DOI: https://doi.org/10.24959/ophcj.18.951

The synthesis and cyclofunctionalization of (1,3-thiazolidin-2-ylidene)ketones

M. B. Litvinchuk, A. V. Bentya, N. Yu. Slyvka, M. V. Vovk

Abstract


Aim. To develop a new approach to the design of (1,3-thiazolidin-2-ylidene)ketones and expansion of their synthetic potential as convenient building blocks in the reactions of [3+2]- and [3+3]-cyclization.

Results and discussion. Еlectrophilic intramolecular cyclization (EIC) of N-allythioamides of β-ketoacids using phosphoric acid or iodine is a convenient synthetic method to obtain new (5-methyl- and 5-iodomethyl-1,3-thiazolidine-2-ylidene)ketones. Cyclization of ketones with maleic anhydride leads to derivatives of 2,3-dihydropyrrolo[2,1-b][1,3]thiazole. [3+3]-Cyclocondensation with methyl propiolate and dimethyl acetylenedicarboxylate results in formation of the functionalized [1,3]thiazolo[3,2-a]pyridine derivatives.

Experimental part. (5-Methyl- and 5-iodomethyl-1,3-thiazolidin-2-ylidene)ketones were synthesized from N-allylthioamides using phosphoric acid or iodine in chloroform. (1,3-Thiazolidin-2-ylidene)ketones react with maleic anhydride, methyl acetylenecarboxylate or dimethyl acetylenedicarboxylate resulting in a 2,3-dihydropyrrolo[2,1-b][1,3]thiazole-5(6H)-one and 2,3-dihydro-5H-[1,3]thiazolo[3,2-a]pyridine derivatives.

Conclusions. A convenient method of [5-methyl- and 5-iodomethyl-1,3-thiazolidin-2-ylidene]ketones preparation based on the EIC of N-allylthioamides of β-ketoacids has been developed using phosphoric acid and iodine. The (1,3-thiazolidin-2-ylidene)ketones synthesized can be useful in cyclization reactions leading to functional pyrrolo[2,1-b][1,3]thiazole and [1,3]thiazolo[3,2-a]pyridine derivatives.


Keywords


N-allylthioamides; electrophilic cyclization; (1,3-thiazolidin-2-ylidene)ketones; tautomerism; pyrrolo[2,1-b][1,3]thiazoles; [1,3]thiazolo[3,2-a]pyridines

References


Huang, Z.–T., & Shi, X. (1990). Synthesis of Heterocyclic KeteneN,S–Acetals and Their Reactions with Esters of α,β–Unsaturated Acids. Synthesis, 1990 (02), 162–167. https://doi.org/10.1055/s-1990-26822

Huang, Z.–T., & Shi, X. (1990). Synthesis, Reactions, and Tautomerism of Ketene N,S–Acetals with Benzothiazoline Ring. Chemische Berichte, 123 (3), 541–547. https://doi.org/10.1002/cber.19901230321

Åberg, V., Sellstedt, M., Hedenström, M., Pinkner, J. S., Hultgren, S. J., & Almqvist, F. (2006). Design, synthesis and evaluation of peptidomimetics based on substituted bicyclic 2–pyridones—Targeting virulence of uropathogenic E. coli. Bioorganic & Medicinal Chemistry, 14 (22), 7563–7581. https://doi.org/10.1016/j.bmc.2006.07.017

Åberg, V., Das, P., Chorell, E., Hedenström, M., Pinkner, J. S., Hultgren, S. J., & Almqvist, F. (2008). Carboxylic acid isosteres improve the activity of ring–fused 2–pyridones that inhibit pilus biogenesis in E. coli. Bioorganic & Medicinal Chemistry Letters, 18 (12), 3536–3540. https://doi.org/10.1016/j.bmcl.2008.05.020

Åberg, V., Norman, F., Chorell, E., Westermark, A., Olofsson, A., Sauer–Eriksson, A. E., & Almqvist, F. (2005). Microwave–assisted decarboxylation of bicyclic 2–pyridone scaffolds and identification of Aβ–peptide aggregation inhibitors. Organic & Biomolecular Chemistry, 3 (15), 2817. https://doi.org/10.1039/b503294f

