Next Article in Journal
(trans-Dihydroxo)Sn(IV)-[5,10,15,20-tetrakis(2-pyridyl)porphyrin]
Next Article in Special Issue
Photoinduced Ring Opening of Methyl 1-Aryl-5-oxo-6,7-dihydro-1H,5H-pyrazolo[1,2-a]pyrazole-2-carboxylates in the Presence of Diaryl Disulfides
Previous Article in Journal
N-(diisopropylphosphanyl)benzamide
Previous Article in Special Issue
5,6-Dihydro-[1,2,5]oxadiazolo[3,4-d]pyridazine-4,7-dione
 
 
Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
Journals
Molbank
Volume 2023
Issue 2
10.3390/M1668
molbank-logo
Submit to this Journal Review for this Journal Propose a Special Issue
► Article Menu

Article Menu

share Share announcement Help format_quote Cite question_answer Discuss in SciProfiles thumb_up
...
Endorse textsms
...
Comment
first_page
settings
Order Article Reprints
Font Type:
Arial Georgia Verdana
Font Size:
Aa Aa Aa
Line Spacing:
Column Width:
Background:
Communication

Synthesis of 5-Aroyl-2-aryl-3-hydroxypyridin-4(1H)-ones

by
Elena V. Steparuk
,
Dmitrii L. Obydennov
* and
Vyacheslav Y. Sosnovskikh
Institute of Natural Sciences and Mathematics, Ural Federal University, 51 Lenina ave., Ekaterinburg 620000, Russia
*
Author to whom correspondence should be addressed.
Molbank 2023, 2023(2), M1668; https://doi.org/10.3390/M1668
Submission received: 18 May 2023 / Revised: 6 June 2023 / Accepted: 8 June 2023 / Published: 10 June 2023
(This article belongs to the Collection Heterocycle Reactions)
Browse Figures
Versions Notes

Abstract

:
A two-stage synthesis of 5-aroyl-2-aryl-3-hydroxypyridin-4(1H)-ones (56–66% overall yields) was carried out by refluxing 5-aroyl-3-(benzyloxy)-2-(het)aryl-4H-pyran-4-ones with ammonium acetate in AcOH and subsequent debenzylation. The prepared N-unsubstituted 4-pyridones exist in the pyridone tautomeric form.

Graphical Abstract

1. Introduction

3-Hydroxy-4-pyridones (3,4-HPOs) are well-known bidentate chelation agents for many metals [1,2,3]. The first marketed drug possessing a 3,4-HPO scaffold, deferiprone (Ferriprox), is an iron chelating agent for treating thalassemia approved in 1999 (Figure 1). Since the pyridine ring offers great possibilities for functionalization, a number of new 3,4-HPO-based polydentate chelators [2,4] and also 3,4-HPO-grafted fabrics for filtering uranium from wastewater [5] were developed afterward. Moreover, there are some natural examples of 3,4-HPOs, such as rubrifacine [6] and mimosine (leucenol), an amitotic agent first isolated from Mimosa pudica [7].
Additionally, 3-hydroxy-4-pyridones have recently received considerable attention as promising metal-binding pharmacophores, such as inhibitors of metalloenzymes, and thus are being now intensively investigated to design novel drugs, including antiviral ones [8]. As a result, approved HIV integrase strand transfer inhibitors (INSTI) dolutegravir, bictegravir, and cabotegravir, as well as several newly developed drug candidates (Figure 1), possess a 3,4-HPO structural motif designed to coordinate magnesium ions of HIV integrase and thus prevent integration of the viral DNA [9,10,11,12,13,14,15]. Additionally, the inhibitors of catechol-O-methyltransferase (contains Mg2+) [16], human cytomegalovirus pUL89 protein (Mn2+) [17], and influenza cap-dependent endonuclease (Mn2+) [18] were discovered.
However, methods for preparing 3,4-HPOs can dramatically differ depending on the substituent location and type and may require multi-stage synthetic schemes with restricted reaction scope [12,19]. For some of them, there is still no efficient synthetic approach.
In this article, we focused our attention on the synthesis of hitherto unknown N-unsubstituted 5-aroyl-2-(het)aryl-3-hydroxypyridin-4(1H)-ones.

