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liming928@qust.edu.cn
Received July 25, 2010
DOI: 10.1021/jo101454q Published on Web 10/27/2010 J. Org. Chem. 2010, 75, 7605–7614 7605
r 2010 American Chemical Society
JOC Article Wen et al.
a
The first step time þ the second step time. bTotal isolated yield.
3, and 7, except 4-nitrobenzaldehyde 3m, proceeded smoothly On the basis of the above experimental results, a plausible
with Et3N (0.4 equiv) in refluxing MeCN followed by stirring mechanism for the synthesis of tetrahydrobenzo[b]imidazo-
the mixture at 81 °C for about 6-8 h, evaporation of the [3,2,1-ij][1,8]naphthyridines 6 or 9 was depicted in Scheme 3.
solvent, and then addition of K2CO3 in DMF for about 1.5- Take Meldrum’s acid 7, for example; first, aldehydes 3 react
2 h and led to the formation of tetrahydrobenzo[b]imidazo[3,2, with 7 through Knoevenagel condensation to give intermedi-
1-ij][1,8]naphthyridines 9 (Table 2). ates A. Then, the heterocyclic ketene aminals 2, due to the
The products 9 have been characterized by their IR, 1H two strongly electron-withdrawing groups at the R-position
NMR, 13C NMR, and HRMS spectroscopic data, which are of the ketene N,N-acetals, acted as heteroene components
in agreement with the proposed structures. react with A to form the intermediates B24b,c,30 which under-
When 3m was used in this process, workup of the go a rapid imine-enamine tautomerization to give C. Next,
reaction mixture did not afford any expected unaroma- intramolecular cyclization of C with losing a molecule of
tized compound 9l, but only an unexpected compound 90 l, acetone and decarboxylation of D led to the formation of
which is more stable by aerobic oxidation (Scheme 2). In fused heterocyclic imidazo[1,2-a]pyridine motifs 8. Finally,
the 1H NMR spectrum of 90 l, the absence of three protons an intramolecular nucleophilic aryl substitution of the
(δ 2.7-4.6 ppm, CH þ CH2) and existence of olefinic o-chloro of aryl group (SNAr) by attack of the NH group leads
proton (δ 6.03 ppm) indicate that 6π electron system exists to new and highly functionalized tetrahydrobenzo[b]imidazo-
in the pyridone moiety (see Supporting Information). [3,2,1-ij][1,8]naphthyridine derivatives 9 with elimination of
From this result, we can deduce that the aldehydes with HCl. The formation of 90 l occurs through an intramolecular
strong electron-withdrawing groups and prolonging reac-
tion time of the second step would make the hydrogen (30) Zhao, M.-X.; Wang, M.-X.; Huang, Z.-T. Tetrahedron 2002, 58,
easier to leave in the air. 1309–1316.
a
The first step time þ the second step time. bTotal isolated yield.
FIGURE 2. Influence of the reaction time for the second step from 1H NMR spectra of 9b: top, 2 h, 9b:90 b = 1:0.00; middle, 3 h, 9b:90 b =
1:0.02; bottom, 12 h, 9b:90 b = 1:0.17.
nucleophilic aryl substitution of the o-chloro of the aryl group SCHEME 2. Reaction of 2a with 4-Nitrobenzaldehyde and
(SNAr) by attack of NH group and quickly undergoing in situ Meldrum’s Acid
oxidation by air and subsequent dehydrogenation.
Conclusion
In summary, we have successfully described the application
of 2-(2-chloroaroyl)methyleneimidazolidines 2 to synthesize
tetrahydrobenzo[b]imidazo[3,2,1-ij][1,8]naphthyridines 6 and 9
in a one-pot, two-step sequential process starting from 2,
arylaldehydes 3, and ethyl acetoacetate 4 or Meldrum’s acid 7.
