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Synlett 2022; 33(14): 1458-1462
DOI: 10.1055/s-0040-1719867
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Organic Chemistry in Thailand

Mechanochemical Synthesis of 2,5-Disubstituted 1,3,4-Oxadiazoles Mediated by PPh3-TCCA

Dolnapa Yamano
a   Department of Chemistry, Faculty of Science, Chiang Mai University, Chiang Mai 50200, Thailand
,
Nittaya Wiriya
a   Department of Chemistry, Faculty of Science, Chiang Mai University, Chiang Mai 50200, Thailand
,
Wong Phakhodee 
a   Department of Chemistry, Faculty of Science, Chiang Mai University, Chiang Mai 50200, Thailand
b   Research Center on Chemistry for Development of Health Promoting Products from Northern Resources, Faculty of Science, Chiang Mai University, Chiang Mai, 50200, Thailand
,
Sirawit Wet-osot
c   Medical Life Science Institute, Department of Medical Sciences, Ministry of Public Health, Nonthaburi, 11000, Thailand
,
Mookda Pattarawarapan∗
a   Department of Chemistry, Faculty of Science, Chiang Mai University, Chiang Mai 50200, Thailand
b   Research Center on Chemistry for Development of Health Promoting Products from Northern Resources, Faculty of Science, Chiang Mai University, Chiang Mai, 50200, Thailand
› Author AffiliationsThis work is partially supported by Chiang Mai University, Thailand and The Thailand Research Fund through the Royal Golden Jubilee (RGJ) Ph.D. Programme (PHD/0023/2559 to D.Y. and PHD/0072/2559 to N.W.).
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Abstract

Mechanochemical synthesis of 2,5-disubstituted 1,3,4-oxadiazoles was developed as an environmentally benign alternative to conventional solvent-based methods. In the presence of triphenylphosphine and trichloroisocyanuric acid, N-acylbenzotriazoles condense with acylhydrazides leading to oxadiazoles derivatives in good to excellent yields within minutes. The approach circumvents the need for strictly anhydrous conditions, external heating, long reaction times, as well as tedious multistep procedures. A range of substrates with reactive functionalities was also well tolerated.

Keywords

N-acylbenzotriazole - liquid-assisted grinding - mechanosynthesis - 1,3,4-oxadiazoles - triphenylphosphine - trichloroisocyanuric acid

Supporting Information

    Supporting information for this article is available online at https://doi.org/10.1055/s-0040-1719867. NMR spectra for new and representative products are included.
  • Supporting Information


