TiO2 Nanoparticles-catalyzed One-pot Synthesis of Quinazolino[2,1-b]phthalazin-8-one and 3-Acylamino Isoindolo[2,1-a]quinazoline Derivatives†

doi:10.7503/cjcu20160292

Abstract

Abstract:

An efficient and simple one-pot method was developed for the synthesis of two kinds of N-fused quinazolinone derivatives using nano TiO₂ particles as catalyst from isatoic anhydride, 2-carboxy benzaldehyde, hydrazides or aromatic hydrazines. Six quinazolino[2,1-b]phthalazin-8-ones and ten 3-acylamino isoindolo[2,1-a]quinazolines were obtained in excellent yields, and the reaction refluxed in aqueous ethanol were environmentally friendly. Attractive features of this methodology were its versatility, mild condition and high efficiency in creating two different structures in a single operation.

Key words: TiO2 Nanoparticles, One-pot reaction, Quinazolino[2, 1-b]phthalazin-8-one, 3-Acylamino isoindolo[2, 1-a]quinazoline

TrendMD:

ZHANG Jin, LIU Jia, MA Yangmin, YANG Xiufang, CHENG Pei, FAN Chao, LU Ping. TiO₂ Nanoparticles-catalyzed One-pot Synthesis of Quinazolino[2,1-b]phthalazin-8-one and 3-Acylamino Isoindolo[2,1-a]quinazoline Derivatives^†[J]. Chem. J. Chinese Universities, 2016, 37(9): 1629.

Figures/Tables 7

Scheme 1 Synthesis of isoindolo[2,1-a]quinazolinone and quinazolino[2,1-b]phthalazine-5,8-dione derivatives

Table 1 Appearance, yields, melting points and HR-MS data of compounds 5a—5f and 6a—6j

Compd.	Appearance	m.p./℃	HRMS(ESI)(calcd.), m/z[M+H]⁺	IR(KBr), $ν ˙$ /cm^-1
5a	White solid	245—246	342.1232(342.1243)	3293.95, 1717.96, 1683.31, 1600.41, 1487.01, 1392.01, 1110.09,
				758.47, 732.64
5b	White solid	252—253	372.1341(372.1348)	3263.77, 2922.53, 1725.46, 1676.33, 1508.99, 1395.38, 1241.86,
				1034.45, 830.91, 759.64
5c	White solid	232—233	376.0849(376.0853)	3444.35, 1731.17, 1653.93, 1489.08, 1092.97, 758.68
5d	White solid	217—218	376.0839(376.0853)	3274.34, 1728.73, 1673.91, 1482.52, 1390.51, 832.60, 746.33
5e	White solid	244—245	406.0950(406.0958)	3337.28, 1727.03, 1672.30, 1489.39, 1170.36, 819.94, 746.97
5f	White solid	211—213	410.0454(410.0463)	3273.08, 1731.55, 1672.65, 1511.90, 1484.64, 1390.70, 1035.14,
				817.26, 743.78
6a	White solid	226—227	370.1192(370.1189)	3201.30, 1722.10, 1696.06, 1653.01, 1483.08, 1401.30, 1278.07,
				898.23, 742.77
6b	White solid	250—251	406.1166(406.1168)	3261.70, 1732.09, 1705.10, 1648.53, 1489.10, 1400.14, 1269.99,
				754.87
6c	White solid	248—249	400.1288(400.1297)	3251.24, 1713.09, 1646.11, 1605.37, 1489.62, 1399.55, 1260.85,
				844.67, 751.28
6d	White solid	221—223	371.1137(371.1144)	3253.69, 1735.64, 1701.98, 1651.96, 1488.34, 1399.09, 1272.24,
				909.02, 756.70
6e	White solid	241—242	308.1026(308.1035)	3293.50, 1729.82, 1703.97, 1662.84, 1605.80, 1489.33, 1398.79,
				756.30, 737.31
6f	White solid	234—235	404.0788(404.0802)	3268.57, 1732.19, 1701.19, 1650.34, 1483.76, 1395.90, 909.89,
				749.42
6g	White solid	214—216	418.0947(418.0958)	3278.24, 1718.74, 1657.16, 1486.11, 1398.10, 175.05, 832.03,
				746.18
Compd.	Appearance	m.p./℃	HRMS(ESI)(calcd.), m/z[M+H]⁺	IR(KBr), $ν ˙$ /cm^-1
6h	White solid	233—234	456.0723(456.0727)	1735.29, 1654.35, 1508.35, 1021.70, 669.81
6i	White solid	199—201	405.0748(405.0754)	3240.55, 1709.44, 1654.75, 1483.51, 1396.86, 1098.93, 913.88,
				744.85
6j	White solid	217—219	342.0636(342.0645)	3274.39, 1733.21, 1705.90, 1668.70, 1485.00, 1397.00, 825.31,
				745.87