2. Results and Discussion

Recently, we synthesized a series of 5-aroyl-3-(benzyloxy)-2-(het)aryl-4H-pyran-4-ones 1 by acylation of enaminodiones with acylbenzotriazoles via soft enolization [20]. To the best of our knowledge, no examples of N-unsubstituted 3,4-HPOs 3 bearing 2-(het)aryl and 5-aroyl substituents have been described in the literature to date. Therefore, we decided to employ the ANRORC reaction of pyrones 1a–c with ammonia to synthesize pyridones 2a–c and then reach desired 3-hydroxy-4-pyridones 3 by the debenzylation of the latter.
We found that pyrones 1a–c on heating at 100 °C for 3 h with ammonium acetate in glacial AcOH afforded corresponding pyridones 2a–c in 61–72% yields (Scheme 1, Table 1). Subsequent dilution with water and recrystallization from toluene made it possible to isolate the products in pure form. In the reaction with ethanolic ammonia solution, however, it turned out that two equivalents of ammonia were involved, and [4-amino-5-(benzyloxy)-6-phenylpyridin-3-yl](phenyl)methanone was obtained from the corresponding pyrone [20]. Additionally, no reaction appeared when pyrones 1 were refluxed in an ethanolic solution of ammonium chloride. The reaction mechanism includes the attack of the ammonia molecule at the C-6 position, followed by the pyrone ring opening and intramolecular cyclization [21].
The debenzylation of products 2a–c under the action of TMSI generated in situ in anhydrous acetonitrile from TMSCl and NaI allowed us to obtain 5-acyl-2-hetaryl substituted 3,4-HPOs 3a–c in 89–92% yields. It is important to note that the purification of products 3 did not require chromatography and could be achieved by simple recrystallization.
The structures of all synthesized compounds were characterized based on 1H, 13C NMR (see SM), and IR spectroscopy data and supported by HRMS values. Although N-unsubstituted pyridones can undergo pyridinol/pyridone tautomerism [22,23], compounds 2 and 3 exist in the pyridone form. The 1H NMR spectra of these compounds display the presence of the characteristic pyridone H-6 singlet or doublet (JH-6,NH = 3.6–6.6 Hz) at δ 7.78–7.90 ppm and the downfield singlet or doublet of the NH group at δ 12.14–12.30 ppm. The 13C NMR spectra show the characteristic peaks of the acyl moiety and the pyridone carbonyl group at δ 192.6–194.1 and 168.6–171.6 ppm, respectively. For compound 2, the NMR signals of the aliphatic methylene group appeared at δ 5.03–5.30 ppm (1H NMR) and 71.5–72.1 ppm (13C NMR).
In summary, we described a convenient two-step way (starting from pyrones) for synthesizing new 5-aroyl-2-(het)aryl-3-hydroxypyridin-4(1H)-ones in 56–66% overall yields. This will expand the design possibilities in the search for new inhibitors of metalloenzymes with antiviral activity.

3. Materials and Methods

NMR spectra were recorded on Bruker Avance III-500 (1H—500 MHz and 13C—126 MHz) spectrometers (Bruker BioSpin GmbH, Rheinstetten, Germany) in DMSO-d6. Chemical shifts are reported relative to TMS as an internal standard in ppm, and J values are given in Hz. IR spectra were recorded on a Shimadzu IRSpirit-T (QATR-S) instrument (FTIR mode, diamond crystal, Shimadzu Corp., Kyoto, Japan). The mass spectra (ESI-MS) were measured with a Waters Xevo QTof instrument (Waters Corp., Milford, MA, USA). All solvents used were dried and distilled per standard procedures. Melting points were determined on a Stuart SMP40 apparatus. Pyrones 1a–c were prepared according to the literature data [20].

