A Simple and Efficient Synthesis of Ethyl 1‐Aryl‐4‐formyl‐1<i>H</i>‐pyrazole‐3‐carboxylates

Matiychuk, V. S.; Potopnyk, Mykhaylo A.; Обушак, Н. Д.

doi:10.1002/jhet.1042

Cited by 9 publications

(6 citation statements)

References 40 publications

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“…The intermediate 3c was synthesized by hydrolysis of ester 4c′ in the presence of aqueous alkali, followed by acidification with aqueous acid. 87 The other core structures, 4-phenylbut-3-en-2-one derivatives ( 6a–6h ), were prepared by KOH-catalyzed condensation of benzaldehyde derivatives with acetone. Finally, KOH-catalyzed condensation between 4a – 4d and 6a–6h furnished the target asymmetric MACs 7a–10h ( Scheme 1 ).…”

Section: Methodsmentioning

confidence: 99%

“…Initially, 1 H -pyrazole-4-carbaldehyde derivatives ( 4a – 4d ) were synthesized through 2–3 consecutive steps, which were described before, − starting from (i) phenyl hydrazine derivatives, and (ii) methyl acetoacetate, ethyl pyruvate, or acetophenone, to afford 1 H -pyrazol-5(4 H )-ones ( 3a and 3b ) or hydrazones ( 3c and 3d ) . Subsequently, via the Vilsmeier–Haack reaction, 3a and 3b underwent a formylation–chlorination process to obtain intermediates 4a and 4b , whereas 3c and 3d underwent a cyclization–formylation process to obtain intermediates 4c′ and 4d , respectively.…”

Section: Methodsmentioning

confidence: 99%

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Synthesis, Biological Evaluation, and Molecular Modeling Studies of 1-Aryl-1H-pyrazole-Fused Curcumin Analogues as Anticancer Agents

et al. 2022

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Addressing the growing burden of cancer and the shortcomings of chemotherapy in cancer treatment are the current research goals. Research to overcome the limitations of curcumin and to improve its anticancer activity via its heterocycle-fused monocarbonyl analogues (MACs) has immense potential. In this study, 32 asymmetric MACs fused with 1-aryl-1 H -pyrazole ( 7a–10h ) were synthesized and characterized to develop new curcumin analogues. Subsequently, via initial screening for cytotoxic activity, nine compounds exhibited potential growth inhibition against MDA-MB-231 (IC 50 2.43–7.84 μM) and HepG2 (IC 50 4.98–14.65 μM), in which seven compounds showing higher selectivities on two cancer cell lines than the noncancerous LLC-PK1 were selected for cell-free in vitro screening for effects on microtubule assembly activity. Among those, compounds 7d , 7h , and 10c showed effective inhibitions of microtubule assembly at 20.0 μM (40.76–52.03%), indicating that they could act as microtubule-destabilizing agents. From the screening results, three most potential compounds, 7d , 7h , and 10c , were selected for further evaluation of cellular effects on breast cancer MDA-MB-231 cells. The apoptosis-inducing study indicated that these three compounds could cause morphological changes at 1.0 μM and could enhance caspase-3 activity (1.33–1.57 times) at 10.0 μM in MDA-MB-231 cells, confirming their apoptosis-inducing activities. Additionally, in cell cycle analysis, compounds 7d and 7h at 2.5 μM and 10c at 5.0 μM also arrested MDA-MB-231 cells in the G 2 /M phase. Finally, the results from in silico studies revealed that the predicted absorption, distribution, metabolism, excretion, and the toxicity (ADMET) profile of the most potent MACs might have several advantages in addition to potential disadvantages, and compound 7h could bind into (Δ G −10.08 kcal·mol –1 ) and access wider space at the colchicine-binding site (CBS) than that of colchicine or nocodazole via molecular docking studies. In conclusion, our study serves as a basis for the design of promising synthetic compounds as anticancer agents in the future.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Synthesis, Biological Evaluation, and Molecular Modeling Studies of 1-Aryl-1H-pyrazole-Fused Curcumin Analogues as Anticancer Agents

et al. 2022

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“…developed another simple and convenient methodology for the synthesis of ethyl 4‐formyl‐1‐phenyl‐1 H ‐pyrazole‐3‐carboxylates ( 64 ) from various diazonium salts ( 62 ) prepared from aromatic amines as presented in Scheme and investigated their hydrolysis and hydrazinolyzation properties. Hydrolysis of 64 was carried out using KOH/HCl to yield the corresponding acids ( 65 ) while hydrazinolyzation of 64 led to the formation of pyrazole fused pyridazine derivatives ( 66 ) (Scheme ) .…”

Section: Synthesis and Applications Of Ethyl 4‐formyl‐1‐aryl‐1h‐pyrazmentioning

confidence: 99%

4‐Formyl‐Pyrazole‐3‐Carboxylate: A Useful Aldo‐X Bifunctional Precursor for the Syntheses of Pyrazole‐fused/Substituted Frameworks

Devi

Shankar

Singh

2017

Journal of Heterocyclic Chem

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Pyrazole, a privileged class of heterocyclic compounds, constitute an interesting template for medicinal chemistry and is represented by several commercial drugs like Sildenafil, Zometapin, Celebrex, and Rimonabant. The presence of two functionalities with different reactivity in pyrazole moiety may open new avenues for insertion of diversity in pyrazole frameworks which may be of high medicinal significance. Ethyl 4‐formyl‐1H‐pyrazole‐3‐carboxylate is a potential Aldo‐X bifunctional building block (AXB3) which may be explored for generating complex pyrazole based molecular frameworks by using various organic transformations. The present manuscript is assimilation of literature pertaining to the synthesis and application of ethyl 4‐formyl‐1H‐pyrazole‐3‐carboxylates and similar AXB3 for the development of pyrazole substituted and fused derivatives.

