Next Article in Journal
A-Ring-Modified Triterpenoids and Their Spermidine–Aldimines with Strong Antibacterial Activity
Previous Article in Journal
Ethyl 6-Methyl-2-oxo-4-{4-[(1-phenyl-1H-1,2,3-triazol-4-yl)methoxy]phenyl}-1,2,3,4-tetrahydropyrimidine-5-carboxylate

Molbank 2019, 2019(3), ; https://doi.org/10.3390/M1077

Short Note
2-(3,5-Dimethyl-1H-pyrazol-1-yl)thiazolo[4,5-b]pyridine
College of Chemistry and Chemical Engineering, Luoyang Normal University, Luoyang 471934, China
*
Author to whom correspondence should be addressed.
Received: 20 July 2019 / Accepted: 19 August 2019 / Published: 20 August 2019

Abstract

:
The compound 2-(3,5-dimethyl-1H-pyrazol-1-yl)thiazolo[4,5-b]pyridine (1) was synthesized with a yield of 71% by the reaction of 1-(thiazolo[4,5-b]pyridine-2-yl)hydrazine and acetylacetone. The structure was characterized by a single-crystal X-ray structure determination as well as 1H and 13C{1H} NMR spectroscopy. X-ray crystallography on 1 confirms the molecule consists of a pyridine–thiazole moiety and the pyrazole ring, and all non-hydrogen atoms are planar.
Keywords:
thiazolo[4,5-b]pyridine; pyrazole; X-ray crystallography

1. Introduction

Heterocyclic compounds such as thiazoles and pyrazoles have attracted much research attention in the field of drug design because of their varied biological activities, such as antibacterial, antifungal, anti-inflammatory, and antitumor activities [1,2,3,4]. It is well known that the incorporation of different heterocyclic systems into a single molecule to form fused hybrids could offer access to new chemical entities with enhanced activities in comparison with their parent rings alone [5,6,7]. For example, some 1H-pyrazolyl derivatives of thiazolo[4,5-d]pyrimidines have exhibited promising anti-inflammatory and antimicrobial activities [8]. On the other hand, thiazolo[4,5-b]pyridine derivatives have been shown to possess antioxidant and anti-inflammatory activities [9,10]. In view of the abovementioned findings, a new thiazolo[4,5-b]pyridine–pyrazole compound was synthesized and structurally characterized.

2. Results

The title compound 2-(3,5-dimethyl-1H-pyrazol-1-yl)thiazolo[4,5-b]pyridine (1) was easily prepared in a good yield (71%) from the hetero-cyclization of 1-(thiazolo[4,5-b]pyridin-2-yl)hydrazine and acetylacetone in methanol using glacial acetic acid as catalyst, as shown in Scheme 1. The reaction consists of two nucleophilic addition and dehydration processes, resulting in the pyrazolyl ring. The product was characterized by 1H, 13C{1H}-NMR, (see Supplementary Materials for original spectra) and X-ray crystallography. An isomer of the title compound, namely 2-(3,5-dimethyl-1H-pyrazol-1-yl)thiazolo[5,4-b]pyridine, has been reported before, but its detailed synthesis method was not given [11].
The molecular structure of compound 1 is shown in Figure 1. The asymmetric unit contains one molecule of the title compound, which is constructed by the pyridine–thiazole moiety and the dimethyl-pyrazole fragment. All non-hydrogen atoms of the title compound are almost planar with a maximum deviation of 0.245(3) Å for C10. The C–N bond distances are in the range of 1.291(3)-1.390(3) Å, which are typical of azocompounds. The C2–S1 and C6–S1 bond lengths of 1.724(3) Å and 1.737(2) Å are intermediate between the double (~1.56 Å) and single (~1.82 Å) bonds. The shortening of the C–S bonds shows the partial double bond character, which was also observed in other pyridine-thiazole compounds [11,12,13]. Comparing with its isomer 2-(3,5-dimethyl-1H-pyrazol-1-yl)thiazolo[5,4-b]pyridine, the shorter C–S bond lengths show a subtle difference between the two thiazole rings. The difference may be caused by different positions of the heteroatoms.

