Shimono Satoshi, Tamura Rui, Ikuma Naohiko, Takimoto Tatsuya, Kawame Naoyuki, Tamada Osamu, Sakai Naoko, Matsuura Hiroaki, Yamauchi Jun
Graduate School of Human and Environmental Studies, Kyoto University, Kyoto 606-8501, Japan.
J Org Chem. 2004 Jan 23;69(2):475-81. doi: 10.1021/jo0354443.
A synthetic procedure for optically active and racemic alpha-nitronyl nitroxides (alpha-NNs) having a stereogenic center at the 4-position of the imidazolyl ring is described. This procedure consists of (1) the synthesis of a dissymmetric vic-dinitro compound by Kornblum reaction, (2) the enantiomeric resolution of the racemate by a diastereomer method for obtaining the optically active sample, (3) the quick reduction of the optically active or racemic vic-dinitro compound to the bis(hydroxyamino) derivative with Al/Hg, (4) the solvent-free condensation of the bis(hydroxyamino) compound with an aldehyde to give the 1,3-dihydroxyimidazolidine, and (5) the final oxidation of the alpha-NN precursor with aqueous NaIO(4). The absolute configuration of the optically active alpha-NNs was assigned by correlating with the X-ray crystal structure of the (-)-(1S,4R)-camphanic acid ester derivative of the optically active vic-dinitro compound. The molecular conformation of the optically active alpha-NNs was found to be folded both in solution and in the solid state by CD spectroscopy and energy minimization with the Monte Carlo method. The magnetic properties of both optically active and racemic alpha-NNs in solution and in the solid state were characterized by EPR spectroscopy and magnetic susceptibility measurement, respectively.
描述了一种用于合成在咪唑环4-位具有手性中心的旋光性和外消旋α-硝酮硝酰自由基（α-NNs）的方法。该方法包括：（1）通过科恩布卢姆反应合成不对称的偕二硝基化合物；（2）采用非对映体方法对外消旋体进行对映体拆分以获得旋光性样品；（3）用铝汞齐将旋光性或外消旋偕二硝基化合物快速还原为双（羟氨基）衍生物；（4）双（羟氨基）化合物与醛在无溶剂条件下缩合生成1,3-二羟基咪唑烷；（5）最后用高碘酸钠水溶液氧化α-NN前体。通过与旋光性偕二硝基化合物的（-）-（1S,4R）-樟脑酸酯衍生物的X射线晶体结构相关联，确定了旋光性α-NNs的绝对构型。通过圆二色光谱和蒙特卡罗方法进行能量最小化计算，发现旋光性α-NNs在溶液和固态中均呈折叠构象。分别通过电子顺磁共振光谱和磁化率测量对旋光性和外消旋α-NNs在溶液和固态中的磁性进行了表征。
