Method for producing ketones

Abstract

The present invention relates to a new method for producing compounds of formula (II) by reacting compounds 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.

Description

[0001] Process for the production of ketones

[0002] The present invention relates to a novel process for the preparation of ketones by oxidation of alcohols with hydrogen peroxide.

[0003] Ketones serve, among other things, as starting materials for the production of hydantoins. These hydantoins, in turn, are important intermediates for the production of pesticides (e.g., WO 2006 / 089633).

[0004] The production of ketones by oxidation of alcohols can be achieved using various long-established methods. In Chem. Corn. 2003, 16, 1977, JACS, 1997, 119, 12386, and Bull. Chem. Soc. Japan, 72(10), 1999, 2287-2306, the production of ketones is carried out by reacting alcohols with hydrogen peroxide as the oxidant, sodium tungsten dihydrate as the catalyst, and optionally a hydrogen sulfate-based phase-transfer catalyst. However, this well-known alcohol oxidation method has significant deficiencies and disadvantages, particularly the low pH value, which makes acid-labile starting materials unsuitable for this reaction.

[0005] It has now been discovered that the reaction for the production of ketones can be advantageously carried out by reacting alcohols with hydrogen peroxide in the presence of a solvent, a catalyst, and a buffer. A stable pH value can be maintained by adding a base during the hydrogen peroxide addition, if necessary. This allows even acid-labile starting compounds to be converted excellently in good yields. Furthermore, it has been discovered that the ketones can be produced in higher purity. The formation of secondary components is greatly minimized, and the ketones can be used directly in subsequent reactions without further processing, e.g., for the production of hydantoins.

[0006] The process according to the invention for preparing compounds of formula (II) can be illustrated by the following scheme:

[0007] (I) (II) In formulas (I) and (II)

[0008] R 1 and R 2 and the carbon atom to which they are attached represents a five- or six-membered ketal which is optionally mono- or disubstituted by methyl or ethyl;

[0009] R 1 and R 2 and the carbon atom to which they are attached, preferentially for a five-membered ketal.

[0010] The following compound of formula (1-1) is particularly preferred: l,4-dioxaspiro[4.5]-decan-8-ol

[0011] Particularly preferred is the following compound of formula (II-l): l,4-dioxaspiro[4.5]-decan-8-one

[0012] (I ).

[0013] Surprisingly, the process according to the invention allows the compounds of formula (II) to be prepared in higher yield and purity than previously known processes. Furthermore, acid-labile starting materials are suitable for this reaction.

[0014] The compounds of formula (I) are either commercially available or can be prepared by known methods (e.g. WO 2006 / 089633).

[0015] Scheme 1

[0016] The course of the process according to the invention is exemplified by the following reaction scheme:

[0017] (I) (II) (III) (IV)

[0018] The compounds of formulas (III) and (IV) are minor components of the reaction. The formation of the minor components of formulas (III) and (IV) is greatly 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.

[0019] Hydrogen peroxide is used as the oxidizing agent. The hydrogen peroxide used is commercially available hydrogen peroxide with concentrations of 10 to 70% hydrogen peroxide in water. Hydrogen peroxide with a concentration of 50% hydrogen peroxide in water is preferred.

[0020] Examples of solvents used for the reaction according to the process of the invention include 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. Water is preferably used as the solvent.

[0021] Suitable catalysts include sodium tungstate, sodium tungstate dihydrate, sodium molybdate, or sodium molybdate dihydrate. Sodium tungstate dihydrate is preferred. Sodium tungstate is also preferred.

[0022] Suitable buffers include, for example, acetates, formates, propionates, phosphates, carbonates, or alkanoates of alkali or alkaline earth metals, or the corresponding ammonium compounds. 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 are preferred. Sodium acetate, ammonium acetate, lithium acetate, potassium acetate, sodium propionate, sodium butyrate, or sodium isobutyrate are particularly preferred. Buffer mixtures of, for example, sodium acetate and acetic acid are also suitable.

