Citation: Liu Qingyun, Zhao Xianghu, Li Jialu, Cao Song. Synthesis of Cyanated Difluorostyrene Derivatives via S_N2' Cyanomethylation of α-(Trifluoromethyl)styrenes with Acetonitrile[J]. Acta Chimica Sinica, ;2018, 76(12): 945-950. doi: 10.6023/A18080322 shu

Synthesis of Cyanated Difluorostyrene Derivatives via S_N2' Cyanomethylation of α-(Trifluoromethyl)styrenes with Acetonitrile

Shanghai Key Laboratory of Chemical Biology, School of Pharmacy, East China University of Science and Technology (ECUST), Shanghai 200237

Corresponding author: Cao Song, scao@ecust.edu.cn
Received Date: 7 August 2018
Available Online: 14 December 2018
Fund Project: Project supported by the National Natural Science Foundation of China (Nos. 21472043, 21272070)the National Natural Science Foundation of China 21272070the National Natural Science Foundation of China 21472043

Figures(4)

Nitriles are important structural motifs found in agrochemicals, pharmaceuticals, and natural products. Furthermore, nitriles are versatile synthetic precursors for organic synthesis because they can be easily converted into various functionalities, such as amides, ketones, esters, primary amines, aldehydes, carboxylic acids, and nitrogen-containing heterocycles. Therefore, the development of efficient methods for the synthesis of nitrile compounds has attracted much attention from synthetic chemists. Cyanomethylation of various substrates is a synthetically useful reaction because a variety of diversely cyano-containing compounds could be readily prepared. Acetonitrile is the simplest commercially available alkyl nitrile, which can act as the cyanomethyl carbanion source. The traditional method for the cyanomethylation of organic molecules is deprotonation of acetonitrile in the presence of strong base. Alternatively, transition-metal-catalyzed C—H bond activation of acetonitrile represents an attractive approach to cyanomethylated compounds due to its atom and step economy. In this communication, we developed a simple and highly efficient method for the synthesis of cyanated difluorostyrene derivatives by cyanomethylation of α-(trifluoromethyl)styrenes using cheap and commercially available acetonitrile as the CH₂CN^- source. The reaction proceeded smoothly in the presence of LiHMDS at room temperature and was finished within 1 h, affording the cyanated gem-difluoroalkenes in moderate to good yields. Furthermore, the cyanomethylation reaction exhibited good substrate scope and functional group compatibility. A general procedure for the cyanomethylation of α-(trifluoromethyl)styrenes with acetonitrile is as following: α-(trifluoromethyl)styrenes 1 (0.5 mmol) was dissolved in acetonitrile 2a (4 mL) at room temperature under argon atmosphere. Subsequently, a solution of the LiHMDS in THF (1.5 mL, 1.0 mol/L, 1.5 mmol, 3.0 equiv.) was added dropwise within 50 min and stirring was continued for further 10 min (monitored by TLC). After completion of the reaction, the reaction mixture was quenched with saturated aqueous solution of NH₄Cl (15 mL) and extracted with ethyl acetate (5 mL×3). The combined organic layer was dried over anhydrous Na₂SO₄, filtered, and concentrated under vacuum. The crude residue was then purified by column chromatography on silica gel [(V(hexane)/V(ethyl acetate)＝10:1~6:1] directly to afford the pure target compounds.