3.1. General Procedure for the Synthesis of 3-Benzyloxypyridin-4(1H)-ones 2

Pyrone 1 (0.27 mmol) was dissolved in glacial AcOH, and NH4OAc (83.2 mg, 1.08 mmol) was added. The resulting mixture was stirred at 100 °C for 3 h, and then excess water was added. The precipitate formed was filtered and recrystallized from toluene.
  • 5-Benzoyl-3-(benzyloxy)-2-(furan-2-yl)pyridin-4(1H)-one (2a). Brown solid (68 mg, 68%), mp 190–191 °C. IR (ATR) ν 2879, 2854, 1655, 1614, 1540, 1314, 1255, 1188, 999, and 743 cm−1. 1H NMR (500 MHz, DMSO-d6) δ 5.30 (s, 2H, CH2), 6.74 (dd, J = 3.4, J = 1.7, 1H, H-4 furan), 7.17 (d, J = 3.4, 1H, H-3 furan), 7.31–7.39 (m, 3H, Ph), 7.41 (d, J = 7.0, 2H, H-2, H-6 Ph), 7.50 (t, J = 7.7, 2H, H-3, H-5 Ph), 7.61 (t, J = 7.4, 1H, H-4 Ph), 7.72 (d, J = 7.2, 2H, H-2, H-6 Ph), 7.79 (s, 1H, H-6 pyridone), 8.01 (d, J = 1.0, 1H, H-5 furan), and 12.14 (s, 1H, NH). 13C NMR (126 MHz, DMSO-d6) δ 71.5 (CH2), 112.9, 114.1, 125.3, 126.4, 128.1, 128.16, 128.2, 128.6, 128.9, 129.1, 129.6, 132.7, 137.0, 137.6, 143.6, 144.6, 171.2 (C=O), and 194.1 (C=O). HRMS (ESI): calculated for C23H18NO4 [M + H]+ 372.1236, found 372.1249.
  • 3-(Benzyloxy)-5-(4-chlorobenzoyl)-2-(furan-2-yl)pyridin-4(1H)-one (2b). Brown solid (79 mg, 72%), mp 194–195 °C. IR (ATR) ν 2779, 2682, 1647, 1616, 1536, 1191, 1008, and 794 cm−1. 1H NMR (500 MHz, DMSO-d6) δ 5.28 (s, 2H, CH2), 6.75 (dd, J = 3.4, J = 1.8, 1H, H-4 furan), 7.16 (d, J = 3.4, 1H, H-3 furan), 7.33 (tt, J = 7.2, J = 1.4, 1H, H-4 Ph), 7.37 (t, J = 7.2, 2H, H-3, H-5 Ph), 7.41 (d, J = 7.0, 2H, H-2, H-6 Ph), 7.56 (d, J = 8.5, 2H, H-3, H-5 Ar), 7.72 (d, J = 8.5, 2H, H-2, H-6 Ar), 7.83 (s, 1H, H-6 pyridone), 8.01 (d, J = 1.0, 1H, H-5 furan), and 12.21 (s, 1H, NH). 13C NMR (126 MHz, DMSO-d6) δ 71.6 (CH2), 112.9, 114.1, 125.7, 128.1, 128.2, 128.2, 128.5, 130.9, 136.4, 137.0, 137.4, 138.2, 143.5, 143.7, 144.6, 171.2 (C=O), and 193.0 (C=O). HRMS (ESI): calculated for C23H17ClNO4 [M + H]+ 406.0846, found 406.0853.
  • 3-(Benzyloxy)-5-(4-chlorobenzoyl)-2-phenylpyridin-4(1H)-one (2c). Brown solid (68 mg, 61%), mp 160–161 °C. IR (ATR) ν 3019, 2866, 1657, 1613, 1535, 1190, and 752 cm−1. 1H NMR (500 MHz, DMSO-d6) δ 5.03 (s, 2H, CH2), 7.10–7.19 (m, 2H, Ph), 7.21–7.26 (m, 3H, Ph), 7.49–7.53 (m, 3H, Ph), 7.54–7.57 (m, 2H, Ph), 7.58 (d, J = 8.5, 2H, H-3, H-5 Ar), 7.77 (d, J = 8.5, 2H, H-2, H-6 Ar), 7.90 (d, J = 6.2, 1H, H-6 pyridone), and 12.18 (d, J = 6.2, 1H, NH). 13C NMR (126 MHz, DMSO-d6) δ 72.1 (CH2), 126.5, 127.7, 128.0, 128.1, 128.25, 128.33, 129.0, 129.6, 131.0, 136.4, 137.1, 138.0, 140.3, 145.5, 171.6 (C=O), and 193.3 (C=O). HRMS (ESI): calculated for C25H18ClNO3 [M + H]+ 416.1053, found 416.1042.

