Download PDF
Synlett 2014; 25(3): 389-392
DOI: 10.1055/s-0033-1340345
letter
© Georg Thieme Verlag Stuttgart · New York

A Convenient Approach to the Synthesis of Novel Substituted Cyclohexadienes by the Vinylogous Michael Addition of α,α-Dicyanoolefins

Abdolali Alizadeh*
Department of Chemistry, Tarbiat Modares University, P.O. Box 14115-175, Tehran, Iran   Fax: +98(21)88006544   Email: aalizadeh@modares.ac.ir   Email: abdol_alizad@yahoo.com
,
Hadi Sedighian
Department of Chemistry, Tarbiat Modares University, P.O. Box 14115-175, Tehran, Iran   Fax: +98(21)88006544   Email: aalizadeh@modares.ac.ir   Email: abdol_alizad@yahoo.com
,
Fahimeh Bayat
Department of Chemistry, Tarbiat Modares University, P.O. Box 14115-175, Tehran, Iran   Fax: +98(21)88006544   Email: aalizadeh@modares.ac.ir   Email: abdol_alizad@yahoo.com
› Author Affiliations
Further Information

Publication History

Received: 18 October 2013

Accepted after revision: 09 November 2013

Publication Date:
16 December 2013 (online)

    Permissions and Reprints All articles of this category


Abstract

A concise and efficient approach to substituted cyclohexadienes has been developed. The method involves vinylogous addition of α,α-dicyanoolefins to Michael adduct intermediates, formed from malononitrile and dialkyl acetylenedicarboxylates, in the presence of triethylamine in ethanol. The method has the advantages of good yields and simple operations, and of not requiring a metal catalyst or an inert atmosphere.

Key words

alkenes - nitriles - alkynes - Michael additions - cyclization - cyclohexadienes - addition
 

