PROCESS FOR PREPARING 3-CHLORO-2-VINYLPHENYLSULFONATES

Abstract

The present invention relates to a new process for preparing 3-chloro-2-vinylphenylsulfonate derivatives.

Claims

1. A process for preparing one or more 3-chloro-2-vinylphenylsulfonate derivatives of formula (I), ##STR00022## wherein R.sup.1 represents C.sub.1-C.sub.6-alkyl, phenyl, 4-methylphenyl or benzyl, comprising (A) reacting 3-chloro-2-methylphenol of formula (II) ##STR00023## with a compound of formula (III), ##STR00024## wherein Hal represents F, Cl, or Br and R.sup.2 represents F, Cl, Br, F.sub.3C, F.sub.2HC, Cl.sub.3C, Cl.sub.2HC, ClH.sub.2C or Cl.sub.3CO, Or reacting with an acid derivative of formula (IV), ##STR00025## wherein R.sup.3 and R.sup.4 independently from each other represent F.sub.3C, F.sub.2HC, Cl.sub.3C, Cl.sub.2HC, ClH.sub.2C, Or reacting with triphosgene in the presence of a base and a solvent to form a compound of formula (V) ##STR00026## wherein R.sup.5 represents F, Cl, CCl.sub.3, CHCl.sub.2, CH.sub.2Cl, CF.sub.3, CHF.sub.2 or 3-chloro-2-methylphenoxy and (B) reacting one or more compounds of formula (V) with a chlorinating agent to produce one or more compounds of formula (VI) ##STR00027## wherein R.sup.6 represents F, Cl, CCl.sub.3, CHCl.sub.2, CH.sub.2Cl, CF.sub.3, CHF.sub.2 or 3-chloro-2-(dichloromethyl)phenoxy and (C) reacting a compound of formula (VI) to 2-chloro-6-hydroxybenzaldehyde (VII) ##STR00028## under acidic conditions or at elevated temperature in water and (D) reacting a compound of formula (VII) or an alkaline or alkaline earth metal salt in the presence of a solvent with a compound of formula (VIII)
Me-Q(VIII), wherein Q represents Li, Na, K, MgCl, MgBr or, MgI to produce 3-chloro-2-(1-hydroxyethyl)phenol (IX) ##STR00029## and (E) forming 3-chloro-2-vinylphenylsulfonate of formula (I) by reacting a compound of formula (IX) in the presence of a base with compound of formula (X)
R.sup.1SO.sub.2W(X), wherein W represents F, Cl, Br or OSO.sub.2R.sup.1.

2. A process according to claim 1, wherein R.sup.1 represents methyl, ethyl, n-propyl, i-propyl, n-butyl, phenyl, 4-methylphenyl or benzyl; R.sup.2 represents F, Cl, F.sub.3C, F.sub.2HC, Cl.sub.3C, Cl.sub.2HC, ClH.sub.2C or Cl.sub.3CO; R.sup.3 and R.sup.4 independently from each other represent F.sub.3C, F.sub.2HC, Cl.sub.3C, Cl.sub.2HC or ClH.sub.2C; R.sup.5 represents F, Cl, CCl.sub.3, CHCl.sub.2, CH.sub.2Cl, CF.sub.3, CHF.sub.2 or 3-chloro-2-methylphenoxy; R.sup.6 represents F, Cl, CCl.sub.3, CHCl.sub.2, CH.sub.2Cl, CF.sub.3, CHF.sub.2 or 3-chloro-2-(dichloromethyl) phenoxy; W represents F, Cl or OSO.sub.2R.sup.1; Q represents Na, K, MgCl or MgBr.

