Ethyl Vinyl Ether as a Synthetic Equivalent of Acetylene in a DABCO-Catalyzed Microwave-Assisted Diels-Alder-Elimination Reaction Sequence Starting from 2H-Pyran-2-ones

Abstract

We present a study of the Diels-Alder reaction between various electron-deficient 2H-pyran-2-ones and ethyl vinyl ether. This microwave-accelerated sequence of a cycloaddition followed by a retro-Diels-Alder reaction (the elimination of CO₂) and a second elimination step of EtOH yields substituted aniline derivatives. The reaction sequence is greatly accelerated by the application of DABCO as a suitable base.

Key words

Diels-Alder reactions - arenes - catalysis with bases - anilines - microwave reactions

References and Notes

• 1 Vijaya R. Dinadayalane TC. Sastry GN. J. Mol. Struct. (Theochem)  2002,  589-590:  291 
• 2a Boyall D. López F. Sasaki H. Frantz D. Carreira EM. Org. Lett.  2000,  2:  4233 
• 2b Paquette LA. Moerck RE. Harirchian B. Magnus PD. J. Am. Chem. Soc.  1978,  100:  1597 
• 2c Jackson PM. Moody CJ. Tetrahedron  1992,  48:  7447 
• 2d Lin YS. Chang SY. Yang MS. Rao CP. Peddinti RK. Tsai YF. Liao CC. J. Org. Chem.  2004,  69:  447 
• 2e Moïse J. Goumont R. Magnier E. Wakselman C. Synthesis  2004,  2297 
• 2f Pearson WH. Lee IY. Mi Y. Stoy P. J. Org. Chem.  2004,  69:  9109 
• 2g Davis AP. Whitham GH. J. Chem. Soc., Chem. Commun.  1980,  639 
• 2h Williams RV. Chauhan K. Gadgil VR. J. Chem. Soc., Chem. Commun.  1994,  1739 
• 3a Afarinkia K. Vinader V. Nelson TD. Posner GH. Tetrahedron  1992,  48:  9111 
• 3b Woodard BT. Posner GH. In Advances in Cycloaddition   Vol. 5:  Harmata M. JAI Press; Greenwich: 1999.  p.47-83  
• 3c Tolmachova NA. Gerus II. Vdovenko SI. Essers M. Fröhlich R. Haufe G. Eur. J. Org. Chem.  2006,  4704 
• 4a Kranjc K. Leban I. Polanc S. Kočevar M. Heterocycles  2002,  58:  183 
• 4b Kranjc K. Kočevar M. New J. Chem.  2005,  29:  1027 
• 4c Kranjc K. Kočevar M. Iosif F. Coman SM. Parvulescu VI. Genin E. Genêt J.-P. Michelet V. Synlett  2006,  1075 
• 4d Kranjc K. Kočevar M. Bull. Chem. Soc. Jpn.  2007,  80:  2001 
• 4e Kranjc K. Kočevar M. Tetrahedron  2008,  64:  45 
• 5a Jung ME. Hagenah JA. J. Org. Chem.  1987,  52:  1889 
• 5b Jung ME. Hagenah JA. Heterocycles  1987,  25:  117 
• 5c Balázs L. Kádas I. Tõke L. Tetrahedron Lett.  2000,  41:  7583 
• 5d Sauer J. Mielert A. Lang D. Peter D. Chem. Ber.  1965,  98:  1435 
• 5e Hamasaki A. Ducray R. Boger DL. J. Org. Chem.  2006,  71:  185 
• 6a Microwaves in Organic Synthesis   Loupy A. Wiley-VCH; Weinheim: 2002. 
• 6b Hayes BL. Microwave Synthesis: Chemistry at the Speed of Light   CEM Publishing; Matthews NC: 2002. 
• 6c Lidström P. Tierney J. Wathey B. Westman J. Tetrahedron  2001,  57:  9225 
• 6d Polshettiwar V. Varma RS. Acc. Chem. Res.  2008,  41:  629 
• 6e Kappe CO. Angew. Chem. Int. Ed.  2004,  43:  6250 
• 6f de la Hoz A. Díaz-Ortiz A. Moreno A. Chem. Soc. Rev.  2005,  34:  164 
• For the synthesis of starting compounds 1, see:
• 7a Kepe V. Kočevar M. Polanc S. Verček B. Tišler M. Tetrahedron  1990,  46:  2081 
• 7b Vraničar L. Polanc S. Kočevar M. Tetrahedron  1999,  55:  271 
• 7c Po˛gan F. Krejan M. Polanc S. Kočevar M. Heterocycles  2006,  69:  123 
• 7d Kepe V. Kočevar M. Petrič A. Polanc S. Verček B. Heterocycles  1992,  33:  843 
• 7e Kepe V. Kočevar M. Polanc S. J. Heterocycl. Chem.  1996,  33:  1707 
• 7f Po˛gan F. Kranjc K. Kepe V. Polanc S. Kočevar M. Arkivoc  2007,  (viii):  97 
• 8 Baidya M. Kobayashi S. Brotzel F. Schmidhammer U. Riedle E. Mayr H. Angew. Chem. Int. Ed.  2007,  46:  6176 
• 9 Hren J. Kranjc K. Polanc S. Kočevar M. Heterocycles  2007,  72:  399 
• 11 Thomsen AD. Lund H. Acta Chem. Scand.  1969,  23:  2930 
• 12 Desai G. Desai KK. Desai CM. J. Indian Chem. Soc.  1987,  64:  370 

