Citation: Zhu Lanping, Zhao Shuai, Cang Zhipeng, Zhou Andi, Chen Xin. An Efficient Method for the Synthesis of 2-Methyl-1-substituted-phenyl-2-propylamines[J]. Chinese Journal of Organic Chemistry, ;2018, 38(7): 1695-1702. doi: 10.6023/cjoc201801029 shu

An Efficient Method for the Synthesis of 2-Methyl-1-substituted-phenyl-2-propylamines

School of Pharmaceutical Engineering & Life Science, Changzhou University, Changzhou 213164

Corresponding author: Chen Xin, xinchen@cczu.edu.cn
Received Date: 21 January 2018
Revised Date: 7 March 2018
Available Online: 4 July 2018
Fund Project: the National Natural Science Foundation of China 21272029Project supported by the National Natural Science Foundation of China (No. 21272029)

Figures(3)

2-Methyl-1-substituted-phenyl-2-propylamines are key intermediates for synthesizing the β₂ adrenoceptor agonists. A series of 2-methyl-1-substituted-phenyl-2-propylamines have been synthesized starting from substituted benzyl chlorides. Isobutyronitrile was alkylated with benzyl chloride, and the resulting 2-methyl-1-aryl-2-butylcynide was hydrolyzed to give the corresponding acid. Curtius rearrangement of the acid and catalytic hydrolgenation of the resulting Cbz-protected amine afforded the title compound. The method is simple and safe to operate, the raw materials are readily available and the overall yields are satisfactory. This method is suitable for the synthesis of 2-methyl-2-(2-methylphenyl)-phenyl-2-propylamine and various kinds of derivatives.
- 2-methyl-1-substituted-phenyl-2-propylamine,
- β₂ adrenoceptor agonist,
- Curtius rearrangement,
- synthesis
1. [1]
  Pasternak, A; Goble, S. D.; Reynalda, K. Bioorg. Med. Chem. Lett. 2009, 19, 6237. doi: 10.1016/j.bmcl.2009.08.076
2. [2]
  Southers, J. A.; Bauman, J. N.; Kalgutkar, A. S. Med. Chem. Lett. 2010, 1, 219. doi: 10.1021/ml100058w
3. [3]
  Jesudason, C. D.; Trankle, W. G.; Shuker, A. J. Med. Chem. Lett. 2011, 2, 583. doi: 10.1021/ml200071k
4. [4]
  Czeskis, B. A.; Wheeler, W. J.; Clodfelter, D. K. J. Labelled Compd. Radiopharm. 2006, 49, 663. doi: 10.1002/(ISSN)1099-1344
5. [5]
  Tautermann, C. S.; Pautsch, A. Med. Chem. Lett. 2011, 2, 414. doi: 10.1021/ml100247s
6. [6]
  Hoenke, C.; Bouyssou, T.; Konetzki, I. Bioorg. Med. Chem. Lett. 2009, 19, 6640. doi: 10.1016/j.bmcl.2009.10.013
7. [7]
  Hoenke, C.; Bouyssou, T.; Konetzki, I. Bioorg. Med. Chem. Lett. 2010, 20, 1410. doi: 10.1016/j.bmcl.2009.12.087
8. [8]
  Goldfuss, B.; Denisenko, D.; Kulhanek, J. Chem.-Eur. J. 2004, 10, 4252. doi: 10.1002/(ISSN)1521-3765
9. [9]
  Ritter, J. J.; Minieri, P. P. J. Am. Chem. Soc. 1948, 70, 4045. doi: 10.1021/ja01192a022
10. [10]
  Florvall, L.; Fagervall, I.; Ask, A.-L.; Ross, S. B. J. Med. Chem. 1986, 29, 2250. doi: 10.1021/jm00161a020
11. [11]
  Wang, J. B.; Sun, X. Q.; Chen, X. Chin. J. Org. Chem. 2013, 33, 634 (in Chinese).
12. [12]
  Ling. P. X.; Fang, S. L.; Yin, X. S.; Chen, K.; Sun, B. Z.; Shi, B. F. Chem.-Eur. J. 2015, 21, 17503. doi: 10.1002/chem.201502621
13. [13]
  Espino, C. G.; Fiori, K. W.; Bois, J. D. J. Am. Chem. Soc. 2004, 126, 15378. doi: 10.1021/ja0446294
14. [14]
  Ninomiya, K.; Shioiri, T.; Yamada, S. Tetrahedron 1974, 30, 2151. doi: 10.1016/S0040-4020(01)97352-1
15. [15]
