DOI: https://doi.org/10.24959/ophcj.18.940

The synthesis and structural functionalization of 6-substituted 2,3-dihydroimidazo[2,1-b] [1,3]thiazol-5-ones

L. M. Saliyeva, R. I. Vas’kevich, N. Yu. Slyvka, M. V. Vovk

Abstract


Aim. To extend the synthetic limits of the reaction of the electrophilic intramolecular cyclization (EIC) on the examples of 5,5-disubstituted and 5-yliden substituted 3-allyl-2-thiohydantoins and the directed structural modification of 2-halogenomethyl-2,3-dihydroimidazo[2,1-b][1,3]thiazole-5-ones obtained.
Results and discussion. It has been found that the cyclization of 5,5-disubstituted and 5-yliden substituted 3-allyl-2-thiohydantoins under the effect of polyphosphoric acid (PPA), bromine and iodine is an effective method for the synthesis of new 2,3-dihydroimidazo[2,1-b][1,3]thiazole-5-ones. The reaction of the nucleophilic substitution of their 2-halogenomethyl representatives was used to obtain a number of sulfur-containing derivatives and azides. The latter were tested in the reaction of [3+2]-cycloaddition with N-phenylmaleinimide and propargyl alcohol.
Experimental part. A series of 2-substituted 2,3-dihydroimidazo[2,1-b][1,3]thiazole-5-ones was synthesized by the reaction of 5,5-disubstituted and 5-yliden substituted 3-allyl-2-thiohydantoins with PPA and halogens with the yields of 66-96 %. A directed modification of the halogenomethyl group of imidazotiazolones produced a series of sulfur-containing derivatives and azides with the yields of 63-93 %. The azides synthesized were used in the [3+2]-cycloaddition reaction with N-phenylmaleinimide and propargyl alcohol leading to 1,2,3-triazoloderivatives with the yields of 51-85 %; their structure was confirmed by the complex spectral analysis.
Conclusions. A convenient method for the synthesis of 2-halogenomethyl-substituted imidazo[2,1-b][1,3] thiazoles, which are effective reagents for the directed structural modification by sulfur- and nitrogen-containing functional groups, has been developed.


Keywords


3-аllyl-2-thiohydantoins; cyclization; 2-halogenomethyl-2,3-dihydroimidazo[2,1-b][1,3]thiazol- 5-ones; nucleophilic substitution; [3+2]-cycloaddition; 1,2,3-triazoles

References


Dangi, R. R., Hussain, N., Talesara, G. L. (2010). Synthesis characterization and biological evaluation of some alkoxyphthalimide derivatives of 3–(4–substituted phenyl)–6,6–diphenyl–3,3a–dihydro–2H–imidazo[2,1–b]pyrazolo[3,4–d][1,3]thiazol–7(6H)–one. Medicinal Chemistry Research,

(9), 1490–1498. doi: 10.1007/s00044–010–9392–4

Gürsoy, E., Güzeldemirci, N. U. (2007). Synthesis and primary cytotoxicity evaluation of new imidazo[2,1–b]thiazole derivatives. European Journal of Medicinal Chemistry, 42 (3), 320–326. doi: 10.1016/j.ejmech.2006.10.012

Andreani, A., Rambaldi, M., Locatelli, A., Bossa, R., Galatulas, I., Ninci, M. (1992). Synthesis and cardiotonic activity of 2,5–dimethyoxyphenylimidazo[2,1–b]thiazoles. European Journal of Medicinal Chemistry, 27 (4), 431–433. doi: 10.1016/0223–5234(92)90159–x

Andreani, A. (1999). 6–Thienyl and 6–phenylimidazo[2,1–b]thiazoles as inhibitors of mitochondrial NADH dehydrogenase. European Journal of Medicinal Chemistry, 34 (10), 883–889. doi: 10.1016/s0223–5234(99)00203–2

Laroche, C., Gilbreath, B., Kerwin, S. M. (2014). Exploring the synthetic utility of 1–alkynylimidazoles: regiocontrolled cyclization to diverse imidazoazines and imidazoazoles. Tetrahedron, 70 (30), 4534–4539. doi: 10.1016/j.tet.2014.04.099

Moser, W., Schindler, C., Keiser, J. (2017). Efficacy of recommended drugs against soil transmitted helminths: systematic review and network meta–analysis. British Medicinal Journal, 357, 1–10. doi: 10.1136/bmj.j4307.

