Next Article in Journal
trans-catena-Poly[[(bis-(µ-N,N′-bis[(pyridin-3-yl)methyl]ethanediamide))-diaqua-cadmium(II)] bis(nitrate) tetrahydrate)]
Previous Article in Journal
5(S)-((3aR,4R,6aR)-2,2-Dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl)-2-phenyl-4,5-dihydrooxazole
Previous Article in Special Issue
8(S)-[(1R,2S,5R)-2-Isopropyl-5-methylcyclohexyloxy]-3,4-dihydro-2H-[1,4]dithiepino[2,3-c]furan-6(8H)-one
 
 
Font Type:
Arial Georgia Verdana
Font Size:
Aa Aa Aa
Line Spacing:
Column Width:
Background:
Short Note

(Z)-N-Carbamoyl-4-hydroxy-4-(4-methoxyphenyl)-2-oxobut-3-enamide

by
Alexandra O. Derevnina
,
Anastasia A. Andreeva
and
Andrey N. Maslivets
*
Department of Chemistry, Perm State University, ul. Bukireva, 15, 614068 Perm, Russia
*
Author to whom correspondence should be addressed.
Molbank 2024, 2024(3), M1844; https://doi.org/10.3390/M1844
Submission received: 29 May 2024 / Revised: 26 June 2024 / Accepted: 27 June 2024 / Published: 29 June 2024
(This article belongs to the Collection Heterocycle Reactions)

Abstract

:
The reaction of 5-(4-methoxyphenyl)furan-2,3-dione with urea in a 1:1 ratio when refluxed in a mixture of 1,2-dichloroethane-DMSO gives (Z)-N-carbamoyl-4-hydroxy-4-(4-methoxyphenyl)-2-oxobut-3-enamide in a good yield. This compound was fully characterized.

1. Introduction

Compounds whose structures are based on an imidazolidinedione fragment (hydantoin) are of particular interest to the pharmaceutical industry as substances with anticancer activity [1,2,3], as kinase [3,4] and COVID-19 [5,6] inhibitors (dantrolene) and anticonvulsant agents [4,7] (Figure 1). Thus, the development of new synthetic approaches to compounds bearing an imidazolidinedione core is in demand.
Currently, our research group is interested in the study of the synthetic potential and other useful properties of enaminones (enaminoketones) fused to a heterocyclic moiety [8,9,10,11]. Eventually, we decided to start an investigation into the imidazolidinedione bearing enaminones, 5-aroylmethylideneimidazolidine-2,4-diones II (Scheme 1) [12]. Earlier, the formation of imidazolidinedione bearing enaminones II was described by fusing 5-arylfuran-2,3-diones I with urea at a temperature of 110–120 °C for 1.5 h (Scheme 1) [12]. Pursuing the development of a synthetic protocol for enaminones II under milder conditions than used in [12], we synthesized an intermediate of the reaction of 5-arylfuran-2,3-diones I and urea, (Z)-N-carbamoyl-4-hydroxy-4-(4-methoxyphenyl)-2-oxobut-3-enamide 1, whose synthesis and characteristics are reported herein.

2. Results and Discussion

The title compound 1 was synthesized in several stages (Scheme 2). Initially, 5-(4- methoxyphenyl)-furan-2,3-dione 2 was obtained in the reaction of 4-(4-methoxyphenyl)-2,4-dioxobutanoic acid with thionyl chloride [8]. Then, as a result of the reaction of compound 2 with urea 3, (Z)-N-carbamoyl-4-hydroxy-4-(4-methoxyphenyl)-2-oxobut-3-enamide 1, the target compound, was obtained for the first time. After three days of exposure in DMSO solution at rt, compound 1 cyclized into 5-hydroxy-5-(2-(4-methoxyphenyl)-2-oxoethyl)imidazolidine-2,4-dione 4. Although compound 4 was observed by NMR, it was not isolated.
The structure of compound 1 was unambiguously confirmed by X-ray diffraction analysis of a single crystal (CCDC 2358753) (Figure 2).

