017,19,3214；J.Catal.,2019,371,196)。在2001年，荷兰的Sheldon等人报道了二苯基二硒化物催化的BV氧化反应方法(J.Org.Chem.,2001,66,2429)，该方法虽然避免了过酸的使用，然而需要使用的过氧化氢浓度达到60％，高浓度的过氧化氢同样也存在安全性问题，因而并不是一种理想的氧化剂。同样在2001年，日本的Ishii等人的专利中描述了一种利用N-羟基邻苯二甲酰亚胺(NHPI)及类似物催化的原位过氧化氢策略，用于内酯类化合物的制备(US patent 6229023 B1)。然而，在该策略中用于产生原位过氧化氢的牺牲醇的消耗量远多于BV反应的酮底物的量，另外，ε-己内酯的收率也不理想(最大收率＝54％)。
综上，(原位)过氧化氢氧化法仍然存在几个显著的问题：一是由于 其反应性上的不足，通常需要用到较高浓度的过氧化氢，存在安全性问题；二是昂贵的六氟异丙醇作为唯一优良的溶剂，严重影响到该方法在化工生产中的应用；三是随着底物转化率的提高，ε-己内酯的收率会明显下降；四是反应体系中存在水，易导致ε-己内酯发生水解，进而降低ε-己内酯的选择性；五是过氧化氢物质的使用效率随着BV反应的进行而下降。
发明内容
为了克服上述当前工艺的问题，本发明提供了一种利用原位过氧化物制备ε-己内酯的方法，该方法操作安全简便，并且ε-己内酯的收率高。
本发明的技术方案如下：
一种利用原位过氧化物制备ε-己内酯的方法，在催化剂、有机溶剂和氧气存在条件下，牺牲醇发生氧化反应得到的过氧化物原位与环己酮发生反应得到环己酮过氧化物中间体，然后该中间体发生分解反应得到ε-己内酯产物；
其反应方程式如下式(A)所示：
Figure PCTCN2021087032-appb-000001
其中，R 1、R 2独立地选自H、C 1-C 10的直链或支链烷基、芳基、或者芳基取代的C 1-C 10的直链或支链烷基；优选地，R 1、R 2独立地选自H、C 1-C 5的直链或支链烷基、芳基或苄基。
本发明分为两个步骤完成，所用到的催化剂包括第一催化剂和第二催化剂，所用到的有机溶剂包括第一有机溶剂和第二有机溶剂；
所述方法的两个步骤：
(1)第一步为环己酮过氧化物中间体制备过程，第一催化剂、第一有机溶剂、牺牲醇和环己酮在氧气存在下进行反应，得到中间反应液；
(2)第二步为环己酮过氧化物分解过程，向第一步得到的中间反应液中加入第二催化剂和第二有机溶剂继续反应，得到所述的ε-己内酯产物。
本发明的原理是，在第一催化剂和第一有机溶剂的作用下，牺牲醇1被氧气氧化，同时得到过氧羟基或过氧化氢化合物，这些过氧化物与环己 酮2发生反应得到环己酮过氧化物中间体3，该中间体在第二催化剂和第二有机溶剂的作用下发生分解反应得到ε-己内酯4产物，具体的如下式(B)所示：
Figure PCTCN2021087032-appb-000002
本发明中，所述的第一催化剂的作用是催化牺牲醇发生氧气氧化反应，制备过氧羟基或过氧化氢化合物等过氧化物，所述的第一催化剂为有机氮氧自由基催化剂前体与偶氮二异丁腈的混合物；进一步的，所述的有机氮氧自由基催化剂前体与偶氮二异丁腈的摩尔比为1：0.4～1。
所述有机氮氧自由基前体选自如下式(I-1)、(I-2)、(I-3)或(I-4)所示的含氮环状化合物，
Figure PCTCN2021087032-appb-000003
式(I-1)、(I-2)、(I-3)或(I-4)中，R 3～R 12独立地选自氢原子、烷基、环烷基、芳香基、杂环、羟基、硝基或卤素，
或者式(I-1)中，R 3、R 4成环；
或者式(I-2)中，R 5、R 6成环；
或者式(I-3)中，R 7、R 8、R 9至少两个成环；
或者式(I-4)中，R 10、R 11、R 12至少两个成环。进一步的，所成的环为芳香环或者脂肪环；更进一步的，所成的环为五元或六元芳香环、五元或六元脂肪环。
进一步的，所述的有机氮氧自由基催化剂前体包括N-羟基邻苯二甲酰亚胺或其他有机氮氧自由基催化剂前体，具体可以为化合物(a)～(i)中的一种：
Figure PCTCN2021087032-appb-000004
本发明中，所述的第二催化剂的作用是催化环己酮过氧化物的分解反应，所述的第二催化剂为双硒化合物，作为优选，所述的第二催化剂为二苯基二硒类化合物，结构式如下：
Figure PCTCN2021087032-appb-000005
其中，R为一个或两个三氟甲基；进一步地，所述的第二催化剂为1,2-二(3,5-二(三氟甲基)苯基)二硒。
本发明创新点之一在于发展了一种基于有机氮氧自由基催化剂/双硒化合物的催化剂组合。两种催化剂协同催化，有机氮氧自由基催化剂催化牺牲醇的氧气氧化过程，双硒化合物催化环己酮过氧化物中间体的分解反应，因而该方法在使用氧气作为氧化剂的同时，兼顾了ε-己内酯产物的高收率。
