How ketones are produced

Abstract

The present invention relates to a novel process for preparing a compound of formula (II) by reacting a compound of formula (I) with hydrogen peroxide in the presence of a solvent, in the presence of a catalyst, in the presence of a buffer and optionally in the presence of a base. TIFF2025509893000008.tif53161

Description

[Technical field]

[0001] The present invention relates to a novel process for producing ketones by oxidation of alcohols with hydrogen peroxide. [Background technology]

[0002] Ketones are used inter alia as starting materials for preparing hydantoins, which are likewise important intermediates in the production of pesticides (eg WO2006 / 089633).

[0003] The preparation of ketones by oxidation of alcohols can be achieved by various methods that have been known for a long time. In Chem.Com.2003, 16, 1977, JACS, 1997, 119, 12386 and Bull.Soc.Japan, 72(10), 1999, 2287-2306, ketones are prepared by reacting alcohols with hydrogen peroxide as an oxidizing agent, sodium tungstate dihydrate as a catalyst, and optionally a hydrogen sulfate-based phase transfer catalyst. However, this known oxidation of alcohols has significant drawbacks and disadvantages, especially low pH, which means that acid-labile starting compounds are not suitable for this transformation. [Prior art documents] [Patent documents]

[0004] [Patent Document 1] International Publication No. 2006 / 089633 [Non-patent literature]

[0005] [Non-Patent Document 1] Chem.Com.2003, 16, 1977 [Non-Patent Document 2] JACS, 1997, 119, 12386 [Non-Patent Document 3] Bull.Soc.Japan, 72(10), 1999, 2287-2306 Summary of the Invention [Problem to be solved by the invention]

[0006] It has been found that the reaction for the preparation of ketones can be advantageously carried out in such a way that the reaction of alcohol with hydrogen peroxide takes place in the presence of a solvent, in the presence of a catalyst, and in the presence of a buffer. A stable pH can be achieved, if necessary, by metering in a base in parallel with the metering in of hydrogen peroxide. This allows even acid-labile starting compounds to react significantly better with excellent yields. It has also been found that it is possible to prepare ketones with higher purity. The formation of secondary components is substantially minimized, and the ketones can be used directly without further purification for further reactions, for example for the preparation of hydantoins. [Means for solving the problem]

[0007] The process of the present invention for preparing compounds of formula (II) can be illustrated by the following scheme: [ka]

[0008] [In the formulas (I) and (II), R 1 and R 2 and the carbon atom to which they are attached represents a 5- or 6-membered ketal, optionally mono- or disubstituted by methyl or ethyl; R 1 and R 2 and the carbon atom to which they are attached preferably represents a 5-membered ketal. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0009] Particularly preferred is the compound of formula (I-1): 1,4-dioxaspiro[4.5]decan-8-ol [ka]

[0010] Particularly preferred is the compound of formula (II-1): 1,4-dioxaspiro[4.5]decan-8-one [ka]

[0011] Surprisingly, the process of the present invention allows the preparation of compounds of formula (II) in higher yields and with higher purity than was possible according to previously known processes. Moreover, acid-labile starting compounds are also suitable for this reaction.

[0012] Compounds of formula (I) are commercially available or can be prepared by known methods (eg WO2006 / 089633).

[0013] Scheme 1 The course of the process according to the invention is illustrated by the following reaction scheme: [ka]

[0014] The compounds of formulae (III) and (IV) are secondary components of the reaction. The formation of secondary components of formulae (III) and (IV) is substantially minimized by the process according to the invention. This minimization represents a major advantage of the process according to the invention over the processes known from the prior art.

[0015] The oxidizing agent used is hydrogen peroxide. The hydrogen peroxide used is a commercially available hydrogen peroxide having a hydrogen peroxide concentration of 10 to 70% in water. Preferably, the hydrogen peroxide has a hydrogen peroxide concentration of 50% in water.

[0016] Examples of solvents used in the reaction according to the method of the present invention are water, ketones such as acetone, methyl ethyl ketone, methyl isobutyl ketone or cyclohexanone; tert-butanol; and ethers such as diisopropyl ether, dioxane, tetrahydrofuran or 1,2-dimethoxyethane. It is preferable to use water as the solvent.

[0017] Examples of suitable catalysts are sodium tungstate, sodium tungstate dihydrate, sodium molybdate or sodium molybdate dihydrate. It is preferable to use sodium tungstate dihydrate. Likewise, it is preferable to use sodium tungstate.

[0018] Examples of suitable buffers are acetates, formates, propionates, phosphates, carbonates or alkoxides of alkali metals or alkaline earth metals, or the corresponding ammonium compounds.Preferably, sodium acetate, potassium acetate, lithium acetate, ammonium acetate, sodium formate, potassium formate, sodium propionate, potassium propionate, sodium butyrate, potassium butyrate, sodium isobutyrate or potassium isobutyrate.It is particularly preferred to use sodium acetate, ammonium acetate, lithium acetate, potassium acetate, sodium propionate, sodium butyrate or sodium isobutyrate.Also suitable are buffer mixtures, for example, of sodium acetate and acetic acid.

[0019] Control of pH during the reaction is important. The pH can be controlled using a base such as aqueous ammonia, sodium hydroxide, potassium hydroxide or lithium hydroxide. It is preferred to use sodium hydroxide for pH control.

[0020] The pH is determined using a calibrated pH electrode.

[0021] The amount of oxidizing agent used is 1-5 mol per mol of the compound of formula (I), preferably 2-4 mol per mol of the compound of formula (I), particularly preferably 2.9-3.5 mol per mol of the compound of formula (I).

[0022] The oxidizing agent is added over a specific period of time, preferably the addition is within a period of 3 to 5 hours. The oxidizing agent may be added uniformly over this period.

[0023] The catalyst is used in an amount of 0.01 to 0.2 mol per mol of the compound of formula (I), preferably 0.01 to 0.1 mol per mol of the compound of formula (I), more preferably 0.01 to 0.04 mol per mol of the compound of formula (I).

