Process for preparing 3-chloro-2-vinylphenol

Abstract

The present invention describes a novel process for preparing 3-chloro-2-vinylphenol which, owing to the chemoselectivity achieved, also allows direct conversion into (3-chloro-2-vinylphenyl)methane-sulphonate.

Claims

1. A process for preparing a compound of formula (I), ##STR00006## comprising reacting a compound of formula (II), ##STR00007## with a base selected from the group consisting of lithium carbonate, sodium carbonate, potassium carbonate, calcium carbonate, triethylamine, diethylisopropylamine, tri-n-butylamine, pyridine, picoline, lutidine, and collidine; and N,N-dimethylacetamide as a dipolar aprotic additive; and optionally in the presence of a solvent selected from the group consisting of methyl tert-butyl ether, tetrahydrofuran, 2-methyltetrahydrofuran, cyclopentyl methyl ether, 1,4-dioxane, ethyl acetate, n-propyl acetate, i-propyl acetate, and n-butyl acetate, to give the compound of formula (I).

2. The process according to claim 1, wherein the base is triethylamine, tri-n-butylamine, calcium carbonate, or lithium carbonate.

3. The process according to claim 1, wherein the base is lithium carbonate.

4. The process according to claim 1, wherein a solvent is used.

5. The process according to claim 4, wherein the solvent is n-butyl acetate.

6. The process according to claim 4, wherein the compound of formula (I) is not isolated but instead is directly converted further into a compound of formula (III) ##STR00008## wherein A is selected from the group consisting of mesyl, tosyl, acyl, phosphonyl, and phosphoryl; using a base and a reagent Q-A, wherein Q is selected from the group consisting of chloride and bromide.

7. The process according to claim 6, wherein Q is chloride and A is mesyl.

Description

PROCESS DESCRIPTION

(1) ##STR00003##

(2) 3-Chloro-2-vinylphenol (I) is prepared by reacting 1,5,5-trichloro-6-vinyl-7-oxabicyclo[4.1.0]heptane (II) in the presence of a base, a dipolar, aprotic additive and optionally a solvent.

(3) Suitable dipolar aprotic additives are, for example, amides (e.g. N,N-dimethylformamide, N,N-dimethylacetamide, N-methylpyrrolidinone), carbonates (propylene carbonate, dimethyl carbonate, diethyl carbonate), nitriles (e.g. acetonitrile, propionitrile), sulphoxide/sulphones (e.g. dimethyl sulphoxide, sulpholane), ureas (N,N-dimethylpropyleneurea, N,N-dimethylethyleneurea) and carbamates (e.g. methyl N,N-dimethylcarbamate, ethyl N,N-dimethylcarbamate). Preferred additives are N,N-dimethylacetamide, propylene carbonate and sulpholane, with particular preference being given to N,N-dimethylacetamide.

(4) Suitable solvents are ethers (e.g. methyl tert-butyl ether, tetrahydrofuran, 2-methyltetrahydrofuran, cyclopentyl methyl ether, 1,4-dioxane), aliphatics and aromatics (e.g. methylcyclohexane, n-heptane, toluene, chlorobenzene, xylene, mesitylene, 1,2-dichlorobenzene), esters (e.g. ethyl acetate, n-propyl acetate, i-propyl acetate, n-butyl acetate), alcohols (e.g. methanol, ethanol, n-propanol, i-propanol, n-butanol) or mixtures of these solvents mentioned. Preferred solvents are ethers and esters. Very particular preference is given to n-butyl acetate.

(5) The reaction according to the invention is carried out either in the presence of a base and a dipolar aprotic additive or in the presence of a base, a dipolar aprotic additive and a solvent.

(6) Preference is given to using a base and N,N-dimethylacetamide as additive.

(7) Preference is also given to using a base, N,N-dimethylacetamide as additive and additionally a solvent.

(8) Preference is also given to using a base, N,N-dimethylacetamide as additive and additionally n-butyl acetate as solvent.