[0023] Controlling the pH during the reaction is important. A base, such as ammonia water, sodium hydroxide, potassium hydroxide, or lithium hydroxide, is used to control the pH. Sodium hydroxide is preferred for pH control. The pH is determined using a calibrated pH electrode.

[0024] The oxidizing agent used is 1 to 5 mol per mol of the compound of formula (I), preferably 2 to 4 mol per mol of the compound of formula (I). Particularly preferably, 2.9 to 3.5 mol per mol of the compound of formula (I) are used.

[0025] The oxidizing agent is added over a period of time, preferably within 3 to 5 hours. The oxidizing agent can be added evenly over this period.

[0026] The catalyst used is 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), particularly preferably 0.01 to 0.04 mol per mol of the compound of formula (I).

[0027] The buffer used is 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), particularly preferably 0.05 mol per mol of the compound of formula (I).

[0028] By adding the base in parallel with hydrogen peroxide, the pH range is maintained. A pH between 5 and 8 is considered optimal. A pH between 5.5 and 7.5 is preferred. It is particularly preferred to repeatedly raise the pH of the reaction mixture to 6.5 by adding the base when pH 5.5 is reached. The amount of base used for pH control is selected to ensure the appropriate pH is maintained.

[0029] The reaction can be carried out at temperatures between 50 and 100 °C. Temperatures between 75 and 85 °C are preferred. A temperature of 80 °C is particularly preferred.

[0030] In a further embodiment, the invention relates to a process for preparing compounds of formula (II) by reacting compounds 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.

[0031] In a further embodiment, the invention relates to a process for preparing compounds of formula (II) by reacting compounds 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.

[0032] In a further embodiment, the invention relates to a process for preparing compounds of formula (II) by reacting compounds 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.

[0033] In a further embodiment, the invention relates to a process for preparing compounds of formula (II) by reacting compounds of formula (I) in water with hydrogen peroxide, in the presence of sodium tungstate or sodium tungstate dihydrate as 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.

[0034] In a further embodiment, the invention relates to a process for preparing compounds of formula (II) by reacting compounds of formula (I) in water with hydrogen peroxide, in the presence of sodium tungstate dihydrate as 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.

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

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

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

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

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

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

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

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

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

[0044] In a further embodiment, the invention relates to a process for preparing compounds of formula (II) by reacting compounds of formula (I) in water with hydrogen peroxide, in the presence of sodium tungsten dihydrate as catalyst, in the presence of sodium propinate as buffer and in the presence of sodium hydroxide as base, wherein the pH is between 5.5 and 7.5.

[0045] In a further embodiment, the invention relates to a process for preparing compounds of formula (II) by reacting compounds of formula (I) in water with hydrogen peroxide, in the presence of sodium tungsten dihydrate as catalyst, in the presence of sodium butyrate as buffer and in the presence of sodium hydroxide as base, wherein the pH is between 5.5 and 7.5.

[0046] In a further embodiment, the invention relates to a process for preparing compounds of formula (II) by reacting compounds of formula (I) in water with hydrogen peroxide, in the presence of sodium tungsten dihydrate as catalyst, in the presence of sodium isobutyrate as buffer and in the presence of sodium hydroxide as base, wherein the pH is between 5.5 and 7.5. In a further embodiment, the invention relates to a process for preparing compounds of formula (II) by reacting compounds of formula (I) in water with hydrogen peroxide, in the presence of sodium tungsten dihydrate as catalyst, in the presence of sodium acetate as buffer and in the presence of sodium hydroxide as base, wherein 0.02 to 0.04 mol of sodium tungstate dihydrate per mole of the compound of formula (I), 3.3 mol of hydrogen peroxide per mole of the compound of formula (I) are used and the pH is between 5.5 and 6.5.

[0047] In a further embodiment, the invention relates to a process for the preparation of compounds of formula (II) by reacting compounds of formula (I) in water with hydrogen peroxide, in the presence of sodium tungstate or sodium tungstate dihydrate as catalyst, in the presence of sodium acetate, ammonium acetate, lithium acetate, potassium acetate, sodium propionate, sodium butyrate or sodium isobutyrate as buffer or in the presence of sodium acetate and acetic acid as buffer mixture and optionally in the presence of sodium hydroxide, potassium hydroxide, lithium hydroxide or ammonia water as base, wherein the pH is between 5.5 and 7.5.