Figure PCTCN2021087032-appb-000006
以往的原位过氧化氢策略中，牺牲醇氧化过程中的过氧羟基中间体不能被直接使用，必须要先转化为过氧化氢，由于过氧化氢不可避免的发生自分解反应，产生对反应不利的水，反应的收率往往很不理想。另一方面，若直接使用过氧化氢与双硒化合物的反应体系，过氧化氢的自分解反应同样不可避免，因而必须采用高浓度过氧化氢，保证反应效率。本发明中使用NHPI与双硒化合物的组合，不仅可以催化产生的过氧化氢，更可以直接使用过氧羟基自由基，因而可以明显减少水的产生，大幅度提高ε-己内酯的收率(式(C))。
本发明中，所述的牺牲醇、环己酮、第二催化剂的摩尔比为150～300：100：1～10，作为优选，所述的牺牲醇、环己酮、第一催化剂、第二催化剂的摩尔比为150～300：100：1～10：1～10，进一步优选为150：100：7.5：3；作为另外一种优选，所述的牺牲醇、环己酮、第一催化剂、第二催化剂的摩尔比为150～300：100：5～50：1～10，进一步优选为150： 100：17：3。其中，第一催化剂为N-羟基邻苯二甲酰亚胺或其他有机氮氧自由基催化剂前体和偶氮二异丁腈的总量。
本发明中，所述的第一有机溶剂具有较宽的选择范围，例如可以为酯类溶剂、烃类溶剂、卤代烃类溶剂、腈类溶剂等中的一种或者多种。所述的第一有机溶剂优选为乙酸乙酯、氯苯、乙腈、苯甲腈、乙酸正丁酯中的一种或多种；最优选为乙酸乙酯。
作为优选，所述的第二有机溶剂为氟取代的醇类溶剂，作为进一步优选，所述的第二有机溶剂为氟取代的C 1～C 6醇类溶剂，作为最优选，所述的第二有机溶剂为三氟乙醇；
所述牺牲醇、环己酮、第一有机溶剂和第二有机溶剂的质量比为2～4：1：1～3：10～50，优选为2.75：1：3：50。
本发明中，所述氧气为纯氧气或者空气中的氧气或者氧气与氮气在不同比例的混合气体。
本发明中，所述第一步的反应温度为65℃～100℃；优选为75℃。第二步的反应温度为25℃～60℃；优选为30℃。
本发明中，所述第一步的反应温度为6～10小时；优选为8小时。第二步的反应温度为3～12小时；优选为6小时。
同现有技术相比，本发明具有如下优点：
1)反应收率显著提高，原子经济性高；2)反应体系对水不敏感，在反应的后半段依然有优秀的ε-己内酯选择性；3)牺牲醇的使用效率进一步提高；4)操作安全简便；5)环境友好；6)催化剂廉价，合成方便。
具体实施方式
结合以下具体实施例，对本发明做出进一步的详细说明，本发明的保护内容不局限于以下实施例。在不背离发明构思的精神和范围下，本领域技术人员能够想到的变化和优点都被包括在本发明中，并且以所附的权利要求书为保护范围。
二苯基二硒类化合物可以参照文献(J.Org.Chem.,2001.66.2429；Appl.Organometal.Chem.,2014,28,652；Catal.Sci.Technol.,2016,6,1804)，利用格氏试剂与硒粉反应合成。在手套箱中，量取25mL 0.5mol/L的3,5-双(三氟甲基)苯基溴化镁THF溶液，逐渐加入0.95g硒粉并不断搅拌，约30 分钟加完，继续反应1小时。反应结束后，加入40mL 1mol/L盐酸水溶液进行水解，同时冰水浴，避免反应温度升高。使用25mL乙醚萃取三次，向萃取得到的有机相加入无水硫酸镁除水后，在室温下，空气氧化24小时。旋干溶剂后即可得到二苯基二硒催化剂(收率为78％)。
实施例1
Figure PCTCN2021087032-appb-000007
向三口瓶中加入N-羟基邻苯二甲酰亚胺(NHPI,75mg,0.45mmol)，偶氮二异丁腈(AIBN,38mg,0.23mmol)，二苯甲醇(1104mg,6mmol)，环己酮(392mg,4mmol)和乙酸乙酯(AcOEt,1.5mL)，抽换气(纯氧)三次，75℃反应8小时。将反应液温度降至30℃，加入1,2-二(3,5-二(三氟甲基)苯基)二硒(Se-Cat1,70mg,0.12mmol)，三氟乙醇(TFE,15mL)，继续反应6小时，得到3a 99％(以联苯为内标，气相收率)，4 99％(以联苯为内标，气相收率)。ε-己内酯产品分离，将反应母液进行减压蒸馏除去溶剂后，加入20mL乙醚溶解，然后用水作为萃取剂进行萃取(10mL×3)，水相经过旋转蒸发干燥后可得419mg(92％)ε-己内酯产品，纯度为97％。
4(ε-己内酯)表征：MS(EI):m/z(％)114(M +,15.4),55(100)； 1H-NMR(500MHz,CDCl 3):4.26-4.18(m,2H),2.69-2.60(m,2H),1.95-1.70(m,6H)； 13C-NMR(125MHz,CDCl 3):176.0,69.3,34.7,29.3,28.9,23.1.