[0024] The buffer is used in an amount of 0.01 to 1 mol per mol of the compound of formula (I), preferably 0.01 to 0.5 mol per mol of the compound of formula (I), more preferably 0.05 mol per mol of the compound of formula (I).

[0025] By metering in parallel with the hydrogen peroxide, the base ensures a stable pH range. A preferred pH is considered to be a pH of 5 to 8. A pH of 5.5 to 7.5 is preferred. Particularly preferably, when the pH of the reaction mixture reaches pH 5.5, it is always raised to pH 6.5 by adding a base. The amount of base for pH control is selected to adjust the pH accordingly.

[0026] The reaction can be carried out at a temperature between 50 and 100° C. A temperature between 75 and 85° C. is preferred. A temperature of 80° C. is very particularly preferred.

[0027] In a further embodiment, the present invention relates to a process for preparing a compound of formula (II) by reacting a compound of formula (I) with hydrogen peroxide in the presence of a solvent, in the presence of a catalyst, in the presence of a buffer, and in the presence of a base.

[0028] In a further embodiment, the present invention relates to a process for preparing a compound of formula (II) by reacting a compound of formula (I) with hydrogen peroxide in the presence of a solvent, in the presence of a catalyst, in the presence of a buffer and optionally in the presence of a base, wherein the pH is between 5.5 and 7.5.

[0029] In a further embodiment, the present invention relates to a process for preparing a compound of formula (II) by reacting a compound of formula (I) with hydrogen peroxide in the presence of a solvent, in the presence of a catalyst, and in the presence of a buffer, wherein the pH is between 5.5 and 7.5.

[0030] In a further embodiment, the present invention relates to a process for preparing a compound of formula (II) by reacting a compound of formula (I) with hydrogen peroxide in water in the presence of sodium tungstate or sodium tungstate dihydrate as a catalyst, in the presence of a buffering agent, and optionally in the presence of a base, wherein the pH is between 5.5 and 7.5.

[0031] In a further embodiment, the present invention relates to a process for preparing a compound of formula (II) by reacting a compound of formula (I) with hydrogen peroxide in water in the presence of sodium tungstate dihydrate as a catalyst, in the presence of a buffering agent, and optionally in the presence of a base, wherein the pH is between 5.5 and 7.5.

[0032] In a further embodiment, the present invention relates to a process for preparing a compound of formula (II) by reacting a compound of formula (I) with hydrogen peroxide in water in the presence of sodium tungstate dihydrate as a catalyst, in the presence of sodium acetate, ammonium acetate, lithium acetate, potassium acetate, sodium propionate, sodium butyrate or sodium isobutyrate as a buffer, in the presence of sodium hydroxide as a base, wherein the pH is between 5.5 and 7.5.

[0033] In a further embodiment, the present invention relates to a process for preparing a compound of formula (II) by reacting a compound of formula (I) with hydrogen peroxide in water in the presence of sodium tungstate dihydrate as a catalyst, in the presence of sodium acetate as a buffer, and in the presence of aqueous ammonia, sodium hydroxide, potassium hydroxide or lithium hydroxide as a base, wherein the pH is between 5.5 and 7.5.

[0034] In a further embodiment, the present invention relates to a process for preparing a compound of formula (II) by reacting a compound of formula (I) with hydrogen peroxide in water in the presence of sodium tungstate dihydrate as a catalyst, in the presence of sodium acetate as a buffer, and in the presence of sodium hydroxide as a base, wherein the pH is between 5.5 and 7.5.

[0035] In a further embodiment, the present invention relates to a process for preparing a compound of formula (II) by reacting a compound of formula (I) with hydrogen peroxide in water in the presence of sodium tungstate dihydrate as a catalyst, in the presence of ammonium acetate as a buffer, and in the presence of sodium hydroxide as a base, wherein the pH is between 5.5 and 7.5.

[0036] In a further embodiment, the present invention relates to a process for preparing a compound of formula (II) by reacting a compound of formula (I) with hydrogen peroxide in water in the presence of sodium tungstate dihydrate as a catalyst, in the presence of ammonium acetate as a buffer, and in the presence of aqueous ammonia as a base, wherein the pH is between 5.5 and 7.5.

[0037] In a further embodiment, the present invention relates to a process for preparing a compound of formula (II) by reacting a compound of formula (I) with hydrogen peroxide in water in the presence of sodium tungstate dihydrate as a catalyst, in the presence of lithium acetate as a buffer, and in the presence of sodium hydroxide as a base, wherein the pH is between 5.5 and 7.5.

[0038] In a further embodiment, the present invention relates to a process for preparing a compound of formula (II) by reacting a compound of formula (I) with hydrogen peroxide in water in the presence of sodium tungstate dihydrate as a catalyst, in the presence of lithium acetate as a buffer, and in the presence of lithium hydroxide as a base, wherein the pH is between 5.5 and 7.5.

[0039] In a further embodiment, the present invention relates to a process for preparing a compound of formula (II) by reacting a compound of formula (I) with hydrogen peroxide in water in the presence of sodium tungstate dihydrate as a catalyst, in the presence of potassium acetate as a buffer, and in the presence of sodium hydroxide as a base, wherein the pH is between 5.5 and 7.5.

[0040] In a further embodiment, the present invention relates to a process for preparing a compound of formula (II) by reacting a compound of formula (I) with hydrogen peroxide in water in the presence of sodium tungstate dihydrate as a catalyst, in the presence of potassium acetate as a buffer, and in the presence of potassium hydroxide as a base, wherein the pH is between 5.5 and 7.5.

[0041] In a further embodiment, the present invention relates to a process for preparing a compound of formula (II) by reacting a compound of formula (I) with hydrogen peroxide in water in the presence of sodium tungstate dihydrate as a catalyst, in the presence of sodium propionate as a buffer, and in the presence of sodium hydroxide as a base, wherein the pH is between 5.5 and 7.5.

