Synlett 2003(10): 1506-1508
DOI: 10.1055/s-2003-40821
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

A Facile Synthesis of 1,6-Diketones via a Three-Component Michael Addition Reaction

Anil Saikia, Apurba Chetia, Utpal Bora, Romesh C Boruah*
Medicinal Chemistry Division, Regional Research Laboratory, Jorhat, 785006, India
e-Mail: rc_boruah@yahoo.co.in;
Further Information

Publication History

Received 22 April 2003
Publication Date:
24 July 2003 (online)

Abstract

A convenient one-pot synthesis of 1,6-diketones has been accomplished by a three-component Michael addition reaction of α-bromoketone, malononitrile and α,β-unsaturated keto compounds.

    References

  • 1a Bouillon JP. Portella C. Bouquant J. Humbel S. J. Org. Chem.  2000,  65:  5823 
  • 1b Nakane M. Hutchinson CR. J. Org. Chem.  1980,  45:  4233 
  • 1c Hays DS. Fu GC. J. Org. Chem.  1998,  63:  6375 
  • 1d Ong CW. Chen CM. Wang LH. Jan JJ. J. Org. Chem.  1998,  63:  9131 
  • 1e Tormo J. Hays DS. Fu GC. J. Org. Chem.  1998,  63:  201 
  • 1f Kiguchi T. Tajiri K. Ninomiya I. Naito T. Hiramatsu H. Tetrahedron Lett.  1995,  36:  253 
  • 2a Ogawa S. Uchida C. Yuming Y. J. Chem. Soc., Chem. Commun.  1992,  886 
  • 2b Ando O. Nakajima M. Hamano K. Itoi K. Takahashi S. Takamatsu Y. Sato A. Enokita R. Okazaki T. Haruyama H. Kinoshita T. J. Antibiot.  1993,  46:  1116 
  • 2c Kobayashi Y. Miyazaki H. Shiozaki M. J. Org. Chem.  1994,  59:  813 
  • 2d Trost BM. Van Vraken DL. J. Am. Chem. Soc.  1993,  115:  444 
  • 3 Lee JC. Ku CH. Synlett  2002,  1679 
  • 4 Brown HC. Racherla US. Singh SM. Synthesis  1984,  922 
  • 5 Nishinaga A. Rindo K. Matsuura T. Synthesis  1986,  1038 
  • 6 Ryu I. Ando M. Ogawa A. Murai S. Sonoda N. J. Am. Chem. Soc.  1983,  105:  7192 
  • 7 Murayama E. Sato T. Tetrahedron Lett.  1977,  47:  4079 
  • 8a Bergmann ED. Ginsberg D. Pappo R. Organic Reactions   Vol.10:  John Wiley and Sons; New York: 1959.  p.179 
  • 8b Grossman RB. Synlett  2001,  13 
  • 8c Shibasaki M. Sasai H. Arai T. Angew. Chem., Int. Ed. Engl.  1997,  36:  1236 
  • 8d Giardini A. Lesma G. Passarella D. Perez M. Silvani A. Synlett  2001,  132 
  • 8e Mukaiyama T. Tamura M. Kobayashi S. Chem. Lett.  1986,  1017 
  • 8f Ranu BC. Saha M. Bhar S. Tetrahedron Lett.  1993,  34:  1989 
  • 8g Cossy J. Lutz F. Alauze V. Meyer C. Synlett  2002,  45 
  • 9a Weber L. Illegen K. Almstetter M. Synlett  1999,  366 
  • 9b Armstrong RW. Combs AP. Tempest PA. Brown SD. Keating TA. Acc. Chem. Res.  1996,  29:  123 
  • 10 Domling A. Ugi I. Angew. Chem. Int. Ed.  2000,  39:  3168 
  • 11a Shestopalov AM. Emeliyanova YM. Shestopalov AA. Rodinovskaya LA. Niazimbetova ZI. Evans DH. Org. Lett.  2002,  423 
  • 11b List B. Castello C. Synlett  2001,  1687 
  • 11c Nair V. Vinod AU. Rajesh C. J. Org. Chem.  2001,  66:  4427 
  • 11d Bagley MC. Dale JW. Bower J. Chem Commun.  2002,  1682 
  • 11e Kappe CO. Tetrahedron  1993,  49:  6973 
  • 11f Cheng JF. Chen M. Arrhenius T. Nadzen A. Tetrahedron Lett.  2002,  43:  6293 
  • 11g Huma HZS. Halder R. Kalra SS. Das J. Iqbal J. Tetrahedron Lett.  2002,  43:  6485 
  • 11h Bertozzi F. Gustafsson M. Olsson R. Org. Lett.  2002,  4:  3147 
  • 11i Yuan Y. Li X. Ding K. Org. Lett.  2002,  4:  3309 
  • 12a Ahmed S. Boruah RC. Tetrahedron Lett.  1996,  37:  8251 
  • 12b Sharma U. Ahmed S. Boruah RC. Tetrahedron Lett.  2000,  41:  3493 
  • 12c Boruah RC. Ahmed S. Sharma U. Sandhu JS. J. Org. Chem.  2000,  65:  922 
  • 13 Sharma U. Bora U. Boruah RC. Sandhu JS. Tetrahedron Lett.  2002,  43:  143 
  • 14 Bora U. Saikia A. Boruah RC. Org. Lett.  2003,  5:  435 
  • 15 Nevar NM. Kelin AV. Kulinkovich OG. Synthesis  2000,  1259 
16

