Method for preparing 2-(cyclohexenylidene) malonic acid derivatives and uses thereof

A compound of formula (3) or (4) or a mixture thereof,

• wherein:
• R4 is selected from a C1-C10 alkyl group, a C6-C12 aryl group or a heteroaryl group containing one or two atoms selected from nitrogen, oxygen and sulfur;
• R1, R2, R3 and R5 each are independently hydrogen, a C1-C10 alkyl group, a C6-C12 aryl group or a heteroaryl group containing one or two atoms selected from nitrogen, oxygen and sulfur;
• and
• X1 and X2 each are independently a cyano group or —COR6 where R6 is selected from hydrogen, a C1-C10 alkyl group, a C1-C10 alkoxy group, a C6-C12 aryloxy group, a C1-C10 alkylamino group, a C6-C12 arylamino group, a di(C1-C10 alkyl) amino group, a (C1-C10 alkyl)(C6-C12 aryl) amino group, a di(C6-C12 aryl) amino group, a C6-C12 aryl group or a heteroaryl group containing one or two atoms selected from nitrogen, oxygen and sulfur.

A method for preparing a 2-aryl malonic acid derivative, comprising:

• 1) cyclizing compound (1) with compound (2) in the presence of a catalyst A to produce compound (4) via intermediate (3);
• or cyclizing compound (1) with compound (2) in the presence of a catalyst A to produce compound (4) directly, as shown in the following reaction scheme:
• and
• 2) aromatizing compound (4) in the presence of a catalyst B to give the 2-aryl malonic acid derivative (5), as shown in the following reaction scheme:
• wherein:
• R1, R2, R3, R4 and R5 each are independently hydrogen, a C1-C10 alkyl group, a C6-C12 aryl group or a heteroaryl group containing one or two atoms selected from nitrogen, oxygen or sulfur;
• and
• X1 and X2 each are independently a cyano group or —COR6 where R6 is selected from hydrogen, a C1-C10 alkyl group, a C1-C10 alkoxy group, a C6-C12 aryloxy group, a C1-C10 alkylamino group, a C6-C12 arylamino group, a di(C1-C10 alkyl) amino group, a (C1-C10 alkyl)(C6-C12 aryl) amino group, a di(C6-C12 aryl) amino group, a C6-C12 arylgroup or a heteroaryl group containing one or two atoms selected from nitrogen, oxygen and sulfur;
• wherein the catalyst A is selected from the group consisting of an organic acid, an organic base, an inorganic base and a mixture thereof;
• and the catalyst B is a metal catalyst.

A method for synthesizing Pinoxaden, comprising:

• 1) cyclizing methacrylaldehyde (1) with 2-(heptan-4-ylidene)malonate (2) to produce 2-(2,6-diethyl-4-methylcyclohex-2-en-1-ylidene)malonate (4) via 2-(2,6-diethyl-3-hydroxy-4-methyl-cyclohexylidene)malonate (3) in the presence of a catalyst A;
• or cyclizing methacrylaldehyde (1) with 2-(heptan-4-ylidene)malonate (2) in the presence of a catalyst A to produce 2-(2,6-diethyl-4-methylcyclohex-2-en-1-ylidene)malonate (4) directly;
• 2) aromatizing 2-(2,6-diethyl-4-methylcyclohex-2-en-1-ylidene)malonate (4) in the presence of a catalyst B to give a 2-(2,6-diethyl-4-methylphenyl)malonate (5);
• and
• 3) reacting 2-(2,6-diethyl-4-methylphenyl)malonate (5) with hexahydro-1,4,5-oxadiazapine (6) to produce compound (7);
• and then adding pivaloyl chloride to the reaction to obtain Pinoxaden, as shown in the following reaction scheme:
• wherein the catalyst A is selected from the group consisting of an organic acid, an organic base, an inorganic base and a mixture thereof;
• and the catalyst B is a metal catalyst;
• wherein R6 is selected from the group consisting of hydrogen, a C1-C10 alkyl group, a C1-C10 alkoxy group, a C6-C12 aryloxy group, a C1-C10 alkylamino group, a C6-C12 arylamino group, a di(C1-C10 alkyl) amino group, a (C1-C10 alkyl)(C6-C12 aryl) amino group, a di(C6-C12 aryl) amino group, a C6-C12 arylgroup and a heteroaryl group containing one or two atoms selected from nitrogen, oxygen and sulfur.