Citation: Luo Xiao, Jiao Ning. From Hydroxylamines to Anilines via Trifluoroacetic Anhydride (TFAA) Assisted Stieglitz Rearrangement[J]. Acta Chimica Sinica, ;2020, 78(8): 758-762. doi: 10.6023/A20050191 shu

From Hydroxylamines to Anilines via Trifluoroacetic Anhydride (TFAA) Assisted Stieglitz Rearrangement

Luo Xiao ,
Jiao Ning ^,

State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191

Corresponding author: Jiao Ning, jiaoning@pku.edu.cn
Received Date: 28 May 2020
Available Online: 9 July 2020
Fund Project: the National Natural Science Foundation of China 21632001the National Natural Science Foundation of China 21772002Project supported by the National Natural Science Foundation of China (Nos. 21632001 and 21772002)

Figures(3)

Hydroxylamines have a wide range of biological properties and have been used as a useful synthon in organic synthesis. In the past decades, many transformations of hydroxylamines have been developed and widely applied. In contrast, one of the interesting reactions of hydroxylamines through C—C bond cleavage, named Stieglitz rearrangement, was less developed. Due to the poor leaving ability of the hydroxyl groups, the reported Stieglitz rearrangement reactions suffered from the harsh conditions and the very limited substrate scope with triarylmethyl hydroxylamine substrates. Since an interesting C—C bond cleavage is involved which will extend the synthetic application of hydroxylamine, the practical method under mild conditions with broad substrate scope for Stieglitz rearrangement is very desired. However, there are three potential problems which need to be addressed. First, the activator must selectively react with the hydroxyl group but not the N-nucleophile of the hydroxylamine substrates. Secondary, a suitable leaving group must be generated to weaken the N—O bond. In addition, the employed activator must be inactive to the formed imine intermediates and the subsequent amine products. Herein, we developed an efficient Stieglitz rearrangement reaction of hydroxylamines under mild conditions for the preparation of corresponding primary aryl amines. This chemistry using simple trifluoroacetic anhydride (TFAA) as an activator resolves the issues mentioned above and therefore provides a practical protocol for the further transformation and application of hydroxylamines. Mechanistic studies demonstrate that the in situ generation of an active trifluoroacetate leaving group derived the aryl migration process via both of the C—C and N—O bond cleavage. A general procedure for the TFAA assisted stieglitz rearrangement is as follows: BF₃·Et₂O (28.4 mg, 0.2 mmol), TFAA (46.2 mg, 0.22 mmol) were added to the solution of hydroxylamine (0.2 mmol) in 2 mL hexafluoroisopropanol (HFIP). The reaction mixture was stirred at room temperature for 1 h. After that, the reaction was quenched by 4 mL 2 mol/L NaOH (aq.) and extracted by the mixture of petroleum ether and ethyl acetate (1:1, V:V). The combined organic phase was concentrated, and purified by flash chromatography on a short silica gel to afford the desired product (eluent: petroleum ether/ethyl acetate).
- C—C bond cleavage,
- Stieglitz rearrangement,
- hydroxylamine,
- aniline,
- aryl migration
1. [1]
  (a) Piechnick, R.; Heck, M.; Sommer, M. E. Biochemistry 2011, 50, 7168; (b) Chen, Y.; Wang, X.; Xiang, W.; He, L.; Tang, M.; Wang, F.; Wang, T.; Yang, Z.; Yi, Y.; Wang, H.; Niu, T.; Zheng, L.; Lei, L.; Li, X.; Song, H.; Chen, L. J. Med. Chem. 2016, 59, 5488.
2. [2]
3. [3]
