DE112021001985T5 - Process for the production of ε-caprolactone using in situ peroxide - Google Patents

Abstract

The present invention discloses a process for the production of ε-caprolactone by means of in situ peroxide, which efficiently utilizes the in situ peroxide obtained in the oxidation of alcohols with oxygen for the oxidation of cyclohexanone to ε-caprolactone, i.e. the catalyst-catalyzed one Oxidation of alcohols to the corresponding ketones making full use of the peroxyhydroxyl or hydrogen peroxide generated by the process to achieve the Baeyer–Villiger oxidation of cyclohexanone to ε-caprolactone. Compared to previous methods for the synthesis of ε-caprolactone, this method provides a significantly higher yield of product and further increases the efficiency of the alcohol use. At the same time, the raw materials and reagents of the process are cheap and available, the operation is simple, the reaction service is mild, clean and environmentally friendly.

Description

TECHNICAL AREA

The present invention belongs to the field of chemistry and relates in particular to a new process for the production of ε-caprolactone based on oxygen oxidation.

STATE OF THE ART

ε-Caprolactone monomer is an important chemical intermediate and its polymer (PCL) is used in a variety of applications including medical polymer resins, environmental materials, adhesives and coatings because of its excellent properties. ε-Caprolactone are produced industrially mainly by the Baeyer-Villiger reaction (BV) between cyclohexanone and peroxide containing active oxygen. (In situ) organoperoxyacids (e.g. peroxybenzoic acid, peroxyacetic acid, trifluoroperoxyacetic acid, etc.) have excellent reactivity and are currently the most commonly used oxidants (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), which, however, due to their instability, the strict Operating conditions and the relatively high costs are gradually replaced. The (in situ) hydrogen peroxide oxidation is safer, more economical and more environmentally friendly than oxidation with peracid and has become an important research topic for BV reactions in recent years (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). In 2001, Sheldon et al. from the Netherlands reported a diphenyldiselenide-catalyzed BV oxidation reaction (J. Org. Chem., 2001, 66, 2429) which avoids the use of peracids but requires the use of hydrogen peroxide in concentrations of up to 60%. Because high concentrations of hydrogen peroxide also have safety issues, it is not an ideal oxidizer. Also in 2001, a patent by Ishii et al. from Japan an in situ hydrogen peroxide strategy to produce lactones by catalyzing N-hydroxyphthalimide (NHPI) and the like ( U.S. Patent 6229023 B1 ). However, the amount of sacrificial alcohol used in this strategy to generate in situ hydrogen peroxide is much larger than the amount of ketone substrate for the BV reaction, and the yield of ε-caprolactone is also unsatisfactory ( maximum yield = 54%).

In summary, (in situ) hydrogen peroxide oxidation still has some significant problems. First, the lack of reactivity usually requires a higher concentration of hydrogen peroxide, which poses safety concerns. Second, the expensive hexafluoroisopropanol, the only good solvent, severely impairs the application of the method in chemical production. Third, as the conversion of the substrate increases, the yield of ε-caprolactone decreases significantly. Fourth, the water in the reaction system tends to hydrolyze ε-caprolactone, which in turn reduces the selectivity of ε-caprolactone. Fifth, the usage efficiency of the hydrogen peroxide substance decreases as the BV reaction progresses.

DISCLOSURE OF THE INVENTION

In order to overcome the above problems of the current process, the present invention offers a process for producing ε-caprolactone using in situ peroxide, which is safe and easy to handle, and which provides a high yield of ε-caprolactone is.

• Verfahren zur Herstellung von ε-Caprolacton mittels In-situ-Peroxid, wobei das durch die Oxidationsreaktion eines Opferalkohols erhaltene Peroxid in situ mit Cyclohexanon in Gegenwart eines Katalysators, eines organischen Lösungsmittels und von Sauerstoff umgesetzt wird, um ein Cyclohexanonperoxid-Zwischenprodukt zu bilden, das dann einer Zersetzungsreaktion unterzogen wird, um das ε-Caprolacton-Produkt zu ergeben; wobei die Reaktionsgleichung von dem Verfahren in Formel (A) unten dargestellt ist:
  
  worin R₁, R₂ unabhängig voneinander ausgewählt sind aus H, geradkettigen oder verzweigten C₁-C₁₀ Alkyl-Gruppen, Aryl-Gruppen oder Aryl-substituierten geradkettigen oder verzweigten C₁-C₁₀ Alkyl-Gruppen; vorzugsweise R₁, R₂ unabhängig voneinander ausgewählt sind aus H, geradkettigen oder verzweigten C₁-C₅ Alkyl-Gruppen, Aryl-Gruppen oder Benzyl-Gruppe.

The technical solutions of the present invention are described below:

• Process for the production of ε-caprolactone using in situ peroxide, in which the peroxide obtained by the oxidation reaction of a sacrificial alcohol is reacted in situ with cyclohexanone in the presence of a catalyst, an organic solvent and oxygen to form a cyclohexanone peroxide intermediate which then undergoing a decomposition reaction to give the ε-caprolactone product; wherein the reaction equation of the process in formula (A) is shown below:
  
  wherein R ₁ , R ₂ are independently selected from H, straight or branched C ₁ -C ₁₀ alkyl groups, aryl groups or aryl-substituted straight or branched C ₁ -C ₁₀ alkyl groups; preferably R ₁ , R ₂ are independently selected from H, straight-chain or branched C ₁ -C ₅ alkyl groups, aryl groups or benzyl groups.

The process of the present invention is carried out in two steps, wherein the catalyst employed comprises a first and a second catalyst and the organic solvent employed comprises a first and a second organic solvent.

• (1) einen ersten Schritt, die Herstellung des Cyclohexanonperoxid-Zwischenprodukts, bei dem der erste Katalysator, das erste organische Lösungsmittel, der Opferalkohol und Cyclohexanon in Gegenwart von Sauerstoff zur Bildung von Zwischenreaktionslösung umgesetzt werden;
• (2) einen zweiten Schritt, die Zersetzung des Cyclohexanonperoxids, bei dem ein zweiter Katalysator und ein zweites organisches Lösungsmittel zu der im ersten Schritt erhaltenen Zwischenreaktionslösung hinzugefügt werden, um die Reaktion fortzusetzen und das ε-Caprolacton-Produkt zu erhalten.

The two steps of the procedure include:

• (1) a first step, the preparation of the intermediate cyclohexanone peroxide, in which the first catalyst, the first organic solvent, the sacrificial alcohol and cyclohexanone are reacted in the presence of oxygen to form an intermediate reaction solution;
• (2) a second step, the decomposition of cyclohexanone peroxide, in which a second catalyst and a second organic solvent are added to the intermediate reaction solution obtained in the first step to proceed the reaction and obtain the ε-caprolactone product.