[0048] The preparation of compounds of formula (II) by the process according to the invention will be illustrated by the following preparation examples:

[0049] Examples

[0050] Example 1 : Preparation of l,4-dioxaspiro[4.5]-decan-8-one

[0051] A mixture of 53.7 g (93%, 0.32 mol) of l,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 is added over a period of 5 h. Upon reaching pH 5.5, the pH of the reaction mixture is repeatedly raised to pH 6.5 by adding 50% sodium hydroxide solution. After 2 h of dosing, a further 1.0 g (0.0032 mol) of sodium tungstate dihydrate is added.

[0052] After the end of the addition, the mixture is stirred for 3 h at 80°C and then cooled to room temperature. Triple extraction with 100 g of methylene chloride each and concentration of the combined extracts yields 44.7 g of a pale beige solid containing 85.4% l,4-dioxaspiro[4.5]-decan-8-one (II-1), 7.8% 1,4-cyclohexanedione (III), and 1.9% 4-hydroxycyclohexanone (IV) (approx. 77% of theory).

[0053] Example 2: Preparation of l,4-dioxaspiro[4.5]-decan-8-one

[0054] A mixture of 53.7 g (93%, 0.32 mol) of l,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 is added over a period of 5 h. Upon reaching pH 6.0, the pH of the reaction mixture is repeatedly raised to pH 7.0 by adding 50% sodium hydroxide solution. After 2 h of dosing, a further 1.0 g (0.003 mol) of sodium tungstate dihydrate is added.

[0055] After the end of the addition, the mixture is stirred for 3 h at 80°C and then cooled to room temperature. Triple extraction with 100 g of methylene chloride each and concentration of the combined extracts yields 46.2 g of a beige-brown solid containing 82.0% l,4-dioxaspiro[4.5]-decan-8-one (II-1), 3.7% 1,4-cyclohexanedione (III), and 2.2% 4-hydroxycyclohexanone (IV) (approx. 77% of theory).

[0056] 3 Preparation of l,4-dioxaspiro[4.5]-decan-8-one

[0057] A mixture of 53.7 g (93%, 0.32 mol) of l,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 is added over a period of 5 h. Upon reaching pH 6.5, the pH of the reaction mixture is repeatedly raised to pH 7.5 by adding 50% sodium hydroxide solution. After 2 h of dosing, a further 1.0 g (0.003 mol) of sodium tungstate dihydrate is added.

[0058] After the end of the addition, the mixture is stirred for 3 h at 80°C and then cooled to room temperature. Triple extraction with 100 g of methylene chloride each and concentration of the combined extracts yields 44.4 g of a beige-brown solid containing 82.8% l,4-dioxaspiro[4.5]-decan-8-one (II-1), 1.7% 1,4-cyclohexanedione (III), and 1.7% 4-hydroxycyclohexanone (IV) (approx. 75% of theory).

[0059] Preparation of l,4-dioxaspiro[4.5]-decan-8-one

[0060] A mixture of 53.7 g (93%, 0.32 mol) of l,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 added over 5 h. Upon reaching pH 5.5, the pH of the reaction mixture is repeatedly raised to pH 6.5 by adding 50% sodium hydroxide solution.

[0061] After the end of the addition, the mixture is stirred for 3 h at 80°C and then cooled to room temperature. Triple extraction with 100 g of methylene chloride each and concentration of the combined extracts yields 45.8 g of a beige-brown solid containing 86.7% l,4-dioxaspiro[4.5]-decan-8-one (II-1), 3.3% 1,4-cyclohexanedione (III), and 1.7% 4-hydroxycyclohexanone (IV) (approx. 80% of theory). Preparation of l,4-dioxaspiro[4.5]-decan-8-one

[0062] A mixture of 53.7 g (93%, 0.32 mol) of l,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 added over 5 h. Upon reaching pH 5.5, the pH of the reaction mixture is repeatedly raised to pH 6.5 by adding 50% sodium hydroxide solution.

