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Short Note

3-(4-Bromophenyl)-1-carbamothioyl-5-(2-carbamothioylhydrazinyl)-4,5-dihydro-1H-pyrazole-5-carboxylic Acid

Department of Chemistry, Perm State University, ul. Bukireva, 15, 614990 Perm, Russia
*
Author to whom correspondence should be addressed.
Molbank 2024, 2024(1), M1757; https://doi.org/10.3390/M1757
Submission received: 29 November 2023 / Revised: 18 December 2023 / Accepted: 19 December 2023 / Published: 2 January 2024
(This article belongs to the Collection Heterocycle Reactions)

Abstract

:
The reaction of 4-(4-bromophenyl)-2,4-dioxobutanoic acid with thiosemicarbazide, in a ratio of 1:2, when boiled in ethanol gives 3-(4-bromophenyl)-1-carbamothioyl-5-(2-carbamothioylhydrazinyl)-4,5-dihydro-1H-pyrazole-5-carboxylic acid with a good yield. This compound was fully characterized.

1. Introduction

Compounds whose structures are based on a pyrazoline fragment are of particular interest to the pharmaceutical industry as substances with anticancer [1,2,3], antimicrobial and antifungal [1,4] activity and to agriculture as herbicide detoxifiers [5] (Figure 1).
As a continuation of the development of methods for the synthesis of pyrazolines containing potentially functionalizable acyl groups at various positions of the pyrazoline cycle through the reaction of polycarbonyl compounds and substituted hydrazines (Scheme 1) [6,7], we synthesized a new representative of functionally substituted 1-carbamothioyl-3-carboxy-1H-pyrazoline 1 via a reaction of aroylpyruvic acid and thiosemicarbazide.

2. Results and Discussion

The title compound 1 was synthesized in several stages (Scheme 2). Initially, 4-(4-bromophenyl)-2,4-dioxobutanoic acid 3 was obtained via the Claisen condensation of 4-bromoacetophenone and diethyl oxalate. Then, as a result of the reaction of compound 3 and thiosemicarbazide 2, 3-(4-bromophenyl)-1-carbamothioyl-5-(2-carbamothioylhydrazinyl)-4,5-dihydro-1H-pyrazole-5-carboxylic acid 1, the target compound, was obtained for the first time.
The structure of compound 1 was unambiguously confirmed by X-ray diffraction analysis of a single crystal (CCDC 2310650) (Figure 2). Compound 1 crystallizes as a racemate in the centrosymmetric space group P21/c.

3. Materials and Methods

3.1. General Information

1H and 13C NMR spectra (Supplementary Materials) were obtained on a Bruker Avance III 400 HD spectrometer (Fällanden, Switzerland) (at 400 and 100 MHz, respectively) in DMSO-d6 using the solvent residual signal (in 1H NMR, 2.50 for DMSO-d6; in 13C NMR, 39.51 for DMSO-d6) as an internal standard. IR spectrum was recorded on a Perkin Elmer Spectrum Two Spectrometer (Shelton, CT, USA) as mulls in mineral oil. The melting point was measured on the device of the Khimlabpribor PTP (USSR). Elemental analysis was carried out on a Vario MICRO Cube analyzer (Langenselbold, Germany). The single crystal X-ray analysis of compound 1 was performed on an Xcalibur Ruby diffractometer (Agilent Technologies, Wroclaw, Poland). An empirical absorption correction was introduced via the multi-scan method using the SCALE3 ABSPACK algorithm [8]. Using OLEX2 [9], the structure was solved with the SHELXT [10] program and refined by a full-matrix least-squares minimization in the anisotropic approximation of all non-hydrogen atoms with the SHELXL [11] program. Hydrogen atoms bound to carbon were positioned geometrically and refined using a riding model. Hydrogen atoms of OH, NH and NH2 groups were refined independently with isotropic displacement parameters. Thin-layer chromatography (TLC) was performed on Macherey-Nagel Alugram Sil G/UV254 (Düren, Germany) plates using EtOAc/MeOH, 3:1 v/v, as eluents and was manifested with iodine vapor. The starting compound 3 was obtained according to the reported procedures [12] from commercially available reagents. All procedures with compound 3 were performed in oven-dried glassware. All other solvents and reagents were purchased from commercial vendors and used as received.