3. Materials and Methods

3.1. General Information

The compound 1-(thiazolo[4,5-b]pyridin-2-yl)hydrazine was synthesized according to the reported method [12]. All other chemicals and solvents were purchased from commercial sources and used without purification. The melting point was determined on a Beijing Keyi apparatus (Beijing synthware glass, Beijing, China). Nuclear magnetic resonance (NMR) spectra were measured on a Bruker AvanceII 400 spectrometer (Bruker BioSpin AG, Fällanden, Switzerland) operating at 400 MHz, using tetramethylsilane (TMS) as an internal standard. The X-ray diffraction data were collected at 298 K on a Bruker Smart CCD area detector (Bruker, Karlsruhe, Germany) with graphite-monochromated Mokα radiation (λ = 0.71073 Å). The structures were solved by direct methods, before further refinement with full-matrix least-squares on F2 was obtained with the SHELXL program package [14].

3.2. Synthesis and Characterization of 1

A mixture of 1-(thiazolo[4,5-b]pyridin-2-yl)hydrazine (0.166 g, 1 mmol) and acetylacetone (0.1 g, 1 mmol) in 30 mL methanol in the presence of catalytic amount of glacial acetic acid was refluxed for 4 h. Then, the mixture was left for slow evaporation under ambient conditions. Colorless crystals were collected after three days. Yield: 0.163 g, 71%. White solid; m.p. 142.5–143.6 °C. 1H–NMR (400 MHz, CDCl3): δ 8.60–8.62 (d, 1H, arom), 8.14–8.16 (d, 1H, arom), 7.23–7.26 (m, 1H, arom), 6.08 (s, 1H, arom), 2.83 (s, 3H, CH3), 2.31 (s, 3H, CH3). 13C-NMR (100 MHz, CDCl3): δ 164.39, 162.88, 153.23, 147.80, 143.51, 130.23, 126.98, 119.41, 111.27, 14.21, 13.75.
Crystal data for C11H10N4S (1): M = 230.29, orthorhombic, Pbca, a = 11.863(7), b = 10.910(7), c = 16.519(10) Å, V = 2138(2) Å3, Z = 8, Dx = 1.431 g cm–3, F(000) = 960 and μ = 0.278 mm–1. CCDC deposition number: 1941839.

Supplementary Materials

The following are available online: 1H and 13C{1H} NMR, and crystallographic data for (1) in crystallographic information file (CIF) format. CCDC 1941839 also contains the supplementary crystallographic data for this paper. These data can be obtained free of charge via http://www.ccdc.cam.ac.uk/conts/retrieving.html.

Author Contributions

H.L. conceived and designed the experiments; M.Z. performed the experiments; M.Z., H.L. and Y.W. analyzed the data; H.L. and M.Z. wrote the paper.

Funding

This research received no external funding.

Acknowledgments

We thank the X-ray crystallography laboratory at Luoyang Normal University for the X-ray intensity data.

Conflicts of Interest

The author declares no conflict of interest.