Kulén, M., Lindgren, M., Hansen, S., Cairns, A. G., Grundström, C., Begum, A., … Almqvist, F. (2018). Structure–Based Design of Inhibitors Targeting PrfA, the Master Virulence Regulator of Listeria monocytogenes. Journal of Medicinal Chemistry, 61 (9), 4165–4175. https://doi.org/10.1021/acs.jmedchem.8b00289

Glennon, R. A., Gaines, J. J., & Rogers, M. E. (1981). Benz–fused mesoionic xanthine analogs as inhibitors of cyclic–AMP phosphodiesterase. Journal of Medicinal Chemistry, 24 (6), 766–769. https://doi.org/10.1021/jm00138a027

Manfroni, G., Meschini, F., Barreca, M. L., Leyssen, P., Samuele, A., Iraci, N., … Cecchetti, V. (2012). Pyridobenzothiazole derivatives as new chemotype targeting the HCV NS5B polymerase. Bioorganic & Medicinal Chemistry, 20 (2), 866–876. https://doi.org/10.1016/j.bmc.2011.11.061

Džambaski, Z., Marković, R., Kleinpeter, E., & Baranac–Stojanović, M. (2013). 2–Alkylidene–4–oxothiazolidine S–oxides: synthesis and stereochemistry. Tetrahedron, 69 (31), 6436–6447. https://doi.org/10.1016/j.tet.2013.05.087

Marković, R., Baranac, M., Džambaski, Z., Stojanović, M., & Steel, P. J. (2003). High regioselectivity in the heterocyclization of β–oxonitriles to 4–oxothiazolidines: X–ray structure proof. Tetrahedron, 59 (39), 7803–7810. https://doi.org/10.1016/s0040-4020(03)01146-3

Marković, R., Vitnik, Ž., Baranac, M., & Juranic, I.(2002). Mechanism of stereoselective synthesis of push–pull (Z)–4–oxothiazolidine derivatives containing an exocyclic double bond. A MNDO–PM3 Study. Journal of Chemical Research, 2002 (10), 485–489. https://doi.org/10.3184/030823402103170673

Marković, R., Baranac, M. (2000) Regioselective Synthesis of New 5–Ethoxycarbonylmethyl–4–oxothiazolidin–2–ylidene Bromides and Rearrangement Reaction Thereof. Synlett, 2000 (05), 607–610. https://doi.org/10.1055/s-2000-6596

Elghandour, A. H. H., Ibrahim, M. K. A., Elshikh, S. M. M., & Ali, F. M. M. (1992). Studies with polyfunctionally substituted heteroaromatics: synthesis of several new thiazoles, pyrazolo[5,1–c]triazines and of polyfunctionally substituted pyridines and pyrimidines. Tetrahedron, 48 (42), 9295–9304. https://doi.org/10.1016/s0040-4020(01)85619-2

Kambe, S., Saito, K., Sakurai, A., & Midorikawa, H. (1980). A Simplified Procedure for the Preparation of 2–Alkoxycarbonyl–5–aryl–4–cyano–3–hydroxy–3–phenyltetrahydrothiophenes. Synthesis, 1980 (10), 839–840. https://doi.org/10.1055/s-1980-29229

Satzinger, G. (1978). Heterocyclen durch Reaktion von Mercapto– und Hydroxycarbonsäureestern mit aktivierten Nitrilen. Justus Liebigs Annalen Der Chemie, 1978 (3), 473–511. https://doi.org/10.1002/jlac.197819780311

Satzinger, G. (1963). Substituierte 2–Methylen–thiazolidone–(4). Justus Liebigs Annalen Der Chemie, 665 (1), 150–165. https://doi.org/10.1002/jlac.19636650118

Dixit, A. N., Venodhar Reddy, K., Deshmukh, A. R. A. S., Rajappa, S., Ganguly, B., & Chandrasekhar, J. (1995). Conformational preferences of α–functionalised keten–S,N–acetals: Potential role of SO and SS interactions in solution. Tetrahedron, 51(5), 1437–1448. https://doi.org/10.1016/0040-4020(94)01023-s