10

General Procedure
A mixture of the starting 2H-pyran-2-one 1 (1 mmol), ethyl vinyl ether (2, 721.1 mg, 10 mmol), and DABCO (11.2 mg, 0.1 mol) in MeCN (2 mL) was irradiated in the focused microwave equipment (CEM Discover) for the time specified (Table  [¹] ). The final temperature was set to 120 ˚C, the power to 120 W, and the ramp time to 5 min. Thereafter, the reaction mixture was cooled, the volatile components were removed in vacuo, the remaining solid was treated with mixture of EtOH and H₂O (10:1), and cooled. The precipitated product 5 was filtered off and washed with EtOH-H₂O (10:1).
Selected Data of the ProductsMethyl 5-(Benzoylamino)-2-[(methoxycarbonyl)-methyl]benzoate (5a) Mp 169-171 ˚C (MeOH). IR (KBr): 3339, 1737, 1720, 1653, 1590, 1526, 1435, 1419 cm^-¹. ^¹H NMR (300 MHz, CDCl₃): δ = 3.71 (s, 3 H, Me), 3.83 (s, 3 H, Me), 3.98 (s, 2 H, CH₂), 7.21 (d, 1 H, J = 8.4 Hz, 3-H), 7.52 (m, 3 H, Ph), 7.86 (m, 3 H, Ph, 4-H), 8.10 (br s, 1 H, NH), 8.18 (d, 1 H, J = 2.1 Hz, 6-H). ^¹³C NMR (75.5 MHz, DMSO-d ₆): δ = 39.1, 51.4, 51.9, 122.0, 123.8, 127.6, 128.4, 129.4, 130.9, 131.7, 132.8, 134.5, 138.3, 165.6, 166.7, 171.5. MS (EI): m/z (%) = 327 (5) [M⁺], 105 (100). Anal. Calcd for C₁₈H₁₇NO₅: C, 66.05; H, 5.23; N, 4.28. Found: C, 66.32; H, 5.17; N, 4.26.
Ethyl 5-(Benzoylamino)-2-[(ethoxycarbonyl)-methyl]benzoate (5b)
Mp 170.5-171.5 ˚C (MeOH). IR (KBr): 3298, 1736, 1714, 1651, 1588, 1523, 1420 cm^-¹. ^¹H NMR (300 MHz, CDCl₃): δ = 1.25 (t, 3 H, J = 7.1 Hz, CH₂CH ₃), 1.37 (t, 3 H, J = 7.1 Hz, CH₂CH ₃), 3.99 (s, 2 H, CH₂), 4.15 (q, 2 H, J = 7.1 Hz, CH ₂CH₃), 4.32 (q, 2 H, J = 7.1 Hz, CH ₂ CH₃), 7.24 (d, 1 H, J = 8.9 Hz, 3-H), 7.53 (m, 3 H, Ph), 7.88 (m, 2 H, Ph), 7.95 (dd, 1 H, J ₁ = 8.9 Hz, J ₂ = 2.4 Hz, 4-H), 7.98 (br s, 1 H, NH), 8.10 (d, 1 H, J = 2.4 Hz, 6-H).
Methyl 5-(Benzoylamino)-2-methylbenzoate (5c)
Mp 126-127 ˚C (EtOH-H₂O). IR (KBr): 3270, 1732, 1720, 1649, 1582, 1528, 1498, 1428 cm^-¹. ^¹H NMR (300 MHz, CDCl₃): δ = 2.57 (s, 3 H, Me), 3.86 (s, 3 H, Me), 7.22 (d,
