The (1H-Tetrazol-1-yl)arenediazonium Salts as Convenient Reagents for Quinones Arylation: Synthesis of 1,3-Benzoxathiol-2-ones and Naphtho[2,1-d][1,3]oxathiol-2-ones Bearing (1H-Tetrazol-1-yl)phenyl Motif

: pp. 304 - 314
Ivan Franko National University of Lviv
Ivan Franko National University of Lviv
Ivan Franko National University of Lviv
Ivan Franko National University of Lviv
Ivan Franko National University of Lviv
Ivan Franko National University of Lviv

A convenient two-step method for the synthesis of novel 1,3-benzoxathiol-2-ones and naphtho[2,1-d][1,3]oxathiol-2-ones bearing (1H-tetrazol-1-yl)phenyl motif was developed. As a key step of the synthesis, an arylation of quinones (1,4-benzoquinone, 1,4-naphtho-quinones) with the (1H-tetrazol-1-yl)arenediazonium salts was studied and efficient protocols were elaborated to obtain a variety of substituted ((1H-tetrazol-1-yl)phenyl) benzo/naphtho-1,4-quinones in good to excellent yields. An alternative synthesis of ((1H-tetrazol-1-yl)phenyl) naphtho-1,4-quinones via Diels-Alder reaction of tetrazolylphenyl-1,4-benzoquinones was demonstrated. The prepared benzo/naphtho-1,4-quinones readily react with thiourea at room temperature in the presence of a strong mineral acid to form intermediate isothiuronium salts, which cyclize with high yields to condense 1,3-oxathiol-2-ones under heating.

  1. Myznikov, L.V.; Vorona, S.V.; Zevatskii, Y.E. Biologically Active Compounds and Drugs in the Tetrazole Series. Chem. Hete-rocycl. Compd. (N Y) 2021, 57, 224-233.
  2. Wei, C.-X.; Bian, M.; Gong, G.-H. Tetrazolium Compounds: Synthesis and Applications in Medicine. Molecules 2015, 20, 5528-5553.
  3. Herr, R.J. 5-Substituted-1H-tetrazoles as Carboxylic Acid Isos-teres: Medicinal Chemistry and Synthetic Methods. Bioorg. Med. Chem. 2002, 10, 3379-3393.
  4. Tang, H.; de Jesus, R.K.; Walsh, S.P.; Zhu, Y.; Yan, Y.; Priest, B.T.; Swensen, A.M.; Alonso-Galicia, M.; Felix, J.P.; Brochu, R.M. et al. Discovery of a Novel Sub-Class of ROMK Channel Inhibitors Typified by 5-(2-(4-(2-(4-(1H-Tetrazol-1-yl)phenyl)acetyl)piperazin-1-yl)ethyl)isobenzofuran-1(3H)-one. Bioorganic Med. Chem. Lett. 2013, 23, 5829-5832.
  5. Abrahamsson, K.; Andersson, P.; Bergman, J.; Bredberg, U.; Brånalt, J.; Egnell, A.-C.; Eriksson, U.; Gustafsson, D.; Hoffman, K.-J.; Nielsen, S. Discovery of AZD8165 - A Clinical Candi-date from a Novel Series of Neutral Thrombin Inhibitors. Med. Chem. Commun. 2016, 7, 272-281.
  6. Tsuchimori, N.; Hayashi, R.; Kitamoto, N.; Asai, K.; Kitazaki, T.; Iizawa, Y.; Itoh, K.; Okonogi, K. In Vitro and In Vivo Antifun-gal Activities of TAK-456, a Novel Oral Triazole with a Broad Antifungal Spectrum. Antimicrob. Agents Chemother. 2002, 46, 1388-1393.
  7. Vembu, S.; Parasuraman, P.; Gopalakrishnan, M. Synthesis, in vitro Antifungal and Antitubercular Evaluation of Novel Amino Pyrimidines Based Tetrazole Derivatives. J. Pharm. Res. 2014, 8, 1552-1558.
  8. Vembu, S.; Parasuraman, P.; Gopalakrishnan, M. Design, in silico Molecular Docking Studies, Synthesis, Spectral Characteriza-tion and in vitro Antifungal Evaluation of 1-(4-(1H-tetrazole-1-yl) phenyl)-3-arylprop-2-en-1-ones. Der Pharma Chem. 2014, 6, 35-44.
