Addressing the unusual reactivity of 2-pyridinecarboxaldehyde and 2-quinolinecarboxaldehyde in base-catalyzed aldol reactions with acetophenone

Wachter-Jurcsak, Nanette; Radu, Constantin; Redin, Kendra

doi:10.1016/s0040-4039(98)00723-0

Cited by 25 publications

(13 citation statements)

References 10 publications

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“…Similar results were obtained when using 3-chloroacetophenone and 4-chloroacetophenone. To our knowledge this unusual reactivity has not previously been reported for 3-pyridinecarboxaldehyde 5, although it has been observed with both 2-pyridinecarboxaldehyde and 2-quinolinecarboxaldehyde when reacted with acetophenone under similar conditions [17]. The addition of one equivalent of pyridine to these reactions was found to prevent this conjugate addition.…”

Section: Chemistrysupporting

confidence: 59%

Synthesis and antitrypanosomal activities of novel pyridylchalcones

Bhambra

Ruparelia

Tan

et al. 2017

European Journal of Medicinal Chemistry

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a b s t r a c tA library of novel pyridylchalcones were synthesised and screened against Trypanosoma brucei rhodesiense. Eight were shown to have good activity with the most potent 8 having an IC 50 value of 0.29 mM.Cytotoxicity testing with human KB cells showed a good selectivity profile for this compound with a selectivity index of 47. Little activity was seen when the library was tested against Leishmania donovani. In conclusion, pyridylchalcones are promising leads in the development of novel compounds for the treatment of human African trypanosomiasis (HAT).

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Section: Chemistrysupporting

confidence: 59%

Synthesis and antitrypanosomal activities of novel pyridylchalcones

Bhambra

Ruparelia

Tan

et al. 2017

European Journal of Medicinal Chemistry

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“…As in the study by Wachter-Jurcsak, we isolated the Michael adduct as the major product in condensations of pyridinecarboxaldehydes 2 and 3. [7] Condensations of 2 using pyridine as an ion scavenger still yielded only the Michael product. Condensations of 3 and pyridine gave inseparable mixtures of the azachalcone and its Michael adduct.…”

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confidence: 99%

“…[7] The cation withdraws electron density from the conjugated system, making the enone a better Michael acceptor (Scheme 2). Only the Michael adducts (e.g., 13 and 14) were isolated from condensations using 2 and 2-quinolinecarboxaldehyde.…”

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confidence: 99%

Organic Base‐Mediated Condensation of Pyridinecarboxaldehydes to Azachalcones

2005

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A DBU-mediated aldol condensation-dehydration sequence has been used to prepare a series of synthetically important substituted 2-and 3-azachalcones. Michael products that typically accompany this sequence with inorganic bases were not observed in this protocol of high practical value.Keywords: aldol reaction; azachalcones; chemoselectivity; organic catalysis; pyridinecarboxaldehydes Azachalcones are valuable intermediates for Diels-Alder and Michael reactions as well as many other conversions.[1] Although there are many ways to prepare azachalcones (Scheme 1), [2 -4] none appear universally applicable to synthesize a wide variety of azachalcones using a common synthetic protocol. All current approaches suffer from subsequent Michael addition to the desired azachalcone to varying degrees. In one case, the precipitate isolated from the condensation of 2 and acetophenone was actually an oily mixture of the Michael adduct 13 or 14 and the desired azachalcone (9 or 10).[2] In condensations of 1 and several substituted benzaldehydes, cyclic products (e.g., 15) were reportedly isolated regardless of the stoichiometry used.[5] These compounds form in high yields under conditions identical to those suggested for the synthesis of the azachalcones, and their structures were confirmed using X-ray crystallography. Aryl-substituted oligopyridines (17) are isolated in 40% yield via the Krçhnke methodology by using Michael adduct 16, generated under conditions identical to those used to prepare the azachalcones.[6] A reliable preparation of azachalcones therefore necessitates the prevention of the Michael pathway.A recent study by Wachter-Jursczak and co-workers proposed that the Michael pathway is favored by coordination of the metal ion to the azachalcone through an interaction with the nitrogen.[7] The cation withdraws electron density from the conjugated system, making the enone a better Michael acceptor (Scheme 2). Only the Michael adducts (e.g., 13 and 14) were isolated from condensations using 2 and 2-quinolinecarboxaldehyde. The study showed that the reaction of 2-quinolinecarboxaldehyde could be stopped at the dehydration product by applying stoichiometric amounts of pyridine to bind the metal ion. The same approach, however, did not prevent Michael addition in reactions involving 2.In order to circumvent all of the problems noted above, we considered application of an organic base to eliminate the metal ion from the reaction mixture. We chose 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) as the base because it is readily available, highly basic, and of low nucleophilicity.[8] In our continuing interest with organocatalysis and specifically the use of thioureas to catalyze Diels-Alder reactions, we sought a series of substituted azachalcones that would elucidate the binding mechanism of thiourea catalysts.[9] Since these catalysts are believed to activate dienophiles through hydrogen bonding, azachalcones present the potential for activation by bidentate chelation.For comparison with literature data, we first pre...

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“…It has been reported that decomposition of chalcone took place in the presence of KOH [55]. The reaction of acetophenone with 2-pyridylcarboxaldehyde, in ethanolic KOH led to Michael addition of acetophenone enolate to the chalcone and provided the Michael adduct as the final product [56]. Under the present study, exclusive formation of chalcone took place during the reaction of 4-methoxyacetophenone with 2-pyridylcarboxaldehyde (entry 17).…”

Section: Resultsmentioning

confidence: 49%

“…The conveour attention to the base-catalyzed reaction. However, long reaction times were needed for the reported base-catalyzed synthesis of chalcones and became detrimental to purity of the desired product due to side reactions such as degradation [55] and Michael addition [56][57][58] under basic medium. We felt that the use of catalytic quantities of a base should minimize the side reactions and the activation of the aldehyde carbonyl group by coordination with the metal counter cation help in carrying out the reaction in short times.…”

Section: Introductionmentioning

confidence: 99%