Ulusoy, N., Kiraz, M., Küçükbasmac, Ö. (2002). New 6–(4–Bromophenyl)–imidazo[2,1–b]thiazole Derivatives: Synthesis and Antimicrobial Activity. Monatshefte Fur Chemie / Chemical Monthly, 133 (10), 1305–1315. doi: 10.1007/s007060200108

Dorn, H., Welfle, H. (1967). Potentielle Cytostatica, X. Mono– und bicyclische Systeme aus Senfölen sowie Rhodan–wasserstoffsäure und Bis–[2–chlor–äthyl]–amin. Chemische Berichte, 100 (10), 3246–3259. doi: 10.1002/cber.19671001014

Tsuge, O., Kanemasa, S., Hamamoto, T. (1982). A novel Tetravalent sulfur compound, 1,3,6–triphenylimidazo[ 1,2–c]thiaivzole; synthesis and peripheral cycloaddition reaction. Chemistry Letters, 11 (9), 1491–1494. doi: 10.1246/cl.1982.1491

Tsuge, O., Kanemasa, S., Hamamoto, T. (1983). Stereospecific reversible cycloaddition reactions of a biperifunctional compound, 1,3,6–triphenylimidazo[1,2–c]thiaivzole. Chemistry Letters, 12 (1), 85–88. doi: 10.1246/cl.1983.85

Kanemasa, S., Tsuge, O., Hamamoto, T. (1984). Synthesis and Cycloaddition Reaction of a Nitrogen–bridged Tetravalent Sulfer Compound 1,3,6–Triphenylimidazo[1,2–c]thiazole. Heterocycles, 21 (2), 573. doi: 10.3987/s–1984–02–0573

Ikeda, K., Hata, S.–I., Tanaka, Y., Yamamoto, T. (2000). Preparation of imidazo[2,1–b]thiazoles and thiazolo[3,2–a]–benzimidazoles using s–ethenylsulfilimines. Organic Preparations and Procedures International, 32 (4), 401–405. doi: 10.1080/00304940009355945

Stalling, T., Pauly, J., Schmidtmann, M., Martens, J. (2013). Multicomponent Synthesis of Bicyclic Thiazolidinethiones and Oxazolidinones in Water. European Journal of Organic Chemistry, 2014 (4), 833–843. doi: 10.1002/ejoc.201301213

Klika, K. D., Bernát, J., Imrich, J., Chomča, I., Sillanpää, R., Pihlaja, K. (2001). Unexpected Formation of a Spiro Acridine and Fused Ring System from the Reaction between anN–Acridinylmethyl–Substituted Thiourea and Bromoacetonitrile under Basic Conditions. The Journal of Organic

Chemistry, 66 (12), 4416–4418. doi: 10.1021/jo001695p

Klika, K. D., Pihlaja, K., Imrich, J., Vilková, M., Bernát, J. (2006). Unusual structures derived fromN–acridin–9–yl methyl N–acridin–9–yl thiourea based on the propensity of N–10 to retain H. Journal of Heterocyclic Chemistry, 43 (3), 739–743. doi: 10.1002/jhet.5570430331

Saliieva, L. M., Slyvka, N. Yu., Vaskevich, R. I. et al. (2016). Ukrainskyi khimichnyi zhurnal, 82 (5), 64–70.

Saliieva, L. M., Slyvka, N. Yu., Vaskevich, А. I. et al. (2016). Zhurnal orhanichnoi ta farmatsevtychnoi khimii, 14 (4), 58–62.