The principle of the present invention is that the sacrificial alcohol 1 is oxidized by oxygen in the presence of a first catalyst and a first organic solvent, meanwhile obtaining a peroxyhydroxyl or hydrogen peroxide compound, and such peroxide reacts with cyclohexanone 2 to form a cyclohexanone peroxide - to obtain intermediate 3 which is subjected to a decomposition reaction in the presence of a second catalyst and a second organic solvent to obtain ε-caprolactone 4 product as represented in formula (B).

In the present invention, the first catalyst serves to catalyze the oxygen oxidation reaction of the sacrificial alcohol to produce a peroxide such as a peroxyhydroxyl or hydrogen peroxide compound, the first catalyst being a mixture of an organic nitroxide radical catalyst precursor and azobis(isobutyronitrile); and further wherein the molar ratio of the organic nitroxide radical catalyst precursor and azobis(isobutyronitrile) is 1:0.4 to 1.

wobei in den Formeln (I-1), (I-2), (I-3) oder (1-4) R₃ bis R₁₂ unabhängig voneinander ausgewählt sind aus Wasserstoffatom, Alkyl-Gruppen, Cycloalkyl-Gruppen, Aryl-Gruppen, Heterocyclen, Hydroxy-Gruppe, Nitro-Gruppe oder Halogenen,
oder wobei in Formel (I-1), R₃ und R₄ einen Ring bilden,
oder wobei in Formel (I-2), R₅ und R₆ einen Ring bilden,
oder wobei in Formel (I-3), mindestens zwei von R₇, R₈ und R₉ einen Ring bilden,
oder wobei in der Formel (I-4), mindestens zwei von R₁₀, R₁₁ und R₁₂ einen Ring bilden. Ferner ist der gebildete Ring ein aromatischer Ring oder ein aliphatischer Ring; noch ferner ist der gebildete Ring ein fünf- oder sechsgliedriger aromatischer Ring, ein fünf- oder sechsgliedriger aliphatischer Ring.The organic nitroxide radical catalyst precursor is selected from the nitrogen-containing cyclic compounds represented by formula (I-1), (I-2), (I-3) or (I-4) below,

wherein in formula (I-1), (I-2), (I-3) or (1-4), R ₃ to R ₁₂ are independently selected from hydrogen atom, alkyl groups, cycloalkyl groups, aryl groups , heterocycles, hydroxy group, nitro group or halogens,
or wherein in formula (I-1), R ₃ and R ₄ form a ring,
or wherein in formula (I-2), R ₅ and R ₆ form a ring,
or wherein in formula (I-3), at least two of R ₇ , R ₈ and R ₉ form a ring,
or wherein in the formula (I-4), at least two of R ₁₀ , R ₁₁ and R ₁₂ form a ring. Further, the ring formed is an aromatic ring or an aliphatic ring; still further, the ring formed is a five- or six-membered aromatic ring, a five- or six-membered aliphatic ring.

Furthermore, the organic nitroxide radical catalyst precursor comprises N-hydroxyphthalimide or other organic nitroxide radical catalyst precursor, in particular one of the compounds (a) to (i) is:

wobei R eine oder zwei Trifluormethyl-Gruppen bedeutet; wobei ferner der zweite Katalysator 1,2-Di(3,5-di(trifluormethyl)phenyl)diselenid ist.In the present invention, the second catalyst serves to catalyze the decomposition reaction of cyclohexanone peroxide, the second catalyst is a diselenide compound, and preferably the second catalyst is a diphenyldiselenide compound having the following structural formula

where R represents one or two trifluoromethyl groups; further wherein the second catalyst is 1,2-di(3,5-di(trifluoromethyl)phenyl)diselenide.

One of the inventive activities of the present invention is the development of a catalyst combination based on an organic nitroxide radical catalyst/diselenide compound. The two catalysts synergistically catalyze, with the oxygen oxidation process of the sacrificial alcohol being catalyzed by the organic nitroxide radical catalyst and the decomposition reaction of the cyclohexanone peroxide intermediate being catalyzed by the diselenide compound, hence the process of high yield of the ε-caprolactone product using oxygen as the oxidant leads.

In previous in situ hydrogen peroxide strategies, the peroxyhydroxyl intermediate from the sacrificial alcohol oxidation process cannot be used directly, but must first be converted to hydrogen peroxide. The yield of the reaction is often very low because the inevitable self-decomposition of the hydrogen peroxide produces water, which is unfavorable to the reaction. On the other hand, when a reaction system of hydrogen peroxide with diselenide compounds is used directly, the self-decomposition of hydrogen peroxide is also inevitable, so that a high concentration of hydrogen peroxide must be used in order to ensure the reaction efficiency. The combination of NHPI and diselenide compounds used in the present invention allows not only to catalyze the hydrogen peroxide produced, but also to use peroxyhydroxyl radicals directly, thereby significantly reducing water production and increasing the yield of ε-caprolactone (formula (C)). is increased.

In the present invention, the molar ratio of the sacrificial alcohol, cyclohexanone, and second catalyst is 150 to 300:100:1 to 10. Preferably, the molar ratio of the sacrificial alcohol, cyclohexanone, first catalyst, and second catalyst is 150 to 300:100 :1 to 10:1 to 10, more preferably 150:100:7.5:3. Also preferably the molar ratio of the sacrificial alcohol, the cyclohexanone, the first catalyst and the second catalyst is from 150 to 300:100:5 to 50:1 to 10, more preferably 150:100:17:3. The first catalyst is the combination of N-hydroxyphthalimide or other organic nitroxide radical catalyst precursor and azobis(isobutyronitrile).

In the present invention, the first organic solvent has a relatively wide range of selection. For example, it may be one or more of ester solvent, hydrocarbon solvent, halocarbon solvent, nitrile solvent, and so on. The first organic solvent is preferably one or more of ethyl acetate, chlorobenzene, acetonitrile, benzonitrile, n-butyl acetate; most preferably ethyl acetate.

Preferably, the second organic solvent is a fluoro-substituted alcohol solvent. More preferably, the second organic solvent is a fluoro-substituted C ₁ -C ₆ alcohol solvent. More preferably, the second organic solvent is trifluoroethanol.

The mass ratio of the sacrificial alcohol, the cyclohexanone, the first organic solvent and the second organic solvent is 2 to 4:1:1 to 3:10 to 50, preferably 2.75:1:3:50.

In the present invention, the oxygen is pure oxygen, oxygen in air, or a mixture of oxygen and nitrogen in various proportions.