- α-(trifluoromethyl)styrenes,
- acetonitrile,
- cyanomethylation,
- cyanated difluorostyrenes
1. [1]
  (a) Wang, J.; Liu, H. Chin. J. Org. Chem. 2012, 32, 1643. (王江, 柳红, 有机化学, 2012, 32, 1643.); (b) Powell, K. J.; Han, L.-C.; Sharma, P.; Moses, J. E. Org. Lett. 2014, 16, 2158.
2. [2]
  (a) Rappoport, Z. The Chemistry of the Cyano Group, Interscience Publishers, London, 1970; (b) Larock, R. C. Comprehensive Organic Transformations: A Guide to Functional Group Preparation, 2nd ed., Wiley-VCH, Weinheim, 1999, p. 821; (c) Ishii, G.; Harigae, R.; Moriyama, K.; Togo, H. Tetrahedron 2013, 69, 1462; (d) Ma, X.-T.; Li, B.; Xiao, Y.-L.; Yu, X.-C.; Su, C.-L.; Xu, Q. Chin. J. Org. Chem. 2017, 37, 2034. (马献涛, 李波, 肖映林, 余小春, 苏陈良, 徐清, 有机化学, 2017, 37, 2034.).
3. [3]
  (a) McManus, J. B.; Nicewicz, D. A. J. Am. Chem. Soc. 2017, 139, 2880; (b) Wen, Q.-D.; Jin, J.-S.; Zhang, L.-P.; Luo, Y.; Lu, P.; Wang, Y.-G. Tetrahedron Lett. 2014, 55, 1271; (c) Anbarasan, P.; Schareina, T.; Beller, M. Chem. Soc. Rev. 2011, 40, 5049; (d) Ye, X.; Zeng, X.-P.; Zhou, J. Acta Chim. Sinica 2016, 74, 984. (叶旭, 曾兴平, 周剑, 化学学报, 2016, 74, 984.); (e) Zhou, Q.-Q.; Liu, D.; Xiao, W.-J.; Lu, L.-Q. Acta Chim. Sinica 2017, 75, 110. (周泉泉, 刘丹, 肖文精, 陆良秋, 化学学报, 2017, 75, 110.); (f) Li, Z.-L.; Sun, K.-K.; Cai, C. Org. Chem. Front. 2018, 5, 1848; (g) Li, J.-P.; Yin, J.-H.; Yu, C.; Zhang, W.-X.; Xi, Z.-F. Acta Chim. Sinica 2017, 75, 733. (李嘉鹏, 殷剑昊, 俞超, 张文雄, 席振峰, 化学学报, 2017, 75, 733.); (h) Zhang, W.; Hu, C.-X.; Zhou, X.-G. Chin. J. Org. Chem. 2017, 37, 1246. (张伟, 胡晨旭, 周向葛, 有机化学, 2017, 37, 1246.).
4. [4]
  (a) López, R.; Palomo, C. Angew. Chem. Int. Ed. 2015, 54, 13170; (b) Zhong, S.-S.; Huang, P.; Wang, X.-Y.; Lin, M.; Ge, C.-H. Chin. J. Org. Chem. 2018, 38, 1199. (仲帅帅, 黄鹏, 王兴越, 林觅, 葛春华, 有机化学, 2018, 38, 1199.); (c) Wang, H.-J.; Zhou, X.-X.; Xia, H.-P. Chin. J. Chem. 2018, 36, 93; (d) Ao, Y.-F.; Wang, Q.-Q.; Wang, D.-X. Chin. J. Org. Chem. 2016, 36, 2333. (敖宇飞, 王其强, 王德先, 有机化学, 2016, 36, 2333.).
5. [5]
  (a) Forslund, K.; Morant, M.; J rgensen, B.; Olsen, C. E.; Asamizu, E.; Sato, S.; Tabata, S.; Bak, S. Plant Physiol. 2004, 135, 71; (b) Fleming, F. F.; Yao, L.-H.; Ravikumar, P. C.; Funk, L.; Shook, B. C. J. Med. Chem. 2010, 53, 7902.
6. [6]
  Fatiadi, A. J. In The Chemistry of Functional Groups, Supplement C: The Chemistry of Triple-Bonded Functional Groups, Part 2, Eds.: Pappoport, Z.; Patai, S., Wiley, London, 1983, p. 1057.
7. [7]
  (a) Ni, Z.-Q.; Huang, X.; Wang, J.-C.; Pan, Y.-J. RSC Adv. 2016, 6, 522; (b) Yu, Y.-L.; Zhuang, S.-Y.; Liu, P.; Sun, P.-P. J. Org. Chem. 2016, 81, 11489; (c) Zhang, J.; Wu, W.; Ji, X.-F.; Cao, S. RSC Adv. 2015, 5, 20562.
8. [8]
