Download PDF
Synlett 2010(11): 1635-1640  
DOI: 10.1055/s-0030-1258091
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

Triflic Acid Promoted Tandem Ring-Closure-Aryl-Migration of 2′-Amino Chalcone Epoxide: A New Synthetic Route to Azaisoflavones

Chandrasekaran Praveena, Kannabiran Parthasarathyb, Paramasivan T. Perumal*a
a Organic Chemistry Division, Central Leather Research Institute, Adyar, Chennai 600 020, India
b Analytical Research & Development, Orchid Chemicals & Pharmaceuticals Ltd., Research & Development Centre, Sholinganallur, Chennai 600 119, India
Fax: +91(44)24911589; e-Mail: ptperumal@gmail.com;
Further Information

Publication History

Received 25 March 2010
Publication Date:
11 June 2010 (online)

    Permissions and Reprints All articles of this category

Abstract

An unprecedented TfOH-promoted tandem ring-closure-aryl-migration of 2′-amino chalcone epoxide leading to 3-aryl-4(1H)-quinolones (azaisoflavones) was achieved. The outcome of the reaction was confirmed by NMR analysis and rationalized through the intermediacy of a phenonium ion. This synthetic protocol furnishes azaisoflavones straightforwardly from simple starting materials under mild conditions.

Key words

2′-amino chalcone epoxide - triflic acid - sequential ring-opening aryl-migration - phenonium ion - azaisoflavones

8

A highly polar new product was observed on TLC. However it was not characterized.

9

The reaction of 1a with AgOTf (1.0 equiv) in wet CH2Cl2 resulted in the formation of 3a in 45% yield. It was thought that AgOTf is hydrolyzed to AgOH and TfOH and the resulting TfOH effects the formation of the product. Similarly, the reaction of 1a with AgOH did not led to any product formation at all. Having observed this, we decided to use TfOH as the catalyst

11

The ring-opening of trans-chalcone epoxide 1a with TfOH (0.5 equiv) gave trans-1,2,3,4-tetrahydro-3-hydroxy-2-phenyl-4 (1H)-quinolone (2a). The spectral data and stereochemistry of the product was consistent with the literature value (ref. 1).

17

Representative procedure for the synthesis of azaisoflavones (3a-k): To a stirred solution of 2′-amino chalcone epoxide 1a (239 mg, 1.0 mmol) in anhydrous CH2Cl2 (1 mL) were added trifluoromethanesulphonic acid (452 mg, 3.0 mmol), dropwise at 0 ˚C. After completion of the reaction as indicated by TLC, the reaction mixture was quenched with ice-cold water and adjusted the pH to 7.5 with NaHCO3, extracted with CH2Cl2 (3 × 15 mL), and the organic extract was dried with anhydrous sodium sulphate. Removal of the solvent under reduced pressure gave the crude product, which was purified by column chromatog-raphy (EtOAc-petroleum ether, 6:4) to afford the pure product 3a as a brown solid. Mp 258-260 ˚C (Lit.¹9 257 ˚C). IR (KBr): 3454, 1621, 1561, 1515, 1356, 1292, 753, 697 cm-¹. ¹H NMR (400 MHz, DMSO-d 6): δ = 7.27 (t, J = 7.4 Hz, 1 H), 7.34-7.42 (m, 3 H), 7.59 (d, J = 8.0 Hz, 1 H), 7.65 (t, J = 8.0 Hz, 1 H), 7.73 (d, J = 7.4 Hz, 2 H), 8.16 (d, J = 6.1 Hz, 1 H), 8.21 (d, J = 7.9 Hz, 1 H), 12.06 (d, J = 5.7 Hz, 1 H, D2O exchangeable). ¹³C NMR (100 MHz, DMSO-d 6): δ = 118.2, 119.7, 123.3, 125.6, 125.8, 126.4, 127.9, 128.5, 131.5, 136.2, 138.1, 139.3, 174.7. MS (ESI): m/z = 222 [M + H]+. Anal. Calcd for C15H11NO: C, 81.43; H, 5.01; N, 6.33. Found: C, 82.01; H, 5.03; N, 6.35