In the present invention, the first step has a reaction temperature of 65°C to 100°C; preferably 75°C. The second step has a reaction temperature of 25°C to 60°C; preferably 30°C

In the present invention, the first step has a reaction time of 6 to 10 hours, preferably 8 hours. The second step has a reaction time of 3 to 12 hours, preferably 6 hours.

• 1) Signifikant höhere Reaktionsausbeuten und hohe Atom Ökonomie;
• 2) Unempfindlichkeit des Reaktionssystems gegen Wasser und noch eine ausgezeichnete ε-Caprolacton-Selektivität in der letzten Hälfte der Reaktion;
• 3) Weitere Verbesserung der Verwendungseffizienz von Opferalkoholen;
• 4) Sicherer und einfacher Betrieb;
• 5) Umweltfreundlichkeit;
• 6) Preiswerte Katalysatoren und einfache Synthese.

Compared to the prior art, the present invention has the following advantages:

• 1) Significantly higher reaction yields and high atom economy;
• 2) insensitivity of the reaction system to water and still excellent ε-caprolactone selectivity in the latter half of the reaction;
• 3) Further improve the use efficiency of sacrificial alcohols;
• 4) Safe and easy operation;
• 5) environmental friendliness;
• 6) Inexpensive catalysts and simple synthesis.

DETAILED DESCRIPTION OF EMBODIMENTS

The present invention will be described in more detail in connection with the following specific embodiments, but the scope of the invention is not limited to the following embodiments. Without departing from the spirit and scope of the inventive concept, variations and advantages that occur to those skilled in the art are included in the present invention. The scope of protection results from the appended claims.

The diphenyldiselenide compounds can be found by referring to the literature (J. Org. Chem., 2001. 66. 2429; Appl. Organometal. Chem., 2014, 28, 652; Catal. Sci. Technol., 2016, 6, 1804) be synthesized by the reaction of Grignard reagent with selenium powder. In a glove box, 25 mL THF solution of 0.5 mol/L 3,5-bis(trifluoromethyl)phenylmagnesium bromide was measured, and 0.95 g selenium powder was gradually added with constant stirring over about 30 minutes; the reaction was continued for 1 hour. At the end of the reaction, 40 mL of aqueous solution of 1 mol/L hydrochloric acid was added for hydrolysis while providing an ice water bath to avoid the reaction temperature rise. 25mL ether was used three times for extraction. The extracted organic phase was dehydrated by adding anhydrous magnesium sulfate and oxidized in air at room temperature for 24 hours. The solvent was spun dry to obtain the diphenyl diselenide catalyst (78% yield).

example 1

In a three-necked flask were added N-hydroxyphthalimide (NHPI, 75 mg, 0.45 mmol), azobis(isobutyronitrile) (AIBN, 38 mg, 0.23 mmol), diphenylmethanol (1104 mg, 6 mmol), cyclohexanone (392 mg, 4th mmol) and ethyl acetate (AcOEt, 1.5 mL) and the gas (pure oxygen) was pumped around three times. The reaction was carried out at 75°C for 8 hours. The temperature of the reaction solution was lowered to 30°C. 1,2-Bis(3,5-di(trifluoromethyl)phenyl)diselenide (Se-Cat1, 70 mg, 0.12 mmol) and trifluoroethanol (TFE, 15 mL) were added and the reaction was continued for 6 hours to 3a 99% (gas phase yield, with biphenyl as internal standard) and 4 99% (gas phase yield, with biphenyl as internal standard). ε-Caprolactone product was separated. The reaction mother liquor was distilled under reduced pressure to remove the solvent. Then, 20 mL of ether was added to dissolve, followed by extraction with water as an extractant (10 mL×3). The aqueous phase was dried by rotary evaporation. 419 mg (92%) ε-caprolactone product with a purity of 97% was obtained.

Characterization of 4 (ε-caprolactone): MS (EI): m/z (%) 114 (M ⁺ , 15.4), 55 (100); ¹ H-NMR (500MHz, CDC1 ₃ ): 4.26-4.18 (m, 2H), 2.69-2.60 (m, 2H), 1.95-1.70 (m, 6H) ; ¹³ C NMR (125MHz, CDC1 ₃ ): 176.0, 69.3, 34.7, 29.3, 28.9, 23.1.

example 2

In a three-necked flask were added N-hydroxyphthalimide (NHPI, 75 mg, 0.45 mmol), azobis(isobutyronitrile) (AIBN, 38 mg, 0.23 mmol), 4,4'-dimethyldiphenylmethanol (1272 mg, 6 mmol), cyclohexanone (392 mg, 4 mmol) and ethyl acetate (AcOEt, 1.5 mL) and the gas (pure oxygen) was pumped around three times. The reaction was carried out at 75°C for 8 hours. The temperature of the reaction solution was lowered to 30°C. 1,2-Bis(3,5-di(trifluoromethyl)phenyl)diselenide (Se-Cat1, 70 mg, 0.12 mmol) and trifluoroethanol (TFE, 15 mL) were added. The reaction was continued for 6 hours to give 3b 99% (gas phase yield, with biphenyl as internal standard) and 4 99% (gas phase yield, with biphenyl as internal standard).

Example 3

In a three-necked flask were added N-hydroxyphthalimide (NHPI, 75 mg, 0.45 mmol), azobis(isobutyronitrile) (AIBN, 38 mg, 0.23 mmol), 4,4'-di-n-propyl-diphenylmethanol (1608 mg , 6 mmol), cyclohexanone (392 mg, 4 mmol) and ethyl acetate (AcOEt, 1.5 mL) and the gas (pure oxygen) was pumped three times. The reaction was carried out at 75°C for 8 hours. The temperature of the reaction solution was lowered to 30°C. 1,2-Bis(3,5-di(trifluoromethyl)phenyl)diselenide (Se-Cat1, 70 mg, 0.12 mmol) and trifluoroethanol (TFE, 15 mL) were added. The reaction was continued for 6 hours to give 3c 99% (gas phase yield, with biphenyl as internal standard) and 4 99% (gas phase yield, with biphenyl as internal standard).

example 4

In a three-necked flask were added N-hydroxyphthalimide (NHPI, 75 mg, 0.45 mmol), azobis(isobutyronitrile) (AIBN, 38 mg, 0.23 mmol), 4-n-propyldiphenylmethanol (1356 mg, 6 mmol), cyclohexanone ( 392 mg, 4 mmol) and ethyl acetate (AcOEt, 1.5 mL) and the gas (pure oxygen) was pumped around three times. The reaction was carried out at 75°C for 8 hours. The temperature of the reaction solution was lowered to 30°C. 1,2-Di(3,5-di(trifluoromethyl)phenyl)diselenide (Se-Cat1, 70 mg, 0.12 mmol) and trifluoroethanol (TFE, 15 mL) were added. The reaction was continued for 6 hours to give 3d 99% (gas phase yield, with biphenyl as internal standard) and 4 99% (gas phase yield, with biphenyl as internal standard).