[0063] After the end of the addition, the mixture is stirred for 3 h at 80°C and then cooled to room temperature. Triple extraction with 100 g of methylene chloride each and concentration of the combined extracts yields 42.9 g of a colorless solid containing 72.8% l,4-dioxaspiro[4.5]-decan-8-one (II-1), 2.0% 1,4-cyclohexanedione (III), and 2.9% 4-hydroxycyclohexanone (IV) (approx. 63% of theory).

[0064] 6 Preparation of l,4-dioxaspiro[4.5]-decan-8-one

[0065] A mixture of 53.7 g (93%, 0.32 mol) of l,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 added over 5 h. Upon reaching pH 5.5, the pH of the reaction mixture is repeatedly raised to pH 6.5 by adding 50% sodium hydroxide solution.

[0066] After the end of the addition, the mixture is stirred for 3 h at 80°C and then cooled to room temperature. Triple extraction with 100 g of methylene chloride each and concentration of the combined extracts yields 44.9 g of a yellowish-beige solid containing 89.7% l,4-dioxaspiro[4.5]-decan-8-one (II-1), 5.1% 1,4-cyclohexanedione (III), and 1.1% 4-hydroxycyclohexanone (IV) (approx. 82% of theory).

[0067] Preparation of l,4-dioxaspiro[4.5]-decan-8-one

[0068] A mixture of 53.7 g (93%, 0.32 mol) of l,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 added over 5 h. Upon reaching pH 5.5, the pH of the reaction mixture is repeatedly raised to pH 6.5 by adding 50% sodium hydroxide solution.

[0069] After the end of the addition, the mixture is stirred for 3 h at 80°C and then cooled to room temperature. Triple extraction with 100 g of methylene chloride each and concentration of the combined extracts yields 45.1 g of a beige solid containing 78.5% l,4-dioxaspiro[4.5]-decan-8-one (II-1), 3.5% 1,4-cyclohexanedione (III), and 2.4% 4-hydroxycyclohexanone (IV) (approx. 72% of theory). Example 8: Preparation of l,4-dioxaspiro[4.5]-decan-8-one

[0070] A mixture of 53.7 g (93%, 0.32 mol) of l,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 added over 5 h. Upon reaching pH 5.5, the pH of the reaction mixture is repeatedly raised to pH 6.5 by adding 50% sodium hydroxide solution.

[0071] After the end of the addition, the mixture is stirred for 3 h at 80°C and then cooled to room temperature. Triple extraction with 100 g of methylene chloride each and concentration of the combined extracts yields 44.2 g of a colorless solid containing 86.6% l,4-dioxaspiro[4.5]-decan-8-one (II-1), 7.4% 1,4-cyclohexanedione (III), and 1.2% 4-hydroxycyclohexanone (IV) (approx. 78% of theory).

[0072] Example 9: Preparation of l,4-dioxaspiro[4.5]-decan-8-one

[0073] The pH of a mixture of 53.7 g (93%, 0.32 mol) of l,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 added over 5 h. Upon reaching pH 5.5, the pH of the reaction mixture is repeatedly raised to pH 6.5 by adding 50% sodium hydroxide solution.

[0074] After the end of the addition, the mixture is stirred for 3 h at 80°C and then cooled to room temperature. Triple extraction with 100 g of methylene chloride each and concentration of the combined extracts yields 41.8 g of a beige solid containing 83.6% l,4-dioxaspiro[4.5]-decan-8-one (II-1), 7.9% 1,4-cyclohexanedione (III), and 2.3% 4-hydroxycyclohexanone (IV) (approx. 71% of theory).

[0075] Example 10: Preparation of l,4-dioxaspiro[4.5]-decan-8-one

[0076] The pH of a mixture of 44.0 g (90.9%, 0.25 mol) of l,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 added over 4 h.