3. A process according to claim 1, wherein R.sup.1 represents methyl, ethyl, n-propyl, phenyl, 4-methylphenyl; R.sup.2 represents F, Cl, F.sub.3C, F.sub.2HC, Cl.sub.3C, Cl.sub.2HC, ClH.sub.2C or Cl.sub.3CO; R.sup.3 and R.sup.4 independently from each other represent F.sub.3C, Cl.sub.3C, Cl.sub.2HC, ClH.sub.2C; R.sup.5 represents F, Cl, CCl.sub.3, CHCl.sub.2, CH.sub.2Cl, CF.sub.3, F.sub.2HC or 3-chloro-2-methylphenoxy; R.sup.6 represents F, Cl, CCl.sub.3, CHCl.sub.2, CH.sub.2Cl, CF.sub.3, F.sub.2HC or 3-chloro-2-(dichloro)methylphenoxy; W represents F, Cl or OSO.sub.2R.sup.1; Q represents Na, K, MgCl or MgBr.

4. A process according to claim 1, wherein R.sup.1 represents methyl or 4-methylphenyl; R.sup.2 represents F, Cl, F.sub.3C or Cl.sub.3CO; R.sup.3 and R.sup.4 independently from each other represent F.sub.3C or Cl.sub.3C; R.sup.5 represents F, Cl, CCl.sub.3, F.sub.3C or 3-chloro-2-methylphenoxy; R.sup.6 represents F, Cl, CCl.sub.3, F.sub.3C or 3-chloro-2-(dichloro)methylphenoxy; W represents F, Cl or OSO.sub.2R.sup.1; Q represents MgCl or MgBr.

5. A process according to claim 1, wherein in (A), 3-methylpyridine and 2-methyl-5-ethylpyridine are used as base and dichloromethane, toluene, chlorobenzene or dichloromethane as solvent.

6. A process according to claim 1, wherein in (B), chlorine is used as chlorinating agent.

7. A process according to claim 1, wherein in (C), HCOOH, CH.sub.3COOH, H.sub.2SO.sub.4, or HCl is used as acid.

8. A process according to claim 1, wherein (C) is performed in water at temperatures between 80 and 140 C.

9. A process according to claim 1, wherein in (D), MeMgCl or MeMgBr is used as organometallic reagent and THF, 2-Me-THF, toluene or xylene as solvent.

10. A process according to claim 1 wherein in (E), alkali metal carbonate or hydroxide, triethylamine or pyridine is used as base.

11. A process for preparing one or more 3-chloro-2-vinylphenylsulfonate derivatives of formula (I), ##STR00030## according to claim 1 comprising transforming one or more compounds of formula (IX) into 3-chloro-2-vinylphenol (XII) ##STR00031## in the presence of an acid and a solvent (F) and then transformed into compounds of formula (I) in the presence of one or more compounds of formula (X) and a base (G).

12. A Compound of formula (V) ##STR00032## wherein R.sup.5 represents F, Cl, CCl.sub.3, CHCl.sub.2, CH.sub.2Cl, CF.sub.3, CHF.sub.2 or 3-chloro-2-methylphenoxy.

13. A Compound of formula (VI) ##STR00033## wherein R.sup.6 represents F, Cl, CCl.sub.3, CHCl.sub.2, CH.sub.2Cl, CF.sub.3, CHF.sub.2, or 3-chloro-2-(dichloromethyl)phenoxy.

14. 3-Chloro-2-(1-hydroxyethyl)phenol (IX) ##STR00034##

Description

EXPERIMENTAL EXAMPLES

Example 1

[0154] ##STR00014##

3-Chloro-2-methylphenyl trichloroacetate

[0155] 142 g of 2-methyl-3-chlorophenol and 90 g of pyridine were placed in 700 ml toluene. 180 g of trichloroacetylchloride were added to this slurry within two h. The mixture was stirred for two h at 20 C. and the precipitate (pyridinium hydrochloride salt) was filtered off. The filtrate was washed two times with 200 ml of cold water and dried over MgSO.sub.4. The solvent was removed in vacuum to give 288 g of a yellow liquid (98% yield).

[0156] m/z=288

[0157] 1H-NMR (CDCl.sub.3): : 7.36 (d, 1H), 7.2 (t, 1H), 7.08 (d, 1H) ppm.