Ohsugi, E., Fujioka, T., Harada, H., Nakamura, M., & Maeda, R. (1989). Synthetic studies on diuretics. 5–(3,3–n,s–substituted–2–propenoyl)–2,3–dihydro–2–benzo(b)furancarboxylic acids. Chemical & pharmaceutical bulletin, 37 (5), 1268–1278. https://doi.org/10.1248/cpb.37.1268

Chandrasekharam, M., Singh, O. M., Ila, H., & Junjappa, H. (1998). Reaction of β–Oxodithioesters With Propargylamine: A Facile Entry to Novel 2–(Acylalkylidene)–5–(Methylene)Thiazolidines. Synthetic Communications, 28 (16), 3073–3079. https://doi.org/10.1080/00397919808004887

Saravanan, S., Mohan, P., & Muthusubramanian, S. (2011). Formation of reagent–selective products from 2–(4,5–dihydrothi– azol–2–ylthio)–1–arylethanone with different nucleophiles. Journal of Sulfur Chemistry, 32 (1), 71–84. https://doi.org/10.1080/17415993.2010.533772

Litvinchuk, M. B., Bentya, A. V., Slyvka, N. Y., & Vovk, M. V. (2017). Halocyclization of products of allyl isothiocyanate addition to acyclic methylene active compounds. Russian Journal of Organic Chemistry, 53 (5), 709–716. https://doi.org/10.1134/s1070428017050104

Żankowska–Jasińska, W., Burgieł, M., Danel, A., Syguła, A. (1988) A novel synthesis of 1,3 Thiazetidine–2–one and 1,3–Oxazine–2–one Derivatives. Journal für Praktische Chemie. 330 (5), 795–800. https://doi.org/10.1002/prac.19883300516

Nishio, T. (1998) Sulfur–Containing Heterocycles Derived by Reaction of ω–Keto Amides withLawesson’s Reagent. Helvetica Chimica Acta. 81 (5–8), 1207–1214. https://doi.org/10.1002/hlca.19980810531

Gupta, A. K., Reddy, K. R., Ila, H., & Junjappa, H. (1995). Cuprous bromide–promoted cyclization of ketene N,S–acetals with prop–2–ynyl bromide: synthesis of regiospecifically substituted and annelated 3–acyl(or nitro)–5–methyl pyrroles. Journal of the Chemical Society, Perkin Transactions 1, (13), 1725. https://doi.org/10.1039/p19950001725

Gupta, A. K., Chakrasali, R. T., Ila, H., & Junjappa, H. (1989). Reaction of Polarized KeteneS,N–Acetals with Bromoacetaldehyde Diethyl Acetal: Synthesis of 1–Substituted 3–Acyl– and 3–Nitro–2–methylthiopyrroles and 1,2–Annulated 3–Acylpyrroles. Synthesis, 1989 (02), 141–142. https://doi.org/10.1055/s-1989-27179

Gupta, A. K., Ila, H., & Junjappa, H. (1988). Cyclocondensation of Acylketene S,N– and N,N–acetals with Maleic Anhydride and Maleimide: A Facile One–Step Synthesis of Pyrano [3,4–c]pyrrole, Pyrrolo [3,4–c]pyridine and Condensed Pyrrole Derivatives. Synthesis, 1988 (04), 284–286. https://doi.org/10.1055/s-1988-27544

Chakrasali, R. T., Ila, H., & Junjappa, H. (1988). Cycloaddition of Aroyl/Acylketene S,N–Acetals with Tosyl Azide: Synthesis of Novel 4–Aroyl/Acyl–5–amino–1H–1,2,3–triazoles and 3,4–Annulated 1,2,3–Triazoles. Synthesis, 1988 (11), 851–854. https://doi.org/10.1055/s-1988-27728

El–Shafei, A. K., El–Saghier, A. M. M., & Soliman, A. M. (1995). Synthesis of Heterocyclic Ketene N,S–Acetals and Their Reactions with α,β–Unsaturated Nitriles. Collection of Czechoslovak Chemical Communications, 60 (6), 1065–1069. https://doi.org/10.1135/cccc19951065

Yan, S., Chen, Y., Liu, L., He, N., & Lin, J. (2010). Three–component solvent–free synthesis of highly substituted bicyclic pyridines containing a ring–junction nitrogen. Green Chemistry, 12 (11), 2043. https://doi.org/10.1039/c0gc00373e