实施例2
Figure PCTCN2021087032-appb-000008
向三口瓶中加入N-羟基邻苯二甲酰亚胺(NHPI,75mg,0.45mmol)，偶氮二异丁腈(AIBN,38mg,0.23mmol)，4,4’-二甲基二苯甲醇(1272mg,6mmol)，环己酮(392mg,4mmol)和乙酸乙酯(AcOEt,1.5mL)，抽换气(纯氧)三次，75℃反应8小时。将反应液温度降至30℃，加入1,2-二(3,5-二(三氟甲基)苯基)二硒(Se-Cat1,70mg,0.12mmol)，三氟乙醇(TFE,15mL)，继续反应6小时，得到3b 99％(以联苯为内标，气相收率)，4 99％(以联苯为内标，气相收率)。
实施例3
Figure PCTCN2021087032-appb-000009
向三口瓶中加入N-羟基邻苯二甲酰亚胺(NHPI,75mg,0.45mmol)，偶氮二异丁腈(AIBN,38mg,0.23mmol)，4,4’-二正丙基二苯甲醇(1608mg,6mmol)，环己酮(392mg,4mmol)和乙酸乙酯(AcOEt,1.5mL)，抽换气(纯氧)三次，75℃反应8小时。将反应液温度降至30℃，加入1,2-二(3,5-二(三氟甲基)苯基)二硒(Se-Cat1,70mg,0.12mmol)，三氟乙醇(TFE,15mL)，继续反应6小时，得到3c 99％(以联苯为内标，气相收率)，4 99％(以联苯为内标，气相收率)。
实施例4
Figure PCTCN2021087032-appb-000010
向三口瓶中加入N-羟基邻苯二甲酰亚胺(NHPI,75mg,0.45mmol)，偶氮二异丁腈(AIBN,38mg,0.23mmol)，4-正丙基二苯甲醇(1356mg,6mmol)，环己酮(392mg,4mmol)和乙酸乙酯(AcOEt,1.5mL)，抽换气(纯氧)三次，75℃反应8小时。将反应液温度降至30℃，加入1,2-二(3,5-二(三氟甲基)苯基)二硒(Se-Cat1,70mg,0.12mmol)，三氟乙醇(TFE,15mL)，继续反应6小时，得到3d 99％(以联苯为内标，气相收率)，4 99％(以联苯为内标，气相收率)。
实施例5
Figure PCTCN2021087032-appb-000011
向三口瓶中加入N-羟基邻苯二甲酰亚胺(NHPI,75mg,0.45mmol)，偶氮二异丁腈(AIBN,38mg,0.23mmol)，4-苯甲基二苯甲醇(1644mg,6mmol)，环己酮(392mg,4mmol)和乙酸乙酯(AcOEt,1.5mL)，抽换气(纯氧)三次，75℃反应8小时。将反应液温度降至30℃，加入1,2-二(3,5-二(三氟甲基)苯基)二硒(Se-Cat1,70mg,0.12mmol)，三氟乙醇(TFE,15 mL)，继续反应6小时，得到3e 99％(以联苯为内标，气相收率)，4 99％(以联苯为内标，气相收率)。
实施例6
Figure PCTCN2021087032-appb-000012
向三口瓶中加入N-羟基邻苯二甲酰亚胺(NHPI,75mg,0.45mmol)，偶氮二异丁腈(AIBN,38mg,0.23mmol)，二苯甲醇(1104mg,6mmol)，环己酮(392mg,4mmol)和乙酸乙酯(AcOEt,1.5mL)，抽换气(纯氧)三次，75℃反应8小时。将反应液温度降至30℃，加入1,2-二(2,4-二(三氟甲基)苯基)二硒(Se-Cat2,70mg,0.12mmol)，三氟乙醇(TFE,15mL)，继续反应6小时，得到3a 99％(以联苯为内标，气相收率)，4 46％(以联苯为内标，气相收率)。
实施例7
Figure PCTCN2021087032-appb-000013
向三口瓶中加入N-羟基邻苯二甲酰亚胺(NHPI,75mg,0.45mmol)，偶氮二异丁腈(AIBN,38mg,0.23mmol)，二苯甲醇(1104mg,6mmol)，环己酮(392mg,4mmol)和乙酸乙酯(AcOEt,1.5mL)，抽换气(纯氧)三次，75℃反应8小时。将反应液温度降至30℃，加入1,2-二(3-三氟甲基苯基)二硒(Se-Cat3,54mg,0.12mmol)，三氟乙醇(TFE,15mL)，继续反应6小时，得到3a 99％(以联苯为内标，气相收率)，4 83％(以联苯为内标，气相收率)。
实施例8
Figure PCTCN2021087032-appb-000014
向三口瓶中加入N-羟基邻苯二甲酰亚胺(NHPI,75mg,0.45mmol)，偶氮二异丁腈(AIBN,38mg,0.23mmol)，二苯甲醇(1104mg,6mmol)，环己酮(392mg,4mmol)和乙酸乙酯(AcOEt,1.5mL)，抽换气(纯氧)三次，75℃反应8小时。将反应液温度降至30℃，加入1,2-二(2-三氟甲基苯基)二 硒(Se-Cat4,54mg,0.12mmol)，三氟乙醇(TFE,15mL)，继续反应6小时，得到3a 99％(以联苯为内标，气相收率)，4 62％(以联苯为内标，气相收率)。