  Jasys, V. J.; Lombardo, F.; Volkmann, R. A. J. Am. Chem. Soc. 2000, 122, 466. doi: 10.1021/ja992652x
16. [16]
  Fleming, F. F.; Ghosh, S.; Steward, O. W. J. Org. Chem. 2008, 73, 2803. doi: 10.1021/jo702681e
17. [17]
  Jiang, X.; Hartwig, J. F. Angew. Chem., Int. Ed. 2017, 56, 8887. doi: 10.1002/anie.v56.30
18. [18]
  Spectral data for the Curtius rearrangement intermediate 2-methyl-1-(2-methylphenyl)-2-propyl isocyanate: ¹H NMR (300 MHz, CDCl₃) δ: 7. 18~7. 17 (m, 4H), 2. 84 (s, 2H), 2. 36 (s, 3H), 1. 38 (s, 6H); ¹³C NMR (75 MHz, CDCl₃) δ: 137. 34, 135. 23, 131. 59, 130. 73, 127. 11, 125. 68, 122. 84, 59. 32, 45. 31, 30. 65, 20. 38; HRMS (ESI, positive) calcd for C₁₂H₁₅NO[M+H]⁺ 190. 1226, found 190. 1306.
19. [19]
  Jung, M. E.; Amico, D. C. J. Am. Chem. Soc. 1995, 117, 7379. doi: 10.1021/ja00133a011
1. [1]
  Jing WU , Puzhen HUI , Huilin ZHENG , Pingchuan YUAN , Chunfei WANG , Hui WANG , Xiaoxia GU . Synthesis, crystal structures, and antitumor activities of transition metal complexes incorporating a naphthol-aldehyde Schiff base ligand. Chinese Journal of Inorganic Chemistry, 2024, 40(12): 2422-2428. doi: 10.11862/CJIC.20240278
2. [2]
  Xinting XIONG , Zhiqiang XIONG , Panlei XIAO , Xuliang NIE , Xiuying SONG , Xiuguang YI . Synthesis, crystal structures, Hirshfeld surface analysis, and antifungal activity of two complexes Na(Ⅰ)/Cd(Ⅱ) assembled by 5-bromo-2-hydroxybenzoic acid ligands. Chinese Journal of Inorganic Chemistry, 2024, 40(9): 1661-1670. doi: 10.11862/CJIC.20240145
3. [3]
  Jiaming Xu , Yu Xiang , Weisheng Lin , Zhiwei Miao . Research Progress in the Synthesis of Cyclic Organic Compounds Using Bimetallic Relay Catalytic Strategies. University Chemistry, 2024, 39(3): 239-257. doi: 10.3866/PKU.DXHX202309093
4. [4]
  Yuanyuan Ping , Wangqing Kong . 光催化碳氢键官能团化合成1-苯基-1,2-乙二醇. University Chemistry, 2025, 40(6): 238-247. doi: 10.12461/PKU.DXHX202408092
5. [5]
  Aiyi Xin , Jiawei Li , Xinyang Ran , Chuanjiang Fu , Zhiguo Wang . Collaborative Science and Education Based Experimental Design in Organic Chemistry: A Case Study of the Nucleophilic Substitution Reaction of 2-Hydroxymethyl-4,6-Di-Tert-Butylphenol. University Chemistry, 2025, 40(5): 366-375. doi: 10.12461/PKU.DXHX202407031
6. [6]
  Anqiu LIU , Long LIN , Dezhi ZHANG , Junyu LEI , Kefeng WANG , Wei ZHANG , Junpeng ZHUANG , Haijun HAO . Synthesis, structures, and catalytic activity of aluminum and zinc complexes chelated by 2-((2,6-dimethylphenyl)amino)ethanolate. Chinese Journal of Inorganic Chemistry, 2024, 40(4): 791-798. doi: 10.11862/CJIC.20230424
7. [7]
  Kangmin Wang , Liqiu Wan , Jingyu Wang , Chunlin Zhou , Ke Yang , Liang Zhou , Bijin Li . Multifunctional 2-(2′-hydroxyphenyl)benzoxazoles: Ready synthesis, mechanochromism, fluorescence imaging, and OLEDs. Chinese Chemical Letters, 2024, 35(10): 109554-. doi: 10.1016/j.cclet.2024.109554
8. [8]
  Huijuan Liao , Yulin Xiao , Dong Xue , Mingyu Yang , Jianyang Dong . Synthesis of 1-Benzyl Isoquinoline via the Minisci Reaction. University Chemistry, 2025, 40(7): 294-299. doi: 10.12461/PKU.DXHX202409092
9. [9]
  Xiaofang Li , Zhigang Wang . Modulating d_z²-orbital occupancy of Au cocatalysts for enhanced photocatalytic H₂O₂ production. Acta Physico-Chimica Sinica, 2025, 41(7): 100080-. doi: 10.1016/j.actphy.2025.100080