Example 5

In a three-necked flask were added N-hydroxyphthalimide (NHPI, 75 mg, 0.45 mmol), azobis(isobutyronitrile) (AIBN, 38 mg, 0.23 mmol), 4-phenylmethyldiphenylmethanol (1644 mg, 6 mmol), cyclohexanone (392 mg , 4 mmol) and ethyl acetate (AcOEt, 1.5 mL) and the gas (pure oxygen) was pumped around three times. The reaction was carried out at 75°C for 8 hours. The temperature of the reaction solution was lowered to 30°C. 1,2-Bis(3,5-di(trifluoromethyl)phenyl)diselenide (Se-Cat1, 70 mg, 0.12 mmol) and trifluoroethanol (TFE, 15 mL) were added. The reaction was continued for 6 hours to give 3e 99% (gas phase yield, with biphenyl as internal standard), 4 99% (gas phase yield, with biphenyl as internal standard).

Example 6

In a three-necked flask were added N-hydroxyphthalimide (NHPI, 75 mg, 0.45 mmol), azobis(isobutyronitrile) (AIBN, 38 mg, 0.23 mmol), diphenylmethanol (1104 mg, 6 mmol), cyclohexanone (392 mg, 4th mmol) and ethyl acetate (AcOEt, 1.5 mL) and the gas (pure oxygen) was pumped around three times. The reaction was carried out at 75°C for 8 hours. The temperature of the reaction solution was lowered to 30°C. 1,2-Bis(2,4-di(trifluoromethyl)phenyl)diselenide (Se-Cat2, 70 mg, 0.12 mmol) and trifluoroethanol (TFE, 15 mL) were added. The reaction was continued for 6 hours to give 3a 99% (gas phase yield, with biphenyl as internal standard) and 4 46% (gas phase yield, with biphenyl as internal standard).

Example 7

In a three-necked flask were added N-hydroxyphthalimide (NHPI, 75 mg, 0.45 mmol), azobis(isobutyronitrile) (AIBN, 38 mg, 0.23 mmol), diphenylmethanol (1104 mg, 6 mmol), cyclohexanone (392 mg, 4th mmol) and ethyl acetate (AcOEt, 1.5 mL) and the gas (pure oxygen) was pumped around three times. The reaction was carried out at 75°C for 8 hours. The temperature of the reaction solution was lowered to 30°C. 1,2-Bis(3-trifluoromethylphenyl)diselenide (Se-Cat3, 54 mg, 0.12 mmol) and trifluoroethanol (TFE, 15 mL) were added. The reaction was continued for 6 hours to give 3a 99% (gas phase yield, with biphenyl as internal standard) and 4 83% (gas phase yield, with biphenyl as internal standard).

example 8

In a three-necked flask were added N-hydroxyphthalimide (NHPI, 75 mg, 0.45 mmol), azobis(isobutyronitrile) (AIBN, 38 mg, 0.23 mmol), diphenylmethanol (1104 mg, 6 mmol), cyclohexanone (392 mg, 4th mmol) and ethyl acetate (AcOEt, 1.5 mL) and the gas (pure oxygen) was pumped around three times. The reaction was carried out at 75°C for 8 hours. The temperature of the reaction solution was lowered to 30°C. 1,2-Bis(2-trifluoromethylphenyl)diselenide (Se-Cat4, 54 mg, 0.12 mmol) and trifluoroethanol (TFE, 15 mL) were added. The reaction was continued for 6 hours to give 3a 99% (gas phase yield, with biphenyl as internal standard) and 4 62% (gas phase yield, with biphenyl as internal standard).

example 9

In a three-necked flask were added N-hydroxyphthalimide (NHPI, 150 mg, 0.9 mmol), azobis(isobutyronitrile) (AIBN, 75 mg, 0.45 mmol), diphenylmethanol (2208 mg, 12 mmol), cyclohexanone (392 mg, 4th mmol) and ethyl acetate (AcOEt, 1.5 mL) and the gas (pure oxygen) was pumped around three times. The reaction was carried out at 75°C for 8 hours. The temperature of the reaction solution was lowered to 30°C. 1,2-Bis(3,5-di(trifluoromethyl)phenyl)diselenide (Se-Cat1, 70 mg, 0.12 mmol) and trifluoroethanol (TFE, 15 mL) were added. The reaction was continued for 6 hours to give 3a 89% (gas phase yield, with biphenyl as internal standard) and 4 99% (gas phase yield, with biphenyl as internal standard).

Example 10

In a three-necked flask were added N-hydroxyphthalimide (NHPI, 49 mg, 0.3 mmol), azobis(isobutyronitrile) (AIBN, 25 mg, 0.15 mmol), diphenylmethanol (1104 mg, 6 mmol), cyclohexanone (392 mg, 4th mmol) and ethyl acetate (AcOEt, 1.5 mL) and the gas (pure oxygen) was pumped around three times. The reaction was carried out at 75°C for 8 hours. The temperature of the reaction solution was lowered to 30°C. 1,2-Bis(3,5-di(trifluoromethyl)phenyl)diselenide (Se-Cat1, 70 mg, 0.12 mmol) and trifluoroethanol (TFE, 15 mL) were added. The reaction was continued for 6 hours to 3a 92% (vap yield, with biphenyl as internal standard) and 4 91% (gas phase yield, with biphenyl as internal standard).

Example 11

In a three-necked flask were added N-hydroxyphthalimide (NHPI, 33 mg, 0.2 mmol), azobis(isobutyronitrile) (AIBN, 16 mg, 0.1 mmol), diphenylmethanol (1104 mg, 6 mmol), cyclohexanone (392 mg, 4th mmol) and ethyl acetate (AcOEt, 1.5 mL) and the gas (pure oxygen) was pumped around three times. The reaction was carried out at 75°C for 8 hours. The temperature of the reaction solution was lowered to 30°C. 1,2-Bis(3,5-di(trifluoromethyl)phenyl)diselenide (Se-Cat1, 70 mg, 0.12 mmol) and trifluoroethanol (TFE, 15 mL) were added. The reaction was continued for 6 hours to give 3a 82% (gas phase yield, with biphenyl as internal standard) and 4 75% (gas phase yield, with biphenyl as internal standard).