  • References

    • 1a Dalko PI, Moisan L. Angew. Chem. Int. Ed. 2004; 43: 5138
      CrossrefPubMed
    • 1b Krause N, Hoffmann-Röder A. Synthesis 2001; 171
    • 1c Seayad J, List B. Org. Biomol. Chem. 2005; 3: 719
      CrossrefPubMed
    • 1d Sibi MP, Manyem S. Tetrahedron 2000; 56: 8033
      Crossref
    • 2a Zanardi F, Rassu G, Battistini L, Curti C, Sartori A, Casiraghi G. In: Targets in Heterocyclic Systems: Chemistry and Properties . Vol. 16. Attanasi OA, Spinelli D. Societa Chimica Italiana; Rome: 2012: 56
      Google Scholar
    • 2b Casiraghi G, Battistini L, Curti C, Rassu G, Zanardi F. Chem. Rev. 2011; 111: 3076
      Crossref
  • 3 Manna MS, Mukherjee S. Chem. Eur. J. 2012; 18: 15277
    CrossrefPubMed
  • 4 Xue D, Li J, Zhang ZT, Deng JG. J. Org. Chem. 2007; 72: 5443
    CrossrefPubMed
  • 5 Babu TH, Karthik K, Perumal PT. Synlett 2010; 1128
    Article in Thieme Connect
  • 6 Elinson MN, Ilovaisky AI, Merkulova VM, Barba F, Batanero B. Tetrahedron 2013; 69: 7125
    Crossref
  • 7 Xue D, Chen Y.-C, Cui X, Wang Q.-W, Zhu J, Deng J.-G. J. Org. Chem. 2005; 70: 3584
    CrossrefPubMed
    • 8a Bell M, Frisch K, Jørgensen KA. J. Org. Chem. 2006; 71: 5407
      CrossrefPubMed
    • 8b Xie J.-W, Yue L, Xue D, Ma X.-L, Chen Y.-C, Wu Y, Zhu J, Deng J.-G. Chem. Commun. 2006; 1563
    • 9a Chen Y.-C, Xue D, Deng J.-G, Cui X, Zhu J, Jiang Y.-Z. Tetrahedron Lett. 2004; 45: 1555
      Crossref
    • 9b Hansch C, Leo A, Taft RW. Chem. Rev. 1991; 91: 165
  • 10 Lu J, Liu F, Zhou W.-J, Loh T.-P. Tetrahedron Lett. 2008; 49: 5389
    Crossref
    • 11a Xie J.-W, Chen W, Li R, Zeng M, Du W, Yue L, Chen Y.-C, Wu Y, Zhu J, Deng J.-G. Angew. Chem. Int. Ed. 2007; 46: 389
      Crossref
    • 11b Kang T.-R, Xie J.-W, Du W, Feng X, Chen Y.-C. Org. Biomol. Chem. 2008; 6: 2673
      Crossref
    • 12a Su W, Ding K, Chen Z. Tetrahedron Lett. 2009; 50: 636
      Crossref
    • 12b Xue D, Chen Y.-C, Wang Q.-W, Cun L.-F, Zhu J, Deng J.-G. Org. Lett. 2005; 7: 5293
      CrossrefPubMed
  • 13 Babu TH, Joseph AA, Muralidharan D, Perumal PT. Tetrahedron Lett. 2010; 51: 994
    Crossref
  • 14 Poulsen TB, Alemparte C, Jørgensen KA. J. Am. Chem. Soc. 2005; 127: 11614
    CrossrefPubMed
  • 15 Esmaeili AA, Moradi A, Khoddam Mohammadi H. Tetrahedron 2010; 66: 3575
    Crossref
  • 16 Attanasi OA, Favi G, Geronikaki A, Mantellini F, Moscatelli G, Paparisva A. Org. Lett. 2013; 15: 2624
    Crossref
    • 17a Peters L, König GM, Wright AD, Pukall R, Stackebrandt E, Eberl L, Reidel K. Appl. Environ. Microbiol. 2003; 69: 3469
      Crossref
    • 17b Peters L, Wright AD, Kehraus S, Gündisch D, Tilotta MC, König GM. Planta Med. 2004; 70: 883
      Article in Thieme Connect
    • 17c Peters L, Wright AD, Krick A, König GM. J. Chem. Ecol. 2004; 30: 1165
      Crossref
  • 18 Gein VL, Gein NV, Voronina ÉV, Kriven’ko AP. Pharm. Chem. J. (Engl. Transl.) 2002; 36: 131