10. [10]
  Weikang Wang , Yadong Wu , Jianjun Zhang , Kai Meng , Jinhe Li , Lele Wang , Qinqin Liu . 三聚氰胺泡沫支撑的S型硫铟锌镉/硫掺杂氮化碳异质结的绿色H₂O₂合成：协同界面电荷转移调控与局域光热效应. Acta Physico-Chimica Sinica, 2025, 41(8): 100093-. doi: 10.1016/j.actphy.2025.100093
11. [11]
  Liyang ZHANG , Dongdong YANG , Ning LI , Yuanyu YANG , Qi MA . Crystal structures, luminescent properties and Hirshfeld surface analyses of three cadmium(Ⅱ) complexes based on 2-(3-(pyridin-2-yl)-1H-pyrazol-1-yl)benzoate. Chinese Journal of Inorganic Chemistry, 2024, 40(10): 1943-1952. doi: 10.11862/CJIC.20240079
12. [12]
  Wei Zhong , Dan Zheng , Yuanxin Ou , Aiyun Meng , Yaorong Su . K原子掺杂高度面间结晶的g-C₃N₄光催化剂及其高效H₂O₂光合成. Acta Physico-Chimica Sinica, 2024, 40(11): 2406005-. doi: 10.3866/PKU.WHXB202406005
13. [13]
  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
14. [14]
  Ziliang KANG , Jiamin ZHANG , Hong AN , Xiaohua LIU , Yang CHEN , Jinping LI , Libo LI . Preparation and water adsorption properties of CaCl₂@MOF-808 in-situ composite moulded particles. Chinese Journal of Inorganic Chemistry, 2024, 40(11): 2133-2140. doi: 10.11862/CJIC.20240282
15. [15]
  Zelong LIANG , Shijia QIN , Pengfei GUO , Hang XU , Bin ZHAO . Synthesis and electrocatalytic CO₂ reduction performance of metal-organic framework catalysts loaded with silver particles. Chinese Journal of Inorganic Chemistry, 2025, 41(1): 165-173. doi: 10.11862/CJIC.20240409
16. [16]
  Chao Liu , Huan Yu , Jiaming Li , Xi Yu , Zhuangzhi Yu , Yuxi Song , Feng Zhang , Qinfang Zhang , Zhigang Zou . Facile synthesis of hierarchical Ti₃C₂/Bi₁₂O₁₇Br₂ Schottky heterojunction with photothermal effect for solar-driven antibiotics photodegradation. Acta Physico-Chimica Sinica, 2025, 41(7): 100075-. doi: 10.1016/j.actphy.2025.100075
17. [17]
  Qiaowen CHANG , Ke ZHANG , Guangying HUANG , Nuonan LI , Weiping LIU , Fuquan BAI , Caixian YAN , Yangyang FENG , Chuan ZUO . Syntheses, structures, and photo-physical properties of iridium phosphorescent complexes with phenylpyridine derivatives bearing different substituting groups. Chinese Journal of Inorganic Chemistry, 2025, 41(2): 235-244. doi: 10.11862/CJIC.20240311
18. [18]
  Yifeng TAN , Ping CAO , Kai MA , Jingtong LI , Yuheng WANG . Synthesis of pentaerythritol tetra(2-ethylthylhexoate) catalyzed by h-MoO₃/SiO₂. Chinese Journal of Inorganic Chemistry, 2024, 40(11): 2155-2162. doi: 10.11862/CJIC.20240147
19. [19]
  Zhaoyang WANG , Chun YANG , Yaoyao Song , Na HAN , Xiaomeng LIU , Qinglun WANG . Lanthanide(Ⅲ) complexes derived from 4′-(2-pyridyl)-2, 2′∶6′, 2″-terpyridine: Crystal structures, fluorescent and magnetic properties. Chinese Journal of Inorganic Chemistry, 2024, 40(8): 1442-1451. doi: 10.11862/CJIC.20240114
20. [20]
  Yue Li , Minghao Fan , Conghui Wang , Yanxun Li , Xiang Yu , Jun Ding , Lei Yan , Lele Qiu , Yongcai Zhang , Longlu Wang . 3D layer-by-layer amorphous MoS_x assembled from [Mo₃S₁₃]^2- clusters for efficient removal of tetracycline: Synergy of adsorption and photo-assisted PMS activation. Chinese Chemical Letters, 2024, 35(9): 109764-. doi: 10.1016/j.cclet.2024.109764

Get Citation

PDF

XML

Metrics

PDF Downloads(23)
Abstract views(1371)
HTML views(277)

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