Next Article in Journal
Novel Schiff Bases of C-Methylresorcinarene Derivatives
Previous Article in Journal
2-Benzyl-3-morpholino-7-(thiophen-2-yl)-6-(thiophen-2-ylmethyl)-6,7-dihydro-5H-pyrrolo[3,4-b]pyridin-5-one
 
 
Order Article Reprints
Font Type:
Arial Georgia Verdana
Font Size:
Aa Aa Aa
Line Spacing:
Column Width:
Background:
Short Note

(E)-3-(2-(4-methylthiazol-2-yl)hydrazineylidene)chromane-2,4-dione

Department of Chemistry, University of Fribourg, Chemin Du Musée 10, 1700 Fribourg, Switzerland
*
Author to whom correspondence should be addressed.
Molbank 2022, 2022(4), M1504; https://doi.org/10.3390/M1504
Received: 18 October 2022 / Revised: 16 November 2022 / Accepted: 18 November 2022 / Published: 24 November 2022

Abstract

:
(E)-3-(2-(4-methylthiazol-2-yl)hydrazineylidene)chromane-2,4-dione was synthesized for the first time and the compound was characterized by 1H and 13C spectroscopy, IR spectroscopy, and UV-Vis. The chemical structure and isomeric configuration of the molecule were confirmed by single-crystal X-ray diffraction.

1. Introduction

Due to their dominance in natural product chemistry, their large variety of pharmacological activities, and optical properties, coumarins are of crucial relevance in medicinal chemistry [1,2,3,4,5]. The 2-aminothiazole derivatives of 4-hydroxycoumarin have demonstrated significant biological activity, with evidence that introduction of methyl groups on the thiazole ring results in an increase in the anticancer activity of the species [6]. Here we report the synthesis of the (E)-3-(2-(4-methylthiazol-2-yl)hydrazineylidene)chromane-2,4-dione isomer (3, Figure 1) as the last elusive isomer of the previously tested compounds [6]. Molecule 3 is further envisaged as a ligand for the preparation of antibiotic and anticancer metal complexes [7].

2. Results and Discussion

2.1. Synthesis of 3

Compound 3 was prepared by coupling 4-methylthiazole-2-diazonium (2) with 4-hydroxycoumarin dissolved in a NaOH solution, according to the synthetic procedure outlined in Scheme 1. Compound 2 was prepared in situ by diazotization of 4-methylthiazol-2-amine (1) under highly acidic conditions using concentrated H2SO4 and a NaNO2 solution (Scheme 1). Compound 3 was isolated in 16 % yield as a red powder.

2.2. X-ray Crystal Structure

The 2-aminothiazole derivatives of 4-hydroxycoumarin have several tautomeric forms (Scheme 2). According to previously published gaseous phase calculation [8], the diketo form (3, Scheme 2) dominates as the most stable tautomeric conformer for this type of compound. There are, however, no examples in the literature of structurally characterized isomers of this species. Therefore, it was important for us to confirm the stereochemistry of 3. Crystals of 3 suitable for X-ray analysis were grown in a dichloromethane solution layered with pentane. Figure 2 shows an ORTEP representation of the X-ray structure. The molecule crystallizes in the monoclinic P21/n space group with two asymmetric units in the unit cell. In the solid state, the molecule is planar, stabilized by intramolecular hydrogen bonding. Planes defined respectively by the thiazole and the coumarin atoms, are tilted by only 5.2°. We are aware of only one other structure which resembles our molecule, namely that of 3-[2-(5-t-butyl-1,2-oxazol-3-yl)hydrazinylidene]chroman-2,4-dione [9]. Unlike 3, this molecule is not planar in the solid state, but rather bent (most likely due to the presence of the bulky t-butyl). Although the same intramolecular hydrogen bonding interaction is also observed in the oxazole derivative, the planes defined respectively by the oxazole ring and the coumarin atoms form an angle of 20.3° [9].

3. Materials and Methods

3.1. General Comments

All commercially available reagents were used without any further purification. (E)-3-(2-(4-methylthiazol-2yl)hydrazineylidene)chromane-2,4-dione was prepared following adapted procedures from the literature [6,10]. 1H and 13C NMR spectra were recorded on a Bruker Advance III 400 MHz. The corresponding chemical shifts were reported in ppm, referenced to residual solvent signals. IR spectra were acquired on a Bruker TENSOR II with the following parameters: 16 scans for the background, and 32 scans for the sample with a resolution of 4 cm−1 in the 4000–400 cm−1 region. UV–Vis spectra were recorded on a Jasco V730 spectrophotometer and the samples were dissolved in DCM. Spectra of the compound are given in Supplementary Materials. Single crystal diffraction data collection of the target molecule was performed on a Stoe STADIVARI diffractometer (CuKα1 (λ = 1.5406 Å)) equipped with a cryostat from Oxford Cryosystems. The structure of 3 was solved with the SHELXT structure solution program using Intrinsic Phasing and refined with the SHELXT refinement package using Least Squares minimization [11,12]. The crystal structure has been deposited at the Cambridge Crystallographic Data Centre. CCDC number 2213454 contains the crystallographic data for this paper.

