Abstract
Microwave-assisted three-component reaction has been established for the regioselective synthesis of benzo[f]azulen-1-ones. The reaction was performed in aqueous media under microwave irradiation by using readily available and inexpensive starting materials. A total of 38 examples were examined to show a broad substrate scope and good overall yields (70–89%). The present new synthesis shows attractive green chemistry characteristics, such as the use of water as reaction media, concise one-pot conditions, short reaction periods (7–24 min), easy work-up/purification and reduced waste production without the use of any strong acids or metal promoters.
Keywords: Tetronic acid, Benzo[f]azulen-1-ones, Microwave-assisted multicomponent reaction, Aqueous media, Green synthesis
1. Introduction
Heterocycles containing benzodiazepine rings belong to important building blocks because of their remarkable depressant activity in central nervous system1 and their being one of the most widely prescribed class of psychotropics.1h-i In addition, some of these compounds also possess bioactivities on analgesic, sedative ans antidepressive as well as hypnotic activities.2 On the other hand, the derivatives of tetronic acid (tetrahydrofuran-2,4-dione) play an essential role in medicinal chemistry3 by serving as HIV-1 protease inhibiting4, anti-inflammatory,5 antifungal,6 antibiotic,7 insecticidal,8 analgesic,9 anticoagulant10 and antiepileptic11 agents. Consequently, benzoazulen-1-one derivatives containing both benzodiazepine and tetronic acid motifs would provide novel leading structures for combinatorial drug-discovery research.
A careful literature survey revealed that benzo[f]azulen-1-one derivatives have been synthesized by the condensation reaction of 4-(2-aminophenylamino)furan-2(5H)-one with aldehyde in normal organic solvents.12 However, the substrate scope of this reaction is limited. It also suffered by other shortcomings, such as multiple steps, long reaction times, low overall yields and environmental unfriendly and uneconomical. So far, there have been a few benzo[f]azulen-1-one compounds produced via this method. The continuing search for new efficient approaches to benzo[f]azulen-1-ones in terms of mild reaction conditions, operational simplicity, economic viability, eco-friendliness and selectivity remains challenging.
In the past several years, our groups and several others have developed a series of multicomponent domino reactions (MDRs) that can provide easy accesses to multifunctionalized heterocyclic structures of chemical and pharmaceutical interest.13–16 Especially, we established a new four-component domino reaction for an efficient synthesis of multifunctionalized quinazoline derivatives.13a The reaction is easily performed by simply mixing readily available starting materials, aromatic aldehydes, cyclopentanone and cyanoacetamide with K2CO3 in ethylene glycol under microwave (MW) irradiation. Interestingly, when aliphatic aldehydes were employed to replace their aromatic counterparts for the above MDR reaction, the reaction was found to undergo along another pathway leading to the formation of multi-functionalized tricyclo[6.2.2.01,6]dodecanes.13b Recently, we have also found that the MDR of Meldrum’s acid, aromatic aldehydes and electron-rich heteroaryl-amines in aqueous phase under microwave irradiation (MW) led to the multifunctionalized spiro{[1,3]dioxanes-pyridine}-4,6-dione with high chemo- regio- and stereoselectivity and good yields.13d
As a continuation of our research devoted to the development of multicomponent domino reactions,13–15 in this communication we would like to report a new green chemistry approach to benzo[f]azulen-1-one derivatives that are of chemical and biomedical importance (Scheme 1). This reaction was achieved by reacting benzene-1,2-diamines, tetronic acid and aldehydes in aqueous phase under microwave irradiation without use of any metal catalyst as represented in Scheme 1.
Scheme 1.
The synthesis of benzoazulen-1-one derivatives
Results and discussion
We started this methodolody by subjecting 3,4-diaminobenzoic acid 1a to the reaction with 4-chlorobenzaldehyde 2a and tetronic acid 3 as the model case for condition optimization. As shown in Table 1, the use of glacial acetic acid (HOAc) as reaction media at 90 ºC allowed the direct conversion of 3,4-diaminobenzoic acid 1a into the corresponding benzo[f]azulen-1-ones 4a in a chemical yield of 55% under microwave irradiation (Table 1, entry 4). Other organic solvents, such as benzene, DCE, DMF, THF, ethanol and glycol gave much lower yields of 10% - 45% at the same temperature (Table 1, entries 1–3); this is due to the fact that the benzo[d]imidazoles 5 were generated as by-products. Since water is an efficient absorber for microwave irradiation, it often leads to many successful reactions under environmentally friendly conditions.17–18 Under this aqueous system, the three-component reaction of 1a with 2a and 3 resulted in benzo[f]azulen-1-ones 4a with a chemical yield of 51%. The reaction proceeded rapidly to completion at 110 ºC within a few minutes. Increasing reaction temperature did not improve chemical yields. Pleasantly, we found that a higher yield of 4a (86%) was obtained when the reaction was conducted in presence of 0.1 equivalent of HOAc at 110 ºC.
Table 1.
Optimization of solvent and temperature for the synthesis of 4a under MW
| Entry | Solvent | T/ºC | Time/min | Yield/%
|
|
|---|---|---|---|---|---|
| 4a | 5 | ||||
| 1 | Benzene | 90 | 16 | 10 | 61 |
| 2 | DCE | 90 | 16 | 15 | 57 |
| 3 | THF | 90 | 16 | 24 | 48 |
| 4 | DMF | 90 | 16 | 34 | 26 |
| 5 | EtOH | 90 | 16 | 45 | 21 |
| 6 | Glycol | 90 | 16 | 40 | 24 |
| 7 | HOAc | 90 | 14 | 55 | trace |
| 8 | Water | 90 | 16 | 51 | trace |
We then investigated the substrate scope of this reaction by subjecting a series of aromatic aldehyde 2b–i to the reaction with 3,4-diaminobenzoic acid 1a under the optimal condition. As shown in Table 2, the reaction of thiophene-2-carbaldehyde with 3,4-diaminobenzoic acid 1a was finished within 12 min to give thienyl-substituted benzo[f]azulen-1-ones 4h in 85% yield. Similarly, benzo[f]azulen-1-ones 4b–g were formed within 12–15 min in good to excellent yields of 74–89% (Table 2, entries 2–7). Moreover, aliphatic aldehydes, such as 2-phenylacetaldehyde (Table 2, entry 9) still displayed high reactivity and clean conversion under this condition. The similar situation exists for the use of 4-chlorobenzene-1,2-diamine 1b for reactions that occurred rapidly to give the desired products 4j–4n in 76–84% yields (Table 2, entries 10–14). It is worth noting that these reactions showed high regioselectivity; only one single regioisomer was generated when 3,4-diaminobenzoic acid and 4-chlorobenzene-1,2-diamine were employed as substrates. The reason for this excellent selectivity is that the amino group attached on meta position of carboxyl group on the phenyl ring shows higher nucleophilic than that on para position, favoring to condense with tetronic acid. While the halogen substitution has an ortho-para directing effect, the amino group on the para position of chloro group shows higher reactivity than that on meta-position, preferring to form enaminones from the reaction with tetronic acid.
Table 2.
Regioselective synthesis of product 4a-n under MW
| ||||
| Entry | 4 | R1 | Time/min | Yield (%) |
| 1 | 4a | 4-Chlorophenyl (2a) | 12 | 86 |
| 2 | 4b | 4-Bromophenyl (2b) | 12 | 85 |
| 3 | 4c | 2,4-Dichlorophenyl (2c) | 12 | 83 |
| 4 | 4d | 4-Nitrophenyl (2d) | 11 | 89 |
| 5 | 4e | 4-Methylphenyl (2e) | 15 | 83 |
| 6 | 4f | 4-Methoxyphenyl (2f) | 15 | 81 |
| 7 | 4g | 2,3-Dimethoxyphenyl (2g) | 15 | 78 |
| 8 | 4h | 2-Thienyl (2h) | 12 | 74 |
| 9 | 4i | Benzyl (2i) | 16 | 70 |
| 10 | 4j | 4-Chlorophenyl (2a) | 10 | 87 |
| 11 | 4k | 2,4-Dichlorophenyl (2b) | 10 | 84 |
| 12 | 4l | 4-Methylphenyl (2e) | 13 | 81 |
| 13 | 4m | 2-Thienyl (2h) | 11 | 80 |
| 14 | 4n | Benzyl (2i) | 15 | 76 |
After we achieved the above mono-substituted benzene-1,2-diamine-based multicomponent reaction, we then subjected symmetric benzene-1,2-diamine (including 1c and 1d) to the reaction with aromatic aldehydes 2 and tetronic acid under the similar conditions. As shown in Table 3, the corresponding products 4 were generated in good to excellent yields of 81–92% (Scheme 2). The reaction is compatible with various substrates including aldehydes with aromatic, heteroaromatic and aliphatic ones and aromatic diamine component with both Cl and COOH substituents. The products has been unambigeously determined by X-ray structural analysis of single crystals of 4g and 4u, which were obtained by carefully evaporating solvents (Fig. 1 and 2).
Table 3.
