Abstract

The oximino(2,6-dichlorophenyl)acetonitrile, H(2,6-diCl-PhCO) has been synthesized in a reasonably high yield of 60%, and characterized using a variety of physical, electrochemical, spectroscopic methods and X-ray analysis. This compound belongs to the family of cyanoximes; a new subclass of oximes with the general formula NC–C(=N–OH)–R (where R is an electron-withdrawing group) which recently emerged as new biologically active compounds. This cyanoxime represents a disubstituted arylcyanoxime that was found to be a powerful inhibitor of the Carbonyl Reductase enzyme involved in the developing of resistance to anticancer treatment, and the making of cardiotoxic derivatives of anthracyclines that are currently used in medicine. The oximino(2,6-dichlorophenyl)acetonitrile, H(2,6-diCl-PhCO) is a weak acid with pKa = 6.17 and does not dissociate in organic polar protic and aprotic solvents. The cyanoxime was obtained as a microcrystalline mixture of two diastereomers (anti- and syn-) and deprotonates in solutions with the formation of yellow anions which exhibit solvatochromic behavior. However, one specific diastereomer—syn—was isolated in crystalline form from a solvent system as colorless blocks overlayed with pentane ether solution in a monoclinic system in a P2/c (#13) space group with unit cell parameters: a = 8.1720(2), b = 8.8013(3), c = 13.0146(4) and β = 102.546(3); Z = 4. A single crystal was studied using filtered CuK_a radiation, providing R_int value of 0.0348 from a full-sphere of reflections. A crystal structure was solved using direct methods, and well refined to R1 = 0.0459, wR2 = 0.1268 and GOF = 1.107. The studied specimen of oximino(2,6-dichlorophenyl)acetonitrile, H(2,6-diCl-PhCO), represents a highly non-planar, rare syn-diastereomer in which the oxime fragment is positioned towards the chlorinated phenyl group. In the crystal, the compound forms a columnar structure extended along the c-direction by using slipped π–π stacking interactions. Columns are interconnected via H-bonding between the oxime OH-group and N atom of the nitrile group with the following parameters: N–H = 1.841 Å, and 169.20° N···H–O angle. No thermal interconversion of syn- into anti- diastereomer was observed upon heating of crystals of one isomer under flow of Ar.

Graphic Abstract

中文翻译：

---

2,6-二氯苯基-氰肟，H(2,6-diCl-PhCO) 顺式异构体的制备、性质和晶体结构：强效羰基还原酶抑制剂

摘要

肟基 (2,6-二氯苯基) 乙腈 H(2,6-diCl-PhCO) 已以 60% 的合理高产率合成，并使用各种物理、电化学、光谱方法和 X 射线分析进行表征. 该化合物属于氰肟家族；一种新的肟亚类，其通式为 NC–C(=N–OH)–R（其中 R 是吸电子基团），最近作为新的生物活性化合物出现。这种氰肟代表一种双取代的芳基氰肟，它被发现是羰基还原酶的强大抑制剂参与抗癌治疗产生抗性的酶，以及制造目前用于医学的蒽环类药物的心脏毒性衍生物。肟基（2,6-二氯苯基）乙腈 H(2,6-diCl-PhCO) 是一种弱酸，pKa = 6.17，在有机极性质子和非质子溶剂中不会解离。得到cyanoxime如两种非对映（的微晶混合物抗和顺式）和去质子化与表现出溶致变色行为黄色的阴离子形成的解决方案。然而，一个特定diastereomer- SYN -was以结晶形式分离从溶剂系统，其为无色的块与在P2 / C（＃13）的空间群，晶胞参数在单斜晶系戊烷乙醚溶液叠加：a  = 8.1720(2), b  = 8.8013(3), c  = 13.0146(4) 和 β = 102.546(3); Z = 4. 使用过滤的 CuK _a辐射研究单晶，提供 R _int来自全反射球体的值为 0.0348。晶体结构使用直接方法求解，并精制为 R1 = 0.0459、wR2 = 0.1268 和 GOF = 1.107。所研究的肟基 (2,6-二氯苯基) 乙腈样品 H(2,6-diCl-PhCO) 是一种高度非平面的罕见顺式非对映异构体，其中肟片段位于氯化苯基组。在晶体中，该化合物通过使用滑动的 π-π 堆积相互作用形成沿 c 方向延伸的柱状结构。柱子通过肟 OH 基团和腈基 N 原子之间的氢键互连，参数如下：N–H = 1.841 Å，和 169.20° N……H–O 角。没有从同步到反的热互变 在Ar流下加热一种异构体的晶体时观察到非对映异构体。

图形摘要