3.2. Synthesis of 3

An amount of 10 mmol of 2-amino-4-methyl thiazole (1) was dissolved in 5 mL of H2SO4. Using an ice–salt bath, the system was cooled and maintained between −5 to 0 °C. An aqueous solution of 7 mL of NaNO2 (10 wt.) was added dropwise to the solution of 1 and mixed for one hour by a magnetic stirrer. After one hour a mixture of 4-hydroxycoumarin (10 mmol) in 10 mL of NaOH (10 wt.) was added. A black voluminous precipitate was obtained. The mixture was stirred for 1 h in the ice bath and then for 3 h at room temperature. The precipitate was then vacuum-filtered and extracted with dichloromethane. A red compound was obtained following solvent evaporation. This was finally recrystallized from a H2O/MeOH mixture. Yield: 16 %. 1H NMR (400 MHz, CD2Cl2-d2) δ ppm 2.40 (d, J = 0.73 Hz, 3 H) 6.79 (s, 1 H) 7.26–7.45 (m, 2 H) 7.73 (ddd, J = 8.47, 7.18, 1.71 Hz, 1 H) 8.10 (d, J = 7.70 Hz, 1 H). 13C NMR (101 MHz, CD2Cl2-d2) δ ppm 17.62 (s, 1 C) 107.14 (s, 1 C) 112.23 (s, 1 C) 118.25 (s, 1 C) 120.57 (s, 1 C) 125.52 (s, 1 C) 127.76 (s, 1 C) 137.74 (s, 1 C) 152.34 (s, 1 C) 155.23 (s, 1 C) 164.58 (s, 1 C) 173.81 (s, 1 C) 179.54 (s, 1 C). IR spectra (cm−1) = 3450–3500 cm−1 (N-H), 1740 cm−1 (C=O) 1605 (C=C stretch aromatic). UV-Vis (CH2Cl2) (λmax/nm) = 260, 350, and 450. Crystals of 3 suitable for X-ray analysis were grown in a dichloromethane solution layered with pentane.

4. Conclusions

In this work, we have described the synthesis and characterization of the new compound (E)-3-(2-(4-methylthiazol-2yl)hydrazineylidene)chromane-2,4-dione, which was obtained by the diazo coupling reaction of 2-amino-4-methyl thiazole and 4-hydroxy coumarin.

Supplementary Materials

The following supporting information associated with this article can be found in the online version: 1H-NMR, 13C-NMR, IR, UV-Vis spectra, and crystallographic details of 3.

Author Contributions

Conceptualization, F.R. and F.Z.; methodology, F.R.; validation, F.Z.; formal analysis, F.R. and A.C.; investigation, F.R.; resources, F.Z.; data curation, F.R. and A.C.; writing—original draft preparation, F.R.; writing—review and editing, F.R., A.C. and F.Z.; supervision, F.Z.; project administration, F.Z.; funding acquisition, F.Z. All authors have read and agreed to the published version of the manuscript.

Funding

Swiss Federal Commission for Scholarships for Foreign Students (FCS) and University of Fribourg, Switzerland.

Institutional Review Board Statement

Not applicable.

Informed Consent Statement

Not applicable.

Data Availability Statement

Not applicable.

Conflicts of Interest

The authors declare no conflict of interest.