[0077] After the end of the addition, the mixture is stirred for 1 h at 80°C and then cooled to room temperature. Triple extraction with 30 g of methylene chloride each and concentration of the combined extracts yields 32.5 g of a pale beige solid containing 92.4% l,4-dioxaspiro[4.5]-decan-8-one (II-1), 2.5% 1,4-cyclohexanedione (III), and 0.8% 4-hydroxycyclohexanone (IV) (approx. 76% of theory). Preparation of l,4-dioxaspiro[4.5]-decan-8-one

[0078] A mixture of 53.7 g (93%, 0.32 mol) of l,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 added over 5 h. Upon reaching pH 5.5, the pH of the reaction mixture is repeatedly raised to pH 6.5 by adding 50% sodium hydroxide solution.

[0079] After the end of the addition, the mixture is stirred for 3 h at 80°C and then cooled to room temperature. Triple extraction with 100 g of methylene chloride each and concentration of the combined extracts yields 43.4 g of a beige-brown solid containing 83.6% l,4-dioxaspiro[4.5]-decan-8-one (II-1), 7.5% 1,4-cyclohexanedione (III), and 2.2% 4-hydroxycyclohexanone (IV) (approx. 74% of theory).

[0080] Preparation of l,4-dioxaspiro[4.5]-decan-8-one

[0081] A mixture of 53.7 g (93%, 0.32 mol) of l,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 added over 5 h. Upon reaching pH 5.5, the pH of the reaction mixture is repeatedly raised to pH 6.5 by adding 25% ammonia water.

[0082] After the end of the addition, the mixture is stirred for 3 h at 80°C and then cooled to room temperature. Triple extraction with 100 g of methylene chloride each and concentration of the combined extracts yields 40.8 g of a brown solid containing 83.6% l,4-dioxaspiro[4.5]-decan-8-one (II-1), 5.9% 1,4-cyclohexanedione (III), and 1.7% 4-hydroxycyclohexanone (IV) (approx. 69% of theory).

[0083] Preparation of l,4-dioxaspiro[4.5]-decan-8-one

[0084] A mixture of 53.7 g (93%, 0.32 mol) of l,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 added over 5 h. Upon reaching pH 5.5, the pH of the reaction mixture is repeatedly raised to pH 6.5 by adding 50% sodium hydroxide solution.

[0085] After the end of the addition, the mixture was stirred for 3 h at 80°C and then cooled to room temperature. An in-process check yielded a mixture of 30.1% l,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). Workup of the mixture was omitted. Preparation of l,4-dioxaspiro[4.5]-decan-8-one

[0086] A mixture of 53.7 g (93%, 0.32 mol) of l,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 added over 5 h. Upon reaching pH 5.5, the pH of the reaction mixture is repeatedly raised to pH 6.5 by adding 50% sodium hydroxide solution.

[0087] After the end of the addition, the mixture is stirred for 3 h at 80°C and then cooled to room temperature. Triple extraction with 100 g of methylene chloride each and concentration of the combined extracts yields 44.9 g of a nearly colorless solid containing 82.5% l,4-dioxaspiro[4.5]-decan-8-one (II-1), 1.6% 1,4-cyclohexanedione (III), and 1.9% 4-hydroxycyclohexanone (IV) (approx. 75% of theory).

[0088] Preparation of l,4-dioxaspiro[4.5]-decan-8-one

[0089] A mixture of 53.7 g (93%, 0.32 mol) of l,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 added over 5 h. Upon reaching pH 5.5, the pH of the reaction mixture is repeatedly raised to pH 6.5 by adding 10% lithium hydroxide solution.

[0090] After the end of the addition, the mixture is stirred for 3 h at 80°C and then cooled to room temperature. Triple extraction with 100 g of methylene chloride each and concentration of the combined extracts yields 40.2 g of a colorless solid containing 86.9% l,4-dioxaspiro[4.5]-decan-8-one (II-1), 4.3% 1,4-cyclohexanedione (III), and 1.4% 4-hydroxycyclohexanone (IV) (approx. 71% of theory).

[0091] Preparation of l,4-dioxaspiro[4.5]-decan-8-one

[0092] A mixture of 53.7 g (93%, 0.32 mol) of l,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 added over 5 h. The pH of the reaction mixture is repeatedly raised to 6.5 by adding 50% potassium hydroxide solution upon reaching pH 5.5.