Typical Procedure for Three-Component Reaction: Preparation of Ethyl-3,3-dicyano-4-( p -toluoyl)valerate (5d): A 100 mL round bottom flask, equipped with a magnetic stirrer, was charged with a mixture of 2-bromo-4′-methylacetophenone 1a (0.5 g, 2.34 mmol), malononitrile (0.17 g, 2.50 mmol) and ethyl acrylate 4d (0.25 g, 2.50 mmol) in MeOH (50 mL). The reaction mixture was cooled to 15 °C and to it was added finely powdered KOH (0.14 g, 2.50 mmol) in small portions at the maximum speed of the magnetic stirrer. The mixture was stirred vigorously at 15-20 °C for 25 min. On completion of reaction (TLC monitored), it was poured into 100 mL H2O and extracted with CH2Cl2 (2 × 30 mL), washed with H2O and dried over Na2SO4(anhyd). Removal of solvent afforded 5d in 78% yield, mp 70 °C (MeOH). IR (KBr): νmax = 2975, 2251, 1733, 1678, 1605, 1453, 1237 cm-1. 1H NMR (CDCl3): δ = 7.60 (2 H, d, J = 8.10 Hz), 7.10 (2 H, d, J = 8.10 Hz), 4.02 (2 H, q, J = 6.8 Hz), 3.55 (2 H, s), 2.50 (4 H, m), 2.20 (3 H, s), 1.20 ( 3H, t, J = 6.8Hz). 13C NMR (CDCl3): δ = 216.7, 182.5, 127.8, 127.3, 125.6, 122.6, 119.6, 118.3, 115.3, 109.7, 59.2, 32.5, 30.2, 28.6, 20.7, 14.6, 13.6. MS (ESI): m/z = 321 (M+ + 23). Anal. Calcd for C17H18N2O3: C, 68.44; H, 6.08; N, 9.39. Found: C, 68.27; H, 6.19; N, 9.31.

17

Preparation of 1,1-Dicyano-3-( p -tolyl)-3-propanone (6): To a 50 mL round bottom flask charged with 2-bromo-4′-methylacetophenone 1a (0.5 g, 2.3 mmol) and malononitrile (0.24 g, 3.6 mmol) in MeOH (20 mL) was added powdered KOH (0.20 g, 3.6 mmol) in small portion and stirred at r.t. TLC monitoring showed completion of reaction after 20 min. The solvent was removed under reduced pressure in a rotavapor and the residue was extracted with chloroform (2 × 15 mL), washed with H2O and dried over anhyd Na2SO4. Removal of solvent gave a crude product which was crystallized from hexane/chloroform (10/90) to obtain 6 in 92% yield, mp 98 °C. IR (KBr): νmax = 2955, 1675, 1605, 1454, 1298 cm-1. 1H NMR (CDCl3): δ = 7.68 (2 H, d, J = 8.0 Hz), 7.18 (2 H, d, J = 8.0 Hz), 4.30 (1 H, t, J = 6.5 Hz), 3.60 (2 H, d, J = 6.5 Hz), 2.40 (3 H, s). MS (ESI): m/z = 221 (M+ + 23). Anal. Calcd for C12H10N2O: C, 72.71; H, 5.08; N, 14.13. Found: C, 72.89; H, 5.02; N, 14.24.

18

Preparation of 3-Benzoyl-2-phenyl-1,1-dicyano-propane (7): To a 50 mL round bottom flask charged with benzylidene acetophenone 4c (0.5 g, 2.4 mmol) and malononitrile (0.24 g, 3.6 mmol) in MeOH (20 mL) was added powdered KOH (0.20 g, 3.6 mmol) in small portions and the mixture stirred at r.t. After 20 min, the solvent was removed under reduced pressure and the residue was extracted with chloroform (2 × 15 mL), washed with H2O, dried over anhyd Na2SO4 and solvent removed. The crude product was crystallized from hexane/chloroform (10/90) to obtain 7 in 88% yield, mp 116 °C. IR (KBr): νmax = 2902, 1682, 1596, 1449, 1235 cm-1. 1H NMR (CDCl3): δ = 7.80-6.95 (10 H, m), 4.50 (1 H, d, J = 6.0 Hz), 3.80 (1 H, m), 3.50 (2 H, d, J = 6.5 Hz). MS (ESI): m/z = 297 (M+ + 23). Anal. Calcd for C18H14N2O: C, 78.81; H, 5.14; N, 10.21. Found: C, 78.96; H, 5.27; N, 10.42.