Reactivity of antipyrine and haloantipyrines in Pd-catalyzed C H bond arylations

Abstract

We reported herein the Pd-catalyzed direct arylation of antipyrine using Pd(OAc) 2 as catalyst associated with KOAc as inexpensive base. In most cases, diethyl carbonate was used a sustainable solvent. The reaction tolerated a wide range of functional groups on the aryl bromide partners (e.g., nitrile, nitro, chloro, fluoro, formyl, acetyl, propionyl, benzoyl, ester, methyl, methoxy). In addition, some nitrogen-containing heteroaryl bromides were also efficiently coupled with antipyrine. We also demonstrated that in contrast to 4-bromoantipyrine, 4-iodoantipyrine could be employed as an efficient heteroaryl source in Pd-catalyzed C-H bond arylation of 5-membered ring heteroarenes.

Polyfluoroalkylated antipyrines in Pd-catalyzed transformations

“…The literature data analysis has shown that antipyrine and its non-uorinated analogs readily undergo the Pd-catalyzed direct arylation with the different arylhalogenides. 46,47 However, our numerous efforts to involve 5-triuoromethyl-antipyrine 1a into the direct arylation with arylhalogenides were ineffective, despite the use of various palladium catalysts {Pd(OAc) 2 , Pd 2 (dba) 3 }, bases (AcOK, K 2 CO 3 , Cs 2 CO 3 , K 3 PO 4 ), ligands (ligand-free, XPhos), solvents (CO(OEt) 2 , EtOH-H 2 O, DMA, toluene, 1,4-dioxane), temperature modes (100-160 C) and ratios of reagents in these reactions. The extended experiments are presented in Table S1 (please see, ESI †).…”

“…56 It explains the weak reactivity of compound 1a in the reactions of electrophile arylation comparing to the non-uorinated antipyrine in analogous transformations. 46,47 Then, we investigated the possibility of modifying polyuoroalkyl-antipyrines 1 at the center C4 in the Pdcatalyzed Suzuki and Sonogashira cross-coupling reactions. At rst, 4-bromo-5-polyuoroalkyl-antipyrines 4a-d and 4-iodo-5-polyuoroalkyl-antipyrines 5a, b were synthesized by the treatment of the initial heterocycles 1a-d with N-bromo-or N-iodosuccinimide (NXS) (Scheme 2).…”

“… 46 Reactivity of para -, meta - and ortho -substituted arylbromides has been investigated in the reaction with antipyrine by Pd(OAc) 2 and K 2 CO 3 . 47 A method has been suggested for the direct introduction of arylthiol and arylselenium residues into antipyrines by di- p -tolyldisulfide or diphenyldiselenide using catalyst system AgOTf/AgOAc. 48 An effective way of carrying out the cross-coupling reaction of 4-iodo-antipyrine with arylboronic acids has been found on Pd/nanoglobular carbon support.…”

Copper-Mediated Decarboxylative Coupling of 3-Indoleacetic Acids with Pyrazolones

“…In the past few decades, the direct C–H functionalization reactions featured with atom- and step-economy have become important tools for modifying organic compounds . Until now, there were some examples about direct C–H functionalization of pyrazolones including arylation, alkenylation, alkynylation, acylation, and thiolation . However, these methods had some disadvantages, such as using precious metals or unavailable starting materials, utilizing strong oxidant, and needing complex reaction conditions.…”