METHOD FOR PREPARING 3-SUBSTITUTED 2-VINYLPHENYL SULFONATES

Abstract

The present invention relates to a method for preparing 3-substituted 2-vinylphenyl sulfonates.

Claims

1. Method for preparing a vinylphenyl sulfonate of formula (I): ##STR00014## in which R.sup.1 is C.sub.1-C.sub.6-alkyl, phenyl, 4-methylphenyl or benzyl, and R.sup.2 is halogen or methyl, that comprising reacting (a) a compound of formula (II) ##STR00015## with an activator in the presence of a base to give a compound of formula (III) ##STR00016## wherein one or more compounds are used as activators selected from the group consisting of thionyl chloride, phosgene, diphosgene, triphosgene, thiophosgene and chloroformic esters, and reacting (b) the compound of the formula (III in the presence of a base with a compound of formula (IV)
R.sup.1SO.sub.2R.sup.3(IV), where R.sup.3 is F, Cl, Br or OSO.sub.2R.sup.1 and R.sup.1 is as defined in formula (I), to give the vinylphenyl sulfonate of the formula (I).

2. Method according to claim 1, wherein a) and b) are carried out in a one-pot process.

3. Method according to claim 1, wherein one or more bases selected from the group consisting of trialkylamines, pyridyl bases, alkoxide bases and amidine bases is used in (a) and (b).

4. Method according to claim 3, wherein the base used is tributylamine.

5. Method according to claim 1, wherein one or more solvents are used in (a) and (b) selected from the group consisting of petroleum ether, n-hexane, n-heptane, cyclohexane, methylcyclohexane, toluene, o-xylene, m-xylene, p-xylene, decaline, chlorobenzene, 1,2-dichlorobenzene, dichloromethane, chloroform, tetrachloromethane, dichloroethane, trichloroethane, diethyl ether, diisopropyl ether, methyl tert-butyl ether, methyl tert-amyl ether, 1,4-dioxane, tetrahydrofuran, 2-methyltetrahydrofuran, 1,2-dimethoxyethane, 1,2-diethoxyethane, diglyme, anisole, acetonitrile, propionitrile, n-butyronitrile, isobutyronitrile, benzonitrile, ethyl acetate, N,N-dimethylformamide, N,N-dimethylacetamide, dimethylsulfoxide.

6. Method according to claim 1, wherein the solvent used is toluene or methyl tert-butyl ether.

7. Method according to claim 1, wherein R.sup.1 is methyl, ethyl, n-propyl, isopropyl, n-butyl, phenyl, 4-methylphenyl or benzyl, R.sup.2 is Cl, F, Br, I or methyl, and R.sup.3 is F, Cl or OSO.sub.2R.sup.1.

8. Method according to claim 1, wherein the compound of the formula (II) is obtained by reacting a compound of the formula (VI) or an alkali metal salt or alkaline earth metal salt of the compound of formula (VI) ##STR00017## with at least one compound of formula (VII)
Me-Q(VII) in the presence of a solvent, where Q is Li, Na, K, MgCl, MgBr or MgI.

9. Method according to claim 8, wherein a deprotonating agent is first added to the compound of the formula (IV) before reacting with the compound of the formula (VII), wherein the deprotonating agent is not a compound of the formula (VII).

10. Method according to claim 9, wherein an alkali metal alkoxide and/or alkali metal hydroxide is used as deprotonating agent.

11. Method according to claim 10, wherein the deprotonating agent is selected from the group consisting of sodium hydroxide, potassium hydroxide, sodium methoxide, sodium ethoxide, sodium tert-butoxide, potassium methoxide and potassium tert-butoxide.

12. Method according to claim 8, wherein the compound of the formula (VI) is obtained by reacting a compound of formula (VIII) ##STR00018## where R.sup.2 is methyl, I, Br or Cl, with a hydroxide base.

13. Method according to claim 8, wherein the hydroxide base used is an aqueous potassium hydroxide solution or an aqueous sodium hydroxide solution.

14. Method according to claim 8, wherein the reaction of the compound of the formula (VIII) to the compound of the formula (VI) is carried out in the presence of an amide solvent, or a mixture of amide solvent or diglyme with ether solvent or aromatic solvent.