[0093] After the end of the addition, the mixture is stirred for 3 h at 80°C and then cooled to room temperature. Triple extraction with 100 g of methylene chloride each and concentration of the combined extracts yields 44.6 g of a nearly colorless solid containing 84.9% l,4-dioxaspiro[4.5]-decan-8-one (II-1), 4.4% 1,4-cyclohexanedione (III), and 1.9% 4-hydroxycyclohexanone (IV) (approx. 77% of theory). Example 17: Preparation of l,4-dioxaspiro[4.5]-decan-8-one

[0094] A mixture of 53.7 g (93%, 0.32 mol) of l,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 added over 5 h. Upon reaching pH 5.5, the pH of the reaction mixture is repeatedly raised to pH 6.5 by adding 50% sodium hydroxide solution.

[0095] After the end of the addition, the mixture is stirred for 3 h at 80°C and then cooled to room temperature. Triple extraction with 100 g of methylene chloride each and concentration of the combined extracts yields 44.9 g of a yellow-beige solid containing 83.8% l,4-dioxaspiro[4.5]-decan-8-one (II-1), 4.4% 1,4-cyclohexanedione (III), and 2.0% 4-hydroxycyclohexanone (IV) (approx. 76% of theory).

[0096] Example 18: Preparation of l,4-dioxaspiro[4.5]-decan-8-one

[0097] A mixture of 53.7 g (93%, 0.32 mol) of l,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 added over 5 h. Upon reaching pH 5.5, the pH of the reaction mixture is repeatedly raised to pH 6.5 by adding 50% sodium hydroxide solution.

[0098] After the end of the addition, the mixture is stirred for 3 h at 80°C and then cooled to room temperature. Triple extraction with 100 g of methylene chloride each and concentration of the combined extracts yields 46.0 g of a colorless solid containing 82.1% l,4-dioxaspiro[4.5]-decan-8-one (II-1), 4.1% 1,4-cyclohexanedione (III), and 2.1% 4-hydroxycyclohexanone (IV) (approx. 77% of theory).

[0099] Example 19: Preparation of l,4-dioxaspiro[4.5]-decan-8-one

[0100] A mixture of 75 g of water and 2.0 g (0.006 mol) of sodium tungstate dihydrate is treated at room temperature with 1.4 g (0.016 mol) of isobutyric acid and then with 2.0 g (0.016 mol) of 32% sodium hydroxide solution. After adding 53.7 g (93%, 0.32 mol) of l,4-dioxaspiro[4.5]-decan-8-ol, the mixture is heated to 80°C. At this temperature, 72 g (1.06 mol) of 50% hydrogen peroxide are added over 5 h. Upon reaching pH 5.5, the pH of the reaction mixture is repeatedly raised to pH 6.5 by adding 50% sodium hydroxide solution.

[0101] After the end of the addition, the mixture is stirred for 3 h at 80°C and then cooled to room temperature. Triple extraction with 100 g of methylene chloride each and concentration of the combined extracts yields 46.3 g of a yellow-beige solid containing 83.4% l,4-dioxaspiro[4.5]-decan-8-one (II-1), 4.2% 1,4-cyclohexanedione (III), and 2.1% 4-hydroxycyclohexanone (IV) (approx. 78% of theory). Preparation of l,4-dioxaspiro[4.5]-decan-8-one

[0102] A mixture of 43.1 g (92.8%, 0.25 mol) of l,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 added over 3 h, followed by a further 22 g (0.32 mol) of 50% hydrogen peroxide over 2 h. The pH of the reaction mixture is repeatedly raised to 6.5 by adding 50% sodium hydroxide solution each time it reaches pH 5.5.

[0103] After the end of the addition, the mixture is stirred for 2 h at 80°C and then cooled to room temperature. Triple extraction with 30 g of methylene chloride each and concentration of the combined extracts yields 34.9 g of a pale beige solid containing 92.9% l,4-dioxaspiro[4.5]-decan-8-one (II-1), 3.5% 1,4-cyclohexanedione (III), and 0.9% 4-hydroxycyclohexanone (IV) (approx. 82% of theory).

