Citation: Xiao-Jian Wang, Yu-Lin Tian, Qing-Yang Zhang, Jian-Guo Qi, Da-Li Yin. An efficient synthesis of substituted 1,4-diazepines by a Pd catalyzed amination and sequential hydrogenation condensation[J]. Chinese Chemical Letters, ;2013, 24(8): 743-746. shu

An efficient synthesis of substituted 1,4-diazepines by a Pd catalyzed amination and sequential hydrogenation condensation

1.
State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Beijing Key Laboratory of Active Substance Discovery and Druggability Evaluation, Institute of Materia Medica, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100050, China

Corresponding author: Da-Li Yin,
Received Date: 20 March 2013
Available Online: 16 April 2013

An efficient synthesis of substituted 1,4-diazepines is developed. The accessible intermediates have been obtained via Pd-catalyzed amination. The subsequent hydrogenation and intramolecular condensation sequences could be conducted successively in one pot without special operation. The mild and general strategy enables the synthesis of various substituted 1,4-diazepines in high yields.
- 1,4-Diazepines,
- Pd-catalyzed amination,
- Hydrogenation,
- Intramolecular condensation
1. [1]
  [1] R.D. Charan, G. Schlingmann, J. Janso, et al., Diazepinomicin, a new antimicrobial alkaloid from a marine Micromonospora sp., J. Nat. Prod. 67 (2004) 1431-1433.
2. [2]
  [2] B. Fulton, K.L. Goa, Olanzapine. A review of its pharmacological properties and therapeutic efficacy in the management of schizophrenia and related psychoses, Drugs 53 (1997) 281-298.
3. [3]
  [3] A. Fitton, R.C. Heel, Clozapine. A review of its pharmacological properties, and therapeutic use in schizophrenia, Drugs 40 (1990) 722-747.
4. [4]
  [4] A.W.H. Wardrop, G.L. Sainsbury, J.M. Harrison, T.D. Inch, Preparation of some dibenz[b,f][1,4]oxazepines and dibenz[b,e]azepines, J. Chem. Soc., Perkin Trans. 1 (1976) 1279-1285.
5. [5]
  [5] X. Xu, S. Guo, Q. Dang, J. Chen, X. Bai, A new strategy toward fused-pyridine heterocyclic scaffolds: Bischler-Napieralski-type cyclization, followed by sulfoxide extrusion reaction, J. Comb. Chem. 9 (2007) 773-782.
6. [6]
  [6] Y. Liao, B.J. Venhuis, N. Rodenhuis, et al., New (sulfonyloxy)piperazinyldibenzazepines as potential atypical antipsychotics: chemistry and pharmacological evaluation, J. Med. Chem. 42 (1999) 2235-2244.
7. [7]
  [7] R.A. Smits, H.D. Lim, B. Stegink, et al., Characterization of the histamine H4 receptor binding site. Part 1. Synthesis and pharmacological evaluation of dibenzodiazepine derivatives, J. Med. Chem. 49 (2006) 4512-4516.
8. [8]
  [8] D. Tsvelikhovsky, S.L. Buchwald, Concise palladium-catalyzed synthesis of dibenzodiazepines and structural analogues, J. Am. Chem. Soc. 133 (2011) 14228-14231.