Table 1 Appearance, yields, melting points and HR-MS data of compounds 5a—5f and 6a—6j

Compd.	Appearance	m.p./℃	HRMS(ESI)(calcd.), m/z[M+H]⁺	IR(KBr), $ν ˙$ /cm^-1
5a	White solid	245—246	342.1232(342.1243)	3293.95, 1717.96, 1683.31, 1600.41, 1487.01, 1392.01, 1110.09,
				758.47, 732.64
5b	White solid	252—253	372.1341(372.1348)	3263.77, 2922.53, 1725.46, 1676.33, 1508.99, 1395.38, 1241.86,
				1034.45, 830.91, 759.64
5c	White solid	232—233	376.0849(376.0853)	3444.35, 1731.17, 1653.93, 1489.08, 1092.97, 758.68
5d	White solid	217—218	376.0839(376.0853)	3274.34, 1728.73, 1673.91, 1482.52, 1390.51, 832.60, 746.33
5e	White solid	244—245	406.0950(406.0958)	3337.28, 1727.03, 1672.30, 1489.39, 1170.36, 819.94, 746.97
5f	White solid	211—213	410.0454(410.0463)	3273.08, 1731.55, 1672.65, 1511.90, 1484.64, 1390.70, 1035.14,
				817.26, 743.78
6a	White solid	226—227	370.1192(370.1189)	3201.30, 1722.10, 1696.06, 1653.01, 1483.08, 1401.30, 1278.07,
				898.23, 742.77
6b	White solid	250—251	406.1166(406.1168)	3261.70, 1732.09, 1705.10, 1648.53, 1489.10, 1400.14, 1269.99,
				754.87
6c	White solid	248—249	400.1288(400.1297)	3251.24, 1713.09, 1646.11, 1605.37, 1489.62, 1399.55, 1260.85,
				844.67, 751.28
6d	White solid	221—223	371.1137(371.1144)	3253.69, 1735.64, 1701.98, 1651.96, 1488.34, 1399.09, 1272.24,
				909.02, 756.70
6e	White solid	241—242	308.1026(308.1035)	3293.50, 1729.82, 1703.97, 1662.84, 1605.80, 1489.33, 1398.79,
				756.30, 737.31
6f	White solid	234—235	404.0788(404.0802)	3268.57, 1732.19, 1701.19, 1650.34, 1483.76, 1395.90, 909.89,
				749.42
6g	White solid	214—216	418.0947(418.0958)	3278.24, 1718.74, 1657.16, 1486.11, 1398.10, 175.05, 832.03,
				746.18
Compd.	Appearance	m.p./℃	HRMS(ESI)(calcd.), m/z[M+H]⁺	IR(KBr), $ν ˙$ /cm^-1
6h	White solid	233—234	456.0723(456.0727)	1735.29, 1654.35, 1508.35, 1021.70, 669.81
6i	White solid	199—201	405.0748(405.0754)	3240.55, 1709.44, 1654.75, 1483.51, 1396.86, 1098.93, 913.88,
				744.85
6j	White solid	217—219	342.0636(342.0645)	3274.39, 1733.21, 1705.90, 1668.70, 1485.00, 1397.00, 825.31,
				745.87

