Skip to main content
SpringerLink
Log in

A convenient four-component one-pot synthesis of 2-amino-1,3,4-thiadiazoles in water

  • Full-Length Paper
  • Published:
Molecular Diversity Aims and scope Submit manuscript

Abstract

A novel four-component one-pot approach for the synthesis of 2-amino-1,3,4-thiadiazoles from primary amines, carbon disulfide, hydrazine, and acyl chlorides has been developed. A series of 5-substituted-2-amino-1,3,4-thiadiazoles were synthesized in medium-to-good yields utilizing this newly developed method.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

Notes

  1. \(^{*}\)“Singlet” is abbreviated as “s” in the rest of this article, while “d” is short for doublet, “dd” for “doublet doublet,” “t” for “triplet,” “m” for “multiplet” etc.

References

  1. Kumar H et al (2008) 1,3,4-Oxadiazole/thiadiazole and 1,2,4-triazole derivatives of biphenyl-4-yloxy acetic acid: synthesis and preliminary evaluation of biological properties. Eur J Med Chem 43:2688–2698. doi:10.1016/j.ejmech.2008.01.039

    Article  PubMed  CAS  Google Scholar 

  2. Mullican MD, Wilson MW et al (1993) Design of 5-(3,5-di-tert-butyl-4-hydroxyphenyl)-1,3,4-thiadiazoles, -1,3,4-oxadiazoles, and -1,2,4-triazoles as orally-active, nonulcerogenic antiinflammatory agents. J Med Chem 36:1090–1099. doi:10.1021/jm00060a017

    Article  PubMed  CAS  Google Scholar 

  3. Song Y et al (1999) Synthesis, structure activity relationships, and in-vivo evaluations of substituted di-tert-butylphenols as a novel class of potent, selective, and orally active cyclooxygenase-2 inhibitors. 2. 1,3,4- and 1,2,4-thiadiazole series. J Med Chem 42:1161–1169. doi:10.1021/jm980570y

    Article  PubMed  CAS  Google Scholar 

  4. Boschelli DH et al (1993) 1,3,4-Oxadiazole, 1,3,4-thiadiazole, and 1,2,4-triazole analogs of the fenamates: in vitro inhibition of cyclooxygenase and 5-lipoxygenase activities. J Med Chem 36:1802–1810. doi:10.1021/jm00065a002

    Article  PubMed  CAS  Google Scholar 

  5. Bhati SK, Kumar A (2008) Synthesis of new substituted azetidinoyl and thiazolidinoyl-1,3,4-thiadiazino (6,5-b) indoles as promising anti-inflammatory agents. Eur J Med Chem 43:2323–2330. doi:10.1016/j.ejmech.2007.10.012

    Article  PubMed  CAS  Google Scholar 

  6. Miyamoto K, Koshiura R, Mori M, Yokoi H, Mori C, Hasegawa T, Takatori K (1985) Antitumor activity of 5-substituted 2-acylamino-1,3,4-thiadiazoles against transplantable rodent tumors. Chem Pharm Bull 33:5126–5129. doi:10.1248/cpb.33.5126

    Article  PubMed  CAS  Google Scholar 

  7. Kumar D, Kumar NM, Chang K, Shah K (2010) Synthesis and anticancer activity of 5-(3-indolyl)-thiadiazoles. Eur J Med Chem 45:4664–4668. doi:10.1016/j.ejmech.2010.07.023

    Article  PubMed  CAS  Google Scholar 

  8. Kumar D, Vaddula R, Chang K, Shah K (2011) One-pot synthesis and anticancer studies of 2-arylamino-5-aryl-1,3,4-thiadiazoles. Bioorg Med Chem Lett 21:2320–2323. doi:10.1016/j.bmcl.2011.02.083

    Article  PubMed  CAS  Google Scholar 

  9. Chou J, Lai S, Pan S, Jow G, Chern J, Guh J (2003) Investigation of anticancer mechanism of thiadiazole-based compound in human non-small cell lung cancer A549 cells. Biochem Pharmacol 66:115–124. doi:10.1016/S0006-2952(03)00254-5

