Synthesis of 3-substituted 1-phenyl-1H-pyrazole-4-carbaldehydes and the corresponding ethanones by Pd-catalysed cross-coupling reactions

Abstract

An efficient synthetic route to construct ortho-substituted 1-phenyl-1H-pyrazole-4-carboxaldehydes and the corresponding ethanones starting from 1-phenyl-1H-pyrazol-3-ol is described. Carbon-carbon bond-forming Pd-catalysed cross-coupling reactions were applied for the functionalisation of the intermediate pyrazole triflates. Detailed NMR spectroscopic investigations were undertaken with all obtained products.

Convenient Synthesis of Pyrazolo[4′,3′:5,6]pyrano[4,3-c][1,2]oxazoles via Intramolecular Nitrile Oxide Cycloaddition

“…As the cinnamyloxy group turned out to be sensitive towards Vilsmeier-Haack reaction conditions, the O-alkylation formylation sequence of compound 1a successfully applied to the synthesis of 3-allyloxypyrazole-4-carbaldehydes 3a-d was reorganized. In short, first, the hydroxy group of pyrazol-3ol (1a) was transformed to a benzyloxy group; then, the obtained 3-benzyloxypyrazole was formylated under the Vilsmeier-Haack reaction conditions, and the protecting OBn group was cleaved by TFA to give 3-hydroxy-1H-pyrazole-4-carbaldehyde 7 [35]. The latter compound was subjected to an alkylation reaction with cinnamyl chloride and the appropriate 3-cinnamyloxy-1H-pyrazole-4-carbaldehyde (8) was obtained in very good (82%) yield.…”

“…c][1,2]oxazole trans-10 was obtained with a fair (62%) yield. Haack reaction conditions, and the protecting OBn group was cleaved by TFA to give 3-hydroxy-1H-pyrazole-4-carbaldehyde 7[35]. The latter compound was subjected to an alkylation reaction with cinnamyl chloride and the appropriate 3-cinnamyloxy-1H-pyrazole-4-carbaldehyde (8) was obtained in very good (82%) yield.…”

Synthesis of 2H-furo[2,3-c]pyrazole ring systems through silver(I) ion-mediated ring-closure reaction

“…As a starting material, we used 1-phenyl-1 H -pyrazol-3-ol ( 1 ), which is readily accessible from the oxidation of 1-phenyl-3-pyrazolidinone [ 25 – 26 ]. Recently, we used this scaffold to obtain the 2 H- pyrazolo[4,3- c ]pyridine [ 27 – 28 ], pyrazolo[4,3- f ][1,2,3]triazolo[5,1- c ][1,4]oxazepine [ 29 ] and pyrazolo[4’,3’:3,4]pyrido[1,2- a ]benzimidazole [ 30 ] ring systems as well as to prepare building blocks for the construction of optoelectronic materials and fluorescent organic nanoparticles [ 31 – 34 ].…”

Ring-closing metathesis as a key step to construct 2,6-dihydropyrano[2,3-c]pyrazole ring system

“…31 To introduce a formyl group at the 4-position of the pyrazole ring, we employed a previously reported procedure based on the Vilsmeier-Haack reaction. 32 Heating compound 2a with POCl3 in N,N-dimethylformamide (DMF) at 60 °C resulted in the formation of the desired pyrazole-4-carbaldehyde 3a in 91% yield (Scheme 1). The characteristic signals of aldehyde 3a in the 1 H NMR spectrum were the singlets at 8.25 (5-H) and 9.88 ppm (CHO).…”