9. [9]
  [9] J.F. Hartwig, Transition metal catalyzed synthesis of arylamines and aryl ethers from aryl halides and triflates: scope and mechanism, Angew. Chem. Int. Ed. 37 (1998) 2046-2067.
10. [10]
  [10] D.S. Surry, S.L. Buchwald, Biaryl phosphane ligands in palladium-catalyzed amination, Angew. Chem. Int. Ed. 47 (2008) 6338-6361.
11. [11]
  [11] K. Liu, D. Yin, Efficient method for the synthesis of 2,3-unsubstituted nitro containing indoles from o-fluoronitrobenzenes, Org. Lett. 11 (2009) 637-639.
12. [12]
  [12] G. Zhang, H. Zhang, X. Wang, et al., Synthesis of new riminophenazines with pyrimidine and pyrazine substitution at the 2-N position, Molecules 16 (2011) 6985-6991.
13. [13]
  [13] G. Li, Q. Xiao, C. Li, X. Wang, D. Yin, A facile preparation of tetralins from arene-1,4-diones using titanium(IV) chloride and triethylsilane, Tetrahedron Lett. 52 (2011) 6827-6830.
14. [14]
  [14] G. Zhang, X. Wang, C. Li, D. Yin, Palladium-catalyzed cross-coupling of electrondeficient heteroaromatic amines with heteroaryl halides, Synth. Commun. 43 (2012) 456-463.
15. [15]
  [15] Compound 5a: ¹H NMR (300 MHz, CD3Cl): δ 7.710 (d, 2H, J = 5.4 Hz), 7.404 (m, 3H), 7.323 (m, 2H), 7.014 (m, 3H), 6.918 (m, 1H), 6.779 (m, 1H), 6.704 (m, 1H), 4.975 (s, 1H). ¹³C NMR (100 MHz, CDC_l3): δ 169.49, 154.45, 142.60, 141.32, 140.85, 132.19, 131.94, 129.93, 128.67, 127.96, 127.56, 126.81, 124.17, 122.42, 119.70. HRMS (m/z) (M+H): Calcd. for C₁₉H₁₄N₂: 271.123, found: 271.1233. Mp 129-131℃. IR (KBr): 3350, 1609, 1571, 1445, 1283, 960. Compound 5b: ¹H NMR (300 MHz, CD3Cl): δ 7.69 (d, 1H, J = 6.6 Hz), 7.44 (m, 3H), 7.38 (td, 1H, J = 7.8 Hz, J = 1.5 Hz), 7.01 (m, 2H), 6.93 (m, 2H), 6.77 (d, 1H, J = 4.5 Hz), 6.72 (dd, 1H, J = 7.8 Hz, J = 2.7 Hz), 6.63 (m, 1H), 4.97 (s, 1H). ¹³C NMR (100 MHz, CDC_l3): δ 170.58, 160.97, 158.58, 154.50, 142.05 (J = 9 Hz), 140.90, 138.64, 132.15 (J = 6 Hz), 130.26, 129.64, 128.01, 127.45, 122.60, 120.08 (J = 9 Hz), 119.69, 114.58 (J = 23 Hz), 112.88 (J = 23 Hz). HRMS (m/z) (M+H): Calcd. for C19H13FN2: 289.1136, found: 289.1142. Mp 103-105℃. IR (KBr): 3352, 1613, 1466, 1216, 1107, 866. Compound 5c: ¹H NMR (300 MHz, CD3Cl): δ 7.70 (d, 2H, J = 7.8 Hz), 7.43 (m, 3H), 7.37 (m, 1H), 6.99 (d, 1H, J = 7.5 Hz), 6.89 (m, 2H), 6.74 (d, 1H, J = 7.5 Hz), 6.60 (s, 2H), 3.77 (s, 3H). ¹³C NMR (100 MHz, CDC_l3): δ 170.00, 156.61, 155.03, 141.67, 141.29, 135.77, 132.15, 131.94, 129.97, 129.58, 127.94, 127.44, 122.28, 120.24, 119.51, 113.13, 112.55, 55.59. HRMS (m/z) (M+H): Calcd. for C₂0H₁₆N₂O: 301.1335, found: 301.1339. Mp 149-152℃. IR (KBr): 3349, 2400, 1666, 1501, 1328, 1243, 1117, 