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Synlett 2009(6): 965-967  
DOI: 10.1055/s-0028-1088197
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

β-Nitroacrylates as Key Starting Materials for the Uncatalysed One-Pot Synthesis of Polyfunctionalized Dihydroquinoxalinone Derivatives, via an anti-Michael Reaction

Roberto Ballini*, Serena Gabrielli, Alessandro Palmieri
‘Green Chemistry Group’, Dipartimento di Scienze Chimiche dell’Università di Camerino, Via S. Agostino 1, 62032 Camerino, Italy
Fax: +39(0737)402297; e-Mail: roberto.ballini@unicam.it;
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Publication History

Received 16 December 2008
Publication Date:
16 March 2009 (online)

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Abstract

The reaction of o-phenylenediamine with β-nitroacrylates allows the in situ preparation of dihydroquinoxalinones, via an anti-Michael reaction, under uncatalysed reaction conditions.

Key words

β-nitroacrylates - anti-Michael reaction - uncatalysed - quinoxalinones

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21

Typical Procedure for the Conjugate Addition of Active Methylene 5 to β-Nitroacrylates 1 β-Nitroacrylate 2 (1 mmol) and o-phenylenediamine 1 (1.25 mmol) were dissolved in EtOAc (2 mL) and mixed at r.t., with magnetic stirring, for 2 h. Then, acetone (2 mL, in order to increase the solubility of 4) and 0.8 g of SiO2 (Silica Gel 60, 0,040-0,063 mm, 230-400 mesh ASTM, Merck), were added and the mixture was stirred for 5 min. Finally, the solvent was removed under vacuum and the crude product (adsorbed on SiO2) was charged onto a chromatography column (cyclohexane-EtOAc) allowing the pure products 4. Spectroscopic Data for Representative Compounds
Compound 4b (diastereomeric mixture): yellow solid. IR (KBr): ν = 1362, 1546, 1686, 3049, 3414 cm-¹. ¹H NMR (400 MHz, acetone): δ = 0.95 (t, 3 H, J = 7.3 Hz), 1.88-2.02 (m, 1 H), 2.07-2.25 (m, 1 H), 4.39 (dd, 0.27 H, J = 3.4, 6.8 Hz), 4.62 (dd, 0.73 H, J = 2.6, 4.3 Hz), 4.76-4.84 (m, 0.27 H), 4.88-4.97 (m, 0.73 H), 5.68 (br s, 0.73 H), 5.81 (br s, 0.27 H), 6.66-6.76 (m, 1 H), 6.79-6.92 (m, 3 H), 9.65 (br s, 1 H). ¹³C NMR (100 MHz, acetone): δ = 10.6, 10.8, 23.1, 24.1, 59.4, 59.8, 90.3, 91.5, 114.9, 115.6, 116.0, 116.1, 119.8, 119.9, 124.4, 124.5, 126.0, 126.3, 132.7, 133.4, 163.6, 164.2. API-ES: m/z = 258.2 [M + Na+]. Anal. Calcd for C1 1H13N3O3 (235.24): C, 56.16; H, 5.57; N, 17.86. Found: C, 56.44; H, 5.71; N, 17.71.
