4-Bromo-3-methoxy-1-phenyl-1H-pyrazole

Abstract

Abstract:The title compound was prepared by treatment of 4-bromo-1-phenyl-1H-pyrazol-3-ol with sodium hydride/methyl iodide in good yield. Detailed spectroscopic data Keywords: pyrazole; 1H-pyrazol-3-ol; methylation; NMR Bromo(hetero)arenes are valuable starting materials for further functionalization, for instance via metalation reactions (halogen-metal exchange) [1] or transition-metal-catalyzed cross coupling reactions [2][3][4]. With an OH-or OR function in ortho-position to the bromo atom, such (hetero)arenes can be considered as potential precursors for condensed systems involving a ring-oxygen atom (condensed furans, pyranes) [5]. However, for some of the above mentioned functionalization reactions, free hydroxy groups are unfavourable, for instance in metalation reactions [6] or in Suzukitype cross couplings [7]. In such cases, the OH group has to be masked. In this regard, a possible option is to transform the OH into the very stable OMe group. The O-Me bond then can be cleaved in the course of the cyclization reaction into the O-containing ring system employing, for instance, pyridine hydrochloride as the reagent [8].We here present the synthesis of 4-bromo-3-methoxy-1-phenyl-1H-pyrazole (2), with a protected OH-group in position 3 and a bromo substituent in position 4 of the pyrazole nucleus, which can be considered as a desirable starting compound for further transformation. The preparation of 2 was carried out according to a standard method for O-alkylation, namely by reaction of 4-bromo-1-phenyl-1H-pyrazol-3-ol (1) [9] with methyl iodide in alkaline medium, which afforded the title compound in 88% yield after column chromatograpy (Scheme 1). OPEN ACCESS

On the Tautomerism of N-Substituted Pyrazolones: 1,2-Dihydro-3H-pyrazol-3-ones versus 1H-Pyrazol-3-ols

“…Again, all these species clearly exist as pyrazol-3-ols in CDCl 3 , as well as in DMSO- d 6 solution based on the 13 C- and 15 N-NMR chemical shift considerations outlined above. Regarding the 4-bromo derivative 5 a “fixed” 3-methoxy derivative 9 has been described already by us, whose data resemble the “free” 1 H -pyrazol-3-ol 5 [ 26 ]. The same is the case for the pair 7 and 10 ( Figure 6 ).…”

“…The synthesis and the 1 H and 13 C-NMR spectra of 9 are described in lit. [ 26 ]. 15 N-NMR (CDCl 3 ): δ 194.7 (pyrazole N-1), 262.6 (pyrazole N-2).…”

3-(tert-Butyl)-N-(4-methoxybenzyl)-1-methyl-1H-pyrazol-5-amine

“…For instance, the antipsychotic agent CDPPB [11], the nonsteroidal anti-inflammatory drugs Lonazolac and Epirizole [12], the histamine H2-receptor agonist Betazole [13], among others marketed drugs have this structural motif of pyrazole, as depicted in Figure 1. The interesting structural features of pyrazoles as well as their diverse applications in medicinal chemistry, drug discovery, and materials science have stimulated chemists to develop novel and efficient synthetic protocols for obtaining structurally diverse pyrazoles [14][15][16][17][18][19].…”

“…Found: C, 70.07; H, 8.36; N, 15.51. MS (EI, 70 eV) m/z (%): 273 (47) [M+], 121 (100), 91(19), 77(25), 67(15).…”

(2E)-3-(3-Methoxy-1-phenyl-1H-pyrazol-4-yl)-2-propenal

“…As a starting material 4-bromo-3-methoxy-1-phenyl-1H-pyrazole (1) was used [14,15]. Palladiumcatalyzed cross coupling of 1 with acrolein diethyl acetal afforded (2E)-3-(3-methoxy-1-phenyl-1H-pyrazol-4-yl)-2-propenal (2).The structure of 2 was confirmed by its spectroscopic data ( 1 H NMR, 13 'directly' detecting broadband observe probe (BBFO) and was referenced against external nitromethane.…”