[0104] Preparation of l,4-dioxaspiro[4.5]-decan-8-one

[0105] A mixture of 53.7 g (93%, 0.32 mol) of l,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 added over 3 h. Upon reaching pH 5.5, the pH of the reaction mixture is repeatedly raised to pH 6.5 by adding 50% sodium hydroxide solution.

[0106] After the end of the addition, the mixture is stirred for 3 h at 80°C and then cooled to room temperature. Triple extraction with 100 g of methylene chloride each and concentration of the combined extracts yields 45.1 g of a beige-brown solid containing 76.9% l,4-dioxaspiro[4.5]-decan-8-one (II-1), 16.5% l,4-dioxaspiro[4.5]-decan-8-ol (I-1), 2.7% 1,4-cyclohexanedione (III), and 2.6% 4-hydroxycyclohexanone (IV) (approx. 70% of theory).

[0107] Preparation of l,4-dioxaspiro[4.5]-decan-8-one

[0108] A mixture of 53.7 g (93%, 0.32 mol) of l,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 added over 5 h. Upon reaching pH 5.5, the pH of the reaction mixture is repeatedly raised to pH 6.5 by adding 50% sodium hydroxide solution.

[0109] After the end of the addition, the mixture is stirred for 3 h at 80°C and then cooled to room temperature. Triple extraction with 100 g of methylene chloride each and concentration of the combined extracts yields 50.0 g of a beige solid containing 76.0% l,4-dioxaspiro[4.5]-decan-8-one (II-1), 12.9% l,4-dioxaspiro[4.5]-decan-8-ol (II-1), 0.2% 1,4-cyclohexanedione (III), and 2.6% 4-hydroxycyclohexanone (IV) (approx. 77% of theory). Preparation of l,4-dioxaspiro[4.5]-decan-8-one

[0110] A mixture of 53.7 g (93%, 0.32 mol) of l,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 added over 5 h. Upon reaching pH 5.5, the pH of the reaction mixture is repeatedly raised to pH 6.5 by adding 50% sodium hydroxide solution.

[0111] After the end of the addition, the mixture is stirred for 3 h at 80°C and then cooled to room temperature. Triple extraction with 100 g of methylene chloride each and concentration of the combined extracts yields 52.8 g of a beige-brown solid containing 62.9% l,4-dioxaspiro[4.5]-decan-8-one (II-1), 27.3% l,4-dioxaspiro[4.5]-decan-8-ol (II-1), 0.1% 1,4-cyclohexanedione (III), and 3.0% 4-hydroxycyclohexanone (IV) (approx. 67% of theory).

[0112] Preparation of l,4-dioxaspiro[4.5]-decan-8-one

[0113] A mixture of 53.7 g (93%, 0.32 mol) of l,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 added over 5 h. Upon reaching pH 5.5, the pH of the reaction mixture is repeatedly raised to pH 6.5 by adding 50% sodium hydroxide solution.

[0114] After the end of the addition, the mixture is stirred for 3 h at 80°C and then cooled to room temperature. Triple extraction with 100 g of methylene chloride each and concentration of the combined extracts yields 43.4 g of a beige solid containing 78.8% l,4-dioxaspiro[4.5]-decan-8-one (II-1), 9.5% l,4-dioxaspiro[4.5]-decan-8-ol (II-1), 0.0% 1,4-cyclohexanedione (III), and 1.4% 4-hydroxycyclohexanone (IV) (approx. 69% of theory). Table 1:

[0115] Preparation of l,4-dioxaspiro[4.5]-decan-8-one analogously to Noyori et al.; Bull. Chem. Soc. Japan, 72(10), 1999, 2287-2306

[0116] A mixture of 53.7 g (93%, 0.32 mol) of l,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 added over 6 h.