实施例9
Figure PCTCN2021087032-appb-000015
向三口瓶中加入N-羟基邻苯二甲酰亚胺(NHPI,150mg,0.9mmol)，偶氮二异丁腈(AIBN,75mg,0.45mmol)，二苯甲醇(2208mg,12mmol)，环己酮(392mg,4mmol)和乙酸乙酯(AcOEt,1.5mL)，抽换气(纯氧)三次，75℃反应8小时。将反应液温度降至30℃，加入1,2-二(3,5-二(三氟甲基)苯基)二硒(Se-Cat1,70mg,0.12mmol)，三氟乙醇(TFE,15mL)，继续反应6小时，得到3a 89％(以联苯为内标，气相收率)，4 99％(以联苯为内标，气相收率)。
实施例10
Figure PCTCN2021087032-appb-000016
向三口瓶中加入N-羟基邻苯二甲酰亚胺(NHPI,49mg,0.3mmol)，偶氮二异丁腈(AIBN,25mg,0.15mmol)，二苯甲醇(1104mg,6mmol)，环己酮(392mg,4mmol)和乙酸乙酯(AcOEt,1.5mL)，抽换气(纯氧)三次，75℃反应8小时。将反应液温度降至30℃，加入1,2-二(3,5-二(三氟甲基)苯基)二硒(Se-Cat1,70mg,0.12mmol)，三氟乙醇(TFE,15mL)，继续反应6小时，得到3a 92％(以联苯为内标，气相收率)，4 91％(以联苯为内标，气相收率)。
实施例11
Figure PCTCN2021087032-appb-000017
向三口瓶中加入N-羟基邻苯二甲酰亚胺(NHPI,33mg,0.2mmol)，偶氮二异丁腈(AIBN,16mg,0.1mmol)，二苯甲醇(1104mg,6mmol)，环己酮(392mg,4mmol)和乙酸乙酯(AcOEt,1.5mL)，抽换气(纯氧)三次，75℃ 反应8小时。将反应液温度降至30℃，加入1,2-二(3,5-二(三氟甲基)苯基)二硒(Se-Cat1,70mg,0.12mmol)，三氟乙醇(TFE,15mL)，继续反应6小时，得到3a 82％(以联苯为内标，气相收率)，4 75％(以联苯为内标，气相收率)。
实施例12
Figure PCTCN2021087032-appb-000018
向三口瓶中加入N-羟基邻苯二甲酰亚胺(NHPI,16mg,0.1mmol)，偶氮二异丁腈(AIBN,8mg,0.05mmol)，二苯甲醇(1104mg,6mmol)，环己酮(392mg,4mmol)和乙酸乙酯(AcOEt,1.5mL)，抽换气(纯氧)三次，75℃反应8小时。将反应液温度降至30℃，加入1,2-二(3,5-二(三氟甲基)苯基)二硒(Se-Cat1,70mg,0.12mmol)，三氟乙醇(TFE,15mL)，继续反应6小时，得到3a 60％(以联苯为内标，气相收率)，4 51％(以联苯为内标，气相收率)。
实施例13
Figure PCTCN2021087032-appb-000019
向三口瓶中加入N-羟基邻苯二甲酰亚胺(NHPI,73mg,0.45mmol)，偶氮二异丁腈(AIBN,19mg,0.12mmol)，二苯甲醇(1104mg,6mmol)，环己酮(392mg,4mmol)和乙酸乙酯(AcOEt,1.5mL)，抽换气(纯氧)三次，75℃反应8小时。将反应液温度降至30℃，加入1,2-二(3,5-二(三氟甲基)苯基)二硒(Se-Cat1,70mg,0.12mmol)，三氟乙醇(TFE,15mL)，继续反应6小时，得到3a 99％(以联苯为内标，气相收率)，4 90％(以联苯为内标，气相收率)。
实施例14
Figure PCTCN2021087032-appb-000020
向三口瓶中加入N-羟基邻苯二甲酰亚胺(NHPI,73mg,0.45mmol)，偶 氮二异丁腈(AIBN,74mg,0.45mmol)，二苯甲醇(1104mg,6mmol)，环己酮(392mg,4mmol)和乙酸乙酯(AcOEt,1.5mL)，抽换气(纯氧)三次，75℃反应8小时。将反应液温度降至30℃，加入1,2-二(3,5-二(三氟甲基)苯基)二硒(Se-Cat1,70mg,0.12mmol)，三氟乙醇(TFE,15mL)，继续反应6小时，得到3a 99％(以联苯为内标，气相收率)，4 96％(以联苯为内标，气相收率)。
实施例15
Figure PCTCN2021087032-appb-000021
向三口瓶中加入N-羟基邻苯二甲酰亚胺(NHPI,75mg,0.45mmol)，偶氮二异丁腈(AIBN,38mg,0.23mmol)，二苯甲醇(1104mg,6mmol)，环己酮(392mg,4mmol)和乙酸乙酯(AcOEt,1.5mL)，抽换气(纯氧)三次，75℃反应8小时。将反应液温度降至30℃，加入1,2-二(3,5-二(三氟甲基)苯基)二硒(Se-Cat1,35mg,0.06mmol)，三氟乙醇(TFE,15mL)，继续反应6小时，得到3a 99％(以联苯为内标，气相收率)，4 81％(以联苯为内标，气相收率)。