Table 2 1H NMR and 13C NMR data of compounds 5a—5f and 6a—6j

Compd.	¹H NMR(400 MHz), δ^a	¹³C NMR(100 MHz), δ^b
5a	8.27(d, J=7.9 Hz, 1H), 8.16(dd, J=7.8, 1.4 Hz, 1H), 8.02(d, J=7.6 Hz, 1H), 7.89(d, J=6.7 Hz, 1H), 7.76—7.69(m, 1H), 7.59(t, J=7.3 Hz, 1H), 7.50(d, J=6.8 Hz, 1H), 7.37(dd, J=12.5, 4.7 Hz, 1H), 7.26(d, J=8.3 Hz, 1H), 7.08—7.00(m, 2H), 6.84(s, 1H), 6.58(s, 2H), 6.37(s, 1H)	165.40, 154.72, 146.89, 133.95, 133.55, 131.48, 129.96, 128.73, 128.44, 126.23, 124.86, 123.93, 121.46, 121.08, 119.97, 118.94, 113.90, 113.54, 72.60
5b	8.27(d, J=8.1 Hz, 1H), 8.16(dd, J=7.8, 1.3 Hz, 1H), 8.02(d, J=7.5 Hz, 1H), 7.91(d, J=7.5 Hz, 1H), 7.75—7.66(m, 1H), 7.59(t, J=7.4 Hz, 1H), 7.52(t, J=7.4 Hz, 1H), 7.41—7.32(m, 1H), 6.63(d, J=6.4 Hz, 3H), 6.56(s, 2H), 6.37(s, 1H), 3.69(s, 3H)	165.89, 154.99, 138.81, 137.43, 134.36, 133.16, 131.98, 130.42, 129.17, 126.89, 125.32, 124.38, 121.46, 120.43, 115.99, 114.32, 112.90, 107.73, 73.05, 55.48
5c	8.27(d, J=8.1 Hz, 1H), 8.15(d, J=9.2 Hz, 1H), 8.03(d, J=7.6 Hz, 1H), 7.84(d, J=7.0 Hz, 1H), 7.77—7.69(m, 1H), 7.61(t, J=7.5 Hz, 1H), 7.52(dd, J=13.2, 6.2 Hz, 1H), 7.37(t, J=7.3 Hz, 1H), 7.02(d, J=2.9 Hz, 2H), 6.81(s, 1H), 6.52(d, J=6.5 Hz, 2H), 6.36(s, 1H)	166.32, 165.78, 146.09, 138.54, 137.51, 134.59, 133.27, 132.00, 130.59, 129.24, 128.94, 126.91, 126.53, 125.42, 124.56, 120.54, 118.37, 115.69, 73.08
5d	8.24(d, J=8.5 Hz, 1H), 8.11(d, J=2.1 Hz, 1H), 8.02(d, J=7.5 Hz, 1H), 7.89(s, 1H), 7.66(dd, J=8.7, 2.1 Hz, 1H), 7.60(t, J=7.2 Hz, 1H), 7.51(s, 1H), 7.08(t, J=25.5 Hz, 2H), 6.85(s, 2H), 6.57(s, 2H), 6.37(s, 1H)	165.29, 164.67, 138.01, 135.45, 135.42, 133.82, 132.87, 131.20, 130.53, 130.10, 128.49, 128.41, 126.34, 124.02, 121.63, 121.41, 113.94, 113.92, 72.58
5e	8.23(d, J=8.7 Hz, 1H), 8.11(d, J=2.4 Hz, 1H), 8.01(d, J=7.5 Hz, 1H), 7.90(d, J=7.4 Hz, 1H), 7.66(dd, J=8.7, 2.5 Hz, 1H), 7.60(t, J=7.4 Hz, 1H), 7.53(t, J=7.4 Hz, 1H), 6.63(dd, J=36.5, 30.4 Hz, 5H), 6.36(s, 1H), 3.69(s, 3H)	165.31, 154.60, 138.11, 133.76, 132.87, 131.18, 130.49, 130.08, 128.35, 126.45, 123.98, 121.38, 115.51, 113.85, 72.39, 54.98
5f	8.23(d, J=8.6 Hz, 1H), 8.10(d, J=2.4 Hz, 1H), 8.02(d, J=7.6 Hz, 1H), 7.84(d, J=6.4 Hz, 1H), 7.67(dd, J=8.7, 2.4 Hz, 1H), 7.61(t, J=7.4 Hz, 1H), 7.53(d, J=6.9 Hz, 1H), 7.01(d, J=6.3 Hz, 2H), 6.84(s, 1H), 6.50(d, J=5.4 Hz, 2H), 6.35(s, 1H)	165.23, 145.27, 137.81, 135.42, 133.99, 133.00, 131.16, 130.61, 130.25, 128.38, 126.52, 126.09, 124.15, 121.49, 115.12, 72.44
6a	11.18(s, 1H), 8.13—8.08(m, 1H), 8.08—8.01(m, 3H), 7.99(d, J=7.4 Hz, 1H), 7.85(s, 1H), 7.81(d, J=8.0 Hz, 1H), 7.76(d, J=7.2 Hz, 1H), 7.69(d, J=7.3 Hz, 1H), 7.61(t, J=7.6 Hz, 2H), 7.51(d, J=7.5 Hz, 1H), 7.46(t, J=7.6 Hz, 1H), 6.84(s, 1H)	166.34, 164.79, 163.41, 138.65, 136.79, 134.34, 133.45, 132.67, 131.52, 131.31, 130.71, 128.84, 127.71, 127.40, 125.56, 125.51, 124.20, 120.39, 118.98, 71.51