  For some examples in recent years: (a) Nguyen, T. B.; Martel, A.; Dhal, R.; Dujardin, G. Org. Lett. 2008, 10, 4493; (b) Guimond, N.; MacDonald, M. J.; Lemieux, V.; Beauchemin, A. M. J. Am. Chem. Soc. 2012, 134, 16571; (c) Pusterla, I.; Bode, J. W. Angew. Chem. Int. Ed. 2012, 51, 513; (d) Li, J.; He, Y.; Ren, X.; Shi, X.; Yang, S.; Gao, X.; Huang, G. Chin. J. Chem. 2013, 31, 1003; (e) Hesp, C. R.; MacDonald, M. J.; Zahedi, M. M.; Bilodeau, D. A.; Zhao, S. B.; Pesant, M.; Beauchemin, A. M. Org. Lett. 2015, 17, 5136; (f) Sun, H. B.; Gong, L.; Tian, Y. B.; Wu, J. G.; Zhang, X.; Liu, J.; Fu, Z.; Niu, D. Angew. Chem. Int. Ed. 2018, 57, 9456.
4. [4]
  (a) Stieglitz, J.; Leech, P. N. Ber. 1913, 46, 2147; (b) Stieglitz, J.; Leech, P. N. J. Am. Chem. Soc. 1914, 36, 272. (c) Morgan, A. F. J. Am. Chem. Soc. 1916, 38, 2095; (d) Newman, M. S.; Hay, P. M. J. Am. Chem. Soc. 1953, 75, 2322; (e) Stolyarov, B. V.; Krylov, A. I.; Ioffe, B. V. Zh. Org. Khim. 1977, 13, 2004.
5. [5]
6. [6]
7. [7]
8. [8]
  Colomer, I.; Chamberlain, A. E. R.; Haughey, M. B.; Donohoe, T. J. Nat. Rev. Chem. 2017, 1, 0088. doi: 10.1038/s41570-017-0088
9. [9]
  (a) Mlynarski, S. N.; Karns, A. S.; Morken, J. P. J. Am. Chem. Soc. 2012, 134, 16449; (b) Xiao, Q.; Tian, L.; Tan, R.; Xia, Y.; Qiu, D.; Zhang, Y.; Wang, J. Org. Lett. 2012, 14, 4230; (c) Zhu, C.; Li, G.; Ess, D. H.; Falck, J. R.; Kurti, L. J. Am. Chem. Soc. 2012, 134, 18253; (d) Voth, S.; Hollett, J. W.; McCubbin, J. A. J. Org. Chem. 2015, 80, 2545.
1. [1]
  Yinuo Wang , Siran Wang , Yilong Zhao , Dazhen Xu . Selective Synthesis of Diarylmethyl Anilines and Triarylmethanes via Multicomponent Reactions: Introduce a Comprehensive Experiment of Organic Chemistry. University Chemistry, 2024, 39(8): 324-330. doi: 10.3866/PKU.DXHX202401063
2. [2]
  Danqing Wu , Jiajun Liu , Tianyu Li , Dazhen Xu , Zhiwei Miao . Research Progress on the Simultaneous Construction of C—O and C—X Bonds via 1,2-Difunctionalization of Olefins through Radical Pathways. University Chemistry, 2024, 39(11): 146-157. doi: 10.12461/PKU.DXHX202403087
3. [3]
  Ronghao Zhao , Yifan Liang , Mengyao Shi , Rongxiu Zhu , Dongju Zhang . Investigation into the Mechanism and Migratory Aptitude of Typical Pinacol Rearrangement Reactions: A Research-Oriented Computational Chemistry Experiment. University Chemistry, 2024, 39(4): 305-313. doi: 10.3866/PKU.DXHX202309101
4. [4]
  Li Jiang , Changzheng Chen , Yang Su , Hao Song , Yanmao Dong , Yan Yuan , Li Li . Electrochemical Synthesis of Polyaniline and Its Anticorrosive Application: Improvement and Innovative Design of the “Chemical Synthesis of Polyaniline” Experiment. University Chemistry, 2024, 39(3): 336-344. doi: 10.3866/PKU.DXHX202309002
5. [5]
  Geyang Song , Dong Xue , Gang Li . Recent Advances in Transition Metal-Catalyzed Synthesis of Anilines from Aryl Halides. University Chemistry, 2024, 39(2): 321-329. doi: 10.3866/PKU.DXHX202308030
6. [6]
  Tingbo Wang , Yao Luo , Bingyan Hu , Ruiyuan Liu , Jing Miao , Huizhe Lu . Quantitative Computational Study on the Claisen Rearrangement Reaction of Allyl Phenyl Ethers: An Introduction to a Computational Chemistry Experiment. University Chemistry, 2024, 39(11): 278-285. doi: 10.12461/PKU.DXHX202403082
7. [7]
  Jiabo Huang , Quanxin Li , Zhongyan Cao , Li Dang , Shaofei Ni . Elucidating the Mechanism of Beckmann Rearrangement Reaction Using Quantum Chemical Calculations. University Chemistry, 2025, 40(3): 153-159. doi: 10.12461/PKU.DXHX202405172
8. [8]
  Jiajia Li , Xiangyu Zhang , Zhihan Yuan , Zhengyang Qian , Jian Zhu . 3D Printing Based on Photo-Induced Reversible Addition-Fragmentation Chain Transfer Polymerization. University Chemistry, 2024, 39(5): 11-19. doi: 10.3866/PKU.DXHX202309073
