Method for preparing arylvinylsulphones
The invention relates to a method of preparing arylvinylsulphones. The method comprises forming o a first reaction mixture comprising a catalyst complex of Cu(I)halide and a ligand, wherein the ligand is selected from mono-, bi- or polydentate amine ligands and further comprises an organic sulphonate; a reactive solvent selected from (meth)acrylonitrile or alkyl (meth)acrylate; and an aryl sulfonyl halide reactant. A reaction is allowed to proceed in the first reaction mixture at an elevated temperature, whereby an intermediate product is obtained. The unreacted reactive solvent is separated from the first reaction mixture, and the intermediate product is dissolved to a low polarity solvent to form a second reaction mixture. A base is added to the second reaction mixture, wherein the intermediate product undergoes a base-catalyzed elimination of the halogen atom from the intermediate product to form the compound according to Formula (I), preferably under cooling. Finally, the desired compound is separated from the second reaction mixture.
1 . A method for preparing a compound of formula (I)
where
R1, R2, and R3 are independently selected from the group consisting of a hydrogen atom; a halogen atom; a hydroxy group, an alkyl group; a hydroxy alkyl group; a haloalkyl group;
an alkoxy group having 1 to 4 carbon atoms; an amino group; an alkylamino group or an acylamido group having 1 to 10 carbon atoms;
A is selected from the group consisting of a hydrogen atom; a C1-C5 alkyl group; or an alkoxycarbonyl group;
B is selected from the group consisting of a nitrile group; a carboxylic acid group, a carboxylic acid ester group or a carboxylic acid amide group;
the method comprising steps of
(a) forming a first reaction mixture comprising
a catalyst complex comprising Cu(I) and a ligand, wherein the ligand is selected from the group consisting of mono-, bi- or polydentate amine ligands;
an organic sulphonate counterion;
a reactive solvent selected from (meth)acrylonitrile or alkyl (meth)acrylate; and
an aryl sulfonyl halide reactant;
(b) allowing a first reaction to proceed in the first reaction mixture at an elevated temperature, whereby an intermediate product is obtained;
(c) separating the unreacted reactive solvent from the first reaction mixture, and dissolving the intermediate product to a low polarity solvent to form a second reaction mixture;
(d) adding a base to the second reaction mixture, and allowing a second reaction to occur wherein the intermediate product undergoes a base-catalyzed elimination of the halogen atom from the intermediate product to form the compound according to Formula (I); and
(e) separating the compound according to Formula (I) from the second reaction mixture.
2 . The method according to claim 1 , wherein the intermediate product is dissolved in step (d) into a low polarity solvent, which has a relative polarity of <0.4 to form the second reaction mixture.
3 . The method according to claim 1 , wherein the first reaction which is effected in step (b) is allowed to proceed at the elevated temperature of 80-95° C.
4 . The method according to claim 1 , wherein the reactive solvent, which is separated from the first reaction mixture in step (c), is recycled back to step (a) for formation of first reaction mixture.
5 . The method according to claim 1 , wherein the second reaction mixture in step (d) is maintained at a temperature of 15-40° C.
6 . The method according to claim 1 , wherein the base in step (d) comprises an inorganic base.
7 . The method according to claim 1 , wherein the base in step (d) comprises an organic base.
8 . The method according to claim 1 , wherein the base in step (d) is a combination of an inorganic base and an organic base, which comprises 0.8-0.95 equivalent of an inorganic base and 0.05-0.2 equivalent of an organic base, given as molar equivalents.
9 . The method according to claim 1 , wherein the amount of Cu(I) halide in the first reaction mixture is 2.5-30 mol-% calculated from the amount of the aryl sulphonyl halide in the first reaction mixture.
10 . The method according to claim 1 , wherein the organic sulphonate in step (a) comprises an aryl sulphonate or alkyl sulphonate.
11 . The method according to claim 1 , wherein the amount of the ligand in the first reaction mixture is 7-45 mol-%, calculated from the amount of the aryl sulphonyl halide in the first reaction mixture and/or wherein aryl sulphonyl halide is added, to form the first reaction mixture in step (a), in amount of 0.2-0.5 equivalents relative to the amount of the reactive solvent in the first reaction mixture.
12 . The method according to claim 1 , wherein step (a) comprises
(i) forming a pre-reaction mixture comprising
a catalyst complex of the Cu(I) and the ligand;
the organic sulphonate counterion; and
a reactive solvent selected from (meth)acrylonitril e or alkyl (meth)acrylate; and
(ii) adding an amount of aryl sulfonyl halide reactant to the pre-reaction mixture to form the first reaction mixture.
13 . The method according to claim 1 , wherein the compound according to formula (I) is 3-[(4-methylphenyl) sulphonyl]-2-propenenitrile.
14 . The method according to claim 1 , wherein the Cu (l) is provided as a Cu(I) halide.
15 . The method according to claim 1 , wherein the organic sulphonate is supplied as a salt.
16 . The method according to claim 2 , wherein the low polarity solvent is selected from the group consisting of ethyl acetate, butyl acetate, tetrahydrofuran, dioxane and toluene.
17 . The method according to claim 1 , wherein in step (d) the base is added to the second reaction mixture under cooling.
18 . The method according to claim 3 , wherein the first reaction in step (b) is allowed to proceed at the elevated temperature of 85-92° C.
19 . The method according to claim 5 , wherein the second reaction mixture in step (d) is maintained at a temperature of 20-35° C.
20 . The method according to claim 6 , wherein the base in step (d) comprises an inorganic base selected from the group consisting of bicarbonates or carbonates of alkali metals or carbonates of earth alkaline metals, or any mixtures thereof.
21 . The method according to claim 7 , wherein the base in step (d) comprises an organic base selected from the group consisting of triethylamine, trimethylamine; N-methylmorpholine; N-methylpyrrolidine; N,N-diisopropylethylamine; 1,4-diazabicyclo[2.2.2]-octane; 1,8-diazabicyclo[5.4.0]undec-7-ene; and 1,5-diazabicyclo[4.3.0]non-5-ene.
22 . The method according to claim 9 , wherein the amount of Cu(I) halide in the first reaction mixture is 5-20 mol-%, calculated from the amount of the aryl sulphonyl halide in the first reaction mixture.
23 . The method according to claim 22 , wherein the amount of Cu(I) halide in the first reaction mixture is 7.5-15 mol-%, calculated from the amount of the aryl sulphonyl halide in the first reaction mixture.
24 . The method according to claim 10 , wherein the organic sulphonate in step (a) comprises an aryl sulphonate or alkyl sulphonate which is selected from the group consisting of methanesulphonate, ethanesulphonate, benzenesulphonate, 4-toluenesulphonate, and xylenesulphonate.
25 . The method according to claim 11 , wherein the amount of the ligand in the first reaction mixture 10-30 mol-%, calculated from the amount of the aryl sulphonyl halide in the first reaction mixture and/or wherein aryl sulphonyl halide is added, to form the first reaction mixture in step (a), in an amount of 0.3-0.5 equivalents, relative to the amount of the reactive solvent in the first reaction mixture.
26 . The method according to claim 12 , wherein the pre-reaction mixture is formed at a temperature of 15-40° C.
27 . The method according to claim 14 , wherein the Cu(I) halide is a Cu(I) chloride.
28 . The method according to claim 14 , wherein the molar amount of halide ions in the first reaction mixture is no more than the molar amount of Cu(I).
29 . The method according to claim 15 , wherein the organic sulphonate is supplied as an ammonium salt.