实施例16
Figure PCTCN2021087032-appb-000022
向三口瓶中加入N-羟基邻苯二甲酰亚胺(NHPI,73mg,0.45mmol)，偶氮二异丁腈(AIBN,38mg,0.23mmol)，二苯甲醇(1104mg,6mmol)，环己酮(392mg,4mmol)和乙酸乙酯(AcOEt,1.5mL)，抽换气(纯氧)三次，75℃反应8小时。将反应液温度降至30℃，加入1,2-二(3,5-二(三氟甲基)苯基)二硒(Se-Cat1,140mg,0.24mmol)，三氟乙醇(TFE,15mL)，继续反应6小时，得到3a 99％(以联苯为内标，气相收率)，4 99％(以联苯为内标，气相收率)。
实施例17
Figure PCTCN2021087032-appb-000023
向三口瓶中加入N-羟基邻苯二甲酰亚胺(NHPI,75mg,0.45mmol)，偶氮二异丁腈(AIBN,38mg,0.23mmol)，二苯甲醇(1104mg,6mmol)，环己酮(392mg,4mmol)和乙腈(MeCN,1.5mL)，抽换气(纯氧)三次，75℃反应8小时。将反应液温度降至30℃，加入1,2-二(3,5-二(三氟甲基)苯基)二硒(Se-Cat1,75mg,0.12mmol)，三氟乙醇(TFE,15mL)，继续反应6小时，得到3a 99％(以联苯为内标，气相收率)，4 85％(以联苯为内标，气相收率)。
实施例18
Figure PCTCN2021087032-appb-000024
向三口瓶中加入N-羟基邻苯二甲酰亚胺(NHPI,75mg,0.45mmol)，偶氮二异丁腈(AIBN,38mg,0.23mmol)，二苯甲醇(1104mg,6mmol)，环己酮(392mg,4mmol)和氯苯(PhCl,1.5mL)，抽换气(纯氧)三次，75℃反应8小时。将反应液温度降至30℃，加入1,2-二(3,5-二(三氟甲基)苯基)二硒(Se-Cat1,75mg,0.12mmol)，三氟乙醇(TFE,15mL)，继续反应6小时，得到3a 99％(以联苯为内标，气相收率)，4 95％(以联苯为内标，气相收率)。
实施例19
Figure PCTCN2021087032-appb-000025
向三口瓶中加入N-羟基邻苯二甲酰亚胺(NHPI,75mg,0.45mmol)，偶氮二异丁腈(AIBN,38mg,0.23mmol)，二苯甲醇(1104mg,6mmol)，环己酮(392mg,4mmol)和乙酸正丁酯(AcOBu n,1.5mL)，抽换气(纯氧)三次，75℃反应8小时。将反应液温度降至30℃，加入1,2-二(3,5-二(三氟甲基)苯基)二硒(Se-Cat1,75mg,0.12mmol)，三氟乙醇(TFE,15mL)，继续反应6小时，得到3a 99％(以联苯为内标，气相收率)，4 98％(以联苯为 内标，气相收率)。
实施例20
Figure PCTCN2021087032-appb-000026
向三口瓶中加入N-羟基邻苯二甲酰亚胺(NHPI,73mg,0.45mmol)，偶氮二异丁腈(AIBN,38mg,0.23mmol)，二苯甲醇(1104mg,6mmol)，环己酮(392mg,4mmol)和乙酸正丙酯(AcOPr n,1.5mL)，抽换气(纯氧)三次，75℃反应8小时。将反应液温度降至30℃，加入1,2-二(3,5-二(三氟甲基)苯基)二硒(Se-Cat1,70mg,0.12mmol)，三氟乙醇(TFE,15mL)，继续反应6小时，得到3a 99％(以联苯为内标，气相收率)，4 99％(以联苯为内标，气相收率)。
实施例21
Figure PCTCN2021087032-appb-000027
向三口瓶中加入N-羟基邻苯二甲酰亚胺(NHPI,73mg,0.45mmol)，偶氮二异丁腈(AIBN,38mg,0.23mmol)，二苯甲醇(1104mg,6mmol)，环己酮(392mg,4mmol)和乙酸异丁酯(AcOBu i,1.5mL)，抽换气(纯氧)三次，75℃反应8小时。将反应液温度降至30℃，加入1,2-二(3,5-二(三氟甲基)苯基)二硒(Se-Cat1,70mg,0.12mmol)，三氟乙醇(TFE,15mL)，继续反应6小时，得到3a 99％(以联苯为内标，气相收率)，4 98％(以联苯为内标，气相收率)。
实施例22
Figure PCTCN2021087032-appb-000028
