Synthetic Methods And Properties Of Novel Quinazoline And Other N-heterocycle Derivatives

Nitrogenous heterocyclic compounds have shown good prospects in pharmaceuticals and agrochemicals due to their high biological activity, low toxicity and high systemic property. Therefore, the synthesis of these compounds, the structural transformation and drug activity has always been an important area of organic chemistry and medicinal chemistry research. In this paper, a series of dihydroquinazoline was prepared by sequential Ugi/Staudinger/intramolecular aza-Wittig reactions. Some of them can be further converted into indolo[2,1-b]quinazolines by a intramolecular Heck reaction. We also synthesized a series of pyrimidine derivatives that have not been reported by using the Baylis-Hillman reaction and intermolecular aza-Wittig reaction. The conditions of the syntheisis and the spectral properties of the above compounds were researched. A series of N-(1-phenylethyl)pyrimidin-4-amines were synthesized based on the lead compound of acinnoline derivatives which have been reported in the literature with good bactericidal activity. Anymore, we synthesized a series of tetrazine derivatives. The fungicidal activities against Magnaporthe grisea of these two types of compounds were tested. It may be summarized as follows:1. The applications of Baylis-Hillman reaction and Ugi reaction in the synthesis of heterocycles, as well as the latest development of aza-Wittig reaction have been reviewed. And the pathogenesis of rice blast and some related fungicides were briefly introduced.2. A series of2,3,4-trisubstituted3,4-dihydroquinazoline3was prepared by intramolecular aza-Wittig reaction of amide carbonyl groups with methyldiphenyl iminophosphorane2(R=Me), which was obtained from a Ugi4CC/Staudinger sequence. The used amines and acids can be varied broadly when we used methyldiphenylphosphine instead of commonly used triphenylphosphine. Further intramolecular Heck reaction of3d’-3g’ in the presence of catalytic amount of Pd(OAc)2gave6,12-dihydroindolo[2,1-b]quinazolines4a-4d in good yields. 3. a-Acylamino-carboxamide azides5, obtained from Ugi reactions of o-azidobenzaldehyde, amines, benzoylformic acid and isocyanides, reacted with triphenylphosphine to give various2-acylquinazolines7and/or3H-1,4-benzodiazepin-3-ones8in moderate to good yields via sequential Staudinger and intramolecular aza-Wittig reaction. The synthetic conditions and properties of the target compounds were studied and discussed. The structures of the target compounds were characterized via IR,1HNMR,13CNMR, MS and elemental analysis, and the spectral properties were also studied. Furthermore, the structure of the quinazoline derivatives was further confirmed and analysised through X-Ray single crystal diffraction by one representative compound.4. Here we wish to report an efficient synthesis of2,3,5-substituted pyrimidin-4(3H)-ones17via aza-Wittig reaction. The easily accessible methyl acrylate reacted with benzaldehyde by a Baylis-Hillman reaction to Baylis-Hillman adduct, which through the acetylation, azide-substituted to give azides. The azides was further treated with triphenylphosphine, and the iminophosphorane13was obtained in high yield via Staudinger reaction. Iminophosphoranes13reacted with aromatic isocyanate to give carbodiimides14, which were allowed to react with amines, phenols or alcohol to provide guanidine intermediates15. In the presence of catalytic amount of base,15were converted easily to16. After the isomerization,2,3,5-substituted pyrimidin-4(3H)-ones17were obtained. This method utilizes easily accessible starting materials and allows mild reaction conditions, straightforward product isolation, and good yields.5. Rice blast, caused by the ascomycete fungus Magnaporthe grisea, is one of the most serious diseases for cultivated rice and causes serious recurrent epidemics throughout rice growing regions in the world. A series of N-(1-phenylethyl)pyrimidin-4-amines were synthesized based on the lead compound of acinnoline derivatives which have been reported in the literature with good bactericidal activity. And we tested the antibacterial activity to the rice blast fungus of these compounds under50ppm.6. A series of1,2,4,5-tetrazine derivatives by using a novel method. Two molecules of hydrazide dehydrated under hexachloroethane、triphenylphosphine and triethylamine gave symmetric tetrazine. We also tested the antibacterial activity to the rice blast fungus of these compounds and found that compound27g could inhibit the growth of melanin very well.