Skip to main content
SpringerLink
Log in

Dual Roles of N,N-Dimethylformamide in Benzothiazoles Synthesis from N-Benzoyl-N′-(2,4,6-trichlorophenyl)thiourea

  • Original Paper
  • Published:
Journal of Chemical Crystallography Aims and scope Submit manuscript

Abstract

N,N-Dimethylformamide (DMF) is not only a common polar solvent in chemistry, but also a reaction reagent, a catalyst and a stabilizer. In this paper, a new reaction was found accidently where DMF acted as both solvent and catalyst. By dissolving N-benzoyl-N′-(2,4,6-trichlorophenyl)-thiourea (BAD) in DMF and evaporating the solvent slowly, single crystals were obtained but their composition was determined to be 2-benzoylamino-4,6-dichloro-benzothiazole (BTT) with DMF molecule (BTT–DMF), not BAD. The single crystals of BAD could be obtained by crystallization from the solvents of acetonitrile or ethanol. The crystal structures of BAD and BTT–DMF were measured and analysed. Based on the hydrogen bonding interactions in their crystal structures, a possible reaction mechanism was proposed. All in all, DMF is a really multifunctional chemical, it may still have other potential functions which are interesting and valuable to be developed.

Graphic Abstract

A new reaction was found by dissolving N-benzoyl-N′-(2,4,6-trichlorophenyl)-thiourea (BAD) in DMF and evaporation of the solvent slowly to grow single crystals.

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

Scheme 1
Scheme 2
Fig. 1
Fig. 2
Scheme 3

Similar content being viewed by others

References

  1. Ding ST, Jiao N (2012) N,N-Dimethylformamide: a multipurpose building block. Angew Chem Int Ed 51(37):9226–9237. https://doi.org/10.1002/anie.201200859

    Article  CAS  Google Scholar 

  2. Liu WB, Chen C, Zhou P (2017) N,N-Dimethylformamide (DMF) as a source of oxygen to access alpha-hydroxy arones via the alpha-hydroxylation of arones. J Org Chem 82(4):2219–2222. https://doi.org/10.1021/acs.joc.6b02751

    Article  CAS  Google Scholar 

  3. Xia HM, Zhang FL, Ye T, Wang YF (2018) Selective alpha-monomethylation by an amine-borane/N,N-dimethylformamide system as the methyl source. Angew Chem Int Ed 57(36):11770–11775. https://doi.org/10.1002/anie.201804794

    Article  CAS  Google Scholar 

  4. Kovala-Demertzi D, Kourkoumelis N, West DX, Valdes-Martinez J, Hernandez-Ortega S (1998) A trinuclear palladium(II) complex with bridging 2-hydroxyacetophenone N-4-ethylthiosemicarbazone ligands—an unusual dimethylformamide promoted deprotonation and aggregation. Eur J Inorg Chem 6:861–863. https://doi.org/10.1002/(SICI)1099-0682(199806)1998:6%3c861:AID-EJIC861%3e3.0.CO;2-Y

    Article  Google Scholar 

  5. Heravi MM, Ghavidel M, Mohammadkhani L (2018) Beyond a solvent: triple roles of dimethylformamide in organic chemistry. Rsc Adv 8(49):27832–27862. https://doi.org/10.1039/c8ra04985h

    Article  CAS  Google Scholar 

  6. Pastoriza-Santos I, Liz-Marzan LM (2009) N,N-Dimethylformamide as a reaction medium for metal nanoparticle synthesis. Adv Funct Mater 19(5):679–688. https://doi.org/10.1002/adfm.200801566

    Article  CAS  Google Scholar 

  7. Muzart J (2009) N,N-Dimethylformamide: much more than a solvent. Tetrahedron 65(40):8313–8323. https://doi.org/10.1016/j.tet.2009.06.091

    Article  CAS  Google Scholar 

  8. Venkatesu P (2010) Thermophysical contribution of N,N-dimethylformamide in the molecular interactions with other solvents. Fluid Phase Equilib 298(2):173–191. https://doi.org/10.1016/j.fluid.2010.07.010

    Article  CAS  Google Scholar 

  9. Lei Y, Li HR, Pan HH, Han SJ (2003) Structures and hydrogen bonding analysis of N,N-dimethylformamide and N,N-dimethylformamide-water mixtures by molecular dynamics simulations. J Phys Chem A 107(10):1574–1583. https://doi.org/10.1021/jp026638+

