May 2012
The Divergent Transformations of Aromatic o-Aminonitrile with Carbonyl Compound
541
dissolved in acetone; the organic phase obtained was combined
with the extracted component of filtrate (using EtOAc) and
evaporated in vacuo, and chromatographed (200–300 mesh
silica gel, ethyl acetate:petroleum = 1:3) to afford product 9.
9b. 6-Nitro-2-(2-nitrophenyl)-2,3-dihydroquinazolin-4(1H)-one.
150.02, 159.00, 161.14; IR (KBr): ꢀv = 3285, 3180, 2920, 1674,
1602 1447 cmꢂ1; MS (ESI): m/z (%) = 225.1 (100) [M+H]+; Anal.
Calcd. for C11H13N2OCl: C 58.80, H 5.83, N 12.47; found C
59.20, H 5.48, N 12.21.
9s. 2-(2-Nitrophenyl)-2,3-dihydroquinazolin-4(1H)-one. M.p.
203–205ꢀC; 1H NMR (DMSO-d6) dH: 6.49 (1H; s, ArCH),
8.32–6.75 (8H; m, ArH), 8.40 (1H; s, NH), 8.58 (1H; s, NH);
13C NMR (DMSO-d6) dC: 62.18, 112.00, 114.23, 124.01,
124.59, 128.68, 128.96, 130.17, 134.38, 135.19, 137.35, 147.09, 151.49,
160.97; IR (KBr): ꢀv = 3378, 3176, 1679, 1610, 1530, 1321 cmꢂ1; MS
(ESI): m/z (%) = 270.2 (100) [M+H]+; Anal. Calcd. for C14H11N3O3:
C 62.45, H 4.12, N 15.61; found C 62.09, H 4.57, N 15.53.
1
M.p. 278–279ꢀC; H NMR (DMSO-d6) dH: 6.59 (1H; s, ArCH),
8.46–6.87 (7H; m, ArH), 8.47 (1H; s, NH), 8.62 (1H; s, NH); 13C
NMR (DMSO-d6) dC: 62.24, 112.05, 114.57, 124.06, 124.78,
128.84, 129.03, 130.33, 134.42, 135.23, 137.40, 147.28, 151.60,
161.01; IR (KBr): ꢀv = 3381, 3183, 1688, 1617, 1532, 1329 cmꢂ1
;
MS (ESI): m/z (%) =315.1 (100) [M+H]+; Anal. Calcd. for
C14H10N4O5: C 53.51, H 3.21, N 17.82; found C 53.69, H 3.30, N 17.62.
9f. 2-(3-Methoxyphenyl)-6-nitro-2,3-dihydroquinazolin-4(1H)-
one. M.p. 208–210ꢀC; 1H NMR (DMSO-d6) dH: 3.76 (3H; s, CH3),
5.99 (1H; s, CH), 6.85 (1H; d, J = 8.0 Hz, ArH), 6.94–6.97
(1H; m, ArH), 7.03 (2H; t, J = 1.6, 1.6 Hz, ArH), 7.34 (1H; t,
J = 8.0, 8.0 Hz, ArH), 8.11 (1H; dd, J = 2.8, 8.0 Hz, ArH), 8.43
(1H; d, J = 2.8 Hz, ArH), 8.59 (1H; s, NH), 8.78 (1H; s, NH); 13C
NMR (DMSO-d6) dC: 55.13, 66.01, 112.30, 112.66, 114.05, 114.23,
118.47, 124.13, 128.93, 129.80, 137.11, 142.65, 152.08, 159.36,
9z. 2-Propyl-2,3-dihydroquinazolin-4(1H)-one. M.p. 213–215ꢀC;
1H NMR (DMSO-d6) dH: 0.81 (3H; t, J = 7.2 Hz, CH3), 1.05–1.11
(2H; m, CH2), 1.30–1.37 (2H; m, CH2), 4.24 (1H; t, J = 5.0 Hz,
CH), 6.21 (1H; d, J = 1.6 Hz, ArH), 6.42 (1H; s, NH), 6.51 (1H; d,
J = 1.6 Hz, ArH), 7.00–7.02 (1H; m, J = 1.6, 1.2, 7.6 Hz, ArH),
7.37 (1H; dd, J = 1.2, 7.6 Hz, ArH), 7.57 (1H; s, NH); 13C NMR
(DMSO-d6) dC: 13.21, 18.21, 34.18, 66.45, 113.69, 114.19, 116.35,
127.16, 133.01, 146.89, 162.72; MS (ESI): IR (KBr): ꢀv = 3382,
3185, 2927, 1645, 1608, 1430 cmꢂ1; m/z (%) = 191.1 (100) [M+H]+;
Anal. Calcd. for C11H14N2O: C 69.44, H 7.42, N 14.73; found
C 69.30, H 7.25, N 14.92.
