【作者】 赵国栋；

【导师】 武文菊；

【作者基本信息】 哈尔滨理工大学 ， 化学工程与技术， 2022， 硕士

【摘要】 氰基作为一种重要的有机官能团,广泛存在于许多天然产物、药物等精细化学品中。在分子中引入氰基最直接的方法就是通过α,β-不饱和羰基化合物的共轭氰化反应,所生成的β-氰基酮是一类重要的有机合成中间体,是合成氨基酸的重要原料,特别是具有光学活性的β-氰基酮可以转化为γ-氨基丁酸（GABA）,另外氰基还可以转化为酰胺、胺、羧酸及其衍生物、醛、酮、醇、含氮杂环等。因此,深入研究α,β-不饱和羰基化合物的氰化反应具有重要的意义。本论文具体研究内容如下:1.α,β-不饱和酮的共轭氰化反应。以丙酮氰醇为氰源,α,β-不饱和酮为底物,实现了β-氰基酮的高效制备。以查尔酮的共轭氰化为模型,分别考察了碱的种类及用量、温度、溶剂、丙酮氰醇用量等因素对反应的影响,确定了最佳实验条件:采用Li OH·H₂O作碱,反应底物、丙酮氰醇、Li OH·H₂O的摩尔比为1:2.5:1.6,以体积比为4:1的DMF和H₂O为溶剂,反应温度为60℃。在最优条件下,β-氰基酮的最高收率可达98%。进一步考察底物适用范围,16种查尔酮衍生物均能以85%～98%的收率得到相应的β-氰基酮产物。2.手性配体的合成。分别以（R）-联二萘酚和（S）-联二萘酚为原料合成了两种基于联二萘酚结构的手性配体L₁、L₂;由丙二腈出发首先制备氨基丙二酸二乙酯,而后分别与手性氨基茚醇和L-苯甘氨醇缩合生成中间体L₃和L₁₁,再由L₃出发得到7种手性双噁唑啉配体L₄?L₁₀,由L₁₁出发得到2种手性双噁唑啉配体L₁₂和L₁₃。3.3,5-二甲基-N-α,β-不饱和酰基吡唑的不对称共轭氰化反应。以3,5-二甲基-N-α,β-不饱和酰基吡唑和丙酮氰醇的共轭氰化反应为模型,通过考察手性配体种类、温度、配位金属种类、催化剂用量、配体和金属比例、溶剂等因素对不对称共轭氰化反应的影响,确立了最佳反应条件:在以20 mol%的双噁唑啉配体L₇与二丁基镁（1:1）形成的络合物作催化剂,以1,2-二氯乙烷为溶剂,反应温度为-18℃时,反应效果最佳,产物收率为87%,er值为86:14。进一步考察底物适用范围,结果表明,12种肉桂吡唑衍生物和丙酮氰醇能以77%?88%的产率和60:40?79:21的er值获得目标产物。在此催化条件下,将氰源换成三甲基氰硅烷同样适用,13种肉桂吡唑底物和TMSCN能以75%?91%的产率和58:42?91:9的er值获得目标产物。更多还原

【Abstract】 As a vital organic functional group,the cyano group widely exists in many natu-ral products,medicines and other fine chemicals.The most direct way to introduce cyano groups into molecules is through the conjugate cyanation ofα,β-unsaturated carbonyl compounds.Theβ-cyano ketone generated by the reaction is a significant class of organic synthesis intermediates,which is a crucial raw material to synthesize amino acids,especially the optically activeβ-cyano ketone can convert intoγ-aminobutyric acid（GABA）.In addition,cyano groups can be converted into amides,amines,carboxylic acids and their derivatives,aldehydes,ketones,alcohols,nitro-gen-containing heterocycles,etc.Therefore,it is of great significance to deeply study the cyanation ofα,β-unsaturated carbonyl compounds.The specific research contents of this paper are as follows:1.Conjugate cyanation ofα,β-unsaturated ketone.Using acetone cyanohydrin as the cyanogen source andα,β-unsaturated ketone as the substrate,the efficient prepa-ration ofβ-cyano ketone was realized.Taking the conjugate cynation of chalcone as a model,the influence factors such as the type and amount of base,temperature,sol-vent,and the amount of acetone cyanohydrin on the reaction were investigated,re-spectively,and the optimal experimental conditions were determined:Li OH·H₂O was used as the base,the molar ratio of the reaction substrate,acetone cyanohydrin,and Li OH·H₂O was 1:2.5:1.6,DMF and H₂O in a volume ratio of 4:1 were used as the solvent,and the reaction temperature was 60°C.Under the optimal conditions,the highest yield ofβ-cyano ketone could reach 98%.Further investigation of the scope of substrate application showed that 16 chalcone derivatives could obtain the corre-spondingβ-cyano ketone products in 85%～98%yields.2.Synthesis of chiral ligands.Two chiral ligands,L1 and L2,which were based on the structure of binaphthol,were synthesized by（R）-binaphthol and（S）-binaphthol as raw materials,respectively.Staring from malononitrile,diethyl ami-nomalonate was prepared,and then condensed with chiral amionoindanol and and L-phenylglycinol to generate intermediates L3 and L11.Seven kinds of chiral bisoxa-zolines L4～L10 were obtained from L3 and two kinds of chiral bisoxazolines L12～L13were obtained from L11.3.Asymmetric conjugation cynation of 3,5-dimethylacylpyrazole.Taking the conjugate cyanation reaction of 3,5-dimethyl-N-α,β-unsaturated acylpyrazole and acetone cyanohydrin as a model,the optimum reaction conditions were established by investigating the effects of chiral ligand,coordination metal,catalyst dosage,ratio of ligand to metal,solvent and temperature on asymmetric conjugate cyanation:.When the complex formed by 20 mol%of bisoxazoline ligand L7 and dibutylmagne-sium（1:1）was used as catalyst,1,2-dichloroethane was used as solvent,and the reac-tion temperature was-18°C,the reaction effect was the best,the product’s yield was87%,and the er value was 86:14.The scope of substrates was further investigated,and the results showed that 12 kinds of cinnamyl pyrazole derivatives and acetone cyanohydrin could obtain the target products with the yield of 77%～88%and the er value of 60:40-79:21.When trimethylsilyl cyanide was used as cyanide source,this catalytic condition was also suitable,and 13 cinnamo pyrazole derivatives could be converted to target products in 75%～91%yield and 58:42～91:9 er value.更多还原