  9. Lamie, P.F.; Philoppes, J.N.; Azouz, A.A.; Safwat, N.M. Novel Tetrazole and Cyanamide Derivatives as Inhibitors of Cyclooxygenase-2 enzyme: Design, Synthesis, Anti-Inflammatory Evaluation, Ulcerogenic Liability and Docking Study. J. Enzyme Inhib. Med. Chem. 2017, 32, 805-820.
  10. Ismael, A.; Henriques, M.S.C.; Marques, C.; Rodrigues, M.; Barreira, L.; Paixao, J.A.; Fausto, R.; Cristiano, M.L.S. Exploring Saccharinate-Tetrazoles as Selective Cu(II) Ligands: Structure, Magnetic Properties and Cytotoxicity of Copper(II) Complexes Based on 5-(3-Aminosaccharyl)-tetrazoles. RSC Adv. 2016, 6, 71628-71637.
  11. Reddy, S.R.K.; Surya, S.M.; Shaik, M.; Kanuparthy, P.R. Copper Complexes of Pyridyl-Tetrazole Ligands with Pendant Amide and Hydrazide Arms: Synthesis, Characterization, DNA-Binding and Antioxidant Properties. Transit. Met. Chem. 2016, 41, 517-523.
  12. Slyvka, Yu.I.; Fedorchuk, A.A.; Pokhodylo, N.T.; Lis, T.; Kityk, I.V.; Mys'kiv, M.G. A Novel Copper (I) Sulfamate π-Complex Based on the 5-(Allylthio)-1-(3,5-dimethylphenyl)-1H-tetrazole Ligand: Alternating-current Electrochemical Crystalliza-tion, DFT Calculations, Structural and NLO Properties Studies. Polyhedron 2018, 147, 86-93.
  13. Slyvka, Y.; Goreshnik, E.; Pokhodylo, N.; Pavlyuk, O.; Mys'kiv, M. Two Related Copper(I) π-Complexes Based on 2-Allyl-5-(2-pyridyl)-2H-tetrazole Ligand: Synthesis and Structure of [Cu(2-apyt)NO3] and [Cu(2-apyt)(H2O)](BF4) Compounds. Acta Chim. Slov. 2016, 63, 399-405.
  14. Slyvka, Y.; Goreshnik, E.; Veryasov, G.; Morozov, D.; Fe-dorchuk, A.A.; Pokhodylo, N.; Kityk, I.; Mys'kiv, M. The Novel Copper(I) π,σ-Complexes with 1-(Aryl)-5-(allylthio)-1H-tetrazoles: Synthesis, Structure Characterization, DFT-Calculation and Third-Order Nonlinear Optics. J. Coord. Chem. 2019, 72, 1049-1063.
  15. Pokhodylo, N.T.; Shyyka, O.Y.; Matiychuk, V.S.; Obushak, M.D. New Convenient Strategy for Annulation of Pyrimidines to Thiophenes or Furans via the One-pot Multistep Cascade Reaction of 1H-Tetrazoles with Aliphatic Amines. ACS Comb. Sci. 2015, 17, 399-403.
  16. Shyyka, O.; Pokhodylo, N.; Finiuk, N.; Matiychuk, V.; Stoika, R.; Obushak, M. Anticancer Activity Evaluation of New Thieno[2,3-d]pyrimidin-4(3H)-ones and Thieno[3,2-d]pyrimidin-4(3H)-one Derivatives. Sci. Pharm. 2018, 86, 28.
  17. Pokhodylo, N.T.; Shyyka, O.Y.; Slyvka, Y.I.; Goreshnik, E.A.; Obushak, M.D. Solvent-Free Synthesis of Cytisine-Thienopyrimidinone Conjugates via Transannulation of 1H-tetrazoles: Crystal and Molecular Structure, Docking Studies and Screening for Anticancer Activity. J. Mol. Struct. 2021, 1240, 130487.