  (a) Shen, J.-X.; Yang, D.-J.; Liu, Y.-X.; Qin, S.-S.; Zhang, J.-W.; Sun, J.-K.; Liu, C.-H.; Liu, C.-Y.; Zhao, X.-M.; Chu, C.-H.; Liu, R.-H. Org. Lett. 2014, 16, 350; (b) Ariafard, A.; Ghari, H.; Khaledi, Y.; Bagi, A. H.; Wierenga, T. S.; Gardiner, M. G.; Canty, A. J. ACS Catal. 2016, 6, 60; (c) Satoh, Y.; Obora, Y. RSC Adv. 2014, 4, 15736; (d) Qiao, K.; Zhang, D.; Zhang, K.; Yuan, X.; Zheng, M.-W.; Guo, T.-F.; Fang, Z.; Wan, L.; Guo, K. Org. Chem. Front. 2018, 5, 1129; (e) Deng, T.; Wang, H.-J.; Cai, C. Eur. J. Org. Chem. 2014, 7259; (f) Voskressensky, L. G.; Festa, A. A.; Storozhenko, O. A.; Le, T. A.; Nguyen, V. T.; Varlamov, A. V. RSC Adv. 2015, 5, 12442.
9. [9]
  (a) Zhang, W.; Yang, S.-P.; Shen, Z.-M. Adv. Synth. Catal. 2016, 358, 2392; (b) Liu, Y.-B.; Yang, K.; Ge, H.-B. Chem. Sci. 2016, 7, 2804; (c) Zhang, Y.-X.; Yan, W.-T.; Wang, Y.-K.; Weng, Z.-Q. Org. Lett. 2017, 19, 5478; (d) Hoff, B. H. Synthesis 2018, 50, 2824; (e) Rossi, L.; Feroci, M.; Inesi, A. Mini-Reviews Org. Chem. 2005, 2, 79; (f) Wu, Q.; Li, Y.-B.; Wang, C.-Y.; Zhang, J.-Y.; Huang, M.-M.; Kim, J. K.; Wu, Y.-J. Org. Chem. Front. 2018, 5, 2496.
10. [10]
  Kumagai, N.; Matsunaga, S.; Shibasaki, M. J. Am. Chem. Soc. 2004, 126, 13632. doi: 10.1021/ja0450509
11. [11]
  (a) Kaiser, E. M.; Hauser, C. R. J. Org. Chem. 1968, 33, 3402; (b) Mamuye, A. D.; Castoldi, L.; Azzena, U.; Holzer, W.; Pace, V. Org. Biomol. Chem. 2015, 13, 1969.
12. [12]
  (a) Ko, E. Y.; Lim, C. H.; Chung, K. H. Bull. Korean Chem. Soc. 2006, 27, 432; (b) Guranova, N. I.; Varlamov, A. V.; Ilyushenkova, V. V.; Sokolova, E. A.; Borisova, T. N.; Aksenov, A. V.; Khrustalev, V. N.; Voskressensky, L. G. Mendeleev Commun. 2017, 27, 506.
13. [13]
  Gao, X.-S.; Dong, W.-H.; Hu, B.; Gao, H.; Yuan, Y.; Xie, X.-M.; Zhang, Z.-G. RSC Adv. 2017, 7, 49299. doi: 10.1039/C7RA10090F
14. [14]
  Rao, V. N. B.; Kumar, K.; Singh, R. P. Org. Biomol. Chem. 2015, 13, 9755. doi: 10.1039/C5OB01560J
15. [15]
  Gajulapalli, V. P. R.; Vinayagam, P.; Kesavan, V. Org. Biomol. Chem. 2014, 12, 4186. doi: 10.1039/c4ob00271g
16. [16]
  Velcicky, J.; Soicke, A.; Steiner, R.; Schmalz, H. J. J. Am. Chem. Soc. 2011, 133, 6948. doi: 10.1021/ja201743j
17. [17]
  (a) Wang, K.-C; Chen, X.; Yuan, M.; Yao, M.; Zhu, H.-C.; Xue, Y.-B.; Luo, Z.-W.; Zhang, Y.-H. J. Org. Chem. 2018, 83, 1525; (b) Wu, T.; Mu, X.; Liu, G.-S. Angew. Chem. 2011, 123, 12786.
18. [18]
  (a) Anxionnat, B.; Pardo, D. G.; Ricci, G.; Cossy, J. Org. Lett. 2011, 13, 4084; (b) Wang, G.-W.; Zhou, A.-X.; Wang, J.-J.; Hu, R.-B.; Yang, S.-D. Org. Lett. 2013, 15, 5270; (c) Tang, S.; Li, S.-H.; Li, Z.-H.; Zhou, D.; Sheng, R.-L. Tetrahedron Lett. 2015, 56, 1423; (d) Kumagai, N.; Matsunaga, S.; Shibasaki, M. J. Am. Chem. Soc. 2004, 126, 13632.
19. [19]
  (a) Chelucci, G. Chem. Rev. 2012, 112, 1344; (b) Amii, H.; Uneyama, K. Chem. Rev. 2009, 109, 2119; (c) Zhang, W.-G.; Wang, Y. Tetrahedron Lett. 2018, 59, 1301.
20. [20]
  (a) Zhang, X.-X.; Cao, S. Tetrahedron Lett. 2017, 58, 375; (b) Liu, Y.; Deng, M.-M.; Zhang, Z.-Y.; Ding, X.-H.; Dai, Z.-Q.; Guan, J.-T. Chin. J. Org. Chem. 2012, 32, 661. (刘运, 邓萌萌, 张智勇, 丁肖华, 戴志群, 关金涛, 有机化学, 2012, 32, 661.).
