Microwave-assisted solvent-free heterocyclic synthesis

Neste trabalho foram usados dois sistemas simples, rápidos (3 min) e versáteis, de transferência de energia de microondas, na ausência de solventes, para a síntese de quinoxalinas (2,3-difenilquinoxalina e seus derivados, 2,3-difenil-4a,5,6,7,8,8a-hexahidroquinoxalina, 2-fenilquinoxalina, piridina-2,3-diamina e 2,3-dihidro-5,6-difenilpirazina). O primeiro método consiste no uso de suportes minerais na reação de 1,2-dicarbonil (benzil) ou α-hidroxicetona (aciloína) com 1,2-diaminas. Entre os suportes minerais, a eficiência da alumina ácida como catalisador foi claramente comprovada (80-86%). Além disso, apresenta um papel importante na oxidação de aciloína ao correspondente sistema 1,2-dicarbonílico. O segundo método consiste no uso de microondas em mistura dos reagentes 1,2-dicarbonil(benzil) e 1,2-diaminas. O excelente rendimento dos produtos (90-97%) e a simples lavagem com água e filtração na ausência de solventes orgânicos fazem desse sistema uma ótima alternativa para a prevenção de poluição, em um processo ambientalmente benigno. Embora os dois métodos tenham sido planejados para evitar passos adicionais de purificação, o último é um processo mais limpo com tratamento reacional mais simples.Two benign, simple, rapid (3 min), solvent-free and versatile microwave energy transfer systems for the synthesis of quinoxalines, i.e. 2,3-diphenylquinoxaline and its derivatives, 2,3-diphenyl-4a,5,6,7,8,8a-hexahydroquinoxaline, and 2-phenylquinoxaline and also pyridine-2,3-diamine and 2,3-dihydro-5,6-diphenylpyrazine have been used. The first approach consists on the use of mineral supports on the reaction of 1,2-dicarbonyl (benzil) or α-hydroxyketone (acyloin) with 1,2-diamines. Among mineral supports, the efficiency of acidic alumina as catalyst was clearly proved (80-86%). Moreover, it has an oxidative role in the tandem oxidation of acyloin to the corresponding 1,2-dicarbonyl. The second approach is the use of polar paste system on the reaction of 1,2-dicarbonyl (benzil) with 1,2-diamines. The excellent products yield (90-97%) and simple washing with water and filtration in the absence of organic solvent makes it an impressive alternative green platform. Although both methods implemented in this study have been designed to circumvent additional purification steps, the latter is cleaner with an easier work-up.

mentioning

confidence: 99%

Benign approaches for the microwave-assisted synthesis of quinoxalines

Mohsenzadeh

Aghapoor

Darabi

2007

“…In terms of reactivity, the specific effect has therefore to be considered according to the reaction mechanism and particularly with regard to how the polarity of the system is altered during the progress of the reaction. 12 In initial attempts, we carried out the reaction under solvent-free conditions during 15-20 min of microwave irradiation in a commercial domestic oven, and then the reactions conditions were optimized in a focused microwaves reactor (CEM Discover TM) twice. In order to improve our initial attempts, different reaction times, power and temperatures were studied for the preparation of (E)-2-(benzo[d]thiazol-2-yl)-3-arylacrylonitriles 3.…”

Section: Resultsmentioning

confidence: 99%

“…7,10,11 Although acrylonitrile derivatives are an-easy-to synthesize template, a great diversity of the methods is available in literature that describe their synthesis under different conditions making use of conventional thermal energy and microwave irradiation conditions. [1][2][3][12][13][14][15][16][17] Typically, Knoevenagel adducts have been obtained under conventional heating conditions for extended periods of reaction in the presence of catalytic amounts of base, obtaining generally from good to very low yields. [18][19][20][21][22][23] Condensation reactions leading to heterocyclic systems have been performed with great success under Vol.…”

Section: Introductionmentioning

confidence: 99%

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

Trilleras¹,

Velásquez²,

Pacheco³

et al. 2011

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.

“…[29][30][31][32][33][34][35] The use of microwaves has an important effect to improve yields and reduce reaction times. [36][37][38][39][40] In this work, we have used solvent-free microwave irradiation for the very efficient solid state synthesis of oxadeazaflavines from o-halobenzylidene barbiturates.…”

Section: Introductionmentioning

confidence: 99%

Synthesis and mechanism of formation of oxadeazaflavines by microwave thermal cyclization of ortho-halobenzylidene barbiturates

Figueroa‐Villar¹,

Oliveira²

2011

A reação de ciclização térmica de o-halobenzilideno barbituratos foi desenvolvida como um simples e eficiente método para a preparação de oxadeazaflavinas. A utilização de condições de reação em estado sólido com irradiação de microondas forneceu os produtos em 5 min e com rendimentos entre 47 e 98%. Os resultados experimentais das sínteses e a análise termogravimétrica das reações concordam com os resultados da simulação do mecanismo por modelagem molecular, indicando que a reação ocorre através de uma ciclização hetero-Diels-Alder intra-molecular, seguida por um processo rápido de re-aromatização.The thermal cyclization reaction of o-halobenzylidene barbiturates was developed as an efficient and simple method for the preparation of oxadeazaflavines. The use of solid state reaction conditions with microwave irradiation afforded the products in 5 min with 47 to 98% yield. Experimental synthetic results and thermogravimetric reaction analyses agree with the molecular modeling mechanism simulation, indicating that this reaction occurs through an intramolecular hetero-Diels-Alder cyclization followed by fast re-aromatization. Keywords: oxadeazaflavines, o-halobenzylidene barbiturates, microwave irradiation, intramolecular hetero-Diels-AlderIntroduction pyrimidine-2,4-(3H)-diones or 10-oxa-5-deazaflavines) are interesting compounds with great potential as intermediates for the synthesis of new heterocyclic systems [1][2][3][4][5][6][7][8] and as selective organic oxidants under mild conditions.3 Also, derivatives and analogues of oxadeazaflavines display important bioactivity, being potential drugs.9-12 For many years, several chemists tried without success to prepare the simplest oxadeazaflavine by the direct reaction of barbituric acid with salicylaldehyde, [13][14][15] thus making necessary the use of more complex synthetic procedures to obtain the desired products. [1][2][3] In the beginning of the 1990 decade there were reported two new simple and complementary methods for the preparation of oxadeazaflavines from barbituric acid. 16,17 The first method uses the condensation reaction of salicylaldehyde and analogues with barbituric acid at room temperature to yield an orange oxonium salt that affords oxadeazaflavines under dehydrating conditions, 16 as shown in Scheme 1. Unfortunately, this method only functions well with salicylaldehydes without effective electron-withdrawing groups at the aromatic ring.The second method, which is based on the thermal cyclization of o-halobenzylidene barbiturates, can be applied with success to starting materials containing electron-withdrawing and electron-donating groups at the aromatic ring. 17 The draw of this last method is the need Scheme 1. Synthesis of oxadeazaflavines from salicylaldehyde and barbituric acid. 16Synthesis and Mechanism of Formation of Oxadeazaflavines J. Braz. Chem. Soc. 2102 for relatively long reaction times at high temperatures, for example 1.5 hours at 260 °C, affording oxadeazaflavines in medium to low yields (50% or lower). On the other hand, ...