异长叶烷酮合成新型喹唑啉衍生物的研究

以异长叶烷酮为原料,叔丁醇作溶剂,通过缩合得到7-(4'-氟苯亚甲基)异长叶烷酮(FBI),再与盐酸胍环化合成了喹唑啉衍生物4-(4'-氟苯基)-6,6,10,10-四甲基-6a,9-桥亚甲基-5,6,6a,7,8,9,10,10a-八氢苯并h]喹唑啉-2-胺(FBQ),考察了催化剂种类及用量、反应温度、反应时间以及FBI与盐酸胍的物质的量比对环化反应的影响,并通过正交试验法确定了环化反应的适宜工艺条件。最优工艺条件为:以叔丁醇钾为催化剂,n(t-Bu OK)∶n(FBI)为2.9∶1,反应温度75℃,反应时间14 h,FBI与盐酸胍的物质的量比为1∶4,产物得率达到79.51%。采用FT-IR、MS、1H NMR、13C NMR及X射线单晶衍射等分析手段,确定了产物的结构及空间构型。通过X射线单晶衍射法测定表明,化合物属于三斜晶系,P-1空间群,晶包参数a=0.660 85(9)nm,b=1.175 27(16)nm,c=1.340 65(17)nm,α=86.229(3)°,β=83.094(4)°,γ=77.558(4)°,V=1.008 6(2)nm3,Z=2,DC=1.203 g/cm3,F(000)=392,Mr=365.48,μ=0.078 mm-1,R=0.099 3,wR=0.156 5。

Synthesis of a Novel Quinazoline Derivative from Isolongifolanone

4-(4′-Fluorophenyl)-6,6,10,10-tetramethyl-6a,9-methano-5,6,6a,7,8,9,10,10a-octahydrobenzo h] quinazolin-2-ylamine ( FBQ ) was synthesized by aldol condensation, to obtain 7-( 4′-fluoro-benzylidene )-isolongifolanone ( FBI ) from isolongifolanone, and then cyclization with guanidine hydrochloride using t-BuOK as the catalyst in t-butanol. The effects of the sort and dosage of catalysts, reaction time, reaction temperature, and the molar ratio of FBI and guanidine hydrochloride on the cyclization were investigated. The optimum cyclization conditions were determined according to the orthogonal experiments. The results were as follows:n(t-BuOK)∶n(FBI) was 2. 9∶1, reaction temperature 75 ℃, reaction time 14 h, the molar ration of FBI and guanidine hydrochloride 1∶4. The yield of final product reached 79. 51% under the above conditions. The chemical structure of FBQ was determined by FT-IR, MS, 1H NMR, and 13C NMR, respectively. Its spatial structure was examined by X-ray single crystal diffraction. According to single-crystal X-ray diffraction analysis, the target compound was of triclinic system, space group P-1 with a=0. 660 85(9)nm,b=1. 175 27(16)nm, c=1. 340 65(17)nm, α=86. 229(3)°, β=83. 094(4)°,γ=77.558(4)°, V=1.008 6(2)nm3, Z=2, DC=1.203 g/cm3, F(000)=392, Mr =365.48,μ=0.078 mm-1, R=0.099 3 and wR=0. 156 5.