Microwave-assisted synthesis under solvent-free conditions of (E)-2-(Benzo[d]thiazol-2-yl)-3-arylacrylonitriles

Abstract

Uma série de (E)-2-(benzo[d]tiazol-2-il)-3-arilacrilonitrilas foi sintetizada pela condensação de Knoevenagel assistida por microondas, na ausência de solvente, partindo do correspondente 2-(benzo[d]tiazo-2-il)acetonitrila e aldeídos aromáticos, contendo tanto grupos doadores de elétrons, como retiradores. Os tempos de reação foram consideravelmente curtos e os produtos, obtidos em rendimentos moderados (50-75%) e boa pureza. A configuração da dupla ligação da acrilonitrila não pôde ser estabelecida por métodos comuns de RMN. No entanto, estudos teóricos sugerem que nesses compostos o isômero E é mais estável do que o Z, o que está de acordo com algumas evidências experimentais.A series of (E)-2-(benzo[d]thiazol-2-yl)-3-arylacrylonitriles was synthesized by microwave assisted Knoevenagel condensation under solvent-free conditions from the corresponding 2-(benzo[d]thiazol-2-yl)acetonitrile and aromatic aldehydes with electrondonating/electronwithdrawing groups. The reaction times were considerably short and the products obtained in moderate yields (50 to 75%) and good purity. The configuration of the acrylonitrile double bond could not be established by regular NMR methods. However, theoretical studies suggest that the E isomer is more stable than Z, which is in good agreement with some experimental evidences.

A Novel Class of Selective Acetylcholinesterase Inhibitors: Synthesis and Evaluation of (E)-2-(Benzo[d]thiazol-2-yl)-3-heteroarylacrylonitriles

“…We have previously reported [ 7 ] the synthesis of a series of novel ( E )-2-(benzo[ d ]thiazol-2-yl)-3-arylacrylonitriles. These products were obtained in moderate yields and good purity after short reaction times.…”

Synthesis of New (E)-2-(1H-Indole-3-ylcarbonyl)-3-heteroaryl-acrylonitriles via Microwave-Assisted Knoevenagel Condensation

“…The reaction was carried out using 3-(cyanoacetyl)indole ( ) as a precursor with different heteroaryl-aldehydes ( a-i) in ethanol, as shown in Scheme 1 and Table 1. Under these optimal conditions the Knoevenagel reaction may follow through the cyanoacetyl system present in the cyanoacetylindole ( ), a methylene-activated system used as a versatile nucleophile in Knoevenagel reaction to obtain acrylonitriles derivatives [7,66,67], influenced by the participation of ethanol as acid (p = 15.9), that deprotonated, will produce ethoxide ion, as strong base, and by the presence of different heteroaryl-aldehydes ( a-i) with the electronwithdrawing and electron-releasing substituents.…”

“…Since the first report of Knoevenagel [2], methylene active compound has been one of the most useful synthetic methods to prepare , -unsaturated systems [3][4][5][6] like alkenes with structural diversity and 3-aryl-2-heteroaryl-acrylonitriles [7][8][9][10][11][12]. The latter are known to have interesting biological properties, including antibacterial and cytotoxic agents [13], compounds with antifungal and antitumor activity [11], antitubercular activity [14], antioxidant compounds [15], tubulin inhibitors [16], and inhibitors of kinase-3 [JNK-3] [17], as well as fluorescent probes for the detection of intracellular thiols [18], DNA detection [19] and chemosensory for detecting cations [20], and others [21][22][23][24].…”

“…Indole nucleus are found in terrestrial plants [37,38], marine organism [36,39,40], and fungi [39] which makes them have a wide range of biological properties, such as antimalarial [41], analgesics [42], nonnucleoside inhibitors of hepatitis C virus [43], inhibitors of human cytosolic phospholipase A 2 [34], antifungal, and antimycobacterial [44], anticarcinogenic [45][46][47], antitubulin agents [48], protein kinases inhibitors [49,50], antioxidants, and scavengers [51,52]. Whereby the indolic derivatives are privileged structures to design and synthetize new library of heteroaryl-acrylonitrile compounds, in this 2 Journal of Chemistry sense, the 3-(cyanoacetyl)indole is a methylene active compound that has been reported as a versatile building block to prepare a wide variety of functionalized alkenes via Knoevenagel reaction [7,8,53].…”

Efficient and convenient synthesis of pyrido [2,1-b]benzothiazole, pyrimidopyrido[2,1-b]benzothiazole and benzothiazolo[3,2-a][1,8]naphthyridine derivatives

“…[31] (Scheme 3). Heating under reflux of compound 6 with malononitrile in ethanol in the presence of a catalytic amount of TEA afforded…”