Claims
- 1. A method of preparing substituted and unsubstituted 1,4-dihydro-4-oxo-2 and -3 quinolinic carboxylic acids which comprises heating an ester selected from the group consisting of substituted and unsubstituted anilinomethylenemalonates, anilinofumurates, anilinomaleates and mixtures thereof in a reaction medium selected from chlorosulfonic acid, oleum and mixtures thereof.
- 2. A method according to claim 1 wherein said ester has the following formula: ##STR4## wherein: R.sub.1 is hydrogen; C.sub.1 -C.sub.5 alkyl; C.sub.3 -C.sub.6 cycloalkyl; C.sub.1 -C.sub.5 halo-substituted C.sub.1 to C.sub.5 alkyl wherein halo is F, Cl, Br or I; aryl or C.sub.1 to C.sub.5 hydroxyalkyl and, C.sub.1 to C.sub.5 mercaptoalkyl, R.sub.1 together with R.sub.2 can be joined with an alkylene, oxyalkylene or thioalkylene group to form a 5 or 6 member heterocyclic ring;
- R.sub.2 is hydrogen, F, Cl, Br, I, C.sub.1 -C.sub.5 alkyl, a halogen substituted C.sub.1 to C.sub.5 alkyl, C.sub.1 -C.sub.5 alkoxy, NO.sub.2 --, R.sub.n N-- wherein R is independently hydrogen or C.sub.1 to C.sub.s alkyl and n=2; R.sub.2 together with R.sub.1 can be joined with an alkylene, oxyalkylene or thioalkylene group to form a 5 or 6 member heterocyclic ring;
- R.sub.3 is hydrogen, F, Cl, B, I, C.sub.1 to C.sub.4 alkyl, a halogen substituted C.sub.1 to C.sub.5 alkyl, C.sub.1 to C.sub.5 alkoxy, NO.sub.2 --, or R.sub.n N-- wherein R is independently hydrogen, or C.sub.1 -C.sub.5 alkyl and n=2;
- R.sub.4 is hydrogen, F, Cl, B, I, C.sub.1 to C.sub.5 alkyl a halogen substituted C.sub.1 to C.sub.5 alkyl, C.sub.1 to C.sub.5 alkoxy, NO.sub.2 --, R.sub.n N-- wherein R is independently hydrogen or C.sub.1 to C.sub.5 alkyl and n=2;
- R.sub.5 is hydrogen, F, Cl, B, I, C.sub.1 -C.sub.5 alkyl, a halogen substituted C.sub.1 to C.sub.5 alkyl, C.sub.1 to C.sub.5 alkoxy, NO.sub.2 --, R.sub.n N-- wherein R is independently hydrogen or C.sub.1 to C.sub.5 alkyl and n=2;
- R.sub.6 is hydrogen, C.sub.1 -C.sub.5 alkyl, C.sub.3 -C.sub.6 cyclo alkyl or phenyl;
- R.sub.7 is hydrogen, C.sub.1 -C.sub.5 alkyl, alkoxycarbonyl wherein said alkoxy portion is a C.sub.1 -C.sub.5 alkoxy or a C.sub.2 -C.sub.6 cycloalkoxy, a phenoxycarbonyl; and
- R.sub.8 is hydrogen, alkoxycarbonyl, as defined above or phenoxycarbonyl which may be substituted with a halogen or alkyl.
- 3. A method according to claim 1 wherein said ester has the following formula: ##STR5## wherein: R.sub.1 is hydrogen; C.sub.1 -C.sub.5 alkyl; C.sub.3 -C.sub.6 cycloalkyl; C.sub.1 -C.sub.5 halo-substituted C.sub.1 to C.sub.5 alkyl wherein halo is F, Cl, Br or I; aryl or C.sub.1 to C.sub.5 hydroxyalkyl and, C.sub.1 to C.sub.5 mercaptoalkyl, R.sub.1 together with R.sub.2 can be joined with an alkylene, oxyalkylene or thioalkylene group to form a 5 or 6 member heterocyclic ring;
- R.sub.2 is hydrogen, F, Cl, B, I, C.sub.1 -C.sub.5 alkyl, halogen substituted C.sub.1 to C.sub.5 alkyl, C.sub.1 -C.sub.5 alkoxy, R.sub.2 together with R.sub.1 can be joined with an alkylene, oxyalkylene or thioalkylene group to form a 5 or 6 member ring;
- R.sub.3 is F, Cl, B, I, halogen substituted C.sub.1 to C.sub.4 alkyl, C.sub.1 to C.sub.5 alkoxy, or R.sub.2 N-- wherein R is independently hydrogen, or C.sub.1 -C.sub.5 alkyl;
- R.sub.4 is F, Cl, B, I, C.sub.1 to C.sub.5 alkyl;
- R.sub.5 is hydrogen, halogen (F, Cl, B, I), C.sub.1 -C.sub.5 alkyl or NO.sub.2 --;
- R.sub.6 is hydrogen, C.sub.1 -C.sub.5 alkyl, C.sub.3 -C.sub.5 cyclo alkyl or phenyl;
- R.sub.7 is hydrogen, C.sub.1 -C.sub.5 alkyl, alkoxycarbonyl wherein said alkoxy portion is a C.sub.1 -C.sub.5 alkoxy or a C.sub.2 -C.sub.6 cycloalkoxy or, a phenoxycarbonyl; and
- R.sub.8 is hydrogen, alkoxycarbonyl, as defined above or phenoxycarbonyl which may be substituted with a halogen or alkyl.
