Download PDF
Synlett 2003(11): 1710-1712
DOI: 10.1055/s-2003-40995
LETTER
© Georg ThiemeVerlag Stuttgart ˙ New York

Solventless Reactions of 5(4H)-Oxazolones with Umbelliferones andSelected Enolcarbonyl Compounds

Massimiliano Cordaroa, Leonardo Di Donnab, Francesco Fotia, Giovanni Grassi*a, Anna Napolib, Francesco Risitanoa, Giovanni Sindonab
a Dipartimento di Chimica Organica e Biologica, Università, Vill. S. Agata, 98166Messina, Italy
Fax: +39(090)393897; e-Mail: ggrassi@isengard.unime.it.;
b Dipartimento di Chimica, Università dellaCalabria, Cubo 15/C, 87030, Arcavacata diRende, Italy
Further Information

Publication History

Received 28 May 2003
Publication Date:
05 August 2003 (online)

    Permissions and Reprints All articles of this category

Abstract

Reactions of oxazolones with umbelliferones and other selectedenolcarbonylic substrates are reported. An original synthetic protocolwas defined which, under solventless conditions, allows excellentcontrol of chemo- and regioselectivity and favours the formationof compounds that would otherwise be inaccessible. Depending onthe substrate employed, this procedure made it possible to obtainO- and C-acylation and cycloaddition products.

Key words

acylation - cycloaddition - chemoselectiviy - hydroxycoumarins - high resolution ESI spectra

    References

  • 1 For a review on azlactones see: Mukerjee AK. Heterocycles  1987,  26:  1077 
    CrossrefGoogle Scholar
  • 2 Mukerjee AK. Kumar P. Heterocycle  1981,  16:  1995 
    Google Scholar
  • 3a Suh J. Lee E. Myoung YC. Kim M. Kim S. J. Org. Chem.,  1985,  50:  977 
    Google Scholar
  • 3b

    Grassi, G.; Cordaro,M.; Risitano, F.; Foti, F. in preparation.
  • 4 Steglich W. Gruber P. Höfle G. Koning W. Angew. Chem., Int. Ed. Engl.  1971,  10:  653 
    Google Scholar
  • 5a Grassi G. Risitano F. Foti F. Cordaro M. Synlett  2001,  812 
    CrossrefGoogle Scholar
  • 5b Grassi G. Cordaro M. Bruno G. Nicolò F. Helv. Chim. Acta  2002,  85:  196 
    CrossrefGoogle Scholar
  • 6a Bickoff EM. Livingston AL. Booth AN. Thompson CR. Hollwell EA. Beinhart EG. J. Anim. Sci.  1960,  19:  4 
    Google Scholar
  • 6b Wong E. Fortschr.Chem. Org. Naturst.  1970,  28:  1 
    Google Scholar
  • 6c Hermodson MA. Barker WM. Link KP. J. Med. Chem.  1971,  14:  167 
    Google Scholar
  • 6d Kralt T. Classen V. In DrugDesign   Vol. 3:  Ariens EJ. Academic Press; New York: 1972.  p.189 
    Google Scholar
  • 6e Feuer G. Prog. Med.Chem.  1973,  10:  85 
    Google Scholar
  • 6f Kazmier FJ. Mayo Clin. Proceed.  1974,  49:  918 
    Google Scholar
  • 6g O’Reilly RA. Ann. Rev. Med.  1976,  27:  245 
    Google Scholar
  • 6h Obaseki O. Porter WR. J. Heterocycl. Chem.  1982,  19:  385 
    Google Scholar
  • 7 Anastas PT. Warner JC. GreenChemistry, Theory and Practice   Oxford UniversiyPress; Oxford: 1998. 
    Google Scholar
  • 8a Gnerre C. Catto M. Leonetti F. Weber P. Carrupt P.-A. Altomare C. Carotti A. Testa B. J. Med. Chem.  2000,  43:  4747 
    Google Scholar
  • 8b Ma Z. Taylor J.-S. Bioorg. Med. Chem.  2001,  9:  2501 
    Google Scholar
  • 8c Bensel N. Reymond MT. Reymond J.-L. Chem.-Eur.J.  2001,  7:  4604 
    Google Scholar
  • 9 Grassi G. Risitano F. Foti F. Cordaro M. Bruno G. Nicolò F. Chem. Commun.  2003,  1868 
    CrossrefGoogle Scholar
10

Typical experimental procedure: Substrate 2 or 4 (2 mmol) andoxazolone 1 (4 mmol) were combined usinga mortar and a pestle, and the resulting powder was transferredin a 5 mL sealable glass vial. Under nitrogen atmosphere, the vial wasthen sealed with a rubber-lined screw cap and teflon tape. Afterheating for 1 h (disappearance of the starting material by TLC)at 100 °C (or 120 °C), the reaction mixture wascooled at room temperature and purified by crystallization frommethanol to afford the indicated product as a white crystallinesolid.

11

Selected data. Compound 3a: mp 156-157 °C; ΙR(Nujol): 3323, 1770, 1744, 1640 cm-1; 1Η NMR(300 MHz, CDCl3): 1.69 (d, J = 7.2Hz, CH 3 CH),5.00 (dq, J = 7.2 Hz, 6.6 Hz, CH3CHNH), 6.38 (d, J = 9.6Hz, CH=CHCOO), 6.71 (d, J = 6.6 Hz, CHNH),7.06-7.75 (m, arom., 8 H), 7.81 (d, J = 9.6 Hz,CH=CHCOO); 13CNMR (75 MHz, CDCl3): 18.1, 48.8, 110.2, 116.3, 116.9,117.0, 118.1, 127.1, 128.7, 131.9, 132.1, 133.5, 142.7, 151.1, 152.9,154.6, 160.2, 167.2, 171.2; HRMS calcd for C19H16NO5:338.1028, found 338.1013. Compound 3b:mp 158-159 °C; ΙR (Nujol): 3301, 1769,1725, 1636 cm-1; 1Η NMR(300 MHz, CDCl3): 1.67 (d, J = 7.2Hz, CH 3 CH),2.39 (s, CH 3), 4.98 (dq, J = 7.2 Hz, 6.8 Hz, CH3CHNH), 6.22 (s, C=CHCOO), 6.87 (d, J = 6.8 Hz,CHNH), 7.07-7.82 (m, arom.,8 H); 13C NMR (75 MHz, CDCl3):18.1, 18.7, 48.8, 110.2, 114.6, 117.8, 118.1, 118.2, 125.5, 127.1,128.5, 128.6, 131.9, 133.4, 151.9, 152.7, 154.1, 160.4, 167.3, 171.3;HRMS calcd for C20H18NO5: 352.1185,found 352.1192. Compound 3c: mp 202-203 °C; ΙR(Nujol): 3328, 1772, 1745, 1682, 1638 cm-1; 1Η NMR (300MHz, DMSO-d 6): 1.57 (d, J = 7.2 Hz, CH 3 CH), 2.58 (s, CH 3 CO), 4.67 (dq, J = 7.2Hz, 6.3, CH3CHNH), 6.75-8.04 (m,arom., 8 H), 8.67 (s, CH=CCOCH3),9.09 (d, J = 6.3 Hz, CHNH); 13CNMR (75 MHz, DMSO-d 6): 18.1,22.0, 49.8, 110.2, 116.3, 117.0, 118.1, 127.1, 128.7, 131.2, 131.9, 132.1,133.5, 150.3, 151.1, 152.9, 154.6, 160.2, 167.2, 171.2, 196.5; HRMScalcd for C21H18NO6: 380.1134,found 380.1122. Compound 3d: mp 151-152 °C; ΙR(Nujol): 3322, 1760, 1737, 1644 cm-1; 1Η NMR(300 MHz, CDCl3): 3.40 (ddd, J = 13.3Hz, 6.6 Hz, 6.3 Hz, PhCHHCH), 5.28 (ddd, J = 6.6 Hz, 6.3 Hz, 7.2 Hz,PhCHHCHNH), 6.39 (d, J = 9.6 Hz,CH=CHCOO), 6.59 (d, J = 7.2 Hz, CHNH),6.96-7.68 (m, arom., 13 H), 7.75 (d, J = 9.6Hz, CH=CHCOO); 13C NMR(75 MHz, CDCl3): 37.8, 53.9, 110.0, 116.0, 116.3, 116.9,118.2, 126.0, 127.0, 127.1, 127.6, 128.6, 128.7, 129.2, 129.4, 131.4,132.0, 133.4, 135.3, 142.7, 152.6, 154.5, 160.2, 167.1, 169.8; HRMScalcd for C25H20NO5: 414.1341,found 414.1318. Compound 3e: mp 178-179 °C; ΙR(Nujol): 3273, 1757, 1733, 1642 cm-1; 1Η NMR(300 MHz, CDCl3): 2.43 (s, CH 3),3.39 (ddd, J = 13.3 Hz, 6.6Hz, 6.3, PhCHHCH), 5.30 (ddd, J = 