Example 2

[0158] ##STR00015##

3-Chloro-2-methylphenyl carbonochloridate

[0159] 14.2 g of 2-methyl-3-chlorophenol and 14 g of phosgene (as 20% solution in toluene) were charged to the reaction flask. The mixture was cooled to 10 C. and 12.2 g of N,N-dimethylaniline ware added within one hour at this temperature. The mixture was stirred for three hours at room temperature. After that the precipitate was filtered off. The toluene was removed in vacuum and the resulting residue was dissolved in 100 ml methyl-tert.-butylether. The formed new precipitate was filtered off and the filtrate concentrated in vacuum yielding 18.4 g of a pale yellow liquid.

[0160] m/z=205

[0161] .sup.1H-NMR (CDCl.sub.3): :7.30 (m, 1H), 7.15 (t, 1H), 7.15 (m, 1H) ppm.

Example 3

[0162] ##STR00016##

3-Chloro-2-(dichloromethyl)phenyl trichloroacetate

[0163] A solution of 85 g (0.295 mol) of compound of example 1 in 280 ml carbon tetrachloride was placed in a glass reactor with an inlet pipe for chlorine gas and a dip tube with a UV-lamp (Heraeus TQ-Strahler 150/56001725). The solution was heated to 60 C. and 96 g (1.354 mol) Cl.sub.2 were passed into the solution under UV-irridation within 490 minutes. The carbon tetrachloride was distilled off to give 111.6 g of a light yellow oil with a purity of 91.2% (GC), representing a yield of 97% of theory.

[0164] GC/MS: m/z=354 (M.sup.+, 6.sup.35Cl, 18%), 319 (M-Cl, 100%).

[0165] .sup.1H-NMR (600 MHz, CDCl.sub.3): =7.2 (m, 1H), 7.3 (s, 1H, ArCH(Cl).sub.2), 7.4-7.47 (m, 2H) ppm.

Example 4

[0166] ##STR00017##

3-Chloro-2-(dichloromethyl)phenyl carbonochloridate

[0167] A solution of 4.1 g (20 mmol) of compound of example 2 in 90 ml 2 carbon tetrachloride was placed in a glass reactor with an inlet pipe for chlorine gas and a dip tube with a UV-lamp (Heraeus TQ-Strahler 150/56001725). The solution was heated to 50 C. and 21 g (296 mmol) Cl.sub.2 were passed into the solution under UV-irridation within 450 minutes. The carbon tetrachloride was distilled off to give 98% yield of the target compound.

[0168] GC/MS: m/z=272 (M.sup.+, 4.sup.35Cl; 18%), 237 (M-35; 40%), 193 (M-OC(O)Cl; 100%).

[0169] .sup.1H-NMR (CDCl.sub.3): =7.3 (m, 1H), 7.38-7.47 (m, 3H) ppm.

Example 5

[0170] ##STR00018##

2-Chloro-6-hydroxybenzaldehyde

[0171] A mixture 36 g of 3-chloro-2-(dichloromethyl)phenyl trichloroacetate, 30 ml of acetic acid and 100 ml water was heated at 90-95 C. After six hours the mixture was cooled to room temperature and the product was extracted three times each with 50 ml of ethylacetate. The organic extract was washed with 100 ml of water and the solvent removed in vacuum to give 14.8 g of a yellow solid.

[0172] m/z=156

[0173] .sup.1H-NMR (CDCl.sub.3): :11.5 (s, 1H), 10.4 (s, 1H), 7.5 (t, 1H), 7.1 (d, 1H), 6.9 (s, 1H) ppm.

Example 6

2-Chloro-6-hydroxybenzaldehyde

[0174] A mixture of 27 g of 3-chloro-2-(dichloromethyl)phenyl carbonochloridate, 30 ml of acetic acid and 80 ml water was heated at 90-95 C. After four hours the mixture was cooled to room temperature and the product was extracted three times with 50 ml of ethylacetate, each. The organic extract was washed with 100 ml of water and the solvent removed in vacuum to give 14.5 g of a yellow solid

[0175] .sup.1H NMR (CDCl.sub.3): :11.5 (s, 1H), 10.4 (s, 1H), 7.5 (t, 1H), 7.1 (d, 1H), 6.9 (s. 1H) ppm.