    Article  CAS  Google Scholar 

  10. Li QJ, Yang CL (2008) Synthesis and crystal structure of a compound with two conformational isomers: N-(2-methylbenzoyl)-N′-(4-nitrophenyl)thiourea. J Chem Crystallogr 38(12):927–930. https://doi.org/10.1007/s10870-008-9413-z

    Article  CAS  Google Scholar 

  11. Li QJ, Wang XF, Xie XQ, Yang CL (2009) Synthesis and crystal structure of centrosymmetric 4,4′-bis(N′-substituted acylthioureido)biphenyls. Chin J Org Chem 29(3):409–413

    Google Scholar 

  12. Rauf MK, Talib A, Badshah A, Zaib S, Shoaib K, Shahid M, Florke U, Imtiaz ud D, Iqbal J (2013) Solution-phase microwave assisted parallel synthesis of N,N′-disubstituted thioureas derived from benzoic acid: biological evaluation and molecular docking studies. Eur J Med Chem 70:487–496. https://doi.org/10.1016/j.ejmech.2013.10.012

    Article  CAS  Google Scholar 

  13. Li Y, Wang YL (2006) Progress in the synthesis of 2-substituent-benzothiazoles. Chin J Org Chem 26(6):878–884. https://doi.org/10.3321/j.issn:0253-2786.2006.06.023

    Article  CAS  Google Scholar 

  14. Zhu N, Zhang ZW, Gao M, Han LM, Suo QL, Hong HL (2013) New progress in the synthesis of 2-substituent-benzothiazole derivatives. Chin J Org Chem 33(7):1423–1436. https://doi.org/10.6023/cjoc201212014

    Article  CAS  Google Scholar 

  15. Banerjee S, Payra S, Saha A (2017) A review on synthesis of benzothiazole derivatives. Curr Organocatal 4(3):164–181. https://doi.org/10.2174/2213337205666180119143539

    Article  CAS  Google Scholar 

  16. Keri RS, Patil MR, Patil SA, Budagumpi S (2015) A comprehensive review in current developments of benzothiazole-based molecules in medicinal chemistry. Eur J Med Chem 89:207–251. https://doi.org/10.1016/j.ejmech.2014.10.059

    Article  CAS  Google Scholar 

  17. Rauf MK, Zaib S, Talib A, Ebihara M, Badshah A, Bolte M, Iqbal J (2016) Solution-phase microwave assisted parallel synthesis, biological evaluation and in silico docking studies of N,N′-disubstituted thioureas derived from 3-chlorobenzoic acid. Bioorgan Med Chem 24(18):4452–4463. https://doi.org/10.1016/j.bmc.2016.07.042

    Article  CAS  Google Scholar 

  18. Papke K, Pohloude R (1967) Uber Die Rhodanierung Halogensubstituierter Aniline.24. Uber Organische Rhodanverbindungen. Pharmazie 22(5):229–233

    CAS  Google Scholar 

  19. Joyce LL, Batey RA (2009) Heterocycle formation via palladium-catalyzed intramolecular oxidative C–H bond functionalization: an efficient strategy for the synthesis of 2-aminobenzothiazoles. Org Lett 11(13):2792–2795. https://doi.org/10.1021/ol900958z

    Article  CAS  Google Scholar 

  20. Guo YJ, Tang RY, Zhong P, Li JH (2010) Copper-catalyzed tandem reactions of 2-halobenzenamines with isothiocyanates under ligand- and base-free conditions. Tetrahedron Lett 51(4):649–652. https://doi.org/10.1016/j.tetlet.2009.11.086

    Article  CAS  Google Scholar 

  21. Qiu JW, Zhang XG, Tang RY, Zhong P, Li JH (2009) Iron-catalyzed tandem reactions of 2-halobenzenamines with isothiocyanates leading to 2-aminobenzothiazoles. Adv Synth Catal 351(14–15):2319–2323. https://doi.org/10.1002/adsc.200900450

    Article  CAS  Google Scholar 

  22. Wang JK, Zong YX, Zhang XX, Gao Y, Li ZL, Yue GR, Quan ZJ, Wang XC (2014) Synthesis of N-benzothiazol-2-yl-amides by an iron-catalyzed oxidative C(sp(2))–H functionalization. Synlett 25(15):2143–2148. https://doi.org/10.1055/s-0034-1378547