6b	8.33(s, 1H), 8.14(dd, J=7.6, 5.2 Hz, 2H), 8.01—7.96(m, 1H), 7.86(d, J=8.0 Hz, 2H), 7.73—7.68(m, 1H), 7.66—7.59(m, 2H), 7.56(d, J=6.2 Hz, 1H), 7.37(d, J=7.7 Hz, 1H), 7.32(d, J=7.8 Hz, 2H), 6.82(s, 1H), 2.47(s, 3H)	167.33, 164.92, 164.04, 143.35, 137.85, 136.61, 133.92, 132.35, 131.84, 130.05, 129.20, 129.12, 127.75, 127.12, 125.01, 124.96, 124.34, 120.18, 118.62, 71.61, 21.18
6c	11.02(s, 1H), 8.10(d, J=7.9 Hz, 1H), 8.05(d, J=7.7 Hz, 1H), 8.00(t, J=8.1 Hz, 3H), 7.84—7.78(m, 2H), 7.77—7.73(m, 1H), 7.47(d, J=7.3 Hz, 2H), 7.14(d, J=8.8 Hz, 2H), 6.82(s, 1H), 3.88(s, 3H)	164.77, 163.51, 162.64, 138.73, 136.79, 135.24, 134.28, 134.18, 133.39, 131.54, 130.67, 129.73, 128.85, 125.46, 124.16, 123.41, 120.34, 119.06, 114.07, 71.53, 55.51
6d	9.20(s, 1H), 8.91—8.75(m, 2H), 8.33(dt, J=7.9, 1.7 Hz, 1H), 8.12(t, J=7.6 Hz, 2H), 7.97(d, J=8.6 Hz, 1H), 7.71(t, J=7.7 Hz, 1H), 7.63(dd, J=5.5, 3.2 Hz, 2H), 7.50(d, J=7.9 Hz, 2H), 7.36(t, J=7.9 Hz, 1H), 6.79(s, 1H)	165.65, 164.92, 163.92, 152.94, 147.75, 137.54, 136.55, 135.40, 134.15, 132.48, 131.76, 130.26, 129.12, 126.75, 125.09, 124.71, 124.50, 123.50, 120.27, 118.35, 71.57
6e	10.52(s, 1H), 8.06(d, J=8.3 Hz, 1H), 8.01(d, J=7.5 Hz, 1H), 7.96(d, J=7.4 Hz, 1H), 7.82(d, J=8.3 Hz, 1H), 7.80—7.73(m, 2H), 7.67(d, J=7.3 Hz, 1H), 7.43(t, J=7.3 Hz, 1H), 6.66(s, 1H), 2.12(s, 3H)	169.64, 164.77, 163.19, 138.61, 136.72, 134.21, 133.37, 131.44, 130.66, 128.78, 125.97, 125.41, 124.07, 120.33, 118.97, 71.25, 20.45
Compd.	¹H NMR(400 MHz), δ^a	¹³C NMR(100 MHz), δ^b
6f	8.68(s, 1H), 8.06(d, J=8.7 Hz, 1H), 7.91(dd, J=8.0, 4.7 Hz, 4H), 7.60(dd, J=8.9, 5.5 Hz, 4H), 7.48(dd, J=16.5, 8.6 Hz, 3H), 6.70(s, 1H)	167.03, 164.66, 163.18, 137.41, 134.97, 133.97, 132.64, 132.58, 131.28, 130.58, 130.27, 130.22, 128.64, 128.54, 127.08, 124.93, 124.41, 121.63, 119.63, 71.37
6g	8.74(s, 1H), 8.04(d, J=8.7 Hz, 1H), 7.87(dd, J=5.1, 3.2 Hz, 2H), 7.80(d, J=8.2 Hz, 2H), 7.63—7.56(m, 3H), 7.48(dd, J=8.4, 3.6 Hz, 1H), 7.22(d, J=8.0 Hz, 2H), 6.65(s, 1H), 2.41(s, 3H)	167.35, 165.12, 163.71, 143.83, 137.90, 135.44, 134.39, 133.03, 131.70, 130.98, 130.63, 129.60, 129.09, 127.85, 127.59, 125.47, 124.82, 122.06, 120.11, 71.82, 21.65
6h	8.57(s, 1H), 8.08(d, J=8.7 Hz, 1H), 7.93(dd, J=14.0, 5.6 Hz, 4H), 7.64(tt, J=7.4, 4.1 Hz, 3H), 7.57—7.50(m, 1H), 6.95(d, J=8.8 Hz, 2H), 6.72(s, 1H), 3.90(s, 3H)	166.96, 165.17, 163.80, 163.45, 138.04, 135.51, 134.39, 133.02, 131.80, 131.03, 130.64, 129.63, 129.12, 125.53, 124.85, 122.94, 122.11, 120.25, 114.22, 71.93, 55.52
6i	11.43(s, 1H), 9.17(s, 1H), 8.88(d, J=4.0 Hz, 1H), 8.44—8.28(m, 1H), 8.14(dd, J=8.7, 2.9 Hz, 1H), 8.03—7.98(m, 2H), 7.91(dd, J=8.7, 2.6 Hz, 1H), 7.82(t, J=7.0 Hz, 1H), 7.76(t, J=7.3 Hz, 1H), 7.67(d, J=3.0 Hz, 1H), 7.59(d, J=7.4 Hz, 1H), 6.85(s, 1H)	165.14, 164.78, 162.24, 153.25, 148.63, 138.34, 135.68, 135.58, 134.26, 133.75, 131.19, 130.89, 129.62, 128.06, 125.78, 124.31, 123.99, 122.41, 120.46, 99.50, 71.46
6j	10.60(s, 1H), 8.06(d, J=8.7 Hz, 1H), 7.95(d, J=7.9 Hz, 2H), 7.83(t, J=7.5 Hz, 2H), 7.76(d, J=7.1 Hz, 1H), 7.64(d, J=7.5 Hz, 1H), 6.64(s, 1H), 2.11(s, 3H)	169.93, 164.86, 162.14, 138.25, 135.48, 134.07, 133.63, 131.04, 130.83, 129.59, 127.93, 125.93, 124.18, 122.34, 120.50, 71.18, 20.34

