C–H Activation: A Versatile Tool for the Synthesis of Niclosamide and Its Derivatives

Rachel Gundamalla; Rajashaker Bantu; B. Sridhar; B. V. Subba Reddy

doi:10.1055/a-2416-2329

Synlett, Table of Contents

Synlett 2024; 35(20): 2520-2524
DOI: 10.1055/a-2416-2329

letter

Special Issue to Celebrate the 75th Birthday of Prof. B. C. Ranu

C–H Activation: A Versatile Tool for the Synthesis of Niclosamide and Its Derivatives

Rachel Gundamalla

^aFluoro-Agrochemicals, CSIR-Indian Institute of Chemical Technology, Hyderabad, 500 007, India

^bAcademy of Scientific and Innovative Research (AcSIR), Ghaziabad, 201002, India

,

Rajashaker Bantu

^aFluoro-Agrochemicals, CSIR-Indian Institute of Chemical Technology, Hyderabad, 500 007, India

,

B. Sridhar

^cLaboratory of X-ray Crystallography, CSIR-Indian Institute of Chemical Technology, Hyderabad, 500 007, India

,

B. V. Subba Reddy∗

^aFluoro-Agrochemicals, CSIR-Indian Institute of Chemical Technology, Hyderabad, 500 007, India

^bAcademy of Scientific and Innovative Research (AcSIR), Ghaziabad, 201002, India

› Author Affiliations

Abstract

All articles of this category

Abstract

A novel strategy has been developed for the direct and regioselective ortho-acetoxylation of N-(2-benzoylphenyl)benzamides through C–H activation using a catalytic amount of Pd(OAc)₂ (5 mol%) and a stoichiometric amount of PhI(OAc)₂ in a mixture of acetic anhydride and acetic acid. By using this protocol, a new series of niclosamide derivatives was produced in good yields. This is the first report on the synthesis of niclosamide and its derivatives by means of C–H functionalization. This newly developed method offers several advantages such as high regioselectivity, operational simplicity, and good to excellent yields. It provides a short three-step process for the synthesis of niclosamide involving acid–amine coupling, ortho-acetoxylation through C–H activation, and deacylation.

Key words

C–H bond activation - transition-metal catalysis - acetoxylation - niclosamide

Full Text

References

References and Notes
1 Andrews P, Thyssen J, Lorke D. Pharmacol. Ther. 1983; 19: 245
2 Pearson RD, Hewlett EL. Ann. Intern. Med. 1985; 102: 550
3 WHO Expert Committee on the Selection and Use of Essential Medicines. The Selection and Use of Essential Medicines, Report of the WHO Expert Committee; Geneva: 2007. World Health Organization
4 Weinbach EC, Garbus J. Nature 1969; 221: 1016
5 Williamson RL, Metcalf RL. Science 1967; 158: 1694
6 Frayha GJ, Smyth JD, Gobert JG, Savel J. Gen. Pharmacol. 1997; 28: 273
7 Swan GE. J. S. Afr. Vet. Assoc. 1999; 70: 61
8 Chen W, Mook RA. Jr, Premont RT, Wang J. Cell Signal. 2018; 41: 89
9 De Clercq E. Expert Rev. Anti-Infect. Ther. 2006; 4: 291
10 Wu C.-J, Jan J.-T, Chen C.-M, Hsieh H.-P, Hwang D.-R, Liu H.-W, Liu C.-Y, Huang H.-W, Chen S.-C, Lin R.-K, Chao Y.-S, Hsu JT. A. Antimicrob. Agents Chemother. 2004; 48: 2693
11 Xu J, Shi P.-Y, Li H, Zhou J. ACS Infect. Dis. 2020; 6: 909
12 Xu J, Berastegui-Cabrera J, Ye N, Carretero-Ledesma M, Pachón-Díaz J, Chen H, Pachón-Ibáñez ME, Sánchez-Céspedes J, Zhou J. J. Med. Chem. 2020; 63: 12830
13 Backer V, Sjöbring U, Sonne J, Weiss A, Hostrup M, Johansen HK, Becker V, Sonne DP, Balchen T, Jellingsø M, Sommer MO. A. Lancet Reg. Health Eur. 2021; 4: 100084
14 Jeon S, Meehyun K, Lee J, Choi I, Byun SY, Park S, Shum D, Kim S. Antimicrob. Agents Chemother. 2020; 64: e00819-20
15 Braga L, Ali H, Secco I, Chiavacci E, Neves G, Goldhill D, Penn R, Jimenez-Guardeño JM, Ortega-Prieto AM, Bussani R, Cannatà A, Rizzari G, Collesi C, Schneider E, Arosio D, Shah AM, Barclay WS, Malim MH, Burrone J, Giacca M. Nature 2021; 594: 88
16 Gassen NC, Papies J, Bajaj T, Emanuel J, Dethloff F, Chua RL, Trimpert J, Heinemann N, Niemeyer C, Weege F, Hönzke K, Aschman T, Heinz DE, Weckmann K, Ebert T, Zellner A, Lennarz M, Wyler E, Schroeder S, Richter A, Niemeyer D, Hoffmann K, Meyer TF, Heppner FL, Corman VM, Landthaler M, Hocke AC, Morkel M, Osterrieder N, Conrad C, Eils R, Radbruch H, Giavalisco P, Drosten C, Müller MA. Nat. Commun. 2021; 12: 3818
17 Blake S, Shaabani N, Eubanks LM, Maruyama J, Manning JT, Beutler N, Paessler S, Ji H, Teijaro JR, Janda KD. ACS Infect. Dis. 2021; 7: 2229
18 Shamim K, Xu M, Hu X, Lee EM, Lu X, Huang R, Shah P, Xu X, Chen CZ, Shen M, Guo H, Chen L, Itkin Z, Eastman RT, Shinn P, Klumpp-Thomas C, Michael S, Simeonov A, Lo DC, Ming G.-l, Song H, Tang H, Zheng W, Huang W. Bioorg. Med. Chem. Lett. 2021; 40: 127906
19 Li Y, Li PK, Roberts MJ, Arend RC, Samant RS, Buchsbaum DJ. Cancer Lett. 2014; 349: 8
20 Natarajan P, Renu C, Rani N, Sakshi Sakshi, Venugopalan P. Tetrahedron Lett. 2020; 61: 151529

