哌啶-1-基膦酰二氯 | 1498-56-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 中文名称: 哌啶-1-基膦酰二氯
• 英文名称: piperidin-1-yl-phosphonic acid dichloride
• 英文别名: piperidinophosphoryl chloride；Phosphonic dichloride, piperidino-；1-dichlorophosphorylpiperidine
• CAS: 1498-56-2
• 化学式: C₅H₁₀Cl₂NOP
• 分子量: 202.02
• InChiKey: FZHNJMKVRJJKBK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  10
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  20.3
• 氢给体数：
  0
• 氢受体数：
  2

安全信息

• 海关编码：
  2933399090

反应信息

• 作为反应物：
  描述：

  哌啶-1-基膦酰二氯 在 仲丁基锂 、 sodium hydride 作用下， 以 四氢呋喃 、 正己烷 为溶剂， 反应 8.25h， 生成 (Z)-(1-butenyl)(ethoxy)(piperidinyl)phosphine oxide
  参考文献：
  名称：

  Synthesis of P-chiral enephosphonic acid derivatives

  摘要：

  An efficient and convenient synthesis of chiral enephosphonic acid derivatives (enephosphonates, enephosphonamides, enephosphinates) was reported by a two-step procedure involving alkylidenediphosphorylation of nucleophiles followed by a Horner-Emmons olefination. Depending on the selected strategy, the synthesis could be executed according to a one-pot or a two-step reaction sequence. Regioselectivity of Horner-Emmons reaction and P-31-NMR study of diphosphorylated anions were described. (C) 2002 Elsevier Science B.V. All rights reserved.

  DOI：

  10.1016/s0022-328x(02)01889-2
• 作为产物：
  描述：

  哌啶盐酸盐 在 三氯氧磷 作用下， 生成 哌啶-1-基膦酰二氯
  参考文献：
  名称：

  Michaelis; Kahnemann, Justus Liebigs Annalen der Chemie, 1903, vol. 326, p. 186

  摘要：

  DOI：

文献信息

• Hydrolysis of cyclic phosphoramides. Evidence for syn lone pair catalysis
  作者：Andrés Núñez、Dyanna Berroterán、Oswaldo Núñez

  DOI：10.1039/b300916e

  日期：——

  Hydrolysis between 1.5 < pH < 4 of five and six membered cyclic phosphoramides has been followed by UV and 31PNMR spectroscopy. The observed rates fit the equation: kobs = kH2O [H+]/([H+] + Ka) + k′H2O, where kH2O and k′H2O are the pseudo first-order rate constants of water attack on the protonated phosphoramide and its unprotonated form, respectively, and Ka is the phosphoramide acidity equilibrium constant. Although, faster hydrolysis rates on the five membered ring are expected due to the energy released in going from a strained cyclic to a “strained free” trigonal-bipyramidal-pentacoordinated intermediate, with one of the cyclic nitrogens occupying the apical position, these compounds react slightly faster (kH2O values) but slower regarding the k′H2O values than the six membered analogs. The balance in reactivity is attributed to the additional stability obtained in the six membered cyclic compounds by a syn orientation of the two lone pairs of the cyclic nitrogen to the water attack. This stabilization does not exist in the five membered phospholidines since the water attack is perpendicular to the electron pairs of the cyclic nitrogen. In agreement with the incoming water orientation, the product ratios from the hydrolysis show that in the five membered rings the main product is the one produced by endocyclic cleavage; meanwhile, in the six membered cyclic phospholines the kinetic product is the one produced by exocyclic cleavage. The syn orientation of two electron pairs on nitrogen stabilizes the transition state of water approach to the phosphoramides by ca. 3 kcal mol−1 when compared to the orthogonal attack.

  在1.5 < pH < 4的条件下，五元环和六元环磷酰胺的水解过程通过紫外光谱和31P核磁共振波谱进行了研究。观察到的反应速率符合以下方程：kobs = kH2O [H+]/([H+] + Ka) + k′H2O，其中kH2O和k′H2O分别是水分子攻击质子化磷酰胺和非质子化磷酰胺的假一级速率常数，Ka是磷酰胺酸度平衡常数。虽然预计五元环的水解速率会更快，因为从受限环状结构转变为“无受限”三角双锥五配位中间态时释放能量，其中一个环状氮原子占据顶端位置，但这些化合物的反应速率（kH2O值）略快，而关于k′H2O值则较慢于六元环的类似物。反应活性的平衡归因于六元环状化合物在水攻击时通过syn取向使环状氮的两个孤对电子与水攻击方向一致所获得的额外稳定性。这种稳定化在五元环磷酯中不存在，因为水攻击方向垂直于环状氮的电子对。与进来的水取向一致，水解产物的比例表明，在五元环中主要产物是由环内断裂产生的；而在六元环磷脂中，动力学产物是由环外断裂产生的。氮原子上两个电子对的syn取向通过与正交攻击相比，大约稳定了磷酰胺水接近过渡态的3 kcal mol−1。
• Chiral Phosphoramide-Catalyzed Enantioselective Addition of Allylic Trichlorosilanes to Aldehydes. Preparative Studies with Bidentate Phosphorus-Based Amides
  作者：Scott E. Denmark、Jiping Fu、Michael J. Lawler

