Direct Preparation of N-Substituted Pyrazoles from Primary Aliphatic or Aromatic Amines

Abstract

Despite a large number of synthesis procedures for pyrazoles known today, those directly employing primary amines as substrates are rare. Herein, we report an original method for the preparation of N -alkyl and N -aryl pyrazoles from primary aliphatic or aromatic amines as a limiting reagent of the reaction. The protocol utilizes no inorganic reagents and requires a short reaction time, mild conditions, and the use of structurally simple and commercially available starting reagents. During this study, pyrazoles containing a wide variety of N -substituents were obtained using the same procedure for both aliphatic and aromatic amines.

Emerging trends in the sustainable synthesis of N–N bond bearing organic scaffolds

“…The product then reacts with the aminating reagent to form C , lowering the pyrazole yield (Scheme 34). 67…”

“…The product then reacts with the aminating reagent to form C, lowering the pyrazole yield (Scheme 34). 67 4.5. Formation of an N-N bondindazole derivatives 4.5.1 Intramolecular oxidation.…”

Iodine/DMSO-mediated one-pot access towards 1-aryl-2-(pyrazol-5-yl)ethane-1,2-diones via a domino reaction from functionalized pent-2-ene-1,5-diones

“…15 Treatment of a primary amine with a 1,3-dicarbonyl compound in the presence of an electrophilic reagent renders N -substituted pyrazoles. 16 The simplest protocol for pyrazole synthesis involves the use of a Michael acceptor as a precursor molecule. 17,18 Precursors such as ketenedithioacetals 19,20 a with hydrazine provide pyrazoles in good to excellent yields.…”

Copper-Promoted Aerobic Oxidative [3+2] Cycloaddition Reactions of N,N-Disubstituted Hydrazines with Alkynoates: Access to Substituted Pyrazoles

“…Due to the promising biological activities of the pyrazoles, developing an efficient synthetic protocol for these compounds remains attractive to organic and medicinal chemists. , Representative examples for these synthetic approaches have been reported previously (Scheme ): (i) [3+2] annulation of various 1,3-dielectrophiles/Michael acceptors (including 1,3-diketones, α,β-unsaturated carbonyl compounds, enaminones, ketene dithioacetals, 1,3-conjugated enynes, 1,3-diols, cross-conjugated enynones, and β-ketonitrile) with hydrazines through condensation, (ii) employing readily available aryldiazonium salts, diazo compounds, azide compounds, and arylazosulfones as N–N or NN precursors to construct pyrazoles through intermolecular annulation, and (iii) synthesis of pyrazoles from hydrazones and tetrazoles through intramolecular or intermolecular [3+2] or [4+1] annulation . In addition, [2+2+1] or [3+1+1] multicomponent/multimolecular annulation strategies have also been explored for the preparation of pyrazoles …”