15. Compound of formula (V), ##STR00019## in which R.sup.2 is halogen or methyl; X is C or S, Y is S or O, and wherein X and Y cannot both be S.

Description

EXAMPLES

[0079] The present invention is elucidated in more detail by the examples which follow, without restricting the invention to these examples.

Example 1

2-Chloro-6-hydroxybenzaldehyde (VI, R.SUP.2.Cl)

[0080] ##STR00009##

[0081] In a 500 ml 4-neck flask, a solution of 50.0 g (0.31 mol, 1.0 eq) of 2-chloro-6-fluorobenzaldehyde in 150 ml of N,N-dimethylacetamide is initially charged at 23 C. under nitrogen. 87.6 g (0.78 mol, 2.5 eq) of 50% aqueous KOH solution is metered in at 20-30 C. over 3 h. The reaction is slightly exothermic and a yellow suspension is obtained. After the addition had ended, the reaction mixture is stirred at 23 C. for a further 1 h. GC shows >99% conversion. With cooling at 10-30 C., 200 ml of water and then 80.0 g of 37% HCl are metered in over 10-20 min (pH=1-2). A beige solid precipitates out.

[0082] Optionally, this solid may be isolated by filtration. After drying at 20 mbar/23 C., 43.0 g of a beige-coloured solid are obtained (88% yield).

[0083] Alternatively, 150 ml of toluene are added and the mixture is stirred at 23 C. for 10 minutes. The aqueous phase is separated and extracted again with 150 ml of toluene. The combined organic phases are washed with 150 ml of 10% HCl and concentrated on a rotary evaporator at 40 C./50 mbar to ca. 250 g. The product solution is used as such in the next step (calculated yield by content determination by means of quant. NMR: 90%).

[0084] .sup.1H-NMR (CDCl.sub.3, 400 MHz) (ppm)=11.91 (s, 1H), 10.42 (s, 1H), 7.42 (t, J=8.3 Hz, 1H), 6.96 (dd, J=8.0 Hz, 1.0 Hz, 1H), 6.90 (d, J=8.4 Hz, 1H).

Example 2

3-Chloro-2-(1-hydroxyethyl)phenol (II, R.SUP.2.Cl)

[0085] ##STR00010##

[0086] In a 1 L 4-neck flask, the product solution from example 1 consisting of 43.8 g (0.28 mol, 1.0 eq) of 2-chloro-6-hydroxybenzaldehyde in toluene (90% determined yield) is initially charged under nitrogen and heated to 60 C. 50.3 g (0.28 mol, 1.0 eq) of 30% sodium methoxide solution in methanol is metered in at 60 C. over 1 h and, after the addition is complete, the mixture is further stirred at 60 C. for 2 h. The yellow suspension is cooled to 23 C., 300 ml of toluene are added and the mixture is concentrated on a rotary evaporator at 40 C./50 mbar down to a residual weight of ca. 250 g. 105.4 g (0.31 mol, 1.1 eq) of 22% methylmagnesium chloride solution in THF is metered in at 20-30 C. over 3 h and the mixture further stirred at 23 C. for 1 h. HPLC shows complete conversion. With cooling at 10-20 C., 250 ml of 10% HCl (pH=1-2) is metered in over 30 minutes. The aqueous phase is separated and extracted with 200 ml of toluene. The combined organic phases are washed with 100 ml of 10% NaHCO.sub.3 solution. The organic phase is separated, washed with 100 ml of water and concentrated on a rotary evaporator at 40 C./50 mbar down to a residual weight of ca. 200 g. The product solution is used in the next step (calculated yield by content determination by means of quant. NMR: 98%).

[0087] .sup.1H-NMR (CDCl.sub.3, 400 MHz) (ppm)=8.84 (s, 1H), 7.07 (t, J=8.0 Hz, 1H), 6.85 (dd, J=8.0 Hz, 1.2 Hz, 1H), 6.78 (dd, J=8.3 Hz, 1.1 Hz, 1H), 5.60 (qd, J=6.5 Hz, 3.1 Hz, 1H), 2.65 (m, 1H), 1.57 (d, J=6.5 Hz, 3H).