Publication History

Received: 08 November 2021

Accepted after revision: 20 December 2021

Article published online:
18 January 2022

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  • References and Notes

    • 1a Kumar KA, Jayaroopa P, Govindappa VK. Int. J. ChemTech Res. 2012; 4: 1782
    • 1b Pangal A, Shaikh JA. Res. J. Chem. Sci. 2013; 3: 79
    • 1c Sun J, Makawana JA, Zhu H.-L. Mini-Rev. Med. Chem. 2013; 13: 1725
      CrossrefPubMed
    • 1d Bhaumik A. Eur. J. Biomed. Pharm. Sci. 2016; 3: 133
    • 1e Paraschivescu CC, Paun A, Matache M. Targets Heterocycl. Syst. 2016; 20: 174
    • 1f Salahuddin Salahuddin, Mazumder A, Yar MS, Mazumder R, Chakraborthy GS, Ahsan MJ, Rahman MU. Synth. Commun. 2017; 47: 1805
      Crossref
    • 1g Chawla G, Naaz B, Siddiqui AA. Mini-Rev. Med. Chem. 2018; 18: 216
      PubMed
    • 1h Sharma D, Salahuddin Salahuddin, Sharma V, Kumar R, Joshi S, Kumari S, Saxena S, Mazumder A, Yar MS, Ahsan MJ. Curr. Top. Med. Chem. 2021; 21: 1377
      CrossrefPubMed
  • 2 Bajaj S, Asati V, Singh J, Roy PP. Eur. J. Med. Chem. 2015; 97: 124
    CrossrefPubMed
  • 3 Soares de Oliveira C, Lira BF, Barbosa-Filho JM, Lorenzo JG. F, Filgueiras de Athayde-Filho P. Molecules 2012; 17: 10192
    CrossrefPubMed
  • 4 Singh AK, Sahu VK. R, Yadav D. Int. J. Pharma Sci. Res. 2011; 2: 135
    CrossrefPubMed
  • 5 Bostroem J, Hogner A, Llinas A, Wellner E, Plowright AT. J. Med. Chem. 2012; 55: 1817
    CrossrefPubMed
  • 6 Paun A, Hadade ND, Paraschivescu CC, Matache M. J. Mater. Chem. C 2016; 4: 8596
    Crossref
  • 7 Patel KD, Prajapati SM, Panchal SN, Patel HD. Synth. Commun. 2014; 44: 1859
    Crossref
    • 8a Borg S, Vollinga RC, Labarre M, Payza K, Terenius L, Luthman K. J. Med. Chem. 1999; 42: 4331
      CrossrefPubMed
    • 8b Friggeri L, Hargrove TY, Wawrzak Z, Blobaum AL, Rachakonda G, Lindsley CW, Villalta F, Nes WD, Botta M, Guengerich FP, Lepesheva GI. J. Med. Chem. 2018; 61: 5679
      CrossrefPubMed
    • 8c Nakajima K, Chatelain R, Clairmont KB, Commerford R, Coppola GM, Daniels T, Forster CJ, Gilmore TA, Gong Y, Jain M, Kanter A, Kwak Y, Li J, Meyers CD, Neubert AD, Szklennik P, Tedesco V, Thompson J, Truong D, Yang Q, Hubbard BK, Serrano-Wu MH. J. Med. Chem. 2017; 60: 4657
      CrossrefPubMed
    • 8d Nieddu V, Pinna G, Marchesi I, Sanna L, Asproni B, Pinna GA, Bagella L, Murineddu G. J. Med. Chem. 2016; 59: 10451
      CrossrefPubMed
    • 8e Chiang IH, Long C.-J, Lin H.-C, Chuang W.-T, Lee J.-J, Lin H.-C. ACS Appl. Mater. Interfaces 2014; 6: 228
      CrossrefPubMed
    • 9a Achar TK, Bose A, Mal P. Beilstein J. Org. Chem. 2017; 13: 1907
      CrossrefPubMed
    • 9b Gaspa S, Porcheddu A, Valentoni A, Garroni S, Enzo S, De Luca L. Eur. J. Org. Chem. 2017; 5519
      Crossref
    • 9c Howard JL, Cao Q, Browne DL. Chem. Sci. 2018; 9: 3080
      CrossrefPubMed