Magd El–Din, A. A., Roaiah, H. F., Elsharabasy, S. A., Hassan, A. Y. (2007). A Novel Synthesis of Some New Imidazothiazole and Glycocyamidine Derivatives and Studies on Their Antimicrobial Activities. Phosphorus, Sulfur, and Silicon and the Related Elements, 182 (3), 529–536. doi: 10.1080/10426500601013224

Diachenko, I. V., Vaskevich, R. I., Vaskevich, A. I. et. al. (2016). Zhurnal organicheskoi khimii, 52(5), 745–752.

Irie, T., Fujii, I., Sawa, M. (2012). Design and combinatorial synthesis of a novel kinase–focused library using click chemistry–based fragment assembly. Bioorganic & Medicinal Chemistry Letters, 22 (1), 591–596. doi: 10.1016/j.bmcl.2011.10.076

Tiew, K.–C., Dou, D., Teramoto, T., Lai, H., Alliston, K. R., Lushington, G. H., Groutas, W. C. (2012). Inhibition of Dengue virus and West Nile virus proteases by click chemistry–derived benz[d]isothiazol–3(2H)–one derivatives. Bioorganic & Medicinal Chemistry, 20 (3), 1213–1221. doi: 10.1016/j.bmc.2011.12.047

Pramitha, P., Bahulayan, D. (2012). Stereoselective synthesis of bio–hybrid amphiphiles of coumarin derivatives by Ugi–Mannich triazole randomization using copper catalyzed alkyne azide click chemistry. Bioorganic & Medicinal Chemistry Letters, 22 (7), 2598–2603. doi: 10.1016/j. bmcl.2012.01.111

Dürüst, Y., Karakuş, H., Kaiser, M., Tasdemir, D. (2012). Synthesis and anti–protozoal activity of novel dihydropyrrolo[3,4–d][1,2,3]triazoles. European Journal of Medicinal Chemistry, 48, 296–304. doi: 10.1016/j.ejmech.2011.12.028

Yoshino, H., Sato, H., Shiraishi, T., Tachibana, K., Emura, T., Honma, A., Kawata, H. (2010). Design and synthesis of an androgen receptor pure antagonist (CH5137291) for the treatment of castration–resistant prostate cancer. Bioorganic & Medicinal Chemistry, 18 (23), 8150–8157. doi: 10.1016/j.bmc.2010.10.023

Garst, M. E., Dolby, L. J., Esdandiari, S., Avey, A. A., Mac Kenzie, V. R., Muchmore D. C. (2007). Synthesis of Imidazole–2–thiones via Thiohydantoins. Pat. WO 2007/041048 A3; declared 22.09.2006; published 12.04.2007.

Khodair, A. I., Gesson, J.–P. (1998). Sulfur glycosylation reactions involving 3–allyl–2–thiohydantoin nucleoside bases as potential antiviral and antitumor agents. Phosphorus, Sulfur, and Silicon and the Related Elements, 142 (1), 167–190. doi: 10.1080/10426509808029674


GOST Style Citations


1. Dangi, R. R. Synthesis characterization and biological evaluation of some alkoxyphthalimide derivatives of 3–(4–substituted phenyl)–6,6–diphenyl–3,3a–dihydro–2H–imidazo[2,1–b]pyrazolo[3,4–d][1,3]thiazol–7(6H)–one / R. R. Dangi, N. Hussain, G. L. Talesara // Med. Chem. Res. – 2011.–Vol. 20, Issue 9. – P. 1490–1498. doi: 10.1007/s00044–010–9392–4

2. Gursoy, E. Synthesis and primary cytotoxicity evaluation of new imidazo[2,1–b]thiazole derivatives / E. Gursoy, N. Ulusoy Guzeldemirci // Eur. J. Med. Chem. – 2007. – Vol. 42, Issue 3. – P. 320–326. doi: 10.1016/j.ejmech.2006.10.012

3. Synthesis and cardiotonic activity of 2,5–dimethoxyphenylimidazo[2,1–b]thiazoles / A. Andreani, M. Rambaldi, A. Locatelli et al. // Eur. J. Med. Chem. – 1992. – Vol. 27, Issue 4. – P. 431–433. doi: 10.1016/0223–5234(92)90159–x