Example 12

In a three-necked flask were added N-hydroxyphthalimide (NHPI, 16 mg, 0.1 mmol), azobis(isobutyronitrile) (AIBN, 8 mg, 0.05 mmol), diphenylmethanol (1104 mg, 6 mmol), cyclohexanone (392 mg, 4th mmol) and ethyl acetate (AcOEt, 1.5 mL) and the gas (pure oxygen) was pumped around three times. The reaction was carried out at 75°C for 8 hours. The temperature of the reaction solution was lowered to 30°C. 1,2-Bis(3,5-di(trifluoromethyl)phenyl)diselenide (Se-Cat1, 70 mg, 0.12 mmol) and trifluoroethanol (TFE, 15 mL) were added. The reaction was continued for 6 hours to give 3a 60% (gas phase yield, with biphenyl as internal standard) and 4 51% (gas phase yield, with biphenyl as internal standard).

Example 13

In a three-necked flask were added N-hydroxyphthalimide (NHPI, 73 mg, 0.45 mmol), azobis(isobutyronitrile) (AIBN, 19 mg, 0.12 mmol), diphenylmethanol (1104 mg, 6 mmol), cyclohexanone (392 mg, 4th mmol) and ethyl acetate (AcOEt, 1.5 mL) and the gas (pure oxygen) was pumped around three times. The reaction was carried out at 75°C for 8 hours. The temperature of the reaction solution was lowered to 30°C. 1,2-Bis(3,5-di(trifluoromethyl)phenyl)diselenide (Se-Cat1, 70 mg, 0.12 mmol) and trifluoroethanol (TFE, 15 mL) were added. The reaction was continued for 6 hours to give 3a 99% (gas phase yield, with biphenyl as internal standard) and 4 90% (gas phase yield, with biphenyl as internal standard).

Example 14

In a three-necked flask were added N-hydroxyphthalimide (NHPI, 73 mg, 0.45 mmol), azobis(isobutyronitrile) (AIBN, 74 mg, 0.45 mmol), diphenylmethanol (1104 mg, 6 mmol), cyclohexanone (392 mg, 4th mmol) and ethyl acetate (AcOEt, 1.5 mL) and the gas (pure oxygen) was pumped around three times. The reaction was carried out at 75°C for 8 hours. The temperature of the reaction solution was lowered to 30°C. 1,2-Bis(3,5-di(trifluoromethyl)phenyl)diselenide (Se-Cat1, 70 mg, 0.12 mmol) and trifluoroethanol (TFE, 15 mL) were added. The reaction was continued for 6 hours to give 3a 99% (gas phase yield, with biphenyl as internal standard) and 4 96% (gas phase yield, with biphenyl as internal standard).

Example 15

In a three-necked flask were added N-hydroxyphthalimide (NHPI, 75 mg, 0.45 mmol), azobis(isobutyronitrile) (AIBN, 38 mg, 0.23 mmol), diphenylmethanol (1104 mg, 6 mmol), cyclohexanone (392 mg, 4th mmol) and ethyl acetate (AcOEt, 1.5 mL) and the gas (pure oxygen) was pumped around three times. The reaction was carried out at 75°C for 8 hours. The temperature of the reaction solution was lowered to 30°C. 1,2-Bis(3,5-di(trifluoromethyl)phenyl)diselenide (Se-Cat1, 35 mg, 0.06 mmol) and trifluoroethanol (TFE, 15 mL) were added. The reaction was continued for 6 hours to give 3a 99% (gas phase yield, with biphenyl as internal standard) and 4 81% (gas phase yield, with biphenyl as internal standard).

Example 16

In a three-necked flask were added N-hydroxyphthalimide (NHPI, 73 mg, 0.45 mmol), azobis(isobutyronitrile) (AIBN, 38 mg, 0.23 mmol), diphenylmethanol (1104 mg, 6 mmol), cyclohexanone (392 mg, 4th mmol) and ethyl acetate (AcOEt, 1.5 mL) and the gas (pure oxygen) was pumped around three times. The reaction was carried out at 75°C for 8 hours. The temperature of the reaction solution was lowered to 30°C. 1,2-Bis(3,5-di(trifluoromethyl)phenyl)diselenide (Se-Cat1, 140 mg, 0.24 mmol) and trifluoroethanol (TFE, 15 mL) were added. The reaction was continued for 6 hours to give 3a 99% (gas phase yield, with biphenyl as internal standard) and 4 99% (gas phase yield, with biphenyl as internal standard).

Example 17

In a three-necked flask were added N-hydroxyphthalimide (NHPI, 75 mg, 0.45 mmol), azobis(isobutyronitrile) (AIBN, 38 mg, 0.23 mmol), diphenylmethanol (1104 mg, 6 mmol), cyclohexanone (392 mg, 4th mmol) and acetonitrile (MeCN, 1.5 mL) and the gas (pure oxygen) was pumped around three times. The reaction was carried out at 75°C for 8 hours. The temperature of the reaction solution was lowered to 30°C. 1,2-Bis(3,5-di(trifluoromethyl)phenyl)diselenide (Se-Cat1, 75 mg, 0.12 mmol) and trifluoroethanol (TFE, 15 mL) were added. The reaction was continued for 6 hours to give 3a 99% (gas phase yield, with biphenyl as internal standard) and 4 85% (gas phase yield, with biphenyl as internal standard).

Example 18

In a three-necked flask were added N-hydroxyphthalimide (NHPI, 75 mg, 0.45 mmol), azobis(isobutyronitrile) (AIBN, 38 mg, 0.23 mmol), diphenylmethanol (1104 mg, 6 mmol), cyclohexanone (392 mg, 4th mmol) and chlorobenzene (PhCl, 1.5 mL) and the gas (pure oxygen) was pumped around three times. The reaction was carried out at 75°C for 8 hours. The temperature of the reaction solution was lowered to 30°C. 1,2-Bis(3,5-di(trifluoromethyl)phenyl)diselenide (Se-Cat1, 75 mg, 0.12 mmol) and trifluoroethanol (TFE, 15 mL) were added. The reaction was continued for 6 hours to give 3a 99% (gas phase yield, with biphenyl as internal standard) and 4 95% (gas phase yield, with biphenyl as internal standard).

Example 19

In a three-necked flask were added N-hydroxyphthalimide (NHPI, 75 mg, 0.45 mmol), azobis(isobutyronitrile) (AIBN, 38 mg, 0.23 mmol), diphenylmethanol (1104 mg, 6 mmol), cyclohexanone (392 mg, 4th mmol) and n-butyl acetate (AcOBu ⁿ , 1.5 mL) and the gas (pure oxygen) was pumped three times. The reaction was carried out at 75°C for 8 hours. The temperature of the reaction solution was lowered to 30°C. 1,2-Di(3,5-di(trifluoromethyl)phenyl)diselenide (Se-Cat1, 75 mg, 0.12 mmol) and trifluoroethanol (TFE, 15 mL) were added. The reaction was continued for 6 hours to give 3a 99% (gas phase yield, with biphenyl as internal standard) and 4 98% (gas phase yield, with biphenyl as internal standard).