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“…Інший підхід до 4-форміл-3-карбоксилатів 21 ґрунтується на використанні методу Кіра -цик-лізації з одночасним формілюванням гідразонів та семікарбазонів естерів піровиноградної кис-лоти подвійною кількістю реагенту Вільсмейє-ра-Хаака [6][7][8][9][10][11] Для синтезу гідразонів 20 автори досліджен-ня [12] вдало застосовували конденсацію гідра-зинів 22 із доступним та стійким піруватом нат-рію (схема 8).…”

Section: синтези пов'язані з формуванням пі-разольного циклуunclassified

“…Для одержання піразолів 75, анельованих по d-грані тіофеновим циклом запропонована ори-гінальна внутрішньомолекулярна циклоконден-сація естерів 1-арил-4-форміл-5-бензоїлметилтіо-піразол-3-карбонових кислот 74, каталізована трифторооцтовою кислотою [10] (схема 32).…”

Section: реакції алкенілуванняunclassified

Esters of 4-formylpyrazol-3-carboxylic acids

Братенко¹,

Барус²,

Вовк³

2017

J. org. pharm. chem.

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Узагальнені та систематизовані літературні джерела, присвячені хімії синтетично привабливих бі-функціональних похідних піразолу -естерів 4-формілпіразол-3-карбонових кислот. Детально висвітлено два основних підходи до отримання такого типу структур: 1) реакції, в яких генерування функціональних альдегідної та естерної груп супряжене із формуванням піразольної системи; 2) синтези, які базуються на цілеспрямованій функціоналізації піразольного ядра. Показано, що перший варіант зазвичай здійсню-ється за схемою [3+2]-циклоприєднання іn situ генерованих нітрилімінів або естерів діазооцтової кислоти із формілацетиленами або їх похідними, а також циклізацією з одночасним формілюванням гідразонів та семікарбазонів естерів піровиноградної кислоти реагентом Вільсмейєра-Хаака. В основі другого варіанту лежить формілювання естерів піразол-3-карбонових кислот або 3-етоксикарбоніл-5-піразолонів в умовах реакції Вільсмейєра-Хаака. Аналіз хімічних властивостей естерів 4-формілпіразол-3-карбонових кислот показав, що їх перетворення найчастіше реалізується за участю альдегідної групи. Найтиповішими серед них є реакції з нітрогеновмісними нуклеофілами, алкенілування, окиснення, відновлення та багатокомпо-нентні взаємодії, які варто розглядати як зручні варіанти структурної функціоналізації піразольного ядра. Не менш важливими також є циклоконденсації, в яких задіяні формільна, естерна та інші функціональні групи, отримані на їх основі. Такі сполуки виявились ефективними субстратами для конструювання біо-Ключові слова: естери 4-формілпіразол-3-карбонових кислот; методи синтезу; хімічні властивості; структурна функціоналізація; поліфункціональні структури M. K. Bratenko, M. M. Barus, M. V. Vovk Esters of 4-formylpyrazol-3-carboxylic acidsThe scientific publications devoted to chemistry of the synthetically promising bifunctional derivatives of pyrazole -esters of 4-formylepyrazole-3-carbonic acids have been generalized and systematized. A special attention has been given to description of two main synthetic approaches: 1) processes of the conjugated formation of aldehyde and ester groups, on one hand, and the pyrazolic system, on the other; 2) synthetic strategies targeted on functionalization of the pyrazolic nucleus. It has been shown that the first approach is performed usually by the scheme [3+2] meaning in situ cyclojoining of the generated nitrilimines or esters of diazoacetic acid with formylacetylenes or their derivatives followed by cyclization with simultaneous formylation of hydrazones and semicarbazones of pyruvic acid by Wilsmaer-Haack reagent. The second approach deals with formylation of esters of pyrazole-3-carbonic acids according to Wilsmaer-Haack reaction. As seen from the analysis of chemical properties of esters of 4-formylpyrazole-3-carbonic acids, the aldehyde group is the most typical target of their chemical transformations. Such transformations are reactions with nitrogen-containing nucleophiles, alkenylation, oxidation, reduction and other multicomponent reactions that can be considered as usual approaches...

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A Simple and Efficient Synthesis of Ethyl 1‐Aryl‐4‐formyl‐1H‐pyrazole‐3‐carboxylates

Abstract: in Wiley Online Library (wileyonlinelibrary.com).A new simple and convenient method of synthesis of ethyl 1-aryl-4-formyl-1H-pyrazole-3-carboxylates from aromatic amines via diazonium salts has been developed. Hydrolysis and hydrazinolyization of these compounds has been investigated.

Cited by 9 publications

References 40 publications

Synthesis, Biological Evaluation, and Molecular Modeling Studies of 1-Aryl-1H-pyrazole-Fused Curcumin Analogues as Anticancer Agents

Synthesis, Biological Evaluation, and Molecular Modeling Studies of 1-Aryl-1H-pyrazole-Fused Curcumin Analogues as Anticancer Agents

4‐Formyl‐Pyrazole‐3‐Carboxylate: A Useful Aldo‐X Bifunctional Precursor for the Syntheses of Pyrazole‐fused/Substituted Frameworks

Esters of 4-formylpyrazol-3-carboxylic acids

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