    Crossref
  • 19 Watanabe CM. H, Bench BJ. US 2007232813, 2007 ; Chem. Abstr. 2007, 147, 427217
  • 20 Urbahns K, Mauler F. DE 19612645, 1997 ; Chem. Abstr. 1997, 127, 307213
    • 21a Bench BJ, Liu C, Evett CR, Watanabe CM. H. J. Org. Chem. 2006; 71: 9458
      CrossrefPubMed
    • 21b Bench BJ, Tichy SE, Perez LM, Benson J, Watanabe CM. H. Bioorg. Med. Chem. 2008; 16: 7573
      Crossref
    • 22a Fishkin N, Pescitelli G, Sparrow JR, Nakanishi K, Berova N. Chirality 2004; 16: 637
      Crossref
    • 22b Fishkin N, Sparrow JR, Allikmets R, Nakanishi K. Proc. Natl. Acad. Sci. U. S. A. 2005; 102: 7091
      Crossref
    • 23a Chou C.-M, Chatterjee I, Studer A. Angew. Chem. Int. Ed. 2011; 50: 8614
      Crossref
    • 23b Barykina OV, Rossi KL, Rybak MJ, Snider BB. Org. Lett. 2009; 11: 5334
      Crossref
  • 24 Dialkyl 5-Amino-4,6,6-tricyano-1-(2-methoxy-2-oxoethyl)cyclohexa-2,4-diene-1-carboxylates (3); General Procedure A mixture of malononitrile (1.0 mmol), dialkyl acetylenedicarboxylate 2 (1.0 mmol), and Et3N (one drop) in EtOH (5 mL) was stirred at r.t. for 20 min. A solution of α,α-dicyanoolefin 1 (1.0 mmol) and Et3N (1 mmol) in EtOH (3 mL) was then added. When the reaction was complete, the solvent was removed under reduced pressure and the residue was purified by column chromatography [silica gel, hexane/EtOAc, (1:8)]. Methyl 5-Amino-4,6,6-tricyano-1-(2-methoxy-2-oxoethyl)-3-phenylcyclohexa-2,4-diene-1-carboxylate (3a) Green powder; yield: 0.27 g (72%); mp = 273–275 °C. IR (KBr): 3448, 3361 (NH2), 2219 (CN), 1726 (CO2Me), 1633 (C=C), 1570, 1504 (Ar), 1256 cm–1 (C–O). 1H NMR (400.1 MHz, DMSO-d 6): δ = 2.71 (AB system, 2 J HH = 15.6 Hz, 2 H, CH 2CO2Me), 3.30 (s, 3 H, OCH3), 3.45 (s, 3 H, OCH3), 6.52 (s, 1 H, CH), 7.18 (s, 2 H, NH2), 7.47–7.49 (m, 2 H, 2 × CH ortho of Ph), 7.53–7.54 (m, 1 H, CH para of Ph), 7.47–7.70 (d, 3 J HH = 6.2 Hz, 2 H, 2 × CH meta of Ph). 13C NMR (100.62 MHz, DMSO-d 6): δ = 35.23 (CH2), 46.08 [C(CN)2], 50.31 (OCH3), 53.14 (OCH3), 58.00 (CCN), 72.11 (C–CO2Me), 114.58 (CN), 114.72 (CN), 115.34 (CN), 118.30 (CH), 128.24 (CH para of Ph), 128.43 (2 × CH meta of Ph), 128.81 (2 × CH ortho of Ph), 133.26 (C ipso ), 154.15 (C–Ph), 169.52 (CH2 CO2Me), 172.41 (C–NH2), 180.50 (CO2Me). MS (EI, 70 eV): m/z = 376 [M+], 344, 310, 303, 291, 279, 263, 247, 219, 192, 163, 140, 128, 113, 100, 87, 77, 63, 51. Anal. Calcd for C20H16N4O4: C, 63.83; H, 4.28; N, 14.89. Found: C, 63.75; H, 4.21; N, 14.84. Methyl 5-Amino-4,6,6-tricyano-1-(2-methoxy-2-oxoethyl)-3-(4-tolyl)cyclohexa-2,4-diene-1-carboxylate (3b) Yellow powder; yield: 0.26 g (66%); mp = 295–298 °C. IR (KBr): 3443, 3323 (NH2), 2220 (CN), 1732 (CO2Me), 1635 (C=C), 1573, 1511 (Ar), 1258 cm–1 (C–O). 1H NMR (400.1 MHz, DMSO-d 6): δ = 2.38 (s, 3 H, CH3), 2.68 (AB system, 2 J HH = 15.6 Hz, 2 H, CH 2CO2Me), 3.30 (s, 3 H, OCH3), 3.44 (s, 3 H, OCH3), 6.53, (s, 1 H, CH), 7.11 (s, 2 H, NH2), 7.35 (d, 3 J HH = 8.0 Hz, 2 H, 2 × CH of Ar), 7.61 (d, 3 J HH = 8.4 Hz, 2 H, 2 × CH of Ar). 