960. Compound 5d: ¹H NMR (300 MHz, CD3Cl): δ 7.70 (d, 2H, J = 6.9 Hz), 7.56 (s, 1H), 7.41 (m, 3H), 7.27 (m, 2H), 6.97 (m, 2H), 6.74 (t, 2H, J = 7.5 Hz), 5.12 (s, 1H). ¹³C NMR (100 MHz, CDC_l3): δ 170.85, 153.40, 145.85, 140.77, 140.72, 132.38, 132.36, 130.41, 129.62, 128.07, 127.50, 126.01, 125.98, 123.51, 123.47, 122.93, 119.99, 119.85. HRMS (m/z) (M+H): Calcd. for C₂₀H₁₃F₃N₂: 339.1104, found: 339.1105. Mp 129-131℃. IR (KBr): 3267, 2400, 1607, 1445, 1325, 1123, 1074, 960, 751. Compound 5e: ¹H NMR (300 MHz, CD3Cl): δ 7.95 (d, 1H, J = 4.8 Hz), 7.68 (d, 2H, J = 7.5 Hz), 7.56 (d, 1H, J = 7.8 Hz), 7.38 (m, 3H), 7.29 (t, 1H, J = 7.5 Hz), 7.01 (m, 2H), 6.92 (m, 1H), 6.83 (d, 1H, J = 5.1 Hz Hz), 6.19 (s, 1H). ¹³C NMR (100 MHz, CDC_l3): δ 171.06, 153.39, 152.01, 145.05, 140.80, 136.52, 135.24, 132.51, 132.30, 130.27, 129.64, 128.01, 127.13, 122.32, 120.40, 119.98. HRMS (m/z) (M+H): Calcd. for C18H13N3: 272.1182, found: 272.1187. Mp 183-186℃. IR (KBr): 3277, 2380, 1703, 1454, 1227, 1021, 960. Compound 5f: ¹H NMR (300 MHz, CD3Cl): δ 7.67 (d, 2H, J = 6.9 Hz), 7.42 (m, 3H), 7.30 (m, 2H), 6.95 (m, 3H), 6.76 (d, 1H, J = 8.1 Hz), 6.61 (d, 1H, J = 8.1 Hz). ¹³C NMR (100 MHz, CDC_l3): δ 170.78, 154.18, 119.84, 141.75, 141.40, 140.71, 132.30, 130.39, 129.67, 129.09, 128.13, 128.04, 127.34, 126.40, 122.71, 120.58. HRMS (m/z) (M+H): Calcd. for C19H14ClN2: 305.0840, found: 305.0845. Mp 191-193℃. IR (KBr): 3274, 2336, 1601, 1423, 1255, 1064, 960. Compound 5g: ¹H NMR (400 MHz, CD3Cl): δ 7.98 (s, 1H), 7,60 (m, 3H), 7.42-7.52 (m, 3H), 7,35 (t, 1H, J = 5.4 Hz), 7.03 (m, 1H), 7.01 (m, 1H), 6.79 (d, 1H, J = 7.6 Hz), 6.73 (d, 1H, J = 7.6 Hz), 5.21 (s, 1H). ¹³C NMR (100 MHz, CDC_l3): δ 166.552, 153.289, 147.334, 140.777, 132.660, 132.477, 132.344, 130.495, 130.320, 130.045, 129.641, 128.398, 128.036, 127.399, 126.095, 122.809, 120.019, 119.592, 51.968. HRMS (m/z) (M+H): Calcd. for C₂₁H₁₇O₂N₂, 329.1284, found 329.1286. Mp 159-162℃. IR (KBr): 3285, 1238, 1078, 1054, 975, 730. Compound 5h: ¹H NMR (400 MHz, CD3Cl): δ 7.60 (d, 2H, J = 8 Hz), 7.29 (m, 2H), 7.19 (m, 2H), 7.02 (m, 3H), 6.91 (t, 1H, J = 7.2 Hz), 6.77 (d, 1H, J = 8 Hz), 6.69 (d, 1H, J = 6.8 Hz), 4.97 (s, 1H). ¹³C NMR (100 MHz, CDC_l3): δ 169.36, 154.39, 142.62, 140.95, 140.12, 138.49, 132.18, 131.82, 129.54, 128.64, 127.59, 126.57, 124.10, 122.32, 119.67, 119.66, 21.38. HRMS (m/z) (M+H): Calcd. for C₂0H₁₆N₂: X.