Table 2 1H NMR and 13C NMR data of compounds 5a—5f and 6a—6j

Compd.	¹H NMR(400 MHz), δ^a	¹³C NMR(100 MHz), δ^b
5a	8.27(d, J=7.9 Hz, 1H), 8.16(dd, J=7.8, 1.4 Hz, 1H), 8.02(d, J=7.6 Hz, 1H), 7.89(d, J=6.7 Hz, 1H), 7.76—7.69(m, 1H), 7.59(t, J=7.3 Hz, 1H), 7.50(d, J=6.8 Hz, 1H), 7.37(dd, J=12.5, 4.7 Hz, 1H), 7.26(d, J=8.3 Hz, 1H), 7.08—7.00(m, 2H), 6.84(s, 1H), 6.58(s, 2H), 6.37(s, 1H)	165.40, 154.72, 146.89, 133.95, 133.55, 131.48, 129.96, 128.73, 128.44, 126.23, 124.86, 123.93, 121.46, 121.08, 119.97, 118.94, 113.90, 113.54, 72.60
5b	8.27(d, J=8.1 Hz, 1H), 8.16(dd, J=7.8, 1.3 Hz, 1H), 8.02(d, J=7.5 Hz, 1H), 7.91(d, J=7.5 Hz, 1H), 7.75—7.66(m, 1H), 7.59(t, J=7.4 Hz, 1H), 7.52(t, J=7.4 Hz, 1H), 7.41—7.32(m, 1H), 6.63(d, J=6.4 Hz, 3H), 6.56(s, 2H), 6.37(s, 1H), 3.69(s, 3H)	165.89, 154.99, 138.81, 137.43, 134.36, 133.16, 131.98, 130.42, 129.17, 126.89, 125.32, 124.38, 121.46, 120.43, 115.99, 114.32, 112.90, 107.73, 73.05, 55.48
5c	8.27(d, J=8.1 Hz, 1H), 8.15(d, J=9.2 Hz, 1H), 8.03(d, J=7.6 Hz, 1H), 7.84(d, J=7.0 Hz, 1H), 7.77—7.69(m, 1H), 7.61(t, J=7.5 Hz, 1H), 7.52(dd, J=13.2, 6.2 Hz, 1H), 7.37(t, J=7.3 Hz, 1H), 7.02(d, J=2.9 Hz, 2H), 6.81(s, 1H), 6.52(d, J=6.5 Hz, 2H), 6.36(s, 1H)	166.32, 165.78, 146.09, 138.54, 137.51, 134.59, 133.27, 132.00, 130.59, 129.24, 128.94, 126.91, 126.53, 125.42, 124.56, 120.54, 118.37, 115.69, 73.08
5d	8.24(d, J=8.5 Hz, 1H), 8.11(d, J=2.1 Hz, 1H), 8.02(d, J=7.5 Hz, 1H), 7.89(s, 1H), 7.66(dd, J=8.7, 2.1 Hz, 1H), 7.60(t, J=7.2 Hz, 1H), 7.51(s, 1H), 7.08(t, J=25.5 Hz, 2H), 6.85(s, 2H), 6.57(s, 2H), 6.37(s, 1H)	165.29, 164.67, 138.01, 135.45, 135.42, 133.82, 132.87, 131.20, 130.53, 130.10, 128.49, 128.41, 126.34, 124.02, 121.63, 121.41, 113.94, 113.92, 72.58
5e	8.23(d, J=8.7 Hz, 1H), 8.11(d, J=2.4 Hz, 1H), 8.01(d, J=7.5 Hz, 1H), 7.90(d, J=7.4 Hz, 1H), 7.66(dd, J=8.7, 2.5 Hz, 1H), 7.60(t, J=7.4 Hz, 1H), 7.53(t, J=7.4 Hz, 1H), 6.63(dd, J=36.5, 30.4 Hz, 5H), 6.36(s, 1H), 3.69(s, 3H)	165.31, 154.60, 138.11, 133.76, 132.87, 131.18, 130.49, 130.08, 128.35, 126.45, 123.98, 121.38, 115.51, 113.85, 72.39, 54.98
5f	8.23(d, J=8.6 Hz, 1H), 8.10(d, J=2.4 Hz, 1H), 8.02(d, J=7.6 Hz, 1H), 7.84(d, J=6.4 Hz, 1H), 7.67(dd, J=8.7, 2.4 Hz, 1H), 7.61(t, J=7.4 Hz, 1H), 7.53(d, J=6.9 Hz, 1H), 7.01(d, J=6.3 Hz, 2H), 6.84(s, 1H), 6.50(d, J=5.4 Hz, 2H), 6.35(s, 1H)	165.23, 145.27, 137.81, 135.42, 133.99, 133.00, 131.16, 130.61, 130.25, 128.38, 126.52, 126.09, 124.15, 121.49, 115.12, 72.44
6a	11.18(s, 1H), 8.13—8.08(m, 1H), 8.08—8.01(m, 3H), 7.99(d, J=7.4 Hz, 1H), 7.85(s, 1H), 7.81(d, J=8.0 Hz, 1H), 7.76(d, J=7.2 Hz, 1H), 7.69(d, J=7.3 Hz, 1H), 7.61(t, J=7.6 Hz, 2H), 7.51(d, J=7.5 Hz, 1H), 7.46(t, J=7.6 Hz, 1H), 6.84(s, 1H)	166.34, 164.79, 163.41, 138.65, 136.79, 134.34, 133.45, 132.67, 131.52, 131.31, 130.71, 128.84, 127.71, 127.40, 125.56, 125.51, 124.20, 120.39, 118.98, 71.51
