Dihydroquinolines, Dihydronaphthyridines and Quinolones by Domino Reactions of Morita-Baylis-Hillman Acetates
Abstract
:1. Introduction
2. Results and Discussion
3. Materials and Methods
3.1. General Methods
3.2. Syntheses of the MBH Acetates
3.2.1. 2-Cyano-1-(2-fluoropyridin-3-yl)allyl Acetate (6)
3.2.2. Ethyl-2-(acetoxy(2,5-difluorophenyl)methyl)acrylate (7)
3.3. Representative Procedure for the Synthesis of Dihydroheteroaromatics Using MBH Acetates and 1° Alkyl or Aromatic Amines
3.3.1. Ethyl-1-methyl-6-nitro-1,2-dihydroquinoline-3-carboxylate (9a) from 1 and Methylamine (8a)
3.3.2. Ethyl-1-hexyl-6-nitro-1,2-dihydroquinoline-3-carboxylate (9b) from 1 and n-hexylamine (8b)
3.3.3. Ethyl-1-isobutyl-6-nitro-1,2-dihydroquinoline-3-carboxylate (9c) from 1 and Isobutylamine (8c)
3.3.4. Ethyl-1-benzyl-6-nitro-1,2-dihydroquinoline-3-carboxylate (9d) from 1 and Benzylamine (8d)
3.3.5. Ethyl-6-nitro-1-phenethyl-1,2-dihydroquinoline-3-carboxylate (9e) from 1 and Phenethylamine (8e)
3.3.6. Ethyl-6-nitro-1-phenyl-1,2-dihydroquinoline-3-carboxylate (9f) from 1 and Aniline (8f)
3.3.7. 1-Methyl-6-nitro-1,2-dihydroquinoline-3-carbonitrile (10a) from 2 and 8a
3.3.8. 1-Hexyl-6-nitro-1,2-dihydroquinoline-3-carbonitrile (10b) from 2 and 8b
3.3.9. 1-Isobutyl-6-nitro-1,2-dihydroquinoline-3-carbonitrile (10c) from 2 and 8c
3.3.10. 1-Benzyl-6-nitro-1,2-dihydroquinoline-3-carbonitrile (10d) from 2 and 8d
3.3.11. 6-Nitro-1-phenethyl-1,2-dihydroquinoline-3-carbonitrile (10e) from 2 and 8e
3.3.12. 6-Nitro-1-phenyl-1,2-dihydroquinoline-3-carbonitrile (10f) from 2 and 8f
3.3.13. Ethyl-6-cyano-1-methyl-1,2-dihydroquinoline-3-carboxylate (11a) from 3 and 8a
3.3.14. Ethyl-6-cyano-1-hexyl-1,2-dihydroquinoline-3-carboxylate (11b) from 3 and 8b
3.3.15. Ethyl-6-cyano-1-isobutyl-1,2-dihydroquinoline-3-carboxylate (11c) from 3 and 8c
3.3.16. Ethyl-1-benzyl-6-cyano-1,2-dihydroquinoline-3-carboxylate (11d) from 3 and 8d
3.3.17. Ethyl-6-cyano-1-phenethyl-1,2-dihydroquinoline-3-carboxylate (11e) from 3 and 8e
3.3.18. Ethyl-6-cyano-1-phenyl-1,2-dihydroquinoline-3-carboxylate (11f) from 3 and 8f
3.3.19. 1-Methyl-1,2-dihydroquinoline-3,6-dicarbonitrile (12a) from 4 and 8a
3.3.20. 1-Hexyl-1,2-dihydroquinoline-3,6-dicarbonitrile (12b) from 4 and 8b
3.3.21. 1-Isobutyl-1,2-dihydroquinoline-3,6-dicarbonitrile (12c) from 4 and 8c
3.3.22. 1-Benzyl-1,2-dihydroquinoline-3,6-dicarbonitrile (12d) from 4 and 8d
3.3.23. 1-Phenethyl-1,2-dihydroquinoline-3,6-dicarbonitrile (12e) from 4 and 8e
3.3.24. Ethyl-1-methyl-1,2-dihydro-1,8-naphthyridine-3-carboxylate (13a) from 5 and 8a
3.3.25. Ethyl-1-hexyl-1,2-dihydro-1,8-naphthyridine-3-carboxylate (13b) from 5 and 8b
3.3.26. Ethyl-1-isobutyl-1,2-dihydro-1,8-naphthyridine-3-carboxylate (13c) from 5 and 8c
3.3.27. Ethyl-1-benzyl-1,2-dihydro-1,8-naphthyridine-3-carboxylate (13d) from 5 and 8d
3.3.28. Ethyl-1-phenethyl-1,2-dihydro-1,8-naphthyridine-3-carboxylate (13e) from 5 and 8e
3.3.29. Ethyl-1-phenyl-1,2-dihydro-1,8-naphthyridine-3-carboxylate (13f) from 5 and 8f
3.3.30. 1-Hexyl-1,2-dihydro-1,8-naphthyridine-3-carbonitrile (14b) from 6 and 8b
3.3.31. 1-Benzyl-1,2-dihydro-1,8-naphthyridine-3-carbonitrile (14d) from 6 and 8d
3.3.32. 1-Benzyl-1,4-dihydro-1,8-naphthyridine-3-carbonitrile (15d) from 6 and 8d
3.3.33. 1-Phenethyl-1,2-dihydro-1,8-naphthyridine-3-carbonitrile (14e) from 6 and 8e
3.3.34. 1-Phenyl-1,4-dihydro-1,8-naphthyridine-3-carbonitrile (15f) from 6 and 8f
3.4. Control Experiment Attempted Substitution of Benzylamine (8d) on 2-fluoropyridine and other SNAr Activated Rings