Examples 3-6

[0088] In analogy to the method description of example 2 for the preparation of the compound of the formula (II) where R.sup.2Cl, the compounds of the formula (II) of examples 3-6 below may be obtained:

Example 3: 3-Fluoro-2-(1-hydroxyethyl)phenol (II, R.SUP.2.F)

[0089] .sup.1H-NMR (CDCl.sub.3, 400 MHz) (ppm)=8.59 (br s, 1H), 7.08 (dt, J=8.3 Hz, 6.5 Hz, 1H), 6.65 (d, J=8.3 Hz, 1H), 6.58-6.51 (m, 1H), 5.48 (q, J=6.5 Hz, 1H), 2.69 (br s, 1H), 1.58 (d, J=6.7 Hz, 3H).

Example 4: 2-(1-Hydroxyethyl)-3-iodophenol (II, R.SUP.2.I)

[0090] .sup.1H-NMR (CDCl.sub.3, 400 MHz) (ppm)=8.88 (br s, 1H), 7.33 (dd, J=7.5 Hz, 1.6 Hz, 1H), 6.88-6.80 (m, 2H), 5.38 (q, J=6.7 Hz, 1H), 2.80 (br s, 1H), 1.54 (d, J=6.7 Hz, 3H).

Example 5: 3-Bromo-2-(1-hydroxyethyl)phenol (II, R.SUP.2.Br)

[0091] .sup.1H-NMR (CDCl.sub.3, 400 MHz) (ppm)=9.02 (br s, 1H), 7.04 (dd, J=8.0 Hz, 1.1 Hz, 1H), 6.99 (t, J=8.0 Hz, 1H), 6.82 (dd, J=8.0 Hz, 1.3 Hz, 1H), 5.53 (q, J=6.7 Hz, 1H), 3.25 (br s, 1H), 1.56 (d, J=6.7 Hz, 3H).

Example 6: 2-(1-Hydroxyethyl)-3-methylphenol (II, R.SUP.2.=Me)

[0092] .sup.1H-NMR (CDCl.sub.3, 400 MHz) (ppm)=8.61 (br s, 1H), 7.04 (t, J=8.0 Hz, 1H), 6.73 (d, J=8.0 Hz, 1H), 6.65 (d, J=7.5 Hz, 1H), 5.33 (q, J=6.7 Hz, 1H), 2.92 (br s, 1H), 2.22 (s, 3H), 1.54 (d, J=6.7 Hz, 3H).

Example 7

3-Chloro-2-vinylphenyl methanesulfonate (I, R.SUP.1.=Me, R.SUP.2.Cl)

[0093] ##STR00011##

Stage a) 3-Chloro-2-vinylphenol (III, R.SUP.2.Cl)

[0094] ##STR00012##

[0095] In a 1 L 4-neck flask, the product solution from example 2 consisting of 46.6 g (0.27 mol, 1.0 eq) of 3-chloro-2-(1-hydroxyethyl)phenol in toluene (98% determined yield) and 222.3 g (1.2 mol, 4.5 eq) of tributylamine are initially charged under nitrogen and a solution consisting of 35.7 g (0.30 mol, 1.1 eq) of thionyl chloride in 30 ml of toluene at 0-5 C. is metered in over a period of 2 h. After the addition has ended, the reaction mixture is stirred at 23 C. for 1 h. HPLC shows >98% conversion to the styrene. Analytical data for 3-chloro-2-vinylphenol (III, R.sup.2Cl) are as follows: .sup.1H-NMR (CDCl.sub.3, 400 MHz) (ppm)=7.08 (dd, J=8.0, 8.0 Hz, 1H), 6.96 (d, J=8.0 Hz, 1H), 6.84 (d, J=8.0 Hz, 1H), 6.79 (dd, J=12.0 Hz, 12.0 Hz, 1H), 5.74 (d, J=12.0 Hz, 1H), 5.73 (s, 1H), 5.68 (d, J=12.0 Hz, 1H).