Synthesis of products 4o-4ll under MW
 | ||||
|---|---|---|---|---|
| Entry | 4 | R1 | Time/min | Yield (%) |
| 2 | 4p | 4-Nitrophenyl (2d) | 10 | 81 |
| 3 | 4q | 4-Methylphenyl (2e) | 9 | 83 |
| 4 | 4r | 2-Thienyl (2h) | 13 | 78 |
| 5 | 4s | Benzyl (2i) | 12 | 80 |
| 6 | 4t | 4-Chlorophenyl (2a) | 15 | 75 |
| 7 | 4u | 4-Bromophenyl (2b) | 9 | 86 |
| 8 | 4v | 2,4-Dichlorophenyl (2c) | 9 | 86 |
| 9 | 4w | 4-Nitrophenyl (2d) | 8 | 88 |
| 10 | 4x | 2-Chlorophenyl (2j) | 7 | 85 |
| 11 | 4y | 3-Nitrophenyl (2k) | 9 | 84 |
| 12 | 4z | 4-Cyanophenyl (2l) | 7 | 87 |
| 13 | 4aa | Phenyl (2m) | 8 | 89 |
| 14 | 4bb | 4-Methylphenyl (2e) | 11 | 83 |
| 15 | 4cc | 2-Methoxyphenyl (2n) | 12 | 82 |
| 16 | 4dd | 3,4,5-Trimethoxyphenyl (2o) | 12 | 79 |
| 17 | 4ee | 4-Dimethylaminophenyl (2p) | 15 | 76 |
| 18 | 4ff | 2-Thienyl (2h) | 14 | 73 |
| 19 | 4gg | Benzyl (2i) | 11 | 79 |
| 20 | 4hh | Isobutyl (2q) | 15 | 73 |
| 21 | 4ii | sec-butyl (2r) | 16 | 72 |
| 22 | 4jj | 1-Methylbutyl (2s) | 17 | 72 |
| 23 | 4kk | Cyclohexyl (2t) | 17 | 76 |
| 24 | 4ll | Isopropyl (2u) | 16 | 75 |
Scheme 2.
Fig. 1.
ORTEP diagram of 4g
Fig. 2.
ORTEP diagram of 4u
To expand the substrate scope of this reaction, the 2-formylbenzoic acid 2v and 2-formyl-4,5-dimethoxybenzoic acid 2w) were employed to react with benzene-1,2-diamine (1c, 1d, or 4,5-dimethylbenzene-1,2-diamine 1e) and tetronic acid 3 (Scheme 3). To our delight, under the above optimized conditions, these reactions proceeded smoothly to give pentacyclic isoindole-fused furo[1,4]diazepines 5a-5f in good to excellent yields (Table 4, entries 1–6). Excellent regioseclectivity was observed in this three-component reaction involving 3,4-diaminobenzoic acid and 2-formylbenzoic acid (Table 4, entries 7–8). It is worth noting that this result is significant with no literature precedent regarding the synthesis of highly functionalized isoindole-fused furo[1,4]diazepines.
Scheme 3.
Table 4.
Synthesis of products 5 under MW
| Entry | Product | Time / min | Yield / % |
|---|---|---|---|
| 1 | 5a, R4 = R2 =R3 = H | 15 | 85 |
| 2 | 5b, R4 = OMe, R2 =R3 = H | 18 | 83 |
| 3 | 5c, R4 = H, R2 =R3 = Me | 20 | 88 |
| 4 | 5d, R4 = OMe, R2 =R3 = Me | 24 | 86 |
| 5 | 5e, R4 = H, R2 =R3 = Cl | 18 | 84 |
| 6 | 5f, R4 = OMe, R2 =R3 = Cl | 18 | 82 |
| 7 | 5g, R4 =H, R2 = COOH, R3 = H | 15 | 81 |
| 8 | 5h, R4 =OMe, R2 = COOH, R3 = H | 16 | 80 |
Similar to our previous multicomponent domino processes,13 the present reaction also showed the following attractive characteristics: (1) fast reaction rates which enable the reaction to be completed within 7–17 min, which can save energy and manpower for future industrial production; (2) the environmentally friendly process in which water is used as a solvent; (3) the convenient work-up which only needs simple filtration since the products directly precipitate out after the reaction is finished, which belongs to GAP chemistry;19–20 (4) readily available starting materials of aldehydes, substituted benzene-1,2-diamine and tetronic acid.
In according to a similar mechanism,12 the formation of 4 is likely to proceed via initial condensation of benzene-1,2-diamine 1 and tetronic acid 3 to give enaminone 6. The following addition of aldehydes 2 to enaminone 6 furnishes the formation of intermediate 7 which is then converted into the final procuct 4 through intramolecular cyclization (Scheme 4). The carbonyl substituent on the aromatic ring 2 was dehydrated upon the treatment with amino group, leading to the formation of pentacyclic isoindole-fused furo[1,4]diazepines. Based on this mechanism, the regioselectivity is controlled by the strong nucleophilicity of amino group on starting material 1, i.e., the formation of 4a-4n depends on the higher nucleophilicity of the amino group in the meta position of carboxyl group than in that on para position.
Scheme 4.
Conclusion
In conclusion, a new microwave-assisted multi-component reaction have been established to afford benzo[f]azulen-1-one and isoindole-fused furo[1,4]diazepine derivatives that can serve as versatile building blocks for both organic and medicinal research. The reactions were conducted in aqueous solution under microwave irradiation using readily available and inexpensive starting materials. The directing effects of substituents on benzene-1,2-diamine ring have been proven to control regioselectivity efficiently. This green synthesis shows several attractive characteristics such as the use of water as reaction media, concise conditions, short reaction periods, easy work-up, and reduced waste production without the use of any strong acids or metal promoters.
Experimental section
Microwave irradiation was carried out with microwave oven Emrys™ Creator from Personal Chemistry, Uppsala, Sweden. Melting points were determined in open capillaries and were uncorrected. IR spectra were taken on a FT-IR-Tensor 27 spectrometer in KBr pellets and reported in cm−1. 1H NMR spectra were measured on a Bruker DPX 400 MHz spectrometer in DMSO-d6 with chemical shift (δ) given in ppm relative to TMS as internal standard. HRMS (ESI) was determined by using microTOF-Q II HRMS/MS instrument (Bruker). X-Ray crystallographic analysis was performed with a Siemens SMART CCD and a Siemens P4 diffractometer.
General procedure for the synthesis of benzo[f]azulen-1-ones 4a
In a 10-mL reaction vial, the benzene-1,2-diamine 1a (1 mmol), tetronic acid 3 (1 mmol), acetic acid (0.1 mmol) and water (2 mL) were mixed and then stiring for 30 min. Subsequently, the aldehydes 2a (1 mmol) was added to the reaction mixture, and the reaction vial was capped and pre-stiring for 20 second. The mixture was subjected to microwave irradiation at 200W (initial power 100W, maximum power 200W) at 110 ºC, for a given time. Upon completion, monitored by TLC, the reaction mixture was cooled to room temperature, filtered to give the crude product, which was further washed by 50% EtOH to give pure product 4a.
10-(4-Chlorophenyl)-1-oxo-3,4,9,10-tetrahydro-1H-2-oxa-4,9-diaza-benzo[f]azulene-6-carboxylic acid 4a
Pale white solid, Mp: 281–282 ºC
IR(KBr): 3373, 3323, 3134, 1725, 1691, 1672, 1601, 1571, 1390, 1197, 1164, 1133, 1051, 1012, 832, 820, cm−1
1HNMR (400 MHz, DMSO-d6): 12.53 (s, 1H, COOH), 10.10 (s, 1H, NH), 7.57 (d, J = 1.6 Hz, 1H, ArH), 7.31–7.27 (m, 3H, ArH), 7.16 (d, J = 8.8 Hz, 2H, ArH), 6.71–6.68 (m, 2H, ArH and NH), 5.08 (d, J = 4.4 Hz, 1H, CH), 4.91 (s, 2H, CH2)
HRMS (ESI) m/z: calc. for [M+H+] C18H14ClN2O4: 357.0637; found: 357.0649.
10-(4-Bromophenyl)-1-oxo-3,4,9,10-tetrahydro-1H-benzo[b]furo[3,4-e][1,4]diazepine-6-carboxylic acid 4b
Pale white solide Mp: 272–273 ºC
IR(KBr): 3360, 3294, 1726, 1705, 1650, 1570, 1516, 1505, 1418, 1406, 1357, 1232, 1184, 1125, 1111, 1039, 1008, 827, cm−1
1HNMR (400 MHz, DMSO-d6): 12.55 (s, 1H, COOH), 10.10 (s, 1H, NH), 7.58 (1H, d, J = 1.6 Hz, ArH), 7.41 (2H, d, J = 8.4 Hz, ArH), 7.30 (dd, J = 1.6, 16.0 Hz, 1H, ArH), 7.10 (d, J = 8.4 Hz, 2H, ArH) 6.71–6.69 (m, 2H, ArH and NH), 5.07 (d, J = 4.4 Hz, 1H, CH), 4.91 (s, 2H, CH2)
HRMS (ESI) m/z: calc. for [M+H+] C18H14BrN2O4: 401.0132; found: 401.0105.
10-(2,4-Dichlorophenyl)-1-oxo-3,4,9,10-tetrahydro-1H-benzo[b]furo[3,4-e][1,4]diazepine-6-carboxylic acid 4c
Pale white solid, Mp: 285–287 ºC
IR(KBr): 3379, 3322, 1724, 1692, 1660, 1571, 1511, 1463, 1392, 1358, 1198, 1167, 1137, 1046, 880, 855, 821, 756 cm−1
1HNMR (400 MHz, DMSO-d6): 12.58 (s, 1H, COOH), 10.21 (s, 1H, NH), 7.61 (d, J = 1.6 Hz, 2H, ArH), 7.29 (dd, J = 1.6, 16.8 Hz, 1H, ArH), 7.17 (dd, J = 2.0, 16.8 Hz, 1H, ArH), 6.83 (d, J = 8.4Hz, 1H, ArH), 6.72 (d, J = 8.4Hz, 1H, ArH), 6.36 (d, J = 4.4 Hz, 1H, NH), 5.45 (d, J = 4.4 Hz, 1H, CH), 4.94 (s, 2H, CH2)
HRMS (ESI) m/z: calc. for [M+H+] C18H13Cl2N2O4: 391.0247; found: 391.0219.