-J. Wang et al. / Chinese Chemical Letters 24 (2013) 743-746 745 285.1386, found: 285.1386. Mp 168-170℃. IR (KBr): 3347, 1577, 1466, 1238, 876. Compound 5i: ¹H NMR (400 MHz, CD3Cl): δ 7.59 (d, 2H, J = 7.6 Hz), 7.29 (m, 1H), 7.20 (m, 2H), 7.03 (m, 2H), 6.94 (m, 1H), 6.78 (d, 1H, J = 8 Hz), 6.71 (m, 1H), 6.62 (m, 1H), 4.92 (s, 1H), 2.40 (s, 3H). ¹³C NMR (100 MHz, CDC_l3): δ 170.43, 160.92, 158.53, 154.43, 142.14, 140.53, 138.66, 138.06, 132.01 (J = 17 Hz), 129.62, 128.69, 127.46, 122.49, 120.11, 119.65, 114.40 (J = 24 Hz), 112.61 (J = 23 Hz), 21.36. HRMS (m/z) (M+H): Calcd. for C20H15FN2: 303.1292, found: 303.1296. Mp 145-148℃. IR (KBr): 3345, 1620, 1487, 1220, 1113, 960. Compound 5j: ¹H NMR (400 MHz, CD3Cl): δ 7.60 (d, 2H, J = 7.6 Hz), 7.31 (m, 1H), 7.19 (d, 2H, J = 7.6 Hz), 7.02 (m, 1H), 6.91 (t, 1H, J = 7.6 Hz), 6.88 (s, 1H), 6.77 (d, 1H, J = 8 Hz), 6.65 (m, 2H). ¹³C NMR (100 MHz, CDC_l3): δ 169.87, 156.60, 154.98, 141.80, 140.20, 138.47, 135.80, 132.19, 131.83, 129.59, 128.65, 127.51, 122.23, 120.18, 119.48, 112.93, 112.44, 55.59, 21.38. HRMS (m/z) (M+H): Calcd. for C21H18N2O: 315.1492, found 315.1495. Mp 178-180℃. IR (KBr): 3300, 1567, 1433, 1203, 1103, 982. Compound 5k: ¹H NMR (400 MHz, CD3Cl): δ 7.60 (d, 2H, J = 8 Hz), 7.55 (m, 1H), 7.31 (m, 1H), 7.21 (m, 5H), 7.05 (m, 1H), 6.95 (m, 1H), 6.75 (m, 2H), 5.11 (s, 1H), 2.41 (s, 3H). ¹³C NMR (100 MHz, CDC_l3): δ 170.67, 153.36, 145.84, 140.91, 140.75, 137.91, 132.41, 132.24, 129.64, 128.87, 127.58, 125.90, 125.87, 123.27, 123.24, 122.87, 119.94, 119.78, 21.42. HRMS (m/z) (M+H): Calcd. for C21H15F3N2: 353.1260, found: 353.1264. Mp 180-183℃. IR (KBr): 3309, 2740, 1637, 1325, 1076, 960, 751. Compound 5l: ¹H NMR (400 MHz, CD3Cl): δ 7.93 (d, 1H, J = 4 Hz), 7.55 (m, 3H), 7.31 (t, 1H, J = 7.6 Hz), 7.21 (d, 2H, J = 7.6 Hz), 6.98 (m, 2H), 6.91 (m, 1H), 6.84 (m, 1H), 5.91 (s, 1H), 2.41 (s, 3H). ¹³C NMR (100 MHz, CDC_l3): δ 170.93, 153.31, 151.96, 144.88, 140.62, 138.00, 136.36, 135.32, 132.42, 132.35, 129.68, 128.74, 127.17, 122.31, 120.37, 120.02, 21.42. HRMS (m/z) (M+H): Calcd. for C19H15N3: 286.1339, found: 286.1347. Mp 175-177℃. IR (KBr): 3223, 2246, 1667, 1411, 1227, 1021, 960.
1. [1]
  Ming Huang , Xiuju Cai , Yan Liu , Zhuofeng Ke . Base-controlled NHC-Ru-catalyzed transfer hydrogenation and α-methylation/transfer hydrogenation of ketones using methanol. Chinese Chemical Letters, 2024, 35(7): 109323-. doi: 10.1016/j.cclet.2023.109323
2. [2]
  Hailian Tang , Siyuan Chen , Qiaoyun Liu , Guoyi Bai , Botao Qiao , Fei Liu . Stabilized Rh/hydroxyapatite Catalyst for Furfuryl Alcohol Hydrogenation: Application of Oxidative Strong Metal-Support Interactions in Reducing Conditions. Acta Physico-Chimica Sinica, 2025, 41(4): 100036-. doi: 10.3866/PKU.WHXB202408004
3. [3]
  Long Jin , Jian Han , Dongmei Fang , Min Wang , Jian Liao . Pd-catalyzed asymmetric carbonyl alkynylation: Synthesis of axial chiral ynones. Chinese Chemical Letters, 2024, 35(6): 109212-. doi: 10.1016/j.cclet.2023.109212
4. [4]