Compound 4d (diastereomeric mixture): yellow solid. IR (KBr): ν = 1363, 1544, 1677, 1735, 3067, 3397 cm-¹. ¹H NMR (400 MHz, acetone): δ = 1.26-1.48 (m, 2 H), 1.51-1.70 (m, 2 H), 1.86-2.02 (m, 1 H), 2.07-2.25 (m, 1 H), 2.26-2.35 (m, 2 H), 3.58 (s, 1.5 H), 3.59 (s, 1.5 H), 4.41 (dd, 0.5 H, J = 3.0, 6.8 Hz), 4.64 (dd, 0.5 H, J = 2.6, 4.3 Hz), 4.85-4.93 (m, 0.5 H), 4.99-5.06 (m, 0.5 H), 5.67 (br s, 0.5 H), 5.82 (br s, 0.5 H), 6.67-6.74 (m, 1 H), 6.78-6.91 (m, 3 H), 9.64 (br s, 1 H). ¹³C NMR (100 MHz, acetone): δ = 24.9, 25.0, 26.0, 26.1, 29.4, 30.3, 33.8, 33.9, 51.6, 59.4, 59.9, 88.7, 89.7, 114.9, 115.5, 116.0, 116.1, 119.8, 119.9, 124.3, 124.4, 126.0, 126.2, 132.6, 133.4, 163.7, 164.1, 173.8, 173.9.
API-ES: m/z = 344.4 [M + Na+]. Anal. Calcd for C15H19N3O5 (321.33): C, 56.07; H, 5.96; N, 13.08. Found: C, 56.38; H, 6.18; N, 12.81.
Compound 4e (diastereomeric mixture): yellow solid. IR (KBr): ν = 1361, 1544, 1679, 3059, 3397 cm-¹. ¹H NMR (400 MHz, acetone): δ = 2.18-2.32 (m, 1 H), 2.40-2.55 (m, 1 H), 2.59-2.74 (m, 2 H), 4.49 (dd, 0.35 H, J = 3.0, 6.8 Hz), 4.66 (dd, 0.65 H, J = 2.6, 4.3 Hz), 4.91-4.98 (m, 0.35 H), 4.99-5.05 (m, 0.65 H), 5.74 (br s, 0.65 H), 5.86 (br s, 0.35 H), 6.65-6.73 (m, 1 H), 6.78-6.90 (m, 3 H), 7.11-7.32 (m, 5 H), 9.67 (br s, 1 H). ¹³C NMR (100 MHz, acetone): δ = 31.6, 32.5, 32.6, 32.7, 59.6, 60.0, 88.1, 89.5, 114.9, 115.4, 116.0, 116.1, 119.8, 119.9, 124.4, 124.5, 125.9, 126.1, 127.1, 129.2, 129.3, 129.4, 129.5, 132.6, 133.2, 141.1, 141.3, 163.7, 164.0. API-ES: m/z = 334.4 [M + Na+]. Anal. Calcd for C17H17N3O3 (311.34): C, 65.58; H, 5.50; N, 13.50. Found: C, 65.84; H, 5.73; N, 13.23.
Compound 4f (diastereomeric mixture): yellow solid. IR (KBr): ν = 1040, 1376, 1553, 1683, 3051, 3389 cm-¹. ¹H NMR (400 MHz, acetone): δ = 1.21-1.26 (m, 3 H), 2.21 (dd, 0.75 H, J = 1.7, 15.4 Hz), 2.38 (dd, 0.25 H, J = 2.6, 15.4 Hz), 2.64-2.79 (m, 1 H), 3.71-3.96 (m, 4 H), 4.33 (dd, 0.25 H, J = 3.0, 7.3 Hz), 4.50 (dd, 0.75 H, J = 2.6, 4.3 Hz), 4.89-4.96 (m, 0.25 H), 5.06-5.13 (m, 0.75 H), 5.66 (br s, 0.75 H), 5.82 (br s, 0.25 H), 6.67-6.76 (m, 1 H), 6.79-6.91 (m, 3 H), 9.67 (br s, 1 H). ¹³C NMR (100 MHz, acetone): δ = 24.3, 24.4, 38.4, 39.0, 60.1, 60.3, 65.4, 65.5, 84.1, 85.7, 108.5, 114.9, 115.7, 115.9, 116.0, 116.1, 119.8, 119.9, 124.4, 124.5, 125.9, 126.0, 132.4, 132.9, 163.4, 163.5. API-ES: m/z = 330.4 [M + Na+ ]. Anal. Calcd for C14H17N3O5 (307.30): C, 54.72; H, 5.58; N, 13.67. Found: C, 54.36; H, 5.31; N, 13.83.