diethyl (difluoro(p-tolyl)methyl)phosphonate | 185965-95-1

• 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: diethyl (difluoro(p-tolyl)methyl)phosphonate
• 英文别名: 1-[Diethoxyphosphoryl(difluoro)methyl]-4-methylbenzene；1-[diethoxyphosphoryl(difluoro)methyl]-4-methylbenzene
• CAS: 185965-95-1
• 化学式: C₁₂H₁₇F₂O₃P
• 分子量: 278.236
• InChiKey: WWQAWGRJQGSRIL-UHFFFAOYSA-N

物化性质

• 沸点：
  330.4±42.0 °C(Predicted)
• 密度：
  1.175±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  18
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  35.5
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  diethyl (difluoro(p-tolyl)methyl)phosphonate 在 劳森试剂 作用下， 以 甲苯 为溶剂， 反应 2.0h， 以65%的产率得到O,O-diethyl difluoro(4-methylphenyl)methylphosphonothioate
  参考文献：
  名称：

  Synthesis of Aryldifluoromethylphosphonothioic Acids from O,O-Diethyl Aryldifluoromethylphosphonothioates

  摘要：

  DOI：

  10.1021/jo000563t
• 作为产物：
  描述：

  diethyl (4-methylbenzoyl)phosphonate 在 4,4'-二氨基二苯乙烯-2,2'-二磺酸 作用下， 以 neat (no solvent) 为溶剂， 以36%的产率得到diethyl (difluoro(p-tolyl)methyl)phosphonate
  参考文献：
  名称：

  新型的不可水解的磷酸酪氨酸模拟物和L-4-（膦二氟甲基）苯丙氨酸L-2,3,5,6-四氟-4-（膦酰基甲基）苯丙氨酸的合成

  摘要：

  通过使用樟脑舒马坦作为手性助剂的对映选择性合成途径，制备了一种新的不可水解的磷酸酪氨酸类似物LF 4 Pmp及其受N-Fmoc保护的衍生物。测定了LF 4 Pmp的侧链pKa 2（6.9）。还描述了LF 2 Pmp的新合成。

  DOI：

  10.1016/s0040-4039(97)00027-0

文献信息

• Copper-Mediated Introduction of the CF₂ PO(OEt)₂ Motif: Scope and Limitations
  作者：Maria V. Ivanova、Alexandre Bayle、Tatiana Besset、Xavier Pannecoucke、Thomas Poisson

  DOI：10.1002/chem.201703542

  日期：2017.12.6

  can be functionalised. The procedure allows the conversion of aryl diazonium salts, as well as aryl, heteroaryl, vinyl and alkynyl iodonium salts, into the corresponding fluorinated molecules at room temperature. Mechanistic studies were performed to gain a better understanding of the reaction pathway. Under similar conditions, vinyl and aryl iodides, allyl halides, and benzyl bromides were also functionalised

  在本文中，报告了访问包含CF 2 PO（OEt）2的分子的一般程序。试剂CuCF 2 PO（OEt）2可以通过简单的协议访问，并且可以对多种底物进行功能化。该方法允许在室温下将芳基重氮盐以及芳基，杂芳基，乙烯基和炔基碘鎓盐转化为相应的氟化分子。进行了机理研究，以更好地了解反应途径。在相似的条件下，乙烯基和芳基碘化物，烯丙基卤化物和苄基溴化物也被官能化，并且研究了反应的范围和局限性。最后，该程序扩展到二硫化物，以提供新的SCF 2通道含PO（OEt）2的分子。
• Copper‐Mediated Formation of Aryl, Heteroaryl, Vinyl and Alkynyl Difluoromethylphosphonates: A General Approach to Fluorinated Phosphate Mimics
  作者：Maria V. Ivanova、Alexandre Bayle、Tatiana Besset、Thomas Poisson、Xavier Pannecoucke

  DOI：10.1002/anie.201507130

  日期：2015.11.2

  A general and efficient access to aryl, heteroaryl, vinyl and alkynyl difluoromethylphosphonates is described. The developed methodology using TMSCF2PO(OEt)2, iodonium salts and a copper salt provided a straightforward manifold to reach these highly relevant products. The reaction proved to be highly functional group tolerant and proceeded under mild conditions, giving the corresponding products in