Example 20

In a three-necked flask were added N-hydroxyphthalimide (NHPI, 73 mg, 0.45 mmol), azobis(isobutyronitrile) (AIBN, 38 mg, 0.23 mmol), diphenylmethanol (1104 mg, 6 mmol), cyclohexanone (392 mg, 4th mmol) and n-propyl acetate (AcOPr", 1.5 mL), and the gas (pure oxygen) was pumped three times. The reaction was carried out at 75°C for 8 hours. The temperature of the reaction solution was lowered to 30°C 1,2-Di(3,5-di(trifluoromethyl)phenyl)diselenide (Se-Cat1, 70 mg, 0.12 mmol) and trifluoroethanol (TFE, 15 mL) were added The reaction was continued for 6 hours. to give 3a 99% (gas phase yield, with biphenyl as internal standard) and 4 99% (gas phase yield, with biphenyl as internal standard).

Example 21

In a three-necked flask were added N-hydroxyphthalimide (NHPI, 73 mg, 0.45 mmol), azobis(isobutyronitrile) (AIBN, 38 mg, 0.23 mmol), diphenylmethanol (1104 mg, 6 mmol), cyclohexanone (392 mg, 4th mmol) and isobutyl acetate (AcOBu ⁱ , 1.5 ml) and the gas (pure oxygen) was pumped around three times. The reaction was carried out at 75°C for 8 hours. The temperature of the reaction solution was lowered to 30°C. 1,2-Di(3,5-di(trifluoromethyl)phenyl)diselenide (Se-Cat1, 70 mg, 0.12 mmol) and trifluoroethanol (TFE, 15 mL) were added. The reaction was continued for 6 hours to give 3a 99% (gas phase yield, with biphenyl as internal standard) and 4 98% (gas phase yield, with biphenyl as internal standard).

Example 22

In a three-necked flask were added N-hydroxyphthalimide (NHPI, 73 mg, 0.45 mmol), azobis(isobutyronitrile) (AIBN, 38 mg, 0.23 mmol), diphenylmethanol (1104 mg, 6 mmol), cyclohexanone (392 mg, 4th mmol) and ethyl acetate (AcOEt, 1.5 mL) and the gas (pure oxygen) was pumped around three times. The reaction was carried out at 75°C for 8 hours. The temperature of the reaction solution was lowered to 30°C. 1,2-Bis(3,5-bis(trifluoromethyl)phenyl)diselenide (Se-Cat1, 70 mg, 0.12 mmol) and 2,2-difluoroethanol (DFE, 15 mL) were added. The reaction was continued for 6 hours to give 3a 99% (gas phase yield, with biphenyl as internal standard) and 4 45% (gas phase yield, with biphenyl as internal standard).

Example 23

In a three-necked flask were added N-hydroxyphthalimide (NHPI, 73 mg, 0.45 mmol), azobis(isobutyronitrile) (AIBN, 38 mg, 0.23 mmol), diphenylmethanol (1104 mg, 6 mmol), cyclohexanone (392 mg, 4th mmol) and ethyl acetate (AcOEt, 1.5 mL) and the gas (pure oxygen) was pumped around three times. The reaction was carried out at 75°C for 8 hours. The temperature of the reaction solution was lowered to 30°C. 1,2-Bis(3,5-di(trifluoromethyl)phenyl)diselenide (Se-Cat1, 70 mg, 0.12 mmol) and hexafluoroisopropanol (HFIP, 15 mL) were added. The reaction was continued for 6 hours to give 3a 99% (gas phase yield, with biphenyl as internal standard) and 4 99% (gas phase yield, with biphenyl as internal standard).

Example 24

In a three-necked flask were added N-hydroxyphthalimide (NHPI, 73 mg, 0.45 mmol), azobis(isobutyronitrile) (AIBN, 38 mg, 0.23 mmol), diphenylmethanol (1104 mg, 6 mmol), cyclohexanone (392 mg, 4th mmol) and ethyl acetate (AcOEt, 1.5 mL) and the gas (pure oxygen) was pumped around three times. The reaction was carried out at 75°C for 8 hours. The temperature of the reaction solution was lowered to 30°C. 1,2-Bis(3,5-di(trifluoromethyl)phenyl)diselenide (Se-Cat1, 70 mg, 0.12 mmol) and trichloroethanol (TCE, 15 mL) were added. The reaction was continued for 6 hours to give 3a 99% (gas phase yield, with biphenyl as internal standard) and 4 38% (gas phase yield, with biphenyl as internal standard).

Example 25

In a three-necked flask were added N-hydroxyphthalimide (NHPI, 75 mg, 0.45 mmol), azobis(isobutyronitrile) (AIBN, 38 mg, 0.23 mmol), diphenylmethanol (1104 mg, 6 mmol), cyclohexanone (392 mg, 4th mmol) and ethyl acetate (AcOEt, 1.5 mL) and the gas (standard air) was pumped around three times. The reaction was carried out at 75°C for 8 hours. The temperature of the reaction solution was lowered to 30°C. 1,2-Bis(3,5-di(trifluoromethyl)phenyl)diselenide (Se-Cat1, 75 mg, 0.12 mmol) and trifluoroethanol (TFE, 15 mL) were added. The reaction was continued for 6 hours to give 3a 79% (gas phase yield, with biphenyl as internal standard) and 4 63% (gas phase yield, with biphenyl as internal standard).

Example 26

In a three-necked flask were added N-hydroxyphthalimide (NHPI, 75 mg, 0.45 mmol), azobis(isobutyronitrile) (AIBN, 38 mg, 0.23 mmol), diphenylmethanol (1104 mg, 6 mmol), cyclohexanone (392 mg, 4th mmol) and ethyl acetate (AcOEt, 1.5 mL) and the gas (pure oxygen) was pumped around three times. The reaction was carried out at 65°C for 8 hours. The temperature of the reaction solution was lowered to 30°C. 1,2-Bis(3,5-di(trifluoromethyl)phenyl)diselenide (Se-Cat1, 75 mg, 0.12 mmol) and trifluoroethanol (TFE, 15 mL) were added. The reaction was continued for 6 hours to give 3a 83% (gas phase yield, with biphenyl as internal standard) and 4 88% (gas phase yield, with biphenyl as internal standard).