[0096] The cyclic intermediate, 5-chloro-4-methyl-4H-1,3,2-benzodioxathiin 2-oxide (V, R.sup.2Cl, XS, YO), cannot be isolated or be detected by diverse analytical methods. The hydrolyzed derivative 1-(2-chloro-6-hydroxyphenyl)ethyl hydrogensulfite, ring-opened by water, can be detected in very low amounts (<5%) during the reaction by LC-MS. Analytical data for 1-(2-chloro-6-hydroxyphenyl)ethyl hydrogensulfite are as follows: ESI neg. m/z=235 [MH].sup.+; retention time: 1.18 min (HPLC column: Phenomenex Kinetex C18, 100 mm2.1 mm1.7 l, eluent A: 0.1% formic acid/water, eluent B: acetonitrile, gradient: 90/10 (0 min).fwdarw.18/82 (2.4 min).fwdarw.0/100 (2.6 min).fwdarw.0/100 (3.59 min), flow rate: 0.8 ml/min, oven: 40 C., inj.: 1.0 l).

Stage b) 3-Chloro-2-vinylphenyl methanesulfonate (I, R.SUP.1.=Me, R.SUP.2.Cl)

[0097] ##STR00013##

[0098] Then, at 0-5 C., 36.6 g (0.32 mol, 1.2 eq) of methanesulfonyl chloride are metered in over 2 h. After the addition is complete, the reaction mixture is stirred at 23 C. for 1 h. HPLC shows >98% conversion to the methanesulfonate. The reaction mixture is metered into 350 ml of 10% HCl at 0-10 C. over 1 h and the aqueous phase is then extracted twice with 200 ml of toluene each time. The combined organic phases are washed with 150 ml of 10% HCl and concentrated on a rotary evaporator at 40 C./50 mbar. The oily residue is taken up in 50 ml of DMAc and at 15-25 C. is metered into a mixture of 125 ml of 37% HCl and 500 ml of water over 1 h. The beige coloured solid is filtered off with suction and washed with 200 ml of water. After drying at 35 C./20 mbar, 63.7 g of a beige coloured solid is obtained (88% yield; 78% yield over all stages; 88% purity according to quant. HPLC).

[0099] By recrystallization from 30 g of ethanol, 51.2 g of colourless crystals are obtained (80% yield; 70% yield over all stages; >98% purity according to quant. HPLC).

[0100] .sup.1H-NMR (CDCl.sub.3, 400 MHz) (ppm)=7.36 (dd, J=8.0, 1.2 Hz, 1H), 7.34 (dd, J=8.0, 1.2 Hz, 1H), 7.23 (t, J=8.0 Hz, 1H), 6.76 (dd, J=18.0 Hz, 11.7 Hz, 1H), 5.91 (dd, J=18.0, 1.6 Hz, 1H), 5.73 (dd, J=11.8, 1.4 Hz, 1H), 3.11 (s, 3H).

Example 8

3-Chloro-2-vinylphenyl Methanesulfonate (I, R.SUP.1.=Me, R.SUP.2.Cl): Variant with Isolated Yield Over the Latter Two Stages and Recycling of Tri-n-Butylamine

Stage a) 3-Chloro-2-vinylphenol (III, R.SUP.2.Cl)

[0101] In a 250 ml 4-neck flask, a solution of 10.0 g (57.9 mmol, 1.0 eq) of 3-chloro-2-(1-hydroxyethyl)phenol and 48.3 g of tri-n-butylamine (260.7 mmol, 4.5 eq) in 50 ml of methyl tert-butyl ether is initially charged under nitrogen and 7.6 g (63.7 mmol, 1.1 eq) of thionyl chloride at 0-5 C. are metered in over a period of 1 h. After the addition is complete, the reaction mixture is stirred at 23 C. for 1 h. HPLC shows >98% conversion to the styrene. Analytical data for 3-chloro-2-vinylphenol (III, R.sup.2Cl) are as follows: .sup.1H-NMR (CDCl.sub.3, 400 MHz) (ppm)=7.08 (dd, J=8.0, 8.0 Hz, 1H), 6.96 (d, J=8.0 Hz, 1H), 6.84 (d, J=8.0 Hz, 1H), 6.79 (dd, J=12.0 Hz, 12.0 Hz, 1H), 5.74 (d, J=12.0 Hz, 1H), 5.73 (s, 1H), 5.68 (d, J=12.0 Hz, 1H).

