Patent EA-000663-B1 (EA)
Title: Process forpreparing benzyl-substituted rhodanine derivatives
Inventor: COPP JAMES D
IPC: C07C323/60
Filed: 1996-09-03
Abstract: 1. A process for preparing a compound of the formula I   wherein: Ar is (i) phenyl, (ii) phenyl substituted with from one to three substituents independently selected from C1-C8 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C8 alkoxy, C1-C8 alkylthio, trifluoromethyl, C1-C4 alkylphenyl, phenyl, F, Cl, hydroxy, phenoxy, C1-C4 alkyloxyphenyl, thiophenyl, C1-C4 alkylthiophenyl, N(R<4>)2 where each R<4> is independently C1-C6 alkyl or (iii) 1- or 2-napthyl; R<1> is H, C1-C6 alkyl, C1-C4 alkylphenyl, phenyl or phenyl-substituted with one or two substituents independently selected from Cl, F, C1-C4 alkyl, C1-C4 alkoxy, trifluoromethyl, -N(C1-C4 alkyl)2 or C1-C4 alkylthio; R<2> is H, C1-C6 alkyl, benzyl or a-methylbenzyl; and R<3> is (i) H, (ii) C1-C6 alkyl, (iii) phenyl, (iv) phenyl substituted with from one to three substituents independently selected from C1-C8 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C8 alkoxy, C1-C8 alkylthio, trifluoromethyl, C1-C4 alkylphenyl, phenyl, F, Cl, hydroxy, phenoxy, C1-C4 alkyloxyphenyl, thiophenyl, C1-C4 alkylthiophenyl, N(R<4>)2 where each R<4> is independently Ci-Cg alkyl or (v) 1- or 2-napthyl; which comprises reacting a compound of the formula III   wherein: Ar, R<3>- and R<2> are as defined above, and X is S, NH, or O; H with an aldehyde of the formula   R<3>-C=O where R<3> is (i) H, (ii) C1-C6 alkyl, (iii) phenyl, (iv) phenyl substituted with from one to three substituents independently selected from C1-C8 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C8 alkoxy, C1-C8 alkylthio, trifluoromethyl, C1-C4 alkylphenyl, phenyl, F, Cl, hydroxy, phenoxy, C1-C4 alkyloxyphenyl, thiophenyl, C1-C4 alkylthiophenyl, N(R<4>)2 where each R<4> is independently C1-C6 alkyl or (v) 1- or 2-napthyl; wherein said reaction is conducted in the presence of an amine of the formula H2NR6 where R<6> is H, C1-C6 alkyl, benzyl or α-methylbenzyl. 2. The process of Claim 1 which employs ammonia as the amine and formaldehyde as the aldehyde. 3. The process of Claim 1 or 2 in which the process is conducted at a temperature from about 60 degree C to about 80 degree C for about 10 to about 20 hours, by mixing a compound of formula III, aldehyde and amine in a liquid medium at superatmospheric pressure using 10 to 14 moles of ammonia and about 0.5 to about 2.0 moles of formaldelyde per mole of the compound of formula III. 4. The process of Claim 1, 2 or 3 which prepares 5-[3,5-bis (1,1 -dimethylethyl)-4-hydroxyphenyl]methyl-4-thiazolidinone. 5. A compound of the formula II   wherein: Ar is (i) phenyl, (ii) phenyl substituted with from one to three substituenfcs independently selected from C1-C8 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C8 alkoxy, C1-C8 alkylthio, trifluoromethyl, C1-C4 alkylphenyl, phenyl, F, Cl, hydroxy, phenoxy, C1-C4 alkyloxyphenyl, thiophenyl, C1-C4 alkylthiophenyl, N(R<4>)2 where each R<4> is independently C1-C6 alkyl or (iii) 1- or 2-napthyl; R<1> is hydrogen C1-C6 alkyl, C1-C4 alkylphenyl, phenyl or phenyl-substituted with one or two substituents independently selected from Cl, F, C1-C4 alkyl, C1-C4 alkoxy, trifluoromethyl, -N (C1-C4 alkyl)2 or C1-C4 alkylthio; R<2> is H, C1-C6 alkyl, benzyl or α-methylbenzyl; and R<5> is H or -CHR<3>OH, where R<3> is (i) H, (ii) C1-C6 alkyl, (iii) phenyl, (iv) phenyl substituted with from one to three substituents independently selected from C1-C8 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C8 alkoxy, C1-C8 alkylthio, trifluoromethyl, C1-C4 alkylphenyl, phenyl, F, Cl, hydroxy, phenoxy, C1-C4 alkyloxyphenyl thiophenyl, C1-C4 alkylthiophenyl, N(R<4>)2 where each R<4> is independently C1-C6 alkyl or (v) 1- or 2-napthyl. 6. The compound of Claim 5 wherein Ar is phenyl-substituted with from one to three substituents independently selected from C1-C8 alkyl, C1-C8 alkoxy, C1-C4 alkylphenyl, phenyl, F, Cl, hydroxy, phenoxy or C1-C4 alkylthiophenyl; R<2> is H; and R<5> is H or -CH2OH. 7. The compound of Claim 6 which is 4-hydroxy-3,5-bis(l,l-dimethylethyl)-α-[(hydroxymethyl)-thio]benzene ethanamide. 8. The compound of Claim 6 which is 4-hydroxy-α-mercapto-3,5-(1,l-dimethylethyl)benzene ethanamide.