  Wujun Jian , Mong-Feng Chiou , Yajun Li , Hongli Bao , Song Yang . Cu-catalyzed regioselective diborylation of 1,3-enynes for the efficient synthesis of 1,4-diborylated allenes. Chinese Chemical Letters, 2024, 35(5): 108980-. doi: 10.1016/j.cclet.2023.108980
5. [5]
  Liangfeng Yang , Liang Zeng , Yanping Zhu , Qiuan Wang , Jinheng Li . Copper-catalyzed photoredox 1,4-amidocyanation of 1,3-enynes with N-amidopyridin-1-ium salts and TMSCN: Facile access to α-amido allenyl nitriles. Chinese Chemical Letters, 2024, 35(11): 109685-. doi: 10.1016/j.cclet.2024.109685
6. [6]
  Tianze Wang , Junyi Ren , Dongxiang Zhang , Huan Wang , Jianjun Du , Xin-Dong Jiang , Guiling Wang . Development of functional dye with redshifted absorption based on Knoevenagel condensation at 1-site in phenyl[b]-fused BODIPY. Chinese Chemical Letters, 2024, 35(6): 108862-. doi: 10.1016/j.cclet.2023.108862
7. [7]
  Rui HUANG , Shengjie LIU , Qingyuan WU , Nanfeng ZHENG . Enhanced selectivity of catalytic hydrogenation of halogenated nitroaromatics by interfacial effects. Chinese Journal of Inorganic Chemistry, 2025, 41(1): 201-212. doi: 10.11862/CJIC.20240356
8. [8]
  Mengjun Zhao , Yuhao Guo , Na Li , Tingjiang Yan . Deciphering the structural evolution and real active ingredients of iron oxides in photocatalytic CO2 hydrogenation. Chinese Journal of Structural Chemistry, 2024, 43(8): 100348-100348. doi: 10.1016/j.cjsc.2024.100348
9. [9]
  Shaoming Dong , Yiming Niu , Yinghui Pu , Yongzhao Wang , Bingsen Zhang . Subsurface carbon modification of Ni-Ga for improved selectivity in acetylene hydrogenation reaction. Chinese Chemical Letters, 2024, 35(12): 109525-. doi: 10.1016/j.cclet.2024.109525
10. [10]
  Jinyuan Cui , Tingting Yang , Teng Xu , Jin Lin , Kunlong Liu , Pengxin Liu . Hydrogen spillover enhances the selective hydrogenation of α,β-unsaturated aldehydes on the Cu-O-Ce interface. Chinese Journal of Structural Chemistry, 2025, 44(1): 100438-100438. doi: 10.1016/j.cjsc.2024.100438
11. [11]
  Zhiwei Chen , Heyun Sheng , Xue Li , Menghan Chen , Xin Li , Qiuling Song . Efficient capture of difluorocarbene by pyridinium 1,4-zwitterionic thiolates: A concise synthesis of difluoromethylene-containing 1,4-thiazine derivatives. Chinese Chemical Letters, 2024, 35(4): 108937-. doi: 10.1016/j.cclet.2023.108937
12. [12]
  Zixuan Zhu , Xianjin Shi , Yongfang Rao , Yu Huang . Recent progress of MgO-based materials in CO₂ adsorption and conversion: Modification methods, reaction condition, and CO₂ hydrogenation. Chinese Chemical Letters, 2024, 35(5): 108954-. doi: 10.1016/j.cclet.2023.108954
13. [13]