    Article  PubMed  CAS  Google Scholar 

  10. Mhasalkar MY, Shah MH, Pilankar PD, Nikam ST, Anantarayanan KG, Deliwala CV (1971) Synthesis and hypoglycemic activity of 3-aryl(or pyridyl)-5-alkyl(or aryl) amino-thiadiazoles and some sulfonylurea serivatives of 4N-1,2,4-triazoles. J Med Chem 14:1000–1003. doi:10.1021/jm00292a035

    Article  PubMed  CAS  Google Scholar 

  11. Chapleo CB, Myres PL, Smith ACB, Stillings MR, Tulloch IF, Walter DS (1988) Substituted -thiadiazoles with anticonvulsant activity. J Med Chem 31:7–11. doi:10.1021/jm00396a004

    Article  PubMed  CAS  Google Scholar 

  12. Kumar S, Kaushik D, Bawa S, Khan SA (2012) Design, synthesis and screening of quinoline-incorporated thiadiazole as a potential anticonvulsant. Chem Biol Drug Des 79:104–111. doi:10.1111/j.1747-0285.2011.01255.x

    Article  PubMed  CAS  Google Scholar 

  13. Grant AM, Krees SV, Mauger AB, Rzezotarski WJ, Wolff FW (1972) Some hypotensive thiadiazole. J Med Chem 15:1082–1084. doi:10.1021/jm00280a028

    Article  PubMed  CAS  Google Scholar 

  14. Bahram H, Ramin M, Uranous N, Alireza F, Abbas S (2007) A mechanistic QSAR study on the leishmanicidal activity of some 5-substituted-thiadiazole derivatives. Chem Biol Drug Des 69:435–443. doi:10.1111/j.1747-0285.2007.00523.x

    Article  Google Scholar 

  15. Alipour E, Emami S, Meymand YA, Nakhjiri M, Johari F, Ardestani SK, Poorrajab F, Hosseini M, Shafiee A, Foroumadi A (2011) Synthesis and antileishmanial activity of 5-(5-nitroaryl)-2-substituted-thio-1,3,4-thiadiazoles. J Enzyme Inhib Med Chem 26:123–128. doi:10.3109/14756361003733654

    Article  PubMed  CAS  Google Scholar 

  16. Poorrajab F, Ardestani SK, Emami S, Behrouzi-Fardmoghadam M, Shafiee A, Foroumadi A (2009) Nitroimidazolyl-1,3,4-thiadiazole-based anti-leishmanial agents: synthesis and in vitro biological evaluation. Eur J Med Chem 44:1758–1762. doi:10.1016/j.ejmech.2008.03.039

    Article  PubMed  CAS  Google Scholar 

  17. Tahghighi A, Marznaki FR, Kobarfard F, Dastmalchi S, Mojarrad JS, Razmi S, Ardestani SK, Emami S, Shafiee S, Foroumadi A (2011) Synthesis and antileishmanial activity of novel 5-(5-nitrofuran-2-y1)-1,3,4-thiadiazoles with piperazinyl-linked benzamidine substituents. Eur J Med Chem 46:2602–2608. doi:10.1016/j.ejmech.2011.03.053

    Article  PubMed  CAS  Google Scholar 

  18. Matysiak J, Opolski A (2006) Synthesis and antiproliferative activity of N-substituted 2-amino-5-(2,4-dihydroxyphenyl)-1,3,4-thiadiazoles. Bioorg Med Chem 14:4483–4489. doi:10.1016/j.bmc.2006.02.027

    Article  PubMed  CAS  Google Scholar 

  19. Matysiak J, Nasulewicz A, Pełczynska M, Switalska M, Jaroszewicz I, Opolski A (2006) Synthesis and antiproliferative activity of some 5-substituted 2-(2,4-dihydroxyphenyl)-1,3,4-thiadiazoles. Eur J Med Chem 41:475–482. doi:10.1016/j.ejmech.2005.12.007

    Article  PubMed  CAS  Google Scholar 

  20. Rajak H, Deshmukh R, Aggarwal N, Kashaw S, Kharya MD, Mishra P (2009) Synthesis of novel 2,5-disubstituted 1,3,4-thiadiazoles for their potential anticonvulsant activity: pharmacophoric model studies. Arch Pharm Chem Life Sci 342:453–461. doi:10.1002/ardp.200800213

    Article  CAS  Google Scholar 

  21. Siddiqui N, Ahsan W (2011) Synthesis, anticonvulsant and toxicity screening of thiazolyl-thiadiazole derivatives. Med Chem Res 20:261–268. doi:10.1007/s00044-010-9313-6