In these reactions, at least six different active sites are involved;
two C-C bonds, two C-N bonds, and two new rings are
constructed with all reactants efficiently utilized in the chemical
transformation. A possible mechanism including Knoevenagel
condensation, aza-ene reaction, intramolecular imine-enamine
tautomerization followed by cyclocondensation and intramole-
cular SNAr was proposed. Undoubtedly, these domino synthetic and washed with cool water. The dry solid then was washed with
strategies open a convenient, effective way to construct the target ethanol.
molecules from readily available starting materials. The wide Ethyl 8-(2,4-dichlorobenzoyl)-5-methyl-7-phenyl-1,2,3,7-tetra-
generation of this process suggests its potential in the synthetic hydroimidazo[1,2-a]pyridine-6-carboxylate (5a): yellow powder;
and medicinal importance of this family of compounds and mp 97-99 °C; IR (KBr, cm-1) 3300, 1691, 1645, 1585, 1554, 1517,
analogues. 1379, 1225, 838, 769, 705; 1H NMR (CDCl3) δ 1.17 (t, J = 7 Hz,
3H, OCH2CH3), 2.40 (s, 3H, CH3), 3.86-3.99 (m, 6H, 2 NCH2
Experimental Section þ OCH2), 4.56 (s, 1H, CH), 6.36-7.49 (m, 8H, ArH), 9.29 (s, 1H,
NH); 13C NMR (CDCl3) δ: 14.2 (pyridine-CH3), 16.4 (OCH2-
General Procedure for the Preparation of Compounds 6 or 9 CH3), 40.4 (7-CH), 42.8 (NCH2), 45.1(NCH2), 59.9 (OCH2), 89.9
(6a, for Example). Et3N (0.040 g, 0.4 mmol, 0.4 equiv) was added (8-C), 109.2 (6-C), 126.0, 126.7, 127.6, 128.6, 130.0, 134.1, 139.3,
to a solution of 2-(2,4-dichlorobenzoyl)methyleneimidazolidine 143.0, 147.6 (5-C), 156.5 (9-C), 167.3 (ester CdO), 188.7 (keto
2a (0.257 g, 1.0 mmol), benzaldehyde 3a (0.127 g, 1.2 mmol), and CdO); HRMS (ESI-TOF, [M þ H]þ) calcd for C24H23Cl2N2O3
ethyl acetoacetate 4 (0.156 g, 1.2 mmol) in 10 mL of MeCN. 457.1086, found 457.1097.
The reaction mixture was refluxed for a certain period of time Ethyl 10-chloro-4-methyl-7-oxo-6-phenyl-1,2,6,7-tetrahydro-
as indicated by TLC (petroleum ether-EtOAc, 2:1, v/v). The benzo[b]imidazo[1,2,3-ij] [1,8]naphthyridine-5-carboxylate (6a):
solvent was removed under vacuum, and the residue together gray powder; mp 263-265 °C; IR (KBr, cm-1) 1687, 1654,
with potassium carbonate (1 mmol) was heated to 100 °C in 1613, 1576, 1520, 1388, 1325, 1223, 762, 699; 1H NMR (DMSO-
DMF. After completion of the reaction as indicated by TLC d6) δ 1.11 (t, J = 7 Hz, 3H, OCH2CH3), 2.49 (s, 3H, CH3), 3.98
(petroleum ether-EtOAc, 2:3, v/v), the mixture was cooled to (q, J = 7 Hz, 2H, OCH2CH3), 4.23-4.47 (m, 4H, 2 NCH2),
room temperature, and an amount of ice-water was added to 5.17 (s, 1H, CH), 7.05-7.95 (m, 8H, ArH); 13C NMR (DMSO-
precipitate the products which were then collected by filtration d6) δ 14.5 (CH3), 16.1 (OCH2CH3), 38.3 (6-CH), 45.4 (NCH2),
SCHEME 3. Proposed Mechanism for the Reaction (Meldrum’s Acid, for Example)
45.5 (NCH2), 59.8 (OCH2), 99.1 (6a-C), 105.5 (5-C), 115.1, OCH2CH3), 4.45-4.63 (m, 4H, 2 NCH2), 5.32 (s, 1H, CH),
122.7, 124.0, 126.3, 127.9, 128.2, 128.2, 136.5, 138.1, 146.2, 6.88-8.06 (m, 7H, ArH); 13C NMR (DMSO-d6) δ 14.6 (CH3), 16.2
147.1, 147.4, 167.2 (ester CdO), 173.1 (keto CdO); HRMS (OCH2CH3), 37.8 (6-CH), 45.4 (NCH2), 45.6 (NCH2), 59.9
(ESI-TOF, [M þ H]þ) calcd for C24H22ClN2O3 421.1319, found (OCH2), 99.0 (6a-C), 105.3 (5-C), 114.7, 114.9, 115.2, 122.9,
421.1329. 124.0, 128.0, 130.0, 136.6, 138.1, 143.7, 146.5, 147.0, 161.0 (d,
1
Ethyl 6-(4-bromophenyl)-10-chloro-4-methyl-7-oxo-1,2,6,7-tetra- J = 240 Hz, F-C couple), 167.2 (ester CdO), 173.2 (keto CdO);
hydrobenzo[b]imidazo[1,2,3-ij][1,8]naphthyridine-5-carboxylate (6b): HRMS (ESI-TOF, [M þ H]þ) calcd for C24H21ClFN2O3 439.1225,
yellow powder; mp 259-260 °C; IR (KBr, cm-1) 1676, 1654, 1613, found 439.1215.