References

  1. Akchurin, I.O.; Yakhutina, A.I.; Bochkov, A.Y.; Solovjova, N.P.; Medvedev, M.G.; Traven, V.F. Novel push-pull fluorescent dyes–7-(diethylamino)furo- and thieno[3,2-c]coumarins derivatives: Structure, electronic spectra and TD-DFT study. J. Mol. Struct. 2018, 1160, 215–221. [Google Scholar] [CrossRef]
  2. Erdogdu, Y.; Baskose, U.C.; Saglam, S.; Erdogdu, M.; Ogutcu, H.; Özçelik, S. Structural, thermal, spectroscopic, electronic and biological activity properties of coumarin-153 dyes for DSSCs: A DFT benchmark study. J. Mol. Struct. 2020, 1221, 128873. [Google Scholar] [CrossRef]
  3. Nagaraja, O.; Bodke, Y.D.; Kenchappa, R.; Ravi Kumar, S. Synthesis and characterization of 3-[3-(1H-benzimidazol-2-ylsulfanyl)-3-phenyl propanoyl]-2H-chromen-2-one derivatives as potential biological agents. Chem. Data Collect 2020, 27, 100369. [Google Scholar] [CrossRef]
  4. Nagaraja, O.; Bodke, Y.D.; Pushpavathi, I.; Ravi Kumar, S. Synthesis, characterization and biological investigations of potentially bioactive heterocyclic compounds containing 4-hydroxy coumarin. Heliyon 2020, 6, e04245. [Google Scholar] [CrossRef] [PubMed]
  5. Panitsiri, A.; Tongkhan, S.; Radchatawedchakoon, W.; Sakee, U. Synthesis and anion recognition studies of novel bis (4-hydroxycoumarin) methane azo dyes. J. Mol. Struct. 2016, 1107, 14–18. [Google Scholar] [CrossRef]
  6. Jashari, A.; Imeri, F.; Ballazhi, L.; Shabani, A.; Mikhova, B.; Dräger, G.; Popovski, E.; Huwiler, A. Synthesis and cellular characterization of novel isoxazolo- and thiazolohydrazinylidene-chroman-2,4-diones on cancer and non-cancer cell growth and death. Bioorg. Med. Chem. 2014, 22, 2655–2661. [Google Scholar] [CrossRef] [PubMed]
  7. Sovari, S.N.; Vojnovic, S.; Bogojevic, S.S.; Crochet, A.; Pavic, A.; Nikodinovic-Runic, J.; Zobi, F. Design, synthesis and in vivo evaluation of 3-arylcoumarin derivatives of rhenium(I) tricarbonyl complexes as potent antibacterial agents against methicillin-resistant Staphylococcus aureus (MRSA). Eur. J. Med. Chem. 2020, 205, 112533. [Google Scholar] [CrossRef] [PubMed]
  8. Stamboliyska, B.; Jashari, A.; Yancheva, D.; Mikhova, B.; Batovska, D.; Popovski, E.; Mladenovska, K. Structure and radical scavenging activity of isoxazolo- and thiazolohydrazinylidenechroman-2,4-diones. Bulg. Chem. Commun. 2017, 49, 99–105. [Google Scholar]
  9. Jashari, A.; Popovski, E.; Mikhova, B.; Nikolova, R.P.; Shivachev, B.L. 3-[2-(5-tert-Butyl-1,2-oxazol-3-yl)hydrazinyl-idene]chroman-2,4-dione. Acta Crystallogr. E 2013, 69, o258. [Google Scholar] [CrossRef] [PubMed]
  10. Manjunatha, B.; Bodke, Y.D.; Nagaraja, O.; Lohith, T.N.; Nagaraju, G.; Sridhar, M.A. Coumarin-Benzothiazole Based Azo Dyes: Synthesis, Characterization, Computational, Photophysical and Biological Studies. J. Mol. Struct. 2021, 1246, 131170. [Google Scholar] [CrossRef]
  11. Sheldrick, G. SHELXT-Integrated space-group and crystal-structure determination. Acta Cryst. A 2015, 71, 3–8. [Google Scholar] [CrossRef] [PubMed]
  12. Sheldrick, G. Crystal structure refinement with SHELXL. Acta Cryst. C 2015, 71, 3–8. [Google Scholar] [CrossRef] [PubMed]
Figure 1. Chemical structure of (E)-3-(2-(4-methylthiazol-2-yl)hydrazineylidene)chromane-2,4-dione (3).
Figure 1. Chemical structure of (E)-3-(2-(4-methylthiazol-2-yl)hydrazineylidene)chromane-2,4-dione (3).
Molbank 2022 m1504 g001
Scheme 1. Preparation of 2-aminothiazole-4-methyl diazonium salt and its coupling with 4-hydroxycoumarin to give 3.
Scheme 1. Preparation of 2-aminothiazole-4-methyl diazonium salt and its coupling with 4-hydroxycoumarin to give 3.
Molbank 2022 m1504 sch001
Scheme 2. Tautomeric forms of (E)-3-(2-(4-methylthiazol-2 yl)hydrazineylidene)chromane-2,4-dione.
Scheme 2. Tautomeric forms of (E)-3-(2-(4-methylthiazol-2 yl)hydrazineylidene)chromane-2,4-dione.
Molbank 2022 m1504 sch002
Figure 2. Crystal structure of (E)-3-(2-(4-methylthiazol-2-yl)hydrazineylidene)chromane-2,4-dione (3). Thermal ellipsoids are at 30% probability.
Figure 2. Crystal structure of (E)-3-(2-(4-methylthiazol-2-yl)hydrazineylidene)chromane-2,4-dione (3). Thermal ellipsoids are at 30% probability.
Molbank 2022 m1504 g002
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Share and Cite

MDPI and ACS Style

Rahmani, F.; Crochet, A.; Zobi, F. (E)-3-(2-(4-methylthiazol-2-yl)hydrazineylidene)chromane-2,4-dione. Molbank 2022, 2022, M1504. https://doi.org/10.3390/M1504

AMA Style

Rahmani F, Crochet A, Zobi F. (E)-3-(2-(4-methylthiazol-2-yl)hydrazineylidene)chromane-2,4-dione. Molbank. 2022; 2022(4):M1504. https://doi.org/10.3390/M1504

Chicago/Turabian Style

Rahmani, Fatlinda, Aurélien Crochet, and Fabio Zobi. 2022. "(E)-3-(2-(4-methylthiazol-2-yl)hydrazineylidene)chromane-2,4-dione" Molbank 2022, no. 4: M1504. https://doi.org/10.3390/M1504

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Metrics

Back to TopTop