- 4. A method according to claim 2 wherein R.sub.1 is a C.sub.2 alkyl, R.sub.2, R.sub.3, and R.sub.4 are fluoro and R.sub.5 is hydrogen.
- 5. A method according to claim 2 wherein said heating is conducted at a temperature of about 40.degree.-180.degree. C.
- 6. A method according to claim 2 wherein said heating is conducted at a temperature of about 60.degree.-150.degree. C.
- 7. A method according to claim 2 wherein said heating is conducted at a temperature of about 70.degree.-90.degree. C.
- 8. A method according to claim 2 wherein said reaction medium contains a diluent.
- 9. A method according to claim 2 wherein R.sub.1 is a C.sub.2 fluoroalkyl, R.sub.2, R.sub.3, R.sub.4 are fluoro, R.sub.5 is hydrogen.
- 10. A method according to claim 2 wherein R.sub.1 is a C.sub.2 alkyl, R.sub.2 is hydrogen, R.sub.3 is chloro, R.sub. 4 is fluoro and R.sub.5 is hydrogen.
- 11. A method according to claim 2 wherein R.sub.1 is a C.sub.2 alkyl, R.sub.2 is hydrogen, R.sub.3 and R.sub.4 are fluoro, R.sub.5 is hydrogen.
- 12. A method according to claim 2 wherein R.sub.1 is cyclopropyl, R.sub.2 is hydrogen, R.sub.3 is chloro, R.sub.4 is fluoro, R.sub.5 is hydrogen.
- 13. A method according to claim 2 wherein R.sub.1 is cyclopropyl, R.sub.2 is hydrogen, R.sub.3 and R.sub.4 are fluoro and R.sub.5 is hydrogen.
- 14. A method according to claim 2 wherein R.sub.1 and R.sub.2 together are a methyloxyethylene ring, R.sub.3, R.sub.4 are fluoro and R.sub.5 is hydrogen.
- 15. A method according to claim 2 wherein R.sub.1 is cyclopropyl, R.sub.2 is methoxy, R.sub.3 and R.sub.4 are fluoro, and R.sub.5 is hydrogen.
- 16. A method according to claim 2 wherein R.sub.1 is cyclopropyl, R.sub.2 is hydrogen, R.sub.3 and R.sub.4 are fluoro, and R.sub.5 is methyl.
- 17. A method according to claim 2 wherein R.sub.1 is cyclopropyl, R.sub.2 is hydrogen, R.sub.3 is chloro, R.sub.4 is fluoro, and R.sub.5 is methyl.
- 18. A method according to claim 2 wherein R.sub.1 is cyclopropyl, R.sub.2, R.sub.3 and R.sub.4 are fluoro, and R.sub.5 is nitro.
- 19. A method according to claim 2 wherein R.sub.1 and R.sub.2 together are fluoromethyl-oxyalkylene ring, R.sub.3 and R.sub.4 are fluoro, and R.sub.5 is hydrogen.
- 20. A method according to claim 2 wherein R.sub.1 and R.sub.2 together are a thioalkylene ring, R.sub.3 and R.sub.4 are fluoro and R.sub.5 is hydrogen.
Parent Case Info
CROSS-REFERENCE TO RELATED APPLICATIONS
This application is a continuation-in-part of U.S. patent application Ser. No. 08/017,583 filed Feb. 16, 1993, abandoned.
US Referenced Citations (1)
Number |
Name |
Date |
Kind |
4528287 |
Itoh et al. |
Jul 1985 |
|
Non-Patent Literature Citations (2)
Entry |
Hui-Yuan et al, Pharmaceutical Industry, pp. 390-394, 1986. |
Bridges et al., J. Heterocyclic Chemistry, vol. 27, pp. 1527-1536, 1990. |
Continuation in Parts (1)
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Number |
Date |
Country |
Parent |
17583 |
Feb 1993 |
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