    Article  CAS  Google Scholar 

  22. Dogan HN, Duran A, Rollas S, Sener G, Uysal MK, Gulen D (2002) Synthesis of new 2,5-disubstituted-1,3,4-thiadiazoles and preliminary evaluation of anticonvulsant and antimicrobial activities. Bioorg Med Chem 10:2893–2898. doi:10.1016/S0968-0896(02)00143-8

    Article  PubMed  CAS  Google Scholar 

  23. Brezeanu M, Marinescu D, Badea M, Stanica N, Iles MA, Supuran CT (1997) 1,3,4-thiadiazole derivatives. Part 8. Binuclear complexes of Cu(II), Mn(II), Co(II), Ni(II) with a Schiff base derived from 5-amino-1,3,4-thiadiazole-2-sulfonamide. Rev Roum Chim 42:727–732

    CAS  Google Scholar 

  24. Scozzafava A, Supuran CT (1998) Carbonic anhydrase inhibitors. Ureido and thioureido derivatives of aromatic sulfonamides possessing increased affinities for isoenzyme I. A novel route to 2,5-disubstituted-1,3,4-thiadiazoles via thioureas, and their interaction with isoenzymes I, II, and IV. J Enzyme Inhib 13:103–123

    Article  PubMed  CAS  Google Scholar 

  25. Supuran CT, Clare BW (1999) Carbonic anhydrase inhibitors - part 57: quantum chemical QSAR of a group of -thiadiazole- and -thiadiazoline disulfonamides with carbonic anhydrase inhibitory properties. Euro J Med Chem 34:41–50. doi:10.1016/S0223-5234(99)80039-7

    Article  CAS  Google Scholar 

  26. Hamad NS, Al-Haidery NH, Al-Masoudi IA, Sabri M, Sabri L, Al-Masoudi NA (2010) Amino acid derivatives, part 4: synthesis and anti-HIV activity of new naphthalene derivatives. Arch Pharm Chem Life Sci 343:397–403. doi:10.1002/ardp.200900293

    Article  CAS  Google Scholar 

  27. Chen Z, Xu W, Liu K, Yang S, Fan H, Bhadury PS, Hu D, Zhang Y (2010) Synthesis and antiviral activity of 5-(4-chlorophenyl)-1,3,4-thiadiazole sulfonamides. Molecules 15:9046–9056. doi:10.3390/molecules15129046

    Article  PubMed  CAS  Google Scholar 

  28. Onkol T, Doruer DS, Uzun L, Adak S, Ozkan S, Ahin FM (2008) Synthesis and antimicrobial activity of new 1,2,4-triazole and 1,3,4-thiadiazole derivatives. J Enzyme Inhib Med Chem 23:277–284. doi:10.1016/j.ejmech.2010.07.023

  29. Padmavathi V, Reddy GD, Reddy SN, Mahesh K (2011) Synthesis and anticancer activity of 5-(3-indolyl)-1,3,4-thiadiazoles. Eur J Med Chem 46:1367–1370. doi:10.1080/14756360701408697

    Article  PubMed  CAS  Google Scholar 

  30. Khalaj A, Nakhjiri N, Negahbani AS, Samadizadeh M, Firoozpour L, Rajabalian S, Samadi N, Faramarzi MA, Adibpour N, Shafiee A, Foroumadi A (2011) Discovery of a novel nitroimidazolyleoxazolidinone hybrid with potent anti gram-positive activity: synthesis and antibacterial evaluation. Eur J Med Chem 46:65–70. doi:10.1016/j.ejmech.2010.10.015

    Article  PubMed  CAS  Google Scholar 

  31. Matysiak J, Malinski Z (2007) 2-(2,4-dihydroxyphenyl)-1,3,4-thiadiazole analogues: antifungal activity in vitro against Candida species. Rus J Bioorg Chem 33:594–601. doi:10.1134/S1068162007060106

    Article  CAS  Google Scholar 

  32. Klip NT, Capan G, Gursoy A, Uzun M, Satana D (2010) Synthesis, structure, and antifungal evaluation of some novel 1,2,4-triazolylmercaptoacetylthiosemicarbazide and 1,2,4-triazolylmercaptomethyl-1,3,4-thiadiazole analogs. J Enzyme Inhib Med Chem 25:126–131. doi:10.3109/14756360903040439