1 H, J = 8.3 Hz, 3-H), 7.50 (m, 3 H, Ph), 7.81 (dd, 1 H, J ₁ = 2.2 Hz, J ₂ = 8.3 Hz, 4-H), 7.86 (m, 2 H, Ph), 8.02 (br s, 1 H, NH), 8.08 (d, 1 H, J = 2.2 Hz, 6-H). ^¹³C NMR (75.5 MHz, CDCl₃): δ = 21.1, 51.9, 122.3, 124.0, 127.0, 128.7, 129.8, 131.9, 132.3, 134.6, 135.7, 136.3, 165.8, 167.5. MS (EI): m/z (%) = 269 (30) [M⁺], 105 (100). Anal. Calcd for C₁₆H₁₅NO₃: C, 71.36; H, 5.61; N, 5.20. Found: C, 71.30; H, 5.68; N, 5.22.
Ethyl 5-(Benzoylamino)-2-methylbenzoate (5d) Mp 119-120.5 ˚C (EtOH-H₂O). IR (KBr): 3296, 1726, 1648, 1583, 1530, 1448, 1404 cm^-¹. ^¹H NMR (300 MHz, CDCl₃): δ = 1.38 (t, 3 H, J = 7.1 Hz, CH₂CH ₃), 2.57 (s, 3 H, Me), 4.35 (q, 2 H, J = 7.1 Hz, CH ₂CH₃), 7.23 (d, 1 H, J = 
8.1 Hz, 3-H), 7.50 (m, 3 H, Ph), 7.87 (m, 3 H, Ph, 4-H), 7.96 (br s, 1 H, NH), 8.02 (d, 1 H, J = 2.4 Hz, 6-H).
N -(3-Acetyl-4-methylphenyl)benzamide (5e) ^¹¹
Mp 131-132 ˚C (EtOH-H₂O); lit.^¹¹ mp 137-138 ˚C (EtOH). IR (KBr): 3410, 1861, 1788, 1699, 1653, 1533, 1492 cm^-¹. ^¹H NMR (300 MHz, CDCl₃): δ = 2.49 (s, 3 H, Me), 2.57 (s, 3 H, Me), 7.21 (d, 1 H, J = 8.4 Hz, 5-H), 7.53 (m, 4 H, Ph,
6-H), 7.87 (m, 2 H, Ph), 8.05 (br s, 1 H, NH), 8.13 (d, 1 H, J = 2.4 Hz, 2-H).
N -(3-Benzoyl-4-methylphenyl)benzamide (5f)
Mp <35 ˚C (EtOH-H₂O). IR (neat): 1671, 1597, 1522, 1501 cm^-¹. ^¹H NMR (300 MHz, CDCl₃): δ = 2.28 (s, 3 H, Me), 7.28 (d, 1 H, J = 8.4 Hz, 5-H), 7.52 (m, 7 H, 2 × Ph, 2-H), 7.77 (dd, 1 H, J ₁ = 2.4 Hz, J ₂ = 8.4 Hz, 6-H), 7.83 (m, 4 H, Ph), 7.94 (br s, 1 H, NH).
N -(3-Acetyl-4-methylphenyl)acetamide (5g) ^¹¹,¹² Mp 86-88 ˚C (EtOH-H₂O); lit.^¹¹ mp 94-95 ˚C (EtOH); lit.^¹² mp 124 ˚C (EtOH). IR (KBr): 3331, 1686, 1668, 1585, 1536, 1497, 1453 cm^-¹. ^¹H NMR (300 MHz, CDCl₃): δ = 2.19 (s, 3 H, Me), 2.47 (s, 3 H, Me), 2.57 (s, 3 H, Me), 7.16 (br s,
1 H, NH), 7.18 (d, 1 H, J = 8.2 Hz, 5-H), 7.40 (dd, 1 H, J ₁ = 2.0 Hz, J ₂ = 8.2 Hz, 6-H), 7.97 (d, 1 H, J = 2.0 Hz, 2-H).