Reaction of o-aminobenzonitriles with ketones in the catalyst
of base. o-Aminobenzonitrile, ketones and base were added into a
50-mL flask. The mixture was heated at certain temperature for the
specified time (see Table 6 and 7). After completion of the reaction
as indicated by TLC (eluent: petrolum ether/ethyl acetate 1:1), the
cooled reaction mixture was quenched with water (10 mL), and the
precipitate was separated by filtration, then the residue was used
appropriate solvent for recrystallization, which can get the product.
161.29; IR (KBr): ꢀv = 3457, 3190, 1653, 1615, 1490, 1323 cmꢂ1
;
MS (ESI): m/z (%) = 300.4 (100) [M+H]+; Anal. Calcd. for
C15H13N3O4: C 60.10, H 4.38, N 14.04; found C 59.80, H 4.42, N 13.78.
9i. 6-Nitro-2-propyl-2,3-dihydroquinazolin-4(1H)-one. M.p.
1
235–237ꢀC; H NMR (DMSO-d6) dH: 0.90 (3H; t, J = 7.2 Hz,
CH3), 1.38–1.42 (2H; m, CH2), 1.61–1.67 (2H; m, CH2), 4.94
(1H; t, J = 5.0 Hz, CH), 6.80 (1H; d, J = 8.8 Hz, ArH), 8.08
(1H; dd, J = 2.7, 8.8 Hz, ArH), 8.13 (1H; s, NH), 8.36 (1H; s,
NH), 8.39 (1H; d, J = 2.7 Hz, ArH); 13C NMR (DMSO-d6)
dC: 13.66, 16.21, 38.18, 63.94, 112.64, 114.12, 124.19, 128.76,
136.76, 152.76, 161.57; IR (KBr): ꢀv = 3362, 3190, 2927, 1689,
1623, 1515, 1450, 1324, 1302 cmꢂ1; MS (ESI): m/z (%) = 236.1
(100) [M+H]+; Anal. Calcd. for C11H13N3O3: C 56.16, H 5.57,
N 17.86; found C 56.19, H 5.48, N 17.46.
Acknowledgments. This work was supported by the grant of
Beijing Institute of Technology. The authors are grateful for
analytical help of Peking University Analysis Center and
Institute of Chemistry, Chinese Academy of Sciences.
9m. 7-Chloro-2-(3-nitrophenyl)-2,3-dihydroquinazolin-4(1H)- one.
1
M.p. 258–260ꢀC; H NMR (DMSO-d6) dH: 6.02 (1H; s, CH), 6.72
(1H; dd, J = 1.8, 8.0 Hz, ArH), 6.83 (1H; d, J = 1.8 Hz, ArH), 7.61
(2H; t, J = 4.0, 4.0 Hz, ArH), 7.72 (1H; t, J = 7.8, 7.8 Hz, ArH), 7.93
(1H; d, J = 8.0 Hz, ArH), 8.21–8.23 (1H; m, J = 1.6, 1.6 Hz, ArH),
8.35 (1H; s, NH), 8.66 (1H; s, NH); 13C NMR (DMSO-d6) dC: 65.09,
113.58, 113.63, 117.47, 121.48, 123.40, 129.42, 130.17, 133.18,
138.05, 143.94, 147.75, 148.22, 162.46; IR (KBr): ꢀv = 3301, 3166,
1665, 1609, 1523, 1345 cmꢂ1; MS (ESI): m/z (%) = 304.0
(100) [M+H]+; Anal. Calcd. for C14H10N3O3Cl: C 55.37, H
3.32, N 13.84; found C 55.76, H 3.35, N 13.75.
