Process for the preparation of 3-alkylsulfinylbenzoyl derivatives
View Patent ↗A process is described for the preparation of 3-alkylsulfinylbenzoyl derivatives of the formula (IIIa) by reaction of 3-alkylsulfinylbenzoic acids of the formula (Ib) with compounds of the formula (II) in the presence of a chlorinating agent and a base. In the formulae specified above, Y is a radical such as pyrazolyl and cyclohexanedionyl. R 1 , R 2 and R 3 are radicals such as halogen, nitro, cyano and alkyl.
1. A process for preparing a 3-alkylsulfinylbenzoyl derivative of formula (IIIa) comprising a reaction of a 3-alkylsulfinylbenzoic acid of formula (Ib) with a compound of formula (II) in the presence of a chlorinating agent and a base selected from the group consisting of pyridine, 3-methylpyridine, and 3,5-dimethylpyridine
in which the radicals, symbols and indices have the following meanings:
R 1 is (C 1 -C 8 )-alkyl, (C 3 -C 8 )-cycloalkyl or benzyl substituted in each case by s radicals selected from the group consisting of halogen, (C 1 -C 2 )-alkoxy and halo-(C 1 -C 2 )-alkyl,
R 2 is hydrogen, mercapto, nitro, halogen, cyano, rhodano, (C 1 -C 6 )-alkyl, (C 1 -C 6 )-haloalkyl, (C 2 -C 6 )-alkenyl, (C 2 -C 6 )-haloalkenyl, (C 2 -C 6 )-alkynyl, (C 3 -C 6 )-haloalkynyl, (C 3 -C 6 )-cycloalkyl, OR 4 , OCOR 4 , OSO 2 R 4 , S(O) n R 4 , SO 2 OR 4 , SO 2 N(R 4 ) 2 , NR 4 SO 2 R 4 , NR 4 COR 4 , (C 1 -C 6 )-alkyl-S(O) n R 4 , (C 1 -C 6 )-alkyl-OR 4 , (C 1 -C 6 )-alkyl-OCOR 4 , (C 1 -C 6 )-alkyl -OSO 2 R 4 , (C 1 -C 6 )-alkyl-SO 2 OR 4 , (C 1 -C 6 )-alkyl-SO 2 N(R 4 ) 2 or (C 1 -C 6 )-alkyl-NR 4 COR 4 ,
R 3 is fluorine, chlorine, bromine, iodine, nitro, CF 3 or the group SO 2 R,
R 4 is hydrogen, (C 1 -C 6 )-alkyl, (C 2 -C 6 )-alkenyl, (C 2 -C 6 )-alkynyl, (C 3 -C 6 )-cycloalkyl, phenyl or phenyl-(C 1 -C 6 )-alkyl, where the six last-mentioned radicals are substituted by s radicals of the group hydroxy, mercapto, amino, cyano, nitro, rhodano, OR 5 , SR 5 , N(R 5 ) 2 , NOR 5 , OCOR 5 , SCOR 5 , NR 5 COR 5 , CO 2 R 5 , COSR 5 , CON(R 5 ) 2 , (C 1 -C 4 )-alkyliminooxy, (C 1 -C 4 )-alkylcarbonyl, (C 1 -C 4 )-alkoxy-(C 2 -C 6 )-alkoxycarbonyl and (C 1 -C 4 )-alkylsulfonyl,
R 5 is hydrogen, (C 1 -C 6 )-alkyl, (C 2 -C 6 )-alkenyl or (C 2 -C 6 )-alkynyl,
R is (C 1 -C 4 )-alkyl,
n is 0, 1 or 2,
s is 0, 1, 2 or 3,
Y is a radical Y1, Y2, Y3, Y4, Y5 or Y6:
R 6 is (C 1 -C 4 )-alkyl,
R 7 is hydrogen or (C 1 -C 4 )-alkyl,
R 8 is hydrogen, (C 1 -C 6 )-alkylsulfonyl, (C 1 -C 4 )-alkoxy-(C 1 -C 6 )-alkylsulfonyl, or phenylsulfonyl, thiophenyl-2-sulfonyl, benzoyl, benzoyl-(C 1 -C 6 )-alkyl or benzyl substituted in each case by s radicals selected from the group consisting of halogen, (C 1 -C 4 )-alkyl and (C 1 -C 4 )-alkoxy,
R 9 is hydrogen, (C 1 -C 6 )-alkyl, (C 3 -C 7 )-cycloalkyl, halo-(C 1 -C 6 )-alkyl, (C 2 -C 6 )-alkenyl, halo-(C 2 -C 6 )-alkenyl, (C 2 -C 6 )-alkynyl, halo-(C 2 -C 6 )-alkynyl, CH 2 R 18 or phenyl substituted by s radicals from the group halogen, nitro, cyano, (C 1 -C 6 )-alkyl, halo-(C 1 -C 6 )-alkyl, (C 3 -C 6 )-cycloalkyl, S(O) n —(C 1 -C 6 )-alkyl, (C 1 -C 6 )-alkoxy, halo-(C 1 -C 6 )-alkoxy, (C 1 -C 6 )-alkoxy-(C 1 -C 4 )-alkyl,
R 9 * is hydrogen, nitro, halogen, cyano, rhodano, (C 1 -C 6 )-alkyl, halo-(C 1 -C 6 )-alkyl, (C 2 -C 6 )-alkenyl, halo-(C 2 -C 6 )-alkenyl, (C 2 -C 6 )-alkynyl, halo-(C 2 -C 6 )-alkynyl, (C 3 -C 6 )-cycloalkyl, (C 3 -C 6 )-cycloalkenyl, halo-(C 3 -C 6 )-cycloalkyl, (C 3 -C 6 )-cycloalkyl-(C 1 -C 6 )-alkyl, halo-(C 3 -C 6 )-cycloalkyl-(C 1 -C 6 )-alkyl, COR 1 , COOR 1 , OCOOR 1 , NR 1 COOR 1 , C(O)N(R 1 ) 2 , NR 1 C(O)N(R 1 ) 2 , OC(O)N(R 1 ) 2 , CO(NOR 1 )R 1 , NR 1 SO 2 R 2 , NR 1 COR 1 , OR 1 , OSO 2 R 2 , S(O) n R 2 , SO 2 OR 1 , SO 2 N(R 1 ) 2 , (C 1 -C 6 )-alkyl-S(O) n R 2 , (C 1 -C 6 )-alkyl-OR 1 , (C 1 -C 6 )-alkyl-OCOR 1 , (C 1 -C 6 )-alkyl-OSO 2 R 2 , (C 1 -C 6 )-alkyl-CO 2 R 1 , (C 1 -C 6 )-alkyl-CN, (C 1 -C 6 )-alkyl-SO 2 OR 1 , (C 1 -C 6 )-alkyl-CON(R 1 ) 2 , (C 1 -C 6 )-alkyl-SO 2 N(R 1 ) 2 , (C 1 -C 6 )-alkyl-NR 1 COR 1 , (C 1 -C 6 )-alkyl-NR 1 SO 2 R 2 , N(R 1 ) 2 , P(O)(OR 5 ) 2 , CH 2 P(O)(OR 5 ) 2 , (C 1 -C 6 )-alkylphenyl, (C 1 -C 6 )-alkylheteroaryl, (C 1 -C 6 )-alkylheterocyclyl, phenyl, heteroaryl or heterocyclyl, where the last 6 radicals are substituted in each case by s radicals from the group halogen, nitro, cyano, (C 1 -C 6 )-alkyl, halo-(C 1 -C 6 )-alkyl, (C 3 -C 6 )-cycloalkyl, S(O) n —(C 1 -C 6 )-alkyl, (C 1 -C 6 )-alkoxy, halo-(C 1 -C 6 )-alkoxy, (C 1 -C 6 )-alkoxy-(C 1 -C 4 )-alkyl and cyanomethyl, and where heterocyclyl carries 0 to 2 oxo groups,
R 10 is hydroxy or SR 17 ,
R 11 and R 16 , independently of one another, are hydrogen or (C 1 -C 4 )-alkyl, or the radicals R 11 and R 16 together form the unit Z, which is an oxygen atom or a sulfur atom or one to four methylene groups,
R 12 and R 15 , independently of one another, are hydrogen or (C 1 -C 4 )-alkyl,
R 13 and R 14 , independently of one another, are hydrogen or (C 1 -C 4 )-alkyl or, together with the carbon atom to which they are bonded, form a carbonyl group,
R 17 is (C 1 -C 4 )-alkyl, phenyl substituted by s radicals from the group consisting of nitro, cyano, (C 1 -C 4 )-alkyl, (C 1 -C 4 )-haloalkyl, (C 1 -C 4 )-alkoxy and (C 1 -C 4 )-haloalkoxy, or partially or completely halogenated phenyl,
R 18 is acetoxy, acetamido, N-methylacetamido, benzoyloxy, benzamido, N-methylbenzamido, methoxycarbonyl, ethoxycarbonyl, benzoyl, methylcarbonyl, piperidinylcarbonyl, morpholinylcarbonyl, trifluoromethylcarbonyl, aminocarbonyl, methylaminocarbonyl, dimethylaminocarbonyl, (C 1 -C 6 )-alkoxy, (C 3 -C 6 )-cycloalkyl or phenyl substituted by s radicals from the group methyl, ethyl, methoxy, trifluoromethyl and halogen.
2. The process as claimed in claim 1 , in which the radicals, symbols and indices have the following meanings:
R 1 is (C 1 -C 4 )-alkyl,
R 2 is nitro, halogen, (C 1 -C 4 )-alkyl, trifluoromethyl, (C 1 -C 4 )-alkoxy, methylsulfonyl, methoxymethyl, methoxymethoxymethyl, ethoxyethoxymethyl, ethoxymethoxymethyl, methoxyethoxymethyl, methoxypropoxymethyl, methylsulfonylmethyl, methylsulfonylethoxymethyl, methoxyethylsulfonylmethyl, methylsulfonylethylsulfonylmethyl,
R 3 is fluorine, chlorine, bromine, iodine, CF 3 or the group SO 2 R,
Y is a radical Y1, Y2, Y3, Y4, Y5 or Y6:
R 6 is methyl, ethyl, n-propyl or isopropyl,
R 7 is hydrogen, methyl, ethyl, n-propyl or isopropyl,
R 8 is hydrogen, (C 1 -C 3 )-alkylsulfonyl, (C 1 -C 2 )-alkoxy-(C 1 -C 4 )-alkylsulfonyl, or phenylsulfonyl, thiophenyl-2-sulfonyl, benzoyl, benzoyl-(C 1 -C 6 )-alkyl or benzyl substituted in each case by s methyl groups,
s is 0, 1, 2 or 3,
R 9 is (C 1 -C 6 )-alkyl, (C 3 -C 7 )-cycloalkyl, halo-(C 1 -C 6 )-alkyl, (C 3 -C 7 )-cycloalkylmethyl, methoxycarbonylmethyl, ethoxycarbonylmethyl, acetylmethyl, methoxymethyl, or phenyl or benzyl substituted by s radicals from the group methyl, methoxy, trifluoromethyl and halogen,
R 9 * is hydrogen, (C 1 -C 6 )-alkyl, halo-(C 1 -C 6 )-alkyl, (C 3 -C 6 )-cycloalkyl, COR 1 , OR 1 , COOR 1 or (C 1 -C 6 )-alkylphenyl,
R 10 is hydroxy,
R 11 and R 16 , independently of one another, are hydrogen or (C 1 -C 4 )-alkyl, or the radicals R 11 and R 16 together form a methylene group or ethylene group,
R 12 and R 15 , independently of one another, are hydrogen, methyl or ethyl,
R 13 and R 14 , independently of one another, are hydrogen, methyl or ethyl.
3. The process as claimed in claim 1 , where the reaction is carried out at a temperature of from −80 to −15° C.
4. The process as claimed in claim 1 , where the reaction is carried out at a temperature of from −50 to −20° C.
5. The process as claimed in claim 1 , where the chlorinating agent is selected from the group consisting of thionyl chloride, phosphorus oxychloride, oxalyl chloride and phosgene.
6. The process as claimed in claim 1 , where the chlorinating agent is selected from the group consisting of thionyl chloride and phosgene.
7. The process as claimed in claim 1 , where the chlorinating agent is thionyl chloride.
8. The process of claim 1 , wherein the compounds of formulae (Ib) and (II) are reacted in a solvent with said chlorinating agent in the presence of said base, optionally in the presence of a cyanide source.
9. The process as claimed in claim 8 , where the solvent is selected from the group consisting of aprotic and dipolar aprotic solvents.
10. The process as claimed in claim 8 , where the solvent is selected from the group consisting of ethyl acetate, propyl acetate, isopropyl acetate, butyl acetate, dichloromethane, dichloroethane, chlorotoluene, acetonitrile, butyronitrile and benzonitrile.
11. The process as claimed in claim 8 , where the solvent is selected from the group consisting of ethyl acetate, dichloromethane and dichloroethane.
12. The process as claimed in claim 8 , where the cyanide source is selected from the group consisting of acetone cyanohydrin and alkali metal cyanides.
13. The process as claimed in claim 8 , where the cyanide source is acetone cyanohydrin.