4. Andreani, A. 6–Thienyl and 6–phenylimidazo[2,1–b]thiazoles as inhibitors of mitochondrial NADH dehydrogenase / A. Andreani // Eur. J. Med. Chem. – 1999. – Vol. 34, Issue 10. – P. 883–889. doi: 10.1016/s0223–5234(99)00203–2

5. Laronche, C. Exploring the synthetic utility of 1–alkynylimidazoles: regiocontrolled cyclization to diverse imidazoazines and imidazoazoles / C. Laroche, B. Gilbreath, S. M. Kerwin // Tetrahedron. – 2014. – Vol. 70, Issue 30. – P. 4534–4539. doi: 10.1016/j.tet.2014.04.099

6. Moser, W. Efficacy of recommended drugs against soil transmitted helminths: systematic review and network meta–analysis / W. Moser, C. Schindler, J. Keiser // British. Med. J. – 2017. – Vol. 357. – P. 1–10. doi: 10.1136/bmj.j4307

7. Ulusoy, N. New 6–(4–Bromophenyl)–imidazo[2,1–b]thiazole Derivatives: Synthesis and Antimicrobial Activity / N. Ulusoy, M. Kiraz, O. Kucukbasmaci // Monatsh. Chem. – 2002. – Vol. 133, Issue 10. – P. 1305–1315. doi: 10.1007/s007060200108

8. Dorn, H. Potentielle Cytostatica, X. Mono– und bicyclisce Systeme aus Senfölen sowie Rhodan–wasserstoffsäure und Bis–[2–chlor–äthyl]–amin / H. Dorn, H. Welfle // Chem. Ber. – 1967. – Vol. 100, Issue 10. – P. 3246–3259. doi: 10.1002/cber.19671001014

9. Tsuge, O. A Novel Tetravalent Sulfur Compound, 1,3,6–triphenylimidazo[1,2–c]thiaIVzole ; Synthesis and Peripheral Cycloaddition Reaction / O. Tsuge, S. Kanemasa, T. Hamamoto // Chem. Lett. – 1982. – Vol. 11, Issue 9. – P. 1491–1494. doi: 10.1246/cl.1982.1491

10. Tsuge, O. Stereospecific Reversible Cycloaddition Reaction of a Biperifunctional Compound, 1,3,6–triphenylimidazo[1,2–c]thiaIVzole / O. Tsuge, S. Kanemasa, T. Hamamoto // Chem. Lett. – 1983. – Vol. 12, Issue 1. – P. 85–88. doi: 10.1246/cl.1983.85

11. Tsuge, O. Synthesis and Cycloaddition Reaction of a Nitrogen–Bridged Tetravalent Sulfur Compound, 1,3,6–Triphenylimidazo[1,2–c]thiazole / O. Tsuge, S. Kanemasa, T. Hamamoto // Heterocycles. – 1984. – Vol. 21, Issue 2. – 573 p. doi: 10.3987/s–1984–02–0573

12. Preparation of Imidazo[2,1–b]thiazoles and Thiazolo[3,2–a]benzimidazoles Using S–ethenylsulfilimines / K. Ikeda, S. Hata, Y. Tanaka et al. // Org. Prep. Proc. – 2000. – Vol. 32, Issue 4. – P. 401–405. doi: 10.1080/00304940009355945

13. Multicomponent Synthesis of Bicyclic Thiazolidinethiones and Oxazolidinones in Water / T. Stalling, J. Pauly, M. Schmidtmann, J. Martens // Eur. J. Org. Chem. – 2013. – Vol. 2014, Issue 4. – P. 833–843. doi: 10.1002/ejoc.201301213

14. Unexpected Formation of a Spiro Acridine and Fused Ring System from the Reaction between an N–Acridinylmethyl–Substituted Thiourea and Bromoacetonitrile under Basic Conditions / K. D. Klika, J. Bernat, J. Imrich et al. // J. Org. Chem. – 2001. – Vol. 66, Issue 12. – P. 4416–4418. doi: 10.1021/jo001695p

15. Unusual Structures Derived from N–Acridin–9–yl methyl N–Acridin–9–yl Thiourea Based on the Propensity of N–10 to Retain H / K. D. Klika, J. Imrich, M. Vilkova et al. // J. Het. Chem. – 2006. – Vol. 43, Issue 3. – P. 739–743. doi: 10.1002/jhet.5570430331

16. Синтез похідних 2,3–дигідроімідазо[2,1–b][1,3]тіазолу електрофільною циклізацією 3–аліл–2–тіоксоімідазолідин–4–онів / Л. М. Салієва, Н. Ю. Сливка, Р. І. Васькевич та ін. // Укр. хім. журн. – 2016. – Т. 82, № 5. – С. 64–70.