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 (Bruker BioSpin AG, Faellanden, Switzerland) (at 400 and 100 MHz, respectively) in DMSO-d6 using the solvent residual signal (in 1H NMR, 2.50 ppm; in 13C NMR, 39.51 ppm) as an internal standard. The IR spectrum was recorded on a Perkin Elmer Spectrum Two Spectrometer (PerkinElmer Inc., Waltham, MA, USA) as mulls in mineral oil. The melting point was measured on the device of the Khimlabpribor PTP (Khimlabpribor, Klin, Moscow, Russia). HRMS were recorded on Bruker MicroTOF (ESI+) (Bruker Daltonik GmbH, Bremen, 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 [13]. Using OLEX2 [14], the structure was solved with the SHELXT [15] program and refined by full-matrix least-squares minimization in the anisotropic approximation of all non-hydrogen atoms with the SHELXL [16] program. Hydrogen atoms bound to carbon were positioned geometrically and refined using a riding model. Hydrogen atoms of the OH, NH, and NH2 groups were refined independently with isotropic displacement parameters. 4-(4-Methoxyphenyl)-2,4-dioxobutanoic acid was obtained according to the reported procedures [17] from commercially available reagents. The starting compound 2 was obtained according to the reported procedures from commercially available reagents [8]. All procedures with compound 2 were performed in oven-dried glassware. All other solvents and reagents were purchased from commercial vendors and used as received.

3.2. (Z)-N-Carbamoyl-4-hydroxy-4-(4-methoxyphenyl)-2-oxobut-3-enamide 1

A solution of 0.423 g (7.05 mmol) of urea 3 in 2 mL of DMSO was added to a solution of 1.44 g (7.05 mmol) of 5-(4-methoxyphenyl)-furan-2,3-dione 2 in 10 mL of anhydrous 1,2-dichloroethane and refluxed for 5 min. Next, the reaction mixture was cooled to room temperature. The formed precipitate was filtered off and recrystallized from chloroform to yield the title compound 1. Yield: 1.14 g (61%); light yellow solid; mp 159–161 °C (decomp.). 1H NMR (DMSO-d6, 400 MHz), mixture of tautomers ∼ 5:1 (A:B): A: δ = 3.88 (s, 3H), 7.09 (s, 1H), 7.11 (d, 2H, J = 8.8 Hz), 7.46 (br.s, 1H), 7.53 (br.s, 1H), 8.07 (d, 2H, J = 8.8 Hz), 10.07 (s, 1H), 14.0 (br.s, 1H) ppm; B: δ = 3.86 (s, 3H), 4.50 (s, 2H), 7.06 (d, 2H, J = 8.8 Hz), 7.27 (br.s, 2H), 7.95 (d, 2H, J = 8.8 Hz), 10.13 (s, 1H) ppm. 13C NMR (DMSO-d6, 100 MHz), mixture of tautomers, A: δ = 55.6, 94.3, 114.5 (2C), 125.7, 130.1 (2C), 152.3, 162.2, 164.1, 174.9, 186.2 ppm. IR (mineral oil): 3420, 3343, 3200, 3100, 1721, 1705, 1583 cm−1. HRMS (ESI+): m/z calcd for C12H12N2O5: 287.0638 [M + Na]+; found: 287.0634. After three days of exposure in DMSO-d6 solution in an NMR tube, compound 1 cyclized into 5-hydroxy-5-(2-(4-methoxyphenyl)-2-oxoethyl)imidazolidine-2,4-dione 4. 1H NMR (DMSO-d6, after three days, 400 MHz): δ = 3.41 (d, 1H, J = 17.6 Hz), 3.63 (d, 1H, J = 17.6 Hz), 3.85 (s, 3H), 6.60 (s, 1H), 7.04 (d, 2H, J = 8.8 Hz), 7.91 (d, 2H, J = 8.8 Hz), 8.10 (s, 1H), 10.51 (s, 1H) ppm. 13C NMR (DMSO-d6, after three days, 100 MHz): δ = 43.6, 55.5, 82.8, 113.9 (2C), 129.1, 130.2 (2C), 156.4, 163.3, 175.0, 194.2 ppm.
Crystal data of compound 1. C12H12N2O5, M = 264.24, triclinic, space group P–1, a = 7.8501(11) Å, b = 8.6851(14) Å, c = 9.8080(15) Å, α = 68.302(15)°, β = 86.023(12)°, γ = 77.008(13)°, V = 605.34(17) Å3, T = 295(2) K, Z = 2, μ(Mo Kα) = 0.115 mm−1. The final refinement parameters: R1 = 0.0476 (for observed 2180 reflections with I > 2σ(I)); wR2 = 0.1377 (for all independent 2801 reflections, Rint = 0.0282), S = 1.058. Largest diff. peak and hole were 0.226 and −0.215 ēÅ−3. Crystal structure of compound 1 was deposited at the Cambridge Crystallographic Data Centre with the deposition number CCDC 2358753.