10-(4-Nitrophenyl)-1-oxo-3,4,9,10-tetrahydro-1H-2-oxa-4,9-diazabenzo[f]azulene-6-carboxylic acid 4d
Pale white solid, Mp: >300 ºC
IR(KBr): 3358, 3316, 3137, 1727, 1686, 1667, 1602, 1572, 1521, 1509, 1240, 1199, 1185, 1163, 1129, 1049, 1017, 820, cm−1
1HNMR (400 MHz, DMSO-d6): 12.58 (s, 1H, COOH), 10.21 (s, 1H, NH), 8.10 (d, J = 8.8 Hz, 1H, ArH), 7.62 (s, 1H, ArH), 7.41 (d, J = 8.8 Hz, 2H, ArH), 7.31 (d, J = 8.4Hz, 1H, ArH), 6.84 (d, J = 4.4 Hz, 1H, NH), 6.72 (d, J = 8.4 Hz, 1H, ArH), 5.21 (d, J = 4.0 Hz, 1H, CH), 4.94 (s, 2H, CH2)
13CNMR (100 MHz, DMSO-d6, 25 ºC) (δ, ppm): 172.9, 167.3, 159.2, 151.7, 146.8, 141.3, 130.4, 128.6, 124.8, 124.0, 122.5, 122.5, 121.8, 96.0, 66.7, 57.0
HRMS (ESI) m/z: calc. for [M+H+] C18H14N3O6: 368.0878; found: 368.0865.
1-Oxo-10-p-tolyl-3,4,9,10-tetrahydro-1H-2-oxa-4,9-diazabenzo[f]azulene-6-carboxylic acid 4e
Pale white solid, Mp: 278–280 ºC
IR(KBr): 3361, 1724, 1702, 1650, 1570, 1513, 1359, 1186, 1170, 1123, 1039, 1008, 754 cm−1
1HNMR (400 MHz, DMSO-d6): 12.49 (s, 1H, COOH), 10.02 (s, 1H, NH), 7.56 (s, 1H, ArH), 7.28 (d, J = 8.0 Hz, 1H, ArH), 7.02 (t, J = 8.4 Hz, 4H, ArH), 6.69 (d, J = 8.4Hz, 1H, ArH), 6.65 (d, J = 4.0 Hz, 1H, NH), 5.05 (d, J = 4.0 Hz, 1H, CH), 4.90 (s, 2H, CH2), 2.19 (s, 3H, CH3)
13CNMR (100 MHz, DMSO-d6, 25 ºC) (δ, ppm): 173.1, 167.3, 158.7, 142.2, 141.2, 136.3, 130.5, 129.2, 127.2, 124.6, 122.7, 122.4, 121.5, 97.3, 66.5, 57.1, 21.0
HRMS (ESI) m/z: calc. for [M+Na+] C19H16NaN2O4: 359.1003; found: 359.0991.
10-(4-Methoxyphenyl)-1-oxo-3,4,9,10-tetrahydro-1H-benzo[b]furo[3,4-e][1,4]diazepine-6-carboxylic acid 4f
Pale white solid, Mp: 251–253 ºC
IR(KBr): 3361, 3079, 1724, 1651, 1570, 1511, 1410, 1347, 1252, 1177, 1114, 1038, 1008, 831, 760 cm−1
1HNMR (400 MHz, DMSO-d6): 12.46 (s, 1H, COOH), 10.02 (s, 1H, NH), 7.55 (d, 1H, J = 1.6 Hz, ArH), 7.27 (dd, J = 1.6 Hz, 16.8 Hz, 1H, ArH), 7.05 (d, J = 8.8 Hz, 2H, ArH), 6.75 (d, J = 8.8 Hz, 1H, ArH), 6.68 (d, J = 8.4 Hz, 1H, ArH), 6.63 (d, J = 4.4 Hz, 1H, NH), 5.02 (d, J = 4.4 Hz, 1H, CH), 4.89 (s, 2H, CH2), 3.65 (s, 3H, CH3)
HRMS (ESI) m/z: calc. for [M+H+] C19H17N2O5: 353.1132; found: 353.1119.
10-(2,3-Dimethoxyphenyl)-1-oxo-3,4,9,10-tetrahydro-1H-benzo[b]furo[3,4-e][1,4]diazepine-6-carboxylic acid 4g
Pale white solid, Mp: >300 ºC
IR(KBr): 3366, 3326, 3250, 3074, 2973, 1720, 1643, 1574, 1514, 1484, 1415, 1393, 1348, 1280, 1259, 1053, 1041, 1000, 852, cm−1
1HNMR (400 MHz, DMSO-d6): 12.51 (s, 1H, COOH), 10.10 (s, 1H, NH), 7.60 (d, 1H, J = 1.6 Hz, ArH), 7.25 (dd, J = 2.0, 16.4 Hz, 1H, ArH), 6.86–6.83 (m, 1H, ArH), 6.77 (t, J = 8.0 Hz, 1H, ArH), 6.66 (d, J = 8.4 Hz, 1H, ArH), 6.26–6.24 (m, 1H, ArH), 6.12 (d, J = 4.4 Hz, 1H, NH), 5.42 (d, J = 4.4 Hz, 1H, CH), 4.91 (s, 2H, CH2), 3.89 (s, 3H, CH3), 3.78 (s, 3H, CH3)
HRMS (ESI) m/z: calc. for [M+Na+] C20H18NaN2O6: 405.1058; found: 405.1073.
1-Oxo-10-thien-2-yl-3,4,9,10-tetrahydro-1H-2-oxa-4,9-diazabenzo[f]azulene-6-carboxylic acid 4h
Pale white solid, Mp: 285–286 ºC
IR(KBr): 3336, 3305, 1720, 1696, 1652, 1572, 1508, 1404, 1353, 1267, 1227, 1144, 1043, 1007, 891, 828 cm−1.
1HNMR (400 MHz, DMSO-d6): 12.56 (s, 1H, COOH), 10.07 (s, 1H, NH), 7.55 (d, J = 0.8Hz, 1H, Thienyl-H), 7.35–7.33 (m, 1H, ArH), 7.26–7.25 (m, 1H, ArH), 6.85 (t, J = 4.0 Hz, 2H, Thienyl-H), 6.80 (d, J = 8.4 Hz, 1H, ArH), 6.77 (d, J = 4.8 Hz, 1H, NH), 5.30 (d, J = 4.4 Hz, 1H, CH), 4.88 (dd, J = 15.6, 17.8 Hz, 2H, CH2)
HRMS (ESI) m/z: calc. for [M+H+] C16H12N2NaO4S: 351.0410; found: 351.0409.
10-Benzyl-1-oxo-3,4,9,10-tetrahydro-1H-2-oxa-4,9-diazabenzo[f]azulene-6-carboxylic acid 4i
Pale white solid, Mp: 249–250 ºC
IR(KBr): 3524, 3350, 3299, 3132, 1688, 1637, 1573, 1516, 1497, 1422, 1353, 1277, 1252, 1231, 1190, 1129, 1047, 1027, 980 cm−1.
1HNMR (400 MHz, DMSO-d6): 12.46 (s, 1H, COOH), 9.81 (s, 1H, NH), 7.51 (d, J = 1.6 Hz, 1H, ArH), 7.37 (dd, J = 2.0, 8.0 Hz, 1H, ArH), 7.24–7.21 (m, 2H, ArH), 7.18–7.14 (m, 1H, ArH), 7.03 (d, J = 7.2 Hz, ArH), 6.78 (1H, d, J = 8.4 Hz, ArH), 6.22 (1H, d, J = 4.4 Hz, 2H, NH), 4.80 (d, J = 15.2 Hz, CH2), 4.69 (d, J = 15.2 Hz, CH2), 4.15–4.11 (m, 1H, CH), 2.85–2.81 (m, 1H, CH2), 2.71–2.65 (m, 1H, CH2)
HRMS (ESI) m/z: calc. for [M+H+] C19H17N2O4: 337.1183; found: 337.1190.
7-Chloro-10-(4-chlorophenyl)-3,4,9,10-tetrahydro-2-oxa-4,9-diazabenzo[f]azulen-1-one 4j
Pale white solide solid, Mp: 250–252 ºC
IR(KBr): 3345, 3273, 3140, 3095, 1715, 1666, 1621, 1563, 1499, 1420, 1398, 1363, 1186, 1057, 1031, 1014, 999, 872 cm−1.
1HNMR (400 MHz, DMSO-d6): 10.00 (s, 1H, NH), 7.31–7.29 (m, 2H, ArH), 7.15–7.13 (m, 2H, ArH), 6.90 (d, J = 8.4 Hz, 1H, ArH), 6.80–6.78 (m, 1H, ArH), 6.68–6.67 (m, 1H, ArH), 6.36 (d, J = 4.4 Hz, 1H, NH), 5.05 (d, J = 4.0 Hz, 1H, CH), 4.90 (s, 2H, CH2)
HRMS (ESI) m/z: calc. for [M+H+] C17H13Cl2N2O2: 347.0349; found: 347.0343.
7-Chloro-10-(2,4-dichlorophenyl)-3,4,9,10-tetrahydro-2-oxa-4,9-diazabenzo[f]azulen-1-one 4k
Pale white solid, Mp: 272–274 ºC
IR(KBr): 3387, 3274, 3088, 1722, 1710, 1628, 1569, 1501, 1464, 1411, 1354, 1331, 1237, 1184, 1103, 1046, 967, 868 cm−1.
1HNMR (400 MHz, DMSO-d6): 10.13 (s, 1H, NH), 7.64 (d, J = 2.0 Hz, 1H, ArH), 7.19 (dd, J = 2.0, 8.4 Hz, 1H, ArH), 6.96 (d, J = 8.8 Hz, 1H, ArH), 6.84 (dd, J = 2.4, 8.6 Hz, 1H, ArH), 6.82 (d, J = 8.4 Hz, 1H, ArH), 6.72 (d, J = 2.4 Hz, 1H, ArH), 6.05 (d, J = 4.4 Hz, 1H, NH), 5.41 (d, J = 4 Hz, 1H, CH), 4.94 (s, 2H, CH2)
HRMS (ESI) m/z: calc. for [M+Na+] C17H11Cl3N2NaO2: 402.9779; found: 402.9796.
