Process for preparing substituted 2-arylethanols

Abstract

The invention relates to a process for preparing substituted 2-arylethanols of the formula (I) by reacting Grignard compounds of the formula (II) in the presence of a copper compound with ethylene oxide. Moreover, the invention relates to novel substituted 2-arylethanols of the formula (I).

Claims

1. A process for preparing a compound of formula (I) ##STR00004## in which R.sup.1, R.sup.5 independently of one another represent C.sub.1-C.sub.6-alkyl, C.sub.1-C.sub.6-fluoroalkyl having 1 to 13 fluorine atoms, optionally substituted C.sub.6-C.sub.10-aryl, fluorine, chlorine, a radical NR.sup.6.sub.2, OR.sup.6 or SR.sup.6, where R.sup.6 represents C.sub.1-C.sub.6-alkyl, C.sub.1-C.sub.2-fluoroalkyl having 1 to 5 fluorine atoms or phenyl, R.sup.2, R.sup.3, R.sup.4 independently of one another represent hydrogen, C.sub.1-C.sub.6-alkyl, C.sub.1-C.sub.6-fluoroalkyl having 1 to 13 fluorine atoms, optionally substituted C.sub.6-C.sub.10-aryl, fluorine, chlorine, a radical NR.sup.6.sub.2, OR.sup.6 or SR.sup.6, where R.sup.6 represents C.sub.1-C.sub.6-alkyl, C.sub.1-C.sub.2-fluoroalkyl having 1 to 5 fluorine atoms or phenyl, the process comprising reacting a compound of the formula (II) ##STR00005## in which the radicals R.sup.1 to R.sup.5 have the meanings given above and X represents chlorine, bromine or iodine, in the presence of a copper compound with ethylene oxide, wherein the compound of formula (I) is 2-(4-chloro-2,6-dimethylphenyl)ethanol.

2. The process for preparing a compound of formula (I) according to claim 1, wherein the copper compound used is copper(I) iodide, copper(I) bromide, copper(II) bromide or copper(I) chloride.

3. The process for preparing a compound of formula (I) according to claim 1, wherein the copper compound is used in an amount of from 0.1 to 50 mol percent, based on the compound of formula (II).

4. The process for preparing a compound of formula (I) according to claim 1, wherein the copper compound is used in an amount of from 0.5 to 15 mol percent, based on the compound of formula (II).

5. The process for preparing a compound of formula (I) according to claim 1, wherein ethylene oxide is used in an amount between 0.9 and 3 mol equivalents, based on the compound of formula (II).

6. The process for preparing a compound of formula (I) according to claim 1, wherein ethylene oxide is used in an amount between 1 and 2 mol equivalents, based on the compound of formula (II).

7. A compound of formula (I) ##STR00006## in which R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5 have the meanings given in the table TABLE-US-00004 R.sup.1 R.sup.2 R.sup.3 R.sup.4 R.sup.5 Me H Cl H Me Me H Cl H Et Et H Cl H Et Me H Cl H n-Pr Et H Cl H n-Pr n-Pr H Cl H n-Pr Me H Cl H iso- Pr Et H Cl H iso- Pr iso- H Cl H iso- Pr Pr iso- H Cl H n-Pr Pr Me H F H Me Me H F H Et Et H F H Et Me H CF.sub.3 H Me Me H CF.sub.3 H Et Et H CF.sub.3 H Et Me H OCF.sub.3 H Me Me H Me H Et Me H Et H Et Me H Et H Me Me Cl H H Me Et Cl H H Me Et H H Cl Me with the proviso that R.sup.3 is selected from Cl, F, CF.sub.3 or OCF.sub.3 or with the proviso that R.sup.2 or R.sup.4 is Cl.

8. The compound of claim 7, wherein R.sup.3 is selected from Cl, F, CF.sub.3 or OCF.sub.3.

9. The compound of claim 7, wherein R.sup.2 or R.sup.4 is Cl.

10. The compound of claim 7, which is 2-(4-chloro-2,6-dimethylphenyl)ethanol.

Description

DETAILED DESCRIPTION OF A PREFERRED EMBODIMENT

(1) The compound of the formula (II) is also intended to include the other forms of the Schlenk equilibrium known to the person skilled in the art, with and without complexation of solvent molecules.