    • 9d Leonardi M, Villacampa M, Menendez JC. Chem. Sci. 2018; 9: 2042
      CrossrefPubMed
    • 9e Perez-Venegas M, Juaristi E. ACS Sustainable Chem. Eng. 2020; 8: 8881
      Crossref
    • 9f Strukil V. Synlett 2018; 29: 1281
      Article in Thieme Connect
    • 9g Ying P, Yu J, Su W. Adv. Synth. Catal. 2021; 363: 1246
      Crossref
    • 10a Gaspa S, Carraro M, Pisano L, Porcheddu A, De Luca L. Eur. J. Org. Chem. 2019; 3544
      Crossref
    • 10b Mendonca GF, de Mattos MC. S. Curr. Org. Synth. 2013; 10: 820
      Crossref
    • 10c Tilstam U, Weinmann H. Org. Process Res. Dev. 2002; 6: 384
      Crossref
  • 11 Rezazadeh S, Akhlaghinia B, Razavi N. Aust. J. Chem. 2015; 68: 145
    Crossref
  • 12 de Andrade VS. C, de Mattos MC. S. Synthesis 2016; 48: 1381
    Article in Thieme Connect
  • 13 Singh M, Singh AS, Mishra N, Agrahari AK, Tiwari VK. Synthesis 2019; 51: 2183
    Article in Thieme Connect
  • 14 Phakhodee W, Yamano D, Pattarawarapan M. Synlett 2020; 31: 703
    Article in Thieme Connect
  • 15 Ghodsinia SS. E, Akhlaghinia B. Phosphorus, Sulfur Silicon Relat. Elem. 2016; 191: 1
    Crossref
  • 16 Khadem Moghaddam R, Aghapour G. Phosphorus, Sulfur Silicon Relat. Elem. 2021; 196: 398
    Crossref
    • 17a Katritzky AR, Mohapatra PP, Huang L. ARKIVOC 2008; (ix): 62
      Crossref
    • 17b Wang X, Yu H, Xu P, Zheng R. J. Chem. Res. 2005; 595
      Crossref
    • 17c Wang Z, Zhang H, Killian BJ, Jabeen F, Pillai GG, Berman HM, Mathelier M, Sibble AJ, Yeung J, Zhou W, Steel PJ, Hall CD, Katritzky AR. Eur. J. Org. Chem. 2015; 5183
      Crossref
  • 18 Synthesis of 2; General Procedure: N-Acylbenzotriazole (0.54 mmol) was mixed with acylhydrazide (0.54 mmol) and ground in mortar for 2–5 min, during which a few drops of acetone/CH2Cl2 (1:2 v/v, less than 1 μL/mg solids) were added to aid the homogeneous mixing. TCCA (0.0502 g, 0.216 mmol), PPh3 (0.1699 g, 0.648 mmol), and NaHCO3 (0.1361 g, 1.62 mmol) were then added before further grinding until completion of the reaction as indicated by TLC. It is noted that the grinding was stopped intermittently for TLC analysis using a glass capillary tube filled with ethanol for TLC sampling. The semi-solid mixture was then dissolved in acetone (ca. 2 mL), followed by filtration of the solids before solvent removal in vacuo. The crude material was purified by column chromatography using ethyl acetate/hexanes as the eluent to afford pure product. Note: Five new compounds including 2k, 2m, 2n, 2t, 2u were fully characterized, while the spectral data for the known products were consistent with the reported data. tert-Butyl (S)-(1-(5-Phenyl-1,3,4-oxadiazol-2-yl)ethyl)carbamate(2k). Yield: 0.1217g (78%); white solid; mp 117–119 °C; Rf 0.31 (20% EtOAc/hexanes). 