6b	8.33(s, 1H), 8.14(dd, J=7.6, 5.2 Hz, 2H), 8.01—7.96(m, 1H), 7.86(d, J=8.0 Hz, 2H), 7.73—7.68(m, 1H), 7.66—7.59(m, 2H), 7.56(d, J=6.2 Hz, 1H), 7.37(d, J=7.7 Hz, 1H), 7.32(d, J=7.8 Hz, 2H), 6.82(s, 1H), 2.47(s, 3H)	167.33, 164.92, 164.04, 143.35, 137.85, 136.61, 133.92, 132.35, 131.84, 130.05, 129.20, 129.12, 127.75, 127.12, 125.01, 124.96, 124.34, 120.18, 118.62, 71.61, 21.18
6c	11.02(s, 1H), 8.10(d, J=7.9 Hz, 1H), 8.05(d, J=7.7 Hz, 1H), 8.00(t, J=8.1 Hz, 3H), 7.84—7.78(m, 2H), 7.77—7.73(m, 1H), 7.47(d, J=7.3 Hz, 2H), 7.14(d, J=8.8 Hz, 2H), 6.82(s, 1H), 3.88(s, 3H)	164.77, 163.51, 162.64, 138.73, 136.79, 135.24, 134.28, 134.18, 133.39, 131.54, 130.67, 129.73, 128.85, 125.46, 124.16, 123.41, 120.34, 119.06, 114.07, 71.53, 55.51
6d	9.20(s, 1H), 8.91—8.75(m, 2H), 8.33(dt, J=7.9, 1.7 Hz, 1H), 8.12(t, J=7.6 Hz, 2H), 7.97(d, J=8.6 Hz, 1H), 7.71(t, J=7.7 Hz, 1H), 7.63(dd, J=5.5, 3.2 Hz, 2H), 7.50(d, J=7.9 Hz, 2H), 7.36(t, J=7.9 Hz, 1H), 6.79(s, 1H)	165.65, 164.92, 163.92, 152.94, 147.75, 137.54, 136.55, 135.40, 134.15, 132.48, 131.76, 130.26, 129.12, 126.75, 125.09, 124.71, 124.50, 123.50, 120.27, 118.35, 71.57
6e	10.52(s, 1H), 8.06(d, J=8.3 Hz, 1H), 8.01(d, J=7.5 Hz, 1H), 7.96(d, J=7.4 Hz, 1H), 7.82(d, J=8.3 Hz, 1H), 7.80—7.73(m, 2H), 7.67(d, J=7.3 Hz, 1H), 7.43(t, J=7.3 Hz, 1H), 6.66(s, 1H), 2.12(s, 3H)	169.64, 164.77, 163.19, 138.61, 136.72, 134.21, 133.37, 131.44, 130.66, 128.78, 125.97, 125.41, 124.07, 120.33, 118.97, 71.25, 20.45
Compd.	¹H NMR(400 MHz), δ^a	¹³C NMR(100 MHz), δ^b
6f	8.68(s, 1H), 8.06(d, J=8.7 Hz, 1H), 7.91(dd, J=8.0, 4.7 Hz, 4H), 7.60(dd, J=8.9, 5.5 Hz, 4H), 7.48(dd, J=16.5, 8.6 Hz, 3H), 6.70(s, 1H)	167.03, 164.66, 163.18, 137.41, 134.97, 133.97, 132.64, 132.58, 131.28, 130.58, 130.27, 130.22, 128.64, 128.54, 127.08, 124.93, 124.41, 121.63, 119.63, 71.37
6g	8.74(s, 1H), 8.04(d, J=8.7 Hz, 1H), 7.87(dd, J=5.1, 3.2 Hz, 2H), 7.80(d, J=8.2 Hz, 2H), 7.63—7.56(m, 3H), 7.48(dd, J=8.4, 3.6 Hz, 1H), 7.22(d, J=8.0 Hz, 2H), 6.65(s, 1H), 2.41(s, 3H)	167.35, 165.12, 163.71, 143.83, 137.90, 135.44, 134.39, 133.03, 131.70, 130.98, 130.63, 129.60, 129.09, 127.85, 127.59, 125.47, 124.82, 122.06, 120.11, 71.82, 21.65
6h	8.57(s, 1H), 8.08(d, J=8.7 Hz, 1H), 7.93(dd, J=14.0, 5.6 Hz, 4H), 7.64(tt, J=7.4, 4.1 Hz, 3H), 7.57—7.50(m, 1H), 6.95(d, J=8.8 Hz, 2H), 6.72(s, 1H), 3.90(s, 3H)	166.96, 165.17, 163.80, 163.45, 138.04, 135.51, 134.39, 133.02, 131.80, 131.03, 130.64, 129.63, 129.12, 125.53, 124.85, 122.94, 122.11, 120.25, 114.22, 71.93, 55.52
6i	11.43(s, 1H), 9.17(s, 1H), 8.88(d, J=4.0 Hz, 1H), 8.44—8.28(m, 1H), 8.14(dd, J=8.7, 2.9 Hz, 1H), 8.03—7.98(m, 2H), 7.91(dd, J=8.7, 2.6 Hz, 1H), 7.82(t, J=7.0 Hz, 1H), 7.76(t, J=7.3 Hz, 1H), 7.67(d, J=3.0 Hz, 1H), 7.59(d, J=7.4 Hz, 1H), 6.85(s, 1H)	165.14, 164.78, 162.24, 153.25, 148.63, 138.34, 135.68, 135.58, 134.26, 133.75, 131.19, 130.89, 129.62, 128.06, 125.78, 124.31, 123.99, 122.41, 120.46, 99.50, 71.46
6j	10.60(s, 1H), 8.06(d, J=8.7 Hz, 1H), 7.95(d, J=7.9 Hz, 2H), 7.83(t, J=7.5 Hz, 2H), 7.76(d, J=7.1 Hz, 1H), 7.64(d, J=7.5 Hz, 1H), 6.64(s, 1H), 2.11(s, 3H)	169.93, 164.86, 162.14, 138.25, 135.48, 134.07, 133.63, 131.04, 130.83, 129.59, 127.93, 125.93, 124.18, 122.34, 120.50, 71.18, 20.34