Example 27

In a three-necked flask were added N-hydroxyphthalimide (NHPI, 75 mg, 0.45 mmol), azobis(isobutyronitrile) (AIBN, 38 mg, 0.23 mmol), diphenylmethanol (1104 mg, 6 mmol), cyclohexanone (392 mg, 4th mmol) and ethyl acetate (AcOEt, 1.5 mL) and the gas (pure oxygen) was pumped around three times. The reaction was carried out at 75°C for 8 hours. The temperature of the reaction solution was lowered to 45°C. 1,2-Bis(3,5-di(trifluoromethyl)phenyl)diselenide (Se-Cat1, 75 mg, 0.12 mmol) and trifluoroethanol (TFE, 15 mL) were added. The reaction was continued for 6 hours to give 3a 99% (gas phase yield, with biphenyl as internal standard) and 4 92% (gas phase yield, with biphenyl as internal standard).

Example 28

In a three-necked flask were added N-hydroxyphthalimide (NHPI, 75 mg, 0.45 mmol), azobis(isobutyronitrile) (AIBN, 38 mg, 0.23 mmol), diphenylmethanol (1104 mg, 6 mmol), cyclohexanone (392 mg, 4th mmol) and ethyl acetate (AcOEt, 1.5 mL) and the gas (pure oxygen) was pumped around three times. The reaction was carried out at 75°C for 10 hours. The temperature of the reaction solution was lowered to 30°C. 1,2-Bis(3,5-di(trifluoromethyl)phenyl)diselenide (Se-Cat1, 75 mg, 0.12 mmol) and trifluoroethanol (TFE, 15 mL) were added. The reaction was continued for 6 hours to give 3a 99% (gas phase yield, with biphenyl as internal standard) and 4 78% (gas phase yield, with biphenyl as internal standard).

Example 29

In a three-necked flask were added N-hydroxyphthalimide (NHPI, 75 mg, 0.45 mmol), azobis(isobutyronitrile) (AIBN, 38 mg, 0.23 mmol), diphenylmethanol (1104 mg, 6 mmol), cyclohexanone (392 mg, 4th mmol) and ethyl acetate (AcOEt, 1.5 mL) and the gas (pure oxygen) was pumped around three times. The reaction was carried out at 75°C for 8 hours. The temperature of the reaction solution was lowered to 30°C. 1,2-Bis(3,5-di(trifluoromethyl)phenyl)diselenide (Se-Cat1, 75 mg, 0.12 mmol) and trifluoroethanol (TFE, 15 mL) were added. The reaction was continued for 3 hours to give 3a 99% (gas phase yield, with biphenyl as internal standard) and 4 90% (gas phase yield, with biphenyl as internal standard).

Example 30

In a three-necked flask were added N-hydroxyphthalimide (NHPI, 75 mg, 0.45 mmol), azobis(isobutyronitrile) (AIBN, 38 mg, 0.23 mmol), diphenylmethanol (1104 mg, 6 mmol), cyclohexanone (392 mg, 4th mmol) and ethyl acetate (AcOEt, 1.5 mL) and the gas (pure oxygen) was pumped around three times. The reaction was carried out at 75°C for 8 hours. The temperature of the reaction solution was lowered to 30°C. 1,2-Bis(3,5-di(trifluoromethyl)phenyl)diselenide (Se-Cat1, 75 mg, 0.12 mmol) and trifluoroethanol (TFE, 15 mL) were added. The reaction was continued for 8 hours to give 3a 99% (gas phase yield, with biphenyl as internal standard) and 4 95% (gas phase yield, with biphenyl as internal standard).

Example 31

In a three-necked flask were added N-hydroxyphthalimide (NHPI, 75 mg, 0.45 mmol), azobis(isobutyronitrile) (AIBN, 38 mg, 0.23 mmol), diphenylmethanol (1104 mg, 6 mmol), cyclohexanone (392 mg, 4th mmol) and ethyl acetate (AcOEt, 1.5 mL) and the gas (pure oxygen) was pumped around three times. The reaction was carried out at 75°C for 8 hours. The temperature of the reaction solution was lowered to 30°C. 1,2-Bis(3,5-di(trifluoromethyl)phenyl)diselenide (Se-Cat1, 75 mg, 0.12 mmol) and trifluoroethanol (TFE, 11.25 mL) were added. The reaction was continued for 6 hours to give 3a 99% (gas phase yield, with biphenyl as internal standard) and 4 89% (gas phase yield, with biphenyl as internal standard).

Example 32

In a three-necked flask were added N-hydroxyphthalimide (NHPI, 75 mg, 0.45 mmol), azobis(isobutyronitrile) (AIBN, 38 mg, 0.23 mmol), diphenylmethanol (1104 mg, 6 mmol), cyclohexanone (392 mg, 4th mmol) and ethyl acetate (AcOEt, 1.5 mL) and the gas (pure oxygen) was pumped around three times. The reaction was carried out at 75°C for 8 hours. The temperature of the reaction solution was lowered to 30°C. 1,2-Bis(3,5-di(trifluoromethyl)phenyl)diselenide (Se-Cat1, 75 mg, 0.12 mmol) and trifluoroethanol (TFE, 18.75 mL) were added. The reaction was continued for 6 hours to give 3a 99% (gas phase yield, with biphenyl as internal standard) and 4 99% (gas phase yield, with biphenyl as internal standard).

Example 33

In a three-necked flask were added N-hydroxysuccinimide (NHS, 52 mg, 0.45 mmol), azobis(isobutyronitrile) (AIBN, 38 mg, 0.23 mmol), diphenylmethanol (1104 mg, 6 mmol), cyclohexanone (392 mg, 4th mmol) and ethyl acetate (AcOEt, 1.5 mL) and the gas (pure oxygen) was pumped around three times. The reaction was carried out at 75°C for 8 hours. The temperature of the reaction solution was lowered to 30°C. 1,2-Di(3,5-di(trifluoromethyl)phenyl)diselenide (Se-Cat1, 70 mg, 0.12 mmol) and trifluoroethanol (TFE, 15 mL) were added. The reaction was continued for 6 hours to give 3a 99% (gas phase yield, with biphenyl as internal standard) and 4 85% (gas phase yield, with biphenyl as internal standard).

Example 34

To a three-necked flask were added 2-hydroxy-1H-pyrrolo[3,4c]pyridine-1,3-2H-dione (NHQI, 75 mg, 0.45 mmol), azobis(isobutyronitrile) (AIBN, 38 mg, 0. 23 mmol), diphenylmethanol (1104 mg, 6 mmol), cyclohexanone (392 mg, 4 mmol) and ethyl acetate (AcOEt , 1.5 mL) and the gas (pure oxygen) was pumped around three times. The reaction was carried out at 75°C for 8 hours. The temperature of the reaction solution was lowered to 30°C. 1,2-Bis(3,5-di(trifluoromethyl)phenyl)diselenide (Se-Cat1, 70 mg, 0.12 mmol) and trifluoroethanol (TFE, 15 mL) were added. The reaction was continued for 6 hours to give 3a 99% (gas phase yield, with biphenyl as internal standard) and 4 92% (gas phase yield, with biphenyl as internal standard).