References

  1. Samir, B.; Wesam, K.; Ahmed, A.F. Synthesis and antimicrobial evaluation of some new thiazole, thiazolidinone and thiazoline derivatives starting from 1-chloro-3,4-dihydronaphthalene-2-carboxaldehyde. Eur. J. Med. Chem. 2007, 42, 948–954. [Google Scholar]
  2. Holla, B.S.; Malini, K.V.; Rao, B.S.; Sarojini, B.K.; Kumari, N.S. Synthesis of some new 2,4-disubstituted thiazoles as possible antibacterial and anti-inflammatory agents. Eur. J. Med. Chem. 2003, 38, 313–318. [Google Scholar] [CrossRef]
  3. Bharti, S.K.; Nath, G.; Tilak, R.; Singh, S.K. Synthesis, anti-bacterial and anti-fungal activities of some novel Schiff bases containing 2,4-disubstituted thiazole ring. Eur. J. Med. Chem. 2010, 45, 651–660. [Google Scholar] [CrossRef] [PubMed]
  4. Rostom, S.A.F. Synthesis and in vitro antitumor evaluation of some indeno[1,2-c]-pyrazol(in)es substituted with sulfonamide, sulfonylurea(-thiourea) pharmacophores, and some derived thiazole ring systems. Bioorg. Med. Chem. 2006, 14, 6475–6485. [Google Scholar] [CrossRef] [PubMed]
  5. Takate, S.J.; Shinde, A.D.; Karale, B.K.; Akolkar, H.; Nawale, L.; Sarkar, D.; Mhaske, P.C. Thiazolyl-pyrazole derivatives as potential antimycobacterial agents. Bioorg. Med. Chem. Lett. 2019, 29, 1199–1202. [Google Scholar] [CrossRef] [PubMed]
  6. Shen, Z.H.; Zhai, Z.W.; Sun, Z.H.; Weng, J.Q.; Tan, C.X.; Liu, X.H. Synthesis, crystal structure and biological activity of 2-chloro-5-(((5-(1-methyl-3-(trifluoromethyl)-1H-pyrazol-4-yl)-4-phenyl-4H-1,2,4-triazol-3-yl)thio)methyl)thiazole. Chin. J. Struct. Chem. 2017, 36, 1137–1141. [Google Scholar]
  7. Metwally, N.H.; Badawy, M.A.; Okpy, D.S. Synthesis and anticancer activity of some new thiopyrano[2,3-d]thiazoles incorporating pyrazole moiety. Chem. Pharm. Bull. 2015, 63, 495–503. [Google Scholar] [CrossRef] [PubMed]
  8. Bekhit, A.A.; Fahmy, H.T.Y.; Rostom, S.A.F.; Baraka, A.M. Design and synthesis of some substituted 1H-pyrazolyl-thiazolo[4,5-d]pyrimidines as anti-inflammatory-antimicrobial agents. Eur. J. Med. Chem. 2003, 38, 27–36. [Google Scholar] [CrossRef]
  9. Klenina, O.; Chaban, T.; Zimenkovsky, B.; Harkov, S.; Ogurtsov, V.; Chaban, I.; Myrko, I. QSAR modeling for antioxidant activity of novel N3 substituted 5,7-dimethyl-3H-thiazolo[4,5-b]pyridin-2-ones. Pharmacia 2017, 64, 49–71. [Google Scholar]
  10. Chaban, T.; Klenina, O.; Harkov, S.; Ogurtsov, V.; Chaban, I.; Nektegaev, I. Synthesis of some new N3 substituted 6-phenylazo-3H-thiazolo[4,5-b]pyridine-2-ones as possible anti-inflammatory agents. Pharmacia 2017, 64, 16–30. [Google Scholar]
  11. Ren, Y.L.; Wang, Q.; Wang, W.M.; Jin, C.X. Crystal structure of 2-(3,5-dimethyl-1H-pyrazol-1-yl)thiazolo[5,4-b]-pyridine, C11H10N4S. Z. Kristallogr. NCS 2014, 229, 145–146. [Google Scholar] [CrossRef]
  12. Miao, S.B.; Ji, B.M.; Zhou, L. Crystal structure of 1-(diphenylmethylene)-2-(thiazolo[4,5-b]pyridine-2-yl)hydrazine. J. Struct. Chem. 2014, 55, 384–387. [Google Scholar] [CrossRef]
  13. Miao, S.B.; Ji, B.M.; Zhou, L. Synthesis and crystal structures of a new thiazole-hydrazone ligand and its Co(III) complex. Synth. React. Inorg. Met. Org. Nano-Met. Chem. 2013, 43, 1296–1300. [Google Scholar] [CrossRef]
  14. Sheldrick, G.M. SHELXL97. Program for the Refinement of Crystal Structure; University of Göttingen: Göttingen, Germany, 1997. [Google Scholar]
Scheme 1. Synthesis of 2-(3,5-dimethyl-1H-pyrazol-1-yl)thiazolo[4,5-b]pyridine.
Scheme 1. Synthesis of 2-(3,5-dimethyl-1H-pyrazol-1-yl)thiazolo[4,5-b]pyridine.
Molbank 2019 m1077 sch001
Figure 1. The molecular structure of 1 showing atom labeling and displacement ellipsoids at the 50% probability.
Figure 1. The molecular structure of 1 showing atom labeling and displacement ellipsoids at the 50% probability.
Molbank 2019 m1077 g001

© 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
Back to TopTop