向三口瓶中加入N-羟基邻苯二甲酰亚胺(NHPI,73mg,0.45mmol)，偶氮二异丁腈(AIBN,38mg,0.23mmol)，二苯甲醇(1104mg,6mmol)，环己酮(392mg,4mmol)和乙酸乙酯(AcOEt,1.5mL)，抽换气(纯氧)三次，75℃反应8小时。将反应液温度降至30℃，加入1,2-二(3,5-二(三氟甲基) 苯基)二硒(Se-Cat1,70mg,0.12mmol)，2,2-二氟乙醇(DFE,15mL)，继续反应6小时，得到3a 99％(以联苯为内标，气相收率)，4 45％(以联苯为内标，气相收率)。
实施例23
Figure PCTCN2021087032-appb-000029
向三口瓶中加入N-羟基邻苯二甲酰亚胺(NHPI,73mg,0.45mmol)，偶氮二异丁腈(AIBN,38mg,0.23mmol)，二苯甲醇(1104mg,6mmol)，环己酮(392mg,4mmol)和乙酸乙酯(AcOEt,1.5mL)，抽换气(纯氧)三次，75℃反应8小时。将反应液温度降至30℃，加入1,2-二(3,5-二(三氟甲基)苯基)二硒(Se-Cat1,70mg,0.12mmol)，六氟异丙醇(HFIP,15mL)，继续反应6小时，得到3a 99％(以联苯为内标，气相收率)，4 99％(以联苯为内标，气相收率)。
实施例24
Figure PCTCN2021087032-appb-000030
向三口瓶中加入N-羟基邻苯二甲酰亚胺(NHPI,73mg,0.45mmol)，偶氮二异丁腈(AIBN,38mg,0.23mmol)，二苯甲醇(1104mg,6mmol)，环己酮(392mg,4mmol)和乙酸乙酯(AcOEt,1.5mL)，抽换气(纯氧)三次，75℃反应8小时。将反应液温度降至30℃，加入1,2-二(3,5-二(三氟甲基)苯基)二硒(Se-Cat1,70mg,0.12mmol)，三氯乙醇(TCE,15mL)，继续反应6小时，得到3a 99％(以联苯为内标，气相收率)，4 38％(以联苯为内标，气相收率)。
实施例25
Figure PCTCN2021087032-appb-000031
向三口瓶中加入N-羟基邻苯二甲酰亚胺(NHPI,75mg,0.45mmol)，偶氮二异丁腈(AIBN,38mg,0.23mmol)，二苯甲醇(1104mg,6mmol)，环 己酮(392mg,4mmol)和乙酸乙酯(AcOEt,1.5mL)，抽换气(标准空气)三次，75℃反应8小时。将反应液温度降至30℃，加入1,2-二(3,5-二(三氟甲基)苯基)二硒(Se-Cat1,75mg,0.12mmol)，三氟乙醇(TFE,15mL)，继续反应6小时，得到3a 79％(以联苯为内标，气相收率)，4 63％(以联苯为内标，气相收率)。
实施例26
Figure PCTCN2021087032-appb-000032
向三口瓶中加入N-羟基邻苯二甲酰亚胺(NHPI,75mg,0.45mmol)，偶氮二异丁腈(AIBN,38mg,0.23mmol)，二苯甲醇(1104mg,6mmol)，环己酮(392mg,4mmol)和乙酸乙酯(AcOEt,1.5mL)，抽换气(纯氧)三次，65℃反应8小时。将反应液温度降至30℃，加入1,2-二(3,5-二(三氟甲基)苯基)二硒(Se-Cat1,75mg,0.12mmol)，三氟乙醇(TFE,15mL)，继续反应6小时，得到3a 83％(以联苯为内标，气相收率)，4 88％(以联苯为内标，气相收率)。
实施例27
Figure PCTCN2021087032-appb-000033
向三口瓶中加入N-羟基邻苯二甲酰亚胺(NHPI,75mg,0.45mmol)，偶氮二异丁腈(AIBN,38mg,0.23mmol)，二苯甲醇(1104mg,6mmol)，环己酮(392mg,4mmol)和乙酸乙酯(AcOEt,1.5mL)，抽换气(纯氧)三次，75℃反应8小时。将反应液温度降至45℃，加入1,2-二(3,5-二(三氟甲基)苯基)二硒(Se-Cat1,75mg,0.12mmol)，三氟乙醇(TFE,15mL)，继续反应6小时，得到3a 99％(以联苯为内标，气相收率)，4 92％(以联苯为内标，气相收率)。
实施例28
Figure PCTCN2021087032-appb-000034
向三口瓶中加入N-羟基邻苯二甲酰亚胺(NHPI,75mg,0.45mmol)，偶氮二异丁腈(AIBN,38mg,0.23mmol)，二苯甲醇(1104mg,6mmol)，环己酮(392mg,4mmol)和乙酸乙酯(AcOEt,1.5mL)，抽换气(纯氧)三次，75℃反应10小时。将反应液温度降至30℃，加入1,2-二(3,5-二(三氟甲基)苯基)二硒(Se-Cat1,75mg,0.12mmol)，三氟乙醇(TFE,15mL)，继续反应6小时，得到3a 99％(以联苯为内标，气相收率)，4 78％(以联苯为内标，气相收率)。
实施例29
Figure PCTCN2021087032-appb-000035