  18. Shyyka, O.Y.; Pokhodylo, N.T.; Palchykov, V.A.; Finiuk, N.S.; Stoika, R.S.; Obushak, M.D. Cage-Like Amines in the Green Protocol of Transannular Thieno[2,3-d]Pyrimidinone Formation as Promising Anticancer Agents. Chem. Heterocycl. Compd. 2020, 56, 793-799.
  19. Burnett, A. R.; Thomson, R. H. Naturally Occurring Qui-nones. Part X. The Quinonoid Constituents of Tabebuia avel-lanedae (Bignoniaceae). J. Chem. Soc. C 1967, 2100-2104.
  20. Ma, W.; Long, Y.-T. Quinone/Hydroquinone-Functionalized Biointerfaces for Biological Applications from the Macro- to Nano-Scale. Chem. Soc. Rev. 2014, 43, 30-41.
  21. Zhang, L.; Zhang, G.; Xu, S.; Song, Y. Recent Advances of Quinones as a Privileged Structure in Drug Discovery. Eur. J. Med. Chem. 2021, 223, 113632.
  22. Calì, V.; Tringali, C. Polyhydroxy-P-Terphenyls and Related P-Terphenylquinones from Fungi: Overview and Biological Properties. Stud. Nat. Prod. Chem. 2003, 29, 263-307.
  23. Deb, A.; Agasti, S.; Saboo, T.; Maiti, D. Generation of Ary-lated Quinones by Iron-Catalyzed Oxidative Arylation of Phenols: Formal Synthesis of Phellodonin, Sarcodonin ε, Leucomelone and Betulinan A. Adv. Synth. Catal. 2014, 356, 705-710.
  24. Fujiwara, Y.; Domingo, V.; Seiple, I.B.; Gianatassio, R.; Del Bel, M.; Baran, P.S. Practical C−H Functionalization of Quinones with Boronic Acids. J. Am. Chem. Soc. 2011, 133, 3292-3295.
  25. Rondestvedt Jr, C.S. Arylation of Unsaturated Compounds by Diazonium Salts (The Meerwein Arylation Reaction). Org. React. 2011.
  26. Honraedt, A.; Le Callonnec, F.; Le Grognec, E.; Fernandez, V.; Felpin, F.-X. C-H Arylation of Benzoquinone in Water through Aniline Activation: Synergistic Effect of Graphite-Supported Cop-per Oxide Nanoparticles. J. Org. Chem. 2013, 78, 4604-4609.
  27. Lamblin, M.; Naturale, G.; Dessolin, J.; Felpin, F.-X. Direct C-H Arylation of Quinones with Anilines. Synlett 2012, 23, 1621-1624.
  28. Itahara, T. Oxidative Coupling of Quinones and Aromatic Compounds by Palladium(II) Acetate. J. Org. Chem. 1985, 50, 5546-5550.
  29. Singh, P.K.; Rohtagi, B.K.; Khanna, R.N. Arylation of Quin-tones with Aryl Mercuryl Chloride Catalyzed by Lithium Palladium Chloride. Synth. Commun. 1992, 22, 987-993.
  30. Best, W.M.; Sims, C.G.; Winslade, M. Palladium-Catalysed Cross Coupling of Arylboronic Acids with 2-Chloro-1,4-naphthoquinones: the Synthesis of 2-Aryl- and 2,3-Bisaryl-1,4-naphthoquinones. Aust. J. Chem. 2001, 54, 401-403.
  31. Gan, X.; Jiang, W.; Wang, W.; Hu, L. An Approach to 3,6-Disubstituted 2,5-Dioxybenzoquinones via Two Sequential Suzuki Couplings. Three-Step Synthesis of Leucomelone. Org. Lett. 2009, 11, 589-592.
  32. Wang, J.; Wang, S.; Wang, G.; Zhang, J.; Yu, X.-Q. Iron-Mediated Direct Arylation with Arylboronic Acids Through an Aryl Radical Transfer Pathway. Chem. Commun. 2012, 48, 11769-11771.
  33. Komeyama, K.; Kashihara, T.; Takaki, K. FeSO4-promoted Direct Arylation of Benzoquinones with ArB(OH)2 or ArBF3K. Tetrahedron Lett. 2013, 54, 1084-1086.