17. Циклосульфенілювання 3–алілтіогідантоїну / Л. М. Салієва, Н. Ю. Сливка, А. І. Васькевич та ін. // ЖОФХ. – 2016. – Т. 14, № 4. – С. 58–62.

18. A Novel Synthesis of Some New Imidazothiazole and Glycocyamidine Derivatives and Studies on Their Antimicrobial Activities / A. A. Magd El–Din, H. F. Roaiah, S. A. Elsharabasy et al. // Phosphorus, Sulfur, and Silicon. – 2007. – Vol. 182, Issue 3. – P. 529–536. doi: 10.1080/10426500601013224

19. Конденсированные пиримидиновые системы XVI.* Электрофильная внутримолекулярная циклизация 2–(алкенилсульфанил)птеридин– 4(3Н)–онов / И. В. Дяченко, Р. И. Васькевич, А. И. Васькевич и др. // ЖОрХ. – 2016. – Т. 52, вып. 5. – С. 755–761.

20. Irie, T. Design and combinatorial synthesis of a novel kinase–focused library using click chemistry–based fragment assembly / T. Irie, I. Fujii, M. Sawa // Bioorg. Med. Chem. Lett. – 2012. – Vol. 22, Issue 1. – P. 591–596. doi: 10.1016/j.bmcl.2011.10.076

21. Inhibition of Dengue virus and West Nile virus proteases by click chemistry–derived benz[d]isothiazol–3(2H)–one derivatives / K.–C. Tiew, D. Dou, T. Teramoto et al. // Bioorg. Med. Chem. Lett. – 2012. – Vol. 20, Issue 3. – P. 1213–1221. doi: 10.1016/j.bmc.2011.12.047

22. Pramitha, P. Stereoselective synthesis of bio–hybrid amphiphiles of coumarin derivatives by Ugi–Mannich triazole randomization using copper catalyzed alkyne azide click chemistry / P. Pramitha, D. Bahulayan // Bioorg. Med. Chem. Lett. – 2012. – Vol. 22, Issue 7. – P. 2598–2603. doi: 10.1016/j.bmcl.2012.01.111

23. Synthesis and anti–protozoal activity of novel dihydropyrrolo[3,4–d][1,2,3]triazoles / Y. Dürüst, H. Karakus, M. Kaiser et al. // Eur. J. Org. Chem. – 2012. – Vol. 48. – P. 296–304. doi: 10.1016/j.ejmech.2011.12.028

24. Design and synthesis of an androgen receptor pure antagonist (CH5137291) for the treatment of castration–resistant prostate cancer / H. Yoshino, H. Sato, T. Shiraishi et al. // Bioorg. Med. Chem. – 2010. – Vol. 18, Issue 23. – P. 8150–8157. doi: 10.1016/j.bmc.2010.10.023

25. Synthesis of Imidazole–2–thiones via Thiohydantoins. Pat. WO 2007/041048 A3 / Garst M. E., Dolby L. J., Esdandiari S., Avey A. A., Mac Kenzie V. R., Muchmore D. C. – declared: 22.09.2006 ; published: 12.04.2007.

26. Khodair, A. I. Sulfur Glycosylation Reactions Involving 3–Allyl–2–thiohydantion Nucleoside Bases as Potential Antivitral and Antitumor Agents / A. I. Khodair, J.–P. Gesson // Phosphorus, Sulfur, and Silicon. – 1998. – Vol. 142, Issue 1. – P. 167–190. doi: 10.1080/10426509808029674





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