1578, 1520, 1385, 1366, 1326, 1221, 828, 778; 1H NMR (DMSO-d6) Ethyl 10-chloro-6-(3-fluorophenyl)-4-methyl-7-oxo-1,2,6,7-tetra-
δ 1.10 (t, J = 7 Hz, 3H, OCH2CH3), 2.47 (s, 3H, CH3), 3.99 (q, J = hydrobenzo[b]imidazo[1,2,3-ij][1,8]naphthyridine-5-carboxylate (6e):
7 Hz, 2H, OCH2CH3), 4.20-4.47 (m, 4H, 2 NCH2), 5.11 (s, gray powder; mp 256-258 °C; IR (KBr, cm-1) 1685, 1651, 1611,
1H, CH), 7.22-7.93 (m, 7H, ArH); 13C NMR (DMSO-d6) δ 14.5 1583, 1509, 1388, 1366, 1325, 1221, 803, 776; 1H NMR (DMSO-d6)
(CH3), 16.2 (OCH2CH3), 38.1 (6-CH), 45.4 (NCH2), 45.5 (NCH2), δ 1.08 (t, J = 7 Hz, 3H, OCH2CH3), 2.48 (s, 3H, CH3), 3.97 (q, J =
59.9 (OCH2), 98.6 (6a-C), 104.8 (5-C), 115.1, 119.3, 122.8, 123.9, 7 Hz, 2H, OCH2CH3), 4.22-4.45 (m, 4H, 2 NCH2), 5.16 (s,
127.8, 130.5, 131.0, 136.6, 138.0, 146.6, 146.8, 146.9, 167.0 (ester 1H, CH), 6.87-7.94 (m, 7H, ArH); 13C NMR (DMSO-d6) δ 14.6
CdO), 173.1 (keto CdO); HRMS (ESI-TOF, [M þ H]þ) calcd for (CH3), 16.2 (OCH2CH3), 38.3 (6-CH), 45.5 (NCH2), 45.6 (NCH2),
C24H21BrClN2O3 499.0424, found 499.0404. 59.9 (OCH2), 98.5 (6a-C), 104.7 (5-C), 113.2, 115.0, 115.2, 122.9,
Ethyl 10-chloro-6-(4-chlorophenyl)-4-methyl-7-oxo-1,2,6,7-tetra- 124.0, 124.3, 127.9, 130.0, 136.7, 138.1, 146.9, 150.2, 162.4 (d, 1J =
hydrobenzo[b]imidazo[1,2,3-ij][1,8]naphthyridine-5-carboxylate (6c): 241 Hz, F-C couple), 167.1 (ester CdO), 173.2 (keto CdO); HRMS
yellow powder; mp 266-268 °C; IR (KBr, cm-1) 1676, 1654, 1611, (ESI-TOF, [M þ H]þ) calcd for C24H21ClFN2O3 439.1225, found
1575, 1525, 1388, 1369, 1325, 1223, 828, 778; 1H NMR (DMSO-d6) 439.1208.