向三口瓶中加入N-羟基邻苯二甲酰亚胺(NHPI,75mg,0.45mmol)，偶氮二异丁腈(AIBN,38mg,0.23mmol)，二苯甲醇(1104mg,6mmol)，环己酮(392mg,4mmol)和乙酸乙酯(AcOEt,1.5mL)，抽换气(纯氧)三次，75℃反应8小时。将反应液温度降至30℃，加入1,2-二(3,5-二(三氟甲基)苯基)二硒(Se-Cat1,75mg,0.12mmol)，三氟乙醇(TFE,15mL)，继续反应3小时，得到3a 99％(以联苯为内标，气相收率)，4 90％(以联苯为内标，气相收率)。
实施例30
Figure PCTCN2021087032-appb-000036
向三口瓶中加入N-羟基邻苯二甲酰亚胺(NHPI,75mg,0.45mmol)，偶氮二异丁腈(AIBN,38mg,0.23mmol)，二苯甲醇(1104mg,6mmol)，环己酮(392mg,4mmol)和乙酸乙酯(AcOEt,1.5mL)，抽换气(纯氧)三次，75℃反应8小时。将反应液温度降至30℃，加入1,2-二(3,5-二(三氟甲基)苯基)二硒(Se-Cat1,75mg,0.12mmol)，三氟乙醇(TFE,15mL)，继续反应8小时，得到3a 99％(以联苯为内标，气相收率)，4 95％(以联苯为内标，气相收率)。
实施例31
Figure PCTCN2021087032-appb-000037
向三口瓶中加入N-羟基邻苯二甲酰亚胺(NHPI,75mg,0.45mmol)，偶氮二异丁腈(AIBN,38mg,0.23mmol)，二苯甲醇(1104mg,6mmol)，环己酮(392mg,4mmol)和乙酸乙酯(AcOEt,1.5mL)，抽换气(纯氧)三次，75℃反应8小时。将反应液温度降至30℃，加入1,2-二(3,5-二(三氟甲基)苯基)二硒(Se-Cat1,75mg,0.12mmol)，三氟乙醇(TFE,11.25mL)，继续反应6小时，得到3a 99％(以联苯为内标，气相收率)，4 89％(以联苯为内标，气相收率)。
实施例32
Figure PCTCN2021087032-appb-000038
向三口瓶中加入N-羟基邻苯二甲酰亚胺(NHPI,75mg,0.45mmol)，偶氮二异丁腈(AIBN,38mg,0.23mmol)，二苯甲醇(1104mg,6mmol)，环己酮(392mg,4mmol)和乙酸乙酯(AcOEt,1.5mL)，抽换气(纯氧)三次，75℃反应8小时。将反应液温度降至30℃，加入1,2-二(3,5-二(三氟甲基)苯基)二硒(Se-Cat1,75mg,0.12mmol)，三氟乙醇(TFE,18.75mL)，继续反应6小时，得到3a 99％(以联苯为内标，气相收率)，4 99％(以联苯为内标，气相收率)。
实施例33
Figure PCTCN2021087032-appb-000039
向三口瓶中加入N-羟基琥珀酰亚胺(NHS,52mg,0.45mmol)，偶氮二异丁腈(AIBN,38mg,0.23mmol)，二苯甲醇(1104mg,6mmol)，环己酮(392mg,4mmol)和乙酸乙酯(AcOEt,1.5mL)，抽换气(纯氧)三次，75℃反应8小时。将反应液温度降至30℃，加入1,2-二(3,5-二(三氟甲基)苯基)二硒(Se-Cat1,70mg,0.12mmol)，三氟乙醇(TFE,15mL)，继续反应6小 时，得到3a 99％(以联苯为内标，气相收率)，4 85％(以联苯为内标，气相收率)。
实施例34
Figure PCTCN2021087032-appb-000040
向三口瓶中加入2-羟基-1H-吡咯[3,4c]-吡啶-1,3-2H-二酮(NHQI,75mg,0.45mmol)，偶氮二异丁腈(AIBN,38mg,0.23mmol)，二苯甲醇(1104mg,6mmol)，环己酮(392mg,4mmol)和乙酸乙酯(AcOEt,1.5mL)，抽换气(纯氧)三次，75℃反应8小时。将反应液温度降至30℃，加入1,2-二(3,5-二(三氟甲基)苯基)二硒(Se-Cat1,70mg,0.12mmol)，三氟乙醇(TFE,15mL)，继续反应6小时，得到3a 99％(以联苯为内标，气相收率)，4 92％(以联苯为内标，气相收率)。
实施例35
Figure PCTCN2021087032-appb-000041
向三口瓶中加入1-羟基哌啶-2,6-二酮(HPD,58mg,0.45mmol)，偶氮二异丁腈(AIBN,38mg,0.23mmol)，二苯甲醇(1104mg,6mmol)，环己酮(392mg,4mmol)和乙酸乙酯(AcOEt,1.5mL)，抽换气(纯氧)三次，75℃反应8小时。将反应液温度降至30℃，加入1,2-二(3,5-二(三氟甲基)苯基)二硒(Se-Cat1,70mg,0.12mmol)，三氟乙醇(TFE,15mL)，继续反应6小时，得到3a 99％(以联苯为内标，气相收率)，4 90％(以联苯为内标，气相收率)。
实施例36