[0042] In a further embodiment, the present invention relates to a process for preparing a compound of formula (II) by reacting a compound of formula (I) with hydrogen peroxide in water in the presence of sodium tungstate dihydrate as a catalyst, in the presence of sodium butyrate as a buffer, and in the presence of sodium hydroxide as a base, wherein the pH is between 5.5 and 7.5.

[0043] In a further embodiment, the present invention relates to a process for preparing a compound of formula (II) by reacting a compound of formula (I) with hydrogen peroxide in water in the presence of sodium tungstate dihydrate as a catalyst, in the presence of sodium isobutyrate as a buffer, and in the presence of sodium hydroxide as a base, wherein the pH is between 5.5 and 7.5.

[0044] In a further embodiment, the present invention relates to a process for preparing a compound of formula (II) by reacting a compound of formula (I) with hydrogen peroxide in water in the presence of sodium tungstate dihydrate as a catalyst, in the presence of sodium acetate as a buffer, and in the presence of sodium hydroxide as a base, wherein 0.02-0.04 mol of sodium tungstate dihydrate per mol of compound of formula (I) and 3.3 mol of hydrogen peroxide per mol of compound of formula (I) are used, and the pH is 5.5-6.5.

[0045] In a further embodiment, the present invention relates to a process for preparing a compound of formula (II) by reacting a compound of formula (I) with hydrogen peroxide in water in the presence of sodium tungstate or sodium tungstate dihydrate as a catalyst, in the presence of sodium acetate, ammonium acetate, lithium acetate, potassium acetate, sodium propionate, sodium butyrate or sodium isobutyrate as a buffer or in the presence of sodium acetate and acetic acid as a buffer mixture, and optionally in the presence of sodium hydroxide, potassium hydroxide, lithium hydroxide or aqueous ammonia as a base, wherein the pH is between 5.5 and 7.5.

[0046] The preparation of compounds of formula (II) by the process according to the invention shall be illustrated by the following preparation examples: EXAMPLES

[0047] Working Example Example 1: Preparation of 1,4-dioxaspiro[4.5]decan-8-one A mixture of 53.7 g (93%, 0.32 mol) of 1,4-dioxaspiro[4.5]decan-8-ol, 75 g of water, 1.3 g (0.016 mol) of sodium acetate and 2.0 g (0.006 mol) of sodium tungstate dihydrate is heated to 80° C. At this temperature, 65.7 g (0.97 mol) of 50% hydrogen peroxide are metered in over a period of 5 hours. During this time, the pH of the reaction mixture is constantly raised to pH 6.5 by adding 50% sodium hydroxide solution once pH 5.5 has been reached. In addition, a further 1.0 g (0.0032 mol) of sodium tungstate is added after an addition time of 2 hours.

[0048] At the end of the metered addition, the mixture is stirred at 80° C. for a further 3 h and then cooled to room temperature. Extraction with 3 portions of 100 g methylene chloride and concentration of the combined extracts gives 44.7 g of a pale beige solid containing 85.4% 1,4-dioxaspiro[4.5]decan-8-one (II-1), 7.8% 1,4-cyclohexanedione (III) and 1.9% 4-hydroxycyclohexanone (IV) (about 77% of theory).

[0049] Example 2: Preparation of 1,4-dioxaspiro[4.5]decan-8-one A mixture of 53.7 g (93%, 0.32 mol) of 1,4-dioxaspiro[4.5]decan-8-ol, 75 g of water, 1.3 g (0.016 mol) of sodium acetate and 2.0 g (0.006 mol) of sodium tungstate dihydrate is heated to 80° C. At this temperature, 65.7 g (0.97 mol) of 50% hydrogen peroxide are metered in over a period of 5 hours. During this time, the pH of the reaction mixture is constantly raised to pH 7.0 by adding 50% sodium hydroxide solution once pH 6.0 has been reached. In addition, a further 1.0 g (0.003 mol) of sodium tungstate is added after an addition time of 2 hours.

[0050] At the end of the metered addition, the mixture is stirred at 80° C. for a further 3 h and then cooled to room temperature. Extraction with 3 portions of 100 g methylene chloride and concentration of the combined extracts gives 46.2 g of a beige-brown solid containing 82.0% 1,4-dioxaspiro[4.5]decan-8-one (II-1), 3.7% 1,4-cyclohexanedione (III) and 2.2% 4-hydroxycyclohexanone (IV) (about 77% of theory).

[0051] Example 3: Preparation of 1,4-dioxaspiro[4.5]decan-8-one A mixture of 53.7 g (93%, 0.32 mol) of 1,4-dioxaspiro[4.5]decan-8-ol, 75 g of water, 1.3 g (0.016 mol) of sodium acetate and 2.0 g (0.006 mol) of sodium tungstate dihydrate is heated to 80° C. At this temperature, 65.7 g (0.97 mol) of 50% hydrogen peroxide are metered in over a period of 5 hours. During this time, the pH of the reaction mixture is constantly raised to pH 7.5 by adding 50% sodium hydroxide solution, once pH 6.5 has been reached. In addition, a further 1.0 g (0.003 mol) of sodium tungstate is added after an addition time of 2 hours.

[0052] At the end of the metered addition, the mixture is stirred at 80° C. for a further 3 h and then cooled to room temperature. Extraction with 3 portions of 100 g methylene chloride and concentration of the combined extracts gives 44.4 g of a beige-brown solid containing 82.8% 1,4-dioxaspiro[4.5]decan-8-one (II-1), 1.7% 1,4-cyclohexanedione (III) and 1.7% 4-hydroxycyclohexanone (IV) (about 75% of theory).