6.6 Hz, 6.3 Hz, 7.2 Hz, PhCHHCHNH),6.28 (s, CHCOO), 6.66 (d, J = 7.2 Hz, CHNH),6.98-7.76 (m, arom., 13 H); 13CNMR (75 MHz, CDCl3): 24.3, 37.0, 57.9, 110.0, 114.2,118.3, 116.9, 118.2, 124.6, 125.7, 127.1, 127.3, 127.4, 127.8, 127.9,128.4 (2), 128.6(2), 131.9, 133.5, 140.2, 151.2, 152.7, 155.0,162.0, 167.9, 169.0; HRMS calcd for C26H22NO5:428.1498, found 428.1501. Compound 5a:mp 229-230 °C; ΙR (Nujol): 3304, 1725,1643 cm-1; 1Η NMR(300 MHz, CDCl3): 1.58 (d, J = 6.9Hz, CH 3CH), 6.00 (dq, J = 6.9 Hz, 7.0 Hz, CH3CHNH), 6.93 (d, J = 7.0Hz, CHNH), 7.30-8.07 (m, arom.,9 H); 13C NMR (75 MHz, CDCl3):18.1, 52.7, 114.7, 117.0, 124.6, 125.6, 127.1 (2), 128.4(2), 131.7,133.9, 136.5, 151.1,154.9, 159.1, 166.7, 178.7, 206.6; HRMS calcdfor C19H16NO5: 338.1028, found338.1018. Compound 5b: mp 219-220 °C; ΙR(Nujol): 3313, 1722, 1644 cm-1; 1Η NMR(300 MHz, CDCl3): 1.57 (d, J = 6.9Hz, CH 3CH), 2.41(s, CH3)5.99 (dq, J = 6.9 Hz, 7.2 Hz,CH3CHNH), 6.99 (d, J = 7.2 Hz, CHNH), 7.17-7.82(m, arom., 8 H); 13C NMR (75 MHz, CDCl3): 18.1,20.8, 52.8, 99.6, 116.8, 124.9(2), 127.1 (2), 127.6, 128.6(2), 131.7,133.9, 134.5, 137.8, 153.1, 166.8, 178.8, 194.4; HRMS calcd forC20H18NO5: 352.1185, found 352.1182.Compound 5c: mp 189-190 °C; ΙR(Nujol): 3297, 1727, 1636 cm-1; 1Η NMR(300 MHz, CDCl3): 1.52 (d, J = 6.9Hz, CH 3 CH),2.28(s, CH3) 5.86 (dq, J = 6.9Hz, 7.2 Hz, CH3CHNH), 5.97(s, CH) 6.94 (d, J = 7.2 Hz,CHNH), 7.40-7.81 (m, arom.,5 H); 13C NMR (75 MHz, CDCl3):13.9, 20.7, 52.5, 101.3, 118.0, 127.0 (2), 128.6(3), 131.6, 134.0, 147.2,151.1, 170.1, 181.6, 195.4; HRMS calcd for C16H16NO5:302.1028, found 302.1009. Compound 6: mp 178-181 °C; ΙR(Nujol): 3232, 1633 cm-1; 1Η NMR(300 MHz, CDCl3): 1.05 (s, 2 CH3), 2.18 (s,CH3), 2.31 (s, CH2), 2.45 (s, CH2),7.24-7.75 (m, arom., 5 H), 8.39 (s, NH); 13C NMR(75 MHz, CDCl3): 10.7, 28.3, 28.4, 34.9, 35.4, 54.1, 112.0,118.0, 122.4, 122.9, 127.7, 127.9. 128.2, 131.6, 133.0, 151.1, 195.0;HRMS calcd for C17H20NO: 254.1545, found 254.1528.

12

The direct use of solid oxazolonesmakes it perfectly reasonable to hope for access to optically purederivatives via this unconventional method. Full details will be discussedin a future report.