7-Chloro-10-p-tolyl-3,4,9,10-tetrahydro-2-oxa-4,9-diazabenzo[f]azulen-1-one 4l
Pale white solid, Mp: 287–289 ºC
IR(KBr): 3346, 3248, 3092, 1716, 1667, 1654, 1564, 1499, 1420, 1405, 1364, 1331, 1187, 1057, 1032, 998, 867 cm−1.
1HNMR (400 MHz, DMSO-d6): 9.94 (s, 1H, NH), 7.04–6.99 (m, 4H, ArH), 6.88 (d, J = 8.4 Hz, 1H, ArH), 6.77–6.75 (m, 1H, ArH), 6.66 (s, 1H, ArH), 6.31 (d, J = 4.4 Hz, 1H, NH), 5.01 (d, J = 4.0 Hz, 1H, CH), 4.90 (s, 2H, CH2), 2.21 (s, 3H, CH3)
HRMS (ESI) m/z: calc. for [M+H+] C18H16ClN2O2: 327.0895; found: 327.0878.
7-Chloro-10-(2-methoxyphenyl)-3,4,9,10-tetrahydro-1H-benzo[b]furo[3,4-e][1,4]diazepin-1-one 4m
Pale white solid, Mp: 248–251 ºC
IR(KBr): 3357, 3248, 3154, 1717, 1672, 1617, 1572, 1503, 1408, 1368, 1064, 1053,1013, 1000, 777 cm−1.
1HNMR (400 MHz, DMSO-d6): 9.96 (s, 1H, NH), 7.18 – 7.12 (m, 1H, ArH), 7.00 (d, J = 8.0 Hz, 1H, ArH), 6.87 (d, J = 8.4 Hz, 1H, ArH), 6.75 (dd, J = 8.4, 2.0 Hz, 1H, ArH), 6.68–6.60 (m, 3H, ArH), 5.75 (d, J = 4.4 Hz, 1H, NH), 5.34 (d, J = 4.4 Hz, 1H, CH), 4.98–4.89 (m, 2H, CH2), 3.90 (s, 3H, CH3).
HRMS (ESI) m/z: calc. for [M+Na+] C18H15ClN2O3Na 365.0664; found: 365.0654.
7-Chloro-10-thien-2-yl-3,4,9,10-tetrahydro-2-oxa-4,9-diazabenzo[f]azulen-1-one 4n
Pale yellow solid, Mp: 294–296 ºC
IR(KBr): 3337, 3244, 3069, 1716, 1667, 1617, 1567, 1499, 1413, 1365, 1190, 1000, 868, 849, 808 cm−1.
1HNMR (400 MHz, DMSO-d6): 9.99 (s, 1H, NH), 7.28–7.27 (m, 1H, ArH), 6.90–6.86 (m, 2H, ArH), 6.83–6.79 (m, 3H, Thienyl-H), 6.77–6.69 (m, 2H, ArH), 6.43 (d, J = 4.4 Hz, 1H, NH), 5.27 (d, J = 4.4 Hz, 1H, CH), 4.87 (dd, J = 15.6, 20.0 Hz, 2H, CH2)
HRMS (ESI) m/z: calc. for [M+H+] C15H12ClN2O2S: 319.0303; found: 319.0290.
10-Benzyl-7-chloro-3,4,9,10-tetrahydro-2-oxa-4,9-diaza-benzo[f]azulen-1-one 4o
White solid, Mp: 234–235 ºC
IR(KBr): 3379, 3276, 3107, 3027, 1721, 1637, 1569, 1496, 1490, 11417, 1362, 1339, 1190, 1037, 1028, 983 cm−1.
1HNMR (400 MHz, DMSO-d6): 9.77 (s, 1H, NH), 7.27 (t, J = 7.2 Hz, 2H, ArH), 7.19 (t, J = 7.8 Hz, 1H, ArH), 7.06 (d, J = 7.2 Hz, 2H, ArH), 6.87 (d, J = 8.4 Hz, 1H, ArH), 6.82–6.78 (m, 2H, ArH), 5.87 (d, J = 4.4 Hz, 1H, NH), 4.77 (dd, J = 15.2, 20.2 Hz, 2H, CH2), 4.11–4.06 (m, 1H, CH), 2.79–2.75 (m, 1H, CH2), 2.68–2.63 (m, 1H, CH2)
HRMS (ESI) m/z: calc. for [M+H+] C18H16ClN2O2: 327.0895; found: 327.0911.
6,7-Dichloro-10-(2,4-dichloro-phenyl)-3,4,9,10-tetrahydro-2-oxa-4,9-diazabenzo[f]azulen-1-one 4p
Pale white solid, Mp: 211–213 ºC
IR(KBr): 3371, 3242, 3074, 1724, 1643, 1563, 1483, 1342, 1183, 1148, 1105, 1042, 1013, 879, 868 cm−1.
1HNMR (400 MHz, DMSO-d6): 10.21 (s, 1H, NH), 7.64 (d, 1H, J = 2.0 Hz, ArH), 7.21 (dd, J = 2.0, 16.8 Hz, 1H, ArH), 7.13 (s, 1H, ArH), 6.91 (s, 1H, ArH), 6.83 (d, J = 8.4 Hz, 1H, ArH), 6.19 (d, J = 4.4 Hz, 1H, NH), 5.41 (d, J = 4.4 Hz, 1H, CH), 4.95 (dd, J = 15.6, 17.4 Hz, 2H, CH2)
HRMS (ESI) m/z: calc. for [M+H+] C17H11Cl4N2O2: 414.9570; found: 414.9551.
6,7-Dichloro-10-(4-nitro-phenyl)-3,4,9,10-tetrahydro-2-oxa-4,9-diazabenzo[f]azulen-1-one 4q
Pale yellow solid, Mp: 296–297 ºC
IR(KBr): 3367, 3256, 3093, 1721, 1647, 1570, 1518, 1488, 1405, 1348, 1244, 1185, 1152, 1049, 1017, 875, 861 cm−1
1HNMR (400 MHz, DMSO-d6): 10.21 (s, 1H, NH), 8.13 (d, J = 8.4 Hz, 2H, ArH), 7.40 (d, J = 8.8 Hz, 2H, ArH), 7.12 (s, 1H, ArH), 6.89 (s, 1H, ArH), 6.64 (d, J = 4.4 Hz, 1H, NH), 5.21 (d, J = 4.0 Hz, 1H, CH), 4.96 (dd, J = 15.6, 18.6 Hz, 2H, CH2)
HRMS (ESI) m/z: calc. for [M+H+] C17H12Cl2N3O4: 392.0200; found: 392.0178.
6,7-Dichloro-10-p-tolyl-3,4,9,10-tetrahydro-2-oxa-4,9-diazabenzo[f]azulen-1-one 4r
Pale white solid, Mp: 282–284 ºC
IR(KBr): 3350, 3286, 3093, 1724, 1646, 1566, 1487, 1403, 1344, 1328, 1242, 1183, 1149, 1044, 1008, 873 cm−1.
1HNMR (400 MHz, DMSO-d6): 10.03 (s, 1H, NH), 7.05–6.98 (m, 5H, ArH), 6.83 (s, 1H, ArH), 6.44 (d, J = 4.4 Hz, 1H, NH), 5.01 (d, J = 4.4 Hz, 1H, CH), 4.91 (s, 2H, CH2), 2.21 (s, 3H, CH3)
HRMS (ESI) m/z: calc. for [M+H+] C18H15Cl2N2O2: 361.0506; found: 361.0495.
6,7-Dichloro-10-thien-2-yl-3,4,9,10-tetrahydro-2-oxa-4,9-diazabenzo[f]azulen-1-one 4s
Pale white solid, Mp: 261–263 ºC
IR(KBr): 3335, 3247, 3096, 2943, 1718, 1665, 1639, 1561, 1487, 1407, 1342, 1255, 1227, 1177, 1143, 1039, 1006, 876 cm−1.
1HNMR (400 MHz, DMSO-d6): 10.08 (s, 1H, NH), 7.29 (d, 1H, J = 5.2 Hz, Thienyl-H), 7.06 (s, 1H, ArH), 6.96 (s, 1H, ArH), 6.88 (m, 1H, Thienyl-H), 6.83 (d, J = 2.8 Hz, 1H, ArH), 6.55 (d, J = 4.4 Hz, 1H, NH), 5.28 d, J = 4.4 Hz, 1H, CH), 4.89 (dd, J = 15.2, 23.6 Hz, 2H, CH2)
HRMS (ESI) m/z: calc. for [M+Na+] C15H10Cl2NaN2O2S: 374.9733; found: 374.9731.
10-Benzyl-6,7-dichloro-3,4,9,10-tetrahydro-2-oxa-4,9-diazabenzo[f]azulen-1-one 4t
White solid, Mp: 276–277 ºC
IR(KBr): 3353, 3299, 3141, 3100, 3028, 1715, 1647, 1602, 1566, 1486, 1416, 1338, 1246, 1187, 1140, 1043, 1028, 987, 870 cm−1.
1HNMR (400 MHz, DMSO-d6): 9.83 (s, 1H, NH), 7.27–7.23 (m, 2H, ArH), 7.20–7.17 (m, 1H, ArH), 7.05 (d, J = 7.2 Hz, 2H, ArH), 7.01 (s, 1H, ArH), 6.93 (s, 1H, ArH), 6.03 (d, J = 4.4 Hz, 1H, NH), 4.78 (dd, J = 15.2, 23.6 Hz, 2H, CH2), 4.12–4.08 (m, 1H, CH), 2.82–2.77 (m, 1H, CH2), 2.70–2.65 (m, 1H, CH2)
HRMS (ESI) m/z: calc. for [M+H+] C18H15Cl2N2O2: 361.0506; found: 361.0491.