  34. Singh, P.P.; Aithagani, S.K.; Yadav, M.; Singh, V.P.; Vish-wakarma, R.A. Iron-catalyzed Cross-Coupling of Electron-Deficient Heterocycles and Quinone with Organoboron Species via Innate C-H Functionalization: Application in Total Synthesis of Pyrazine Alkaloid Botryllazine A. J. Org. Chem. 2013, 78, 2639-2648.
  35. Deb, A.; Manna, S.; Maji, A.; Dutta, U.; Maiti, D. Iron-Catalyzed Direct C-H Arylation of Heterocycles and Quinones with Arylboronic Acids. Eur. J. Org. Chem. 2013, 2013, 5251-5256.
  36. Ashok, P.; Ilangovan, A. Transition Metal Mediated Selective C vs N Arylation of 2-Aminonaphthoquinone and its Application Toward the Synthesis of Benzocarbazoledione. Tetrahedron Lett. 2018, 59, 438-441.
  37. Molina, M.T.; Navarro, C.; Moreno, A.; Csákÿ, A.G. Aryla-tion of Benzo-Fused 1,4-Quinones by the Addition of Boronic Acids under Dicationic Pd(II)-Catalysis. Org. Lett. 2009, 11, 4938-4941.
  38. Patil, P.; Nimonkar, A.; Akamanchi, K.G. Aryl-Free Radical-Mediated Oxidative Arylation of Naphthoquinones Using o-Iodoxybenzoic Acid and Phenylhydrazines and Its Application toward the Synthesis of Benzocarbazoledione. J. Org. Chem. 2014, 79, 2331-2336.
  39. oon, Y.; Jeong, Y.; Kook, D.; Hong, S. Rh(III)-catalyzed Direct C-H/C-H Cross-Coupling of Quinones with Arenes Assisted by a Directing Group: Identification of Carbazole Quinones as GSKβ Inhibitors. Org. Biomol. Chem. 2015, 13, 3918-3923.
  40. Wang, D.; Ge, B.; Li, L.; Shan, J.; Ding, Y. Transition Metal-Free Direct C-H Functionalization of Quinones and Naphthoqui-nones with Diaryliodonium Salts: Synthesis of Aryl Naphthoqui-nones as β-Secretase Inhibitors. J. Org. Chem. 2014, 79, 8607-8613.
  41. Wang, Y.; Zhu, S.; Zou, L.-H. Recent Advances in Direct Functionalization of Quinones. Eur. J. Org. Chem. 2019, 2019, 2179-2201.
  42. Gaponik, P.N.; Karavai, V.P.; Davshko, I.E.; Degtyarik, M.M.; Bogatikov, A.N. Synthesis and Properties of Phenylenebis-1H-tetrazoles. Chem. Heterocycl. Compd. 1990, 26, 1274-1278.
  43. Herbst, R.M.; Roberts, C.W.; Givens, H.T.F.; Harvill, E.K. The Synthesis of Nitro- and Amino-Phenyltetrazoles. J. Org. Chem. 1952, 17, 262-271.
  44. Zuo, Z.; Chen, M.; Shao, X.; Qian, X.; Liu, X.; Zhou, X.; Xiang, J.; Deng, P.; Li, Y.; Jie, H. et al. Design and Biological Evaluation of Tetrahydropyridine Derivatives as Novel Human GPR119 Agonists. Bioorg. Med. Chem. Lett. 2020, 30, 126855.
  45. Shurukhin, Y.V.; Klyuev, N.A.; Grandberg, I.I.; Konchits, V.A. Thermal Reactions of 1-Aryl-5-methyltetrazoles. Chem. Hete-rocycl. Compd. 1984, 20, 1177-1182.
  46. Scott, F.; Britten, F.; Reilly, J. Notes - Polynitrogen Systems from the Hydrazinocarbonic Acids. Part VII. Some Reactions of 1-Phenyl-5-methylmercaptotetrazole. J. Org. Chem. 1956, 21, 1191-1193.
  47. Neamati, N.; Petasis, N.; Yamada, R. Propynoic acid carba-moyl methyl-almides and pharmaceutical compositions and methods based thereon. WO2012129452A2, 2012.
