1,3-偶极环加成反应合成螺杂环化合物的研究
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摘要
本论文是关于1,3-偶极环加成反应合成一系列新的螺杂环化合物的研究。
以环酮及噻唑啉酮与芳香醛缩合合成了双芳亚甲基环烷酮，3,5-二芳亚甲基-1-苄基-4-哌啶酮，3-烷基-5-芳亚甲基-噻唑烷-2,4-二酮等4个系列共37种带环外双键的亲偶极体；以四氢嘧啶-2-硫酮，咪唑烷-2-硫酮，3(5)-巯基-1,2,4-三唑等与芳香醛，氯乙酸一锅合成了2-芳亚甲基-6,7-二氢-5H-噻唑并[3,2-a]嘧啶-3-酮，2-芳亚甲基-5,6-二氢-咪唑并[2,1-b]噻唑-3-酮和5-芳亚甲基-噻唑并[3,2-b]1,2,4-三唑-6-酮等5个系列共35个带环外双键的稠合噻唑啉酮类亲偶极体。
以合成的亲偶极体与由靛红，肌氨酸原位反应生成的甲亚胺叶立德偶极体的1,3-偶极环加成反应合成了9个系列共58种未见文献报导的新螺杂环化合物，其中包括10个新的母体环系。对得到的新螺杂环化合物进行了红外、核磁共振氢谱、核磁共振碳谱分析，对新的母体杂环进行了X射线单晶衍射分析，确定了空间构型。首次发现了甲亚胺叶立德偶极体的环加成产物在质谱中的逆1,3-偶极环加成碎裂反应(RDA)。初步探讨了带环外双键的亲偶极体与甲亚胺叶立德偶极体的1,3-偶极环加成反应的区域选择性和立体选择性。
以自制的亲偶极体与腈氧化物偶极体的1,3-偶极环加成反应合成了5个系列共32种未见文献报导的新螺杂环化合物，其中包括7个新的母体环系。对得到的新螺杂环化合物进行了红外、核磁共振氢谱、核磁共振碳谱分析，对得到的新的母体杂环进行了X射线单晶衍射分析，确定了空间构型。
在6-31G*水平上用从头算方法研究了腈氧化物与3-(4-氯)苯亚甲基二氢呋喃-2-酮的1,3-偶极环加成反应。通过对反应过程能量的分析及前线轨道分析讨论了反应的两种可能途径。其中途径一生成3,4-二芳基螺异噁唑啉，途径二生成3,5-二芳基螺异噁唑啉。能量分析显示反应途径一的活化能比反应途径二的活化能低。反应优先生成了3,4-二芳基螺异噁唑啉，即生成腈氧化物的氧原子连接在螺碳原子上的产物。前线轨道分析表明了反应的区域选择性由LUMO偶极体-HOMO亲偶极体相互作用控制，反应按途径一进行，与实验结果吻合。
The paper focus on the synthesis of a number of novel spiroheterocycles by the 1,3-dipolar cycloaddition reaction.
37 dipolarphiles with exo-cyclic double bond were synthesized by the conde- nsation of cycloalkanones and aryl aldehydes. 35 dipolarphiles with exo-cyclic double bond including 2-arylidene-benzo[4,5]imidazo[2,1-b]thiazol-3-one, 2-arylidene- 6,7-dihydro-5H-thiazolo[3,2-a]pyrimidin-3-one, 2-arylidene-5,6-dihydro-imidazo[2,1-b]thiaz-
ol-3-one,7-methyl-2-arylidene-3-oxo-5-phenyl-2,3- dihydro-5H-thiazolo[3,2-a]pyrimidine-6-
carboxylic acid ethyl ester, 2-arylmethylene-9-benzylidene-5-phenyl-6,7,8,9-tetrahydro-5H- thiazolo[2,3-b]quinazolin-3-one and 5-arylidene-thiazolo[3,2-b][1,2,4]tria-zol-6-one were sy-
nthesized by the one-pot alkylation and condensation of chloroacetic acid , aryl aldehydes and fused thiazolidine compounds.