(2) Preference is given to the preparation of 2-arylethanols of the formula (I) in which R.sup.1, R.sup.5 independently of one another represent C.sub.1-C.sub.6-alkyl, C.sub.1-C.sub.6-fluoroalkyl having 1 to 13 fluorine atoms, optionally substituted C.sub.6-C.sub.10-aryl, fluorine, chlorine, a radical NR.sup.6.sub.2, OR.sup.6 or SR.sup.6, where R.sup.6 represents C.sub.1-C.sub.6-alkyl, C.sub.1-C.sub.2-fluoroalkyl having 1 to 5 fluorine atoms or phenyl, R.sup.2, R.sup.3, R.sup.4 independently of one another represent hydrogen, C.sub.1-C.sub.6-alkyl, C.sub.1-C.sub.2-fluoroalkyl having 1 to 5 fluorine atoms, phenyl optionally substituted by C.sub.1-C.sub.4-alkyl, C.sub.1-C.sub.4-alkoxy, fluorine or chlorine, fluorine, chlorine or a radical OR.sup.6, where R.sup.6 represents C.sub.1-C.sub.6-alkyl, C.sub.1-C.sub.2-fluoroalkyl having 1 to 5 fluorine atoms or phenyl.

(3) Particular preference is given to the preparation of 2-arylethanols of the formula (I) in which R.sup.1, R.sup.5 independently of one another represent methyl, ethyl, n-propyl, iso-propyl, trifluoromethyl, phenyl optionally substituted by methyl, ethyl, n-propyl, iso-propyl, methoxy, ethoxy or fluorine, fluorine, chlorine or a radical OR.sup.6, where R.sup.6 represents methyl, ethyl, n-propyl, iso-propyl, n-butyl, tert-butyl, CHF.sub.2, CF.sub.3 or C.sub.2F.sub.5 and R.sup.2, R.sup.3, R.sup.4 independently of one another represent hydrogen, methyl, ethyl, n-propyl, iso-propyl, trifluoromethyl, phenyl optionally substituted by methyl, ethyl, n-propyl, iso-propyl, methoxy, ethoxy or fluorine, fluorine, chlorine or a radical OR.sup.6, where R.sup.6 represents methyl, ethyl, n-propyl, iso-propyl, n-butyl, tert-butyl, CHF.sub.2, CF.sub.3 or C.sub.2F.sub.5.

(4) Very particular preference is given to the preparation of the following 2-arylethanols: 2-(4-chloro-2,6-dimethylphenyl)ethanol 2-(4-chloro-2,6-diethylphenyl)ethanol 2-(2,6-dimethyl-4-trifluoromethylphenyl)ethanol 2-(4-fluoro-2,6-dimethylphenyl)ethanol 2-(2,6-dimethyl-4-trifluoromethoxyphenyl)ethanol 2-(2-ethyl-4,6-dimethylphenyl)ethanol 2-(2,4-diethyl-6-methylphenyl)ethanol 2-(3-chloro-2,6-dimethylphenyl)ethanol.

(5) Emphasis is given to the preparation of 2-(4-chloro-2,6-dimethylphenyl)ethanol.

(6) The above-listed general radical definitions and elucidations or those listed in preferred ranges may be combined arbitrarily with one another, in other words including combinations between the respective ranges and preferred ranges. They apply both to the end products and correspondingly to the intermediates.

(7) The preparation of the Grignard compounds of the formula (II) takes place by generally known methods of organic chemistry from the corresponding substituted aryl halide and magnesium. The aryl halides that can be used here are the chloro-, bromo- or iodoaromatics. Preference is given to using the bromo- and iodoaromatics, particularly preferably the bromoaromatics.

(8) Suitable solvents for the preparation of the Grignard compounds of the formula (II) are for example open-chain and cyclic ethers such as, for example, diethyl ether, methyl tertiary-butyl ether, tertiary-amyl methyl ether, tetrahydrofuran, 2-methyltetrahydrofuran, 2,5-dimethyltetrahydrofuran, methyl cyclopentyl ether or 1,4-dioxane; aromatic hydrocarbons such as toluene, xylenes or mesitylene; mixtures of these solvents. Preference is given to working in cyclic ethers or in mixtures of cyclic ethers with aromatic hydrocarbons.

(9) The temperature during the preparation of the Grignard compounds of the formula (II) can vary within wide limits. Preference is given to working at between 20 C. and 100 C.

(10) The magnesium is generally used in an excess based on the haloaromatics, usually 1.05 to 1.2 equivalents.

(11) After the reaction of the haloaromatic with the magnesium has taken place, the not fully reacted excess magnesium can be removed by a filtration.