3.2. General Procedure for the Synthesis of 3-Hydroxypyridin-4(1H)-ones 3

Corresponding pyridone 2 (0.25 mmol) and NaI (69 mg, 0.37 mmol) were dissolved in anhydrous MeCN (3 mL), and Me3SiCl (53 mg, 0.49 mmol) was added. The solution was stirred at 80 °C for 1.5 h (TLC monitoring). Then, water (4 mL) was added, and the precipitated product was filtered and recrystallized from toluene.
  • 5-Benzoyl-2-(furan-2-yl)-3-hydroxypyridin-4(1H)-one (3a). Brown solid (63 mg, 89%), mp 234–235 °C. IR (ATR) ν 3334, 3054, 1600, 1482, 1233, and 746 cm−1. 1H NMR (500 MHz, DMSO-d6) δ 6.77 (dd, J = 3.3, J = 1.3, 1H, H-4 furan), 7.13 (d, J = 3.3, 1H, H-3 furan), 7.46 (t, J = 7.6, 2H, H-3, H-5 Ph), 7.59 (t, J = 7.3, 1H, H-4 Ph), 7.75 (d, J = 7.5, 2H, H-2, H-6 Ph), 7.78 (d, J = 3.6, 1H, H-6 pyridone), 7.99 (s, 1H, H-5 furan), and 12.24 (s, 1H, NH); the OH proton was not observed. 13C NMR (126 MHz, DMSO-d6) δ 112.5, 112.8, 119.2, 121.2, 128.0, 129.2, 132.4, 136.6, 137.9, 143.8, 144.1, 144.5, 168.6 (C=O), and 193.7 (C=O). HRMS (ESI): calculated for C16H12NO4 [M + H]+ 282.0766, found 282.0764.
  • 5-(4-Chlorobenzoyl)-2-(furan-2-yl)-3-hydroxypyridin-4(1H)-one (3b). Brown solid (72 mg, 92%), mp 298–299 °C. IR (ATR) ν 3311, 3060, 2958, 1648, 1523, 1405, 1273, and 736 cm−1. 1H NMR (500 MHz, DMSO-d6) δ 6.77 (dd, J = 3.1, J = 1.6, 1H, H-4 furan), 7.13 (d, J = 3.3, 1H, H-3 furan), 7.53 (d, J = 8.4, 2H, H-3, H-5 Ar), 7.75 (d, J = 8.4, 2H, H-2, H-6 Ar), 7.81 (d, J = 6.6, 1H, H-6 pyridone), 7.99 (s, 1H, H-5 furan), and 12.30 (d, J = 6.6, 1H, NH); the OH proton was not observed. 13C NMR (126 MHz, DMSO-d6) δ 112.6, 112.9, 119.3, 120.8, 128.1, 131.1, 136.7, 137.0, 137.2, 143.8, 144.1, 144.7, 168.7 (C=O), and 192.6 (C=O). HRMS (ESI): calculated for C16H10ClNO4 [M + H]+ 316.0377, found 316.0376.
  • 5-(4-Chlorobenzoyl)-3-hydroxy-2-phenylpyridin-4(1H)-one (3c). Brown solid (75 mg, 92%), mp 292–293 °C. IR (ATR) ν 3234, 3070, 1641, 1594, 1379, 1263, 1087, and 752 cm−1. 1H NMR (500 MHz, DMSO-d6) δ 7.48 (tt, J = 7.3, J = 1.2, 1H, H-4 Ph), 7.52–7.57 (m, 4H, Ph, Ar), 7.75–7.79 (m, 4H, Ar, Ph), 7.88 (d, J = 6.1, 1H, H-6 pyridone), 8.40–9.40 (br s, 1H, OH), and 12.22 (d, J = 6.1, 1H, NH). 13C NMR (126 MHz, DMSO-d6) δ 120.8, 127.4, 128.1, 128.40, 128.43, 129.1, 131.16, 131.19, 136.6, 136.9, 137.3, 146.1, 169.0 (C=O), and 192.7 (C=O). HRMS (ESI): calculated for C18H12ClNO3 [M + H]+ 326.0584, found 326.0599.

