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

Abstract

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, ...

Microwave Irradiation Assists the Synthesis of a Novel Series of bis-Arm s-Triazine Oxy-Schiff Base and Oxybenzylidene Barbiturate Derivatives

“…Due to the presence of the azomethine (R-NH-N=C-R) in Schiff bases moiety, these compounds have gained great importance in medicinal chemistry as well as coordination chemistry [ 28 , 29 , 30 , 31 , 32 , 33 , 34 ]. In addition, barbiturate derivatives have shown remarkable biological activity [ 35 , 36 ] and are considered as important intermediates for the synthesis of several heterocyclic compounds [ 37 , 38 ]. Herein, we report the synthesis and characterization of a novel series of bis -arm s -triazine oxy-Schiff bases and oxybenzylidene barbiturate derivatives using conventional heating and microwave irradiation as a new template, which might be important in coordination and medicinal chemistry for researchers in this field.…”