<i>N</i>‐acyliminium intermediates in solid‐phase synthesis

Benzoyl and ferrocenoyl 3,4-dihydropyrimidin-2(1H)-ones (-thiones) (DHPMs) were synthesized in modest yields via catalyst-free and solvent-free Biginelli condensation of 1-phenylbutane-1,3-dione or 1-ferrocenylbutane-1,3-dione, hydroxyl benzaldehyde, and urea or thiourea. This synthetic protocol revealed that catalysts may not be necessary for the self-assembling Biginelli reaction. The radical-scavenging abilities of the obtained 11 DHPMs were carried out by reacting with 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonate) cationic radical (ABTS(+•)), galvinoxyl radical, and 2,2'-diphenyl-1-picrylhydrazyl radical (DPPH), respectively. The variation of the concentration of these radicals with the reaction time (t) followed exponential function, [radical] = Ae(-t/a) + Be(-t/b) + C. Then, the differential style of this equation led to the relationship between the reaction rate (r) and the reaction time (t), -d[radical]/dt = (A/a)e(-t/a) + (B/b)e(-t/b), which can be used to calculate the reaction rate at any time point. On the basis of the concept of the reaction rate, r = k[radical][antioxidant], the rate constant (k) can be calculated with the time point being t = 0. By the comparison of k of DHPMs, it can be concluded that phenolic ortho-dihydroxyl groups markedly enhanced the abilities of DHPMs to quench ABTS(+•), but the introduction of ferrocenoyl group made DHPMs efficient ABTS(+•) scavengers even in the absence of phenolic hydroxyl group. This phenomenon was also found in DHPM-scavenging galvinoxyl radical. In contrast, the ferrocenoyl group cannot enhance the abilities of DHPMs to scavenge DPPH, and phenolic ortho-dihydroxyl groups still played the key role in this case.

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“…32 The reaction can also take place on the surface of resin linked with urea via a N atom, leading to convenient isolation of DHPMs. 33 The…”

Section: ■ Introductionmentioning

confidence: 99%

Solvent-Free and Catalyst-Free Biginelli Reaction To Synthesize Ferrocenoyl Dihydropyrimidine and Kinetic Method To Express Radical-Scavenging Ability

Wang

Liu

2012

J. Org. Chem.

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“…The resulting value of the Gibbs energy in solution, G • (soln) , is related to the absolute formal redox potential, E abs , according to Eq. (2).…”

Section: Redox Potential Calculationsmentioning

confidence: 99%

“…Eq (1)(2) were also used to calculate the redox potential for the concerted step, being now thermodynamic cycle that represented in Fig. 2.…”

Section: Redox Potential Calculationsmentioning

confidence: 99%

“…In particular, the C-H functionalization via N-acyliminium ions has proven to be a valuable strategy due to their ability to react with a wide variety of nucleophiles [1]. N-acyliminium ions are almost exclusively produced in situ during the course of the desired reaction by a variety of suitable techniques [2]. Among them, the electrochemical ␣-alkoxylation, where the N-acyliminium ion obtained is trapped by an alkoxy group [3,4], stands out because it occurs in neutral reaction conditions and is friendly for the environment as it leads to high yields of stable products and minimizes unproductive decomposition pathways of the iminium ion.…”

Section: Introductionmentioning

confidence: 99%

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Regioselectivity of Electrochemical C-H Functionalization Via Iminium Ion

Haya

Pardo

Mainar

et al. 2014

Electrochimica Acta

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“…Most of the reported solid-supported Pictet-Spengler reactions rely on the intermediacy of N-alkyliminium ions, [7] but since the pioneering work of Wang and Ganesan on the synthesis of fumitremorgin derivatives, [8] the more activated N-acyl intermediates have also been frequently utilized. Using masked aldehyde building blocks, Meldal and coworkers developed methods for the formation and reaction Abstract: An efficient approach for the solid-phase synthesis of structurally diverse heterocyclic compounds is presented.…”

Section: Introductionmentioning

confidence: 99%

Solid‐Phase Synthesis of Structurally Diverse Heterocycles by an Amide–Ketone Condensation/N‐Acyliminium Pictet–Spengler Sequence

Komnatnyy

Givskov

Nielsen

2012

Chemistry A European J

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An efficient approach for the solid-phase synthesis of structurally diverse heterocyclic compounds is presented. Under acidic reaction conditions, peptidic levulinamides undergo intramolecular ketone-amide condensation reactions to form cyclic N-acyliminium intermediates. In the presence of a tethered nucleophile, a second cyclization reaction results in the formation of a fused bicyclic ring system. The scope of the methodology was demonstrated by several combinations of substituted ketones and nucleophiles, the latter conveniently originating from amino acids with functionalized side chains, such as tryptophan, substituted phenylalanines, and cysteine. The cyclization sequence provides diastereomerically pure products in high yields. In one extension of the methodology, the resulting relative stereochemistry of the products enables the formation of bridged ring systems by a unique cyclative release mechanism.

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N‐acyliminium intermediates in solid‐phase synthesis

Cited by 31 publications

References 66 publications

Solvent-Free and Catalyst-Free Biginelli Reaction To Synthesize Ferrocenoyl Dihydropyrimidine and Kinetic Method To Express Radical-Scavenging Ability

Solvent-Free and Catalyst-Free Biginelli Reaction To Synthesize Ferrocenoyl Dihydropyrimidine and Kinetic Method To Express Radical-Scavenging Ability

Regioselectivity of Electrochemical C-H Functionalization Via Iminium Ion

Solid‐Phase Synthesis of Structurally Diverse Heterocycles by an Amide–Ketone Condensation/N‐Acyliminium Pictet–Spengler Sequence

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