Ila, H., Junjappa, H., Chakrabarti, S., Panda, K., & Misra, N. C. (2005). Aza–Annulation of Polarized N,S– and N,N–Ketene Acetals with Itaconic Anhydride: Synthesis of Novel Functionalized 1,2,3,4–Tetrahydro–2–pyridones and Related Azabicycles. Synlett, (9), 1437–1441. https://doi.org/10.1055/s-2005-868491

Singh, A., Srivastava, A., & Singh, M. S. (2018). Metal–Free One–Pot Four–Component Cascade Annulation in Ionic Liquids at Room Temperature: Convergent Access to Thiazoloquinolinone Derivatives. The Journal of Organic Chemistry, 83 (15), 7950–7961. https://doi.org/10.1021/acs.joc.8b00814


GOST Style Citations


1.         Huang, Z.–T. Synthesis of Heterocyclic Ketene N,S–Acetals and Their Reactions with Esters of α,β–Unsaturated Acids / Z.–T. Huang, X. Shi // Synthesis. – 1990, Issue 2. – P. 162–167. https://doi.org/10.1055/s-1990-26822 

2.         Huang, Z.–T. Synthesis, Reactions, and Tautomerism of Ketene N,S–Acetals with Benzothiazoline Ring / Z.–T. Huang, X. Shi // Chem. Ber. – 1990. – Vol. 123, Issue 3. – P. 541–547. https://doi.org/10.1002/cber.19901230321 

3.         Design, synthesis and evaluation of peptidomimetics based on substituted bicyclic 2–pyridones – Targeting virulence of uropathogenic E. coli / V. Åberg, M. Sellstedt, M. Hedenström et al. // Bioorg. Med. Chem. – 2006. – Vol. 14, Issue 22. – Р. 7563–7581. https://doi.org/10.1016/j.bmc.2006.07.017 

4.         Carboxylic acid isosteres improve the activity of ring–fused 2–pyridones that inhibit pilus biogenesis in E. coli / V. Åberg, P. Das, E. Chorell et al. // Bioorg. Med. Chem. Lett. – 2008. – Vol. 18, Issue 12. – P. 3536–3540. https://doi.org/10.1016/j.bmcl.2008.05.020 

5.         Microwave–assisted decarboxylation of bicyclic 2–pyridone scaffolds and identification of Aβ–peptide aggregation inhibitors / V. Åberg, F. Norman, E. Chorell et al. // Org. Biomol. Chem. – 2005. – Vol. 3, Issue 15. – P. 2817–2823. https://doi.org/10.1039/b503294f 

6.         Structure–Based Design of Inhibitors Targeting PrfA, the Master Virulence Regulator of Listeria monocytogenes / M. Kulén, M. Lindgren, S. Hansen et al. // J. Med. Chem. – 2018. – Vol. 61, Issue 9. – P. 4165–4175. https://doi.org/10.1021/acs.jmedchem.8b00289 

7.         Glennon, R. A. Benz–fused mesoionic xanthine analogs as inhibitors of cyclic–AMP phosphodiesterase / R. A. Glennon, J. J. Gaines, M. E. Rogers // J. Med. Chem. – 1981. – Vol. 24, Issue 6. – P. 766–769. https://doi.org/10.1021/jm00138a027 

8.         Pyridobenzothiazole derivatives as new chemotype targeting the HCV NS5B polymerase / G. Manfroni, F. Meschini, M. L. Barreca et al. // Bioorg. Med. Chem. – 2012. – Vol. 20, Issue 2. – P. 866–876. https://doi.org/10.1016/j.bmc.2011.11.061 

9.         2–Alkylidene–4–oxothiazolidine S–oxides: synthesis and stereochemistry / Z. Džambaski, R. Marković,E. Kleinpeter, M. Baranac–Stojanović // Tetrahedron. – 2013. – Vol. 69, Issue 31. – P. 6436–6447. https://doi.org/10.1016/j.tet.2013.05.087 

10.       High regioselectivity in the heterocyclization of β–oxonitriles to 4–oxothiazolidines: X–ray structure proof / R. Marković, M. Baranac, Z. Džambaski et al. // Tetrahedron. – 2003. – Vol. 59, Issue 39. – P. 7803–7810. https://doi.org/10.1016/s0040-4020(03)01146-3 .