  48. Allen, C.F.H.; Bell, A. 2,3-Dimethyl-1,3-butadiene. Organic Synth. 1942, 22, 39.
  49. Pokhodylo, N.T.; Matiychuk, V.S.; Obushak, M.D. Synthesis of Isothiocoumarin Derivatives. Chem. Heterocycl. Compd. 2010, 46, 140-145.
  50. Pokhodylo, N.; Finiuk, N.; Klyuchivska, O.; Stoika, R.; Ma-tiychuk, V.; Obushak, M. Bioisosteric Replacement of 1H-1,2,3-Triazole with 1H-Tetrazole Ring Enhances Anti-Leukemic Activity of (5-Benzylthiazol-2-yl)benzamides. Eur. J. Med. Chem. 2023, 250, 115126.
  51. Marini-Bettòlo, G.B.; Rossi, C. Action of Diazo Compounds on Quinones. II. Reaction between Diazocompounds and Naphtho-quinones; Preparation of Phenylnaphthalenes. Gazz. chim. ital. 1942, 72, 208-215. (Chem. Abstr. 1943, 37, 4386-4387).
  52. Wurm, G.; Gurka, H.-J. Phenyl-1,4-naphthochinonderivate mit Hydroxylierungsmustern von Bioflavonoiden. Pharmazie 1997, 52, 739-743.
  53. Fiedler, H. Darstellung von Hydroxy-2-oxo- bzw.−2-thion-1.3-benzoxathiolen. Chemische Berichte 1962, 95, 1771-1785.
  54. Klemm, K.; Geiger, B. Addition von Dithiocarbonsäure-Derivaten an p-Chinone. Justus Liebigs Ann. Chem. 1969, 726, 103-109.
  55. Harris, R.L.N.; Oswald, L.T. The Addition of Dithiocarbamic Acids to p-Benzoquinone. Aust. J. Chem. 1974, 27, 1309-1316.
  56. Hartmann, H.; Mohn, F. Kationische Farbstoffe und Vorstu-fen. XVI. Styrylcyanine der 1,3-Oxathiolium-Reihe. J. Prakt. Chem. 1972, 314, 419-427.
  57. Fabian, K.; Hartmann, H. Kationische Farbstoffe und Vorstu-fen. VI. Versuche zur Cyclisierung von S-Ketomethylen-sowie o-Hydroxyphenyl-thiolester-Derivaten zu 1,3-Oxathiolium- bzw. 1,3-Dithiolium-Salzen. J. Prakt. Chem.1971, 313, 722-729.
  58. Shadyro, O.I.; Timoshchuk, V.A.; Polozov, G.I.; Povalishev, V.N.; Andreeva, O.T.; Zhelobkovich, V.E. Synthesis and Antiviral Activity of Spatially-Screened Phenols: 1,3-Benzoxathiolan-2-one Derivatives. Pharm. Chem. J. 1999, 33, 366-369.
  59. Obushak, N.D.; Matiichuk, V.S.; Martyak, R.L. Synthesis of Heterocycles Based on Products of Anion Arylation of Unsaturated Compounds. 5. Reaction of 2-Aryl-1,4-benzoquinones with Thiou-rea. Chem. Heterocycl. Compd. 2001, 37, 909-915.
  60. Vellasco, W.T.; Gomes, C.R.B.; Vasconcelos, T.R.A. Chemi-stry and Biological Activities of 1,3-Benzoxathiol-2-ones. Mini-Rev. Org. Chem. 2011, 8, 103-109.
  61. Musyanovych, R. Reactions of Sulfenyl Chlorides of Substi-tuted 1,4-Naphthoquinone. Chem. Chem. Technol. 2011, 5, 367-372.
  62. Shakh, Y.; Slesarchuk, M.; Syngaevsky, V.; Bolibrukh, K.; Karkhut, A.; Polovkovych, S.; Shevchuk, L.; Novikov, V. Interac-tion of 5-Substituted 1,4-Naphthoquinones and Amino Thiotria-zoles: Reaction Ways and Regioselectivity. Chem. Chem. Technol. 2018, 12, 167-175.
  63. Thurman, D.E.; Stollings, H.W. Synthesis of Some 5-Hydroxynaphth[2,1-d]-1,3-oxathiol-2-ones. J. Heterocycl. Chem. 1973, 10, 117-119.