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Short Note

3-Methyl-1-phenyl-1H-pyrazol-5-yl 2-Bromo-3-furan-carboxylate

1
Department of Drug and Natural Product Synthesis, University of Vienna, Althanstrasse 14, A-1090 Vienna, Austria
2
Department of Chemistry, Capital Normal University, Xisanhuanbei Road 105, Beijing 100048, China
*
Author to whom correspondence should be addressed.
Molbank 2009, 2009(3), M603; https://doi.org/10.3390/M603
Submission received: 29 May 2009 / Accepted: 1 July 2009 / Published: 3 July 2009

Abstract

:
The reaction of 3-methyl-1-phenyl-2-pyrazolin-5-one and 2-bromo-3-furoyl chloride in the presence of Ca(OH)2 in 1,4-dioxane gave the title compound. The latter was also obtained in much higher yield upon reaction of the starting materials in the system dichloromethane / triethylamine. Detailed spectroscopic data (1H NMR, 13C NMR, 15N NMR, IR, MS) are presented.

In a series of papers we recently described a short and efficient approach to novel heterocyclic systems containing a pyrano[2,3-c]pyrazol-4(1H)-one substructure via reaction of 2-pyrazolin-5-ones 1 with o-haloheteroarenecarbonyl chlorides 2 under the conditions of the ‘Jensen’-reaction (calcium hydroxide, refluxing 1,4-dioxane) and subsequent cyclization of the thus obtained 4-aroylpyrazol-5-ols 3 into the target compounds 4 (Scheme 1) [1,2,3,4,5,6].
In the course of these investigations we were also interested in furo[3’,2’:5,6]pyrano[2,3-c]pyrazol-4(1H)-ones (4, Het = furane). The synthesis of a corresponding representative 4a (R1 = Ph, R3 = Me) should be carried out similarly as outlined in Scheme 1, i.e. by reaction of 3-methyl-1-phenyl-2-pyrazolin-5-one (1a) and 2-bromo-3-furoyl chloride (2a) under ‘Jensen’-conditions [7] followed by cyclization of the key intermediate 3a (Scheme 2).
However, the reaction of 1a and 2a in the presence of Ca(OH)2 in refluxing 1,4-dioxane did not afford the expected C-aroyl product 3a but resulted in a complex reaction mixture, from which the ester 5 was isolated as the main component. Compound 5 could be easily identified considering its characteristic spectral data. Thus, the 1H-NMR spectrum of 5 exhibits a singlet signal of pyrazole H-4 at δ 6.25 ppm, the corresponding pyrazole C-4 resonance (δ 95.8 ppm) shows a dublet structure in the 1H-coupled 13C NMR spectrum (1J = 181.7 Hz). Moreover, the carbonyl absorption at 1752 cm-1 in the IR spectrum is typical for an ester-carbonyl moiety and definitely rules out a diaryl ketone substructure with intramolecular hydrogen bond as present in 3a. For the C=O absorption in the latter a much smaller value (~ 1620 cm-1) for νC=O has to be expected [3].
Expectedly, reaction of 1a and 2a in dichloromethane in the presence of triethylamine according to ref. [8] afforded the title compound 5 as the sole product in high yields (82% after purification by column chromatography).

Experimental

Mass spectrum: Shimadzu QP 1000 instrument (EI, 70 eV). IR spectrum: Perkin-Elmer FTIR Spectrum 1000 instrument (KBr-disc). The elemental analysis was performed at the Microanalytical Laboratory, University of Vienna. 1H and 13C NMR spectra were recorded on a Varian UnityPlus 300 spectrometer at 28 °C (299.95 MHz for 1H, 75.43 MHz for 13C). The centre of the solvent signal was used as an internal standard which was related to TMS with δ = 7.26 ppm (1H in CDCl3), and δ = 77.0 ppm (13C in CDCl3). The digital resolutions were 0.2 Hz/data point in the 1H and 0.4 Hz/data point in the 1H-coupled 13C-NMR spectra (gated decoupling). 15N NMR spectra were obtained on a Bruker Avance 500 instrument (50.69 MHz for 15N) with a ‘directly’ detecting broadband observe probe and were referenced against external nitromethane. The reactants 1a and 2a are commercially available.