Supplementary Materials

The following supporting information can be downloaded online: Full 1H and 13C NMR spectra of all synthesized compounds.

Author Contributions

Conceptualization and methodology were provided by V.Y.S. and D.L.O.; E.V.S. conceived and designed the experiments.; the experimental work was conducted by E.V.S.; D.L.O. and E.V.S. analyzed the results; E.V.S. studied and systemized the spectral data; project administration and funding acquisition were carried out by V.Y.S. and D.L.O. All authors have read and agreed to the published version of the manuscript.

Funding

This research was funded by the Russian Science Foundation, grant number 22-73-10236 (https://rscf.ru/project/22-73-10236/ (accessed on 24 April 2023)).

Data Availability Statement

Data is contained within the article and Supplementary Materials.

Acknowledgments

Analytical studies were carried out using equipment at the Center for Joint Use ‘Spectroscopy and Analysis of Organic Compounds’ at the Postovsky Institute of Organic Synthesis of the Russian Academy of Sciences (Ural Branch) and the Laboratory of Complex Investigations and Expert Evaluation of Organic Materials of the Center for Joint Use at the Ural Federal University.

Conflicts of Interest

The authors declare no conflict of interest.

References

  1. Santos, M.A.; Marques, S.M.; Chaves, S. Hydroxypyridinones as “Privileged” Chelating Structures for the Design of Medicinal Drugs. Coord. Chem. Rev. 2012, 256, 240–259. [Google Scholar] [CrossRef]
  2. Santos, M.A.; Irto, A.; Buglyó, P.; Chaves, S. Hydroxypyridinone-Based Metal Chelators towards Ecotoxicity: Remediation and Biological Mechanisms. Molecules 2022, 27, 1966. [Google Scholar] [CrossRef] [PubMed]
  3. Zhou, D.; Tian, Y.; Ma, Y. Preparation of 5-Functionalised Pyridine Derivatives Using a Br/Mg Exchange Reaction: Application to the Synthesis of an Iron-Chelator Prodrug. J. Chem. Res. 2017, 41, 627–630. [Google Scholar] [CrossRef]
  4. Zhou, X.; Dong, L.; Shen, L. Hydroxypyridinones as a very Promising Platform for Targeted Diagnostic and Therapeutic Radiopharmaceuticals. Molecules 2021, 26, 6997. [Google Scholar] [CrossRef] [PubMed]
  5. Zhang, M.; Yuan, M.; Zhang, M.; Wang, M.; Chen, J.; Li, R.; Qiu, L.; Feng, X.; Hu, J.; Wu, G. Efficient Removal of Uranium from Diluted Aqueous Solution with Hydroxypyridone Functionalized Polyethylene Nonwoven Fabrics. Radiat. Phys. Chem. 2020, 171, 108742. [Google Scholar] [CrossRef]
  6. Feistner, G.; Budzikiewicz, H. On the Structure of Rubrifacine. Can. J. Chem. 1985, 63, 495–499. [Google Scholar] [CrossRef]
  7. Adams, R.; Cristol, S.J.; Anderson, A.A.; Albert, A.A. The Structure of Leucenol. I. J. Am. Chem. Soc. 1945, 67, 89–92. [Google Scholar] [CrossRef]