Stage b) 3-Chloro-2-vinylphenyl methanesulfonate (I, R.SUP.1.=Me, R.SUP.2.Cl)

[0102] Then, at 0-5 C., 8.0 g (69.5 mmol, 1.2 eq) of methanesulfonyl chloride are metered in over 1 h. After the addition is complete, the reaction mixture is stirred at 23 C. for 1 h. HPLC shows >98% conversion to the methanesulfonate. 100 ml of 10% HCl are metered in to the reaction mixture at 10-15 C. and the phases are subsequently separated. The aqueous phase is extracted twice with 100 ml of methyl tert-butyl ether each time. The combined organic phases are washed twice with 50 ml of 10% HCl each time, dried over MgSO4 and concentrated on a rotary evaporator at 40 C./10 mbar (13.9 g; purity according to quant. HPLC: 83%; 86% yield). The material thus obtained is recrystallized from ethanol/n-heptane (10.8 g; purity by quant. HPLC: 99%; 80% yield).

[0103] The aqueous phase is brought to a pH of 11-12 by addition of 50% NaOH. The organic phase that separates out is separated off and is distilled over on the rotary evaporator at 90 C./10 mbar.

[0104] A colourless liquid is obtained, which can be identified as tri-n-butylamine by comparison with literature data (1H-NMR) (43.6 g; 90% recovery).

Examples 9-13

[0105] In analogy to the method descriptions of examples 7 and 8, the following specified compounds of the formula (III) or (I) may be obtained:

Example 9: 3-Bromo-2-vinylphenol (III, R.SUP.2.Br)

[0106] .sup.1H-NMR (CDCl.sub.3, 400 MHz) (ppm)=7.13 (dd, J=7.8, 1.3 Hz, 1H), 7.00 (t, J=7.8 Hz, 1H), 6.94 (dd, J=8.0, 1.3 Hz, 1H), 6.74 (dd, J=18.1 Hz, 11.4 Hz, 1H), 5.72 (dd, J=18.1, 1.6 Hz, 1H), 5.70 (dd, J=11.4, 1.6 Hz, 1H).

Example 10: 3-Bromo-2-vinylphenyl Methanesulfonate (I, R.SUP.1.=Me, R.SUP.2.Br)

[0107] .sup.1H-NMR (CDCl.sub.3, 600 MHz) (ppm)=7.56 (dd, J=8.1, 1.1 Hz, 1H), 7.38 (d, J=8.2 Hz, 1H), 7.16 (t, J=8.1 Hz, 1H), 6.72 (dd, J=17.9 Hz, 11.7 Hz, 1H), 5.84 (dd, J=17.9, 1.3 Hz, 1H), 5.71 (dd, J=11.7, 1.3 Hz, 1H), 3.11 (s, 3H).

Example 11: 3-Fluoro-2-vinylphenyl Methanesulfonate (I, R.SUP.1.=Me, R.SUP.2.F)

[0108] .sup.1H-NMR (CDCl.sub.3, 400 MHz) (ppm)=7.27-7.24 (m, 1H), 7.23-7.19 (m, 1H), 7.10-7.04 (m, 1H), 6.75 (dd, J=18.0 Hz, 11.9 Hz, 1H), 6.06 (dd, J=18.0, 1.3 Hz, 1H), 5.68 (dd, J=11.9, 1.6 Hz, 1H), 3.15 (s, 3H).

Example 12: 3-Iodo-2-vinylphenyl Methanesulfonate (I, R.SUP.1.=Me, R.SUP.2.I)

[0109] .sup.1H-NMR (CDCl.sub.3, 400 MHz) (ppm)=7.84 (dd, J=8.1 Hz, 1.1 Hz, 1H), 7.41 (dd, J=8.1 Hz, 1.1 Hz, 1H), 7.00 (t, J=8.0 Hz, 1H), 6.60 (dd, J=17.8 Hz, 11.6 Hz, 1H), 5.72 (dd, J=17.8, 1.4 Hz, 1H), 5.67 (dd, J=11.6, 1.4 Hz, 1H), 3.11 (s, 3H).

