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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)

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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

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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.

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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.

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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.