[0053] Example 4: Preparation of 1,4-dioxaspiro[4.5]decan-8-one A mixture of 53.7 g (93%, 0.32 mol) of 1,4-dioxaspiro[4.5]decan-8-ol, 75 g of water, 1.3 g (0.016 mol) of sodium acetate and 2.0 g (0.006 mol) of sodium tungstate dihydrate is heated to 80° C. At this temperature, 72 g (1.06 mol) of 50% hydrogen peroxide are metered in over a period of 5 hours. During this time, the pH of the reaction mixture is constantly raised to pH 6.5 by adding 50% sodium hydroxide solution, once a pH of 5.5 has been reached.

[0054] At the end of the metered addition, the mixture is stirred for a further 3 h at 80° C. and then cooled to room temperature. Extraction with 3 portions of 100 g methylene chloride and concentration of the combined extracts gives 45.8 g of a beige-brown solid containing 86.7% 1,4-dioxaspiro[4.5]decan-8-one (II-1), 3.3% 1,4-cyclohexanedione (III) and 1.7% 4-hydroxycyclohexanone (IV) (about 80% of theory).

[0055] Example 5: Preparation of 1,4-dioxaspiro[4.5]decan-8-one A mixture of 53.7 g (93%, 0.32 mol) of 1,4-dioxaspiro[4.5]decan-8-ol, 75 g of water, 1.3 g (0.016 mol) of sodium acetate and 1.0 g (0.003 mol) of sodium tungstate dihydrate is heated to 80° C. At this temperature, 72 g (1.06 mol) of 50% hydrogen peroxide are metered in over a period of 5 hours. During this time, the pH of the reaction mixture is constantly raised to pH 6.5 by adding 50% sodium hydroxide solution, once a pH of 5.5 has been reached.

[0056] At the end of the metered addition, the mixture is stirred at 80° C. for a further 3 h and then cooled to room temperature. Extraction with 3 portions of 100 g methylene chloride and concentration of the combined extracts gives 42.9 g of a colorless solid containing 72.8% 1,4-dioxaspiro[4.5]decan-8-one (II-1), 2.0% 1,4-cyclohexanedione (III) and 2.9% 4-hydroxycyclohexanone (IV) (about 63% of theory).

[0057] Example 6: Preparation of 1,4-dioxaspiro[4.5]decan-8-one A mixture of 53.7 g (93%, 0.32 mol) of 1,4-dioxaspiro[4.5]decan-8-ol, 75 g of water, 1.3 g (0.016 mol) of sodium acetate and 4.0 g (0.012 mol) of sodium tungstate dihydrate is heated to 80° C. At this temperature, 72 g (1.06 mol) of 50% hydrogen peroxide are metered in over a period of 5 hours. During this time, the pH of the reaction mixture is constantly raised to pH 6.5 by adding 50% sodium hydroxide solution, once pH 5.5 has been reached.

[0058] At the end of the metered addition, the mixture is stirred for a further 3 h at 80° C. and then cooled to room temperature. Extraction with 3 portions of 100 g methylene chloride and concentration of the combined extracts gives 44.9 g of a yellowish-beige solid containing 89.7% 1,4-dioxaspiro[4.5]decan-8-one (II-1), 5.1% 1,4-cyclohexanedione (III) and 1.1% 4-hydroxycyclohexanone (IV) (about 82% of theory).

[0059] Example 7: Preparation of 1,4-dioxaspiro[4.5]decan-8-one A mixture of 53.7 g (93%, 0.32 mol) of 1,4-dioxaspiro[4.5]decan-8-ol, 75 g of water, 1.3 g (0.016 mol) of sodium acetate and 2.0 g (0.006 mol) of sodium tungstate dihydrate is heated to 75° C. At this temperature, 72 g (1.06 mol) of 50% hydrogen peroxide are metered in over a period of 5 hours. During this time, the pH of the reaction mixture is constantly raised to pH 6.5 by adding 50% sodium hydroxide solution, once a pH of 5.5 has been reached.

[0060] At the end of the metered addition, the mixture is stirred at 80° C. for a further 3 h and then cooled to room temperature. Extraction with 3 portions of 100 g methylene chloride and concentration of the combined extracts gives 45.1 g of a beige solid containing 78.5% 1,4-dioxaspiro[4.5]decan-8-one (II-1), 3.5% 1,4-cyclohexanedione (III) and 2.4% 4-hydroxycyclohexanone (IV) (about 72% of theory).

[0061] Example 8: Preparation of 1,4-dioxaspiro[4.5]decan-8-one A mixture of 53.7 g (93%, 0.32 mol) of 1,4-dioxaspiro[4.5]decan-8-ol, 75 g of water, 1.3 g (0.016 mol) of sodium acetate and 2.0 g (0.006 mol) of sodium tungstate dihydrate is heated to 85° C. At this temperature, 72 g (1.06 mol) of 50% hydrogen peroxide are metered in over a period of 5 hours. During this time, the pH of the reaction mixture is constantly raised to pH 6.5 by adding 50% sodium hydroxide solution, once a pH of 5.5 has been reached.

[0062] At the end of the metered addition, the mixture is stirred at 80° C. for a further 3 h and then cooled to room temperature. Extraction with 3 portions of 100 g of methylene chloride and concentration of the combined extracts gives 44.2 g of a colorless solid containing 86.6% of 1,4-dioxaspiro[4.5]decan-8-one (II-1), 7.4% of 1,4-cyclohexanedione (III) and 1.2% of 4-hydroxycyclohexanone (IV) (about 78% of theory).

[0063] Example 9: Preparation of 1,4-dioxaspiro[4.5]decan-8-one The pH of a mixture of 53.7 g (93%, 0.32 mol) of 1,4-dioxaspiro[4.5]decan-8-ol, 75 g of water, 1.3 g (0.016 mol) of sodium acetate and 2.0 g (0.006 mol) of sodium tungstate dihydrate is lowered to pH 7.0 by adding 99-100% acetic acid. After heating to 80 ° C, 65.7 g (0.97 mol) of 50% hydrogen peroxide are metered in over 5 hours. During this time, the pH of the reaction mixture is constantly raised to pH 6.5 by adding 50% sodium hydroxide solution, once it has reached pH 5.5.

