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. 2023 Feb 13;8(7):6940-6944.
doi: 10.1021/acsomega.2c07736. eCollection 2023 Feb 21.

Metal-Free Synthesis of Functionalized Quinolines from 2-Styrylanilines and 2-Methylbenzothiazoles/2-Methylquinolines

Xiaoying Liu  1 , Xianglong Chu  1
Affiliations

Metal-Free Synthesis of Functionalized Quinolines from 2-Styrylanilines and 2-Methylbenzothiazoles/2-Methylquinolines

Xiaoying Liu et al. ACS Omega. .

Abstract

A facile functionalization of C(sp3)-H bonds and tandem cyclization strategy to synthesize quinoline derivatives from 2-methylbenzothiazoles or 2-methylquinolines and 2-styrylanilines has been developed. This work avoids the requirement for transition metals, offering a mild approach to activation of C(sp3)-H bonds and formation of new C-C and C-N bonds. This strategy features excellent functional group tolerance and scaled-up synthetic capability, thus providing an efficient and environmentally friendly access to medicinally valuable quinolines.

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Conflict of interest statement

The authors declare no competing financial interest.

Figures

Figure 1
Figure 1
Selected quinoline- and benzothiazole-based structures.
Scheme 1
Scheme 1. (a and b) Synthesis of Quinoline Derivatives from 2-Styrylanilines
Scheme 2
Scheme 2. Cyclization of 2-Methylbenzothiazoles with 2-Styrylanilinesa
Reaction conditions: 1 (0.3 mmol), 2 (0.54 mmol), I2 (0.2 equiv), TBHP (3 equiv), 1.5 mL of DMSO, 120 °C. Reaction with 2-hydrazinylpyridine.
Scheme 3
Scheme 3. Cyclization of 2-Methylquinolines with 2-Styrylanilinesa
Reaction Conditions: 4 (0.3 mmol), 2 (0.54 mmol), I2 (0.2 equiv), TBHP (3 equiv), CH3COOH (1 equiv), 1.5 mL of DMSO, 120 °C.
Scheme 4
Scheme 4. Gram-Scale Synthesis
Scheme 5
Scheme 5. (a–d) Control Experiments
Scheme 6
Scheme 6. Proposed Mechanism
See this image and copyright information in PMC

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