21. [21]
  (a) Zhang, Z.-K.; Zhou, Q.; Yu, W.-Z.; Li, T.-J.; Wu, G.-J; Zhang, Y.; Wang, J.-B. Org. Lett. 2015, 17, 2474; (b) Ichitsuka, T.; Fujita, T.; Ichikawa, J. ACS Catal. 2015, 5, 5947; (c) Li, C.-P.; Zhang, D.-Y.; Zhu, W.; Wan, P.-H.; Liu, H. Org. Chem. Front. 2016, 3, 1080; (d) Liu, Y.; Zhou, Y.-H.; Zhao, Y.-L.; Qu, J.-P. Org. Lett. 2017, 19, 946; (e) Dai, W.-P.; Lin, Y.-Y.; Wan, Y.; Cao, S. Org. Chem. Front. 2018, 5, 55; (f) Wu, X.-T.; Xie, F.; Gridnev, I. D.; Zhang, W.-B. Org. Lett. 2018, 20, 1638; (g) Ji, X.-F.; Liu, Y.-S.; Shi, H.-Y.; Cao, S. Tetrahedron 2018, 74, 4155; (h) Kojima, R.; Akiyama, S.; Ito, H. Angew. Chem., Int. Ed. 2018, 57, 7196; (i) Hu, M.-Y.; Ni, C.-F.; Li, L.-C.; Han, Y.-X.; Hu, J.-B. J. Am. Chem. Soc. 2015, 137, 14496; (j) Fuchibe, K.; Takahashi, M.; Ichikawa, J. Angew. Chem., Int. Ed. 2012, 51, 12059.
22. [22]
  (a) Fuchibe, K.; Jyono, H.; Fujiwara, M.; Kudo, T.; Yokota, M.; Ichikawa, J. Chem. Eur. J. 2011, 17, 12175; (b) Li, L.-Y.; Xiao, T.-B.; Chen, H.-G.; Zhou, L. Chem. Eur. J. 2017, 23, 2249; (c) Fuchibe, K.; Hatta, H.; Oh, K.; Oki, R.; Ichikawa, J. Angew. Chem., Int. Ed. 2017, 56, 5890; (d) Zhang, Z.-K.; Yu, W.-Z.; Zhou, Q.; Li, T.-J.; Zhang, Y.; Wang, J.-B. Chin. J. Chem. 2016, 34, 473; (e) Zhang, Z.-K.; Zhou, Q.; Yu, W.-Z.; Li, T.-J.; Zhang, Y.; Wang, J.-B. Chin. J. Chem. 2017, 35, 387.
23. [23]
  Bordwell, F. G. Acc. Chem. Res. 1988, 21, 456. doi: 10.1021/ar00156a004
1. [1]
  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
2. [2]
  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
3. [3]
  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
4. [4]
  Tiantian MA , Sumei LI , Chengyu ZHANG , Lu XU , Yiyan BAI , Yunlong FU , Wenjuan JI , Haiying YANG . Methyl-functionalized Cd-based metal-organic framework for highly sensitive electrochemical sensing of dopamine. Chinese Journal of Inorganic Chemistry, 2024, 40(4): 725-735. doi: 10.11862/CJIC.20230351
5. [5]
  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
6. [6]
  Zhiquan Zhang , Baker Rhimi , Zheyang Liu , Min Zhou , Guowei Deng , Wei Wei , Liang Mao , Huaming Li , Zhifeng Jiang . Insights into the Development of Copper-based Photocatalysts for CO₂ Conversion. Acta Physico-Chimica Sinica, 2024, 40(12): 2406029-. doi: 10.3866/PKU.WHXB202406029
7. [7]
  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
8. [8]
  Xiaoning TANG , Shu XIA , Jie LEI , Xingfu YANG , Qiuyang LUO , Junnan LIU , An XUE . Fluorine-doped MnO₂ with oxygen vacancy for stabilizing Zn-ion batteries. Chinese Journal of Inorganic Chemistry, 2024, 40(9): 1671-1678. doi: 10.11862/CJIC.20240149
9. [9]
  Tingting Yu , Si Chen , Lianglong Sun , Tongtong Shi , Kai Sun , Xin Wang . Comprehensive Experimental Design for the Photochemical Synthesis, Analysis, and Characterization of Difluoropyrroles. University Chemistry, 2024, 39(11): 196-203. doi: 10.3866/PKU.DXHX202401022
10. [10]
