- Mild, Metal-Free and Protection-Free Transamidation of N-Acyl-2-piperidones to Amino Acids, Amino Alcohols and Aliphatic Amines and Esterification of N-Acyl-2-piperidones
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Amides are indispensable building blocks of biological systems, pharmaceuticals, and materials. We report a highly selective method for the synthesis of amides via transamidation process. Transamidation of N-acyl-2-piperidones with a broad range of amines is demonstrated under exceedingly mild and metal-free reaction condition that relies on the amide bond twist to weaken the amidic resonance. Transamidation proceeds under the neat condition at room temperature, in short reaction times (30–90 min) with good yields. Considerable variation is tolerated with both amine and imide substrates. Of note, amines bearing carboxylic acids (glycine and serine) and hydroxyl groups (dopamine, tyramine, etc.) are well tolerated which are otherwise problematic under the metal-catalyzed protocol. Our current method is applicable for transamidation of both alkyl and aryl-N-acyl-2-piperidones. The practical value of the method is highlighted by the synthesis of four natural product amide alkaloids in high yields under mild reaction conditions. In the absence of nucleophilic amines, N-acyl-2-piperidones undergoes esterification with EtOH at elevated temperature. Single crystal X-ray analysis of an N-acyl-2-piperidone shows amide bond twist, τ = –20.39° and pyramidalization, χN = –11.73°. This weakens the amidic conjugation and might be the factor controlling the reactivity and selectivity of these imides. We envision that the N-acyl-2-piperidone scaffold would be useful in the synthesis of pharmaceuticals and materials.
- Subramani, Muthuraman,Rajendran, Saravana Kumar
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p. 3677 - 3686
(2019/06/08)
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- A simple synthesis of trans-3,4,5-trimethoxycinnamamides and evaluation of their biologic activity
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A simple synthesis and biologic evaluation of trans-3,4,5- trimethoxycinnamamides 10a-e and 11 as novel antinarcotic agents is described. The synthetic key strategies involve condensation reaction and coupling reaction to generate trans-3,4,5-trimethoxycinnamamides 10a-e and 11. They were evaluated for free radical scavenging, inhibitory action for neurotoxicity in cultured neurons, and antinarcotic activity in mice. It was found that compounds 10a, 10d, and 10e displayed significant inhibitory action of the glutamate-induced neurotoxicity and 10a-e and 11 showed high antinarcotic activity in mice.
- Jung, Jae-Chul,Min, Dongguk,Lim, Heena,Moon, Sohyeon,Jung, Mankil,Oh, Seikwan
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p. 4615 - 4621
(2013/09/23)
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- Synthesis and antidepressant-like action of N-(2-hydroxyethyl) cinnamamide derivatives in mice
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This study described the chemical synthesis and pharmacological evaluation of a series of N-(2-hydroxyethyl) cinnamamide derivatives. The structures of them were characterized by IR, 1H-NMR, MS and elemental analysis. Their antidepressant activities were evaluated by the forced swimming test (FST) and tail suspension test (TST). Pharmacological results of these compounds showed that some of them, given orally, significantly reduced the immobility time in the FST and TST, indicating the antidepressant-like action. Among them, compounds N-(2-hydroxyethyl)cinnamamide (1g), (E)-3-(4-hydroxy-3- methoxyphenyl)-N-(2-hydroxyethyl)acrylamide (1i) and (E)-N-(2-hydroxyethyl)-3- (3-hydroxyphenyl)acrylamide (1n), active in the two models, were considered as the most promising compounds in this study. Springer Science+Business Media, LLC 2010.
- Deng, Xian-Qing,Wu, Di,Wei, Cheng-Xi,Quan, Zhe-Shan
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p. 1273 - 1279
(2012/05/20)
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