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

Atul Goel; Fateh V. Singh; Ashoke Sharon; Prakas R. Maulik

doi:10.1055/s-2005-862365

LETTER

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

Atul Goel*^a, Fateh V. Singh^a, Ashoke Sharon^b, Prakas R. Maulik^b
^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

Abstract

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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

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References

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

<A NAME="RG38404ST-2A">2a</A> Smith D. In Comprehensive Organic Chemsitry Vol. 4: Sames PG. Pergamon; Oxford: 1979. p.3

<A NAME="RG38404ST-2B">2b</A> Bailey T. Goe G. Scriven E. In Heterocyclic Compounds Part 5, Vol. 14: Newkome GR. Wiley; New York: 1984. p.215

<A NAME="RG38404ST-2C">2c</A> Fodor GB. Colasanti B. In Alkaloids: Chemical and Biological Perspectives Vol. 3: Pelletier SW. Wiley; New York: 1985. p.1-90

<A NAME="RG38404ST-3A">3a</A> Spivak DA. Shea KJ. Anal. Chim. Acta 1999, 435: 4627

<A NAME="RG38404ST-3B">3b</A> Kròl I. Rospenk M. Sobczyk L. J. Mol. Struct. 2000, 552: 312

<A NAME="RG38404ST-3C">3c</A> Sugeta H. Bull. Chem. Soc. Jpn. 1981, 54: 3706

<A NAME="RG38404ST-4">4</A> Niño A. Muñoz-Caro C. Carbò-Dorca R. Gironés X. Biophys. Chem. 2003, 104: 417

<A NAME="RG38404ST-5">5</A> Sata N. Shibata T. Jitsuoka M. Ohno T. Takahashi T. Hirohashi T. Kanno T. Iwaasa H. Kanatani A. Fukami T. Bioorg. Med. Chem. Lett. 2004, 14: 1761

<A NAME="RG38404ST-6">6</A> Carlsson C. Rosen I. Nilsson E. Acta Anaesthesiol. Scand. 1993, 27: 87

<A NAME="RG38404ST-7A">7a</A> Curran D. Liu H. J. Am. Chem. Soc. 1992, 114: 5863

<A NAME="RG38404ST-7B">7b</A> Schultz A. Chem. Rev. 1973, 73: 385

<A NAME="RG38404ST-7C">7c</A> Kelly T. Bell S. Osashi N. Armstrong-Chong J. J. Am. Chem. Soc. 1988, 110: 6471

<A NAME="RG38404ST-8A">8a</A> Cox R. O’Hagan D. J. Chem. Soc., Perkin Trans. 1 1991, 2537

<A NAME="RG38404ST-8B">8b</A> Rigby J. Balasubramanian N. J. Org. Chem. 1989, 54: 224

<A NAME="RG38404ST-9">9</A> Williams D. Lowder P. Gu Y.-G. Tetrahedron Lett. 1997, 38: 327

<A NAME="RG38404ST-10">10</A> Teshima Y. Shin-ya K. Shimazu A. Furihota K. Chul HS. Furihata K. Hayakawa Y. Nagai K. Seto H. J. Antibiot. 1991, 44: 685

<A NAME="RG38404ST-11">11</A> Matyus P. Kasztreiner E. Diesler E. Behr A. Varga I. Kosary J. Rabloczky G. Jaszlits L. Arch. Pharm. 1994, 327: 543

<A NAME="RG38404ST-12">12</A> Narusevicius E. Garaliene V. Krauze A. Duburs G. Khim. Farm. Zh. 1989, 23: 1459

<A NAME="RG38404ST-13A">13a</A> Tieckelmann H. In Heterocyclic Compounds, Pyridine and its Derivatives Supplement Part 3: Abramovitch RA. Wiley-Intersciences; New York: 1974. p.597

<A NAME="RG38404ST-13B">13b</A> Murray T. Zimmerman S. Tetrahedron Lett. 1995, 36: 7627

<A NAME="RG38404ST-14A">14a</A> Sakurai A. Midorikawa H. Bull. Chem. Soc. Jpn. 1968, 41: 430

