N-亚硝基氧氮五元杂环化合物的研究
摘要
本博士论文研究了:(1)N-亚硝基氧氮五元杂环化合物的合成及结构鉴定;(2)手性N-亚硝基氧氮五元杂环化合物的合成;高立体选择性地合成了(2S,4S)N-亚硝基氧氮五元杂环化合物;(3)N-亚硝基化合物与汉斯酯的反应。获得了如下结果:
1.NO与邻羟基亚胺反应,生成N-亚硝基氧氮五元杂环化合物。应用~1H,~(13)CNMR,X-ray对产物进行了鉴定。由于N-N键的旋转,在溶液中出现E,Z两种构型,固态下只有E一种构型。推测反应机理是氮氧五元杂环(ring-2)结构中的氮作为Lewis碱进攻N203上的氮,生成N-亚硝基化合物。在Gaussian 98程序包中运用DFT(density functional theory,密度泛函理论)计算了E,Z式构型化合物的能量,化合物的平衡常数和~1H,~(13)C NMR的化学位移,计算结果与实验数据基本一致。
2.NO与(S)-邻羟基亚胺在0℃下反应,高立体选择性地生成(2S,4S)N-亚硝基氧氮五元杂环化合物。手性是(S)-邻羟基亚胺(chain-2)向氧氮五元杂环(ring-2)转换过程产生的,氧上孤对电子进攻极化的N=C双键,产生(2S,4S)五元环过渡态,最终转换为手性产物。
3.催化量的N-亚硝基化合物可以将汉斯酯芳环化。催化机理是汉斯酯氮上的孤对电子进攻N-亚硝基化合物上的氮,经历一个transnitrosation反应,转换为N-亚硝基汉斯酯和邻羟基亚胺,N-亚硝基汉斯酯均裂放出NO,其与邻羟基亚胺反应再生成N-亚硝基化合物。
In this dissertation were carried out the studies on: (a) synthesis and identification of (E)-and (Z)-N-nitroso-2-aryl-1,3-oxazolidines, (b) N-nitrosation of chiral (E)-2-(benzylidene-amino) ethanols with nitric oxide, and (c) N-Nitroso-2 -aryl-1,3-oxazolidines catalyzed aromatization of Hantzsch 1,4-dihydropyridines. The principal results are listed as follows.
(1) Reaction of (E)-2-(benzylideneamino)ethanol 2 with nitric oxide affords anE-rotamer dominant mixture of (E)- and (Z)-N-nitroso-2-aryl-1,3-oxazolidines 3 at room temperature in good overall yields. Two sets of ~1H,~(13)C NMR peaks display 3 existing in solution as a mixture of two conformers, (E)-3 and (Z)-3. Displacement of the good leaving group nitrite (~-ONO) from N_2O_3 by the Lewis basic nitrogen of ring-2 leads to the formation of 3 (Scheme 1).The conformational isomerization of 3 was studied using density functional theory (DFT) calculations on total energies,~1H NMR chemical shifts, and equilibrium constants K for rotamers.
(2) N-nitrosation of chrial (E)-(S)-2-(benzylidene-amino)ethanols 2 with nitric oxide occurs highly diastereoselctively, giving (2S,4S) diastereomer dominant N-nitroso-(2S,4S)-1,3-oxazolidines at 0℃in good yield. The N=C double bond of (E)-chain-2 is polarized to result in mostδ~+ on the carbon atom. It favors an intramolecular nucleophilic attack of the Lewis basic oxygen on the carbon atom withδ~+ to undergo a cycloaddition, giving an intermediate (25,45)-ring-2' with a (S) configuration at C-2 (Scheme 2).
(3) A catalytic amount of N-nitroso-2-aryl-1,3-oxazolidines 2 leading to the aromatization of Hantzsch 1,4-dihydropyridines (DHPs) 1 is successfully achieved. A catalytic mechanism for the reaction is proposed. A nucleophilic attack of the nitrogen atom of 1 at the nitrogen atom of the N-nitroso of 2 most likely undergoes a transnitrosation to give a nitronium ion 4 and an oxazolidine anion 5. Followed by a proton transfer,N-nitrosodihydropyridine 6 and 7 are produced. Homolysis of 6 gives an aminyl radical 8 and NO.The 7 reacts with NO released from 6 to regenerate 2 (Scheme 3).