  Xiaoning TANG , Junnan LIU , Xingfu YANG , Jie LEI , Qiuyang LUO , Shu XIA , An XUE . Effect of sodium alginate-sodium carboxymethylcellulose gel layer on the stability of Zn anodes. Chinese Journal of Inorganic Chemistry, 2024, 40(8): 1452-1460. doi: 10.11862/CJIC.20240191
11. [11]
  Lei Shi . Nucleophilicity and Electrophilicity of Radicals. University Chemistry, 2024, 39(11): 131-135. doi: 10.3866/PKU.DXHX202402018
12. [12]
  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
13. [13]
  Yuhao SUN , Qingzhe DONG , Lei ZHAO , Xiaodan JIANG , Hailing GUO , Xianglong MENG , Yongmei GUO . Synthesis and antibacterial properties of silver-loaded sod-based zeolite. Chinese Journal of Inorganic Chemistry, 2024, 40(4): 761-770. doi: 10.11862/CJIC.20230169
14. [14]
  Doudou Qin , Junyang Ding , Chu Liang , Qian Liu , Ligang Feng , Yang Luo , Guangzhi Hu , Jun Luo , Xijun Liu . Addressing Challenges and Enhancing Performance of Manganese-based Cathode Materials in Aqueous Zinc-Ion Batteries. Acta Physico-Chimica Sinica, 2024, 40(10): 2310034-. doi: 10.3866/PKU.WHXB202310034
15. [15]
  Yuanyin Cui , Jinfeng Zhang , Hailiang Chu , Lixian Sun , Kai Dai . Rational Design of Bismuth Based Photocatalysts for Solar Energy Conversion. Acta Physico-Chimica Sinica, 2024, 40(12): 2405016-. doi: 10.3866/PKU.WHXB202405016
16. [16]
  Tengjiao Wang , Tian Cheng , Rongjun Liu , Zeyi Wang , Yuxuan Qiao , An Wang , Peng Li . Conductive Hydrogel-based Flexible Electronic System: Innovative Experimental Design in Flexible Electronics. University Chemistry, 2024, 39(4): 286-295. doi: 10.3866/PKU.DXHX202309094
17. [17]
  Dan Li , Hui Xin , Xiaofeng Yi . Comprehensive Experimental Design on Ni-based Catalyst for Biofuel Production. University Chemistry, 2024, 39(8): 204-211. doi: 10.3866/PKU.DXHX202312046
18. [18]
  Rui Gao , Ying Zhou , Yifan Hu , Siyuan Chen , Shouhong Xu , Qianfu Luo , Wenqing Zhang . Design, Synthesis and Performance Experiment of Novel Photoswitchable Hybrid Tetraarylethenes. University Chemistry, 2024, 39(5): 125-133. doi: 10.3866/PKU.DXHX202310050
19. [19]
  Yufang GAO , Nan HOU , Yaning LIANG , Ning LI , Yanting ZHANG , Zelong LI , Xiaofeng LI . Nano-thin layer MCM-22 zeolite: Synthesis and catalytic properties of trimethylbenzene isomerization reaction. Chinese Journal of Inorganic Chemistry, 2024, 40(6): 1079-1087. doi: 10.11862/CJIC.20240036
20. [20]
  Wen YANG , Didi WANG , Ziyi HUANG , Yaping ZHOU , Yanyan FENG . La promoted hydrotalcite derived Ni-based catalysts: In situ preparation and CO₂ methanation performance. Chinese Journal of Inorganic Chemistry, 2024, 40(3): 561-570. doi: 10.11862/CJIC.20230276

Get Citation

PDF

XML

Metrics

PDF Downloads(27)
Abstract views(1648)
HTML views(265)

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

Synthesis of Cyanated Difluorostyrene Derivatives via SN2' Cyanomethylation of α-(Trifluoromethyl)styrenes with Acetonitrile

Metrics

通讯作者: 陈斌, bchen63@163.com

Synthesis of Cyanated Difluorostyrene Derivatives via S_N2' Cyanomethylation of α-(Trifluoromethyl)styrenes with Acetonitrile