58 novel spiroheterocycle compounds were synthesized by the 1,3-dipolar cycloaddition of azomethine ylide which generated in situ from sarcosine and isatin and self- synthesized dipolarphiles with exo-cyclic double bond. There are 10 new parent heterocycle among them. All the novel spiroheterocycle compounds were charactered by IR and 1H NMR. The stereo conformation of 10 new parent heterocycle were achieved by X-ray single crystal analyses. The retro-cyclo- addition reaction of cycloaddition products was discovered first times. The regioselectivity and steroselectivity of the reaction was discussed.
32 novel spiroheterocycle compounds were synthesized by the 1,3-dipolar cycloaddition of 2,6-dichlorobenzonitrile oxide and self- synthesized dipolarphiles with exo-cyclic double bond. There are 7 new parent heterocycle among them. All the novel spiroheterocycle compounds were charactered by IR and 1H NMR. The stereo conformation of 12 new parent heterocycle were achieved by X-ray single crystal analyses.
The regioselectivity of 1,3-dipole cycloaddition between 2,6-dichlorobenzon-
itrile oxide and 3-(4-chlorobenzylidene)dihydrofuran-2-one was studied using ab initial RHF theory with the 6-31G* basis set. Two possible reactions approachs which lead to 3,4-disubstituted(approach 1) and 3,5-disubstituted(approach 2) isoxazoline respectively were investigated using energy analysis and frontier mol-
ecular orbital analysis. Energy analysis shows that the activity energy of approach
2 is higher than approach 1. The high activity energy of approach 2 prevent the fo-
rmation of 3,5-disubstituted isoxazoline and give 3,4-disubstituted isoxazoline as energy favored product. The frontier molecular orbital analysis shows the reaction was controlled by LUMOdipolar-HOMOdipolarphile interaction, and the reaction will follow approach 1 which in agree with experimental result.
以环酮及噻唑啉酮与芳香醛缩合合成了双芳亚甲基环烷酮，3,5-二芳亚甲基-1-苄基-4-哌啶酮，3-烷基-5-芳亚甲基-噻唑烷-2,4-二酮等4个系列共37种带环外双键的亲偶极体；以四氢嘧啶-2-硫酮，咪唑烷-2-硫酮，3(5)-巯基-1,2,4-三唑等与芳香醛，氯乙酸一锅合成了2-芳亚甲基-6,7-二氢-5H-噻唑并[3,2-a]嘧啶-3-酮，2-芳亚甲基-5,6-二氢-咪唑并[2,1-b]噻唑-3-酮和5-芳亚甲基-噻唑并[3,2-b]1,2,4-三唑-6-酮等5个系列共35个带环外双键的稠合噻唑啉酮类亲偶极体。
以合成的亲偶极体与由靛红，肌氨酸原位反应生成的甲亚胺叶立德偶极体的1,3-偶极环加成反应合成了9个系列共58种未见文献报导的新螺杂环化合物，其中包括10个新的母体环系。对得到的新螺杂环化合物进行了红外、核磁共振氢谱、核磁共振碳谱分析，对新的母体杂环进行了X射线单晶衍射分析，确定了空间构型。首次发现了甲亚胺叶立德偶极体的环加成产物在质谱中的逆1,3-偶极环加成碎裂反应(RDA)。初步探讨了带环外双键的亲偶极体与甲亚胺叶立德偶极体的1,3-偶极环加成反应的区域选择性和立体选择性。
以自制的亲偶极体与腈氧化物偶极体的1,3-偶极环加成反应合成了5个系列共32种未见文献报导的新螺杂环化合物，其中包括7个新的母体环系。对得到的新螺杂环化合物进行了红外、核磁共振氢谱、核磁共振碳谱分析，对得到的新的母体杂环进行了X射线单晶衍射分析，确定了空间构型。
在6-31G*水平上用从头算方法研究了腈氧化物与3-(4-氯)苯亚甲基二氢呋喃-2-酮的1,3-偶极环加成反应。通过对反应过程能量的分析及前线轨道分析讨论了反应的两种可能途径。其中途径一生成3,4-二芳基螺异噁唑啉，途径二生成3,5-二芳基螺异噁唑啉。能量分析显示反应途径一的活化能比反应途径二的活化能低。反应优先生成了3,4-二芳基螺异噁唑啉，即生成腈氧化物的氧原子连接在螺碳原子上的产物。前线轨道分析表明了反应的区域选择性由LUMO偶极体-HOMO亲偶极体相互作用控制，反应按途径一进行，与实验结果吻合。
The paper focus on the synthesis of a number of novel spiroheterocycles by the 1,3-dipolar cycloaddition reaction.
