Microwave-Promoted and Lewis Acid Catalysed Synthesis of 2,4,6-Triarylpyridines Using Urea as Benign Source of Ammonia

Abstract

An efficient method for the synthesis of 2,4,6-triaryl­pyridines via microwave-promoted and BF₃˙OEt₂-catalysed one-pot reaction of ω-pyrrolidinoacetophenone with chalcone is reported. This method illustrates urea as an environmentally benign source of ammonia for the synthesis of 2,4,6-triarylpyridines.

Key words

2,4,6-triarylpyridine - urea - microwave - Lewis acid

References and Notes

• 1a Jetti RKR. Nagia A. Xue F. Mark TCW. Chem. Commun.  2001,  919 
• 1b Constable EC. Housecroft CE. Neuburger M. Phillips D. Raithby PR. Schofield E. Sparr E. Tocher DA. Zehnder M. Zimmermann Y. J. Chem. Soc., Dalton Trans.  2000,  2219 
• 1c Cave GWV. Hardie MJ. Roberts BA. Raston CL. Eur. J. Org. Chem.  2001,  3227 
• 2a Enyedy IJ. Sakamuri S. Zaman WA. Johnson KM. Wang S. Bioorg. Med. Chem. Lett.  2003,  13:  513 
• 2b Kim BY. Ahn JB. Lee HW. Kang SK. Lee JH. Shin JS. Ahn SK. Hong CI. Yoon SS. Eur. J. Med. Chem.  2004,  39:  433 
• 2c Pillai AD. Rathod PD. Franklin PX. Patel M. Nivsarkar M. Vasu KK. Padh H. Sudarsanam V. Biochem. Biophys. Res. Commun.  2003,  301:  183 
• 3a Katritzky AR. Adamson J. Elisseou EM. Musumarra G. Patel RC. Sakizadeh K. Yeung WK.
  J. Chem. Soc., Perkin Trans. 2  1982,  1041 
• 3b Katritzky AR. Tetrahedron  1980,  36:  679 
• 4 Marquat J. Moreno-Manas M. Pacheco P. Prat M. Katritzky AR. Brycki B. Tetrahedron  1990,  46:  5333 
• 5 Abramovitch RA. Beckert JM. Chinnasamy P. Xiaohua H. Pennington W. Sanjivamurthy ARV. Heterocycles  1989,  28:  623 
• 6 Katritzky AR. Aurrecoechea JM. Quian KK. Anna E. Palenik GJ. Heterocycles  1987,  25:  387 
• 7 Kendurkar PS. Tewari RS. Z. Naturforsch., B  1974,  29:  552 
• 8 Leonard KA. Nelen MI. Simard TP. Davies SR. Gollnick SO. Oseroff AR. Gibson SL. Hilf R. Chen LB. Detty MR. J. Med. Chem.  1999,  42:  3953 
• 9a Krohnke F. Zecher W. Angew. Chem., Int. Ed. Engl.  1962,  1:  626 
• 9b Krohhnke F. Synthesis  1976,  1 
• 9c Newkome GR. Hager DC. Kiefer GE. J. Org. Chem.  1985,  51:  850 
• 10a Tewari RS. Dubey AK. Indian J. Chem., Sect. B  1980,  19:  153 
• 10b Tewari RS. Dubey AK. J. Chem. Eng. Data  1980,  25:  91 
• 11a Verma AK. Koul S. Pannu APS. Razdan TK. Tetrahedron  2007,  63:  8715 
• 11b Kumar A. Koul S. Razdan TK. Kapoor KK. Tetrahedron Lett.  2006,  47:  837 
• 12 Tu S. Li T. Shi F. Fang F. Zhu S. Wei X. Zong Z. Chem. Lett.  2005,  34:  732 
• 13 Cave GWV. Raston CL. Chem. Commun.  2000,  2199 
• 14 Abid M. Tahermansouri H. Koloongani SA. Mohmaddi B. Bijanzadeh HR. Tetrahedron Lett.  1996,  37:  5957 
• 15 Katritzky AR. Abdel-Fattah AAA. Tymoshenko DO. Synthesis  1999,  2114 
• 16 Kobayashi T. Kakuichi H. Kato H. Bull. Chem. Soc. Jpn.  1991,  64:  392 
• 17 Huang XQ. Li HX. Wang JX. Jia XF. Chin. Chem. Lett.  2005,  16:  607 
• 18 Palacios F. de Retana AMO. Oyarzabal J. Tetrahedron Lett.  1996,  37:  4577 
• 19a Varma RS. In Microwaves: Theory and Application in Material Processing IV   Clark DE. Sutton WH. Lewis DA. American Ceramic Society; Westerville OH: 1997.  p.357-365  
• 19b Varma RS. Dahiya R. Tetrahedron  1998,  54:  6293 
• 19c Varma RS. Meshram HM. Tetrahedron Lett.  1997,  38:  7973 
• 20a Kabalka GW. Wang L. Pagni RM. Synlett  2001,  676 
• 20b Ranu BC. Hajra A. Jana U. Tetrahedron Lett.  2000,  41:  531 
• 20c Bose AK. Manhas MS. Ganguly SN. Sharma AH. Banik BK. Synthesis  2002,  1578 
• 21a Groebke K. Weber L. Mehlin F. Synlett  1998,  661 
• 21b Quiroga J. Cisneros C. Insuasty B. Abonia R. Nogueras M. Sanchez A. Tetrahedron Lett.  2001,  42:  5625 
• 21c Varma RS. Kumar D. Tetrahedron Lett.  1999,  40:  7665 
• 21d Ranu BC. Hajra A. Tetrahedron  2001,  57:  4767 
• 21e Balalaie S. Arabanian A. Green Chem.  2000,  2:  274 
• 22a Barthakur MG. Borthakur M. Devi P. Saikia CJ. Saikia A. Bora U. Chetia A. Boruah RC. Synlett  2007,  223 
• 22b Borthakur M. Boruah RC. Steroids  2008,  73:  637 
• 23a Chetia A. Saikia CJ. Lekhok KC. Boruah RC. Tetrahedron Lett.  2004,  45:  2649 
• 23b Boruah RC. Ahmed S. Sharma U. Sandhu JS. J. Org. Chem.  2000,  65:  922 
• 23c Sharma U. Ahmed S. Boruah RC. Tetrahedron Lett.  2000,  41:  3493 
• 23d Ahmed S. Boruah RC. Tetrahedron Lett.  1996,  37:  8231 