Table 3 Optimization of the reaction conditionsa

Entry	Catalyst	Catalyst loading(%, molar fraction)	Solvent	Volume ratio of EtOH to H₂O	Yield^b(%)
1	—	—	EtOH/H₂O	1:1	Trace
2	Nano TiO₂	5	EtOH	—	32
3	Nano TiO₂	5	MeOH	—	20
4	Nano TiO₂	5	H₂O	—	40
5	Nano TiO₂	5	EtOH/H₂O	5:1	55
6	Nano TiO₂	5	EtOH/H₂O	3:1	64
7	Nano TiO₂	5	EtOH/H₂O	1:1	89
8	Nano TiO₂	5	EtOH/H₂O	1:3	71
9	Nano TiO₂	5	EtOH/H₂O	1:5	40
10	Nano TiO₂	3	EtOH/H₂O	1:1	66
11	Nano TiO₂	8	EtOH/H₂O	1:1	89
12	Nano TiO₂	10	EtOH/H₂O	1:1	89
13	Nano TiO₂	12	EtOH/H₂O	1:1	89

Table 4 One-pot synthesis of isoindolo[2,1-a]quinazolinone and quinazolino[2,1-b] phthalazine-5,8-dione derivatives

Entry	Compd.	R¹	R²	R³	Yield^*(%)
1	5a	H	H	—	89
2	5b	H	OCH₃	—	93
3	5c	H	Cl	—	85
4	5d	Cl	H	—	80
5	5e	Cl	OCH₃	—	85
6	5f	Cl	Cl	—	80
7	6a	H	—	Ph	83
8	6b	H	—	4-CH₃-Ph	91
9	6c	H	—	4-OCH₃-Ph	90
10	6d	H	—	3-Pyridyl	79
11	6e	H	—	CH₃	80
12	6f	Cl	—	Ph	81
13	6g	Cl	—	4-CH₃-Ph	87
14	6h	Cl	—	4-OCH₃-Ph	87
15	6i	Cl	—	3-Pyridyl	73
16	6j	Cl	—	CH₃	79