δ 1.10 (t, J = 7 Hz, 3H, OCH2CH3), 2.49 (s, 3H, CH3), 3.97 (q, J = Ethyl 10-chloro-6-(2-fluorophenyl)-4-methyl-7-oxo-1,2,6,7-tetra-
7 Hz, 2H, OCH2CH3), 4.23-4.47 (m, 4H, 2 NCH2), 5.15 (s, hydrobenzo[b]imidazo[1,2,3-ij][1,8]naphthyridine-5-carboxylate (6f ):
1H, CH), 7.22-7.95 (m, 7H, ArH); 13C NMR (DMSO-d6) δ 14.5 gray powder; mp >300 °C; IR (KBr, cm-1) 1685, 1657, 1616, 1580,
(CH3), 16.2 (OCH2CH3), 38.0 (6-CH), 45.4 (NCH2), 45.5 (NCH2), 1520, 1388, 1328, 1226, 872, 759; 1H NMR (DMSO-d6) δ 1.09
59.9 (OCH2), 98.7 (6a-C), 104.8 (5-C), 115.1, 122.8, 123.9, 127.9, (t, J=7 Hz, 3H, OCH2CH3), 2.47 (s, 3H, CH3), 3.94 (q, J=7 Hz,
128.1, 130.1, 130.8, 136.6, 138.1, 146.3, 146.7, 147.0, 167.0 (ester 2H, OCH2CH3), 4.27-4.43 (m, 4H, 2 NCH2), 5.34 (s, 1H,
CdO), 173.1 (keto CdO); HRMS (ESI-TOF, [M þ H]þ) calcd for CH), 6.97-7.89 (m, 7H, ArH); 13C NMR (DMSO-d6) δ 14.4
C24H21Cl2N2O3 455.0929, found 455.0931. (CH3), 16.1 (OCH2CH3), 32.7 (6-CH), 45.4 (2C, NCH2), 59.8
Ethyl 10-chloro-6-(4-fluorophenyl)-4-methyl-7-oxo-1,2,6,7-tetra- (OCH2), 98.4 (6a-C), 104.5 (5-C), 115.1, 122.9, 123.9, 124.29,
hydrobenzo[b]imidazo[1,2,3-ij][1,8]naphthyridine-5-carboxylate (6d): 127.8, 128.3, 131.5, 134.5, 134.6, 136.6, 138.1, 146.4, 147.2,
white powder; mp 267-268 °C; IR (KBr, cm-1) 1690, 1654, 1613, 159.9 (d, 1J = 245 Hz, F-C couple), 167.1 (ester CdO), 173.0
1575, 1520, 1388, 1328, 1221, 833; 1H NMR (acetone-d6) δ 1.14 (t, (keto CdO); HRMS (ESI-TOF, [M þ H]þ) calcd for C24H21-
J = 7 Hz, 3H, OCH2CH3), 2.62 (s, 3H, CH3), 4.02 (q, J = 7 Hz, 2H, ClFN2O3 439.1225, found 439.1220.