  8. Chen, A.Y.; Adamek, R.N.; Dick, B.L.; Credille, C.V.; Morrison, C.N.; Cohen, S.M. Targeting Metalloenzymes for Therapeutic Intervention. Chem. Rev. 2019, 119, 1323–1455. [Google Scholar] [CrossRef] [PubMed]
  9. Ji, M.; Lazerwith, S.E.; Pyun, H.-J. Polycyclic-Carbamoylpyridone Compounds and Their Pharmaceutical Use. U.S. Patent US9700554, 11 July 2017. [Google Scholar]
  10. Miyazaki, S.; Isoshima, H.; Oshita, K.; Kawashita, S.; Nagahashi, N.; Terashita, M. Substituted Spiropyrido[1,2-a]Pyrazine Derivative and Medicinal Use Thereof as HIV Integrase Inhibitor. U.S. Patent US10087178, 2 October 2018. [Google Scholar]
  11. Kankanala, J.; Kirby, K.A.; Liu, F.; Miller, L.; Nagy, E.; Wilson, D.J.; Parniak, M.A.; Sarafianos, S.G.; Wang, Z. Design, Synthesis, and Biological Evaluations of Hydroxypyridonecarboxylic Acids as Inhibitors of HIV Reverse Transcriptase Associated RNase H. J. Med. Chem. 2016, 59, 5051–5062. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  12. Kawasuji, T.; Johns, B.A.; Yoshida, H.; Taishi, T.; Taoda, Y.; Murai, H.; Kiyama, R.; Fuji, M.; Yoshinaga, T.; Seki, T.; et al. Carbamoyl Pyridone HIV-1 Integrase Inhibitors. 1. Molecular Design and Establishment of an Advanced Two-Metal Binding Pharmacophore. J. Med. Chem. 2012, 55, 8735–8744. [Google Scholar] [CrossRef] [PubMed]
  13. Rostami, M.; Sirous, H.; Zabihollahi, R.; Aghasadeghi, M.R.; Sadat, S.M.; Namazi, R.; Saghaie, L.; Memarian, H.R.; Fassihi, A. Design, Synthesis and Anti-HIV-1 Evaluation of a Series of 5-Hydroxypyridine-4-One Derivatives as Possible Integrase Inhibitors. Med. Chem. Res. 2015, 24, 4113–4127. [Google Scholar] [CrossRef]
  14. Sayyed, S.K.; Quraishi, M.; Jobby, R.; Rameshkumar, N.; Kayalvizhi, N.; Krishnan, M.; Sonawane, T. A Computational Overview of Integrase Strand Transfer Inhibitors (INSTIs) against Emerging and Evolving Drug-Resistant HIV-1 Integrase Mutants. Arch. Microbiol. 2023, 205, 142. [Google Scholar] [CrossRef] [PubMed]
  15. Sirous, H.; Fassihi, A.; Brogi, S.; Campiani, G.; Christ, F.; Debyser, Z.; Gemma, S.; Butini, S.; Chemi, G.; Grillo, A.; et al. Synthesis, Molecular Modelling and Biological Studies of 3-Hydroxypyrane-4-One and 3-Hydroxy-Pyridine-4-One Derivatives as HIV-1 Integrase Inhibitors. Med. Chem. 2019, 15, 755–770. [Google Scholar] [CrossRef] [PubMed]
  16. De Beer, J.; Petzer, J.P.; Lourens, A.C.U.; Petzer, A. Design, Synthesis and Evaluation of 3-Hydroxypyridin-4-Ones as Inhibitors of Catechol-O-Methyltransferase. Mol. Divers. 2021, 25, 753–762. [Google Scholar] [CrossRef] [PubMed]
  17. Senaweera, S.; Edwards, T.C.; Kankanala, J.; Wang, Y.; Sahani, R.L.; Xie, J.; Geraghty, R.J.; Wang, Z. Discovery of N-Benzyl Hydroxypyridone Carboxamides as a Novel and Potent Antiviral Chemotype against Human Cytomegalovirus (HCMV). Acta Pharm. Sin. B 2022, 12, 1671–1684. [Google Scholar] [CrossRef] [PubMed]