10-(4-Chlorophenyl)-3,4,9,10-tetrahydro-2-oxa-4,5,9-triazabenzo[f]azulen-1-one 4u
White solid, Mp: 262–264 ºC
IR(KBr): 3352, 3247, 3150, 3104, 3083, 1716, 1670, 1617, 1595, 1568, 1508, 1478, 1390, 1365, 1062, 1052, 1032, 1011 cm−1.
1HNMR (400 MHz, DMSO-d6): 9.87 (s, 1H, NH), 7.25 (d, J = 8.0 Hz, 2H, ArH), 7.15 (d, J = 8.4 Hz, 2H, ArH), 6.90 (d, J = 7.6 Hz, 1H, ArH), 6.77–6.69 (m, 2H, ArH), 6.59 (d, J = 7.2 Hz, 1H, ArH), 6.09 (d, J = 4.4 Hz, 1H, NH), 5.06 (d, J = 4.0 Hz, 1H, CH), 4.90 (s, 2H, CH2)
13CNMR (100 MHz, DMSO-d6, 25 ºC) (δ, ppm): 173.2, 159.5, 143.1, 137.5, 132.1, 131.7, 129.4, 128.4, 123.5, 123.4, 121.4, 120.1, 96.7, 66.6, 57.2
HRMS (ESI) m/z: calc. for [M+H+] C17H14ClN2O2: 313.0739; found: 313.0712.
10-(4-Bromophenyl)-3,4,9,10-tetrahydro-2-oxa-4,9-diazabenzo[f]azulen-1-one 4v
White solid, Mp: >300 ºC
IR(KBr): 3352, 3247, 3150, 3104, 1716, 1670, 1617, 1595, 1568, 1508, 1478, 1454, 1403, 1390, 1365, 1334, 1062, 1052, 774, cm−1.
1HNMR (400 MHz, DMSO-d6): 9.88 (s, 1H, NH), 7.39 (d, J = 8.0 Hz, 2H, ArH), 7.09 (d, J = 8.4 Hz, 2H, ArH), 6.90 (d, J = 7.6 Hz, 1H, ArH), 6.77–6.69 (m, 2H, ArH), 6.59 (d, J = 7.6 Hz, 1H, ArH), 6.09 (d, J = 4.4 Hz, 1H, NH), 5.04 (d, J = 4.0 Hz, 1H, CH), 4.90 (s, 2H, CH2)
13CNMR (100 MHz, DMSO-d6, 25 ºC) (δ, ppm): 173.2, 159.5, 143.6, 137.5, 132.1, 131.3, 129.8, 123.5, 123.4, 121.4, 120.2, 120.1, 96.7, 66.6, 57.3
HRMS (ESI) m/z: calc. for [M+Na+] C17H13BrNaN2O2: 379.0053; found: 379.0037.
10-(2,4-Dichlorophenyl)-3,4,9,10-tetrahydro-2-oxa-4,9-diazabenzo[f]azulen-1-one 4w
White solid, Mp: 204–205 ºC
IR(KBr): 3352, 3247, 3150, 3104, 3083, 1716, 1670, 1617, 1595, 1568,1508, 1478, 1403, 1390, 1365, 1334, 1062, 1032, 774, cm−1.
1HNMR (400 MHz, DMSO-d6):10.00 (s, 1H, NH), 7.60 (s, 1H, ArH), 7.14 (d, J = 8.0 Hz, 1H, ArH), 6.96 (d, J = 8 Hz, 1H, ArH), 6.81 (m, 2H, ArH), 6.71 (t, J = 7.6 Hz, 1H, ArH), 6.58 (d, J = 7.6 Hz, 1H, ArH), 5.71 (d, J = 4.0 Hz, 1H, NH), 5.41 (d, J = 4.4 Hz, 1H, CH), 4.94 (s, 2H, CH2)
13CNMR (100 MHz, DMSO-d6, 25 ºC) (δ, ppm): 172.7, 160.4, 139.6, 136.6, 134.6, 132.7, 132.7, 129.3, 129.3, 127.2, 123.8, 122.2, 120.1, 96.0, 66.8, 54.8
HRMS (ESI) m/z: calc. for [M+H+] C17H13Cl2N2O2: 347.0349; found: 347.0347.
10-(4-Nitrophenyl)-3,4,9,10-tetrahydro-2-oxa-4,9-diazabenzo[f]azulen-1-one 4x
Yellow solid, Mp: 219–220 ºC
IR(KBr): 3352, 3247, 3150, 3104, 3083, 1716, 1670, 1617, 1595, 1568,1508, 1478, 1403, 1390, 1365, 1334, 1062, 1032, 774, cm−1.
1HNMR (400 MHz, DMSO-d6): 9.99 (s, 1H, NH), 8.08 (d, J = 8.0 Hz, 2H, ArH), 7.40 (d, J = 8.4 Hz, 2H, ArH), 6.94 (d, J = 7.6 Hz, 1H, ArH), 6.78 (t, J = 7.2 Hz, 1H, ArH), 6.72 (d, J = 7.2 Hz, 1H, ArH), 6.61 (d, J = 7.6 Hz, 1H, ArH), 6.26 (d, J = 4.4 Hz, 1H, NH), 5.18 (d, J = 4.4 Hz, 1H, CH), 4.94 (s, 2H, CH2)
13CNMR (100 MHz, DMSO-d6, 25 ºC) (δ, ppm): 173.1, 159.7, 151.8, 146.7, 137.1, 132.0, 128.7, 123.7, 123.7, 123.3, 121.7, 120.3, 96.0, 66.7, 57.4
HRMS (ESI) m/z: calc. for [M+H+] C17H14N3O4: 324.0979; found: 324.0956.
10-(2-Chlorophenyl)-3,4,9,10-tetrahydro-2-oxa-4,9-diazabenzo[f]azulen-1-one 4y
White solid, Mp: 233–235 ºC
IR(KBr):3395, 3156, 3063, 2989, 2952, 2930, 2899, 1725, 1652, 1574, 1506, 1484, 1444, 1398, 1363, 1233, 1122, 1046, 985, cm−1
1HNMR (400 MHz, DMSO-d6): 9.98 (s, 1H, NH),7.43 (d, J = 4.0 Hz, 1H, ArH), 7.16 (t, J = 7.2 Hz, 1H, ArH), 7.03 (t, J = 7.6 Hz, 1H, ArH), 6.96 (d, J = 7.6 Hz, 1H, ArH), 6.79 (t, J = 7.6 Hz, 2H, ArH), 6.68 (t, J = 7.2 Hz, 1H, ArH), 6.56 (d, J = 7.6 Hz, 1H, ArH), 5.63 (d, J = 4.4 Hz, 1H, NH), 5.47 (d, J = 4.4 Hz, 1H, CH), 4.95 (s, 2H, CH2)
13CNMR (100 MHz, DMSO-d6, 25 ºC) (δ, ppm): 172.8, 160.4, 140.4, 136.7, 133.7, 132.6, 130.0, 129.2, 128.0, 127.1, 123.7, 123.6, 122.0,120.0,96.4, 66.7, 55.3
HRMS (ESI) m/z: calc. for [M+H+] C17H14ClN2O2: 313.0739; found: 313.0724.
10-(3-Nitrophenyl)-3,4,9,10-tetrahydro-2-oxa-4,9-diazabenzo[f]azulen-1-one 4z
Yellow solid, Mp: 252–255 ºC
IR(KBr): 3352, 3247, 3150, 3104, 3083, 1716, 1670, 1617, 1595, 1568, 1478, 1454, 1438, 1403, 1365, 1062, 1032, 1011, 774, cm−1.
1HNMR (400 MHz, DMSO-d6): 9.97 (s, 1H, NH), 8.09 (s, 1H, ArH), 8.00 (d, J = 8.0 Hz, 1H, ArH), 7.55–7.47 (m, 2H, ArH), 6.94 (d, J = 7.6 Hz, 1H, ArH), 6.79–6.70 (m, 2H, ArH), 6.62 (d, J = 8.0 Hz, 1H, ArH), 6.25 (d, J = 4.4 Hz, 1H, NH), 5.22 (d, 1H, J = 4 Hz, CH), 4.95 (s, 2H, CH2)
13CNMR (100 MHz, DMSO-d6, 25 ºC) (δ, ppm): 173.2, 159.9, 148.1, 146.4, 137.1, 133.9, 132.2, 130.0, 123.7, 123.4, 122.4, 122.2, 121.8, 120.3, 96.1, 66.7, 57.4
HRMS (ESI) m/z: calc. for [M+H+] C17H14N3O4: 324.0979; found: 324.0957.
4-(1-Oxo-3,4,9,10-tetrahydro-1H-2-oxa-4,9-diazabenzo[f]azulen-10-yl)-benzonitrile 4aa
Pale white solid, Mp: 279–281 ºC
IR(KBr): 3352, 3247, 3150, 3104, 3083, 1716, 1670, 1617, 1595, 1508, 1478, 1454, 1438, 1390, 1365, 1334, 1062, 1032, 774, cm−1.
1HNMR (400 MHz, DMSO-d6): 9.96 (s, 1H, NH),7.68 (d, J = 8.4 Hz, 2H, ArH), 7.32 (d, J = 8.0 Hz, 2H, ArH), 6.93 (d, J = 7.2 Hz, 1H, ArH), 6.79–6.70 (m, 2H, ArH), 6.59 (d, J = 7.6 Hz, 1H, ArH), 6.22 (d, J = 4.0 Hz, 1H, NH), 5.12 (d, J = 4 Hz, 1H, CH), 4.92 (s, 2H, CH2)
13CNMR (100 MHz, DMSO-d6, 25 ºC) (δ, ppm): 173.1, 159.7, 149.7, 137.2, 132.5, 132.0, 128.5, 123.6, 123.3, 121.6, 120.2, 119.2, 109.9, 96.0, 66.7, 57.6
HRMS (ESI) m/z: calc. for [M+H+] C18H14N3O2: 304.1081; found: 304.1071.