Example 13: 3-Methyl-2-vinylphenyl Methanesulfonate (I, R.SUP.1.=Me, R.SUP.2.=Me)

[0110] .sup.1H-NMR (CDCl.sub.3, 400 MHz) (ppm)=7.24 (dd, J=8.0, 1.8 Hz, 1H), 7.19 (t, J=7.8 Hz, 1H), 7.15 (dd, J=7.5, 1.3 Hz, 1H), 6.71 (dd, J=17.8 Hz, 11.8 Hz, 1H), 5.66 (dd, J=11.8, 1.8 Hz, 1H), 5.63 (dd, J=17.8, 1.8 Hz, 1H), 3.09 (s, 3H), 2.37 (s, 3H).

Example 14

Alternative Conditions for the Preparation of 3-chloro-2-vinylphenol (III, R.SUP.2.Cl) from 3-chloro-2-(1-hydroxyethyl)phenol (II, R.SUP.2.Cl)

[0111] a) 3-Picoline as base

[0112] 1.0 g of 3-chloro-2-(1-hydroxyethyl)phenol (5.8 mmol, 1.0 eq) are initially charged in 9 ml of DMAc and 2.43 g of 3-picoline (26.1 mmol, 4.5 eq) are added. 0.76 g of thionyl chloride (6.4 mmol, 1.1 eq) are metered in at 0-5 C. over 1 h and the mixture is then stirred at 23 C. for 1 h. HPLC shows >95% conversion to 3-chloro-2-[1-(3-methylpyridinium-1-yl)ethyl]phenolate. Analytical data for 3-chloro-2-[1-(3-methylpyridinium-1-yl)ethyl] phenolate are as follows: ESI pos. m/z=248 [M+H].sup.+; .sup.1H-NMR (CDCl.sub.3, 400 MHz) (ppm)=8.88 (d, J=6.2 Hz, 1H), 8.73 (s, 1H), 8.25 (d, J=8.0 Hz, 1H), 7.95 (t, J=6.2 Hz, 1H), 7.59 (dd, J=8.4 Hz, 1.0 Hz, 1H), 7.14 (t, J=8.3 Hz, 1H), 6.89 (dd, J=8.0 Hz, 1.1 Hz, 1H), 6.46 (q, J=7.0 Hz, 1H), 2.59 (s, 3H), 2.22 (d, J=7.0 Hz, 3H).

[0113] The reaction mixture is then heated to 120 C. and stirred at this temperature for 2 h. HPLC shows >85% 3-chloro-2-vinylphenol (III, R.sup.2Cl, analytical data: see examples 7 and 8, stage a).

b) Phosgene as Activator (with Conversion of Intermediate (V) to the Compound (III) at 110 C.)

[0114] 5.0 g of 3-chloro-2-(1-hydroxyethyl)phenol (29.0 mmol, 1.0 eq) are initially charged in 50 ml of toluene and 21.5 g of tributylamine (115.9 mmol, 4.0 eq) are added. At 0-5 C., 5.8 g of phosgene (58.0 mmol, 2.0 eq) are introduced over 1 h and the mixture is then stirred at 23 C. for 1 h. HPLC-MS shows >80% 5-chloro-4-methyl-4H-1,3-benzodioxin-2-one (V, R.sup.2Cl, XC, YO) as intermediate. Analytical data for 5-chloro-4-methyl-4H-1,3-benzodioxin-2-one (V, R.sup.2Cl, XC, YO) are as follows: ESI pos. m/z=199 [M+H].sup.+; retention time: 1.02 min (HPLC column: Zorbax Eclipse Plus C18, 50 mm2.1 mm1.8 al; eluent A: 0.1% formic acid/acetonitrile; eluent B: 0.1% formic acid/water; gradient: 10/90 47%/min.fwdarw.95/5 (0.7 min); flow rate: 1 ml/min; oven: 55 C.; injection: 0.8 l).