  DOI：10.1021/jo052203h

  日期：2006.2.1

  that more than one Lewis basic moiety (phosphoramide) is involved in the rate- and stereochemistry-determining step of enantioselective allylation, bidentate chiral phosphoramides were developed. Different chiral phosphoramide moieties were connected by tethers of methylene chains of varying length. The rate and enantioselectivity of allylation with allyltrichlorosilane promoted by the bidentate phosphoramides

  基于机械学的见解，即对映选择性烯丙基化的速率和立体化学决定步骤涉及多个路易斯基本部分（磷酰胺），开发了二齿手性磷酰胺。通过不同长度的亚甲基链的束缚连接不同的手性磷酰胺部分。发现由二齿磷酰胺促进的与烯丙基三氯硅烷的烯丙基化的速率和对映选择性高度依赖于系链长度。设计了一种新的基于2,2'-双吡咯烷骨架的磷酰胺，在烯丙基化反应中具有良好的收率，有效的转化率和高的对映选择性。对映体纯的2,2'-双吡咯烷的合成很容易通过吡咯烷的光二聚化，然后用四氢呋喃进行拆分而大规模完成。l（或d）酒石酸。用各种取代的烯丙基三氯硅烷和不饱和醛检查了烯丙基化反应的范围。通过添加不对称的γ-二取代的烯丙基三氯硅烷，该方法已应用于立体异构的季中心的构建。
• Synthesis of Phosphoramides for the Lewis Base-Catalyzed Allylation and Aldol Addition Reactions
  作者：Scott E. Denmark、Xiping Su、Yutaka Nishigaichi、Diane M. Coe、Ken-Tsung Wong、Stephen B. D. Winter、Jun Young Choi

  DOI：10.1021/jo9820723

  日期：1999.3.1

  Both chiral and achiral phosphoramides of diverse structure were prepared from diamines by the coupling to phosphorus(V) or phosphorus(III) reagents. Several enantiopure 1,2-diphenyl-1,2-ethanediamine analogues have been prepared by the reductive coupling of the corresponding N-silylimine with NbCl(4)(THF)(2) and subsequent resolution by the formation of diastereomeric menthyl carbamates. (S,S)-N,

  通过与磷（V）或磷（III）试剂偶联，由二胺制备了多种结构的手性和非手性磷酰胺。几种对映体纯的1,2-二苯基-1,2-乙二胺类似物是通过将相应的N-硅酰亚胺与NbCl（4）（THF）（2）还原偶联而制备的，随后通过形成非对映异构的氨基甲酸薄荷酯进行拆分。（S，S）-N，N′-二-（1-萘基）-1,2-二苯基-1,2-乙二胺15是通过（S，S）-1,2-二苯基-1的芳基化制备的，2-乙二胺与碘化萘。
• Synthesis and Biological Evaluation of 5-Fluoro-2'-deoxyuridine Phosphoramidate Analogs
  作者：Kristin M. Fries、Carolyn Joswig、Richard F. Borch

  DOI：10.1021/jm00014a019

  日期：1995.7

  compound, the piperidine analog 1g was only 2-fold less potent, confirming that nitrogen basicity may be as important as the presence of an alkylating group. Addition of thymidine reversed the growth inhibition of the morpholine and piperidine analogs, suggesting that these compounds may also undergo intracellular conversion to 5-fluoro-2'-deoxyuridine 5'monophosphate. The thymidine and deoxyuridine derivatives

  已经制备了一系列5-氟-2'-脱氧尿苷的烷基化氨基磷酸酯类似物，并在体外评估了它们对鼠L1210白血病和B16黑素瘤细胞的生长抑制活性。这些化合物被设计为可在胞内释放氨基磷酸酯阴离子，希望它们可作为胸苷酸合酶的不可逆抑制剂起作用。期望的是核苷部分的结合将随后经由氨基磷酸酯使酶烷基化。氯化物，溴化物，碘化物和甲苯磺酸酯类似物是L1210细胞增殖的高效抑制剂，在较高的药物浓度和较长的暴露时间下均观察到抑制作用增强。胸苷的添加完全逆转了所有化合物的抑制作用，提示这些化合物通过抑制胸苷酸合酶起作用。尽管非烷基化吗啉类似物1f为约。哌啶类似物1g的效力比甲基（氯乙基）氨基化合物低50倍，效力仅低2倍，这证明氮的碱性与烷基化基团的存在同样重要。胸苷的添加逆转了吗啉和哌啶类似物的生长抑制，表明这些化合物也可能经历细胞内转化为5-氟-2'-脱氧尿苷5'单磷酸酯。胸苷和脱氧尿苷衍生物2和3在L1210分析中
• Asymmetric allylation of aromatic aldehydes catalyzed by chiral phosphoramides prepared from (S)-proline
  作者：Katsuhiko Iseki、Yoshichika Kuroki、Mie Takahashi、Satoshi Kishimoto、Yoshiro Kobayashi

  DOI：10.1016/s0040-4020(97)00084-7

  日期：1997.3

  Chiral phosphoramides prepared from (S)-proline were used to catalyze the allylation and crotylation of aromatic aldehydes with allylic trichlorosilanes in good enantioselective yields. Phosphoramides 4d and 4m gave chiral homoallylic alcohols and their enantiomers, respectively, with similar levels of enantioselectivity.

  由（S）-脯氨酸制备的手性磷酰胺用于催化芳族醛与烯丙基三氯硅烷的烯丙基化和丁烯酰化，并具有良好的对映选择性。磷酰胺4d和4m分别得到手性均烯醇和它们的对映异构体，具有相似的对映选择性。