  Chong-Yang Shi , Jian-Xing Gong , Zhen Li , Chao Shu , Long-Wu Ye , Qing Sun , Bo Zhou , Xin-Qi Zhu . Gold-catalyzed intermolecular amination of allyl azides with ynamides: Efficient construction of 3-azabicyclo[3.1.0] scaffold. Chinese Chemical Letters, 2025, 36(2): 109895-. doi: 10.1016/j.cclet.2024.109895
14. [14]
  Wen-Tao Ouyang , Jun Jiang , Yan-Fang Jiang , Ting Li , Yuan-Yuan Liu , Hong-Tao Ji , Li-Juan Ou , Wei-Min He . Sono-photocatalytic amination of quinoxalin-2(1H)-ones with aliphatic amines. Chinese Chemical Letters, 2024, 35(10): 110038-. doi: 10.1016/j.cclet.2024.110038
15. [15]
  Yan-Li Li , Zhi-Ming Li , Kai-Kai Wang , Xiao-Long He . Beyond 1,4-addition of in-situ generated (aza-)quinone methides and indole imine methides. Chinese Chemical Letters, 2024, 35(7): 109322-. doi: 10.1016/j.cclet.2023.109322
16. [16]
  Kuan Deng , Fei Yang , Zhi-Qi Cheng , Bi-Wen Ren , Hua Liu , Jiao Chen , Meng-Yao She , Le Yu , Xiao-Gang Liu , Hai-Tao Feng , Jian-Li Li . Construction of wavelength-tunable DSE quinoline salt derivatives by regulating the hybridization form of the nitrogen atom and intramolecular torsion angle. Chinese Chemical Letters, 2024, 35(10): 109464-. doi: 10.1016/j.cclet.2023.109464
17. [17]
  Yue Sun , Liming Yang , Yaohang Cheng , Guanghui An , Guangming Li . Pd(I)-catalyzed ring-opening arylation of cyclopropyl-α-aminoamides: Access to α-ketoamide peptidomimetics. Chinese Chemical Letters, 2024, 35(6): 109250-. doi: 10.1016/j.cclet.2023.109250
18. [18]
  An Lu , Yuhao Guo , Yi Yan , Lin Zhai , Xiangyu Wang , Weiran Cao , Zijie Li , Zhixia Zhao , Yujie Shi , Yuanjun Zhu , Xiaoyan Liu , Huining He , Zhiyu Wang , Jian-Cheng Wang . Nanomedicine integrating the lipidic derivative of 5-fluorouracil, miriplatin and PD-L1 siRNA for enhancing tumor therapy. Chinese Chemical Letters, 2024, 35(6): 108928-. doi: 10.1016/j.cclet.2023.108928
19. [19]
  Ting Pan , Dinghu Zhang , Guomei You , Xiaoxia Wu , Chenguang Zhang , Xinyu Miao , Wenzhi Ren , Yiwei He , Lulu He , Yuanchuan Gong , Jie Lin , Aiguo Wu , Guoliang Shao . PD-L1 targeted iron oxide SERS bioprobe for accurately detecting circulating tumor cells and delineating tumor boundary. Chinese Chemical Letters, 2025, 36(1): 109857-. doi: 10.1016/j.cclet.2024.109857
20. [20]
  Yuexiang Liu , Xiangqiao Yang , Tong Lin , Guantian Yang , Xiaoyong Xu , Bubing Zeng , Zhong Li , Weiping Zhu , Xuhong Qian . Efficient continuous synthesis of 2-[3-(trifluoromethyl)phenyl]malonic acid, a key intermediate of Triflumezopyrim, coupling with esterification-condensation-hydrolysis. Chinese Chemical Letters, 2025, 36(1): 109747-. doi: 10.1016/j.cclet.2024.109747

Get Citation

PDF

XML

Metrics

PDF Downloads(0)
Abstract views(702)
HTML views(10)

通讯作者: 陈斌, bchen63@163.com

1.
沈阳化工大学材料科学与工程学院沈阳 110142