Citation: Shuai Chen, Anzai Shi, Guoqing Yang, Pengfei Xie, Feng Liu, Youai Qiu. Electrochemical demethoxyl-cyanation of methoxyarenes via S_NAr[J]. Chinese Chemical Letters, ;2025, 36(9): 110810. doi: 10.1016/j.cclet.2024.110810 shu

Electrochemical demethoxyl-cyanation of methoxyarenes via S_NAr

Shuai Chen ^a ,
Anzai Shi ^a ,
Guoqing Yang ^a ,
Pengfei Xie ^a ,
Feng Liu ^{b, *,} ,
Youai Qiu ^{a, *,}

a.
State Key Laboratory and Institute of Elemento-Organic Chemistry, Frontiers Science Center for New Organic Matter, Haihe Laboratory of Sustainable Chemical Transformations, College of Chemistry, Nankai University, Tianjin 300071, China
b.
Department of Chemistry, Fudan University, Shanghai 200438, China

liufeng@fudan.edu.cn

qiuyouai@nankai.edu.cn

Received Date: 22 November 2024
Revised Date: 26 December 2024
Accepted Date: 28 December 2024
Available Online: 29 December 2024

Figures(4)

Herein, a metal-free electrochemical demethoxyl-cyanation of methoxyarenes via aromatic nucleophilic substitution (S_NAr) using TMSCN as a cheap cyanide source under mild conditions has been presented. This transformation utilizes commercially available reagents, cheap electrodes, and simple equipment. Diverse aryl nitriles were successfully obtained in a direct and efficient way with broad substrate scope, excellent functional group tolerance, and selective C−O bond cleavage. Furthermore, late-stage modification of biorelevant compounds and gram-scale synthesis highlighted the potential application of the strategy. Mechanistic investigations suggest that the arene cation radical was considered as the key intermediate for the transformation, and undergoing the followed S_NAr process.
- Electrochemistry,
- Aromatic nucleophilic substitution (S_NAr),
- Cyanation,
- Aryl nitriles,
- Organic electrosynthesis
1. [1]
  R.A. Rossi, A.B. Pierini, A.B. Peñéñory. Chem. Rev. 103 (2003) 71-167.
2. [2]
  G.G. Wubbels, Tetrahedron Lett. 55 (2014) 5066-5069.
3. [3]
  M.P. Drapeau, T. Ollevier, M. Taillefer, Chem. Eur. J. 20 (2014) 5231-5236.
4. [4]
  C.F. Bernasconi, Acc. Chem. Res. 11 (1978) 147-152. doi: 10.1021/ar50124a004
5. [5]
  F.A. Carey, R.M. Giuliano, N.T. Allison, et al., Electrophilic and nucleophilic aromatic substitution, in Organic Chemistry ISE, 12th ed., McGraw-Hill Education, New York, 2024, pp. 478-533.
6. [6]
  M. Mąkosza, Chem. Soc. Rev. 39 (2010) 2855-2868. doi: 10.1039/b822559c
7. [7]
  C.N. Neumann, J.M. Hooker, T. Ritter, Nature 534 (2016) 369-373. doi: 10.1038/nature17667
8. [8]
  S.M. Wales, R.K. Saunthwal, J. Clayden, Acc. Chem. Res. 55 (2022) 1731-1747. doi: 10.1021/acs.accounts.2c00184
9. [9]
  M.L. Tan, Q.H. Guo, X.Y. Wang, et al., Angew. Chem. Int. Ed. 59 (2020) 23649-23658. doi: 10.1002/anie.202013149
10. [10]
  Z. Qiu, C.J. Li, Chem. Rev. 120 (2020) 10454-10515. doi: 10.1021/acs.chemrev.0c00088
11. [11]
  X. Cong, F. Fan, P. Ma, et al., J. Am. Chem. Soc. 139 (2017) 15182-15190. doi: 10.1021/jacs.7b08579
12. [12]
  K. Ouyang, W. Hao, W.X. Zhang, et al., Chem. Rev. 115 (2015) 12045-12090. doi: 10.1021/acs.chemrev.5b00386
13. [13]
  C.N. Neumann, T. Ritter, Acc. Chem. Res. 50 (2017) 2822-2833. doi: 10.1021/acs.accounts.7b00413
14. [14]
  M. Tobisu, N. Chatani, Acc. Chem. Res. 48 (2015) 1717-1726. doi: 10.1021/acs.accounts.5b00051
15. [15]
  N.E.S. Tay, D.A. Nicewicz, J. Am. Chem. Soc. 139 (2017) 16100-16104. doi: 10.1021/jacs.7b10076
16. [16]
  J. Lu, I. Paci, D.C. Leitch, Chem. Sci. 13 (2022) 12681-12695. doi: 10.1039/d2sc04041g
17. [17]
  Z. You, K. Higashida, T. Iwai, et al., Angew. Chem. Int. Ed. 60 (2021) 5778-5782. doi: 10.1002/anie.202013544
18. [18]
  F.L. Qing, X.Y. Liu, J.A. Ma, et al., CCS Chem. 4 (2022) 2518-2549. doi: 10.31635/ccschem.022.202201935
19. [19]
  P.S. Fier, J.F. Hartwig, J. Am. Chem. Soc. 134 (2012) 10795-10798. doi: 10.1021/ja304410x
20. [20]
  A.C. Sather, S.L. Buchwald, Acc. Chem. Res. 49 (2016) 2146-2157. doi: 10.1021/acs.accounts.6b00247
21. [21]
  L.S. Sharninghausen, S. Preshlock, S.T. Joy, et al., J. Am. Chem. Soc. 144 (2022) 7422-7429. doi: 10.1021/jacs.2c01959
22. [22]
  X. Wu, W. Chen, N. Holmberg-Douglas, et al., Chem 9 (2023) 343-362.
23. [23]
  N. Holmberg-Douglas, D.A. Nicewicz. Org. Lett. 21 (2019) 7114-7118. doi: 10.1021/acs.orglett.9b02678
24. [24]
  Z. Zhang, T. Niwa, K. Watanabe, et al., Angew. Chem. Int. Ed. 62 (2023) e202302956.
25. [25]
  L. Shi, M. Wang, C.A. Fan, et al., Org. Lett. 5 (2003) 3515-3517.
26. [26]
  Q. Shen, J.F. Hartwig, J. Am. Chem. Soc. 128 (2006) 10028-10029. doi: 10.1021/ja064005t
27. [27]
  Q.K. Kang, Y. Lin, Y. Li, et al., Angew. Chem. Int. Ed. 60 (2021) 20391-20399. doi: 10.1002/anie.202106440
28. [28]
  Y. Wang, C. Zhou, R. Wang, Green Chem. 17 (2015) 3910-3915.
29. [29]
  D.W. Widlicka, R.A. Singer, I. Hotham, et al., Org. Process Res. Dev. 28 (2024) 2732-2742. doi: 10.1021/acs.oprd.4c00108
30. [30]
  M. Majek, A. J. von Wangelin, Acc. Chem. Res. 49 (2016) 2316-2327. doi: 10.1021/acs.accounts.6b00293
31. [31]
  S. Pimparkar, A. Koodan, S. Maiti, et al., Chem. Commun. 57 (2021) 2210-2232. doi: 10.1039/d0cc07783f
32. [32]
  Y. Wang, W. Yu, C. Wang, et al., eScience 4 (2024) 100228.
33. [33]
  H.Y. Zhou, H.T. Tang, W.M. He, Chin. J. Catal. 46 (2023) 4-10.
34. [34]
  M. Yan, Y. Kawamata, P.S. Baran, Chem. Rev. 117 (2017) 13230-13319. doi: 10.1021/acs.chemrev.7b00397
35. [35]
  W. Zeng, Y. Qiu, Sci. China Chem. 67 (2024) 3223-3246.
36. [36]
  J. Zhong, Y. Yu, D. Zhang, et al., Chin. Chem. Lett. 32 (2021) 963-972.
37. [37]
  P. Li, Y. Wang, H. Zhao, Y. Qiu, Acc. Chem. Res. (2024) https://doi.org/10.1021/acs.accounts.4c00652. doi: 10.1021/acs.accounts.4c00652
38. [38]
  C. Zhu, N.W.J. Ang, T.H. Meyer, et al., ACS Central Sci. 7 (2021) 415-431. doi: 10.1021/acscentsci.0c01532
39. [39]
  Z. Zhang, Y. Lei, W. Huang, et al., Chin. Chem. Lett. 33 (2022) 3623-3631.
40. [40]
  Y. Yu, Y. Jiang, S. Wu, et al., Chin. Chem. Lett. 33 (2022) 2009-2014.
41. [41]
  Y. Yuan, J. Yang, A. Lei, Chem. Soc. Rev. 50 (2021) 10058-10086. doi: 10.1039/d1cs00150g
42. [42]
  S. Andreades, EW. Zahnow, J. Am. Chem. Soc. 91 (1969) 4181-4190. doi: 10.1021/ja01043a028
43. [43]
  R. Möckel, J. Hille, E. Winterling, et al., Angew. Chem. Int. Ed. 57 (2018) 442-445. doi: 10.1002/anie.201711293
44. [44]
  J. Li, S. Zhang, K. Xu, Chin. Chem. Lett. 32 (2021) 2729-2735.
45. [45]
  Y. Zhong, H. Xiong, J. Low, et al., eScience 3 (2023) 100086.
46. [46]
  X. Cheng, A. Lei, T. Mei, et al., CCS Chem. 4 (2022) 1120-1152. doi: 10.31635/ccschem.021.202101451
47. [47]
  T. Wang, F. He, W. Jiang, et al., Angew. Chem. Int. Ed. 63 (2024) e202316140.
48. [48]
  Y.M. Cai, X.T. Liu, L.L. Xu, et al., Angew. Chem. Int. Ed. 63 (2024) e202315222.
49. [49]
  M. Li, X. Cheng, Nat. Commun. 15 (2024) 7540.
50. [50]
  X. Liu, R. Liu, J. Qiu, et al., Angew. Chem. Int. Ed. 59 (2020) 13962-13967. doi: 10.1002/anie.202005765
51. [51]
  A. Shi, Y. Liu, R. Zhang, et al., eScience 4 (2024) 100255.
52. [52]
  Z. Zhao, R. Zhang, Y. Liu, et al., Nat. Commun. 15 (2024) 3832.
53. [53]
  Y. Wang, Q. Wang, L. Wu, et al., Nat. Commun. 15 (2024) 2780.
54. [54]
  T. Feng, S. Wang, Y. Liu, et al., Angew. Chem. Int. Ed. 61 (2022) e202115178.
55. [55]
  P. Li, C. Guo, S. Wang, et al., Nat. Commun. 13 (2022) 3774.
56. [56]
  Y. Wang, S. Tang, G. Yang, et al., Angew. Chem. Int. Ed. 61 (2022) e202207746.
57. [57]
  Y. Wang, Z. Zhao, D. Pan, et al., Angew. Chem. Int. Ed. 61 (2022) e202210201.
58. [58]
  Z. Zhao, Y. Liu, S. Wang, et al., Angew. Chem. Int. Ed. 62 (2023) e202214710.
59. [59]
  Y. Liu, P. Li, Y. Wang, et al., Angew. Chem. Int. Ed. 62 (2023) e202306679.
60. [60]
  K. Yang, T. Feng, Y. Qiu, et al., Angew. Chem. Int. Ed. 62 (2023) e202312803.
61. [61]
  P. Li, G. Kou, T. Feng, et al., Angew. Chem. Int. Ed. 62 (2023) e202311941.
62. [62]
  M. Liu, T. Feng, Y. Wang, et al., Nat. Commun. 14 (2023) 6467.
63. [63]
  V. Bonatto, R.F. Lameiro, F.R. Rocho, et al., RSC Med. Chem. 14 (2023) 201-217. doi: 10.1039/d2md00204c
64. [64]
  M. Liu, S. Li, Nat. Prod. Rep. 41 (2024) 649-671. doi: 10.1039/d3np00028a
65. [65]
  T. Ohshima, T. Komyoji, S. Mitani, et al., J. Pest Sci. 29 (2004) 147-152. doi: 10.1584/jpestics.29.147
66. [66]
  C. Jiang, P. Chen, G. Liu, et al., CCS Chem. 3 (2021) 1884-1893. doi: 10.31635/ccschem.020.202000435
67. [67]
  L. Guillemard, N. Kaplaneris, L. Ackermann, et al., Nat. Rev. Chem. 5 (2021) 522-545;. doi: 10.1038/s41570-021-00300-6
68. [68]
  R. Cannalire, S. Pelliccia, L. Sancineto, et al., Chem. Soc. Rev. 50 (2021) 766-897. doi: 10.1039/d0cs00493f
69. [69]
  J. Wencel-Delord, F. Glorius, Nat. Chem. 5 (2013) 369-375. doi: 10.1038/nchem.1607
70. [70]
  M. Guerram, Z.Z. Jiang, L.Y. Zhang, Chin. J. Nat. Med. 10 (2012) 161-169. doi: 10.3724/SP.J.1009.2012.00161
71. [71]
  S. Desbène, S. Giorgi-Renault. Curr. Med. Chem. Anti-Cancer Agents 2 (2002) 71-90.
72. [72]
  H. Ekiert, J. Świątkowska, E. Knut, et al., Front. Pharmacol. 12 (2021) 653993.
73. [73]
  P. Rossi, L. Bao, A. Luciani, et al., J. Agric. Food Chem. 55 (2007) 7332-7336. doi: 10.1021/jf070674u
74. [74]
  S. Y. Shim, Chem. Eur. J. 29 (2023) e202302620.
75. [75]
  J. Patocka, K. Kuca, Mil. Med. Sci. Lett. 82 (2013) 162-171. doi: 10.31482/mmsl.2013.026
76. [76]
  S. Burstein, M. Gut, Steroids 14 (1969) 207-217.
77. [77]
  L.V. Langenhove, R. Paul, Insect repellent finishes for textiles, in: Functional Finishes for Textiles, Elsevier Ltd., 2015, pp. 333-360.
78. [78]
  A.S. Wikaputri, D.J. Irvine, R.A. Stockman, et al., J. Agr. Food Res. 16 (2024) 101186.
79. [79]
  V.A. Pistritto, M.E. Schutzbach-Horton, D.A. Nicewicz, J. Am. Chem. Soc. 142 (2020) 17187-17194. doi: 10.1021/jacs.0c09296
80. [80]
  K.A. Margrey, J.B. McManus, S. Bonazzi, et al., J. Am. Chem. Soc. 139 (2017) 11288-11299. doi: 10.1021/jacs.7b06715
1. [1]
  Yang Li , Yanan Dong , Zhihong Wei , Changzeng Yan , Zhen Li , Lin He , Yuehui Li . Fluoride-promoted Ni-catalyzed cyanation of C–O bond using CO₂ and NH₃. Chinese Chemical Letters, 2025, 36(5): 110206-. doi: 10.1016/j.cclet.2024.110206
2. [2]
  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
3. [3]
  Xue Xin , Qiming Qu , Islam E. Khalil , Yuting Huang , Mo Wei , Jie Chen , Weina Zhang , Fengwei Huo , Wenjing Liu . Hetero-phase zirconia encapsulated with Au nanoparticles for boosting electrocatalytic nitrogen reduction. Chinese Chemical Letters, 2024, 35(5): 108654-. doi: 10.1016/j.cclet.2023.108654
4. [4]
  Zixuan Guo , Xiaoshuai Han , Chunmei Zhang , Shuijian He , Kunming Liu , Jiapeng Hu , Weisen Yang , Shaoju Jian , Shaohua Jiang , Gaigai Duan . Activation of biomass-derived porous carbon for supercapacitors: A review. Chinese Chemical Letters, 2024, 35(7): 109007-. doi: 10.1016/j.cclet.2023.109007
5. [5]
  Qiang Cao , Xue-Feng Cheng , Jia Wang , Chang Zhou , Liu-Jun Yang , Guan Wang , Dong-Yun Chen , Jing-Hui He , Jian-Mei Lu . Graphene from microwave-initiated upcycling of waste polyethylene for electrocatalytic reduction of chloramphenicol. Chinese Chemical Letters, 2024, 35(4): 108759-. doi: 10.1016/j.cclet.2023.108759
6. [6]
  Yuemin Chen , Yunqi Wu , Guoao Wang , Feihu Cui , Haitao Tang , Yingming Pan . Electricity-driven enantioselective cross-dehydrogenative coupling of two C(sp³)-H bonds enabled by organocatalysis. Chinese Chemical Letters, 2024, 35(9): 109445-. doi: 10.1016/j.cclet.2023.109445
7. [7]
  Li Li , Zhi-Xin Yan , Chuan-Kun Ran , Yi Liu , Shuo Zhang , Tian-Yu Gao , Long-Fei Dai , Li-Li Liao , Jian-Heng Ye , Da-Gang Yu . Electro-reductive carboxylation of CCl bonds in unactivated alkyl chlorides and polyvinyl chloride with CO₂. Chinese Chemical Letters, 2024, 35(12): 110104-. doi: 10.1016/j.cclet.2024.110104
8. [8]
  Yan-Jiang Li , Shu-Lei Chou , Yao Xiao . Detecting dynamic structural evolution based on in-situ high-energy X-ray diffraction technology for sodium layered oxide cathodes. Chinese Chemical Letters, 2025, 36(2): 110389-. doi: 10.1016/j.cclet.2024.110389
9. [9]
  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
10. [10]
  Jianfeng Yan , Yating Xiao , Xin Zuo , Caixia Lin , Yaofeng Yuan . Comprehensive Chemistry Experimental Design of Ferrocenylphenyl Derivatives. University Chemistry, 2024, 39(4): 329-337. doi: 10.3866/PKU.DXHX202310005
11. [11]
  Yongming Zhu , Huili Hu , Yuanchun Yu , Xudong Li , Peng Gao . Construction and Practice on New Form Stereoscopic Textbook of Electrochemistry for Energy Storage Science and Engineering: Taking Basic Course of Electrochemistry as an Example. University Chemistry, 2024, 39(8): 44-47. doi: 10.3866/PKU.DXHX202312086
12. [12]
  Yifei Cheng , Jiahui Yang , Wei Shao , Wanqun Zhang , Wanqun Hu , Weiwei Li , Kaiping Yang . Learning Goes Beyond the Written Word: Practical Insights from the “Leaf Electroplating” Popular Science Experiment. University Chemistry, 2024, 39(9): 319-327. doi: 10.3866/PKU.DXHX202310033
13. [13]
  Kuaibing Wang , Honglin Zhang , Wenjie Lu , Weihua Zhang . Experimental Design and Practice for Recycling and Nickel Content Detection from Waste Nickel-Metal Hydride Batteries. University Chemistry, 2024, 39(11): 335-341. doi: 10.12461/PKU.DXHX202403084
14. [14]
  Cen Zhou , Biqiong Hong , Yiting Chen . Application of Electrochemical Techniques in Supramolecular Chemistry. University Chemistry, 2025, 40(3): 308-317. doi: 10.12461/PKU.DXHX202406086
15. [15]
  Zihan Lin , Wanzhen Lin , Fa-Jie Chen . Electrochemical Modifications of Native Peptides. University Chemistry, 2025, 40(3): 318-327. doi: 10.12461/PKU.DXHX202406089
16. [16]
  Yongjian Zhang , Fangling Gao , Hong Yan , Keyin Ye . Electrochemical Transformation of Organosulfur Compounds. University Chemistry, 2025, 40(5): 311-317. doi: 10.12461/PKU.DXHX202407035
17. [17]
  Kuaibing Wang , Feifei Mao , Weihua Zhang , Bo Lv . Design and Practice of a Comprehensive Teaching Experiment for Preparing Biomass Carbon Dots from Rice Husk. University Chemistry, 2025, 40(5): 342-350. doi: 10.12461/PKU.DXHX202407042
18. [18]
  Shuhui Li , Rongxiuyuan Huang , Yingming Pan . Electrochemical Synthesis of 2,5-Diphenyl-1,3,4-Oxadiazole: A Recommended Comprehensive Organic Chemistry Experiment. University Chemistry, 2025, 40(5): 357-365. doi: 10.12461/PKU.DXHX202407028
19. [19]
  Xinyi Zhang , Kai Ren , Yanning Liu , Zhenyi Gu , Zhixiong Huang , Shuohang Zheng , Xiaotong Wang , Jinzhi Guo , Igor V. Zatovsky , Junming Cao , Xinglong Wu . Progress on Entropy Production Engineering for Electrochemical Catalysis. Acta Physico-Chimica Sinica, 2024, 40(7): 2307057-0. doi: 10.3866/PKU.WHXB202307057
20. [20]
  Zehao Zhang , Zheng Wang , Haibo Li . Preparation of 2D V₂O₃@Pourous Carbon Nanosheets Derived from V₂CF_x MXene for Capacitive Desalination. Acta Physico-Chimica Sinica, 2024, 40(8): 2308020-0. doi: 10.3866/PKU.WHXB202308020

Get Citation

PDF

XML

Metrics

PDF Downloads(0)
Abstract views(11)
HTML views(1)

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

Electrochemical demethoxyl-cyanation of methoxyarenes via SNAr

Metrics

通讯作者: 陈斌, bchen63@163.com

Electrochemical demethoxyl-cyanation of methoxyarenes via S_NAr