239-241 °C; IR (KBr, cm-1) 1687, 1646, 1616, 1583, 1517, 1369, 10-Chloro-6-(4-methoxyphenyl)-1,2,5,6-tetrahydrobenzo[b]im-
1229, 839, 781; 1H NMR (DMSO-d6) δ 2.71 (d, J = 17 Hz, 1H, idazo[1,2,3-ij][1,8]naphthyridine-4,7-dione (9h): yellow powder;
C(O)CH2), 3.17 (dd, J = 8 Hz, 16.5 Hz, 1H, C(O)CH2), 4.12-4.51 mp 224-226 °C; IR (KBr, cm-1) 1702, 1685, 1651, 1615, 1588,
(m, 5H, 2 NCH2 þ CH), 7.20-8.07 (m, 7H, ArH); 13C NMR 1540, 1514, 1373, 1248, 839, 782; 1H NMR (DMSO-d6) δ 2.66 (d,
(DMSO-d6) δ 34.1 (6-CH), 39.2 (5-CH2), 43.0 (NCH2), 46.0 (NCH2), J = 16 Hz, 1H, C(O)CH2), 3.11 (dd, J = 8 Hz, 17 Hz, 1H, C(O)-
99.3 (6a-C), 115.8, 123.7, 124.0, 128.3, 129.2, 129.5, 130.8, 137.0, CH2), 3.68 (s, 3H, OCH3), 4.12-4.54 (m, 5H, 2 NCH2 þ CH),
138.4, 143.5, 148.6, 167.9 (4-CdO), 173.3 (7-CdO); HRMS (ESI- 6.79-8.08 (m, 7H, ArH); 13C NMR (DMSO-d6) δ 33.7 (6-CH),
TOF, [M þ H]þ) calcd for C20H15BrClN2O2 429.0005, found 42.9 (NCH2), 45.8 (NCH2), 55.5 (OCH3), 100.2 (6a-C), 114.3,
429.0024. 123.5, 124.0, 128.1, 135.9, 136.8, 138.3, 148.3, 158.4, 168.2 (4-CdO),
10-Chloro-6-(4-chlorophenyl)-1,2,5,6-tetrahydrobenzo[b]im- 173.3 (7-CdO); HRMS (ESI-TOF, [M þ H]þ) calcd for C21H18-
idazo[1,2,3-ij][1,8]naphthyridine-4,7-dione (9c): yellow powder; mp ClN2O3 381.1006, found 381.1011.
223-225 °C; IR (KBr, cm-1) 1701, 1687, 1638, 1616, 1578, 1520, 9-Chloro-6-phenyl-1,2,5,6-tetrahydrobenzo[b]imidazo[1,2,3-ij]-
1369, 1229, 839, 784; 1H NMR (DMSO-d6) δ 2.67 (d, J = 16.5 Hz, [1,8]naphthyridine-4,7-dione (9i): yellow powder; mp >300 °C;
1H, C(O)CH2), 3.16 (dd, J = 9.5 Hz, 17 Hz, 1H, C(O)CH2), 4.12- IR (KBr, cm-1) 1691, 1641, 1616, 1587, 1547, 1515, 1418, 1382,
4.51 (m, 5H, 2 NCH2 þ CH), 7.26-8.07 (m, 7H, ArH); 13C NMR 1321, 1231, 1166, 907, 705; 1H NMR (DMSO-d6) δ 2.70 (d, J = 16.5
(DMSO-d6) δ 34.1 (6-CH), 39.2 (5-CH2), 43.0 (NCH2), 46.0 Hz, 1H, C(O)CH2), 3.15 (dd, J = 7.5 Hz, 17 Hz, 1H, C(O)CH2),
(NCH2), 99.4 (6a-C), 115.8, 123.7, 124.0, 128.3, 128.9, 129.1, 4.17-4.53 (m, 5H, 2 NCH2 þ CH), 7.18-8.01 (m, 8H, ArH); 13C
131.7, 137.0, 138.3, 143.0, 148.6, 167.9 (4-CdO), 173.3 (7-CdO); NMR (DMSO-d6) δ 34.6 (6-CH), 42.9 (NCH2), 45.9 (NCH2), 99.8
HRMS (ESI-TOF, [M þ H]þ) calcd for C20H15Cl2N2O2 385.0511, (6a-C), 118.5, 125.3, 126.5, 127.1, 128.1, 129.0, 132.0, 136.1, 144.0,
found 385.0514. 148.5, 168.1 (4-CdO), 172.7 (7-CdO); HRMS (ESI-TOF, [M þ
10-Chloro-6-(4-fluorophenyl)-1,2,5,6-tetrahydrobenzo[b]im- H]þ) calcd for C20H16ClN2O2 351.0900, found 351.0887.
