Reactivity of Cross-Conjugated Enynones in Cyclocondensations with Hydrazines: Synthesis of Pyrazoles and Pyrazolines

Abstract

The cyclocondensation of cross-conjugated enynones, dienynones, and trienynones (easily available due to low-cost starting compounds) with arylhydrazines leads to the regioselective synthesis of pyrazole derivatives (dihetaryl-substituted ethens, buta-1,3-diens, and hexa-1,3,5-triens) or results in 4,5-dihydro-1H-pyrazoles in good yield. The reaction path is controlled by the character of the substituent in enynone: the pyrazoles are obtained from the reaction of substrates that contain five-membered heteroaromatic substituents with arylhydrazines, and the 4,5-dihydro-1H-pyrazoles are obtained from the reaction of 1,5-diphenylpent-1-en-4-yn-3-one with arylhydrazines consistently. Despite the presence of a substituent, cyclocondensation of 2-hydrazinylpyridine with all of examined cross-conjugated enynones leads to the formation of pyrazoles. The reaction does not require special conditions (temperature, catalyst, inert atmosphere). The cyclocondensation pathways are determined by the electronic effect of an electron-rich five-membered heteroaromatic ring in the substrate. The synthesis allows use of various substituents and functional groups in enynone and hydrazine. The present method features high yields and simplicity of the product purification. The obtained pyrazoles possess fluorescent properties with a quantum yield up to 31%.

Synthesis of Trifluoromethylated Pyrazolidines, Pyrazolines and Pyrazoles via Divergent Reaction of β-CF3-1,3-Enynes with Hydrazines

“…Privileged N–N bond-containing heterocycles, such as pyrazolidines, pyrazolines, and pyrazoles are three types of valuable compounds, because of their universality in many natural products and pharmacologically active molecules, as well as versatile utility as cornerstones in organic synthesis (Figure ). As a result, much attention has been paid to the development of efficient strategies for the construction and functionalization of these three types of privileged N–N bond-containing heterocycles with high structural diversity . On the other hand, the trifluoromethyl (CF 3 ) group plays important roles in the pharmaceutical and agrochemical industries, because trifluoromethylated compounds generally show better physicochemical and biological properties than their nonfluorinated counterparts .…”

Ketone Derivatives of Propargylamines as Synthetic Equivalents of Conjugated 2,4,1-Enynones in the Synthesis of Acetylenic 2-Pyrazolines and Pyrazoles

“…So, to solve the problem, we have compared the spectroscopic characteristics of compound 5a with its relative isomer synthesized before, 1,5-diphenyl-3-(phenylethynyl)-4,5-dihydro-1 H -pyrazole 7 (see Figure ). , …”

“…For the purpose of the expansion of their synthetic potential, we explored transformations of corresponding 2,3-adducts (ketone derivatives of propargylamines) with arylhydrazines. This indicates a reaction that may lead to biologically active and fluorescent derivatives of pyrazoline and pyrazole. ,, …”

“…Conjugated enynones are applied successfully as substrates in the synthesis of various functional derivatives of oxygen-, − nitrogen-, − and sulfur-containing , heterocycles. This can be attributed to the high reactivity of the conjugated π-system and chemical diversity of their reaction centers, as well as the possibility of the presence of enynones in the form of three isomers with different relative positions of multiple bonds (conjugated 2,4,1-, 1,4,3-, and 4,2,1-enynones and 2-methylenebut-3-yn-1-ones). − − …”

“…This indicates a reaction that may lead to biologically active and fluorescent derivatives of pyrazoline and pyrazole. 7,31,32 ■ RESULTS AND DISCUSSION First of all, we attempted to evaluate quantitatively the relative activity of carbon−carbon double and triple bonds in a model substrate (E)-1,5-diphenylpent-2-en-4-yn-1-one 1a in the addition reaction of morpholine 2a. At temperatures below 40 °C, the rate constant ratio of 2,3-and 4,5-addition reactions exceeded 10 3 (see Table 1).…”