Abstract
The title compound was obtained by the reaction of tosylated glycerol carbonate with 1-phenyl-1H-pyrazol-3-ol in a good 71% yield. Detailed spectroscopic data (1H-NMR, 13C-NMR, 15N-NMR, IR, MS) are presented.
1-Phenylpyrazole derivatives are known to have a broad spectrum of biological activities [1,2,3,4,5,6]. Recently, 1-phenyl-1H-pyrazol-3-ol was used as a versatile synthon for the preparation of various (het)aryl- and carbo-functionally substituted pyrazole derivatives employing Pd-catalyzed cross-coupling reactions [7,8]. In the present work, functionalization of 1-phenyl-1H-pyrazol-3-ol with tosylated glycerol 1,2-carbonate (TGC) was investigated. TGC is relatively new and efficient reagent, which have found application as an initiator of cationic ring-opening polymerization [9] and as a versatile bis-electrophile to access new functionalized glycidol derivatives [10,11]. TGC can be easily obtained by tosylation of glycerol carbonate (4-(hydroxymethyl)-1,3-dioxan-2-one) [10], the latter is an industrial product of glycerol valorization [12].
It is known that TGC reacts with 4-methoxyphenol in DMF in the presence of K2CO3 to afford O-alkylated product, 4-(3-methoxyphenoxy)methyl-1,3-dioxolan-2-one, in only 41% yield [11], while 55% of the arylsulfanyl analogue is obtained in analogous conditions from m-methoxythiophenol [10]. The reaction of 1-phenyl-1H-pyrazol-3-ol 1 with TGC 2 was carried out in DMF in the presence of K2CO3 and gave chemoselectively 4-{[(1-phenyl-1H-pyrazol-3-yl)oxy]methyl}-1,3-dioxolan-2-one 3 in 71% isolated yield. The structure of compound 3 was confirmed by its spectroscopic data (1H NMR, 13C and 15N NMR, IR, MS) as well as by elemental analysis.
Scheme 1.
Synthesis of the title compound 3.
Scheme 1.
Synthesis of the title compound 3.
Experimental
The melting point was determined on a Reichert–Kofler hot-stage microscope and is uncorrected. Mass spectrum: Shimadzu QP 1000 instrument (EI, 70 eV). IR spectrum: Perkin-Elmer FTIR Spectrum 1605 spectrophotometer (KBr-disc). The elemental analysis was performed at the Microanalytical Laboratory, University of Vienna. NMR spectra were recorded from CDCl3 solutions on a Bruker Avance 500 instrument with a ‘directly’ detecting broadband observe probe (BBFO) at 298 K (500.13 MHz for 1H, 125.76 MHz for 13C, 50.68 MHz for 15N). 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). The 15N-NMR spectrum (gradient-selected 15N, 1H-HMBC) was referenced against external nitromethane.
4-{[(1-Phenyl-1H-pyrazol-3-yl)oxy]methyl}-1,3-dioxolan-2-one (3)
To a solution of 1-phenyl-1H-pyrazol-3-ol (1) (1.6 g, 1.0 mmol) in DMF (15 mL) K2CO3 (2.76 g, 2.0 mmol) and tosylate (2) (2.72 g, 1.0 mmol) were added. The mixture was stirred at r.t. for 48 h (TLC control, eluent: ethyl acetate–n-hexane, 1:2; Rf 0.25). Then, 50 mL of water were added and the mixture was extracted with 3 × 60 mL of ethyl acetate. The organic layers were combined, washed with brine, dried over anhydrous Na2SO4 and filtered. The solvent was evaporated under reduced pressure and the residue was purified by column chromatography (silica gel, eluent: ethyl acetate–n-hexane, 1:2) to give pure 3 as yellowish crystals, m.p. 95–96 °C. Yield: 1.86 g (71%).
IR (KBr) ν (cm−1): 1786 (C=O), 1600, 1546, 1475, 1396, 1315, 1186, 1094, 989, 774, 751, 682.
MS (EI, 70 eV): (m/z, %) 260 (M+, 29), 160 (93), 77 (100), 51 (35), 43 (20).
1H-NMR (CDCl3): (ppm) 4.48 (dd, 1H, 2J(H1A,H2A) = 11.9 Hz, 3J(H1A,HB) = 4.0 Hz, H1A), 4.51 (dd, 1H, 2J(H1C,H2C) = 8.5 Hz, 3J(HB,H1C) = 6.1 Hz, H1C), 4.54 (dd, 1H, 2J(H1A,H2A) = 11.9 Hz, 3J(H2A,HB) = 3.9 Hz, H2A), 4.60 (t, 1H, 2J(H1C,H2C) = 8.5 Hz, 3J(HB,H2C) = 8.5 Hz, H2C), 5.07 (dddd, 1H, 3J(HB,H2C) = 8.5 Hz, 3J(HB,H1C) = 6.1 Hz, 3J(H1A,HB) = 4.0 Hz, 3J(H2A,HB) = 3.9 Hz, HB), 5.92 (d, 1H, 3J(4-H,5-H) = 2.6 Hz, 4-H), 7.22 (m, 1H, Ph 4-H), 7.41 (m, 2H, Ph 3,5-H), 7.57 (m, 2H, Ph 2,6-H), 7.74 (d, 1H, 3J(4-H,5-H) = 2.6 Hz, 5-H).
13C-NMR (CDCl3): δ (ppm) 66.1 (CC), 67.4 (CA), 74.2 (CB), 93.9 (C-4, 1J(C-4,4-H) = 180.6 Hz, 2J(C-4,5-H) = 8.1 Hz), 117.8 (Ph C-2,6), 125.6 (Ph C-4), 128.2 (C-5, 1J(C-5,5-H) = 187.0 Hz, 2J(C-5,4-H) = 8.3 Hz), 129.4 (Ph C-3,5), 139.8 (Ph C-1), 154.7 (C=O), 163.3 (C-3, 2J(C-3,4-H) = 2.2 Hz, 3J(C-3,5-H) = 10.5 Hz, 3J(C-3,OCH2) = 2.2 Hz).
15N-NMR (CDCl3): δ (ppm) −185.5 (N-1), N-2 was not found.
Anal. Calcd for C13H12N2O4: C, 60.00%; H, 4.65%; N, 10.76%. Found: C, 59.78%; H, 4.50%; N, 10.74%.
Supplementary materials
Supplementary File 1Supplementary File 2Supplementary File 3References and Notes
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