10-Phenyl-3,4,9,10-tetrahydro-2-oxa-4,9-diazabenzo[f]azulen-1-one 4bb
White solid, Mp: 290–291 ºC
IR(KBr): 3352, 3247, 3150, 3104, 3083, 1716, 1670, 1617, 1595, 1568,1508, 1478, 11403, 1390, 1334, 1062, 1052, 1011, 774, cm−1.
1HNMR(400 MHz, DMSO-d6): 9.83 (s, 1H, NH), 7.20–7.09 (m, 5H, ArH), 6.89 (d, J = 7.8 Hz, 1H, ArH), 6.75–6.66 (m, 2H, ArH), 6.59 (d, J = 6.8 Hz, 1H, ArH), 6.07 (d, J = 4.4 Hz, 1H, NH), 5.05 (d, J = 4.4 Hz, 1H, CH), 4.90 (s, 2H, CH2)
13CNMR (100 MHz, DMSO-d6, 25 ºC) (δ, ppm): 173.3, 159.2, 144.2, 137.8, 131.9, 128.4, 127.5, 127.0, 123.3, 123.3, 121.1, 120.0, 97.2, 66.5, 57.8
HRMS (ESI) m/z: calc. for [M+H+] C17H15N2O2: 279.1129; found: 279.1127.
10-p-Tolyl-3,4,9,10-tetrahydro-2-oxa-4,9-diazabenzo[f]azulen-1-one 4cc
White solid, Mp: 287–288 ºC
IR(KBr): 3351, 3246, 3202, 3149, 3102, 3083, 2965, 1717, 1645, 1639, 1568, 1509, 1487, 1387, 1197, 1061, 1033, 995, 851, 845 cm−1.
1HNMR (400 MHz, DMSO-d6): 9.81 (s, 1H, NH), 7.00 (dd, J = 8.0, 14.4 Hz, 4H, ArH), 6.89 (d, J = 7.6 Hz, 1H, ArH), 6.74–6.66 (m, 2H, ArH), 6.58 (d, J = 7.2 Hz, 1H, ArH), 6.03 (d, J = 4.0 Hz, 1H, NH), 5.02 (d, J = 4.0 Hz, 1H, CH), 4.89 (s, 2H, CH2), 2.18 (s, 3H, CH3)
13CNMR (100 MHz, DMSO-d6, 25 ºC) (δ, ppm): 173.2, 159.5, 143.6, 137.5, 132.1, 131.3, 129.8, 123.5, 123.4, 121.4, 120.2, 120.1, 96.7, 66.6, 57.3
HRMS (ESI) m/z: calc. for [M+H+] C18H17N2O2: 293.1285; found: 293.1279.
10-(2-Methoxyphenyl)-3,4,9,10-tetrahydro-2-oxa-4,9-diazabenzo[f]azulen-1-one 4dd
White solid, Mp: 247–259 ºC
IR(KBr): 3352, 3247, 3150, 3104, 3083, 1716, 1670, 1617, 1595, 1568,1508, 1478, 1438,1403, 1390, 1062, 1052, 1032,1011, 774 cm−1.
1HNMR (400 MHz, DMSO-d6): 9.88 (s, 1H, NH), 7.39 (d, J = 8.0 Hz, 2H, ArH), 7.09 (d, J = 8.4 Hz, 2H, ArH), 6.90 (d, J = 7.6 Hz, 1H, ArH), 6.77–6.69 (m, 2H, ArH), 6.59 (d, J = 7.6 Hz, 1H, ArH), 6.09 (d, J = 4.4 Hz, 1H, NH), 5.04 (d, J = 4.0 Hz, 1H, CH), 4.90 (s, 2H, CH2)
13CNMR (100 MHz, DMSO-d6, 25 ºC) (δ, ppm): 173.2, 159.5, 143.6, 137.5, 132.1, 131.3, 129.8, 123.5, 123.4, 121.4, 120.2, 120.1, 96.7, 66.6, 57.3
HRMS (ESI) m/z: calc. for [M+H+] C18H17N2O3: 309.1234; found: 309.1220.
10-(3,4,5-Trimethoxyphenyl)-3,4,9,10-tetrahydro-2-oxa-4,9-diazabenzo[f]azulen-1-one 4ee
Pale white solid, Mp: 259–260 ºC
IR(KBr): 3323, 3301, 3105, 2994, 2945, 2832, 1716, 1661, 1627, 1603, 1565, 1485, 1418, 1390, 1305, 1252, 1153, 1047, 783, cm−1.
1HNMR (400 MHz, DMSO-d6): 9.83 (s, 1H, NH), 6.91–6.89 (m, 1H, ArH), 6.78–6.71 (m, 2H, ArH), 6.67–6.64 (m, 1H, ArH), 6.41 (s, 2H, ArH), 6.01 (d, J = 4.4 Hz, 1H, NH), 4.97 (d, J = 4.0 Hz, 1H, CH), 4.90 (d, J = 15.6 Hz, 1H, CH2), 4.86 (d, J = 15.6 Hz, 1H, CH2), 3.58 (s, 6H, CH3), 3.55 (s, 3H, CH3)
HRMS (ESI) m/z: calc. for [M+Na+] C20H20NaN2O5: 391.1265; found: 391.1262.
10-(4-Dimethylaminophenyl)-3,4,9,10-tetrahydro-2-oxa-4,5,9-triazabenzo[f]azulen-1-one 4ff
Pale white solid, Mp: 273–276 ºC
IR(KBr):3352, 3247, 3150, 3104, 3083, 1716, 1670, 1617, 1595, 1568,1508, 1454, 1438, 1390, 1365, 1334, 1062, 1011, 774, cm−1.
1HNMR (400 MHz, DMSO-d6): 9.74 (s, 1H, NH), 6.94 (d, J = 8.4 Hz, 2H, ArH), 6.87 (d, J = 7.2 Hz, 1H, ArH), 6.73~6.66 (m, 2H, ArH), 6.60 (d, J = 7.2 Hz, 1H, ArH), 6.53 (d, J = 8.8 Hz, 2H, ArH), 5.94 (d, J = 4.4 Hz, 1H, NH), 4.96 (d, J = 4.0 Hz, 1H, CH), 4.87 (s, 2H,CH2), 2.79 (s, 6H, CH3)
13CNMR (100 MHz, DMSO-d6, 25 ºC) (δ, ppm): 173.4, 158.9, 149.6, 138.2, 132.0, 128.2, 123.3, 123.2, 119.8, 112.4, 197.9, 66.4, 57.2
HRMS (ESI) m/z: calc. for [M+H+] C19H20N3O2: 322.1551; found: 322.1551.
10-Thien-2-yl-3,4,9,10-tetrahydro-2-oxa-4,9-diazabenzo[f]azulen-1-one 4gg
Pale yellow solid, Mp: 282–283 ºC
IR(KBr): 3352, 3247, 3150, 3104, 3083, 1716, 1670, 1617, 1595, 1508, 1478, 1454, 1403, 1390, 1365, 1062, 1052, 1032, 774 cm−1.
1HNMR (400 MHz, DMSO-d6): 9.88 (1H, s, NH),7.39 (d, J = 8.0 Hz, 2H, ArH), 7.09 (d, J = 8.4 Hz, 2H, ArH), 6.90 (d, J = 7.6 Hz, 1H, ArH), 6.77–6.69 (m, 2H, ArH), 6.59 (d, J = 7.6 Hz, 1H, ArH), 6.09 (d, J = 4.4 Hz, 1H, NH), 5.04 (d, J = 4.0 Hz, 1H, CH), 4.90 (s, 2H, CH2)
13CNMR (100 MHz, DMSO-d6, 25 ºC) (δ, ppm): 173.0, 159.1, 148.6, 137.6, 132.1, 127.0, 125.1, 123.7, 123.5, 121.6, 120.1, 98.2, 66.5, 53.3
HRMS (ESI) m/z: calc. for [M+Na+] C15H12N2NaO2S: 307.0512; found: 307.0513.
10-Benzyl-3,4,9,10-tetrahydro-2-oxa-4,9-diazabenzo[f]azulen-1-one 4hh
White solid, Mp: 229–231 ºC
IR(KBr): 3349, 3287, 3154, 3101, 1720, 1640, 1568, 1507, 1489, 1438, 1396, 1335, 1192, 1047, 766, 747, 702 cm−1.
1HNMR (400 MHz, DMSO-d6): 9.66 (s, 1H, NH), 7.28 (t, J = 7.4 Hz, 2H, ArH), 7.20 (t, J = 7.2 Hz, 1H, ArH), 7.09 (d, J = 7.2 Hz, 2H, ArH), 6.90 (d, J = 7.2 Hz, 1H, ArH), 6.86–6.78 (m, 2H, ArH), 6.72 (d, J = 7.2 Hz, 1H, ArH), 5.43 (d, J = 4.0 Hz, 1H, NH), 4.76 (dd, J = 15.2, 4.0 Hz, 2H, CH2), 2.78–2.73 (m, 1H, CH2), 2.64–2.58 (m, 1H, CH2)
13CNMR (100 MHz, DMSO-d6, 25 ºC) (δ, ppm): 173.1, 158.5, 139.1,137.3, 131.8, 129.8, 128.7, 126.6, 123.7, 123.2, 121.0, 120.1, 98.6,66.5, 55.7, 44.3
HRMS (ESI) m/z: calc. for [M+H+] C18H17N2O2: 293.1285; found: 293.1287.
10-Isobutyl-3,4,9,10-tetrahydro-2-oxa-4,9-diazabenzo[f]azulen-1-one 4ii
White solid, Mp: 208–210 ºC
IR(KBr): 3346, 2952, 2926, 1737, 1666, 1560, 1502, 1475, 1390, 1363, 1337, 1186, 1030, 1011, 969, 758, 647 cm−1.