Figure PCTCN2021087032-appb-000042
向三口瓶中加入2-羟基异喹啉-1,3(2H，4H)-二酮(HQD,80mg,0.45mmol)，偶氮二异丁腈(AIBN,38mg,0.23mmol)，二苯甲醇(1104mg,6mmol)，环己酮(392mg,4mmol)和乙酸乙酯(AcOEt,1.5mL)，抽换气(纯 氧)三次，75℃反应8小时。将反应液温度降至30℃，加入1,2-二(3,5-二(三氟甲基)苯基)二硒(Se-Cat1,70mg,0.12mmol)，三氟乙醇(TFE,15mL)，继续反应6小时，得到3a 99％(以联苯为内标，气相收率)，4 93％(以联苯为内标，气相收率)。

Claims (12)

  1. 一种利用原位过氧化物制备ε-己内酯的方法，其特征在于，在催化剂、有机溶剂和氧气存在条件下，首先牺牲醇发生氧化反应得到的过氧化物原位与环己酮反应生成环己酮过氧化物中间体，然后该中间体发生分解反应得到所述的ε-己内酯产物；
    所述的牺牲醇的结构如下式所示：
    Figure PCTCN2021087032-appb-100001
    R 1和R 2独立地选自H、C 1-C 10的直链或支链烷基、芳基、或者芳基取代的C 1-C 10的直链或支链烷基。
  2. 根据权利要求1所述的利用原位过氧化物制备ε-己内酯的方法，其特征在于，反应分为两步进行，所用到的催化剂分别是第一催化剂和第二催化剂，所用到的有机溶剂分别是第一有机溶剂和第二有机溶剂；
    所述方法的两个步骤如下：
    (1)第一步为环己酮过氧化物中间体制备过程：在第一催化剂、第一有机溶剂存在下，牺牲醇、环己酮和氧气发生反应，得到中间反应液；
    (2)第二步为环己酮过氧化物分解过程：向第一步得到的中间反应液中加入第二催化剂和第二有机溶剂继续反应，得到所述的ε-己内酯产物。
  3. 根据权利要求2所述的利用原位过氧化物制备ε-己内酯的方法，其特征在于，所述的第一催化剂为有机氮氧自由基催化剂前体与偶氮二异丁腈的混合物：
    所述有机氮氧自由基催化剂前体选自如下式(I-1)、(I-2)、(I-3)或(I-4)所示的含氮环状化合物：
    Figure PCTCN2021087032-appb-100002
    式(I-1)、(I-2)、(I-3)或(I-4)中，R 3～R 12独立地选自氢原子、烷基、环烷基、芳香基、杂环、羟基、硝基或卤素，
    或者式(I-1)中，R 3、R 4成环；
    或者式(I-2)中，R 5、R 6成环；
    或者式(I-3)中，R 7、R 8、R 9至少两个成环；
    或者式(I-4)中，R 10、R 11、R 12至少两个成环。
  4. 根据权利要求3所述的利用原位过氧化物制备ε-己内酯的方法，其特征在于，所述的有机氮氧自由基催化剂前体为化合物(a)～(i)中的一种：
    Figure PCTCN2021087032-appb-100003
  5. 根据权利要求3或4所述的利用原位过氧化物制备ε-己内酯的方法，其特征在于，所述的有机氮氧自由基催化剂前体与偶氮二异丁腈的摩尔比为1：0.4～1。
  6. 根据权利要求2所述的利用原位过氧化物制备ε-己内酯的方法，其特征在于，所述的第二催化剂为二苯基二硒类化合物，结构式如下：
    Figure PCTCN2021087032-appb-100004
    其中，R为一个或两个三氟甲基。
  7. 根据权利要求2所述的利用原位过氧化物制备ε-己内酯的方法，其特征在于，所述的牺牲醇、环己酮、第二催化剂的摩尔比为150～300：100：1～10。
  8. 根据权利要求2所述的利用原位过氧化物制备ε-己内酯的方法，其特征在于，所述的牺牲醇、环己酮、第一催化剂、第二催化剂的摩尔比为150～300：100：1～10：1～10。
  9. 根据权利要求2所述的利用原位过氧化物制备ε-己内酯的方法，其特征在于，所述的牺牲醇、环己酮、第一催化剂、第二催化剂的摩尔比为150～300：100：5～50：1～10。
  10. 根据权利要求2所述的利用原位过氧化物制备ε-己内酯的方法，其特征在于，所述的第一有机溶剂为乙酸乙酯、氯苯、乙腈、苯甲腈、乙酸正丁酯中的一种或多种，所述的第二有机溶剂为三氟乙醇。
  11. 根据权利要求2所述的利用原位过氧化物制备ε-己内酯的方法，其特征在于，所述牺牲醇、环己酮、第一有机溶剂和第二有机溶剂的质量比为2～4：1：1～3：10～50。
  12. 根据权利要求2所述的利用原位过氧化物制备ε-己内酯的方法，其特征在于，第一步的反应温度为65℃～100℃，第一步的反应时间为6～10小时；
    第二步的反应温度为25℃～60℃，第二步的反应时间为3～12小时。
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