[0064] At the end of the metered addition, the mixture is stirred at 80° C. for a further 3 h and then cooled to room temperature. Extraction with 3 portions of 100 g methylene chloride and concentration of the combined extracts gives 41.8 g of a beige solid containing 83.6% 1,4-dioxaspiro[4.5]decan-8-one (II-1), 7.9% 1,4-cyclohexanedione (III) and 2.3% 4-hydroxycyclohexanone (IV) (about 71% of theory).

[0065] Example 10: Preparation of 1,4-dioxaspiro[4.5]decan-8-one The pH of a mixture of 44.0 g (90.9%, 0.25 mol) of 1,4-dioxaspiro[4.5]decan-8-ol, 60 g of water, 4.0 g (0.048 mol) of sodium acetate and 1.7 g (0.006 mol) of sodium tungstate dihydrate is lowered to pH 7.2-7.5 by adding 99-100% acetic acid. After heating to 80 ° C, 50 g (0.74 mol) of 50% hydrogen peroxide are metered in over 4 hours.

[0066] At the end of the metered addition, the mixture is stirred at 80° C. for a further hour and then cooled to room temperature. Extraction with three 30 g portions of methylene chloride and concentration of the combined extracts gives 32.5 g of a pale beige solid containing 92.4% 1,4-dioxaspiro[4.5]decan-8-one (II-1), 2.5% 1,4-cyclohexanedione (III) and 0.8% 4-hydroxycyclohexanone (IV) (about 76% of theory).

[0067] Example 11: Preparation of 1,4-dioxaspiro[4.5]decan-8-one A mixture of 53.7 g (93%, 0.32 mol) of 1,4-dioxaspiro[4.5]decan-8-ol, 75 g of water, 1.2 g (0.016 mol) of ammonium acetate and 2.0 g (0.006 mol) of sodium tungstate dihydrate is heated to 80° C. At this temperature, 72 g (1.06 mol) of 50% hydrogen peroxide are metered in over a period of 5 hours. During this time, the pH of the reaction mixture is constantly raised to pH 6.5 by adding 50% sodium hydroxide solution, once a pH of 5.5 has been reached.

[0068] At the end of the metered addition, the mixture is stirred for a further 3 h at 80° C. and then cooled to room temperature. Extraction with 3 portions of 100 g methylene chloride and concentration of the combined extracts gives 43.4 g of a beige-brown solid containing 83.6% 1,4-dioxaspiro[4.5]decan-8-one (II-1), 7.5% 1,4-cyclohexanedione (III) and 2.2% 4-hydroxycyclohexanone (IV) (about 74% of theory).

[0069] Example 12: Preparation of 1,4-dioxaspiro[4.5]decan-8-one A mixture of 53.7 g (93%, 0.32 mol) of 1,4-dioxaspiro[4.5]decan-8-ol, 75 g of water, 1.2 g (0.016 mol) of ammonium acetate and 2.0 g (0.006 mol) of sodium tungstate dihydrate is heated to 80° C. At this temperature, 72 g (1.06 mol) of 50% hydrogen peroxide are metered in over a period of 5 hours. During this time, the pH of the reaction mixture is constantly raised to pH 6.5 by adding 25% aqueous ammonia when a pH of 5.5 is reached.

[0070] At the end of the metered addition, the mixture is stirred at 80° C. for a further 3 h and then cooled to room temperature. Extraction with 3×100 g methylene chloride and concentration of the combined extracts gives 40.8 g of a brown solid containing 83.6% 1,4-dioxaspiro[4.5]decan-8-one (II-1), 5.9% 1,4-cyclohexanedione (III) and 1.7% 4-hydroxycyclohexanone (IV) (about 69% of theory).

[0071] Example 13: Preparation of 1,4-dioxaspiro[4.5]decan-8-one A mixture of 53.7 g (93%, 0.32 mol) of 1,4-dioxaspiro[4.5]decan-8-ol, 75 g of water, 1.3 g (0.016 mol) of sodium acetate and 1.3 g (0.006 mol) of sodium molybdate is heated to 80° C. At this temperature, 72 g (1.06 mol) of 50% hydrogen peroxide are metered in over a period of 5 hours. During this time, the pH of the reaction mixture is constantly raised to pH 6.5 by adding 50% sodium hydroxide solution, once pH 5.5 has been reached.

[0072] At the end of the metered addition, the mixture is stirred at 80° C. for a further 3 hours and then cooled to room temperature. In-process control gives a mixture of 30.1% 1,4-dioxaspiro[4.5]decan-8-one (II-1), 61.3% 1,4-dioxaspiro[4.5]decan-8-ol (I-1), 0.4% 1,4-cyclohexanedione (III) and 7.0% 4-hydroxycyclohexanone (IV). This batch was not worked up.

[0073] Example 14: Preparation of 1,4-dioxaspiro[4.5]decan-8-one A mixture of 53.7 g (93%, 0.32 mol) of 1,4-dioxaspiro[4.5]decan-8-ol, 75 g of water, 1.0 g (0.016 mol) of lithium acetate and 2.0 g (0.006 mol) of sodium tungstate dihydrate is heated to 80° C. At this temperature, 72 g (1.06 mol) of 50% hydrogen peroxide are metered in over a period of 5 hours. During this time, the pH of the reaction mixture is constantly raised to pH 6.5 by adding 50% sodium hydroxide solution when pH 5.5 is reached.

[0074] At the end of the metered addition, the mixture is stirred at 80° C. for a further 3 h and then cooled to room temperature. Extraction with 3 portions of 100 g of methylene chloride and concentration of the combined extracts gives 44.9 g of an almost colorless solid containing 82.5% 1,4-dioxaspiro[4.5]decan-8-one (II-1), 1.6% 1,4-cyclohexanedione (III) and 1.9% 4-hydroxycyclohexanone (IV) (about 75% of theory).

