Synthesis of pyrazoles and pyrazolones from 1,3- and 1,4-diketones of the adamantane series

Abstract

Various pyrazole and dihydropyrazolones containing an adamantane fragment were synthesized from adamantyl-substituted 1,3-and 1,4-diketones, ethyl 4-(1-adamantyl)-2-R-4-oxobutanoates (R = CN, Ac), and ethyl 2-(1-adamantylcarbonyl)-4-oxo-4-phenylbutanoate.Methods of synthesis and chemical properties of 1,2-diazoles and their derivatives have been well documented [1][2][3][4][5]. Compounds of this series attract interest as pyrazolone dyes and drugs. Examples of the latter are Phenazone, Aminophenazone, and Metamizole sodium. However, there are only a few publications on the synthesis of 1,2-diazoles and pyrazolones having an adamantane fragment. N-Phenyl-3-adamantyl-and N-phenyl-3-adamantylmethylpyrazolones were synthesized for the first time from the corresponding oxo esters [6,7]. Later on, reactions of dioxo esters with hydrazine and phenylhydrazine were reported [8,9]. It was found that, depending on the initial ester structure, either adamantanecarboxylic acid hydrazide or 3-(1-adamantylmethyl)-4,5-dihydro-1H-pyrazol-5-one and 3-(1-adamantylmethyl)-1-phenyl-4,5-dihydro-1H-pyrazol-5-one were formed. The reaction of ethyl 3-(1-adamantyl)-2-(1-adamantylcarbonyl)-3-oxopropanoate with hydrazine gave ethyl 3,5-bis(1-adamantyl)-1H-pyrazole-4-carboxylate [8].In this paper we describe the synthesis of heterocyclic compounds on the basis of 1,3-and 1,4-diketones of the adamantane series, as well as from ethyl 4-(1-adamantyl)-2-R-4-oxobutanoates [R = CN, Ac] and ethyl 2-(1-adamantylcarbonyl)-4-oxo-4-phenylbutanoate. Known procedures for the preparation of 1,3-diketones are based on the Claisen condensation, i.e., acylation of ketones with esters in the presence of strong bases such as metallic sodium, sodium hydride, sodium amide, and others [10], reaction of ketones with carboxylic acid anhydrides in the presence of boron trifluoride-ether complex [11,12], acylation of ketones (preliminarily treated with lithium diisopropylamide and chlorotrimethylsilane) with carboxylic acid chlorides in the presence of Lewis acids (TiCl 4 , SnCl 4 , ZnCl 2 ) [13], and acylation of ketones with carboxylic acid anhydrides in the presence of ZnCl 2 and SiCl 4 [14]. We synthesized adamantyl-substituted 1,3-diketones I and II by reaction of 1-adamantyl methyl ketone with carboxylic acid anhydrides catalyzed by boron trifluoride-ether complex (Scheme 1). However, we failed to obtain the corresponding 1,3-diketone from adamantane-1-carboxylic anhydride under analogous conditions. We also tried to perform acylation of 1-adamantyl methyl ketone with carboxylic acid anhydrides in the presence of ZnCl 2 and SiCl 4 in boiling methylene chloride, but the yields were lower than in the reactions catalyzed by BF 3 · Et 2 O.Ethyl 4-(1-adamantyl)-2-R-4-oxobutanoates III and IV (R= CN, Ac) were obtained by reactions of (1-ada-

An Extremely Bulky Tris(pyrazolyl)methanide: A Tridentate Ligand for the Synthesis of Heteroleptic Magnesium(II) and Ytterbium(II) Alkyl, Hydride, and Iodide Complexes

“…The 3-pyrazolyl substituent chosen for these investigations was the adamantyl group, as it is both rigid and has previously been incorporated into one of the most sterically hindered tris(pyrazolyl)borate ligands. [8] The tris(pyrazolyl)methane proligand, HC(3-Ad-5-Mepz) 3 [1, 3-Ad-5-Mepz = 3-(1-adamantyl)-5-methylpyrazolyl], was synthesized in moderate yield by reaction of the known pyrazole 3-Ad-5-MepzH [9] with chloroform under phase-transfer conditions (Scheme 1). This synthetic route was similar to those reported for less bulky tris(pyrazolyl)methanes.…”

“…3-(1-Adamantyl)-5-methyl-1H-pyrazole was synthesized by a literature procedure. [9] All other reagents were used as received.…”

Boron Difluoride Complex Dyes: Synthesis and Photophysical Properties

“…These new type of pyrazoline-1,3-dione based-complexes demonstrated photophysical properties that are extremely reliant to the solvent polarity and aggregation conditions. The molecular assembly of the crystal structure resulted in physically powerful charge transfer characterized with an extended excited state lifetime [53]. Reacting those 2-formyl ketone-based boron difluoride complexes with organometallic reagents has been reported to comprise an efficient preparation of 2-alkylidene ketones.…”