(12) In the inventive step of the process, the Grignard compound of the formula (II) prepared as described above is reacted in the presence of a copper compound with ethylene oxide.

(13) Suitable solvents for the inventive step of the process are the solvents that are used for the preparation of the Grignard compound of the formula (II): Open-chain and cyclic ethers such as diethyl ether, methyl tertiary-butyl ether, tertiary-amyl methyl ether, tetrahydrofuran, 2-methyltetrahydrofuran, 2,5-dimethyltetrahydrofuran, methyl cyclopentyl ether or 1,4-dioxane; aromatic hydrocarbons such as toluene, xylenes or mesitylene; mixtures of these solvents. Preference is given to working in cyclic ethers or in mixtures of cyclic ethers with aromatic hydrocarbons. Particular preference is given to tetrahydrofuran, 2-methyltetrahydrofuran, methyl cyclopentyl ether, mixtures of these ethers and mixtures of these ethers with toluene.

(14) The copper compounds used in the inventive step of the process are copper(I) or copper(II) compounds. By way of example, mention may be made of copper(I) iodide, copper(I) bromide, copper(I) chloride, copper(I) oxide, copper(II) bromide, copper(II) chloride, copper(II) oxide, copper(II) sulphate, copper(II) nitrate, copper(II) acetate. Preference is given to using copper(I) iodide, copper(I) bromide, copper(II) bromide and copper(I) chloride, particularly preferably copper(I) iodide, copper(I) bromide and copper(II) bromide.

(15) The amount of copper compound in the inventive step of the process can be varied within wide limits. Preference is given to using the smallest amount of copper compound necessary to bring about the desired effect. Preference is given to using 0.1 to 50 mol percent, based on the Grignard compound of the formula (II); particularly preferably 0.5 to 15 mol percent.

(16) The amount of ethylene oxide in the inventive step of the process can likewise be varied within wide limits. Preference is given to using between 0.9 and 3 mol equivalents of ethylene oxide, based on the Grignard compound of the formula (II). Particular preference is given to using between 1 and 2 mol equivalents of ethylene oxide.

(17) The ethylene oxide can either be introduced as a gas into the solution of the Grignard compound of the formula (II), or the ethylene oxide is metered in as a solution. Suitable solvents here are preferably those solvents that have been used in the preparation of the Grignard compound of the formula (II).

(18) The reaction temperature in the inventive step of the process is between 30 and +100 C. Preferably, it is between 0 and 80 C., particularly preferably between +10 and +50 C.

(19) The reaction in the inventive step of the process can in principle also be carried out under reduced or increased pressure. Preference is given to working at atmospheric pressure.

(20) The work-up of the reaction mixtures takes place by customary and known methods of organic chemistry.

(21) The present invention likewise provides novel substituted 2-arylethanols of the formula (I)

(22) ##STR00003##
in which the radicals R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5 have the meanings given in Table 1.

(23) TABLE-US-00001 TABLE 1 Compound R.sup.1 R.sup.2 R.sup.3 R.sup.4 R.sup.5 I-1 Me H Cl H Me I-2 Me H Cl H Et I-3 Et H Cl H Et I-4 Me H Cl H n-Pr I-5 Et H Cl H n-Pr I-6 n-Pr H Cl H n-Pr I-7 Me H Cl H iso-Pr I-8 Et H Cl H iso-Pr I-9 iso-Pr H Cl H iso-Pr I-10 iso-Pr H Cl H n-Pr I-11 Me H F H Me I-12 Me H F H Et I-13 Et H F H Et I-14 Me H CF.sub.3 H Me I-15 Me H CF.sub.3 H Et I-16 Et H CF.sub.3 H Et I-17 Me H OCF.sub.3 H Me I-18 Me H Me H Et I-19 Me H Et H Et I-20 Me H Et H Me I-21 Me Cl H H Me I-22 Et Cl H H Me I-23 Et H H Cl Me Me = Methyl, Et = Ethyl, n-Pr = n-Propyl, iso-Pr = iso-Propyl

(24) Particular preference is given to novel substituted 2-arylethanols of the formula (I) in which the radicals R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5 have the meanings given in Table 2.