(9) Suitable bases are carbonates, (e.g. lithium carbonate, sodium carbonate, potassium carbonate and calcium carbonate), phosphates (e.g. potassium phosphate, sodium phosphate and lithium phosphate), carboxylates (e.g. potassium acetate, sodium acetate and lithium acetate, and also potassium formate, sodium formate and lithium formate), hydroxides (e.g. potassium hydroxide, sodium hydroxide and lithium hydroxide) and also organic bases (e.g. triethylamine, diethylisopropylamine, tri-n-butylamine, pyridine, picoline, lutidine and collidine). The bases are preferably used in stoichiometric amounts in order to take up exactly the amount of two equivalents of hydrogen chloride formed and constantly keep the pH neutral. The use of carbonates and organic bases is preferred. Particular preference is given to using lithium carbonate, sodium carbonate, potassium carbonate, calcium carbonate, triethylamine, diethylisopropylamine, tri-n-butylamine, pyridine, picoline, lutidine and collidine. Very particular preference is given to using triethylamine, tri-n-butylamine, calcium carbonate and lithium carbonate. The use of lithium carbonate is very particularly preferred.

(10) A preferred embodiment of the process of the invention is as follows: the compound of the formula (II) is placed together with the additive and the base in an organic solvent in a reaction vessel and the reaction vessel is closed. The reaction mixture is subsequently heated while stirring well for a period of from 2 to 24 hours until the reaction is complete.

(11) A very particularly preferred embodiment of the process of the invention is as follows: the compound of the formula (II) is placed together with N,N-dimethylacetamide and lithium carbonate in n-butyl acetate in a reaction vessel and the reaction vessel is closed. The reaction mixture is subsequently heated while stirring well for a period of from 2 to 48 hours until the reaction is complete.

(12) The process of the invention is usually carried out at temperatures in the range from 50 C. to 150 C., preferably in the range from 110 C. to 130 C.

(13) The process of the invention is carried out either under atmospheric pressure or at a pressure of up to 5 bar, depending on the solvent. It is preferably carried out at atmospheric pressure.

(14) The work-up and isolation of the compound of the formula (I) is then carried out by cooling the reaction mixture to 15-35 C. and subsequently either filtering off the salts or by washing with deionized water. The organic phase is, if necessary, preferably dried azeotropically and the product is either reacted further in a solution to effect subsequent functionalization of the hydroxy group or isolated as an oil after removal of the solvent under reduced pressure.

(15) The reaction time can vary greatly, in the range from a few minutes to some hours, depending on the solvent, the concentration and the external temperature applied.

(16) The work-up and isolation of the compound of the formula (I) is generally carried out by cooling the reaction mixture to a temperature range from 20 C. to 25 C. After aqueous removal of the salts and the dipolar, aprotic additive, the compound of the formula (I) is isolated as an oil from the organic phase after removal of the solvent or extractant under reduced pressure.

(17) If the compound of the formula (I) obtained in this way is provided with bases, the corresponding salts, viz. the phenoxides, are formed.

(18) A further advantage of the process is that the compound of the formula (I) is prepared in a purity which allows a direct subsequent reaction without prior purification. For example, it is possible for 3-chloro-2-vinylphenol (I) to be reacted further in the solvent or extractant after an aqueous scrub and drying of the organic phase in an alkylation reaction as described in the patent US 2011/224257 (e.g. allylation, propargylation or 2-methoxyethylation) or else a sulphonation or acylation reaction,

(19) ##STR00004##
where

(20) A is selected from among mesyl, tosyl, acyl, phosphonyl, phosphoryl.

(21) In a preferred embodiment, the compound of the formula (I) is converted directly into the substance (3-chloro-2-vinylphenyl)methanesulphonate of the formula (III-I)

(22) ##STR00005##

(23) The compound of the formula (II) is known from US 1995/5424460.

(24) The following example illustrates the process of the invention:

