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Synlett 2012(4): 611-621  
DOI: 10.1055/s-0031-1290344
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

Efficient and General Synthesis of 3-Aryl Coumarins Using Cyanuric Chloride [¹]

Koneni V. Sashidhara*, Gopala Reddy Palnati, Srinivasa Rao Avula, Abdhesh Kumar
Medicinal and Process Chemistry Division, Central Drug Research Institute, CSIR-CDRI, Lucknow 226 001, India
Fax: +91(522)2623405; e-Mail: sashidhar123@gmail.com; e-Mail: kv_sashidhara@cdri.res.in;
Further Information

Publication History

Received 22 December 2011
Publication Date:
10 February 2012 (online)

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Abstract

An efficient and general protocol for a rapid synthesis of different substituted 3-aryl coumarins is reported. A series of different substituted phenyl acetic acids have been successfully reacted with different substituted 2-hydroxy benzaldehydes in the presence of cyanuric chloride (2,4,6-trichloro-1,3,5-triazine) and N-methyl morpholine to afford 3-aryl coumarins in good to excellent yields.

Key words

synthesis - 3-aryl coumarins - cyanuric chloride - 2-­hydroxy benzaldehyde

1

Part VIII in the series ‘Studies on Novel Synthetic Methodologies’.

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1

Part VIII in the series ‘Studies on Novel Synthetic Methodologies’.

37

Representative Experimental Procedure for the Synthesis of 3-(4′-Methoxy Phenyl) Coumarin (1c)
A mixture of cyanuric chloride (377 mg, 1.0 mmol), NMM (331 mg, 1.5 mmol), and 4-methoxyphenylacetic acid (1b, 340 mg, 1 mmol) in DMF (5 mL) was stirred at r.t. for 10 min. After this time 2-hydroxybenzaldehyde (1a, 250 mg, 1 mmol) was added. Subsequently, the resulting reaction mixture was refluxed for 45 min. Completion of the reaction was monitored by TLC. The reaction mixture was diluted with H2O (10 mL) and extracted 3 times with EtOAc (15 mL). The combined organic layers were dried over Na2SO4, filtered, and concentrated to dryness under reduced pressure. The residue was purified by column chromatography (Al2O3, 70-230 mesh, neutral, hexane-CH2Cl2) to provide pure 1c [3-(4′-methoxyphenyl)coumarin] as a colorless crystalline solid; yield 95%; mp 146-148 ˚C. IR (KBr): 3033, 1705, 1633, 1020 cm-¹. ¹H NMR (300 MHz, CDCl3): δ = 7.75 (s, 1 H), 7.68 (d, J = 8.8 Hz, 2 H), 7.53-7.47 (m, 2 H), 7.36-7.28 (m, 2 H), 6.97 (d, J = 8.8 Hz, 2 H), 3.85 (s, 3 H). ¹³C NMR (75 MHz, CDCl3): δ = 160.8, 160.2, 153.3, 138.5, 131.0, 129.9, 127.9, 127.8, 127.1, 124.5, 119.9, 116.4, 113.9, 55.4. ESI-MS: m/z = 252 [M + H]+.