REFERENCES AND NOTES
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[2] (a) Friedlander, P. Ber 1882, 15, 2572; (b) Zhao, Y. L.; Zhang,
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Chem 2003, 68, 9371; (e) Cheng, C. C.; Yan, S. J. In Organic Reactions;
Dauben, W. G., Ed.; Wiley: New York, 1982; Vol. 28,Chapter 2; (f) For
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Comprehensive Heterocyclic Chemistry II; Ramsden, C. A., Ed.;
Pergamon: Tarrytown, 1996; Vol.5,Chapter 5.05; (h) Jones, G. In Com-
prehensive Heterocyclic Chemistry; Boulton, A. J., McKillop, A. Eds.;
Pergamon: New York, 1984, Vol. 2,Chapter 2.08.
9p. 7-Chloro-2-(4-chlorophenyl)-2,3-dihydroquinazolin-
1
4(1H)- one. M.p. 242–244ꢀC; H NMR (DMSO-d6) dH: 5.85 (1H;
s, CH), 6.70 (1H; dd, J = 2.0, 8.4 Hz, ArH), 6.80 (1H; d, J = 2.0 Hz,
ArH), 7.43 (1H; s, NH), 7.47–7.52 (4H; m, J = 2.4 Hz, ArH), 7.61
(1H; d, J = 8.4 Hz, ArH), 8.48 (1H; s, NH); 13C NMR (DMSO-d6)
dC: 65.69, 113.51, 113.59, 117.20, 128.42 (2C), 128.65 (2C),
129.36, 133.15, 137.93, 140.34, 148.56, 162.61; IR (KBr): ꢀv = 3251,
3166, 1649, 1609, 1484 cmꢂ1; MS (ESI): m/z (%) = 294.0
(100) [M+H]+; Anal. Calcd. for C14H10N2OCl2: C 57.36, H
3.44, N 9.56; found C 57.51, H 3.47, N 9.66.
[3] Moore, J. A.; Kornreich, L. D. Tetrahedron Lett 1963, 20, 1277.
[4] Summers, W. K.; Majovski, L. V.; Marsh, G. M.; Summers,
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[5] Elmegeed, G. A.; Wardakhan, W. W.; Younis, M.; Louca, N.
A. Pharmazie 2004, 337, 140.
9q. 7-Chloro-2-propyl-2,3-dihydroquinazolin-4(1H)-one. M.p.
1
222–223ꢀC; H NMR (DMSO-d6) dH: 0.93 (3H; t, J = 7.2 Hz,
CH3), 1.71–1.77 (2H; m, CH2), 2.56–2.59 (2H; m, CH2), 5.38
(1H; t, J = 5.0 Hz, CH), 7.48 (1H; dd, J = 2.0, 8.4 Hz, ArH),
7.64 (1H; d, J = 2.0 Hz, ArH), 8.06 (1H; d, J = 8.4 Hz, ArH),
8.19 (1H; s, NH), 8.38 (1H; s, NH); 13C NMR (DMSO-d6) dC:
13.40, 20.08, 36.31, 65.21, 125.89, 126.14, 127.73, 138.83,
[6] (a) Sestili, I.; Borioni, A.; Mustazza, C.; Rodomonte, A.;
Turchetto, L.; Sbraccia, M.; Riitano, D.; Del Giudice, M. R. Eur J Med
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet