Research Progress in Synthesis and Application of 3-Cyanopyridines

doi:10.6023/cjoc202512034

Abstract

3-Cyanopyridine (nicotinonitrile) compounds have garnered significant attention as versatile molecular scaffolds due to their broad pharmacological activities, including antitumor and antibacterial effects, as well as their extensive applications in optical materials. Furthermore, they serve as crucial synthetic intermediates in the preparation of various compounds. This review summarizes the synthetic advances of these compounds over the past decade, with an emphasis on the construction of the 3-cyanopyridine framework through multicomponent reactions, novel cyclization strategies, and functional group transformations. Additionally, the applications of 3-cyanopyridine compounds in synthetic chemistry, medicinal chemistry, and materials science are systematically outlined. Looking forward, the development of photo- and electrocatalytic green synthetic methodologies for 3-cyanopyridine compounds, along with the exploration of high-performance fluorescent probes and new energy materials based on these scaffolds, remains a key research focus.

Key words: multi-component reaction, 3-cyanopyridine, green synthesis, synthon, bioactivity, fluorescent probe

Cite this article

Chen Guiyuan, Li Shengyu, Guo Jilin, Wang Xiang, Liu Yetong, Xiao Beining, Wang Zhaoyang. Research Progress in Synthesis and Application of 3-Cyanopyridines[J]. Chinese Journal of Organic Chemistry, doi: 10.6023/cjoc202512034.

Export EndNote|Reference Manager|ProCite|BibTeX|RefWorks

share this article

References

[1] Zhou X. X.; Hu S. W.; Zhuo Q. D.; Luo G.; Shima T.; Hou, Z. M. J. Am. Chem. Soc.2025, 147(45), 41462-41471.
[2] Wu Y. R.; Wu T.; Huang Y. Arch. Pharm.2023, 356(7), 2300067.
[3] Wang, J.-Q; Long, Y.-J; Song, K.-Z; Han, Y.; Chen, C.-F. Angew. Chem., Int. Ed.2025, 64(42), e202514366.
[4] Ershova A. I.; Alekseeva A. U.; Ershov O.; Ievlev M. Y.; Bardasov, I. N. Dyes Pigm.2022, 197, 109914.
[5] Cao X.-Y.; Li Z.-H.; Cao X.-H.; Li Z.; Pang C.-M.; Zhang Z.-Q.; Wang Z.-Y. Green Chem.2025, 27(24), 7300-7306.
[6] Chen H.; Sun S. H.; Liu Y. A.; Liao, X. B. ACS Catal.2020, 10(2), 1397-1405.
[7] Zhang M.; Zhou Q. Y.; Luo H.; Tang Z.-L.; Xu X. F.; Wang, X.-C. Angew. Chem., Int. Ed.2023, 62(6). e202216894.
[8] Anwer K. E.; Sayed, G. H. Russ. J. Org. Chem.2024, 60(11), 2170-2227.
[9] Mahesha P.; Shetty N. S. ChemistrySelect.2024, 9(20), e202401770.
[10] De Souza J. M.; Abdiaj I.; Chen J. Q.; Hanson K.; De Oliveira K. T.; McQuade, D. T. Org. Biomol. Chem.2021, 19(9), 1991-1999.
[11] Ibrahim M. M.; Al-Refai M.; Azmi M. N.; Osman H.; Abu Bakar M. H.; Geyer, A. J. Iran. Chem. Soc.2019, 16(4), 715-722.
[12] Xiao L. W.; Peng X. X.; Zhou Q. X.; Kou W.; Shi, Y. R. Chin. J. Org. Chem.2015, 35(6), 1204-1215 (in Chinese).
(肖立伟, 彭晓霞, 周秋香, 寇伟, 时亚茹, 有机化学, 2015, 35(6), 1204-1215.)
[13] Luo J.; Li Y. W.; Wang H. Q.; Liu G. X.; Kang Z. H.; Qian Y.; Ke Z. F.; Fu X.; Hu, W. H. J. Am. Chem. Soc.2025, 147(23), 19458-19464.
[14] Zonouzi A.; Hosseinzadeh, F. Polycycl. Aromat. Compd.2025, 45(2), 205-217.
[15] Abdellah I. M.; Eletmany M. R.; Abdelhamid A. A.; Alghamdi H. S.; Abdalla A. N.; Elhenawy A. A.; Abd El Latif, F. M. J. Mol. Struct.2023, 1289, 135864.
[16] Rashidi S.; Soleiman-Beigi M. RSC Adv.2025, 15(31), 25274-25290.
[17] Bhadke P. K.; Gadkari Y. U.; Salim S. S.; Masram L. B.; Telvekar, V. N. J. Chem. Sci.2023, 135(3), 68.
[18] Yadav P. U.; Zade V. D.; Gadkari, Y. U. Res. Chem. Intermed.2024, 50(11), 5371-5384.
[19] Krishna A.; Sarveswari S. ChemistrySelect2019, 4(34), 9987-9992.
[20] Khalili, D. Tetrahedron Lett. 2016, 57(15), 1721-1723.
[21] Mirjalili B. B. F.; Khabnadideh S.; Gholami A.; Zamani L.; Nezamalhosseini L. S. M.; Kalantari, N. Bull. Chem. Soc. Ethiop.2020, 34(1), 149-156.
[22] Khaksar S.; Yaghoobi, M. J. Fluor. Chem.2012, 142, 41-44.
[23] Sayahi M. H.; Saghanezhad S. J.; Mandavi, M. Chem. Heterocycl. Comp.2019, 55(8), 725-728.
[24] Liao S. L.; Shang S. B.; Shen M. G.; Rao X. P.; Si H. Y.; Song J.; Song, Z. Q. Bioorg. Med. Chem. Lett.2016, 26(6), 1512-1515.
[25] Kibou Z.; Aissaoui N.; Daoud I.; Seijas J. A.; Vazquez-Tato M. P.; Khelil N. K.; Choukchou-Braham N. Molecules2022, 27(11), 3439.
[26] Lei Z. G.; Dai C. N.; Hallett J.; Shiflett M. Chem. Rev.2024, 124(12), 7533-7535.
[27] Jalali-Mola S.; Torabi M.; Yarie M.; Zolfigol, M. A. RSC Adv.2022, 12(53), 34730-34739.
[28] Tamaddon F.; Azadi, D. J. Mol. Liq.2018, 249, 789-794.
[29] Das S.; Paul S.; Kashyap N.; Saikia P.; Borah R. ChemistrySelect2024, 9(11), e202304103.
[30] Zhou J.; Liu D.; Wu F. S.; Xiong Y.; Sheykhahmad, F. R. Mater. Res. Express2019, 6(10), 105086.
[31] Arlan F. M.; Marjani A. P.; Javahershenas R.; Khalafy J.New J. Chem. 2021,45(28), 12328-12345.
[32] Niya H. F.; Hazeri N.; Maghsoodlou M. T.; Fatahpour, M. Res. Chem. Intermed.2021, 47(4), 1315-1330.
[33] Afradi M.; Pour S. A.; Dolat M.; Yazdani-Elah-Abadi, A. Appl. Organomet. Chem.2018, 32(2), e4103.
[34] Torabi M.; Yarie M.; Zolfigol, M. A. Appl. Organomet. Chem.2019, 33(6), e4933.
[35] Akbarpoor T.; Khazaei A.; Seyf J. Y.; Sarmasti N.; Gilan, M. M. Res. Chem. Intermed.2020, 46(2), 1539-1554.
[36] Li C. H.; Yang Y. Y.; Li J. Y.; Yuan, F. L. Angew. Chem., Int. Ed.2025, 64(48), e202513847.
[37] Li Y.; Wang Q. F.; Huang N.; Li Z.; Lu J. Q.; Wang, Z. Y. Guangzhou Chem.2025, 50(2), 20-27 (in Chinese).
(李贇, 王群芳, 黄楠, 李宗, 卢嘉谦, 汪朝阳, 广州化学, 2025, 50(2), 20-27.)
[38] Ahmadi E.; Akbarpour T.; Khazaei A.; Mohammadi M.; Gorji, A. J. Iran Chem. Soc.2025, 22(9), 1969-1990.
[39] Solgi M.; Khazaei A.; Akbarpour T.Res. Chem. Intermed. 2022,48(6), 2443-2468.
[40] Riadi Y.; Mamouni R.; Routier S.; Guillaumet G.; Lazar, S. Environ. Chem. Lett.2014, 12(4), 523-527.
[41] Dalal D. S.; Patil D. R.; Tayade, Y. A. Chem. Rec.2018, 18(11), 1560-1582.
[42] Mitra B.; Pariyar G. C.; Ghosh P. RSC Adv.2021, 11(3), 1271-1281.
[43] Talaiefar S.; Habibi-Khorassani S. M.; Sharaki M.; Mollashahi, E. Polycycl. Aromat. Compd.2021, 41(1), 143-159.
[44] Amer A. A.; Abdelhamid, A. A. J. Heterocycl. Chem.2017, 54(6), 3126-3132.
[45] Yang K.; Wang Z. Y.; Fu J. H.; Tan, Y. H. Prog. Chem.2010, 22(11), 2126-2133 (in Chinese).
(杨凯, 汪朝阳, 傅建花, 谭越河, 化学进展, 2010, 22(11), 2126- 2133.)
[46] Dev S.; Dhaneshwar S. R.; Mathew, B. Comb. Chem. High Throughput Screening2018, 21(2), 138-148.
[47] Kalaria P. N.; Satasia S. P.; Avalani J. R.; Raval, D. K. Eur. J. Med. Chem.2014, 83, 655-664.
[48] Challa C. S.; Katari N. K.; Nallanchakravarthula V.; Nayakanti D.; Kapavarapu R.; Pal, M. J. Mol. Struct.2021, 1240, 130541.
[49] Erşatır M.; Yıldırım M. Synth. Commun.2021, 51(8), 1252-1265.
[50] Jasim H. A.; Nahar L.; Jasim M. A.; Moore S. A.; Ritchie K. J.; Sarker S. D. Biomolecules2021, 11(8), 1203.
[51] Sabour R.; Harras M. F.; Mehany, A. B. M. Bioorg. Chem.2020, 94, 103358.
[52] Sabour R.; Harras M. F.; Al Kamaly O. M.; Altwaijry N. Molecules2020, 25(21), 4892.
[53] Ibrahim M. H.; Harras M. F.; Mostafa S. K.; Mohyeldin S. M.; Al Kamaly O.; Altwaijry N.; Sabour R. Bioorg. Chem.2022, 129, 106122.
[54] Zeng Y.; Chen J.-Y.; Li Y.; Guo J.-L.; Pang C.-M.; Li S.-Y.; Wang, Z.-Y. New J. Chem.2025, 49(42), 18502-18509.
[55] Ismail M. M. F.; Farrag A. M.; Harras M. F.; Ibrahim M. H.; Mehany, A. B. M. Bioorg. Chem.2020, 94, 103481.
[56] Li Z. H.; Zeng Y.; Zeng Y.; Xu W. J.; Cao X. Y.; Guo Y. T.; Shen Q.; Wang Z. Y.Chin. J. Org. Chem. 2024,44(11), 3345-3356 (in Chinese).
(黎忠昊, 曾玉, 曾咏, 徐文锦, 曹西颖, 郭玉婷, 沈晴, 汪朝阳, 有机化学, 2024, 44(11), 3345-3356.)
[57] Wu D.; Tao S.; Wang T.; Tang J.-Y.; Chen F.; Du Z.-H.; Bo C.-B.; Li M.; Dai B.; Liu, N. J. Org. Chem.2025, 90(46), 16317-16325.
[58] Rakshit A.; Kumar P.; Alam T.; Dhara H.; Patel, B. K. J. Org. Chem.2020, 85(19), 12482-12504.
[59] Zeng Y.; Li Z. H.; Deng S. W.; Chen Z. J.; Chen B. Y.; Yu S. W.; Shen Q.; Wang Z. Y.Chin. J. Org. Chem. 2024 ,44(9), 2722-2731 (in Chinese).
(曾玉, 黎忠昊, 邓思威, 陈祖佳, 陈璧瑜, 宇世伟, 沈晴, 汪朝阳, 有机化学, 2024 , 44(9), 2722-2731.)
[60] Dhara H. N.; Rakshit A.; Alam T.; Sahoo A. K.; Patel, B. K. Org. Lett.2023, 25(3), 471-476.
[61] Chen Z.-J.; Guo J.-L.; Chen G.-Y.; Li Z.; Ye Y.-Y.; Liu Y.-T.; Wang Z.-Y. Dyes Pigm.2026, 247, 113529.
[62] Wang B.-W.; Jiang K.; Li J.-X.; Luo S.-H.; Wang Z.-Y.; Jiang, H.-F. Angew. Chem., Int. Ed.2020, 59(6), 2338-2343.
[63] Li Z.-H.; Li Y.; Li Z.; Zeng Y.; Ye W.-X.; Cao X.-Y.; Wang, Z.-Y. Curr. Sci. Eng. Technol.2025, 5, e22102981380493.
[64] Cao X. Y.; Li Z. H.; Yu R. R.; Ye Y. Y.; Xie J. Y.; Li H.; Wang Z. Y.Guangzhou Chem. 2025,50(2), 7-14 (in Chinese).
(曹西颖, 黎忠昊, 于冉冉, 叶蕴仪, 谢佳瑜, 李煌, 汪朝阳, 广州化学, 2025, 50(2), 7-14.)
[65] Cao X.-Y.; Huang Y.; Chen S.-H.; Yu S.-W.; Chen Z.-J.; Li Z.-H.; Zeng Y.; Chen N.; Cao L.; Wang Z.-Y. iScience2024, 27(7), 110024.
[66] Shen Q.; Zeng Y.; Li Z. H.; Cao X. Y.; Guo Y. T.; Ye Y. Y.; Wang Z. Y.Chin. J. Org. Chem. 2025,45(4), 1194-1205 (in Chinese).
(沈晴, 曾玉, 黎忠昊, 曹西颖, 郭玉婷, 叶蕴仪, 汪朝阳, 有机化学, 2025, 45(4), 1194-1205.)
[67] Tang Y.; Wu N.; Xu J. Y.; Zhang X. P.; Li Y. B.; Wang X. S. Molecules2024, 29(12), 2792.
[68] Kadi I.; Güldeniz S.; Boulebd H.; Zebbiche Z.; Tekin S.; Küçükbay F.; Gönül Z.; Küçükbay H.; Boumoud, T. Polycyclic Aromat. Compd.2024, 44(10), 6615-6629.
[69] Kadi I.; Seyhan G.; Zebbiche Z.; Sari S.; Barut B.; Boumoud T.; Mermer A.; Boulebd H. Chem. Biodiversity2025, 22(7), e202402915.
[70] Salamanca‐Perdigón K.; Hurtado‐Rodríguez D.; Portilla J.; Iriepa I.; Rojas H.; Becerra D.; Castillo J.-C. ChemPlusChem2024, 89(9), e202400172.
[71] Hegde H.; Sinha R. K.; Kulkarni S. D.; Shetty, N. S. J. Photochem. Photobiol., A2020, 389, 112222.
[72] Salamanca-Perdigón K.; Lozano J. D.; Hurtado-Rodríguez D.; Becerra D.; Rojas H.; Macías M. A.; Castillo, J.-C. New J. Chem.2025, 49(42), 18369-18383.
[73] Keshk R. M.; Izzularab, B. M. Curr. Org. Synth.2021, 18(5), 483-492.
[74] Mansour B.; Salem Y. A.; Attallah K. M.; El-kawy O. A.; Ibrahim I. T.; Abdel-Aziz, N. I. ACS Omega2023, 8(22), 19351-19366.
[75] Damodara D.; Arundhathi R.; Likhar, P. R. Adv. Synth. Catal.2014, 356(1), 189-198.
[76] Jagadeesh R. V.; Junge H.; Beller M. ChemSusChem2015, 8(1), 92-96.
[77] Ganesan M.; Nagaraaj, P. Org. Chem. Front.2020, 7(22), 3792-3814.
[78] Verbitskiy E. V.; Cheprakova E. M.; Pervova M. G.; Danagulyan G. G.; Rusinov G. L.; Chupakhin O. N.; Charushin, V. N. Russ. Chem. Bull.2015, 64(3), 689-694.
[79] Keshk, R. M. J. Heterocycl. Chem.2020, 57(9), 3384-3393.
[80] Liu Y. J.; Yang D.; Hong Z. X.; Guo S.; Liu M. Y.; Zuo D. Y.; Ge D. D.; Qin M. Z.; Sun, D. Y. Eur. J. Med. Chem.2018, 146, 185-193.
[81] Mansour S. Y.; Sayed G. H.; Marzouk M. I.; Shaban, S. S. Synth. Commun.2021, 51(8), 1160-1170.
[82] Abdelrehim E. M.; El-Sayed, D. S. Curr. Org. Synth.2020, 17(3), 211-223.
[83] Ghattas A. A. G.; Khodairy A.; Moustafa H. M.; Hussein, B. R. M. J. Heterocycl. Chem.2017, 54(2), 879-888.
[84] Panda D.; Kumar A.; Nidhi; Verma, A. K. Org. Lett.2025, 27(43), 12053-12058.
[85] Zhang B. B.; Li B.; Zhang X. Y.; Fan X. S.Org. Lett. 2017,19(9), 2294-2297.
[86] Mohareb R. M.; Abouzied A. S.; Abbas, N. S. Anti-cancer Agents Med. Chem.2018, 17(14), 1951-1962.
[87] Kadi I.; Şekerci G.; Boulebd H.; Zebbiche Z.; Tekin S.; Benarous K.; Serseg T.; Küçükbay, F.; Küçükbay, H.; Boumoud, T.J. Biochem. Mol. Toxicol. 2024, 38(9), e23819.
[88] Bass A. K. A. S.; Nageeb E. M.; El-Zoghbi M. S.; Mohamed M. F. A.; Badr M.; Abuo-Rahma, G. E. A. Bioorg. Chem.2022, 119, 105564.
[89] Gao F.; Zhang X.; Wang T. F.; Xiao, J. Q. Eur. J. Med. Chem.2019, 165, 59-79.
[90] Hussein B. R. M.; Mohammed H. H.; Ahmed E. A.; Alshazly O.; Mohamed M. F. A.; Omran, O. A. Mol. Diversity2025, 29(3), 2565-2584.
[91] Abouzid K. A. M.; Al-Ansary G. H.; El-Naggar, A. M. Eur. J. Med. Chem.2017, 134, 357-365.
[92] Farrag A. M.; Ibrahim M. H.; Mehany A. B. M.; Ismail, M. M. F. Bioorg. Chem.2020, 105, 104378.
[93] Song Y.-L.; Tian C.-P.; Wu Y.; Jiang L.-H.; Shen L.-Q. Steroids2019, 143, 53-61.
[94] Lu J.-H.; Lai W.-J.; Jiang L.-H.; Lei F.-H.; Shen L.-Q.; Wu A.-Q. Med. Chem.2023, 19(3), 246-262.