Example 7

2-Chloro-6-hydroxybenzaldehyde

[0176] A mixture of 36 g of 3-chloro-2-(dichloromethyl)phenyl trichloroacetate, 30 ml of formic acid and 100 ml water was heated at 90 C. After six hours the mixture was cooled to room temperature and the product was extracted three times with 50 ml of ethylacetate, each. The organic extract was washed with 100 ml of water and the solvent was removed in vacuum to give 14.7 g of a yellow solid.

[0177] .sup.1H NMR (CDCl.sub.3): :11.5 (s, 1H), 10.4 (s, 1H), 7.5 (t, 1H), 7.1 (d, 1H), 6.9 (s, 1H) ppm.

Example 8

[0178] ##STR00019##

3-Chloro-2-(1-hydroxyethyl)phenol

[0179] To 500 ml of a 3M THF solution of MeMgCl is added 107 g of a 60 C. warm melt of 2-chloro-6-hydroxybenzaldehyde over 30-60 min. The temperature of the mixture is maintained at reflux during the addition. Gas evolution is observed. After complete addition the mixture was cooled to room temperature and added to 650 ml 10% aqueous HCl under ice cooling. The organic layer is washed with saturated aqueous NaHCO.sub.3, dried with MgSO.sub.4, filtered and the solvent removed to give 123 g of 3-chloro-2-(1-hydroxyethyl)phenol (91% of theory)

[0180] Quant. NMR: 87%

[0181] .sup.1H NMR (DMSO-d6): =10.0 (br s, 1H), 7.1 (t, 1H), 6.9 (d, 1H), 6.7 (s, 1H), 5.28-5.31 (m, 1H), 1.4 (d, 3H) ppm.

Example 9

3-Chloro-2-(1-hydroxyethyl)phenol

[0182] To a mixture of 5.8 g of the potassium salt of 2-chloro-6-hydroxybenzaldehyde in 20 g THF was added 10.4 ml of a 3M MeMgCl solution in THF within 30 min at reflux temperature. The HPLC showed 80% conversion.

Example 10

3-Chloro-2-(1-hydroxyethyl)phenol

[0183] To a mixture of 1.1 g of the potassium salt of 2-chloro-6-hydroxybenzaldehyde in 9 g THF was added 3.5 ml Methyllithium of a 1.6M solution in ether at 0 C. The HPLC showed 1:3 mixture of product:aldehyde.

Example 11

3-Chloro-2-vinylphenol

[0184] ##STR00020##

[0185] To a solution of 50 g 3-chloro-2-(1-hydroxyethyl)phenol (87% purity) in 280 g DMAc is added 24 g of methansulfonic acid at 160 C. and stirred for 90 min. The mixture is cooled, 250 ml toluene and 200 ml water are added, the organic layer washed with saturated aqueous NaHCO.sub.3. The crude product is concentrated via thin film distillation to obtain 3-chloro-2-vinylphenol as a 60 wt-% solution in DMAc (determined by quant. NMR), which corresponds to circa 78% yield.

[0186] .sup.1H NMR (DMSO-d6): =10.1 (s, 1H), 7.06 (t, 1H), 6.90-6.79 (m, 3H), 6.13-6.10 (m, 1H), 5.54-5.51 (m, 1H) ppm.

Example 12

3-Chloro-2-vinylphenol

[0187] To a mixture of 16.8 g 3-chloro-2-(1-hydroxyethyl)phenol in DMAC/xylene (27 g/54 g) is added 9.3 g of methansulfonic acid at 160 C. and stirred for 90 min. The mixture is concentrated via thin film distillation to obtain 37.5 g 3-chloro-2-vinylphenol as a solution in DMAC (34% purity determined by quant. NMR), which corresponds to 85% yield.