1H NMR (400 MHz, CDCl3): δ = 8.02–7.99 (m, 2 H), 7.53–7.44 (m, 3 H), 5.35 (d, J = 8.4 Hz, 1 H), 5.16 (quint, J = 7.2 Hz, 1 H), 1.63 (d, J = 7.2 Hz, 3 H), 1.44 (s, 9 H). Benzyl (S)-(2-Phenyl-1-(5-phenyl-1,3,4-oxadiazol-2-yl)ethyl)carbamate(2l). Yield: 0.1702g (79%); yellow solid; mp 109–111 °C; Rf 0.31 (20% EtOAc/hexanes). 1H NMR (400 MHz, CDCl3): δ = 7.97 (d, = 7.2 Hz, 2 H), 7.53 (t, J = 7.2 Hz, 1 H), 7.47 (t, J = 7.6 Hz, 2 H), 7.33–7.19 (m, 10 H), 6.10 (br s, 1 H), 5.49 (dd, J = 15.2, 7.6 Hz, 1 H), 5.13 (dd, J = 15.2, 12.4 Hz, 2 H), 3.43–3.31 (m, 2 H). (9H-Fluoren-9-yl)methyl (S)-(2-(4-(tert-Butoxy)phenyl)-1-(5-phenyl-1,3,4-oxadiazol-2-yl)ethyl)carbamate (2m). Yield: 0.2446g (81%); colorless oil; Rf 0.30 (20% EtOAc/hexanes). 1H NMR (400 MHz, CDCl3): δ = 7.96 (d, J = 8.4 Hz, 2 H), 7.75 (d, J = 7.6 Hz, 2 H), 7.58 (t, J = 7.6 Hz, 2 H), 7.53 (t, J = 7.6 Hz, 1 H), 7.45 (t, J = 7.6 Hz, 2 H), 7.38 (t, J = 7.6 Hz, 2 H), 7.29 (d, J = 7.6 Hz, 2 H), 7.05 (d, J = 7.6 Hz, 2 H), 6.88 (d, J = 8.4 Hz, 2 H), 6.06 (d, J = 9.2 Hz, 1 H), 5.42 (q, J = 7.6 Hz, 1 H), 4.46–4.35 (m, 2 H), 4.19 (t, J = 6.8 Hz, 1 H), 3.29 (d, J = 6.8 Hz, 2 H), 1.27 (s, 9 H). 13C{1H} NMR (100 MHz, CDCl3): δ = 166.0, 165.0, 155.6, 154.6, 143.74, 143.68, 141.3, 131.9, 130.1, 129.9, 129.0, 127.7, 127.1, 126.9, 125.1, 124.3, 123.5, 120.0, 78.5, 67.2, 49.2, 47.1, 39.3, 28.8. HRMS (ESI/QTOF): m/z [M + H]+ calcd for C35H34N3O4: 560.2544; found: 560.2541.2-(5-(4-Fluorobenzyl)-1,3,4-oxadiazol-2-yl)phenol (2t). Yield: 0.0904 g (62%); white solid; mp 97–99 °C; Rf 0.41(10% EtOAc/hexanes).1H NMR (400 MHz, CDCl3): δ = 10.06 (s, 1 H), 7.66 (dd, J = 8.0, 1.6 Hz, 1 H), 7.41 (ddd, J = 8.0,7.2, 1.6 Hz, 1 H), 7.36–7.31 (m, 2 H), 7.10–7.03 (m, 3 H), 6.96 (ddd, J = 8.0,7.2, 1.6 Hz, 1 H), 4.26 (s, 2 H).13C{1H} NMR (100 MHz, CDCl3): δ = 164.9, 164.0, 163.61, 161.16 (d, 1 J C–F = 345.0 Hz), 157.6, 133.7, 130.63, 130.55 (d, 3 J C–F = 8.0 Hz), 129.23, 129.20 (d, 4 J C–F = 3.0 Hz), 126.6, 119.9, 117.6, 116.16, 115.95 (d, 2 J C–F = 21.0 Hz), 108.0, 31.0. HRMS (ESI/QTOF): m/z [M + H]+ calcd for C15H12FN2O2: 271.0877; found: 271.0875.2-(5-(Pyridin-3-yl)-1,3,4-oxadiazol-2-yl)phenol(2u). Yield: 0.0839 g (65%); white solid; mp 132–134 °C; Rf 0.37(20% EtOAc/hexanes 2× developed). 1H NMR (400 MHz, CDCl3): δ = 10.02 (s, 1 H), 9.31 (dd, J = 2.4, 1.2 Hz, 1 H), 8.78 (dd, J = 4.8, 1.2 Hz, 1 H), 8.38 (dt, J = 8.0, 4.8, 1.6 Hz, 1 H), 7.80 (dd, J = 8.0, 7.2, 1.6 Hz, 1 H), 7.49–7.40 (m, 2 H), 7.09 (dd, J = 8.4, 1.2 Hz, 1 H), 7.00 (ddd, J = 8.4,7.2, 1.2 Hz, 1 H). 13C{1H} NMR (100 MHz, CDCl3): δ = 164.7, 161.2, 157.8, 152.8, 148.0, 134.3, 134.1, 126.6, 124.0, 120.1, 119.9, 117.8, 107.7.
    • 19a Freydank A, Janietz S, Schulz B. J. Electroanal. Chem. 1998; 456: 61
      Crossref
    • 19b Wang H, Ryu J.-T, Cao C, Kwon Y. J. Nanosci. Nanotechnol. 2008; 8: 4846
      CrossrefPubMed
    • 19c Yang C, Song H.-S, Liu D.-B. J. Mater. Sci. 2013; 48: 6719
      Crossref