[95] Maghrabi I. A.; Alghamdi S.; Alrobaian M.; Eldeab H. A. Molecules2016, 21(4), 477-487.
[96] Rasooll M. M.; Ahmadi H.; Sepehrmansourie H.; Zolfigol M. A.; Ghytasranjbar E.; Mohammadzadeh A. RSC Adv.2025, 15(6), 4636-4651.
[97] Guo J.-L.; Liu Y.-T.; Ye W.-X.; Wang W.; Yang S.-H.; Chen G.-Y.; Cui H.-J.; Wang, Z.-Y. J. Photochem. Photobiol., A2026, 472, 116792.
[98] Vishnumurthy K. A.; Sunitha M. S.; Safakath K.; Philip R.; Adhikari A. V. Polymer2011, 52(19), 4174-4183.
[99] Manohara H. M.; Devaiah C. T.; Hemavathi B.; Ahipa T. N.J. Lumin. 2019,206, 284-291.
[100] Masuda Y.; Sasabe H.; Arai H.; Onuma N.; Kido J. Front. Chem.2019, 7, 254.
[101] Ahipa T. N.; Kumar V.; Adhikari A. V.Struct. Chem. 2014,25(4), 1165-1174.
[102] Hemavathi B.; Akash S.; Shanmukappagouda; Kusuma J.; Devaiah C. T.; Shwetharani R.; Balakrishna R. G.; Ahipa T. N.J. Photochem. Photobiol., A 2019, 377, 75-79.
[103] Srikanth G.; Narayanan A.; Devadiga D.; Samrudhi B. M.; Devadiga D.; Padaki M.; Selvakumar M.; Ahipa T. N.Energy Fuels 2025,39(1), 895-905.
[104] Ahmad A.; Sinha R. K.; Kulkarni S. D.; Lewis P. M.; Bhat P.; Shetty N. S.J. Photochem. Photobiol., A 2023,437, 114494.
[105] Chen S.-H.; Chen Z.-H.; Jiang K.; Cao X.-Y.; Chen L.-Y.; Ouyang J.; Wang, Z.-Y. Spectrochim. Acta, Part A2023, 300, 122905.
[106] Chen Z.-H.; Chen Z.-J.; Zeng Y.; Liang Y.-T.; Guo J.-L.; Yang S.-H.; Wang, Z.-Y. Spectrochim. Acta, Part A2025, 326, 125281.
[107] Yang S.-H.; Li Z.; Xie J.-Y.; Guo Y.-T.; Chen G.-Y.; Li Y.; Wang, Z.-Y. J. Photochem. Photobiol., A2026, 472, 116846.
[108] Devi L.; Sasan S.; Changotra A.; Kapoor, K. K. New J. Chem.2024, 48(26), 11854-11863.
[109] Li H. Q.; Chen Z. H.; Chen Z. J.; Qiu Q. W.; Zhang Y. C.; Chen S. H.; Wang Z. Y.Chin. J. Org. Chem. 2023,43(9), 3067-3077 (in Chinese).
(李焕清, 陈兆华, 陈祖佳, 邱琪雯, 张又才, 陈思鸿, 汪朝阳, 有机化学, 2023, 43(9), 3067-3077.)
[110] Elmas S. N. K.; Dincer Z. E.; Erturk A. S.; Bostanci A.; Karagoz A.; Koca M.; Sadi G.; Yilmaz, I. Spectrochim. Acta, Part A2020, 224, 117402.
[111] Mohyeldin S. M.; Talaat W.; Kamal M. F.; Daabees H. G.; El-Tahawy M. M. T.; Keshk, R. M. Sci. Rep.2024, 14(1), 2927.
[112] Yang M. K.; Wang M.; Zhang H. M.; Qin S.; Zaman M.; Luo J. Y.; Zhan S. P.; Wang X.; Zhang C.; Wang S. D.; Gao H.; Zhou Z.; Hashmi A. S. K.; Yi W.; Zeng, Z. Y. Chem Catal.2025, 5(6), 101326.
[113] Qin S.; Yang M. K.; Xu M. Y.; Peng Z.-H.; Cai J. T.; Wang S. D.; Gao H.; Zhou Z.; Hashmi A. S. K.; Yi W.; Zeng, Z. Y. Nat. Commun.2024, 15(1), 7428.
[114] Dutta J.; Ghosh S.; De Sarkar S.Angew. Chem., Int. Ed. 2026, e21953.

3-氰基吡啶类化合物的合成与应用研究进展