11.       Mechanism of stereoselective synthesis of push–pull (Z)–4–oxothiazolidine derivatives containing an exocyclic double bond. A MNDO–PM3 Study / R. Marković, Ž. Vitnik, M. Baranac,I. Juranic // J. Chem. Res. (S). – 2002. – Issue 10. – P. 485–489. https://doi.org/10.3184/030823402103170673 

12.       Marković, R. Regioselective Synthesis of New 5–Ethoxycarbonylmethyl–4–oxothiazolidin–2–ylidene Bromides and Rearrangement Reaction Thereof / R. Marković, M. Baranac // Synlett. – 2000. – Issue 5. – P. 607–610. https://doi.org/10.1055/s-2000-6596 

13.       Studies with polyfunctionally substituted heteroaromatics: synthesis of several new thiazoles, pyrazolo[5,1–c]triazines and of polyfunctionally substituted pyridines and pyrimidines / A. H. H. Elghandour, M. K. A. Ibrahim, S. M. M. Elshikh, F. M. M. Ali // Tetrahedron. – 1992. – Vol. 48, Issue 42. – P. 9295–9304. https://doi.org/10.1016/s0040-4020(01)85619-2 

14.       A Simplified Procedure for the Preparation of 2–Alkoxycarbonyl–5–aryl–4–cyano–3–hydroxy–3–phenyltetrahydrothiophenes / S. Kambe, K. Saito, A. Sakurai, H. Midorikawa // Synthesis. – 1980. – Issue 10. – P. 839–840. https://doi.org/10.1055/s-1980-29229 

15.       Satzinger, G. Heterocyclen durch Reaktion von Mercapto– und Hydroxycarbonsäureestern mit aktivierten Nitrilen / G. Satzinger // Liebigs Ann Chem. – 1978. – Issue 3. – P. 473–511. https://doi.org/10.1002/jlac.197819780311 

16.       Satzinger, G. Substituierte 2–Methylen–thiazolidone–(4) / G. Satzinger // Liebigs Ann Chem. – 1963. – Vol. 665, Issue 1. – P. 150–165. https://doi.org/10.1002/jlac.19636650118 

17.       Conformational preferences of α–functionalised keten–S,N–acetals: Potential role of S..O and S..S interactions in solution / A. N. Dixit, K. V. Reddy, A. R. A. S. Deschmukh et al. // Tetrahedron. – 1995. – Vol. 51, Issue 5. – P. 1437–1448. https://doi.org/10.1016/0040-4020(94)01023-s 

18.       Synthetic studies on diuretics. 5–(3,3–N,S–substituted–2–propenoyl)–2,3–dihydro–2–benzo[b]furancarboxylic acids / E. Ohsugi, T. Fujioka, H. Harada et al. // Chem. Pharm. Bull. – 1989. – Vol. 37, Issue 5. – P. 1268–1278. https://doi.org/10.1248/cpb.37.1268 

19.       Reaction of β–Oxodithioesters With Propargylamine: A Facile Entry to Novel 2–(Acylalkylidene)–5–(Methylene)Thiazolidines / M. Chandrasekharam, O. M. Singh, H. Ila, H. Junjappa // Synth. Commun. – 1998. – Vol. 28, Issue 16. – P. 3073–3079. https://doi.org/10.1080/00397919808004887

20.       Saravanan, S. Formation of reagent–selective products from 2–(4,5–dihydrothi– azol–2–ylthio)–1–arylethanone with different nucleophiles / S. Saravanan, P. Mohan,S. Muthusubramanian// J. Sulfur Chem. – 2011. – Vol. 32, Issue 1. – P. 71–84. https://doi.org/10.1080/17415993.2010.533772 

21.       Halocyclization of products of allyl isothiocyanate addition to acyclic methylene active compounds / M. B. Litvinchuk, A. V. Bentya, N. Y. Slyvka, M. V. Vovk // Russ. J. Org. Chem. – 2017. – Vol. 53. – P. 709–716. https://doi.org/10.1134/s1070428017050104 