  18. Fujishita, T.; Mikamiyama, M.; Kawai, M.; Akiyama, T. Substituted 3-Hydroxy-4-Pyridone Derivative. U.S. Patent US8835461, 16 September 2014. [Google Scholar]
  19. Ma, Y.; Hider, R.C. Novel Synthetic Approach to Fluoro- and Amido-Disubstituted 3-Hydroxypyridin-4-Ones. J. Fluor. Chem. 2015, 173, 29–34. [Google Scholar] [CrossRef]
  20. Obydennov, D.L.; Viktorova, V.V.; Chernyshova, E.V.; Shirinkin, A.S.; Usachev, S.A.; Sosnovskikh, V.Y. Direct Synthesis of 5-Acyl-3-Oxy-4-Pyrones Based On Acid-Catalyzed Acylation of Enaminodiones with Acylbenzotriazoles via Soft Enolization. Synthesis 2020, 52, 2267–2276. [Google Scholar] [CrossRef]
  21. Obydennov, D.L.; Khammatova, L.R.; Steben’kov, V.D.; Sosnovskikh, V.Y. Synthesis of novel polycarbonyl Schiff bases by ring-opening reaction of ethyl 5-acyl-4-pyrone-2-carboxylates with primary mono- and diamines. RSC Advances 2019, 9, 40072–40083. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  22. Obydennov, D.L.; Simbirtseva, A.E.; Piksin, S.E.; Sosnovskikh, V.Y. 2,6-Dicyano-4-pyrone as a Novel and Multifarious Building Block for the Synthesis of 2,6-Bis(hetaryl)-4-pyrones and 2,6-Bis(hetaryl)-4-pyridinols. ACS Omega 2020, 5, 33406–33420. [Google Scholar] [CrossRef] [PubMed]
  23. Usachev, S.A.; Nigamatova, D.I.; Mysik, D.K.; Naumov, N.A.; Obydennov, D.L.; Sosnovskikh, V.Y. 2-Aryl-6-Polyfluoroalkyl-4-Pyrones as Promising RF-Building-Blocks: Synthesis and Application for Construction of Fluorinated Azaheterocycles. Molecules 2021, 26, 4415. [Google Scholar] [CrossRef] [PubMed]
Molbank 2023 m1668 g001 550
Figure 1. Some important 3-hydroxy-4-pyridones.
Figure 1. Some important 3-hydroxy-4-pyridones.
Molbank 2023 m1668 g001
Molbank 2023 m1668 sch001 550
Scheme 1. Synthesis of pyridones 2 and 3,4-HPOs 3.
Scheme 1. Synthesis of pyridones 2 and 3,4-HPOs 3.
Molbank 2023 m1668 sch001
Table
Table 1. Yields of products 2 and 3.
Table 1. Yields of products 2 and 3.
EntryCompounds 1–3R1R2Yield of 2Yield of 3
1aPhfuran-2-yl6889
2b4-ClC6H4furan-2-yl7292
3c4-ClC6H4Ph6192
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

Steparuk, E.V.; Obydennov, D.L.; Sosnovskikh, V.Y. Synthesis of 5-Aroyl-2-aryl-3-hydroxypyridin-4(1H)-ones. Molbank 2023, 2023, M1668. https://doi.org/10.3390/M1668

AMA Style

Steparuk EV, Obydennov DL, Sosnovskikh VY. Synthesis of 5-Aroyl-2-aryl-3-hydroxypyridin-4(1H)-ones. Molbank. 2023; 2023(2):M1668. https://doi.org/10.3390/M1668

Chicago/Turabian Style

Steparuk, Elena V., Dmitrii L. Obydennov, and Vyacheslav Y. Sosnovskikh. 2023. "Synthesis of 5-Aroyl-2-aryl-3-hydroxypyridin-4(1H)-ones" Molbank 2023, no. 2: M1668. https://doi.org/10.3390/M1668

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