Regioselective preparation and NMR spectroscopy study of 2-chloro-4-ethoxy-quinoline for the synthesis of 2-((3-aminopropyl)amino)quinolin-4(1H)-one

Author(s)

Vasconcelos Vontobel, Pedro Henrique ^[1] ; dos Santos Fuscaldo, Rodrigo ^[1] ; Paulo dos Santos, Francisco ^[1] ; Sobieski da Costa, Jessie ^[1]

Affiliation

^[1] Univ Fed Rio Grande do Sul, Inst Chem, Ave Bento Goncalves 9500, BR-91501970 Porto Alegre, RS - Brazil

• Document type: Journal article
• Source: Magnetic Resonance in Chemistry; v. 58, n. 4 DEC 2019.
• Web of Science Citations: 0

Abstract

Herein, we describe the C4-ethoxylation of 2,4-dichloroquinoline to prepare 2-chloro-4-ethoxy-quinoline (3), which is a prominent intermediate used for the synthesis of 2-substituted quinolones. To achieve this goal, we studied different conditions for the reaction between 2,4-dichloroquinoline and sodium ethoxide. We discovered that the use of 18-crown-6 ether as an additive and dimethylformamide as the reaction solvent allowed us to obtain the desired product 3 in very good yield and selectivity. In addition, a definitive distinction between the C2 and C4 ethoxylation products was achieved using (HN)-H-1-N-15 heteronuclear multiple bond correlation. Compound 3 is an intermediate used for the synthesis of 2-((3-aminopropyl)amino)quinolin-4(1H)-one, which displays peculiar behavior during H-1 nuclear magnetic resonance analysis, such as the broadening of the H8 singlet and unexpected deuteration at the C8-position. Effort has been dedicated to understand these findings. (AU)

• FAPESP's process: 15/08541-6 - Nuclear magnetic resonance spectroscopy: beyond molecular structure assignment
• Grantee: Claudio Francisco Tormena
• Support Opportunities: Research Projects - Thematic Grants