22.       A novel synthesis of 1,3 Thiazetidine–2–one and 1,3–Oxazine–2–one Derivatives / W. Żankowska–Jasińska, M. Burgieł, A. Danel, A. Syguła // J. Prakt. Chem. – 1988. – Vol. 330, Issue 5. – P. 795–800. https://doi.org/10.1002/prac.19883300516 

23.       Nishio, T. Sulfur–Containing Heterocycles Derived by Reaction of ω–Keto Amides with Lawesson’s Reagent / T. Nishio // Helv. Chim. Acta. – 1998. – Vol. 81, Issue 5–8. – P. 1207–1214. https://doi.org/10.1002/hlca.19980810531 

24.       Cuprous bromide–promoted cyclization of ketene N,S–acetals with prop–2–ynyl bromide: synthesis of regiospecifically substituted and annelated 3–acyl(or nitro)–5–methyl pyrroles / A. K. Gupta, K. R. Reddy, H. Ila, H. Junjappa // J. Chem. Soc., Perkin Trans. 1. – 1995. – Issue 13. – P. 1725–1727. https://doi.org/10.1039/p19950001725 

25.       Reaction of Polarized Ketene S,N–Acetals with Bromoacetaldehyde Diethyl Acetal: Synthesis of 1–Substituted 3–Acyl– and 3–Nitro–2–methylthiopyrroles and 1,2–Annulated 3–Acylpyrroles / A. K. Gupta, R. T. Chakrasali, H. Ila, H. Junjappa // Synthesis. – 1989. – Issue 2. – P. 141–142. https://doi.org/10.1055/s-1989-27179 

26.       Gupta, A. K. Cyclocondensation of Acylketene S,N– and N,N–acetals with Maleic Anhydride and Maleimide: A Facile One–Step Synthesis of Pyrano [3,4–c]pyrrole, Pyrrolo [3,4–c]pyridine and Condensed Pyrrole Derivatives / A. K. Gupta, H. Ila, H. Junjappa // Synthesis. – 1988. – Issue 4. – P. 284–286. https://doi.org/10.1055/s-1988-27544 

27.       Chakrasali, R. T. Cycloaddition of Aroyl/Acylketene S,N–Acetals with Tosyl Azide: Synthesis of Novel 4–Aroyl/Acyl–5–amino–1H–1,2,3–triazoles and 3,4–Annulated 1,2,3–Triazoles / R. T. Chakrasali, H. Ila, H. Junjappa // Synthesis. – 1988. – Issue 11. – P. 851–854. https://doi.org/10.1055/s-1988-27728 

28.       El–Shafei, A. K. Synthesis of Heterocyclic Ketene N,S–Acetals and Their Reactions with α,β–Unsaturated Nitriles / A. K. El–Shafei, A. M. M. El–Saghier, A. M. Soliman // Collect. Czech. Chem. Commun. – 1995. – Vol. 60, Issue 6. – P. 1065–1069. https://doi.org/10.1135/cccc19951065 

29.       Three–component solvent–free synthesis of highly substituted bicyclic pyridines containing a ring–junction nitrogen / S. Yan, Y. Chen, L. Liu et al. // Green Chem. – 2010. – Vol. 12, Issue 11. – P. 2043–2052. https://doi.org/10.1039/c0gc00373e 

30.       Aza–Annulation of Polarized N,S– and N,N–Ketene Acetals with Itaconic Anhydride: Synthesis of Novel Functionalized 1,2,3,4–Tetrahydro–2–pyridones and Related Azabicycles / S. Chakrabarti, K. Panda, N. C. Misra et al. // Synlett. – 2005. – Issue 9. – P. 1437–1441. https://doi.org/10.1055/s-2005-868491 

31.       Singh, A. Metal–Free One–Pot Four–Component Cascade Annulation in Ionic Liquids at Room Temperature: Convergent Access to Thiazoloquinolinone Derivatives / A. Singh, A. Srivastava, M. S. Singh // J. Org. Chem. – 2018. – Vol. 83, Issue 15. – P. 7950–7961. https://doi.org/10.1021/acs.joc.8b00814 





Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.

Abbreviated key title: Ž. org. farm. hìm.

ISSN 2518-1548 (Online), ISSN 2308-8303 (Print)