1HNMR (400 MHz, DMSO-d6): 9.64 (s, 1H, NH), 6.88 (d, J = 7.2 Hz, 2H, ArH), 6.83–6.76 (m, 2H, ArH), 5.69 (d, J = 4.4 Hz, 1H, NH), 4.77 (dd, J = 15.2, 18.8 Hz, 2H, CH2), 3.92–3.87 (m, 1H, CH), 1.72–1.65 (m, 1H, CH), 1.28–1.22 (m, 1H, CH2), 1.12–1.05 (m, 1H, CH2), 0.88 (d, J = 6.4 Hz, 3H, CH3), 0.83 (d, J = 6.4 Hz, 3H, CH3)
HRMS (ESI) m/z: calc. for [M+Na+] C15H18NaN2O2: 281.1261; found: 281.1274.
10-sec-Butyl-3,4,9,10-tetrahydro-2-oxa-4,9-diazabenzo[f]azulen-1-one 4jj
White solid, Mp: 173–175 ºC
IR(KBr): 3355, 3293, 3109, 2963, 2929, 2874, 1731, 1651, 1567, 1490, 1437, 1393, 1359, 1335, 1186, 1151, 1122, 1043, 772 cm−1.
1HNMR (400 MHz, DMSO-d6): 9.65 (s, 1H, NH), 6.90–6.84 (m, 2H, ArH), 6.82–6.78 (m, 1H, ArH), 6.75–6.72 (m, 1H, ArH), 5.83–5.80 (m, 1H, NH), 4.77 (s, 2H, CH2), 3.92–3.87 (m, 1H, CH), 3.60–3.54 (m, 1H, CH), 1.56–1.26 (m, 2H, CH2), 1.17–0.94 (m, 1H, CH), 0.81–0.72 (m, 6H, CH3)
HRMS (ESI) m/z: calc. for [M+Na+] C15H18N2NaO2: 281.1261; found: 281.1276.
10-(1-Methylbutyl)-3,4,9,10-tetrahydro-2-oxa-4,9-diazabenzo[f]azulen-1-one 4kk
White solid, Mp: 173–174 ºC
IR(KBr): 3352, 2963, 2930, 2871, 1731, 1651, 1566, 1488, 1436, 1393, 1360, 1333, 1186, 1153, 1042, 1030, 986, 772, 756 cm−1.
1HNMR (400 MHz, DMSO-d6): 9.66 (s, 1H, NH), 6.91–6.85 (m, 2H, ArH), 6.82–6.79 (m, 1H, ArH), 6.77–6.73 (m, 1H, ArH), 5.82 (d, 1H, J = 4.8 Hz, NH), 4.76 (m, 2H, CH2), 3.56–3.53 (m, 1H, CH),1.51–1.26 (m, 3H, CH and CH2), 1.13–0.96 (m, 2H, CH2), 0.80–0.71 (m, 6H, CH3)
HRMS (ESI) m/z: calc. for [M+Na+] C16H20N2NaO2: 295.1417; found: 295.1410.
10-Cyclohexyl-3,4,9,10-tetrahydro-2-oxa-4,9-diaza-benzo[f]azulen-1-one 4ll
White solid, Mp: 256–257 ºC
IR(KBr): 3483, 3350, 3325, 3058, 2934, 2853, 1731, 1706, 1654, 1616, 1565, 1508, 1486, 1434, 1393, 1191, 1178, 1041, 801 cm−1.
1HNMR (400 MHz, DMSO-d6): 9.64 (s, 1H, NH), 6.89–6.84 (m, 2H, ArH), 6.80 (t, J = 7.6 Hz, 1H, ArH), 6.76–6.72 (m, 1H, ArH), 5.83 (d, J = 4.8 Hz, 1H, NH), 4.78 (d, J = 15.2 Hz, 1H, CH2), 4.73 (d, J = 15.2 Hz, 1H, CH2), 3.49 (dd, J = 4.8, 15.2 Hz, 1H, CH), 1.85–1.84 (m, 1H, CH), 1.62–1.39 (m, 4H, CH2), 1.15–0.98 (m, 4H, CH2), 0.94–0.87 (m, 2H, CH2)
HRMS (ESI) m/z: calc. for [M+H+] C17H21N2O2: 285.1598; found: 285.1595.
10-Isopropyl-3,4,9,10-tetrahydro-2-oxa-4,9-diaza-benzo[f]azulen-1-one 4mm
White solid, Mp: 254–256 ºC
IR(KBr):3469, 3329, 3276, 3152, 3101, 2960, 1708, 1652, 1570, 1508, 1479, 1435, 1395, 1364, 1333, 1232, 1045, 998, 849 cm−1.
1HNMR (400 MHz, DMSO-d6): 9.66 (s, 1H, NH), 6.91–6.85 (m, 2H, ArH), 6.82–6.79 (m, 1H, ArH), 6.77–6.73 (m, 1H, ArH), 5.82 (d, J = 4.8 Hz, 1H, NH), 4.77 (s, 2H, CH2), 3.46 (dd, J = 4.8, 8.4 Hz, 1H, CH), 1.53–1.44 (m, 1H, CH), 0.86 (d, J = 6.4 Hz, 3H, CH3), 0.82 (d, J = 6.8 Hz, 3H, CH3)
HRMS (ESI) m/z: calc. for [M+Na+] C14H17N2O2: 245.1285; found: 245.1289.
General procedure for the synthesis of products 5a
In a 10-mL reaction vial, the benzene-1,2-diamine 1a (1 mmol), tetronic acid 3 (1 mmol), acetic acid (0.1 mmol) and water (2 mL) were mixed and then stiring for 10 min. Subsequently, the 2-formylbenzoic acids 2 (1 mmol) was added to the reaction mixture, and the reaction vial was capped and pre-stiring for 20 second. The mixture was subjected to microwave irradiation at 200W (initial power 100W, maximum power 200W) at 150 ºC, for 15 min. Upon completion, monitored by TLC, the reaction mixture was cooled to room temperature, filtered to give the crude product, which was further washed by 50% EtOH to give pure product 5a.
4bH-Benzo[2,3]furo[3’,4’:5,6][1,4]diazepino[7,1-a]isoindole-5,14(7H,8H)-dione 5a
White solid, MP: 286–289 ºC
IR(KBr): 3277, 3220, 3147, 3108, 1734, 1704, 1688, 1730, 1595, 1543, 1506, 1397, 1348, 1194, 1045, 1023, 766 cm−1
1HNMR (400 MHz, DMSO-d6): 9.99(s, 1H, NH), 8.41 (d, 1H, J = 8.0 Hz, ArH), 7.78 (d, 1H, J = 7.6 Hz, ArH), 7.70–7.66 (m, 1H, ArH), 7.59–7.55 (m, 1H, ArH), 7.40–7.34 (m, 2H, ArH), 7.21–7.14 (m, 2H, ArH), 5.74 (s, 1H, CH), 4.83 (d, J = 15.2 Hz, 1H, CH2), 4.78 (d, J = 15.2 Hz, 1H, CH2)
13CNMR (100 MHz, DMSO-d6, 25 ºC) (δ, ppm): 171.8, 165.8,158.5, 143.9, 136.8, 131.6, 130.7, 130.6, 128.8, 128.2, 126.3, 123.3, 123.1, 119.4, 94.4, 66.6, 59.3.
HRMS (ESI) m/z: calc. for [M-H+] C18H11N2O3:303.0764; found: 303.0761.
1,2-Dimethoxy-4bH-benzo[2,3]furo[3’,4’:5,6][1,4]diazepino[7,1-a]isoindole-5,14(7H,8H)-dione 5b
White solid, Mp: 291–293 ºC
IR(KBr): 3251, 3201, 3141, 3092, 1752, 1677, 1655, 1596, 1557, 1497, 1376, 1337, 1272, 1062, 1040, 1011, 773 cm−1
1HNMR (400 MHz, DMSO-d6): 9.93 (s, 1H, NH), 8.06 (d, 1H, J = 8.4 Hz, ArH), 7.37–7.32 (m, 3H, ArH), 7.19–7.13 (m, 2H, ArH), 5.58 (s, 1H, CH), 4.87 (d, J = 15.2 Hz, CH2), 4.83 (d, J = 15.2 Hz, CH2), 4.87 (d, J = 15.2 Hz, 1H, CH2), 4.85 (d, J = 15.2 Hz, 1H, CH2), 3.85 (s, 3H, OCH3), 3.83 (s, 3H, OCH3)
13CNMR (100 MHz, DMSO-d6, 25 ºC) (δ, ppm): 171.8, 163.9, 158.3, 152.4, 146.3, 137.1, 136.8, 130.9, 128.1, 126.4, 123.0, 121.6, 119.4, 116.8, 95.1, 66.5, 61.6, 58.0, 56.4.
HRMS (ESI) m/z: calc. for [M-H+] C20H15N2O5:363.0975; found: 363.0976.
10,11-Dimethyl-4bH-benzo[2,3]furo[3’,4’:5,6][1,4]diazepino[7,1-a]isoindole-5,14(7H,8H)-dione 5c
White solid, Mp: >300 ºC
IR(KBr): 3270, 3186, 3124, 3082, 1753, 1687, 1653, 1614, 1510, 1398, 1362, 1340, 1211, 1195, 1141, 1115, 1065, 1024, 760 cm−1
1HNMR (400 MHz, DMSO-d6): 9.94 (s, 1H, NH), 8.40 (d, 1H, J = 7.6 Hz, ArH), 7.75 (d, 1H, J = 7.2 Hz, ArH), 7.67 (t, 1H, J = 7.6 Hz, ArH), 7.58–7.54 (m, 1H, ArH), 7.14 (s, 1H, ArH), 6.95 (s, 1H, ArH), 5.67 (s, 1H, CH), 4.84 (d, J = 15.2 Hz, 1H, CH2), 4.74 (d, J = 15.2 Hz, 1H, CH2), 2.24 (s, 3H, CH3), 2.20 (s, 3H, CH3)
HRMS (ESI) m/z: calc. for [M-H+] C20H15N2O3:331.1077; found: 331.1075.