37 dipolarphiles with exo-cyclic double bond were synthesized by the conde- nsation of cycloalkanones and aryl aldehydes. 35 dipolarphiles with exo-cyclic double bond including 2-arylidene-benzo[4,5]imidazo[2,1-b]thiazol-3-one, 2-arylidene- 6,7-dihydro-5H-thiazolo[3,2-a]pyrimidin-3-one, 2-arylidene-5,6-dihydro-imidazo[2,1-b]thiaz-
ol-3-one,7-methyl-2-arylidene-3-oxo-5-phenyl-2,3- dihydro-5H-thiazolo[3,2-a]pyrimidine-6-
carboxylic acid ethyl ester, 2-arylmethylene-9-benzylidene-5-phenyl-6,7,8,9-tetrahydro-5H- thiazolo[2,3-b]quinazolin-3-one and 5-arylidene-thiazolo[3,2-b][1,2,4]tria-zol-6-one were sy-
nthesized by the one-pot alkylation and condensation of chloroacetic acid , aryl aldehydes and fused thiazolidine compounds.
58 novel spiroheterocycle compounds were synthesized by the 1,3-dipolar cycloaddition of azomethine ylide which generated in situ from sarcosine and isatin and self- synthesized dipolarphiles with exo-cyclic double bond. There are 10 new parent heterocycle among them. All the novel spiroheterocycle compounds were charactered by IR and 1H NMR. The stereo conformation of 10 new parent heterocycle were achieved by X-ray single crystal analyses. The retro-cyclo- addition reaction of cycloaddition products was discovered first times. The regioselectivity and steroselectivity of the reaction was discussed.
32 novel spiroheterocycle compounds were synthesized by the 1,3-dipolar cycloaddition of 2,6-dichlorobenzonitrile oxide and self- synthesized dipolarphiles with exo-cyclic double bond. There are 7 new parent heterocycle among them. All the novel spiroheterocycle compounds were charactered by IR and 1H NMR. The stereo conformation of 12 new parent heterocycle were achieved by X-ray single crystal analyses.
The regioselectivity of 1,3-dipole cycloaddition between 2,6-dichlorobenzon-
itrile oxide and 3-(4-chlorobenzylidene)dihydrofuran-2-one was studied using ab initial RHF theory with the 6-31G* basis set. Two possible reactions approachs which lead to 3,4-disubstituted(approach 1) and 3,5-disubstituted(approach 2) isoxazoline respectively were investigated using energy analysis and frontier mol-
ecular orbital analysis. Energy analysis shows that the activity energy of approach
2 is higher than approach 1. The high activity energy of approach 2 prevent the fo-
rmation of 3,5-disubstituted isoxazoline and give 3,4-disubstituted isoxazoline as energy favored product. The frontier molecular orbital analysis shows the reaction was controlled by LUMOdipolar-HOMOdipolarphile interaction, and the reaction will follow approach 1 which in agree with experimental result.
引文
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