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]
  Lingyun Shen , Shenxiang Yin , Qingshu Zheng , Zheming Sun , Wei Wang , Tao Tu . A rechargeable and portable hydrogen storage system grounded on soda water. Chinese Chemical Letters, 2025, 36(3): 110580-. doi: 10.1016/j.cclet.2024.110580
2. [2]
  Zunjie Zhang , Mengran Liu , Bingcheng Ge , Tianfang Yang , Shuaitong Wang , Yang Liu , Shuyan Gao . In-situ reconstructed Cu/NiO nanosheets synergistically boosting nitrate electroreduction to ammonia. Chinese Chemical Letters, 2025, 36(8): 110657-. doi: 10.1016/j.cclet.2024.110657
3. [3]
  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
4. [4]
  Minghui Zhang , Na Zhang , Qian Zhao , Chao Wang , Alexander Steiner , Jianliang Xiao , Weijun Tang . Cobalt pincer complex-catalyzed highly enantioselective hydrogenation of quinoxalines. Chinese Chemical Letters, 2025, 36(4): 110081-. doi: 10.1016/j.cclet.2024.110081
5. [5]
  Hailian Tang , Siyuan Chen , Qiaoyun Liu , Guoyi Bai , Botao Qiao , Liu Fei . 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): 100036-0. doi: 10.3866/PKU.WHXB202408004
6. [6]
  Wenliang Wang , Weina Wang , Tian Sheng , Nan Wei , Sufan Wang , Tao Zhou . 过渡金属/氧化物催化CO₂加H₂还原生成甲醇的甲酸盐与甲酰基路径的前线轨道对称性分析. University Chemistry, 2026, 41(9): 405-411. doi: 10.12461/PKU.DXHX202508059
7. [7]
  Junhua Li , Yu Fu , Yian Shi . A rapid access to fused polycyclic indolo[2,1-a]isoquinolins via Pd-catalyzed sequential Heck/C-H activation/amination reaction with diaziridinone. Chinese Chemical Letters, 2026, 37(3): 111376-. doi: 10.1016/j.cclet.2025.111376
8. [8]
  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
9. [9]
  Yanxin Jiang , Kwai Wun Cheng , Zhiping Yang , Jun (Joelle) Wang . Pd-catalyzed enantioselective and regioselective asymmetric hydrophosphorylation and hydrophosphinylation of enynes. Chinese Chemical Letters, 2025, 36(5): 110231-. doi: 10.1016/j.cclet.2024.110231
10. [10]
  Junhua Li , Tianci Shen , Yahui Zhuang , Yu Fu , Yian Shi . Pd-Catalyzed highly regioselective migratory hydroesterification of internal olefins with formates. Chinese Chemical Letters, 2025, 36(7): 110599-. doi: 10.1016/j.cclet.2024.110599
11. [11]
  Jiaxuan YANG , Chenfa DENG , Jingyang LIU , Chenzexi XU , Hongxin CHEN , Yahui ZHU , Ying LI , Shuhua WANG , Rongping ZHOU , Chao CHEN . Advances in selective hydrogenation of α, β-unsaturated aldehydes/ketones catalyzed by metal-organic frameworks and their derivatives: A review. Chinese Journal of Inorganic Chemistry, 2025, 41(10): 1973-2010. doi: 10.11862/CJIC.20250175
12. [12]
  Huihua GONG , Tianhua CUI , Li JI , Jichuan ZHANG , Liyuan ZHANG , Yan CHEN , Zhenye WANG , Jiaqi XU , Ruixiang LI . Hydrogenation of CO₂ to formate catalyzed by N-heterocyclic carbene-nitrogen-phosphine chelated iridium(Ⅰ) complexes. Chinese Journal of Inorganic Chemistry, 2025, 41(12): 2609-2620. doi: 10.11862/CJIC.20250170
13. [13]
  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
14. [14]
  Ruixue Liu , Xiaobing Ding , Qiwei Lang , Gen-Qiang Chen , Xumu Zhang . Enantioselective and divergent construction of chiral amino alcohols and oxazolidin-2-ones via Ir-f-phamidol-catalyzed dynamic kinetic asymmetric hydrogenation. Chinese Chemical Letters, 2025, 36(3): 110037-. doi: 10.1016/j.cclet.2024.110037
15. [15]
  Qi Li , Zi-Lu Wang , Yun-He Xu . Copper-catalyzed 1,4-silylcyanation of 1,3-enynes: A silyl radical-initiated approach for synthesis of difunctionalized allenes. Chinese Chemical Letters, 2025, 36(3): 109991-. doi: 10.1016/j.cclet.2024.109991
16. [16]
  Qi Wang , Bichu Cheng , Minjie Liu , Fen-Er Chen . A concise asymmetric synthesis of (–)-oseltamivir phosphate via a biphasic Pd-catalyzed Heck-type cyclization. Chinese Chemical Letters, 2026, 37(5): 111555-. doi: 10.1016/j.cclet.2025.111555
17. [17]
  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
18. [18]
  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
19. [19]
  Fangxiang SUN , Qing ZHANG , Yifan ZHANG , Haoyi SUN , Akim V. Shmal′ko , Sergey A. Anufriev , Igor B. Sivaev , Deshuang TU , Hong YAN . Pd-catalyzed B—H bond activation and annulation of nido-carborane with terminal olefins: Facile construction of 2D-3D fused polycyclic compounds. Chinese Journal of Inorganic Chemistry, 2026, 42(3): 467-478. doi: 10.11862/CJIC.20250347
20. [20]
  Dongyan Ju , Hui Wang , Chuang Zhao , Jiahang Li , Luoluo Li , Xiaoyan Liu , Jie Tao , Junliang Zhang , Jinbo Zhao . A facile entry toward multi-substituted chiral cyclic nitrones and N-heterocycles via Pd-catalyzed enantioselective cyclization coupling of alkenyl oxime. Chinese Chemical Letters, 2026, 37(7): 112000-. doi: 10.1016/j.cclet.2025.112000

Get Citation

PDF

XML

Metrics

PDF Downloads(0)
Abstract views(1949)
HTML views(75)

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