Example 35

In a three-necked flask were added 1-hydroxypiperidine-2,6-dione (HPD, 58 mg, 0.45 mmol), azobis(isobutyronitrile) (AIBN, 38 mg, 0.23 mmol), diphenylmethanol (1104 mg, 6 mmol), Cyclohexanone (392 mg, 4 mmol) and ethyl acetate (AcOEt, 1.5 mL) were added and the gas (pure oxygen) was pumped around three times. The reaction was carried out at 75°C for 8 hours. The temperature of the reaction solution was lowered to 30°C. 1,2-Bis(3,5-di(trifluoromethyl)phenyl)diselenide (Se-Cat1, 70 mg, 0.12 mmol) and trifluoroethanol (TFE, 15 mL) were added. The reaction was continued for 6 hours to give 3a 99% (gas phase yield, with biphenyl as internal standard) and 4 90% (gas phase yield, with biphenyl as internal standard).

Example 36

In a three-necked flask were added 2-hydroxyisoquinoline-1,3(2H,4H)-dione (HQD, 80 mg, 0.45 mmol), azobis(isobutyronitrile) (AIBN, 38 mg, 0.23 mmol), diphenylmethanol (1104 mg , 6 mmol), cyclohexanone (392 mg, 4 mmol) and ethyl acetate (AcOEt, 1.5 mL) and the gas (pure oxygen) was pumped around three times. The reaction was carried out at 75°C for 8 hours. The temperature of the reaction solution was lowered to 30°C. 1,2-Bis(3,5-di(trifluoromethyl)phenyl)diselenide (Se-Cat1, 70 mg, 0.12 mmol) and trifluoroethanol (TFE, 15 mL) were added. The reaction was continued for 6 hours to give 3a 99% (gas phase yield, with biphenyl as internal standard) and 4 93% (gas phase yield, with biphenyl as internal standard).

QUOTES INCLUDED IN DESCRIPTION

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Patent Literature Cited

• US6229023B1 [0002]

Claims (12)

Process for the production of ε-caprolactone using in situ peroxide, characterized in that first the peroxide obtained by the oxidation reaction of a sacrificial alcohol is reacted in situ with cyclohexanone in the presence of a catalyst, an organic solvent and oxygen to form a cyclohexanone peroxide intermediate which then undergoes a decomposition reaction to yield the ε-caprolactone product, the structure of the sacrificial alcohol being represented by the following formula:

wherein R ₁ and R ₂ are independently selected from H, straight or branched C ₁ -C ₁₀ alkyl groups, aryl groups, or aryl-substituted straight or branched C ₁ -C ₁₀ alkyl groups. Process for the production of ε-caprolactone using in situ peroxide claim 1 , characterized in that the reaction is carried out in two steps, wherein the catalysts used are each a first and a second catalyst and the organic solvents used are each a first and a second organic solvent, the two steps of the process comprising: (1 ) a first step, the preparation of the intermediate cyclohexanone peroxide, in which the sacrificial alcohol and cyclohexanone are reacted with the oxygen in the presence of the first catalyst and the first organic solvent to form an intermediate reaction solution; (2) a second step, the decomposition of cyclohexanone peroxide, in which a second catalyst and a second organic solvent are added to the intermediate reaction solution obtained in the first step to proceed the reaction and obtain the ε-caprolactone product. Process for the production of ε-caprolactone using in situ peroxide claim 2 , characterized in that the first catalyst is a mixture of an organic nitroxide radical catalyst precursor and azobis(isobutyronitrile), wherein the organic nitroxide radical catalyst precursor is selected from nitrogen-containing cyclic compounds of the following formulas (I-1), (I-2), (I -3) or (I-4) is selected

wherein in the formulas (I-1), (I-2), (I-3) or (I-4), R ₃ to R ₁₂ are independently selected from hydrogen atom, alkyl groups, cycloalkyl groups, aryl groups, heterocycles, hydroxy group, nitro group or halogens, or where in formula (I-1), R ₃ and R ₄ form a ring, or where in formula (I-2), R ₅ and R ₆ form a ring or wherein in formula (I-3), at least two of R ₇ , R ₈ and R ₉ form a ring, or wherein in formula (I-4) at least two of R ₁₀ , R ₁₁ and R ₁₂ form a ring form. Process for the production of ε-caprolactone using in situ peroxide claim 3 , characterized in that the organic nitroxide radical catalyst precursor is any one of the compounds (a) to (i).

Process for the production of ε-caprolactone using in situ peroxide claim 3 or 4 characterized in that the molar ratio of the organic nitroxide radical catalyst precursor and azobis(isobutyronitrile) is 1:0.4 to 1. Process for the production of ε-caprolactone using in situ peroxide claim 2 , characterized in that the second catalyst is a diphenyldiselenide compound having the following structural formula

where R is one or two trifluoromethyl groups. Process for the production of ε-caprolactone using in situ peroxide claim 2 , characterized in that the molar ratio of the sacrificial alcohol, the cyclohexanone and the second catalyst is 150 to 300:100:1 to 10. Process for the production of ε-caprolactone using in situ peroxide claim 2 , characterized in that the molar ratio of the sacrificial alcohol, the cyclohexanone, the first catalyst and the second catalyst is 150 to 300:100:1 to 10:1 to 10. Process for the production of ε-caprolactone using in situ peroxide claim 2 , characterized in that the molar ratio of the sacrificial alcohol, the cyclohexanone, the first catalyst and the second catalyst is 150-300:100:5-50:1-10. Process for the production of ε-caprolactone using in situ peroxide claim 2 characterized in that the first organic solvent is one or more of ethyl acetate, chlorobenzene, acetonitrile, benzonitrile, n-butyl acetate and the second organic solvent is trifluoroethanol. Process for the production of ε-caprolactone using in situ peroxide claim 2 , characterized in that the mass ratio of the sacrificial alcohol, the cyclohexanone, the first organic solvent and the second organic solvent is 2 to 4: 1: 1 to 3: 10 to 50. Process for the production of ε-caprolactone using in situ peroxide claim 2 , characterized in that the first step has a reaction temperature of 65°C to 100°C and a reaction time of 6 to 10 hours, and the second step has a reaction temperature of 25°C to 60°C and a reaction time of 3 to 12 hours having.