Supplementary Materials

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

Author Contributions

Conceptualization, A.N.M.; methodology, A.O.D., A.A.A. and A.N.M.; validation, A.O.D. and A.N.M.; investigation, A.O.D. (synthetic chemistry); writing—original draft preparation, A.O.D. and A.N.M.; writing—review and editing, A.O.D. and A.N.M.; visualization, A.O.D.; 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 of the Ministry of Science and Higher Education of the Russian Federation (FSNF-2023-0004) and of 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 conflicts of interest.

References

  1. Chahat; Bhatia, R.; Kumar, B. p53 as a potential target for treatment of cancer: A perspective on recent advancements in small molecules with structural insights and SAR studies. Eur. J. Med. Chem. 2023, 247, 115020. [Google Scholar] [CrossRef] [PubMed]
  2. Chaurasiya, A.; Sahu, C.; Wahan, S.K.; Chawla, P.A. Targeting cancer through recently developed purine clubbed heterocyclic scaffolds: An overview. J. Mol. Struct. 2023, 1280, 134967. [Google Scholar] [CrossRef]
  3. Jerin, S.; Harvey, A.J.; Lewis, A. Therapeutic Potential of Protein Tyrosine Kinase 6 in Colorectal Cancer. Cancers 2023, 15, 3703. [Google Scholar] [CrossRef] [PubMed]
  4. Naufal, M.; Hermawati, E.; Syah, Y.M.; Hidayat, A.T.; Hidayat, I.W.; Al-Anshori, J. Structure–Activity Relationship Study and Design Strategies of Hydantoin, Thiazolidinedione, and Rhodanine-Based Kinase Inhibitors: A Two-Decade Review. ACS Omega 2024, 9, 4186–4209. [Google Scholar] [CrossRef] [PubMed]
  5. Alkazmi, L.; Al-kuraishy, H.M.; Al-Gareeb, A.I.; El-Bouseary, M.M.; Ahmed, E.A.; Batiha, G.E.S. Dantrolene and ryanodine receptors in COVID-19: The daunting task and neglected warden. Clin. Exp. Pharmacol. Physiol. 2023, 50, 335–352. [Google Scholar] [CrossRef] [PubMed]
  6. Song, L.; Gao, S.; Ye, B.; Yang, M.; Cheng, Y.; Kang, D.; Yi, F.; Sun, J.-P.; Menéndez-Arias, L.; Neyts, J.; et al. Medicinal chemistry strategies towards the development of non-covalent SARS-CoV-2 Mpro inhibitors. Acta Pharm. Sin. B 2024, 14, 87–109. [Google Scholar] [CrossRef] [PubMed]
  7. Abd-Allah, W.H.; El-Mohsen Anwar, M.A.; Mohammed, E.R.; El Moghazy, S.M. Anticonvulsant Classes and Possible Mechanism of Actions. ACS Chem. Neurosci. 2023, 14, 4076–4092. [Google Scholar] [CrossRef] [PubMed]
  8. Stepanova, E.E.; Lukmanova, D.N.; Kasatkina, S.O.; Dmitriev, M.V.; Maslivets, A.N. Facile Synthesis of Regioisomeric N-Alkyl Substituted 3-Methylene-3,4-dihydroquinoxalin-2(1H)-ones. ChemistrySelect 2019, 4, 12774–12778. [Google Scholar] [CrossRef]
  9. Stepanova, E.E.; Dmitriev, M.V.; Maslivets, A.N. Synthesis of 1,4-benzothiazinones from acylpyruvic acids or furan-2,3-diones and o-aminothiophenol. Beilstein J. Org. Chem. 2020, 16, 2322–2331. [Google Scholar] [CrossRef] [PubMed]
  10. Dmitriev, M.V.; Khramtsova, E.E.; Apuskin, D.Y.; Andreev, A.I.; Kovalenko, I.I.; Mashevskaya, I.V.; Maslivets, A.N. Synthesis and Anti-Inflammatory Activity of (Z)-4-(2-(3-Oxopiperazin-2-ylidene)acetyl)benzoic Acid. Molbank 2024, 2024, M1772. [Google Scholar] [CrossRef]