13C NMR (100.62 MHz, DMSO-d 6): δ = 21.00 (CH3), 36.30 (CH2), 43.56 [C(CN)2], 48.70 (OCH3), 50.29 (OCH3), 58.83 (CCN), 72.00 (C–CO2Me), 112.59 (2 × CN), 114.79 (CN), 120.14 (CH), 128.16 (2 × CH of Ar), 130.10 (2 × CH of Ar), 130.31 (Cipso –CH3), 133.10 (C ipso ), 155.89 (C–Ph), 169.59 (CH2 CO2Me), 172.73 (C–NH2), 180.78 (CO2Me). MS (EI, 70 eV): m/z = 390 [M+], 360, 330, 291, 260, 232, 217, 205, 190, 178, 151, 140, 115, 102, 91. Anal. Calcd for C21H18N4O4: C, 64.61; H, 4.65; N, 14.35. Found: C, 64.55; H, 4.73; N, 14.40. Ethyl 5-Amino-4,6,6-tricyano-1-(2-ethoxy-2-oxoethyl)-3-phenylcyclohexa-2,4-diene-1-carboxylate (3c) Yellow powder; yield: 0.24 g (58%); mp = >300 °C. IR (KBr): 3456, 3372 (NH2), 2359, 2224 (CN), 1734 (CO2Et), 1639 (C=C), 1575, 1515 (Ar), 1265 cm–1 (C–O). 1H NMR (400.1 MHz, DMSO-d 6): δ = 1.02 (t, 3 J HH = 7.2 Hz, 3 H, OCH2CH 3), 1.03 (, t, 3 J HH = 7.2 Hz, 3 H, OCH2CH 3), 2.67 (2 H, AB system, 2 J HH = 16.0 Hz, CH 2CO2Et), 3.62–3.71 (m, 2 H, OCH 2CH3), 3.85–3.96 (m, 2 H, OCH 2CH3), 6.48 (s, 1 H, CH), 7.15 (s, 2 H, NH2), 7.47–7.50 (m, 2 H, 2 × CH meta of Ph), 7.53–7.55 (m, 1 H, CH para of Ph), 7.70 (d, 3 J HH = 6.4 Hz, 2 H, 2 × CH ortho of Ph). 13C NMR (100.62 MHz, DMSO-d 6): δ = 10.35 (OCH2 CH3), 14.36 (OCH2 CH3), 36.83 (CH2), 44.01 [C(CN)2], 58.71 (CCN), 62.19 (OCH2CH3), 58.80 (OCH2CH3), 70.24 (C–CO2Et), 112.60 (2 × CN), 114.8 (CN), 123.91 (CH), 128.17 (2 × CH meta of Ph), 130.08 (2 × CH ortho of Ph), 130.34 (CH para of Ph), 133.28 (C ipso ), 156.09 (C–Ph), 164.53 (CH2 CO2 Et), 169.54 (C–NH2), 180.7 (CO2Et). MS (EI, 70 eV): m/z = 404 [M+], 347, 319, 291, 256, 243, 217, 205, 194, 173, 159, 145, 129, 117, 103, 91, 71, 59. Anal. Calcd for C22H20N4O4: C, 65.34; H, 4.98; N, 13.85. Found: C, 65.42; H, 4.90; N, 13.91. Ethyl 5-Amino-4,6,6-tricyano-1-(2-ethoxy-2-oxoethyl)-3-(4-tolyl)cyclohexa-2,4-diene-1-carboxylate (3d) Yellow powder; yield: 0.30 g (70%); mp = >300 °C. IR (KBr): 3462, 3364, (NH2), 2213 (CN), 1729 (CO2Et), 1630 (C=C), 1553, 1540 (Ar), 1227 and 1150 cm–1 (C–O). 1H NMR (400.1 MHz, DMSO-d 6): δ = 1.01 (t, 3 J HH = 7.2 Hz, 3 H, OCH2CH 3), 1.03 (t, 3 J HH = 7.2 Hz, 3 H, OCH2CH 3), 2.38 (s, 3 H, CH3), 2.65 (AB system, 2 J HH = 15.6 Hz, 2 H, CH 2COOCH2CH3), 3.61–3.70 (m, 2 H, OCH 2CH3), 3.81–3.98 (m, 2 H, OCH 2CH3), 6.42 (s, 1 H, CH), 7.10 (s, 2 H, NH2), 7.35 (d, 3 J HH = 8.00 Hz, 2 H, 2 × CH of Ar), 7.61 (d, 3 J HH = 8.00 Hz, 2 H, 2 × CH of Ar). 