dimethyl α-hydroxy-α-methyl-4-fluorobenzylphosphonate | 401610-05-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: dimethyl α-hydroxy-α-methyl-4-fluorobenzylphosphonate
• 英文别名: dimethyl (1-(4-fluorophenyl)-1-hydroxyethyl)phosphonate；dimethyl 1-(4-fluorophenyl)-1-hydroxyethylphosphonate；1-Dimethoxyphosphoryl-1-(4-fluorophenyl)ethanol
• CAS: 401610-05-7
• 化学式: C₁₀H₁₄FO₄P
• 分子量: 248.191
• InChiKey: HDHFAHHYMOOBLK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.48
• 重原子数：
  16.0
• 可旋转键数：
  4.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  55.76
• 氢给体数：
  1.0
• 氢受体数：
  4.0

反应信息

• 作为产物：
  描述：

  在 N-羟基邻苯二甲酰亚胺 、 copper(II) choride dihydrate 、 氧气 、 三苯基膦 作用下， 以 乙腈 为溶剂， 100.0 ℃ 、101.33 kPa 条件下， 反应 10.0h， 以77%的产率得到dimethyl α-hydroxy-α-methyl-4-fluorobenzylphosphonate
  参考文献：
  名称：

  通过膦酸酯化合物的直接羟基 化催化有氧合成季α-羟基膦酸酯†

  摘要：

  已经开发了高效的铜催化的膦酸酯化合物的直接羟基化。该转化为以高收率合成α-羟基膦酸酯季盐提供了一种有力的方法。直接转化过程，区域特异性选择性以及对各种取代基的良好耐受性使其成为所报道方案的替代方法。

  DOI：

  10.1039/c4nj02072c

文献信息

• The Preparation of Dimethyl α -Hydroxyphosphonates and the Chemical Shift Non-Equivalence of Their Diastereotopic Methyl Ester Groups
  作者：Harry R. Hudson、Ramon O. Yusuf、Ray W. Matthews

  DOI：10.1080/10426500701690905

  日期：2008.6.9

  alkanals, aryl aldehydes (or aryl methyl ketones), furfuraldehyde, and 2- or 3-thiophenecarboxaldehyde, respectively, thus confirming the general utility of this synthetic procedure. The 1H and 13C nmr spectra of the products exhibit characteristic chemical shift non-equivalence of the diastereotopic methyl ester groups, for which a tentative order of non-equivalence is reported and discussed.

  通过亚磷酸二甲酯与相应的烷醛、芳基醛（或芳基甲基酮）、糠醛和 2- 或 3- 噻吩甲醛，分别，从而证实了这种合成程序的通用性。产物的 1H 和 13C nmr 光谱表现出非对映甲基酯基团的特征化学位移非等价性，对此报告和讨论了非等价性的暂定顺序。
• Synthesis and anticancer cytotoxicity with structural context of an α-hydroxyphosphonate based compound library derived from substituted benzaldehydes
  作者：Zita Rádai、Tímea Windt、Veronika Nagy、András Füredi、Nóra Zsuzsa Kiss、Ivan Ranđelović、József Tóvári、György Keglevich、Gergely Szakács、Szilárd Tóth

  DOI：10.1039/c9nj02144b

  日期：——

  active clusters, which encouraged us to synthesize further dibenzyl-α-diphenyl-OPP derivatives that elicited pronounced cell killing. Further structure–activity relationships showed the relevance of hydrophobicity and the position of substituents on the main benzene ring as determinants of toxicity. The most active analogs proved to be equally, or even more toxic to the multidrug resistant (MDR) cell line

  我们合成了取代的苯甲醛衍生的α-羟基膦酸酯（αOHP），α-羟基膦酸（αOHPA）和α-膦酰氧基膦酸酯（αOPP），并表征了它们对一组癌细胞系的细胞毒性。使用基于荧光的细胞毒性试验，针对Mes-Sa亲本和Mes-Sa / Dx5多药耐药子宫肉瘤细胞系筛选了包含56个类似物的文库。细胞毒性筛选显示，二苄基-αOHP和二甲基-α-二苯基-OPP是最活跃的簇，这鼓励我们合成进一步的二苄基-α-二苯基-OPP衍生物，引起明显的细胞杀伤作用。进一步的结构-活性关系显示疏水性和主苯环上取代基的位置与毒性有关。事实证明，最活跃的类似物是同等的，
• Reactions of acyl phosphonates with organoaluminum reagents: a new method for the synthesis of secondary and tertiary α-hydroxy phosphonates
  作者：Ozlem Seven、Sidika Polat-Cakir、Md. Shakhawoat Hossain、Mustafa Emrullahoglu、Ayhan S. Demir

  DOI：10.1016/j.tet.2011.03.036

  日期：2011.5

  ) with aryl and alkyl acyl phosphonates, which lead to the formation of α-hydroxy phosphonates in moderate to good yields, are reported. This method provides easy access to secondary and tertiary α-hydroxy phosphonates depending on the reaction conditions. The reactions of triethylaluminum with a series of acyl phosphonates at 0 °C gave the secondary α-hydroxy phosphonates, while at −100 °C they afford

  报道了有机铝试剂（三甲基铝，三乙基铝等）与芳基和烷基酰基膦酸酯的反应，导致以中等至良好的产率形成α-羟基膦酸酯。根据反应条件，该方法可轻松获得仲和叔α-羟基膦酸酯。三乙基铝与一系列酰基膦酸酯在0°C的反应生成仲α-羟基膦酸酯，而在-100°C时，它们生成叔α-羟基膦酸酯。
• Synthesis of Quaternary<i>α</i>-Hydroxy Phosphonates<i>via</i>Direct Hydroxylation of Phosphonate Compounds
  作者：Jiyan Liu、Wei Wang、Rui Wang、Lijun Gu

  DOI：10.1002/cjoc.201400858

  日期：2015.5

  It was found for the first time that Cs2CO3 serves as highly efficient catalyst for the direct hydroxylation reactions of phosphonates under mild conditions. This reaction provides an efficient approach to quaternary α‐hydroxy phosphonates, which possess intriguing biological activities and are widely used in many areas.

  首次发现在温和条件下，Cs 2 CO 3可以用作膦酸酯直接羟基化反应的高效催化剂。该反应提供了一种有效的方法来处理季铵化的α-羟基膦酸酯，其具有令人着迷的生物学活性，并在许多领域得到了广泛的应用。
• Highly Efficient Synthesis of Quaternary α-Hydroxy Phosphonates<i>via</i>Lewis Acid-Catalyzed Hydrophosphonylation of Ketones
  作者：Xin Zhou、Yanling Liu、Lu Chang、Jiannan Zhao、Deju Shang、Xiaohua Liu、Lili Lin、Xiaoming Feng

  DOI：10.1002/adsc.200900531

  日期：2009.11

  A Lewis acid catalyst has been first applied to the hydrophosphonylation of ketones, giving the corresponding quaternary α-hydroxy phosphonates in high yields (up to 98%). The present method was highly tolerable for functionalized ketones. Moreover, the first catalytic enantioselective hydrophosphonylation of an unactivated ketone was also realized by using a tridentate Schiff base-titanium complex

  路易斯酸催化剂已首先应用于酮的氢膦酰化反应，从而以高收率（高达98％）得到相应的季α-羟基膦酸酯。本方法对于官能化的酮具有高度的耐受性。此外，还通过使用三齿席夫碱-钛络合物实现了未活化的酮的第一催化对映体选择性氢膦酰基化。