Theoretical and experimental investigation of the polyeletrophilic β-enamino diketone: straightforward and highly regioselective synthesis of 1,4,5-trisubstituted pyrazoles and pyrazolo[3,4-d]pyridazinones

Abstract

A highly efficient regioselective synthesis of 1,4,5-trisubstituted pyrazoles and pyrazolo[3,4-d]pyridazinones from enamino diketone along with a theoretical and experimental study of the chemical reactivity enamino diketone.

The Wonderful World of β‐Enamino Diketones Chemistry

“…The symmetric β‐enamino diketone 3 was synthesized, and the reactivity of the five electrophilic centers toward nitrogen nucleophiles was studied (Scheme 10). [ 43 ] When aniline was treated with 3 , the β‐enaminone 23 was obtained in Z‐ configuration, which allowed a hydrogen bond with the carbonyl carbon. [ 44 ] When hydrazines were used, the reaction was highly sensitive to both temperature and time; for example, in refluxing EtOH, a mixture of the targeted pyrazole 24 , its hydrazone 25 , and pyridazinone 26 derivatives were obtained.…”

“…Pyridazinones 26 were selectively prepared upon the addition of AcOH in refluxing EtOH for 12 h, at yields of 69–89 % (Scheme 10). [ 43 ]…”

“…As shown in earlier sections of this review, the pyridazinone‐pyrazole hybrid 26 was obtained as a by‐product when attempts were made to selectively prepare the corresponding carboxyethyl pyrazole. [ 43 ] The authors in that study were able to synthesize 26 in a one‐pot methodology, by reacting β‐enamino diketone 3 with 2 equivalents of arylhydrazine, which furnished 26 at moderate yields (53–65 %, Scheme 22).…”

“…Using a similar approach, but aiming for the synthesis of novel NAH derivatives, pyrazole 19 (in which R = CO 2 Et) was converted into the pyridazinones 66 (hydrazine hydrate, AcOH, reflux for 12 h) at yields of 69–87 %, which were later reacted with hydrazine hydrate in refluxing EtOH/MeCN for 24 h to yield hydrazides 67 at yields of 92–95 %. [ 43,77 ] The NAH derivatives 68 were finally achieved by reaction with benzaldehydes, to yield the products at 94–98 % (Scheme 24).…”

Divergent and Regioselective Synthesis of (Trifluoromethyl/carboxyethyl)benzo[4,5]imidazo[1,2‐a]pyrimidines from β‐Enamino Diketones

“…[ 18 ] To overcome the selectivity issue, β‐enamino diketones (see Scheme 1) have emerged as suitable starting materials for the synthesis of several heterocyclic scaffolds, due to presenting high selectivity in most of the cyclocondensation reactions performed. [ 19–21 ] Even though the chemistry of carboxyethyl β‐enamino diketones 1 has been explored, [ 22–29 ] trifluoromethyl 2 ones have been far less used in heterocyclic synthesis. [ 21,30–34 ] Thus, this work aims to study the cyclocondensation reaction between β‐enamino diketones ( CCC building blocks) and 2‐aminobenzimidazole ( NCN ‐dinucleophile), observing the regioselectivity of the obtained products.…”