13C NMR (100.62 MHz, DMSO-d 6): δ = 11.42 (OCH2CH 3), 14.36 (OCH2CH 3), 21.01 (CH3), 36.75 (CH2), 44.01 [C(CN)2], 57.91 (CCN), 58.71 (OCH 2CH3), 61.77 (OCH 2CH3), 72.44 (C–CO2Et), 112.60 (2 × CN), 114.80 (CN), 123.91 (CH), 128.17 (2 × CH of Ar), 130.08 (2 × CH of Ar), 130.90 (Cipso–CH3), 133.42 (C ipso ), 155.78 (C–Ph), 164.57 (CH2 CO2Et), 171.90 (C–NH2), 179.95 (CO2Et). MS (EI, 70 eV): m/z = 418 [M+], 405, 345, 319, 305, 291, 259, 205, 173, 159, 144, 129, 103, 91, 71, 59. Anal. Calcd for C23H22N4O4: C, 66.02; H, 5.30; N, 13.39. Found: C, 65.98; H, 5.36; N, 13.31. Methyl 3-Amino-2,2,4-tricyano-1-(2-methoxy-2-oxoethyl)-1,2,9,10-tetrahydrophenanthrene-1-carboxylate (3e) Green powder; yield: 0.30 g (75%); mp = 293 °C (dec.). IR (KBr): 3445 (NH2), 2939 (CH), 2359, 2226 (CN), 1721 (CO2Me), 1655 (C=C), 1570, 1450 (Ar), 1196 (C–O) cm–1. 1H NMR (400.1 MHz, DMSO-d 6): δ = 2.15–2.18 (m, 2 H, CH2), 2.24–2.27 (m, 2 H, CH2), 2.71 (AB system, 2 J HH = 15.6 Hz, 2 H, CH 2CO2Me, 3.58 (s, 3 H, OCH3), 3.90 (s, 3 H, OCH3), 7.16 (s, 2 H, NH2), 7.44 (t, 3 J HH = 7.2 Hz, 1 H, CH of Ar), 7.55 (t, 3 J HH = 7.2 Hz, 1 H, CH of Ar), 7.72 (d, 3 J HH = 7.6 Hz, 1 H, CH of Ar), 7.89 (d, 3 J HH = 7.6 Hz, 1 H, CH of Ar). 13C NMR (100.62 MHz, DMSO-d 6): δ = 23.79 (CH2), 24.42 (CH2), 40.57 (CH2), 41.59 [C(CN)2], 51.00 (OCH3), 54.90 (OCH3), 55.89 (CCN), 75.47 (C–CO2Me), 113.24 (CN), 113.78 (CN), 114.09 (CN), 126.47 (CH of Ar), 126.58 (C=C–CH2), 128.17 (CH of Ar), 129.75 (CH of Ar), 133.69 (CH of Ar), 133.77 (C ipso ), 139.54 (C ipso ), 139.73 (C=C–CH2), 173.58 (CH2 CO2Me), 174.46 (C–NH2), 181.55 (CO2Me). MS (EI, 70 eV): m/z = 402 [M+], 386, 368, 321, 209, 193, 178, 166, 151, 139, 128, 115, 102, 83, 69, 57. Anal. Calcd for C22H18N4O4: C, 65.67; H, 4.51; N, 13.92. Found: C, 65.73; H, 4.44; N, 13.84. Ethyl 3-Amino-2,2,4-tricyano-1-(2-ethoxy-2-oxoethyl)-1,2,9,10-tetrahydrophenanthrene-1-carboxylate (3f) Yellow powder; yield: 0.27 g (63%); mp = >300 °C. IR (KBr): 3450, 3368 (NH2,), 2925 (CH), 2220 (CN), 1732 (CO2Et), 1636 (C=C), 1573, 1513 (Ar), 1263 (C–O) cm–1. 1H NMR (400.1 MHz, DMSO-d 6): δ = 1.18 (t, 3 J HH = 7.2 Hz, 3 H, OCH2CH 3), 1.40 (t, 3 J HH = 7.2 Hz, 3 H, OCH2CH 3), 2.10–2.18 (m, 2 H, CH2), 2.20–2.28 (m, 2 H, CH2), 2.67 (AB system, 2 J HH = 15.6 Hz, 2 H, CH 2CO2Et), 4.00–4.10 (m, 2 H, OCH 2CH3), 4.28–4.41 (m, 2 H, OCH 2CH3), 7.16 (s, 2 H, NH2), 7.45 (t, 3 J HH = 7.2 Hz, 1 H, CH6 of Ar), 7.54 (t, 3 J HH = 7.2 Hz, 1 H, CH7 of Ar), 7.68 (d, 3 J HH = 7.6 Hz, 1 H, CH8 of Ar), 7.59 (d, 3 J HH = 7.6 Hz, 1 H, CH5 of Ar). 13C NMR (100.62 MHz, DMSO-d 6): δ = 10.34 (OCH2 CH3), 14.38 (OCH2 CH3), 23.78 (CH2), 24.41 (CH2), 40.73 (CH2), 41.59 [C(CN)2], 55.77 (CCN), 58.79 (OCH2CH3), 62.17 (OCH2CH3), 75.46 (C–CO2Et), 113.54 (CN), 113.78 (CN), 114.07 (CN), 126.47 (CH of Ar), 126.58 (C=C–CH2), 128.16 (CH of Ar), 129.74 (CH of Ar), 133.69 (CH of Ar), 133.77 (C ipso ), 139.53 (C ipso ), 139.76 (C=C–CH2), 173.47 (CH2 CO2Et), 177.16 (C–NH2), 182.60 (CO2Et). MS (EI, 70 eV): m/z = 386, 362, 321, 209, 193, 178, 166, 151, 139, 128, 115, 102, 89, 77, 63, 51. Anal. Calcd for C24H22N4O4: C, 66.97; H, 5.15; N, 13.02. Found: C, 66.91; H, 5.10; N, 13.09.
  • 25 Kazemi B, Javanshir S, Maleki A, Safari M, Khavasi HR. Tetrahedron Lett. 2012; 53: 6977
    Crossref