[0075] Example 15: Preparation of 1,4-dioxaspiro[4.5]decan-8-one A mixture of 53.7 g (93%, 0.32 mol) of 1,4-dioxaspiro[4.5]decan-8-ol, 75 g of water, 1.0 g (0.016 mol) of lithium acetate and 2.0 g (0.006 mol) of sodium tungstate dihydrate is heated to 80° C. At this temperature, 72 g (1.06 mol) of 50% hydrogen peroxide are metered in over a period of 5 hours. During this time, the pH of the reaction mixture is constantly raised to pH 6.5 by adding 10% lithium hydroxide solution when pH 5.5 is reached.

[0076] At the end of the metered addition, the mixture is stirred at 80° C. for a further 3 h and then cooled to room temperature. Extraction with 3 portions of 100 g of methylene chloride and concentration of the combined extracts gives 40.2 g of a colorless solid containing 86.9% of 1,4-dioxaspiro[4.5]decan-8-one (II-1), 4.3% of 1,4-cyclohexanedione (III) and 1.4% of 4-hydroxycyclohexanone (IV) (about 71% of theory).

[0077] Example 16: Preparation of 1,4-dioxaspiro[4.5]decan-8-one A mixture of 53.7 g (93%, 0.32 mol) of 1,4-dioxaspiro[4.5]decan-8-ol, 75 g of water, 1.0 g (0.016 mol) of potassium acetate and 2.0 g (0.006 mol) of sodium tungstate dihydrate is heated to 80° C. At this temperature, 72 g (1.06 mol) of 50% hydrogen peroxide are metered in over a period of 5 hours. During this time, the pH of the reaction mixture is constantly raised to pH 6.5 by adding 50% potassium hydroxide solution when pH 5.5 is reached.

[0078] At the end of the metered addition, the mixture is stirred for a further 3 h at 80° C. and then cooled to room temperature. Extraction with 3 portions of 100 g methylene chloride and concentration of the combined extracts gives 44.6 g of an almost colorless solid containing 84.9% 1,4-dioxaspiro[4.5]decan-8-one (II-1), 4.4% 1,4-cyclohexanedione (III) and 1.9% 4-hydroxycyclohexanone (IV) (about 77% of theory).

[0079] Example 17: Preparation of 1,4-dioxaspiro[4.5]decan-8-one A mixture of 53.7 g (93%, 0.32 mol) of 1,4-dioxaspiro[4.5]decan-8-ol, 75 g of water, 1.0 g (0.016 mol) of sodium propionate and 2.0 g (0.006 mol) of sodium tungstate dihydrate is heated to 80° C. At this temperature, 72 g (1.06 mol) of 50% hydrogen peroxide are metered in over a period of 5 hours. During this time, the pH of the reaction mixture is constantly raised to pH 6.5 by adding 50% sodium hydroxide solution when pH 5.5 is reached.

[0080] At the end of the metered addition, the mixture is stirred at 80° C. for a further 3 h and then cooled to room temperature. Extraction with 3 portions of 100 g methylene chloride and concentration of the combined extracts gives 44.9 g of a yellow-beige solid containing 83.8% 1,4-dioxaspiro[4.5]decan-8-one (II-1), 4.4% 1,4-cyclohexanedione (III) and 2.0% 4-hydroxycyclohexanone (IV) (about 76% of theory).

[0081] Example 18: Preparation of 1,4-dioxaspiro[4.5]decan-8-one A mixture of 53.7 g (93%, 0.32 mol) of 1,4-dioxaspiro[4.5]decan-8-ol, 75 g of water, 1.0 g (0.016 mol) of sodium butyrate and 2.0 g (0.006 mol) of sodium tungstate dihydrate is heated to 80° C. At this temperature, 72 g (1.06 mol) of 50% hydrogen peroxide are metered in over a period of 5 hours. During this time, the pH of the reaction mixture is constantly raised to pH 6.5 by adding 50% sodium hydroxide solution when pH 5.5 is reached.

[0082] At the end of the metered addition, the mixture is stirred at 80° C. for a further 3 h and then cooled to room temperature. Extraction with 3 portions of 100 g of methylene chloride and concentration of the combined extracts gives 46.0 g of a colorless solid containing 82.1% of 1,4-dioxaspiro[4.5]decan-8-one (II-1), 4.1% of 1,4-cyclohexanedione (III) and 2.1% of 4-hydroxycyclohexanone (IV) (about 77% of theory).

[0083] Example 19: Preparation of 1,4-dioxaspiro[4.5]decan-8-one To a mixture of 75 g of water and 2.0 g (0.006 mol) of sodium tungstate dihydrate, 1.4 g (0.016 mol) of isobutyric acid is added at room temperature, followed by 2.0 g (0.016 mol) of 32% sodium hydroxide. 53.7 g (93%, 0.32 mol) of 1,4-dioxaspiro[4.5]decan-8-ol are added and the mixture is then heated to 80° C. At this temperature, 72 g (1.06 mol) of 50% hydrogen peroxide are metered in over a period of 5 hours. During this time, the pH of the reaction mixture is constantly raised to pH 6.5 by adding 50% sodium hydroxide solution when pH 5.5 is reached.

[0084] At the end of the metered addition, the mixture is stirred at 80° C. for a further 3 h and then cooled to room temperature. Extraction with 3 portions of 100 g methylene chloride and concentration of the combined extracts gives 46.3 g of a yellow-beige solid containing 83.4% 1,4-dioxaspiro[4.5]decan-8-one (II-1), 4.2% 1,4-cyclohexanedione (III) and 2.1% 4-hydroxycyclohexanone (IV) (about 78% of theory).

