Catalyst-free Biginelli-type synthesis of new functionalized 4,7-dihydropyrazolo[1,5-a]pyrimidines

Abstract

New pyrazolopyrimidines and pyrazoloquinazolines were synthesized through the uncatalyzed reaction of 5-amino-3-arylpyrazole-4-carbonitriles with aldehydes and 1,3-dicarbonyl compounds.

A microdroplet-accelerated Biginelli reaction: mechanisms and separation of isomers using IMS-MS

“…Based on previous reports, [13][14][15] we expected that an increase in the temperature of the electrosprayed droplets would alter the ratio of products and intermediates. To probe this effect, we carried out the in-droplet reaction while varying the temperature of the electrospray emitter from 5 C to 65 C (Fig.…”

“…7 Furthermore, the reaction has enabled the synthesis of both racemic 6 and enantioenriched [8][9][10][11] molecules that exhibit signicant anti-cancer, anti-microbial, anti-inammatory, antiviral, and calcium-channel inhibitory properties. 6 While the Biginelli reaction proceeds with a wide range of catalysts, including Lewis acids, Brønsted acids, hydrogen-bond donors, and even transition metals, 12 attempts to realize a catalyst-free Biginelli reaction [13][14][15] have been met with mixed success. 16 The development of a mild, room temperature protocol for the production of dihydropyrimidinones remains an important goal in the eld.…”

Revisiting the Structure and Chemistry of 3(5)-Substituted Pyrazoles

“…Aside from the exocyclic amino group, another nucleophilic element from the ring system is needed to promote ring closure. In this step, either one ring nitrogen can participate, leading to structures such as pyrazolo [1,5-a] The duality in reactivity offered by the 3(5)-aminopyrazole frame towards 1,3-dielectrophilic agents demands a close attention to the synthetic methodologies in pursuit of chemoselectivity, as for example C4/NH2 cyclization products (pathway 2 of Scheme 12) are favored upon introduction of substituents at N1 [122] and the opposite effect occurs upon substitution at position 4 carbon, favoring the formation of N(H)1/NH2 products (pathway 1 of Scheme 12) [117]. However, C4 substituents must be considered attentively in the synthesis of bicyclic fused pyrazoloazines from 3(5)-aminopyrazoles since activation promoted by electrophilic or nucleophilic substituents may assist intramolecular cyclization through pathway 2 (Scheme 12).…”

Visible Light-Mediated C(sp2)–H Selenylation of Amino Pyrazole and Amino Uracils in the Presence of Rose Bengal as an Organophotocatalyst

“…Finally, taking que from a literature report, we tried to utilize some of our synthesized selenoethers of aminopyrazoles for the preparation of dihydropyrazolo­[1,5- a ]­pyrimidines by a three-component reaction. For this, we took a mixture of ethyl acetoacetate (0.2 mmol) and benzaldehyde (0.21 mmol) in 1.0 mL of dimethylformamide (DMF), and the resultant mixture was kept at 100 °C under constant stirring.…”