Preparation of 3-chloro-2-vinylphenol

(25) 15.00 g (80% purity, 52.7 mmol, 1.0 eq.) of 1,5,5-trichloro-6-vinyl-7-oxabicyclo[4.1.0]heptane and 4.70 g (52.7 mmol, 1.0 eq.) of lithium carbonate and 19.2 g of N,N-dimethylacetamide (220.5 mmol, 4.18 eq.) were placed in 28.8 g of n-butyl acetate (247.9 mmol, 4.7 eq.) in a reaction vessel and heated while stirring to an internal temperature of 125 C. (external temperature of 135 C.). After 8 hours, complete conversion of the starting material into 3-chloro-2-vinylphenol was detected by GC analysis. The suspension was then cooled to an internal temperature of 25 C. by removal of the heating bath and admixed with 25 ml of deionized water. The phases were subsequently separated and the organic phase was washed with 220 ml of half-concentrated sodium chloride solution and also 220 ml of deionized water. The organic phase was then freed of water and solvent under reduced pressure and the product was isolated as a yellow oil: yield 6.93 g (85% of theory) .sup.1H-NMR (CDCl.sub.3, 400 MHz) (ppm)=7.08 (dd, J=8.0, 8.0 Hz, 1H, H.sub.5-Ar), 6.96 (d, J=8.0 Hz, 1H, H.sub.4-Ar), 6.84 (d, J=8.0 Hz, 1H, H.sub.6-Ar), 6.79 (dd, J=12.0, 12.0 Hz, 1H, H.sub.c-Vin), 5.74 (d, J=12.0 Hz, 1H, H.sub.b-Vin), 5.73 (s, 1H, OH), 5.68 (d, J=12.0 Hz, 1H, H.sub.a-Vin).

(26) The effect of various bases on the chemoselectivity and thus yield of the reaction which was otherwise carried out under identical conditions may be demonstrated by a few examples in the following table:

(27) TABLE-US-00001 Base Yield 1.0 equivalent of lithium carbonate 85% 1.0 equivalent of calcium carbonate 84% 1.0 equivalent of sodium carbonate 73% 1.0 equivalent of potassium carbonate 62% 2.0 equivalents of triethylamine 84%

Direct Preparation of (3-chloro-2-vinylphenyl)methanesulphonate Via 3-chloro-2-vinylphenol

(28) 15.00 g (80% purity, 52.7 mmol, 1.0 eq.) of 1,5,5-trichloro-6-vinyl-7-oxabicyclo[4.1.0]heptane and 4.70 g (52.7 mmol, 1.0 eq.) of lithium carbonate and 19.2 g of N,N-dimethylacetamide (220.5 mmol, 4.18 eq.) were placed in 28.8 g of n-butyl acetate (247.9 mmol, 4.7 eq.) in a reaction vessel and heated while stirring to an internal temperature of 125 C. (external temperature of 135 C.). After 8 hours, complete conversion of the starting material into 3-chloro-2-vinylphenol was detected by GC analysis. The suspension was then cooled to an internal temperature of 25 C. by removal of the heating bath and admixed with 25 ml of deionized water. The phases were subsequently separated and the organic phase was washed with 220 ml of half-concentrated sodium chloride solution and 220 ml of deionized water. The organic phase was then dried azeotropically under reduced pressure and a small amount of solvent was distilled off. The distillation residue was subsequently admixed with 5.90 g (58.28 mmol, 1.3 eq.) of triethylamine, cooled to 0 C. and 6.67 g (58.28 mmol, 1.3 eq.) of methanesulphonyl chloride was introduced into the reaction solution over a period of 15 minutes. After the addition was complete, the mixture was heated to 22 C. and the suspension was admixed with 50 ml of deionized water. The phases were subsequently separated, the aqueous phase was extracted with 25 ml of n-butyl acetate and the combined, organic phases were washed with 50 ml of deionized water. Remaining water and a major part of the solvent were subsequently distilled off from the organic phase. Digestion with n-heptane and subsequent cooling to 20 C. made it possible to obtain the target compound as a light-yellow solid by crystallization, filtration and drying. Yield 8.71 g (71% of theory over two stages), .sup.1H-NMR (CDCl.sub.3, 400 MHz) (ppm)=7.36 (dd, J=8.0, 1.2 Hz, 1H, H.sub.4-Ar), 7.34 (dd, J=8.0, 1.2 Hz, 1H, H.sub.2-Ar), 7.23 (dd, J=8.0, 1.2 Hz, 1H, H.sub.3-Ar), 6.80 (dd, J=18.0, 12.0 Hz, 1H, H.sub.c-Vin), 5.92 (dd, J=18.0, 1.6 Hz, 1H, H.sub.b-Vin), 5.74 (dd, J=12.0, 1.6 Hz, 1H, H.sub.a-Vin), 3.12 (s, 3H, OSO.sub.2CH.sub.3).