[0117] After the end of the addition, the mixture is stirred for 2 h at 80°C, then cooled to room temperature and the pH is raised to pH 6.0-6.5 with sodium bicarbonate. Triple extraction with 100 g of methylene chloride each and concentration of the combined extracts yields 22.6 g of a colorless solid containing 38.4% 1,4-dioxaspiro[4.5]-decan-8-one (II-1), 3.0% l,4-dioxaspiro[4.5]-decan-8-ol (II-1), 30.3% 1,4-cyclohexanedione (III), and 5.3% 4-hydroxycyclohexanone (IV) (approx. 18% of theory). Example 2:

[0118] Preparation of l,4-dioxaspiro[4.5]-decan-8-one analogously to Noyori et al.; Bull. Chem. Soc. Japan, 72(10), 1999, 2287-2306

[0119] A mixture of 53.7 g (93%, 0.32 mol) of l,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 added over 6 h.

[0120] After the end of the addition, the mixture is stirred for 2 h at 80°C, then cooled to room temperature and the pH is raised to pH 6.0-6.5 with sodium bicarbonate. Triple extraction with 100 g of methylene chloride each and concentration of the combined extracts yields 7.9 g of a colorless solid containing 41.0% 1,4-dioxaspiro[4.5]-decan-8-one (II-1), 0.5% l,4-dioxaspiro[4.5]-decan-8-ol (II-1), 50.9% 1,4-cyclohexanedione (III) and 3.7% 4-hydroxycyclohexanone (IV) (approx. 7% of theory).

[0121] Comparison example 3:

[0122] Preparation of l,4-dioxaspiro[4.5]-decan-8-one analogously to Noyori et al.; Bull. Chem. Soc. Japan, 72(10), 1999, 2287-2306

[0123] A mixture of 53.7 g (93%, 0.32 mol) of l,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 added over 3 h.

[0124] After the end of the addition, the mixture is stirred for 4 h at 80°C, then cooled to room temperature and the pH is raised to pH 6.0-6.5 with sodium bicarbonate. Triple extraction with 100 g of methylene chloride each and concentration of the combined extracts yields 22.7 g of a colorless solid containing 58.3% 1,4-dioxaspiro[4.5]-decan-8-one (II-1), 1.3% l,4-dioxaspiro[4.5]-decan-8-ol (II-1), 25.5% 1,4-cyclohexanedione (III) and 4.8% 4-hydroxycyclohexanone (IV) (approx. 27% of theory).

Claims

Patent claims 1. Method for the preparation of compounds of formula (II) in which R 1 and R 2 and the carbon atom to which they are bonded represents a five- or six-membered ketal, optionally one to two times substituted by methyl or ethyl, characterized in that the compound of formula (I) in which R 1 and R 2 the above-mentioned meanings are reacted 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. Method for producing compounds of formula (II) according to claim 1, wherein R 1 and R 2 and the carbon atom to which they are bonded represents a five-membered ketal.

3. Method for the preparation of compounds of formula (II) according to claim 1, in which the compound of formula (1-1) represents 1,4-dioxaspiro[4.5]-decan-8-ol and the compound of formula (II-1) represents 1,4-dioxaspiro[4.5]-decan-8-one.

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

5. 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 buffer.

6. Method according to claim 1, wherein sodium acetate is used as the buffer.

7. Method according to claim 1, wherein ammonia water, sodium hydroxide, potassium hydroxide or lithium hydroxide is used as the base.

8. Method according to claim 1, wherein sodium hydroxide is used as the base.

9. Method according to claim 1, wherein the pH of the reaction mixture is maintained between 5.5 and 7.

5.

10. Method according to claim 1, wherein the pH of the reaction mixture is maintained between 5.5 and 6.

5.

11. Method according to claim 1, wherein the oxidizing agent is used in amounts of 1 to 5 mol per mol of the compound of formula (I).

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

13. Method according to claim 1, wherein the addition of the oxidizing agent takes place within 3 to 5 hours.

14. Method according to claim 1, wherein the buffer is used in amounts of 0.01 to 1 mol per mol of the compound of formula (I).

15. Method according to claim 1, wherein the catalyst is used in amounts of 0.01 to 0.2 mol per mol of the compound of formula (I).

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

17. The method according to claim 1, 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 buffer and optionally in the presence of a base, wherein the pH of the reaction mixture is maintained between 5.5 and 7.5.

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