(25) TABLE-US-00002 TABLE 2 Compound R.sup.1 R.sup.2 R.sup.3 R.sup.4 R.sup.5 I-1 Me H Cl H Me I-2 Me H Cl H Et I-3 Et H Cl H Et I-4 Me H Cl H n-Pr I-5 Et H Cl H n-Pr I-6 n-Pr H Cl H n-Pr I-11 Me H F H Me I-12 Me H F H Et I-13 Et H F H Et I-18 Me H Me H Et I-19 Me H Et H Et I-20 Me H Et H Me I-21 Me Cl H H Me I-22 Et Cl H H Me I-23 Et H H Cl Me

(26) Very particular preference is given to novel substituted 2-arylethanols of the formula (I) in which the radicals R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5 have the meanings given in Table 3.

(27) TABLE-US-00003 TABLE 3 Compound R.sup.1 R.sup.2 R.sup.3 R.sup.4 R.sup.5 I-1 Me H Cl H Me I-2 Me H Cl H Et I-3 Et H Cl H Et I-11 Me H F H Me I-12 Me H F H Et I-13 Et H F H Et I-18 Me H Me H Et I-19 Me H Et H Et I-20 Me H Et H Me I-21 Me Cl H H Me

(28) Over and above this, preference is given to the following compound: 2-(4-chloro-2,6-dimethylphenyl)ethanol (compound I-1).

(29) The oxidation of the substituted 2-arylethanols of the formula (I) to the substituted phenylacetic acids required as building blocks for example for insecticidal or herbicidal cyclic ketoenols can take place by methods of organic chemistry known in principle. By way of example, mention may be made of the oxidation with potassium permanganate or the Zhao-Anelli oxidation with 2,2,6,6-tetramethylpiperidinyloxyl, sodium hypochlorite and sodium chlorite (Organic Syntheses, 81, 195-203; 2005).

(30) The present invention will be illustrated in more detail by the examples below, without any intention of limiting it thereto.

EXAMPLES

Example 1: 2-(4-Chloro-2,6-dimethylphenyl)ethanol (Compound I-1)

(31) To a solution of bromo(4-chloro-2,6-dimethylphenyl)magnesium, prepared at 30-35 C. from 50 mmol of 4-chloro-2,6-dimethylbromobenzene, 1 mmol of bromo(4-chloro-2,6-dimethylphenyl)magnesium (to start the Grignard synthesis) and 55.5 mmol of magnesium in 50 ml of tetrahydrofuran, were added 5 mmol of copper(I) iodide. Then, 48 ml of a 2.5-3.3 molar solution of ethylene oxide in tetrahydrofuran (120 mmol, calculated for a concentration of 2.5 M) were metered in at 20 C. over the course of 30 minutes. After 16 hours at 20 C., the reaction mixture was placed on 100 g of ice and adjusted to pH 1 with sulphuric acid. After triple extraction with in each case 50 ml of methylene chloride, the combined organic phases were extracted once by shaking with 30 ml of water, dried over magnesium sulphate and concentrated on a rotary evaporator. There remained an oil, in which, according to GC/MS analysis, the ratio of 2-(4-chloro-2,6-dimethylphenyl)ethanol to 1-(4-chloro-2,6-dimethylphenyl)ethanol was >99:1.

(32) GC/MS: m/e=184 (M.sup.+ (.sup.35Cl), 25%), 153 (.sup.35Cl, 100%).

(33) .sup.1H-NMR (600 MHz, d-DSMO): =2.28 (s, 6H), 2.75 (m, 2H), 3.45 (m, 2H), 4.74 (m, 1H), 7.0 (s, 2H) ppm.

Example 2: 2-(4-Chloro-2,6-dimethylphenyl)ethanol (Compound I-1)

(34) To a solution of bromo(4-chloro-2,6-dimethylphenyl)magnesium, prepared at 30-35 C. from 10 mmol of 4-chloro-2,6-dimethylbromobenzene, 1 mmol of bromo(4-chloro-2,6-dimethylphenyl)magnesium (to start the Grignard synthesis) and 11.1 mmol of magnesium in 10 ml of tetrahydrofuran, were added 0.1 mmol of copper(I) iodide. Then, 9.6 ml of a 2.5-3.3 molar solution of ethylene oxide in tetrahydrofuran (24 mmol, calculated for a concentration of 2.5 M) were metered in at 20 C. over the course of 30 minutes. After 16 hours at 20 C., the reaction mixture was placed on 100 g of ice and adjusted to pH 1 with sulphuric acid. After triple extraction with in each case 50 ml of methylene chloride, the combined organic phases were extracted once by shaking with 30 ml of water, dried over magnesium sulphate and concentrated on a rotary evaporator. There remained an oil, in which, according to GC/MS analysis, the ratio of 2-(4-chloro-2,6-dimethylphenyl)ethanol to 1-(4-chloro-2,6-dimethylphenyl)ethanol was >99:1.