    Article  PubMed  Google Scholar 

  33. Chen C, Song B, Yang S, Xu G, Bhadury PS, Jin L, Hu D, Li Q, Liu F, Xue W, Lu P, Chen Z (2007) Synthesis and antifungal activities of 5-(3,4,5-trimethoxyphenyl)-2-sulfonyl-1, 3,4-thiadiazole and 5-(3,4,5-trimethoxyphenyl)-2-sulfonyl-oxadiazole derivatives. Bioorg Med Chem 15:3981–3989. doi:10.1016/j.bmc.2007.04.014

    Article  PubMed  CAS  Google Scholar 

  34. Jin GY, Hou Z, Zhao GF, Cao CY, Li YC (1997) The synthesis and biological activity of 1-aryl-4-substituted pyrazoloyl thiosemicarbazides and related heterocyclic compounds. Chem J Chin Univ 18:409–411

    CAS  Google Scholar 

  35. Lu SM, Chen RY (2000) Facile and efficient synthesis of \(\alpha \)-aminophosphonate derivatives of 1,3,4-oxadiazole and 1,3,4-thiadiazole. Org Prep Proced Int 32:302–306. doi: 10.1080/00304940009355932

    Article  CAS  Google Scholar 

  36. Zareba S (1993) Spectrophotometric determination of iron(II) in drug formulations using azo dyes of the 1,3,4-thiadiazole and 1,2,4-triazole series. Pharmazie 48:782–783

    CAS  Google Scholar 

  37. Gao YJ, Zhang ZJ, Xue QJ (1999) Study on -thiadiazole derivatives as novel multifunctional oil additives. Mater Res Bull 34:1867–1874. doi:10.1016/S0025-5408(99)00226-3

    Article  CAS  Google Scholar 

  38. Choi US, Kim TW, Jung SW, Kim CJ (1998) Theoretical study of the nonlinear optical properties of thiophene, furan, pyrrole, (1,2,4-triazole), (1,3,4-oxadiazole), and (1,3,4-thiadiazole) monomers and oligomers. Bull Korean Chem Soc 19:299–307

    CAS  Google Scholar 

  39. Chen SL, Ji SX, Zhu ZH, Yao ZG (1993) Color photographic development accelerators. Part IV: adsorption of hydrazines containing the 1,3,4-thiadiazole heterocyclic system on silver halides. Dyes Pigm 23:275–283. doi:10.1016/0143-7208(93)80042-Y

    Article  CAS  Google Scholar 

  40. Korkusuz E, Yildirim I (2010) Synthesis and reactions of 4-benzoyl-1,5-diaryl-1H-pyrazole-3-carbonyl chlorides with various semi- and thiosemicarbazides. J Heterocycl Chem 47:472–476. doi:10.1002/jhet.306

    CAS  Google Scholar 

  41. Severinsen R, Kilburn JP, Lau JF (2005) Versatile strategies for the solid phase synthesis of small heterocyclic scaffolds: 1,3,4-thiadiazoles and 1,3,4-oxadiazoles. Tetrahedron 61:5565–5575. doi:10.1016/j.tet.2005.03.084

    Article  CAS  Google Scholar 

  42. Werber G, Buccheri F, Gentile M, Librici LJ (1977) Reactivity of the A-CH=N=NR-CX-B system. 1,3,4-thiadiazoles and 2-thiadiazolines. J Heterocycl Chem 14:853–855. doi:10.1002/jhet.5570140525

    Article  CAS  Google Scholar 

  43. Fezzeh A, Azim ZH, Mohammad RS (2010) Dithiocarbamate as an efficient intermediate for the synthesis of 2-amino-thiadiazoles in water. Tetrahedron Lett 51:790–792. doi:10.1016/j.tetlet.2009.11.100

    Article  Google Scholar 

  44. Rostamizadeh S, Aryan R, Hamid RG, Ali MA (2010) Efficient synthesis of 1,3,4-thiadiazoles using hydrogen bond donor thio-urea derivatives as organocatalysts. J Heterocycl Chem 47:616–623. doi:10.1002/jhet.367