Scheme 2 Proposed formation mechanism of compounds 5 and 6

Fig.1 Recyclability of the catalyst for the one-pot synthesis of compound 5a under the optimal reaction

References 24

[1]	Khan I., Ibrar A., Abbas N., Saeed A., Eur. J. Med. Chem., 2014, 76, 193—244
[2]	Khan I., Ibrar A., Ahmed W., Saeed A., Eur. J. Med. Chem., 2015, 90, 124—169
[3]	Servais A., Azzouz M., Lopes D., Courillon C., Malacria M., Angew Chem. Int. Ed., 2007, 46(4), 576—579
[4]	Granger B. A., Kaneda K., Martin S. F., Org. Lett., 2011, 13(17), 4542—4545
[5]	Bandekar P. P., Roopnarine K. A., Parekh V. J., Mitchell T. R., Novak M. J., Sinden R. R., J. Med. Chem., 2010, 53(9), 3558—3565
[6]	Grover G., Kini S. G., Eur. J. Med. Chem., 2006, 41(2), 256—262
[7]	Manivannan E., Chaturvedi S. C., Bioorg. Med. Chem., 2011, 19(15), 4520—4528
[8]	Giardina D., Martarelli D., Sagratini G., Angeli P., Ballinari D., Gulini U., Melchiorre C., Poggesi E., Pompei P., J Med. Chem., 2009, 52(15), 4951—4954
[9]	Kashaw S. K., Kashaw V., Mishra P., Jain N. K., Stables J. P., Eur. J. Med. Chem., 2009, 44(11), 4335—4343
[10]	Jain K. S., Bariwal J. B., Kathiravan M. K., Phoujdar M. S., Sahne R. S., Chauhan B. S., Shah A. K., Yadav M. R., Bioorg. Med. Chem., 2008, 16(9), 4759—4800
[11]	Kumar K. S., Kumar P. M., Kumar K. A., Sreenivasulu M., Jafar A. A., Rambabu D., Krishna G. R., Reddy C. M., Kapavarapu R., Shivakumar K., Priya K. K., Parsa K. V., Pal M., Chem. Commun., 2011, 47(17), 5010—5012
[12]	Siva Kumar K., Mahesh Kumar P., Sreenivasa Rao V., Jafar A. A., Meda C. L. T., Kapavarapu R., Parsa K. V. L., Pal M., Org. Biomol. Chem., 2012, 10(15), 3098—3103
[13]	Yang W., Chen J., Huang X., Ding J., Liu M., Wu H., Org. Lett., 2014, 16(20), 5418—5421
[14]	Hou Y., Wu S., Ma L., Bai J., Liu Z., Zhao Y., Chem. Res. Chinese Universities,2015, 31(5), 766—773
[15]	Zhang J., Zhao J., Wang L., Liu J., Ren D., Ma Y., Tetrahedron,2016, 72(7), 936—943
[16]	Tang J. H., Shi D. X., Wang X. Z., Liu X., Li J. R., Chem. J. Chinese Universities,2012, 33(3), 501—506
	(唐健红, 史大昕, 王秀珍, 刘璇, 李加荣. 高等学校化学学报,2012, 33(3), 501—506)
[17]	Zhang J., Ren D., Ma Y., Wang W., Wu H., Tetrahedron,2014, 70(34), 5274—5282
[18]	Yang W., Qiao R., Chen J., Huang X., Liu M., Gao W., Ding J., Wu H., J. Org. Chem., 2015, 80(1), 482—489
[19]	Chen D., Dou G., Li Y., Liu Y., Wang X., J. Org. Chem., 2013, 78(11), 5700—5704
[20]	Yang W., Ye L., Huang D., Liu M., Ding J., Chen J., Wu H., Tetrahedron,2013, 69(46), 9852—9856
[21]	Avalani J. R., Patel D. S., Raval D. K., J. Mol. Catal. B: Enzym., 2013, 90, 70—75
[22]	Reddy G. R., Reddy T. R., Chary R. G., Joseph S. C., Mukherjee S., Pal M., Tetrahedron Lett., 2013, 54(49), 6744—6746
[23]	Santra S., Bagdi A. K., Majee A., Hajra A., RSC Adv., 2013, 3(47), 24931—24935
[24]	Milad T., Haniyeh A., Hamideh N., Chem. Res. Chinese Universities,2014, 30(3), 405—408

TiO₂ Nanoparticles-catalyzed One-pot Synthesis of Quinazolino[2,1-b]phthalazin-8-one and 3-Acylamino Isoindolo[2,1-a]quinazoline Derivatives^†

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