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Microwave experiments were conducted in open reaction vessels of a Synthwave 402 reactor manufactured by M/s Prolabo, 54 rue Roger Salengro, Cedex, France. The temperature of the reaction mixture was set at 140 ˚C and measured by a computer controlled sensor using 80% power (maximum output 300 Watts) with an operating frequency of 2.45 GHz. The reaction time specified is the total irradiation time. The hold time at final temperature is 25% of the total time.

25

Spectral and Analytical Data of Selected Compounds:
Compound B: mp 97-99 ˚C; R _f = 0.7 (EtOAc-hexane, 10:90). IR (KBr): 3059, 3028, 2922, 1686, 1653, 1606, 1448, 1217, 1180, 1010, 755 cm^-¹. ^¹H NMR (300 MHz, CDCl₃): δ = 8.01 (d, 2 H, J = 7.4 Hz), 7.92 (d, 2 H, J = 7.4 Hz), 7.88 (d, 2 H, J = 8.0 Hz), 7.18-7.54 (m, 6 H), 5.25 (s, 1 H), 4.84 (s, 2 H), 2.40 (s, 3 H). ^¹³C NMR (75 MHz, CDCl₃): δ = 196.0, 190.5, 152.7, 152.0, 143.3, 141.7, 136.9, 136.2, 134.2, 132.9, 132.4, 129.1, 129.0, 128.5 (2 × C), 128.4, 128.3, 128.2, 128.2, 128.0, 126.5, 123.3, 42.7, 21.4. MS (ESI): m/z = 341 [M⁺ + 1].
Compound 3a: mp 135-36 ˚C; R _f = 0.8 (EtOAc-hexane, 10:90). IR (KBr): 3035, 2924, 1595, 1550, 1495, 1449, 1180, 756 cm^-¹. ^¹H NMR (300 MHz, CDCl₃): δ = 8.21 (m, 4 H), 7.89 (s, 2 H), 7.75 (d, 2 H, J = 7.0), 7.03-7.53 (m, 9 H). ^¹³C NMR (75 MHz, CDCl₃): δ = 157.2 (2 × C), 149.9, 139.3 (2 × C), 138.8, 128.9 (2 × C), 128.8, 128.7 (3 × C), 128.4 (3 × C), 126.9 (3 × C), 126.9 (3 × C), 116.9 (2 × C). MS (ESI): m/z = 308 [M⁺ + 1].
Compound 3k: mp 152-54 ˚C; R _f = 0.8 (EtOAc-hexane, 10:90). IR (KBr): 3056, 2922, 1596, 1544, 1492, 1184 cm^-¹. ^¹H NMR (300 MHz, CDCl₃): δ = 7.32-8.14 (m, 13 H), 7.82 (s, 2 H), 2.42 (s, 3 H). ^¹³C NMR (75 MHz, CDCl₃): δ = 157.3, 157.1, 155.8, 150.0, 149.7, 138.9, 138.7, 137.8, 136.6, 136.3, 134.8, 129.2, 129.1, 128.9, 128.8, 128.6, 128.1, 126.9, 126.7 (2 × C), 125.6, 116.8, 116.3, 21.1. MS (ESI): m/z = 356 [M⁺ + 1].
Compound 3n: mp 133-35 ˚C; R _f = 0.7 (EtOAc-hexane, 10:90). IR (KBr): 3034, 2924, 1597, 1546, 1496, 1417, 1185 cm^-¹. ^¹H NMR (300 MHz, CDCl₃): δ = 8.20 (m, 4 H), 7.87 (s, 2 H), 7.64 (d, 2 H, J = 5.8 Hz), 7.14-7.51 (m, 7 H), 2.42 (s, 3 H), 1.34 (s, 3 H). ^¹³C NMR (75 MHz, CDCl₃): δ = 157.2 (2 × C), 139.4 (2 × C), 129.6 (3 × C), 128.7 (3 × C), 128.4 (3 × C), 126.9 (4 × C), 126.7 (4 × C), 116.6 (2 × C), 29.5, 21.0. MS (ESI): m/z = 336 [M⁺ + 1].