    CAS  Google Scholar 

  45. Yang SJ, Lee SH, Kwak HJ, Gong YD (2013) Regioselective synthesis of 2-amino-substituted-oxadiazole and -thiadiazole derivatives via reagent-based cyclization of thiosemicarbazide intermediate. J Org Chem 78:438–444. doi:10.1021/jo302324r

    Article  PubMed  CAS  Google Scholar 

  46. Tejedor D, Garcia-Tellado F (2007) Chemo-differentiating ABB’ multicomponent reactions. privileged building blocks. Chem Soc Rev 36:484–491. doi:10.1039/b608164a

    Article  PubMed  CAS  Google Scholar 

  47. Zhu J, Bienayme HE, Wiley-VCH Weinheim (2005) Multicomponent reactions in the total synthesis of natural products. Multicomponent reactions pp 342–397: doi:10.1002/3527605118.ch12

  48. Toure BB, Hall DG (2009) Natural product synthesis using multicomponent reaction strategies. Chem Rev 109:4439–4486. doi:10.1021/cr800296p

    Article  PubMed  CAS  Google Scholar 

  49. Wang ZQ, Ge ZM, Cheng TM, Li RT (2009) An efficent four-compent, one-pot synthesis of poly-substituted pyrimidines in water. Chin J Chem 27:834–838. doi:10.1002/cjoc.200990139

    Article  CAS  Google Scholar 

  50. Wang ZQ, Ge ZM, Cheng TM, Li RT (2009) Synthesis of highly substituted pyridines via a one-pot, three-component cascade reaction of malononitrile with aldehydes and s-alkylisothiouronium salts in water. Synlett 12:2020–2022. doi:10.1055/s-0029-1217529

    Google Scholar 

  51. Yan X, Zhou S, Wang YQ, Ge ZM, Cheng TM, Li RT (2012) Propylene oxide assisted one-pot, tandem synthesis of substituted-oxadiazole-2(3H)-ones in water. Tetrahedron 68:7978–7983. doi:10.1016/j.tet.2012.07.004

    Article  CAS  Google Scholar 

  52. Whitehead CW et al (1955) Reactions of orthoesters with ureas. II. J Am Chem Soc 77:5872–5877. doi:10.1021/ja01627a029

    Article  CAS  Google Scholar 

  53. Coburn RA et al (1974) Mesoionic purinone analogs. 7. in vitro antibacterial activity of mesoionic 1,3,4-thiadiazolo[3,2,-a]pyrimidine-5,7-diones. J Med Chem 17:1025–1027. doi:10.1021/jm00255a029

    Article  PubMed  CAS  Google Scholar 

  54. Horlein U (1952) Aminothiodiazoles. United States Patent No. 2619489.

  55. Zhang ZY et al (1987) Acylthiosemicarbazides and related heterocyclic derivatives I. synthesis of 1-cyanoacetyl-4-arylthiosemicarbazides and related heterocyclic derivatives. Huaxue Xuebao 45:403–407

  56. Suman SP et al (1979) Synthesis of 2-(arylamino)-5-[aryl(or aryloxy)methyl]-1,3,4-oxadiazoles, 2-(arylamino)-5-[aryl(or aryl- oxy)methyl]-1,3,4-thiadiazoles, N-[aryl(or aryloxy)acetyl]-3,5-dimethylpyrazoles and N-[aryl(or aryloxy)acetyl]-3-methyl-5-pyrazolones as possible fungicides. J Indian Chem Soc 56:374–376

Download references

Acknowledgments

We are grateful for the financial support from the National Natural Science Foundation of China (No. 21172011).

Author information

Authors and Affiliations

  1. State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing , 100191, People’s Republic of China

    Peng Liu, Ao-Ze Su, Yuan-Qiang Wang, Ze-Mei Ge, Tie-Ming Cheng & Run-Tao Li

Authors
  1. Peng Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ao-Ze Su
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yuan-Qiang Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ze-Mei Ge
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Tie-Ming Cheng
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Run-Tao Li
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Ze-Mei Ge or Run-Tao Li.

Additional information

Peng Liu and Ao-Ze Su: These authors contributed equally to this work.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (doc 1921 KB)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Liu, P., Su, AZ., Wang, YQ. et al. A convenient four-component one-pot synthesis of 2-amino-1,3,4-thiadiazoles in water. Mol Divers 18, 737–743 (2014). https://doi.org/10.1007/s11030-014-9526-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11030-014-9526-6

Keywords

Search

Navigation