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Synlett 2018; 29(07): 949-953
DOI: 10.1055/s-0037-1609151
DOI: 10.1055/s-0037-1609151
letter
The Application of Vinamidinium Salt to the Synthesis of 3-Chloro-α-carbolines
This work was supported by Opening Fund of Key Laboratory of Chemical Biology and Traditional Chinese Medicine Research (Ministry of Education of China), Hunan Normal University (KLCBTCMR201802), and Natural Science Foundation of Zhejiang Province (LY14H300004).
Further Information
Publication History
Received: 19 November 2017
Accepted after revision: 18 December 2017
Publication Date:
26 February 2018 (online)
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.
Supporting Information
- Supporting information for this article is available online at https://doi.org/10.1055/s-0037-1609151.
- Supporting Information
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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]+.