3-Methyl-1-phenyl-1H-pyrazol-5-yl 2-bromo-3-furancarboxylate (5)

(a) To a mixture of 3-methyl-1-phenyl-2-pyrazolin-5-one (1a) (87 mg, 0.5 mmol) and Ca(OH)2 (74 mg, 1 mmol) in 4 mL of dry 1,4-dioxane was slowly added a solution of 2-bromo-3-furoyl chloride (2a) (105 mg, 0.5 mmol) in 1,4-dioxane (1 mL) and the whole was heated to reflux for 3 h. After cooling to rt, 2N HCl (2 mL) was added and the mixture was stirred for 15 min before it was poured onto H2O (30 mL). The aqueous phase was extracted with EtOAc (4 × 20 mL), the combined organic phases were washed with H2O, dried (Na2SO4) and evaporated under reduced pressure. The residue was subjected to column chromatography (silica gel, eluent: petroleum ether – EtOAc, 5:1). The main component (least retarded fraction) turned out to be compound 5. Yield: 35 mg (20%) of a yellowish oil which slowly solidified on standing.
(b) A mixture of 1a (174 mg, 1 mmol), 2a (230 mg, 1 mmol) and triethylamine (1 mL) in CH2Cl2 (20 mL) was refluxed for 3 h. Then solid products were filtered off, the filtrate was concentrated under reduced pressure and the residue was purified by column chromatography (silica gel, eluent: petroleum ether – EtOAc, 5:1) to afford 283 mg (82%) of 5.
1H NMR (300 MHz, CDCl3): δ (ppm) 7.57 (m, 2H, Ph H-2/6), 7.48 (d, 3J = 2.2 Hz, 1H, furane H-5), 7.43 (m, 2H, Ph H-3/5), 7.32 (m, 1H, Ph H-4), 6.76 (d, 3J = 2.2 Hz, 1H, furane H-4), 6.25 (s, 1H, pyrazole H-4), 2.35 (s, 3H, Me).
13C NMR (75 MHz, CDCl3): δ (ppm) 156.9 (C=O), 149.1 (pyrazole C-3, 2J(C3,3-Me) = 6.7 Hz, 2J(C3, H4) = 4.1 Hz), 144.9 (furane C-5, 1J = 210.3 Hz, ²J(C5,H4) = 9.7 Hz), 143.8 (pyrazole C-5, 2J(C5,H4) = 4.7 Hz), 138.0 (Ph C-1), 131.6 (furane C-2, 3J(C2,H4) = 8.4 Hz, 3J(C2,H5) = 8.4 Hz), 129.0 (Ph C-3/5), 127.3 (Ph C-4), 123.5 (Ph C-2/6), 115.7 (furane C-3, 2J(C3,H4) = 3.0 Hz, 3J(C3,H5) = 5.8 Hz), 112.6 (furane C-4, 1J = 182.7 Hz, 2J(C4,H5) = 12.9 Hz), 95.8 (pyrazole C-4, 1J = 181.7 Hz, 3J(C4,3-Me) = 3.5 Hz), 14.5 (Me, 1J = 127.7 Hz).
15N NMR (50 MHz, CDCl3): δ (ppm) −183.6 (pyrazole N-1), −96.7 (pyrazole N-2).
IR (KBr) ν (cm−1): 1752 (C=O).
MS (m/z, %): 348 (M+, 4), 346 (M+, 4), 173 (100).
Elemental Analysis: Calculated for C15H11BrN2O3 (347.16): C, 51.90%; H, 3.19%; N, 8.07%. Found: C, 51.90%; H, 3.26%; N, 7.77%.

Supplementary materials

Supplementary File 1Supplementary File 2Supplementary File 3

Acknowledgements

Changbin Guo gratefully acknowledges a scholarship provided by the Eurasia-Pacific Uninet program.

