Absolute Configuration Determination of Chiral Compounds Using a Novel Crystalline Agent

手性酮是一类用途广泛的天然产物中间体，广泛存在于萜类、信息素等生物活性化合物的结构中。然而，文献中几乎没有发现直接法确定这些手性酮的绝对构型的研究。X射线结晶学分析是确定分子绝对构型的唯一方法。为了确定绝对组态，必须利用重原子的反常色散效应。肼类化合物是众所周知的酮的良好结晶剂。因此，使用具有卤素原子的苯肼衍生物作为结晶剂。我们设计并合成了一些联氨类结晶剂，发现2-氯-4，6-二硝基苯肼是各种手性酮类化合物的结晶剂。2-氯代-4，6-二硝基苯胺是一种弱碱，因为有两个硝基和一个氯原子，所以在转换…时不会发生重氮化反应更有针对性的方式。因此，用亚硝酸钠和硫酸反应制得的亚硝基硫酸盐重氮化溶解于热乙酸乙酯中的苯胺，再用碘化钾碘化得到1-氯-2-碘-3，5-二硝基苯。在室温下，与一水合肼在甲醇中搅拌，得到所需的联氨。联氨与手性酮的反应得到了适合于X射线单晶分析的单晶。利用氯原子的反常色散效应，确定了相应化合物的晶体结构和绝对构型。通过对Bijvoet对的Flack参数和强度比较，成功地确定了绝对构型。这是一种简单直接的方法，这种方法的潜力被清楚地展示出来。2-氯-4，6-二硝基苯肼是一种用于绝对构型测定的结晶剂。该方法适用于萜类和信息素的测定，有助于确定各种手性酮类化合物的绝对构型。较少

Chiral ketones are versatile intermediates of natural products and seen in the structure of biologically active compounds such as terpenes, pheromones, and so on. However, few studies are found in the literature for the direct method to determine the absolute configurations of these chiral ketones. X-Ray crystallographic analysis is the only method to determine the absolute configuration of a molecule. The anomalous dispersion effect of a heavy atom must be used for the determination of the absolute configuration. Hydrazines are well-known to be good crystalline agents for ketones. Thus, a phenylhydrazine derivative having a halogen atom is employed as a crystalline agent. We designed and synthesized some hydrazines as crystalline agents, and found that 2-chloro-4,6-dinitrophenyihydrazine is the useful crystalline agent for various chiral ketones. 2-Chooro-4,6-dinitroaniline is a weak base because of two nitro groups and a chlorine atom, so that diazotization does not occur with a conv … More entional way. Therefore, the aniline dissolved in hot acetic add was diazotized with nitrosyl sulfate prepared from sodium nitrite and sulfuric acid, and iodinated with potassium iodide to afford 1-chloro-2-iodo-3,5-dinitrobenzene. It was stirred with hydrazine monohydrate in methanol at room temperature to give the desired hydrazine. The reaction of the hydrazine and a chiral ketone gave the single crystal suitable for X-ray crystallographic analysis. The crystal structure and absolute configuration of the corresponding hydrazone was determined using the anomalous dispersion effect of a chlorine atom. The absolute configurations were successfully determined by Flack parameter and intensities comparison of Bijvoet pairs. This is the simple and direct method and the potential of this methodology was clearly demonstrated. 2-Chloro-4,6-dinitrophenylhdrazine is a useful crystalline agent for the absolute configuration determination. This method can be applied to terpenes and pheromones, and is helpful for the determination of the absolute configuration of various chiral ketones. Less