[0085] Example 20: Preparation of 1,4-dioxaspiro[4.5]decan-8-one A mixture of 43.1 g (92.8%, 0.25 mol) of 1,4-dioxaspiro[4.5]decan-8-ol, 60 g of water, 1.0 g (0.012 mol) of sodium acetate and 1.7 g (0.005 mol) of sodium tungstate dihydrate is heated to 80° C. At this temperature, 38 g (0.56 mol) of 50% hydrogen peroxide are metered in over a period of 3 hours, followed by a further 22 g (0.32 mol) of 50% hydrogen peroxide over a period of 2 hours. During this time, the pH of the reaction mixture is constantly raised to pH 6.5 by adding 50% sodium hydroxide solution each time a pH of 5.5 is reached.

[0086] At the end of the metered addition, the mixture is stirred at 80° C. for a further 2 h and then cooled to room temperature. Three extractions with 30 g portions of methylene chloride and concentration of the combined extracts give 34.9 g of a pale beige solid containing 92.9% 1,4-dioxaspiro[4.5]decan-8-one (II-1), 3.5% 1,4-cyclohexanedione (III) and 0.9% 4-hydroxycyclohexanone (IV) (about 82% of theory).

[0087] Example 21: Preparation of 1,4-dioxaspiro[4.5]decan-8-one A mixture of 53.7 g (93%, 0.32 mol) of 1,4-dioxaspiro[4.5]decan-8-ol, 75 g of water, 1.3 g (0.016 mol) of sodium acetate and 2.0 g (0.006 mol) of sodium tungstate dihydrate is heated to 80° C. At this temperature, 72 g (1.06 mol) of 50% hydrogen peroxide are metered in over a period of 3 hours. During this time, the pH of the reaction mixture is constantly raised to pH 6.5 by adding 50% sodium hydroxide solution when pH 5.5 is reached.

[0088] At the end of the metered addition, the mixture is stirred at 80° C. for a further 3 hours and then cooled to room temperature. Three extractions with 100 g portions of methylene chloride and concentration of the combined extracts give 45.1 g of a beige-brown solid containing 76.9% 1,4-dioxaspiro[4.5]decan-8-one (II-1), 16.5% 1,4-dioxaspiro[4.5]decan-8-ol (I-1), 2.7% 1,4-cyclohexanedione (III) and 2.6% 4-hydroxycyclohexanone (IV) (about 70% of theory).

[0089] Example 22: Preparation of 1,4-dioxaspiro[4.5]decan-8-one A mixture of 53.7 g (93%, 0.32 mol) of 1,4-dioxaspiro[4.5]decan-8-ol, 75 g of water, 5.2 g (0.06 mol) of sodium acetate and 2.0 g (0.006 mol) of sodium tungstate dihydrate is heated to 80° C. At this temperature, 72 g (1.06 mol) of 50% hydrogen peroxide are metered in over a period of 5 hours. During this time, the pH of the reaction mixture is constantly raised to pH 6.5 by adding 50% sodium hydroxide solution when pH 5.5 is reached.

[0090] At the end of the metered addition, the mixture is stirred at 80° C. for a further 3 hours and then cooled to room temperature. Extraction with 3 portions of 100 g of methylene chloride and concentration of the combined extracts gives 50.0 g of a beige solid containing 76.0% 1,4-dioxaspiro[4.5]decan-8-one (II-1), 12.9% 1,4-dioxaspiro[4.5]decan-8-ol (I-1), 0.2% 1,4-cyclohexanedione (III) and 2.6% 4-hydroxycyclohexanone (IV) (about 77% of theory).

[0091] Example 23: Preparation of 1,4-dioxaspiro[4.5]decan-8-one A mixture of 53.7 g (93%, 0.32 mol) of 1,4-dioxaspiro[4.5]decan-8-ol, 75 g of water, 13.0 g (0.16 mol) of sodium acetate and 2.0 g (0.006 mol) of sodium tungstate dihydrate is heated to 80° C. At this temperature, 72 g (1.06 mol) of 50% hydrogen peroxide are metered in over a period of 5 hours. During this time, the pH of the reaction mixture is constantly raised to pH 6.5 by adding 50% sodium hydroxide solution when pH 5.5 is reached.

[0092] At the end of the metered addition, the mixture is stirred at 80° C. for a further 3 hours and then cooled to room temperature. Extraction with 3 portions of 100 g methylene chloride and concentration of the combined extracts gives 52.8 g of a beige-brown solid containing 62.9% 1,4-dioxaspiro[4.5]decan-8-one (II-1), 27.3% 1,4-dioxaspiro[4.5]decan-8-ol (I-1), 0.1% 1,4-cyclohexanedione (III) and 3.0% 4-hydroxycyclohexanone (IV) (about 67% of theory).

[0093] Example 24: Preparation of 1,4-dioxaspiro[4.5]decan-8-one A mixture of 53.7 g (93%, 0.32 mol) of 1,4-dioxaspiro[4.5]decan-8-ol, 75 g of water, 1.3 g (0.016 mol) of sodium acetate and 10.0 g (0.030 mol) of sodium tungstate dihydrate is heated to 80° C. At this temperature, 72 g (1.06 mol) of 50% hydrogen peroxide are metered in over a period of 5 hours. During this time, the pH of the reaction mixture is constantly raised to pH 6.5 by adding 50% sodium hydroxide solution when pH 5.5 is reached.

[0094] At the end of the metered addition, the mixture is stirred at 80° C. for a further 3 hours and then cooled to room temperature. Extraction with 3 portions of 100 g of methylene chloride and concentration of the combined extracts gives 43.4 g of a beige solid containing 78.8% 1,4-dioxaspiro[4.5]decan-8-one (II-1), 9.5% 1,4-dioxaspiro[4.5]decan-8-ol (I-1), 0.0% 1,4-cyclohexanedione (III) and 1.4% 4-hydroxycyclohexanone (IV) (about 69% of theory).

[0095] Comparative Example 1: Preparation of 1,4-dioxaspiro[4.5]decan-8-one in a similar manner to Noyori et al; Bull. Chem. Soc. Japan, 72(10), 1999, 2287-2306 A mixture of 53.7 g (93%, 0.32 mol) of 1,4-dioxaspiro[4.5]decan-8-ol, 75 g of water and 2.0 g (0.006 mol) of sodium tungstate dihydrate is heated to 80° C. At this temperature, 54 g (0.79 mol) of 50% hydrogen peroxide are metered in over a period of 6 hours.