idazo[1,2,3-ij][1,8]naphthyridine-4,7-dione (9d): yellow powder; mp 10-Chloro-9-fluoro-6-phenyl-1,2,5,6-tetrahydrobenzo[b]im-
169-171 °C; IR (KBr, cm-1) 1707, 1638, 1611, 1569, 1534, 1366, idazo[1,2,3-ij][1,8]naphthyridine-4,7-dione (9j): yellow powder; mp
1232, 842, 781, 691; 1H NMR (DMSO-d6) δ 2.67 (d, J = 16.5 Hz, 240-242 °C; IR (KBr, cm-1) 1691, 1644, 1594, 1547, 1518, 1421,
1H, C(O)CH2), 3.15 (dd, J = 8 Hz, 17 Hz, 1H, C(O)CH2), 4.12- 1378, 1238, 1015, 950, 795, 768, 698; 1H NMR (DMSO-d6) δ 2.70 (d,
4.50 (m, 5H, 2 NCH2 þ CH), 7.04-8.07 (m, 7H, ArH); 13C NMR J = 15.5 Hz, 1H, C(O)CH2), 3.16 (dd, J = 8 Hz, 16.5 Hz, 1H,
(DMSO-d6) δ 33.9 (6-CH), 43.0 (NCH2), 45.9 (NCH2), 99.8 (6a-C), C(O)CH2), 4.14-4.54 (m, 5H, 2 NCH2 þ CH), 7.17-7.91 (m,
115.6, 115.7, 123.6, 124.0, 128.3, 129.0, 129.1, 136.9, 138.3, 140.2, 7H, ArH); 13C NMR (DMSO-d6) δ 34.1 (6-CH), 42.4 (NCH2), 45.7
148.5, 161.5 (d, 1J = 241 Hz, F-C couple), 168.0 (4-CdO), 173.3 (NCH2), 99.0 (6a-C), 112.0, 112.2, 118.1, 123.8, 124.0, 124.9, 126.6,
(7-CdO); HRMS (ESI-TOF, [M þ H]þ) calcd for C20H15ClFN2O2 128.5, 133.9, 143.4, 148.2, 153.3 (d, 1J = 242 Hz, F-C couple), 167.6
369.0806, found 369.0789. (4-CdO), 172.0 (7-CdO); HRMS (ESI-TOF, [M þ H]þ) calcd for
10-Chloro-6-(2-chlorophenyl)-1,2,5,6-tetrahydrobenzo[b]im- C20H15ClFN2O2 369.0806, found 369.0809.
idazo[1,2,3-ij][1,8]naphthyridine-4,7-dione (9e): yellow powder; mp 6-Phenyl-1,2,5,6-tetrahydrobenzo[b]imidazo[1,2,3-ij][1,8]naph-
242-244 °C; IR (KBr, cm-1) 1705, 1648, 1616, 1587, 1540, 1472, thyridine-4,7-dione (9k): yellow powder; mp 254-256 °C; IR
1371, 1277, 961, 784, 748, 677; 1H NMR (DMSO-d6) δ 2.52 (dd, J = (KBr, cm-1) 1698, 1637, 1616, 1576, 1540, 1522, 1468, 1446,
8 Hz, 15.5 Hz, 1H, C(O)CH2), 3.24 (dd, J = 9 Hz, 17 Hz, 1H, 1310, 1159, 766, 738, 709; 1H NMR (DMSO-d6) δ 2.70 (d, J =
C(O)CH2), 4.16-4.80 (m, 5H, 2 NCH2 þ CH), 7.04-8.02 (m, 16.5 Hz, 1H, C(O)CH2), 3.15 (dd, J = 8 Hz, 17 Hz, 1H, C(O)CH2),
7H, ArH); 13C NMR (DMSO-d6) δ: 32.2 (6-CH), 38.6 (5-CH2), 43.0 4.11-4.53 (m, 5H, 2 NCH2 þ CH), 7.14-8.10 (m, 9H, ArH); 13C
(NCH2), 46.1 (NCH2), 97.9 (6a-C), 115.9, 123.7, 124.0, 128.0, 128.2, NMR (DMSO-d6) δ 34.6 (6-CH), 42.8 (NCH2), 45.6 (NCH2), 99.3
129.1, 130.3, 133.0, 137.1, 138.6, 140.5, 149.5, 167.2 (4-CdO), 173.2 (6a-C), 116.0, 123.3, 125.4, 126.2, 127.0, 127.1, 128.9, 132.1, 137.4,
(7-CdO); HRMS (ESI-TOF, [M þ H]þ) calcd for C20H15Cl2N2O2 144.2, 148.0, 168.1 (4-CdO), 173.9 (7-CdO); HRMS (ESI-TOF,
385.0511, found 385.0510. [M þ H]þ) calcd for C20H17N2O2 317.1290, found 317.1282.