[0115] The reaction mixture is then heated to 110 C. and stirred at this temperature for 12 h. HPLC shows >90% 3-chloro-2-vinylphenol (III, R.sup.2Cl, analytical data see examples 7 and 8, stage a).

b) Phosgene as Activator (with Conversion of Intermediate (V) to the Compound (III) at Room Temperature)

[0116] 10.0 g of 3-chloro-2-(1-hydroxyethyl)phenol (57.9 mmol, 1.0 eq) are initially charged in 50 ml of toluene and 43 g of tributylamine (231 mmol, 4.0 eq) are added. At 0-6 C., 8.6 g of phosgene (86.9 mmol, 1.5 eq) are introduced over 30 min and the mixture is then stirred at 0 C. for 1 h. HPLC-MS shows 80% 5-chloro-4-methyl-4H-1,3-benzodioxin-2-one (V, R.sup.2Cl, XC, YO) as intermediate. Analytical data for 5-chloro-4-methyl-4H-1,3-benzodioxin-2-one (V, R.sup.2Cl, XC, YO) are as follows: ESI pos. m/z=199 [M+H].sup.+; retention time: 1.02 min (HPLC column: Zorbax Eclipse Plus C18, 50 mm2.1 mm1.8 l; eluent A: 0.1% formic acid/acetonitrile; eluent B: 0.1% formic acid/water; gradient: 10/90 47%/min.fwdarw.95/5 (0.7 min); flow rate: 1 ml/min; oven: 55 C.; injection: 0.8 al).

[0117] The reaction mixture is then brought to room temperature and excess phosgene is driven off by introducing an argon gas stream. 50 ml of methanol are then added at room temperature and the mixture is stirred for 1 h. LCMS shows >80% 3-chloro-2-vinylphenol. The mixture is set to pH 10-11 with dilute NaOH, the phases are separated and the organic phase is extracted again 2 with dilute NaOH. The aqueous phases are combined, set to pH 2 with dilute HCl and extracted 3 with ethyl acetate. The combined organic phase is dried over sodium sulfate and concentrated on the rotary evaporator. This gives 7.9 g of 3-chloro-2-vinylphenol (III, R.sup.2Cl, analytical data see examples 7 and 8, stage a) at a purity of 87% (yield: 76.7% of theory) as a yellow oil.

d) Thiophosgene as Activator (with Isolation and Characterization of the Intermediate (V))

[0118] 1.0 g of 3-chloro-2-(1-hydroxyethyl)phenol (5.8 mmol, 1.0 eq) is initially charged in 5 ml of MTBE and 2.15 g of tri-n-butylamine (11.6 mmol, 2.0 eq) are added. 0.76 g of thiophosgene (6.4 mmol, 1.1 eq) are metered in at 0-50 C. over 1 h and the mixture is then stirred at 23 C. for 1 h. HPLC shows >80% 5-chloro-4-methyl-4H-1,3-benzodioxin-2-thione (V, R.sup.2Cl, X C, YS) as intermediate. Ca. 1 ml of the reaction solution is withdrawn and worked-up on a small scale by washing with 10% HCl. The organic phase is then concentrated on the rotary evaporator. Analytical data for 5-chloro-4-methyl-4H-1,3-benzodioxin-2-thione (V, R.sup.2Cl, XC, YS) are as follows: CI m/z=215 [M+H].sup.+; .sup.1H-NMR (CDCl.sub.3, 400 MHz) (ppm)=7.35 (t, J=8.3 Hz, 1H), 7.27 (dd, J=8.0 Hz, 1.1 Hz, 1H), 7.11 (dd, J=8.3 Hz, 0.8 Hz, 1H), 5.75 (q, J=6.7 Hz, 3.1 Hz, 1H), 1.72 (d, J=6.7 Hz, 3H).

[0119] 1.61 g of tri-n-butylamine (8.7 mmol, 1.5 eq) are added to the remaining reaction mixture which is then heated to 80 C. HPLC shows >80% conversion to 3-chloro-2-vinylphenol (III, R.sup.2Cl, analytical data: see examples 7 and 8, stage a).