    Article  CAS  Google Scholar 

  23. Feng EG, Huang H, Zhou Y, Ye DJ, Jiang HL, Liu H (2010) Metal-free synthesis of 2-substituted (N, O, C) benzothiazoles via an intramolecular C–S bond formation. J Comb Chem 12(4):422–429. https://doi.org/10.1021/cc9001839

    Article  CAS  Google Scholar 

  24. Mostafavi H, Islami MR, Ghonchepour E, Tikdari AM (2018) Synthesis of 1H-1,3-benzimidazoles, benzothiazoles and 3H-imidazo[4,5-c]pyridine using DMF in the presence of HMDS as a reagent under the transition-metal-free condition. Chem Pap 72(12):2973–2978. https://doi.org/10.1007/s11696-018-0540-5

    Article  CAS  Google Scholar 

  25. Rauf MK, Bolte M, Badshah A (2009) 1-(4-Chlorobenzoyl)-3-(2,4,6-trichlorophenyl)thiourea hemihydrate. Acta Crystallogr Sect E Crystallogr Commun 65:O143–U2501. https://doi.org/10.1107/s1600536808041251

    Article  Google Scholar 

  26. Li QJ, Yang CL, Xie XQ (2007) N-(2,4-Dichlorophenoxyacetyl)-N′-(2,4,6-trichlorophenyl)thiourea. Acta Crystallogr Sect E Crystallogr Commun 63:o773–o774. https://doi.org/10.1107/S1600536806054201

    Article  CAS  Google Scholar 

  27. Frisch MJ, Trucks GW, Schlegel HB, Scuseria GE, Robb MA, Cheeseman JR, Scalmani G, Barone V, Petersson GA, Nakatsuji H, Li X, Caricato M, Marenich A, Bloino J, Janesko BG, Gomperts R, Mennucci B, Hratchian HP, Ortiz JV, Izmaylov AF, Sonnenberg JL, Williams-Young D, Ding F, Lipparini F, Egidi F, Goings J, Peng B, Petrone A, Henderson T, Ranasinghe D, Zakrzewski VG, Gao J, Rega N, Zheng G, Liang W, Hada M, Ehara M, Toyota K, Fukuda R, Hasegawa J, Ishida M, Nakajima T, Honda Y, Kitao O, Nakai H, Vreven T, Throssell K, Montgomery JA Jr, Peralta JE, Ogliaro F, Bearpark M, Heyd JJ, Brothers E, Kudin KN, Staroverov VN, Keith T, Kobayashi R, Normand J, Raghavachari K, Rendell A, Burant JC, Iyengar SS, Tomasi J, Cossi M, Millam JM, Klene M, Adamo C, Cammi R, Ochterski JW, Martin RL, Morokuma K, Farkas O, Foresman JB, Fox DJ (2009) Gaussian 09. Gaussian Inc, Wallingford

    Google Scholar 

Download references

Acknowledgements

We acknowledge the financial supports from the National Natural Science Foundation of China (21705073, 21603116 and 51406074) and the Fundamental Research Funds for the Central Universities of China (KYZ201223).

Author information

Authors and Affiliations

  1. School of Public Health, Nanchang University, Nanchang, 330019, Jiangxi, China

    Qianjin Li

  2. College of Science, Nanjing Agricultural University, Nanjing, 210095, Jiangsu, China

    Qianjin Li, Min Chen & Chunlong Yang

  3. College of Chemistry, Nanchang University, Nanchang, 330029, Jiangxi, China

    Dan Wang, Qianyong Cao & Fenying Wang

  4. School of Chemistry and Chemical Engineering, Qufu Normal University, Qufu, 273165, Shandong, China

    Baoping Ling

  5. Institute of Chemical Technology and Engineering, Poznań University of Technology, Pl. M. Skłodowskiej – Curie 2, 60-965, Poznan, Poland

    Piotr Kujawski

Authors
  1. Qianjin Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Dan Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Min Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Baoping Ling
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Piotr Kujawski
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Chunlong Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Qianyong Cao
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Fenying Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Qianjin Li, Chunlong Yang or Qianyong Cao.

Ethics declarations

Conflict of interest

All authors states that there is no conflict of interest.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Li, Q., Wang, D., Chen, M. et al. Dual Roles of N,N-Dimethylformamide in Benzothiazoles Synthesis from N-Benzoyl-N′-(2,4,6-trichlorophenyl)thiourea. J Chem Crystallogr 50, 287–294 (2020). https://doi.org/10.1007/s10870-019-00796-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10870-019-00796-3

Keywords

Search

Navigation