10-Chloro-6-(2,4-dichlorophenyl)-1,2,5,6-tetrahydrobenzo[b]im- 10-Chloro-6-(4-nitrophenyl)-1,2-dihydrobenzo[b]imidazo[1,2,3-ij]-
idazo[1,2,3-ij][1,8]naphthyridine-4,7-dione (9f): yellow powder; mp [1,8]naphthyridine-4,7-dione (90 l): yellow powder; mp 279-281 °C;
182-184 °C; IR (KBr, cm-1) 1697, 1648, 1617, 1584, 1541, 1521, IR (KBr, cm-1) 1665, 1635, 1594, 1564, 1536, 1509, 1347, 1292, 935,
1472, 1373, 1093, 817, 785; 1H NMR (DMSO-d6) δ 2.54 (1H, 836, 784; 1H NMR (DMSO-d6) δ 4.45 (t, J = 9.5 Hz, 2H, NCH2),
C(O)CH2), 3.26 (dd, J = 9 Hz, 16.5 Hz, 1H, C(O)CH2), 4.15-4.76 4.61 (t, J = 9.5 Hz, 2H, NCH2), 6.03 (s, 1H, =CH), 7.37-8.24 (m,
(m, 5H, 2 NCH2 þ CH), 7.10-8.04 (m, 6H, ArH); 13C NMR 7H, ArH); 13C NMR (TFA-d) δ 46.5 (NCH2), 49.5 (NCH2), 102.7
(DMSO-d6) δ 31.9 (6-CH), 38.2 (5-CH2), 43.0 (NCH2), 46.0 (6a-C), 120.3, 126.1, 129.8, 130.3, 131.3, 139.7, 145.0, 147.8, 150.6,
(NCH2), 97.4 (6a-C), 115.8, 123.7, 123.8, 127.9, 128.1, 129.6, 151.5, 153.8, 172.9 (7-CdO); HRMS (ESI-TOF, [M þ H]þ) calcd
129.7, 132.6, 133.9, 137.0, 138.5, 139.7, 149.4, 166.8 (4-CdO), for C20H13ClN3O4 394.0595, found 394.0595.
173.1 (7-CdO); HRMS (ESI-TOF, [M þ H]þ) calcd for C20H14-
N2O2Cl3 419.0121, found 419.0134. Acknowledgment. This work was financially supported by
10-Chloro-6-(p-tolyl)-1,2,5,6-tetrahydrobenzo[b]imidazo[1,2,3-ij]-
the National Natural Science Foundation of China (No.
[1,8]naphthyridine-4,7-dione (9g): yellow powder; mp 196-198 °C;
IR (KBr, cm-1) 1692, 1648, 1617, 1584, 1540, 1519, 1372, 1229, 824, 20872074 and 21072110), Natural Science Foundation of
783; 1H NMR (DMSO-d6) δ 2.21 (s, 3H, CH3), 2.65 (d, J = 16.5 Shandong Province (No. Z2008B03), and the Doctoral Foun-
Hz, 1H, C(O)CH2), 3.11 (dd, J = 8 Hz, 16.5 Hz, 1H, C(O)CH2), dation of Qingdao University of Science and Technology.
4.11-4.52 (m, 5H, 2 NCH2 þ CH), 7.03-8.07 (m, 7H, ArH); 13C
NMR (DMSO-d6) δ 21.0 (Ar-CH3), 34.1 (6-CH), 42.9 (NCH2), Supporting Information Available: Experimental proce-
45.8 (NCH2), 100.0 (6a-C), 115.7, 123.5, 124.0, 126.9, 128.3, 129.5, dures, copies of 1H NMR, 13C NMR, and HRMS spectra of
136.1, 136.8, 138.3, 141.0, 148.4, 168.1 (4-CdO), 173.3 (7-CdO); all new compounds, and X-ray data for compound 6a (CIF).
HRMS (ESI-TOF, [M þ H]þ) calcd for C21H18ClN2O2 365.1057, This material is available free of charge via the Internet at http://
found 365.1051. pubs.acs.org.