21a Li R, Zhang Z, Huang S, Peng K, Ziang H, Shen J, Zhang B, Jiang X. Eur. J. Med. Chem. 2023; 253: 115320
21b Borui K, Mottamal M, Zhong Q, Bratton M, Zhang C, Guo S, Hossain A, Ma P, Zhang Q, Wang G, Payton-Stewart F. Pharmaceuticals 2023; 16: 735

22a Jagadish M, Reddy BV. S. Tetrahedron 2024; 150: 133768
22b Sahoo T, Reddy BV. S. Tetrahedron Lett. 2022; 97: 153783
22c Gundamalla R, Bantu R, Reddy BV. S. Results Chem. 2023; 5: 100993
22d Gundamalla R, Bantu R, Reddy BV. S. ARKIVOC 2024; (vii): 202412204

23a Joshi SD, Dixit SR, Basha J, Kulkarni VH, Aminabhavi TM, Nadagouda MN, Lherbert C. Bioorg. Chem. 2018; 81: 440
23b Begum Z, Bhavan G, Sridhar B, Reddy BV. S. Synthesis 2018; 50: 4089

24a Cheng X.-F, Li Y.-Y, Su Y.-M, Yin F, Wang J.-Y, Sheng J, Vora HU, Wang X.-S, Yu J.-Q. J. Am. Chem. Soc. 2013; 135: 1236
24b Lyons TW, Sanford MS. Chem. Rev. 2010; 110: 1147
24c Kancharla SR, Bantu R, Sridhar B, Venkata Narasaiah A, Reddy BV. S. Tetrahedron 2024; 163: 134128

25 CCDC 2373126 contains the supplementary crystallographic data for compound 2. The data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/structures

26a Reddy BV. S, Reddy RL, Corey EJ. Org. Lett. 2006; 8: 3391
26b Large B, Bourdreux A, Damond A, Gaucher A, Prim D. Catalysts 2018; 8: 139
26c Dick AR, Hull KL, Sanford MS. J. Am. Chem. Soc. 2004; 126: 2300
26d Yoneyama T, Crabtree RH. J. Mol. Catal. A 1996; 108: 35

27 4-Chloro-2-{[(2-chloro-4-nitrophenyl)amino]carbonyl}phenyl Acetate (2); Typical Procedure PhI(OAc)₂ (1.14 g, 3.54 mmol) was added with stirring to 3-chloro-N-(2-chloro-4-nitrophenyl)benzamide (1; 1.0 g, 3.22 mmol) in 1:1 AcOH–Ac₂O (10 mL), and the mixture was stirred for 5 min. Pd(OAc)₂ (5 mol%, 36 mg) was then added at r.t., and the mixture was heated to 100 °C for 12 h until the reaction was complete (TLC). The resulting mixture was extracted with EtOAc (2 × 150 mL), and the combined organic layers were washed with H₂O (50 mL), dried (Na₂SO₄), and concentrated under reduced pressure. The crude product was purified by column chromatography (silica gel, 10–15% EtOAc–hexane) to give a white solid; yield: 0.71 g (60%); mp 156–157 °C. ¹H NMR (400 MHz, CDCl₃): δ = 9.05 (s, 1 H), 8.85 (d, J = 9.2 Hz, 1 H), 8.35 (d, J = 2.5 Hz, 1 H), 8.23 (dd, J = 9.2, 2.5 Hz, 1 H), 7.97 (d, J = 2.6 Hz, 1 H), 7.55 (dd, J = 8.7, 2.6 Hz, 1 H), 7.18 (d, J = 8.7 Hz, 1 H), 2.40 (s, 3 H). ¹³C NMR (126 MHz, CDCl₃): δ = 168.3, 162.2, 146.4, 143.4, 140.1, 133.2, 132.4, 130.6, 128.1, 125.1, 124.8, 123.8, 122.3, 120.7, 21.3. HRMS (ESI): m/z [M – H]⁺ calcd for C₁₅H₉Cl₂N₂O₅: 366.98940; found: 366.99077.

Supplementary Material

Supporting Information