[0096] At the end of the metered addition, the mixture is stirred at 80 °C for a further 2 h, then cooled to room temperature and the pH adjusted to pH 6.0-6.5 with sodium bicarbonate. By extracting three times with 100 g portions of methylene chloride and concentrating the combined extracts, 22.6 g of a colorless solid is obtained containing 38.4% 1,4-dioxaspiro[4.5]decan-8-one (II-1), 3.0% 1,4-dioxaspiro[4.5]decan-8-ol (I-1), 30.3% 1,4-cyclohexanedione (III) and 5.3% 4-hydroxycyclohexanone (IV) (about 18% of theoretical).

[0097] Comparative Example 2: Preparation of 1,4-dioxaspiro[4.5]decan-8-one in a similar manner to Noyori et al; Bull. Chem. Soc. Japan, 72(10), 1999, 2287-2306 A mixture of 53.7 g (93%, 0.32 mol) of 1,4-dioxaspiro[4.5]decan-8-ol, 75 g of water and 2.0 g (0.006 mol) of sodium tungstate dihydrate is heated to 80° C. At this temperature, 72 g (1.06 mol) of 50% hydrogen peroxide are metered in over a period of 6 hours.

[0098] At the end of the metered addition, the mixture is stirred at 80 °C for a further 2 h, then cooled to room temperature and the pH adjusted to pH 6.0-6.5 with sodium bicarbonate. By extracting three times with 100 g portions of methylene chloride and concentrating the combined extracts, 7.9 g of a colorless solid is obtained containing 41.0% 1,4-dioxaspiro[4.5]decan-8-one (II-1), 0.5% 1,4-dioxaspiro[4.5]decan-8-ol (I-1), 50.9% 1,4-cyclohexanedione (III) and 3.7% 4-hydroxycyclohexanone (IV) (about 7% of theoretical).

[0099] Comparative Example 3: Preparation of 1,4-dioxaspiro[4.5]decan-8-one in a similar manner to Noyori et al; Bull. Chem. Soc. Japan, 72(10), 1999, 2287-2306 A mixture of 53.7 g (93%, 0.32 mol) of 1,4-dioxaspiro[4.5]decan-8-ol, 75 g of water and 2.0 g (0.006 mol) of sodium tungstate dihydrate is heated to 80° C. At this temperature, 72 g (1.06 mol) of 50% hydrogen peroxide are metered in over the course of 3 hours.

[0100] At the end of the metered addition, the mixture is stirred at 80 °C for a further 4 h, then cooled to room temperature and the pH adjusted to pH 6.0-6.5 with sodium bicarbonate. Extraction with 3 portions of 100 g methylene chloride and concentration of the combined extracts gives 22.7 g of a colourless solid containing 58.3% 1,4-dioxaspiro[4.5]decan-8-one (II-1), 1.3% 1,4-dioxaspiro[4.5]decan-8-ol (I-1), 25.5% 1,4-cyclohexanedione (III) and 4.8% 4-hydroxycyclohexanone (IV) (about 27% of theoretical).

Claims

1. Formula (II) 【Chemistry 1】 [During the ceremony, R １ and R ２ and the carbon atom to which they are attached represents a 5- or 6-membered ketal, optionally mono- or disubstituted by methyl or ethyl. A process for preparing a compound of the formula Formula (I) 【Chemistry 2】 [In the formula, R １ and R ２ is as defined above. with hydrogen peroxide in the presence of a solvent, in the presence of a catalyst, in the presence of a buffer, and optionally in the presence of a base.

2. R １ and R ２ and the carbon atom to which they are attached represents a five-membered ketal.

3. A process for preparing a compound of formula (II) according to claim 1, wherein the compound of formula (I-1) is 1,4-dioxaspiro[4.5]-decan-8-ol and the compound of formula (II-1) is 1,4-dioxaspiro[4.5]-decan-8-one.

4. 2. The process according to claim 1, wherein sodium tungstate or sodium tungstate dihydrate is used as the catalyst.

5. 2. The method according to claim 1, wherein sodium acetate, ammonium acetate, lithium acetate, potassium acetate, sodium propionate, sodium butyrate or sodium isobutyrate is used as the buffering agent.

6. 2. The method of claim 1, wherein sodium acetate is used as a buffering agent.

7. 2. The process according to claim 1, wherein aqueous ammonia, sodium hydroxide, potassium hydroxide or lithium hydroxide is used as the base.

8. 2. The process according to claim 1, wherein sodium hydroxide is used as the base.

9. The process of claim 1, wherein the pH of the reaction mixture is maintained at 5.5 to 7.

5.

10. The process of claim 1, wherein the pH of the reaction mixture is maintained at 5.5 to 6.

5.

11. The process according to claim 1, wherein the oxidizing agent is used in an amount of 1 to 5 mol per mol of the compound of formula (I).

12. The process according to claim 1, wherein the oxidizing agent is used in an amount of 2 to 4 mol per mol of the compound of formula (I).

13. The method of claim 1, wherein the oxidizing agent is added for a period of 3 to 5 hours.

14. The method according to claim 1, wherein the buffering agent is used in an amount of 0.01 to 1 mol per mol of the compound of formula (I).

15. The process according to claim 1, wherein the catalyst is used in an amount of 0.01 to 0.2 mol per mol of the compound of formula (I).

16. The method according to claim 1 , wherein water is used as the solvent.

17. 2. The process of claim 1, wherein the pH of the reaction mixture is maintained at 5.5 to 7.5 in the presence of water as a solvent, in the presence of sodium tungstate or sodium tungstate dihydrate as a catalyst, in the presence of a buffering agent, and optionally in the presence of a base.

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