  描述了一般和有效地获得芳基，杂芳基，乙烯基和炔基二氟甲基膦酸酯的方法。使用TMSCF 2 PO（OEt）2，碘鎓盐和铜盐开发的方法为获得这些高度相关的产品提供了直接途径。该反应被证明是高度官能团耐受的，并且在温和的条件下进行，从而给出相应的产物，收率良好至优异。该方法代表了这一重要类别的氟化支架的第一个通用合成路线，众所周知，该支架为体内稳定的磷酸盐替代物。
• Copper-Mediated Synthesis of Aryldifluoromethylphosphonates: A Sandmeyer Approach
  作者：Alexandre Bayle、Chloé Cocaud、Cyril Nicolas、Olivier R. Martin、Thomas Poisson、Xavier Pannecoucke

  DOI：10.1002/ejoc.201500373

  日期：2015.6

  Difluoromethylated arenes are scaffolds of great interest. We report herein a mild and general method for the introduction of the CF2PO(OEt)2 moiety into arenes. The CuCF2PO(OEt)2 species, which is generated in situ from the corresponding silylated derivatives, in combination with aryl diazonium salts furnished the highly valuable aryl difluoromethylphosphonates in moderate to good yields. This represents

  二氟甲基化芳烃是非常受关注的支架。我们在此报告了一种将 CF2PO(OEt)2 部分引入芳烃的温和且通用的方法。CuCF2PO(OEt)2 物质是由相应的甲硅烷基化衍生物原位生成的，与芳基重氮盐相结合，以中等至良好的产率提供了非常有价值的二氟甲基膦酸芳基酯。这是在温和条件下引入二氟甲基膦酸酯的第一种通用方法。
• Nickel and Copper Catalyzed <i>ipso</i> ‐Phosphonodifluoromethylation of Arylboronic Acids with BrCF ₂ P(O)(OEt) ₂ for the Synthesis of Phosphonodifluoromethylarenes
  作者：Alexander Knieb、Vinayak Krishnamurti、Xanath Ispizua‐Rodriguez、G. K. Surya Prakash

  DOI：10.1002/chem.202200457

  日期：2022.7.20

  The presented method allows the preparation of ipso-phosphonodifluoromethylarenes utilizing a heterobimetallic catalytic system of nickel and copper. The protocol represents an advantage over traditional palladium catalysed Suzuki coupling due to the short reaction times and the use of earth-abundant metals.

  所提出的方法允许利用镍和铜的异质双金属催化体系制备异膦酰基二氟甲基芳烃。由于反应时间短和使用地球上丰富的金属，该协议比传统的钯催化 Suzuki 耦合具有优势。
• Structure of Protein Tyrosine Phosphatase 1B in Complex with Inhibitors Bearing Two Phosphotyrosine Mimetics
  作者：Zongchao Jia、Qilu Ye、A. Nicole Dinaut、Qingping Wang、Deena Waddleton、Paul Payette、Chidambaram Ramachandran、Brian Kennedy、Gabriel Hum、Scott D. Taylor

  DOI：10.1021/jm010266w

  日期：2001.12.1

  Protein tyrosine phosphatases (PTPases) are signal-transducing enzymes that dephosphorylate intracellular proteins that have phosphorylated tyrosine residues. It has been demonstrated that protein tyrosine phosphatase 1B (PTP1B) is an attractive therapeutic target because of its involvement in regulating insulin sensitivity (Elcheby et al. Science 1999,283, 1544-1548). The identification of a second binding site in PTP1B (Puius et al., Proc. Natl. Acad. Sci. U.S.A 1997, 94, 13420-13425) suggests a new strategy for inhibitor design, where appropriate compounds may be made to simultaneously occupy both binding sites to gain much higher affinity and selectivity. To test this hypothesis and gain further insights into the structural basis of inhibitor binding, we have determined the crystal structure of PTP1B complexed with two non-peptidyl inhibitors, 4 and 5, both of which contain two aryl difluoromethylenephosphonic acid groups, a nonhydrolyzable phosphate mimetic. The structures were determined and refined to 2.35 and 2.50 Angstrom resolution, respectively. Although one of the inhibitors seems to have satisfied the perceived requirement for dual binding, it did not bind both the active site and the adjacent noncatalytic binding site as expected. The second or distal phosphonate group instead extends into the solvent and makes water-mediated interactions with Arg-47. The selectivity of the more potent of these two inhibitors, as well as four other inhibitors bearing two such phosphate mimetics for PTP1B versus seven other PTPases, was examined, In general, selectivity was modest to good when compared to PTPases Cdc25a, PTPmeg-1, PTP beta, and CD45. However, selectivity was generally poor when compared to other PTPases such as SHP-1, SHP-2, and especially TCPTP, for which almost no selectivity was found. The implications these results have concerning the utility of dual-binding inhibitors are discussed.