References and Notes

  1. Eller, G.A.; Wimmer, V.; Haring, A.W.; Holzer, W. An Efficient Approach to Heterocyclic Analogues of Xanthone: A Short Synthesis of all possible Pyrido[5,6]pyrano[2,3-c]pyrazol-4(1H)-ones. Synthesis 2006, 24, 4219–4229. [Google Scholar] [CrossRef]
  2. Eller, G.A.; Haring, A.W.; Datterl, B.; Zwettler, M.; Holzer, W. Tri- and Tetracyclic Heteroaromatic Systems: Synthesis of Novel Benzo-, Benzothieno- and Thieno-Fused Pyrano[2,3-c]pyrazol-4(1H)-ones. Heterocycles 2007, 71, 87–104. [Google Scholar] [CrossRef]
  3. Eller, G.A.; Holzer, W. A Convenient Approach to Heterocyclic Building Blocks: Synthesis of Novel Ring Systems Containing a [5,6]Pyrano[2,3-c]pyrazol-4(1H)-one Moiety. Molecules 2007, 12, 60–73. [Google Scholar] [CrossRef] [PubMed]
  4. Eller, G.A.; Datterl, B.; Holzer, W. Pyrazolo[4’,3’:5,6]pyrano[2,3-b]quinoxalin-4(1H)-one: Synthesis and Characterization of a Novel Tetracyclic Ring System. J. Heterocycl. Chem. 2007, 44, 1139–1144. [Google Scholar] [CrossRef]
  5. Eller, G.A.; Wimmer, V.; Holzer, W. Synthesis of Novel Polycyclic Ring Systems Containing two Pyrano[2,3-c]pyrazol-4(1H)-one Moieties. Khim. Geterotsikl. Soedin. 2007, 1251–1255. [Google Scholar] (Chem. Heterocycl. Comp. 2007, 43, 1060–1064.).
  6. Eller, G.A.; Habicht, D.; Holzer, W. Synthesis of a Novel Pentacycle: 8-Methyl-10-phenylpyrazolo[4’,3’:5,6]pyrano[3,2-c][1,10]phenanthrolin-7(10H)-one. Khim. Geterotsikl. Soedin. 2008, 884–890. [Google Scholar] (Chem. Heterocycl. Comp. 2008, 44, 709–714.).
  7. Jensen, B.S. Synthesis of 1-phenyl-3-methyl-4-acyl-5-pyrazolones. Acta Chem. Scand. 1959, 13, 1668–1670. [Google Scholar] [CrossRef]
  8. Maruoka, H.; Yamagata, K.; Okabe, F.; Tomioka, Y. Synthesis of 1-Acyl-1,2-dihydro-3H-pyrazol-3-ones via Lewis Acid-Mediated Rearrangement of 3-Acyloxypyrazoles. J. Heterocycl. Chem. 2006, 43, 859–865. [Google Scholar] [CrossRef]
Scheme 1. Synthesis of annelated pyrano[2,3-c]pyrazol-4(1H)-ones 4.
Scheme 1. Synthesis of annelated pyrano[2,3-c]pyrazol-4(1H)-ones 4.
Molbank 2009 m603 sch001
Scheme 2. Reaction of 1a and 2a under ‘Jensen’-conditions.
Scheme 2. Reaction of 1a and 2a under ‘Jensen’-conditions.
Molbank 2009 m603 sch002

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MDPI and ACS Style

Holzer, W.; Guo, C.; Schalle, K. 3-Methyl-1-phenyl-1H-pyrazol-5-yl 2-Bromo-3-furan-carboxylate. Molbank 2009, 2009, M603. https://doi.org/10.3390/M603

AMA Style

Holzer W, Guo C, Schalle K. 3-Methyl-1-phenyl-1H-pyrazol-5-yl 2-Bromo-3-furan-carboxylate. Molbank. 2009; 2009(3):M603. https://doi.org/10.3390/M603

Chicago/Turabian Style

Holzer, Wolfgang, Changbin Guo, and Karin Schalle. 2009. "3-Methyl-1-phenyl-1H-pyrazol-5-yl 2-Bromo-3-furan-carboxylate" Molbank 2009, no. 3: M603. https://doi.org/10.3390/M603

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