<A NAME="RG38404ST-14B">14b</A> Latif N. Girgis NS. Indian J. Chem., Sect. B: Org. Chem. Incl. Med. Chem. 1981, 20: 147

<A NAME="RG38404ST-15A">15a</A> Vorbrüggen H. Adv. Heterocycl. Chem. 1990, 49: 117

<A NAME="RG38404ST-15B">15b</A> Matsumoto K. Minatogawa H. Munakata M. Toda M. Tsukube H. Tetrahedron Lett. 1990, 27: 3923

<A NAME="RG38404ST-15C">15c</A> Matsumoto K. Hashimoto S. Otani S. J. Chem. Soc., Chem. Commun. 1991, 306

<A NAME="RG38404ST-16A">16a</A> McKillop A. Boulton AJ. In Comprehensive Heterocyclic Chemistry Vol. 2: Katritzky AR. Rees CW. Pergamon Press; New York: 1984. p.67

<A NAME="RG38404ST-16B">16b</A> McKillop A. Boulton AJ. In Comprehensive Heterocyclic Chemistry Vol. 2: Katritzky AR. Rees CW. Pergamon Press; New York: 1984. p.460-463

<A NAME="RG38404ST-17">17</A> Farhanullah Agarwal N. Goel A. Ram VJ. J. Org. Chem. 2003, 68: 2983

<A NAME="RG38404ST-18">18</A> Katritzky AR. Belyakov SA. Sorochinsky AE. Henderson SA. Chen J. J. Org. Chem. 1997, 62: 6210

<A NAME="RG38404ST-19A">19a</A> Decker H. Chem. Ber. 1892, 25: 443

<A NAME="RG38404ST-19B">19b</A> Mohrle H. Weber H. Tetrahedron 1970, 26: 2953

<A NAME="RG38404ST-20">20</A> Jones G. In Comprehensive Heterocyclic Chemistry Vol. 2: Katritzky AR. Rees CW. Pergamon Press; New York: 1984. p.395

<A NAME="RG38404ST-21">21</A> Rastogi RR. Kumar A. Ila H. Junjappa H. J. Chem. Soc., Perkin Trans. 1 1978, 549

<A NAME="RG38404ST-22">22</A> Ghosez L. Jnoff E. Bayard P. Sainte F. Beaudegnies R. Tetrahedron 1999, 55: 3387

<A NAME="RG38404ST-23">23</A> Brun EM. Gil S. Mestres R. Parra M. Synthesis 2000, 273

<A NAME="RG38404ST-24">24</A> Takaoka K. Aoyama T. Shioiri T. Tetrahedron Lett. 1996, 37: 4973

<A NAME="RG38404ST-25A">25a</A> Ram VJ. Goel A. Chem. Lett. 1997, 10: 1021

<A NAME="RG38404ST-25B">25b</A> Nath M. Srivastava P. Goel A. Ram VJ. Eur. J. Org. Chem. 1998, 2083

<A NAME="RG38404ST-25C">25c</A> Srivastava P. Saxena AS. Ram VJ. Synthesis 2000, 544

<A NAME="RG38404ST-25D">25d</A> Ram VJ. Srivastava P. Curr. Org. Chem. 2001, 5: 571

<A NAME="RG38404ST-26A">26a</A> Tominaga Y. Ushirogouchi A. Matsuda Y. Kobayashi G. Chem. Pharm. Bull. 1984, 32: 3384

<A NAME="RG38404ST-26B">26b</A> Tominaga Y. Ushirogouchi A. Matsuda Y. J. Heterocycl. Chem. 1987, 24: 1557

<A NAME="RG38404ST-26C">26c</A> Ram VJ. Verma M. Hussaini FA. Shoeb A. J. Chem. Res., Synop. 1991, 98

<A NAME="RG38404ST-26D">26d</A> Ram VJ. Hussaini FA. Singh SK. Shoeb A. J. Chem. Res., Synop. 1993, 110

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.

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.