The Application of Vinamidinium Salt to the Synthesis of 3-Chloro-α-carbolines

Shaixiao Tian; Yu Mao; Yongjun Jiang; Guangyu Xu

doi:10.1055/s-0037-1609151

Synlett, Table of Contents

Synlett 2018; 29(07): 949-953
DOI: 10.1055/s-0037-1609151

letter

The Application of Vinamidinium Salt to the Synthesis of 3-Chloro-α-carbolines

Authors

Shaixiao Tian

^aKey Laboratory of Chemical Biology and Traditional Chinese Medicine Research (Ministry of Education), College of Chemistry and Chemical Engineering, Hunan Normal University, Changsha 410081, P. R. of China Email: gyxu@hunnu.edu.cn
Yu Mao

^aKey Laboratory of Chemical Biology and Traditional Chinese Medicine Research (Ministry of Education), College of Chemistry and Chemical Engineering, Hunan Normal University, Changsha 410081, P. R. of China Email: gyxu@hunnu.edu.cn
Yongjun Jiang

^bSchool of Biotechnology and Chemical Engineering, Institute of Technology, Zhejiang University, Ningbo, P. R. of China
Guangyu Xu*

^aKey Laboratory of Chemical Biology and Traditional Chinese Medicine Research (Ministry of Education), College of Chemistry and Chemical Engineering, Hunan Normal University, Changsha 410081, P. R. of China Email: gyxu@hunnu.edu.cn

Abstract

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Abstract

A convenient synthesis of 3-chloro-α-carbolines by the condensation of vinamidinium salt with 2-indolinones via two steps is reported. This protocol has the advantages of readily available starting materials, high yields and easy workup.

Key words

α-carboline - 3-chloro-α-carboline - synthesis - vinamidinium salt - 2-indolinone

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References

References and Notes
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25 Procedure for the Synthesis of 3-(3-Amino-2-chloropropylidene)-6-chloro-2-indolinone (4a) To a one-neck round-bottom flask equipped with magnetic stirring was added 6-chloro-2-indolinone (2a, 1.00 g, 6.0 mmol), vinamidinium salt 3 ²⁴ (2.02 g, 12.0 mmol), Et₃N (1.82 g, 18.0 mmol), and DMF (10 mL). The mixture was stirred for 20 h at r.t., after the reaction was complete (monitored by TLC, EtOAc/MeOH = 20:1), 30 mL EtOAc and 30 mL water was added, then the aqueous layer was extracted with 30 mL EtOAc. The combined EtOAc layer was washed with sat. NaCl solution (15 mL) and water (15 mL) then dried over Na₂SO₄. After filtering the desiccant, the solvent was concentrated under vacuum to a volume of about 5 mL. The mixture was titrated with 15 mL n-hexane to give a yellow precipitant, the solid was filtered, and dried under vacuum to give 4a (1.34 g, yield 88%), a yellow powder, which was used in the next step without further purification; mp > 250 °C. ¹H NMR (500 MHz, DMSO): δ = 10.34 (s, 1 H), 8.10 (d, J = 8.0 Hz, 1 H), 7.97 (s, 1 H), 7.75 (t, J = 11.0 Hz, 1 H), 7.44 (s, 2 H), 6.88 (d, J = 8.5 Hz, 1 H), 6.78 (s, 1 H). ¹³C NMR (125 MHz, DMSO): δ = 170.53, 151.17, 141.75, 138.14, 129.98, 125.26, 122.07, 120.20, 109.96, 109.14, 101.24. ESI-HRMS: m/z calcd for C₁₁H₉Cl₂N₂O⁺: 255.0086; found: 255.0078 [M + H]⁺.
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27 In a 25 mL three-necked flask compound 4a (1.28 g, 5.0 mmol) and 25 mL 1,4-dioxane were added, and POCl₃ (1.53 g, 10.0 mmol) was added to the mixture dropwise at 0 °C under continuous stirring. The reaction mixture was stirred for 2 h at r.t. then heated at reflux for 20 h. After the reaction was complete (monitored by TLC, PE/EtOAc = 3:1), the solvent and POCl₃ were evaporated under vacuum, then 60 mL EtOAc was added. The organic phase was successively washed with water (25 mL), 8% aq NaHCO₃ (25 mL) and water (25 mL), then dried with Na₂SO₄ and evaporated under vacuum to yield a brown solid which on flash chromatography (SiO₂, EtOAc/hexane = 1:6) elution yielded 3,7-dichloro-α-carboline (1a, 1.08 g, 93%) as a yellow solid; mp >250 °C. ¹H NMR (500 MHz, DMSO): δ = 12.27 (s, 1 H), 8.72 (s, 1 H), 8.43 (s, 1 H), 8.23 (d, J = 8.5 Hz, 1 H), 7.54 (s, 1 H), 7.27 (d, J = 8.5 Hz, 1 H). ¹³C NMR (125 MHz, DMSO): δ = 150.81, 144.91, 140.72, 132.21, 128.72, 123.71, 122.68, 120.53, 118,89, 116.28, 111.60. ESI-HRMS: m/z calcd for C₁₁H₇Cl₂N₂ ⁺: 236.9981; found: 236.9973 [M + H]⁺.

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