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Synlett 2005(4): 623-626  
DOI: 10.1055/s-2005-862365
LETTER
© Georg Thieme Verlag Stuttgart · New York

Regioselective Syntheses of Functionalized 2-Aminopyridines and 2-Pyridinones through Nucleophile-Induced Ring Transformation Reactions [1]

Atul Goel*a, Fateh V. Singha, Ashoke Sharonb, Prakas R. Maulikb
a Division of Medicinal and Process Chemistry, Central Drug Research Institute, Lucknow 226001, India
Fax: +91(522)2623405; e-Mail: agoel13@yahoo.com;
b Division of Molecular and Structural Biology, Central Drug Research Institute, Lucknow 226001, India
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Publikationsverlauf

Received 20 October 2004
Publikationsdatum:
22. Februar 2005 (online)

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Abstract

An efficient one-pot synthesis of 2-amino-6-aryl-4-­methylsulfanylpyridines and 6-aryl-3-cyano-4-methylsulfanyl-2(1H)-pyridinone has been illustrated through ring transformation of 6-aryl-3-cyano-4-methylsulfanyl-2H-pyran-2-ones by urea through different reaction conditions. Various solvents and bases were employed to selectively prepare either 2-aminopyridines or 2-pyridinones. In case of direct fusion of 2H-pyran-2-one with urea in solvent-free conditions, both the products were obtained in 1:1 ratio, while the reaction in pyridine at reflux temperature ex­clusively afforded 2-aminopyridine in 80-90% yield. The reaction of 6-aryl-3-carbomethoxy-4-methylsulfanyl-2H-pyran-2-ones with urea at 150 °C afforded 2-pyridinone derivatives in good yield (70-80%).

Key words

2-pyranone - 2-aminopyridine - 2-pyridinone - urea - ring transformation reaction

1

C.D.R.I. Communication No. 6544.

1

C.D.R.I. Communication No. 6544.

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Synthesis of 2-Amino-6-aryl-4-methylsulfanyl-pyridines (2a-h) and 6-Aryl-3-cyano-4-methylsulfanyl-2 (1 H )-pyridinones (3a-h), General Procedure.
A mixture of 6-aryl-3-cyano-4-methylsulfanyl-2H-pyran-2-ones (1, 1 mmol) and urea (2.3 mmol) was fused at 150 °C for 5-15 min. After completion, the reaction was cooled to r.t. and H2O was added (10 mL) to give the crude compound. The pure compounds were isolated on silica gel column, using CHCl3-hexane (1:1) as eluent.

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Spectroscopic and Elemental Analyses Data of Selected Compounds. Compound 2a: yellow solid; mp 136-138 °C. 1H NMR (200 MHz, CDCl3): δ = 2.50 (s, 3 H, SCH3), 4.23 (br s, 2 H, NH2), 6.30 (s, 1 H, PyH), 6.90 (s, 1 H, PyH), 7.41-7.44 (m, 3 H, ArH), 7.87-7.90 (m, 2 H, ArH). IR (KBr): 3430 cm-1 (NH2). MS (FAB): 217 [M+ + 1]. Anal. Calcd for C12H12N2S: C, 66.63; H, 5.59; N, 12.95. Found: C, 66.69; H, 5.61; N, 12.83.
Compound 3a: CCDC No. 238556; white solid; mp >250 °C. 1H NMR (200 MHz, DMSO-d 6): δ = 2.73 (s, 3 H, SCH3), 6.61 (s, 1 H, CH), 7.56-7.59 (m, 3 H, ArH), 7.83-7.87 (m, 2 H, ArH), 12.50 (br s, 1 H, NH). IR (KBr): 1645 (CO), 2214 (CN), 3444 cm-1 (NH). MS (FAB): 243 [M+ + 1]. Anal. Calcd for C13H10N2OS: C, 64.44; H, 4.16; N, 11.56. Found: C, 64.66; H, 4.28; N, 11.62.
Compound 5c: white solid; mp 133-134 °C. 1H NMR (200 MHz, DMSO-d 6): δ = 2.44 (s, 3 H, CH3), 2.56 (s, 3 H, SCH3), 6.12 (s, 1 H, CH), 6.47 (s, 1 H, CH), 7.31 (d, J = 8.0 Hz, 2 H, ArH), 7.62 (d, J = 8.0 Hz, 2 H, ArH), 11.50 (br s, 1 H, NH). IR (KBr): 1628 (CO), 3383 cm-1 (NH). MS (FAB): 232 [M+ + 1]. Anal. Calcd for C13H13NOS: C, 67.50; H, 5.66; N, 6.06. Found: C, 67.62; H, 5.69; N, 6.18.