3.2. 3-(4-Bromophenyl)-1-carbamothioyl-5-(2-carbamothioylhydrazinyl)-4,5-dihydro-1H-pyrazole-5-carboxylic Acid 1

A suspension of 2 g (7.4 mmol) 4-(4-bromophenyl)-2,4-dioxobutanoic acid 3 and 1.345 g (14.8 mmol) thiosemicarbazide 2 in 30 mL EtOH was refluxed for 2 h. Next, the reaction mixture was cooled to room temperature. The formed precipitate was filtered off and recrystallized from ethanol to yield the title compound 1. Yield: 1,84 г (76%); yellow solid; mp 253–255 °C (decomp.). 1H NMR (DMSO-d6, 400 MHz): δ = 3.50 d, 3.64 d (2H), 6.33 (s, 1H), 7.60–7.97 (m, 2H), 7.68 (d, 2H), 7.79 (d, 2H), 8.15 (d, 2H), 8.39 (s, 1H), 13.47 (br.s, 1H). 13C NMR (DMSO-d6, 100 MHz): δ = 41.9, 83.5, 124.0, 128.8, 129.5, 131.6, 150.2, 169.1, 175.7, 183.3. IR (mineral oil): 3439, 3309, 3176, 1766, 1660 cm−1. Anal.Calcd (%) for C12H13BrN6O2S2: C 34.54; H 3.14; N 20.14. Found: C 34.79; H 3.08; N 20.06.
Crystal Data of 1. C12H13BrN6O2S2∙H2O, M = 435.33, monoclinic, space group P21/c, a = 9.2792(15) Å, b = 17.129(4) Å, c = 10.939(2) Å, β = 92.809(15)°, V = 1736.6(6) Å3, T = 295(2) K, Z = 4, μ(Mo Kα) = 2.632 mm−1. The final refinement parameters: R1 = 0.0479 (for observed 3031 reflections with I > 2σ(I)); wR2 = 0.1232 (for all independent 4020 reflections, Rint = 0.0446), S = 1.034. Largest diff. peak and hole were 0.451 and –0.907 ēÅ−3. Crystal structure of compound 1 was deposited at the Cambridge Crystallographic Data Centre with the deposition number CCDC 2310650.

Supplementary Materials

Copies of the NMR spectra for the new compound can be downloaded online.

Author Contributions

Conceptualization, A.N.M.; methodology, A.A.A. and A.N.M.; validation, A.A.A. and A.N.M.; investigation, A.A.A. (synthetic chemistry) and M.V.D. (X-ray analysis); writing—original draft preparation, A.A.A. and A.N.M.; writing—review and editing, A.A.A. and A.N.M.; visualization, A.A.A.; supervision, A.N.M.; project administration, A.N.M.; funding acquisition, A.N.M. All authors have read and agreed to the published version of the manuscript.

Funding

This study was performed with financial support from the Perm Research and Educational Center “Rational subsoil use”.

Institutional Review Board Statement

Not applicable.

Informed Consent Statement

Not applicable.

Data Availability Statement

The presented data are available in this article.

Conflicts of Interest

The authors declare no conflict of interest.

References

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Figure 1. Potential pharmaceutical substances bearing a pyrazoline core.
Figure 1. Potential pharmaceutical substances bearing a pyrazoline core.
Molbank 2024 m1757 g001
Scheme 1. Synthesis of pyrazolines via a reaction of acylpyruvic acids and substituted hydrazines.
Scheme 1. Synthesis of pyrazolines via a reaction of acylpyruvic acids and substituted hydrazines.
Molbank 2024 m1757 sch001
Scheme 2. Synthesis of 3-(4-bromophenyl)-1-carbamothioyl-5-(2-carbamothioylhydrazinyl)-4,5-dihydro-1H-pyrazole-5-carboxylic acid 1.
Scheme 2. Synthesis of 3-(4-bromophenyl)-1-carbamothioyl-5-(2-carbamothioylhydrazinyl)-4,5-dihydro-1H-pyrazole-5-carboxylic acid 1.
Molbank 2024 m1757 sch002
Figure 2. Structure of compound 1, obtained by X-ray diffraction analysis.
Figure 2. Structure of compound 1, obtained by X-ray diffraction analysis.
Molbank 2024 m1757 g002
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MDPI and ACS Style

Andreeva, A.A.; Dmitriev, M.V.; Maslivets, A.N. 3-(4-Bromophenyl)-1-carbamothioyl-5-(2-carbamothioylhydrazinyl)-4,5-dihydro-1H-pyrazole-5-carboxylic Acid. Molbank 2024, 2024, M1757. https://doi.org/10.3390/M1757

AMA Style

Andreeva AA, Dmitriev MV, Maslivets AN. 3-(4-Bromophenyl)-1-carbamothioyl-5-(2-carbamothioylhydrazinyl)-4,5-dihydro-1H-pyrazole-5-carboxylic Acid. Molbank. 2024; 2024(1):M1757. https://doi.org/10.3390/M1757

Chicago/Turabian Style

Andreeva, Anastasia A., Maksim V. Dmitriev, and Andrey N. Maslivets. 2024. "3-(4-Bromophenyl)-1-carbamothioyl-5-(2-carbamothioylhydrazinyl)-4,5-dihydro-1H-pyrazole-5-carboxylic Acid" Molbank 2024, no. 1: M1757. https://doi.org/10.3390/M1757

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