9. [9]
  Jiaqi AN , Yunle LIU , Jianxuan SHANG , Yan GUO , Ce LIU , Fanlong ZENG , Anyang LI , Wenyuan WANG . Reactivity of extremely bulky silylaminogermylene chloride and bonding analysis of a cubic tetragermylene. Chinese Journal of Inorganic Chemistry, 2024, 40(8): 1511-1518. doi: 10.11862/CJIC.20240072
10. [10]
  Yonghui ZHOU , Rujun HUANG , Dongchao YAO , Aiwei ZHANG , Yuhang SUN , Zhujun CHEN , Baisong ZHU , Youxuan ZHENG . Synthesis and photoelectric properties of fluorescence materials with electron donor-acceptor structures based on quinoxaline and pyridinopyrazine, carbazole, and diphenylamine derivatives. Chinese Journal of Inorganic Chemistry, 2024, 40(4): 701-712. doi: 10.11862/CJIC.20230373
11. [11]
  Jinyao Du , Xingchao Zang , Ningning Xu , Yongjun Liu , Weisi Guo . Electrochemical Thiocyanation of 4-Bromoethylbenzene. University Chemistry, 2024, 39(6): 312-317. doi: 10.3866/PKU.DXHX202310039
12. [12]
  Lei Wan , Yizhou Tong , Xi Lu , Yao Fu . Cobalt-catalyzed reductive alkynylation to construct C(sp)-C(sp³) and C(sp)-C(sp²) bonds. Chinese Chemical Letters, 2024, 35(7): 109283-. doi: 10.1016/j.cclet.2023.109283
13. [13]
  Chengqian Mao , Yanghan Chen , Haotong Bai , Junru Huang , Junpeng Zhuang . Photodimerization of Styrylpyridinium Salt and Its Application in Silk Screen Printing. University Chemistry, 2024, 39(5): 354-362. doi: 10.3866/PKU.DXHX202312014
14. [14]
  Xiuyun Wang , Jiashuo Cheng , Yiming Wang , Haoyu Wu , Yan Su , Yuzhuo Gao , Xiaoyu Liu , Mingyu Zhao , Chunyan Wang , Miao Cui , Wenfeng Jiang . Improvement of Sodium Ferric Ethylenediaminetetraacetate (NaFeEDTA) Iron Supplement Preparation Experiment. University Chemistry, 2024, 39(2): 340-346. doi: 10.3866/PKU.DXHX202308067
15. [15]
  Jiao Li , Chenyang Zhang , Chuhan Wu , Yan Liu , Xuejian Zhang , Xiao Li , Yongtao Li , Jing Sun , Zhongmin Su . Defined organic-octamolybdate crystalline superstructures derived Mo₂C@C as efficient hydrogen evolution electrocatalysts. Chinese Chemical Letters, 2024, 35(6): 108782-. doi: 10.1016/j.cclet.2023.108782
16. [16]
  Junmeng Luo , Qiongqiong Wan , Suming Chen . Chemistry-driven mass spectrometry for structural lipidomics at the C=C bond isomer level. Chinese Chemical Letters, 2025, 36(1): 109836-. doi: 10.1016/j.cclet.2024.109836
17. [17]
  Baitong Wei , Jinxin Guo , Xigong Liu , Rongxiu Zhu , Lei Liu . Theoretical Study on the Structure, Stability of Hydrocarbon Free Radicals and Selectivity of Alkane Chlorination Reaction. University Chemistry, 2025, 40(3): 402-407. doi: 10.12461/PKU.DXHX202406003
18. [18]
  Yongpo Zhang , Xinfeng Li , Yafei Song , Mengyao Sun , Congcong Yin , Chunyan Gao , Jinzhong Zhao . Synthesis of Chlorine-Bridged Binuclear Cu(I) Complexes Based on Conjugation-Driven Cu(II) Oxidized Secondary Amines. University Chemistry, 2024, 39(5): 44-51. doi: 10.3866/PKU.DXHX202309092
19. [19]
  Shengkai Li , Yuqin Zou , Chen Chen , Shuangyin Wang , Zhao-Qing Liu . Defect engineered electrocatalysts for C–N coupling reactions toward urea synthesis. Chinese Chemical Letters, 2024, 35(8): 109147-. doi: 10.1016/j.cclet.2023.109147
20. [20]
  Kebo Xie , Qian Zhang , Fei Ye , Jungui Dai . A multi-enzymatic cascade reaction for the synthesis of bioactive C-oligosaccharides. Chinese Chemical Letters, 2024, 35(6): 109028-. doi: 10.1016/j.cclet.2023.109028

Get Citation

PDF

XML

Metrics

PDF Downloads(17)
Abstract views(1889)
HTML views(484)

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