Example 3: 2-(4-Chloro-2,6-dimethylphenyl)ethanol (Compound I-1)

(35) To a solution of bromo(4-chloro-2,6-dimethylphenyl)magnesium, prepared at 30-35 C. from 10 mmol of 4-chloro-2,6-dimethylbromobenzene, 1 mmol of bromo(4-chloro-2,6-dimethylphenyl)magnesium (to start the Grignard synthesis) and 11.1 mmol of magnesium in 10 ml of tetrahydrofuran, were added 1 mmol of copper(I) iodide. Then, 9.6 ml of a 2.5-3.3 molar solution of ethylene oxide in tetrahydrofuran (24 mmol, calculated for a concentration of 2.5 M) were metered in at 50 C. over the course of 30 minutes. After 16 hours at 50 C., the reaction mixture was placed on 100 g of ice and adjusted to pH 1 with sulphuric acid. After triple extraction with in each case 50 ml of methylene chloride, the combined organic phases were extracted once by shaking with 30 ml of water, dried over magnesium sulphate and concentrated on a rotary evaporator. There remained an oil, in which, according to GC/MS analysis, the ratio of 2-(4-chloro-2,6-dimethylphenyl)ethanol to 1-(4-chloro-2,6-dimethylphenyl)ethanol was >99:1.

Comparative Example 1: 2-(4-Chloro-2,6-dimethylphenyl)ethanol

(36) To a solution of bromo(4-chloro-2,6-dimethylphenyl)magnesium, prepared at 30-50 C. from 10 mmol of 4-chloro-2,6-dimethylbromobenzene and 11.1 mmol of magnesium in 10 ml of tetrahydrofuran, were metered in 8.8 ml of a 2.5-3.3 molar solution of ethylene oxide in tetrahydrofuran (22 mmol, calculated for a concentration of 2.5 M) at 50 C. over the course of 30 minutes. After 3 hours at 50 C., the reaction mixture was placed on 100 g of ice and adjusted to pH 1 with sulphuric acid. After triple extraction with in each case 50 ml of methylene chloride, the combined organic phases were extracted once by shaking with 30 ml of water, dried over magnesium sulphate and concentrated on a rotary evaporator. There remained an oil, in which, according to GC/MS analysis, the ratio of 2-(4-chloro-2,6-dimethylphenyl)ethanol to 1-(4-chloro-2,6-dimethylphenyl)ethanol was 87:13.

Comparative Example 2: 2-(4-Chloro-2,6-dimethylphenyl)ethanol

(37) To a solution of bromo(4-chloro-2,6-dimethylphenyl)magnesium, prepared at 30-35 C. from 10 mmol of 4-chloro-2,6-dimethylbromobenzene, 1 mmol of bromo(4-chloro-2,6-dimethylphenyl)magnesium (to start the Grignard synthesis) and 11.1 mmol of magnesium in 10 ml of tetrahydrofuran, were metered in 9.6 ml of a 2.5-3.3 molar solution of ethylene oxide in tetrahydrofuran (24 mmol, calculated for a concentration of 2.5 M) at 50 C. over the course of 30 minutes. After 16 hours at 50 C., the reaction mixture was placed on 100 g of ice and adjusted to pH 1 with sulphuric acid. After triple extraction with in each case 50 ml of methylene chloride, the combined organic phases were extracted once by shaking with 30 ml of water, dried over magnesium sulphate and concentrated on a rotary evaporator. There remained an oil, in which, according to GC/MS analysis, the ratio of 2-(4-chloro-2,6-dimethylphenyl)ethanol to 1-(4-chloro-2,6-dimethylphenyl)ethanol was 78:22.

Example 4: 2-(4-Chloro-2,6-dimethylphenyl)ethanol (Compound I-1)

(38) To a solution of 20 mmol of bromo(4-chloro-2,6-dimethylphenyl)magnesium in 20 ml tetrahydrofuran were added 2 mmol of copper(I) bromide. Then, 16 ml of a 2.5-3.3 molar solution of ethylene oxide in tetrahydrofuran (40 mmol, calculated for a concentration of 2.5 M) were metered in at 20 C. over the course of 30 minutes. After 16 hours at 20 C., the reaction mixture was placed on 100 g of ice and adjusted to pH 1 with sulphuric acid. After triple extraction with in each case 50 ml of methylene chloride, the combined organic phases were extracted once by shaking with 30 ml of water, dried over magnesium sulphate and concentrated on a rotary evaporator. There remained an oil, in which, according to GC/MS analysis, the ratio of 2-(4-chloro-2,6-dimethylphenyl)ethanol to 1-(4-chloro-2,6-dimethylphenyl)ethanol was >99:1.