3.5. Control Experiment Capture of Intermediate (Z)-2-((benzylamino)methyl)-3-(2-fluoro-5-nitrophenyl)acrylonitrile (16)
3.6. Representative Procedure for Preparation of Fluorodihydroquinolines Using MBH Acetates and Primary Amines
3.6.1. Ethyl-6-fluoro-1-methyl-1,2-dihydroquinoline-3-carboxylate (18a) from 7 and 8a
3.6.2. Ethyl-6-fluoro-1-hexyl-1,2-dihydroquinoline-3-carboxylate (18b) from 7 and 8b
3.6.3. Ethyl-6-fluoro-1-isobutyl-1,2-dihydroquinoline-3-carboxylate (18c) from 7 and 8c
3.6.4. Ethyl-1-benzyl-6-fluoro-1,2-dihydroquinoline-3-carboxylate (18d) from 7 and 8d
3.6.5. Ethyl-6-fluoro-1-phenethyl-1,2-dihydroquinoline-3-carboxylate (18e) from 7 and 8e
3.7. Representative Procedure for Synthesis of Fluoroquinolones
3.7.1. Ethyl-6-fluoro-1-methyl-4-oxo-1,4-dihydroquinoline-3-carboxylate (19a) from 7 and 8a
3.7.2. Ethyl-6-fluoro-1-isobutyl-4-oxo-1,4-dihydroquinoline-3-carboxylate (19c) from 7 and 8c
3.7.3. Ethyl-1-benzyl-6-fluoro-4-oxo-1,4-dihydroquinoline-3-carboxylate (19d) from 7 and 8d
3.7.4. Ethyl-6-fluoro-4-oxo-1-phenethyl-1,4-dihydroquinoline-3-carboxylate (19e) from 7 and 8e
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Substrate | Amine | R a | X | Y | Product (%) |
---|---|---|---|---|---|
8a | CH3 | CO2Et | NO2 | 9a (93) | |
8b | n-Hex | CO2Et | NO2 | 9b (87) | |
8c | i-Bu | CO2Et | NO2 | 9c (93) | |
8d | CH2Ph | CO2Et | NO2 | 9d (92) | |
8e | CH2CH2Ph | CO2Et | NO2 | 9e (83) | |
8f | Ph | CO2Et | NO2 | 9f (89) | |
8a | CH3 | CN | NO2 | 10a (88) | |
8b | n-Hex | CN | NO2 | 10b (78) | |
8c | i-Bu | CN | NO2 | 10c (79) | |
8d | CH2Ph | CN | NO2 | 10d (80) | |
8e | CH2CH2Ph | CN | NO2 | 10e (82) | |
8f | Ph | CN | NO2 | 10f (81) | |
8a | CH3 | CO2Et | CN | 11a (91) | |
8b | n-Hex | CO2Et | CN | 11b (82) | |
8c | i-Bu | CO2Et | CN | 11c (85) | |
8d | CH2Ph | CO2Et | CN | 11d (79) | |
8e | CH2CH2Ph | CO2Et | CN | 11e (85) | |
8f | Ph | CO2Et | CN | 11f (83) | |
8a | CH3 | CN | CN | 12a (82) | |
8b | n-Hex | CN | CN | 12b (77) | |
8c | i-Bu | CN | CN | 12c (81) | |
8d | CH2Ph | CN | CN | 12d (86) | |
8e | CH2CH2Ph | CN | CN | 12e (88) |
Substrate | Amine | R a | X | Product (%) |
---|---|---|---|---|
8a | CH3 | CO2Et | 13a (88) | |
8b | n-Hex | CO2Et | 13b (80) | |
8c | i-Bu | CO2Et | 13c (80) | |
8d | CH2Ph | CO2Et | 13d (81) | |
8e | CH2CH2Ph | CO2Et | 13e (83) | |
8f | Ph | CO2Et | 13f (77) | |
8b | n-Hex | CN | 14b (82) | |
8d | CH2Ph | CN | 14d (6) + 15d (82) | |
8e | CH2CH2Ph | CN | 14e (80) | |
8f | Ph | CN | 15f (72) b |
Substrate | Amine | R a | Product (%) |
---|---|---|---|
8a | CH3 | 18a (91) | |
8b | n-Hex | 18b (80) | |
8c | i-Bu | 18c (88) | |
8d | CH2Ph | 18d (84) | |
8e | CH2CH2Ph | 18e (89) | |
8a | CH3 | 19a (85) | |
8b | n-Hex | b | |
8c | i-Bu | 19c (86) | |
8d | CH2Ph | 19d (83) | |
8e | CH2CH2Ph | 19e (84) |
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Annor-Gyamfi, J.K.; Ametsetor, E.; Meraz, K.; Bunce, R.A. Dihydroquinolines, Dihydronaphthyridines and Quinolones by Domino Reactions of Morita-Baylis-Hillman Acetates. Molecules 2021, 26, 890. https://doi.org/10.3390/molecules26040890
Annor-Gyamfi JK, Ametsetor E, Meraz K, Bunce RA. Dihydroquinolines, Dihydronaphthyridines and Quinolones by Domino Reactions of Morita-Baylis-Hillman Acetates. Molecules. 2021; 26(4):890. https://doi.org/10.3390/molecules26040890
Chicago/Turabian StyleAnnor-Gyamfi, Joel K., Ebenezer Ametsetor, Kevin Meraz, and Richard A. Bunce. 2021. "Dihydroquinolines, Dihydronaphthyridines and Quinolones by Domino Reactions of Morita-Baylis-Hillman Acetates" Molecules 26, no. 4: 890. https://doi.org/10.3390/molecules26040890