1,2-Dimethoxy-10,11-dimethyl-4bH-benzo[2,3]furo[3’,4’:5,6][1,4]diazepino[7,1-a]isoindole-5,14(7H,8H)-dione 5d
White solid, Mp: >300 ºC
IR(KBr): 3255, 3196, 3127, 3088, 3001, 1749, 1682, 1667, 1620, 1557, 1448, 1400, 1270, 1197, 1117, 1060, 1015, 958 cm−1
1HNMR (400 MHz, DMSO-d6): 9.77 (s, 1H, NH), 8.05 (d, J = 8.4 Hz, 1H, ArH), 7.34 (d, J = 8.4 Hz, 1H, ArH), 7.11 (s, 1H, ArH), 6.93 (s, 1H, ArH), 5.51 (s, 1H, CH), 4.83 (d, J = 15.2 Hz, 1H, CH2), 4.72 (d, J = 15.2 Hz, 1H, CH2), 3.84 (s, 3H, OCH3), 3.83 (s, 3H, OCH3), 2.23 (s, 3H, CH3), 2.20 (s, 3H, CH3)
13CNMR (100 MHz, DMSO-d6, 25 ºC) (δ, ppm): 171.9, 163.9, 158.4, 152.3, 146.2, 138.8, 136.4, 134.5, 131.1, 131.0, 123.8, 123.0, 121.6, 120.0, 116.6, 94.4, 66.4, 61.6, 58.0, 56, 4, 19.1, 18.5.
HRMS (ESI) m/z: calc. for [M-H+] C22H19N2O5:391.1288; found: 391.1284.
10,11-Dichloro-4bH-benzo[2,3]furo[3’,4’:5,6][1,4]diazepino[7,1-a]isoindole-5,14(7H,8H)-dione 5e
Pale white solid, Mp: >300 ºC
IR(KBr): 3330, 3281, 3134, 3102, 1747, 1715, 1662, 1626, 1597, 1557, 1487, 1408, 1259, 1179, 1135, 1014, 871 cm−1
1HNMR (400 MHz, DMSO-d6): 10.18 (s, 1H, NH), 8.41 (d, J = 7.6 Hz, 1H, ArH), 7.80 (d, J = 7.6 Hz, 1H, ArH), 7.73–7.69 (m, 2H, ArH), 7.61–7.57 (m, 1H, ArH), 7.39 (s, 1H, ArH), 5.76 (s, 1H, CH), 4.91 (d, J = 15.2 Hz, 1H, CH2), 4.79 (d, J = 15.2 Hz, 1H, CH2)
13CNMR (100 MHz, DMSO-d6, 25 ºC) (δ, ppm): 171.6, 165.9, 157.8, 143.7, 137.1, 132.1, 132.0, 130.2, 130.5, 129.0, 126.3, 124.0, 123.5, 120.4, 112.7, 95.6, 66.6, 59.0.
HRMS (ESI) m/z: calc. for [M-H+] C18H9Cl2N2O3:370.9984; found: 370.9982.
10,11-Dichloro-1,2-dimethoxy-4bH-benzo[2,3]furo[3’,4’:5,6][1,4]diazepino[7,1-a]isoindole-5,14(7H,8H)-dione 5f
Pale white solid, Mp: 263–265 ºC
IR(KBr): 3249, 1747, 1681, 1672, 1592, 1537, 1489, 1474, 1393, 1342, 1194, 1134, 1111, 1055, 1027, 742 cm−1
1HNMR (400 MHz, DMSO-d6): 10.10 (s, 1H, NH), 8.06 (d, J = 8.4 Hz, 1H, ArH), 7.68 (s, 1H, ArH), 7.39–7.37 (m, 2H, ArH), 5.59 (s, 1H, CH), 4.90 (d, J = 15.2 Hz, 1H, CH2), 4.76 (d, J = 15.2 Hz, 1H, CH2), 3.85 (s, 3H, OCH3), 3.84 (s, 3H, OCH3).
13CNMR (100 MHz, DMSO-d6, 25 ºC) (δ, ppm): 171.5, 163.9, 157.6, 152.4, 146.4, 137.3, 136.5, 132.3, 129.9, 126.1, 123.9, 122.5, 121.6, 120.3, 117.2, 96.2, 66.6, 61.6, 57.6, 56.4.
HRMS (ESI) m/z: calc. for [M-H+] C20H13Cl2N2O5:432.0196; found: 432.0199.
5,14-Dioxo-5,7,8,14-tetrahydro-4bH-benzo[2,3]furo[3’,4’:5,6][1,4]diazepino[7,1-a]isoindole-10-carboxylic acid 5g
Pale white solid, MP: >300 ºC
IR(KBr): 3340, 3116, 1748, 1701, 1687, 1616, 1562, 1516, 1404, 1390, 1342, 1268, 1314, 1182, 1058, 1023, 771 cm−1
1HNMR (400 MHz, DMSO-d6): 13.21 (s, 1H, COOH), 10.17(s, 1H, NH), 8.43 (d, 1H, J = 7.6 Hz, ArH), 7.83 (d, 1H, J = 2.0 Hz, ArH), 7.80 (d, 1H, J = 7.6 Hz, ArH), 7.73–7.68 (m, 2H, ArH), 7.61–7.57 (m, 1H, ArH), 7.52 (d, 1H, J = 8.0 Hz, ArH), 5.80 (s, 1H, CH), 4.90 (d, J = 15.2 Hz, 1H, CH2), 4.81 (d, J = 15.2 Hz, 1H, CH2).
13CNMR (100 MHz, DMSO-d6, 25 ºC) (δ, ppm): 171.6, 166.4, 165.9, 158.3, 143.9, 136.7, 135.9, 131.9, 131.0, 130.4, 130.3, 130.0, 128.9, 126.4, 123.4, 120.5, 94.7, 66.5, 59.2.
HRMS (ESI) m/z: calc. for [M-H+] C19H11N2O5: 347.0662; found: 347.0659.
1,2-Dimethoxy-5,14-dioxo-5,7,8,14-tetrahydro-4bH-benzo[2,3]furo[3’,4’:5,6][1,4]diazepino[7,1-a]isoindole-10-carboxylic acid 5h
Pale white solid, Mp: 277–280 ºC
IR(KBr): 3313, 3138, 1750, 1689, 1672, 1558, 1499, 1400, 1275, 1061, 1047, 783, 774, 755 cm−1
1HNMR (400 MHz, DMSO-d6): 13.18 (s, 1H, COOH), 10.11 (s, 1H, NH), 8.08 (d, 1H, J = 8.4 Hz, ArH), 7.81 (s, 1H, ArH), 7.68–7.66(m, 1H, ArH), 7.51–7.49 (m, 1H, ArH), 7.38 (d, 1H, J = 8.4 Hz, ArH), 5.62 (s, 1H, CH), 4.89 (d, J = 15.2 Hz, 1H, CH2), 4.78 (d, J = 15.2 Hz, 1H, CH2), 3.85 (s, 3H, OCH3), 3.84 (s, 3H, OCH3).
13CNMR (100 MHz, DMSO-d6, 25 ºC) (δ, ppm): 171.7, 166.4, 163.9, 158.1, 152.4, 146.4, 136.9, 136.7, 131.1, 130.3, 130.1, 123.3, 122.8, 121.7, 120.5, 117.0, 95.2, 66.5, 61.6, 57.8, 56.4.
HRMS (ESI) m/z: calc. for [M-H+] C21H15N2O7: 407.0874; found: 407.0880.
Crystal data for 4g: C26H32N4O8, pale white, crystal dimension 0.40 × 0.35 × 0.14 mm, Monoclinic, space group P2(1)/c, a = 11.9237(11) Å, b = 14.1491(13) Å, c = 16.7626(14) Å, α = γ = 90 ºC, β = 99.5980(10) ºC, V = 2788.4(4) Å3, Mr = 528.56, Z = 4, Dc = 1.259 Mg/m3, λ = 0.71073 Å, μ(Mo Kα) = 0.094 mm−1, F(000) = 1120, R = 0.0552, wR2 = 0.1182, S = 1. 036, largest diff. Peak and hole: 0.508 and −0.324 e/Å3. CCDC-823409 contains the supplementary crystallographic data for this paper
Crystal data for 4u: C17H13BrN2O2, pale white, crystal dimension 0.35 × 0.20 × 0.11 mm, Monoclinic, space group P2(1)/c, a = 14.6324(15) Å, b = 12.0632(12) Å, c = 8.5627(9) Å, α = γ = 90 ºC, β = 94.7470(10) ºC, V = 1506.2(3) Å3, Mr = 357.20, Z = 4, Dc = 1.575 Mg/m3, λ = 0.71073 Å, μ(Mo Kα) = 2.737 mm−1, F(000) = 720, R = 0.0320, wR2 = 0.0630, S = 1. 011, largest diff. Peak and hole: 0.279 and −0.343 e/Å3. CCDC-823410 contains the supplementary crystallographic data for this paper
Supplementary Material
Acknowledgments
We are grateful for financial support from are grateful to financial support from the National Science Foundation of China (Nos. 20928001, 21072163 and 21002083), Science Foundation in Interdisciplinary Major Research Project of Xuzhou Normal University (No. 09XKXK01), Doctoral Research Foundation of Xuzhou Normal Univ. (XZNU, No. 10XLR20), Robert A. Welch Foundation (D-1361), NIH (R03DA026960) and PAPD of Jiangsu Higher Education Institutions for their generous support.
Footnotes
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References and notes
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