Example 13

3-Chloro-2-vinylphenol

[0188] To a mixture of 17.4 g 3-chloro-2-(1-hydroxyethyl)phenol in 180 g DMAC is added 7.6 g of trifluoromethylsulfonic acid at 160 C. and stirred for 30 min. The mixture is cooled and concentrated via thin film distillation to obtain 35.7 g 3-chloro-2-vinylphenol as a solution in DMAC (34% purity determined by quant. NMR), which corresponds to 77% yield.

Example 14

3-Chloro-2-vinylphenol

[0189] To a mixture of 7.4 g 3-chloro-2-(1-hydroxyethyl)phenol in DMAC/toluene (18 g/36 g) is added 4.1 g of methansulfonic acid at 160 C. and stirred for 120 min. The produced water is continuously removed via Dean-Stark apparatus. The mixture is cooled, the organic layer washed with saturated aqueous NaHCO.sub.3. The crude product is concentrated to obtain 8.5 g 3-chloro-2-vinylphenol as a 57 wt-% solution in DMAC (determined by quant. NMR), which corresponds to 73% yield.

Example 15

3-Chloro-2-vinylphenol

[0190] To a mixture of 1 g 3-chloro-2-(1-hydroxyethyl)phenol in 9 g tetramethylurea is added 0.5 g of methansulfonic acid at 140 C. and stirred for 60 min. HPLC indicates 88% conversion and 82% 3-chloro-2-vinylphenol.

Example 16

3-Chloro-2-vinylphenol

[0191] To a mixture of 0.5 g 3-chloro-2-(1-hydroxyethyl)phenol in 4.5 g DMAc is added 0.025 g of methansulfonic acid at 160 C. and stirred for 120 min. HPLC indicates 94% conversion and 77% 3-chloro-2-vinylphenol.

Example 17

[0192] ##STR00021##

3-Chloro-2-vinylphenyl methanesulfonate

[0193] The DMAC solution of example 11 is added to 17 g triethylamine in 400 g MTBE. At 0-5 C. 19.1 g of methansulfonic acid chloride is added within one hour via syringe pump. After stirring for another 10 min the mixture is added to 250 ml of 15% aqueous hydrochloric acid, the organic layer dried over MgSO.sub.4 and concentrated in vacuo to give 53 g crude 3-chloro-2-vinylphenyl methanesulfonate (Quant. NMR 82% purity; 95% of theory)

[0194] Recrystallization in methylcyclohexane/MTBE gives 34.5 g product (quant. NMR: 96% purity; 72% of theory).

[0195] .sup.1H NMR (DMSO-d6): =7.52-7.51 (m, 1H), 7.44-7.39 (m, 2H), 6.75-6.70 (m, 1H), 5.87-5.84 (m, 1H), 5.76-5.74 (m, 1H), 5.54-5.51 (m, 1H), 3.44 (s, 3H) ppm.

Example 18

3-Chloro-2-vinylphenyl methanesulfonate

[0196] To a solution of 2.59 g of 3-chloro-2-(1-hydroxyethyl)phenol and 4.3 g of methansulfonic acid chloride in 50 ml methyl-tert.-butylether 3.79 g of triethylamine was slowly added at 0 C. The mixture was stirred 1 h at 0 C. and 5 h at 20 C. 50 ml of water were added to the formed suspension and the organic phase was separated and washed with 50 ml water. The solvent was evaporated and the product was purified via crystallization from the mixture MCH/MTBE yielding 2.64 g (76%) of the white solid.

[0197] .sup.1H NMR (DMSO-d6): =7.52-7.51 (m, 1H), 7.44-7.39 (m, 2H), 6.75-6.70 (m, 1H), 5.87-5.84 (m, 1H), 5.76-5.74 (m, 1H), 5.54-5.51 (m, 1H), 3.44 (s, 3H) ppm.