1.NO与邻羟基亚胺反应,生成N-亚硝基氧氮五元杂环化合物。应用~1H,~(13)CNMR,X-ray对产物进行了鉴定。由于N-N键的旋转,在溶液中出现E,Z两种构型,固态下只有E一种构型。推测反应机理是氮氧五元杂环(ring-2)结构中的氮作为Lewis碱进攻N203上的氮,生成N-亚硝基化合物。在Gaussian 98程序包中运用DFT(density functional theory,密度泛函理论)计算了E,Z式构型化合物的能量,化合物的平衡常数和~1H,~(13)C NMR的化学位移,计算结果与实验数据基本一致。
2.NO与(S)-邻羟基亚胺在0℃下反应,高立体选择性地生成(2S,4S)N-亚硝基氧氮五元杂环化合物。手性是(S)-邻羟基亚胺(chain-2)向氧氮五元杂环(ring-2)转换过程产生的,氧上孤对电子进攻极化的N=C双键,产生(2S,4S)五元环过渡态,最终转换为手性产物。
3.催化量的N-亚硝基化合物可以将汉斯酯芳环化。催化机理是汉斯酯氮上的孤对电子进攻N-亚硝基化合物上的氮,经历一个transnitrosation反应,转换为N-亚硝基汉斯酯和邻羟基亚胺,N-亚硝基汉斯酯均裂放出NO,其与邻羟基亚胺反应再生成N-亚硝基化合物。
In this dissertation were carried out the studies on: (a) synthesis and identification of (E)-and (Z)-N-nitroso-2-aryl-1,3-oxazolidines, (b) N-nitrosation of chiral (E)-2-(benzylidene-amino) ethanols with nitric oxide, and (c) N-Nitroso-2 -aryl-1,3-oxazolidines catalyzed aromatization of Hantzsch 1,4-dihydropyridines. The principal results are listed as follows.
(1) Reaction of (E)-2-(benzylideneamino)ethanol 2 with nitric oxide affords anE-rotamer dominant mixture of (E)- and (Z)-N-nitroso-2-aryl-1,3-oxazolidines 3 at room temperature in good overall yields. Two sets of ~1H,~(13)C NMR peaks display 3 existing in solution as a mixture of two conformers, (E)-3 and (Z)-3. Displacement of the good leaving group nitrite (~-ONO) from N_2O_3 by the Lewis basic nitrogen of ring-2 leads to the formation of 3 (Scheme 1).The conformational isomerization of 3 was studied using density functional theory (DFT) calculations on total energies,~1H NMR chemical shifts, and equilibrium constants K for rotamers.
(2) N-nitrosation of chrial (E)-(S)-2-(benzylidene-amino)ethanols 2 with nitric oxide occurs highly diastereoselctively, giving (2S,4S) diastereomer dominant N-nitroso-(2S,4S)-1,3-oxazolidines at 0℃in good yield. The N=C double bond of (E)-chain-2 is polarized to result in mostδ~+ on the carbon atom. It favors an intramolecular nucleophilic attack of the Lewis basic oxygen on the carbon atom withδ~+ to undergo a cycloaddition, giving an intermediate (25,45)-ring-2' with a (S) configuration at C-2 (Scheme 2).
(3) A catalytic amount of N-nitroso-2-aryl-1,3-oxazolidines 2 leading to the aromatization of Hantzsch 1,4-dihydropyridines (DHPs) 1 is successfully achieved. A catalytic mechanism for the reaction is proposed. A nucleophilic attack of the nitrogen atom of 1 at the nitrogen atom of the N-nitroso of 2 most likely undergoes a transnitrosation to give a nitronium ion 4 and an oxazolidine anion 5. Followed by a proton transfer,N-nitrosodihydropyridine 6 and 7 are produced. Homolysis of 6 gives an aminyl radical 8 and NO.The 7 reacts with NO released from 6 to regenerate 2 (Scheme 3).
引文
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