Example 5: 2-(4-Chloro-2,6-dimethylphenyl)ethanol (Compound I-1)

(39) The procedure was as in Example 4 but now using 1 mmol of copper(II) bromide instead of Cu(I)Br. The ratio of 2-(4-chloro-2,6-dimethylphenyl)ethanol to 1-(4-chloro-2,6-dimethylphenyl)ethanol was >99:1.

Example 6: 2-(4-Chloro-2,6-dimethylphenyl)ethanol (Compound I-1)

(40) The procedure was as in Example 4 but now using 1 mmol of copper(I) chloride instead of Cu(I)Br. The ratio of 2-(4-chloro-2,6-dimethylphenyl)ethanol to 1-(4-chloro-2,6-dimethylphenyl)ethanol was >99:1.

Example 7: 2-(2,6-Dimethylphenyl)ethanol

(41) To a solution of 2,6-dimethylphenylmagnesium, prepared at 30-35 C. from 20 mmol of 2,6-dimethylbromobenzene and 22.2 mmol of magnesium in 10 ml of tetrahydrofuran, were added 0.2 mmol of copper(I) iodide. Then, 8.8 ml of a 2.5-3.3 molar solution of ethylene oxide in tetrahydrofuran (22 mmol, calculated for a concentration of 2.5 M) were metered in at 20 C. over the course of 30 minutes. After 16 hours at 20 C., the reaction mixture was placed on 100 g of ice and adjusted to pH 1 with sulphuric acid. After triple extraction with in each case 50 ml of methylene chloride, the combined organic phases were extracted once by shaking with 30 ml of water, dried over magnesium sulphate and concentrated on a rotary evaporator. There remained an oil, in which, according to GC/MS analysis, the ratio of 2-(2,6-dimethylphenyl)ethanol to 1-(2,6-dimethylphenyl)ethanol was 97.5:2.5.

Comparative Example 3: 2-(2,6-Dimethylphenyl)ethanol

(42) Into a solution of 2,6-dimethylphenylmagnesium, prepared at 40-55 C., towards the end for a few minutes at 65 C., from 200 mmol of 2,6-dimethylbromobenzene and 222 mmol of magnesium in 100 ml of tetrahydrofuran, were introduced 215 mmol of ethylene oxide at 30-35 C. over the course of about 2 hours. After 3 hours at 60 C., the reaction mixture was placed on 200 g of ice and adjusted to pH 1 with sulphuric acid. After triple extraction with in each case 50 ml of methylene chloride, the combined organic phases were extracted once by shaking with 30 ml of water, dried over magnesium sulphate and concentrated on a rotary evaporator. There remained an oil, in which, according to GC/MS analysis, the ratio of 2-(2,6-dimethylphenyl)ethanol to 1-(2,6-dimethylphenyl)ethanol was 81:19.

Use Example 1: 4-Chloro-2,6-dimethylphenylacetic acid

(43) To a solution of 5 g of 2-(4-chloro-2,6-dimethylphenyl)ethanol (24 mmol, purity 90%) in 20 g of acetonitrile were added 38 mg of 2,2,6,6-tetramethylpiperidinyloxyl (0.24 mmol) at room temperature. To this solution were added, at 45 C., 0.8 ml of 11.05% strength sodium hypochlorite solution and then 4.3 g of sodium chlorite (36 mmol), dissolved in 12.5 g of a phosphate buffer (10.65 g of Na.sub.2HPO.sub.4 and 10.21 g of KH.sub.2PO.sub.4 per 1000 ml of water) were added dropwise over the course of one hour using a metering pump. When the addition was complete, the mixture was after-stirred for 30 min and cooled to 5-10 C. and 3 g of sodium sulphite were added in portions. The reaction mixture was then after-stirred for one hour and adjusted to pH 13.5 with 45% strength sodium hydroxide solution and the resulting suspension was extracted twice with in each case 25 ml of MTBE. The aqueous phase was adjusted to pH 3.38 with 10% strength hydrochloric acid and extracted three times with in each case 30 ml of MTBE. The combined organic phases of the acid extraction were dried and concentrated. This gave 4.3 g of product (87% of theory; purity 98% according to HPLC and quant. NMR).