  11. Stepanova, E.E.; Balandina, S.Y.; Drobkova, V.A.; Dmitriev, M.V.; Mashevskaya, I.V.; Maslivets, A.N. Synthesis, in vitro antibacterial activity against Mycobacterium tuberculosis, and reverse docking-based target fishing of 1,4-benzoxazin-2-one derivatives. Arch. Pharm. 2021, 354, e2000199. [Google Scholar] [CrossRef] [PubMed]
  12. Andreichikov, Y.S.; Nekrasov, D.D.; Rudenko, M.A.; Nalimova, Y.A. Reaction of 5-aryl-2,3-dihydrofuran-2,3-diones with N-substituted ureas and their thio and seleno analogs. Chem. Heterocycl. Compd. 1988, 10, 1411–1413. [Google Scholar]
  13. CrysAlisPro, Version 1.171.42.74a. Rigaku Oxford Diffraction: Wroclaw, Poland. 2022. Available online: https://www.rigaku.com/products/crystallography/crysalis (accessed on 5 April 2024).
  14. Dolomanov, O.V.; Bourhis, L.J.; Gildea, R.J.; Howard, J.A.K.; Puschmann, H. OLEX2: A complete structure solution, refinement and analysis program. J. Appl. Cryst. 2009, 42, 339–341. [Google Scholar] [CrossRef]
  15. Sheldrick, G.M. SHELXT–Integrated space-group and crystal-structure determination. Acta Crystallogr. Sect. A Found. Adv. 2015, 71, 3–8. [Google Scholar] [CrossRef] [PubMed]
  16. Sheldrick, G.M. Crystal structure refinement with SHELXL. Acta Crystallogr. Sect. C Struct. Chem. 2015, 71, 3–8. [Google Scholar] [CrossRef] [PubMed]
  17. Andreychikov, Y.S. Guidelines for Student Research Work: Methods of Synthesis of Biologically Active Heterocyclic Compounds; Perm University: Perm, Russia, 1988; p. 9. [Google Scholar]
Figure 1. Potential pharmaceutical substances bearing an imidazolidinedione core.
Figure 1. Potential pharmaceutical substances bearing an imidazolidinedione core.
Molbank 2024 m1844 g001
Scheme 1. Synthesis of imidazolidinediones II via a reaction of 5-arylfuran-2,3-diones I and urea (imidazolidinedione moiety is marked in red; enaminone moiety is highlighted in yellow).
Scheme 1. Synthesis of imidazolidinediones II via a reaction of 5-arylfuran-2,3-diones I and urea (imidazolidinedione moiety is marked in red; enaminone moiety is highlighted in yellow).
Molbank 2024 m1844 sch001
Scheme 2. Synthesis of (Z)-N-carbamoyl-4-hydroxy-4-(4-methoxyphenyl)-2-oxobut-3-enamide 1.
Scheme 2. Synthesis of (Z)-N-carbamoyl-4-hydroxy-4-(4-methoxyphenyl)-2-oxobut-3-enamide 1.
Molbank 2024 m1844 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 m1844 g002
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content.

Share and Cite

MDPI and ACS Style

Derevnina, A.O.; Andreeva, A.A.; Maslivets, A.N. (Z)-N-Carbamoyl-4-hydroxy-4-(4-methoxyphenyl)-2-oxobut-3-enamide. Molbank 2024, 2024, M1844. https://doi.org/10.3390/M1844

AMA Style

Derevnina AO, Andreeva AA, Maslivets AN. (Z)-N-Carbamoyl-4-hydroxy-4-(4-methoxyphenyl)-2-oxobut-3-enamide. Molbank. 2024; 2024(3):M1844. https://doi.org/10.3390/M1844

Chicago/Turabian Style

Derevnina, Alexandra O., Anastasia A. Andreeva, and Andrey N. Maslivets. 2024. "(Z)-N-Carbamoyl-4-hydroxy-4-(4-methoxyphenyl)-2-oxobut-3-enamide" Molbank 2024, no. 3: M1844. https://doi.org/10.3390/M1844

Note that from the first issue of 2016, this journal uses article numbers instead of page numbers. See further details here.

Article Metrics

Back to TopTop