4-methyl-N-(methyl-d3)aniline | 922543-66-6

• 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: 4-methyl-N-(methyl-d3)aniline
• 英文别名: 4-Methyl-N-methyl(D3)-aniline；4-methyl-N-(trideuteriomethyl)aniline
• CAS: 922543-66-6
• 化学式: C₈H₁₁N
• 分子量: 124.158
• InChiKey: QCIFLGSATTWUQJ-BMSJAHLVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.04
• 重原子数：
  9.0
• 可旋转键数：
  2.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  12.03
• 氢给体数：
  1.0
• 氢受体数：
  1.0

反应信息

• 作为反应物：
  描述：

  4-methyl-N-(methyl-d3)aniline 、 对溴三氟甲苯 在 1-[2,6-bis(isopropyl)phenyl]-2-[tert-butyl(2-pyridinyl)phosphino]-1H-Imidazole 、 palladium diacetate 、 potassium hydroxide 作用下， 以 1,4-二氧六环 为溶剂， 反应 12.0h， 以78%的产率得到C₁₅H₁₁⁽²⁾H₃F₃N
  参考文献：
  名称：

  钯催化硝基芳烃与甲醇的甲基化

  摘要：

  开发了使用甲醇作为绿色甲基化剂直接从硝基芳烃合成N-甲基-芳基胺的方法。成功的关键是使用由乙酸钯和配位体的1- [2,6-双（异丙基）苯基] -2- [叔-丁基（2-吡啶基）膦基] -1的特定催化剂体系的ħ -咪唑（L1）。在相对温和的条件下合成20多种N-甲基-芳基胺证明了该方案的普遍性。将这种新颖的方法与使用相同催化剂的后续偶联工艺相结合，可以使芳香族硝基化合物有效地分散为包括药物分子在内的各种胺类。

  DOI：

  10.1002/anie.201814146
• 作为产物：
  描述：

  isobutyl N-p-tolylcarbamate 在 lithium aluminium deuteride 作用下， 以 四氢呋喃 为溶剂， 以87 mg的产率得到4-methyl-N-(methyl-d3)aniline
  参考文献：
  名称：

  与叔丁基过氧化氢的氧化曼尼希反应的机理研究。过渡金属盐的作用

  摘要：

  提出了过渡金属催化 N,N-二烷基苯胺与叔丁基过氧化氢 (TBHP) 作为氧化剂的氧化曼尼希反应的一般机制。该机制包括从 4-甲氧基到 4-氰基-N,N-二甲基苯胺均匀的限速单电子转移 (SET)。叔丁基过氧自由基是决定速率的 SET 步骤中的主要氧化剂，随后是竞争性向后 SET 和 α 位碳氢键的不可逆异裂裂解为氮。第二个 SET 完成 N,N-二甲基苯胺向亚胺离子的转化，亚胺离子随后在形成曼尼希加合物之前被亲核溶剂或氧化剂捕获。Rh(2)(cap)(4)、RuCl(2)(PPh(3))(3)、CuBr、FeCl(3) 和 Co(OAc)(2) 在 N 中的一般作用，T-HYDRO 氧化 N-二烷基苯胺是为了启动 TBHP 向叔丁基过氧自由基的转化。第二种途径涉及 O(2) 作为氧化剂，存在于铜盐、铁盐和钴盐中。讨论了线性自由能关系 (LFER) 分析、动力学和产物同位素效应（KIE 和

  DOI：

  10.1021/ja3113559

文献信息

• <i>N</i>-Demethylation of <i>N,N</i>-Dimethylanilines by the Benzotriazole <i>N</i>-Oxyl Radical: Evidence for a Two-Step Electron Transfer−Proton Transfer Mechanism
  作者：Enrico Baciocchi、Massimo Bietti、Osvaldo Lanzalunga、Andrea Lapi、Daniele Raponi

  DOI：10.1021/jo100040y

  日期：2010.3.5

  The reaction of the benzotriazole N-oxyl radical (BTNO) with a series of 4-X-N,N-dimethylanilines (X = CN, CF3, CO2CH2CH3, CH3, OC6H5, OCH3) has been investigated in CH3CN. Product analysis shows that the radical, 4-X-C6H4N(CH3)CH2•, is first formed, which can lead to the N-demethylated product or the product of coupling with BTNO. Reaction rates were found to increase significantly by increasing the

  苯并三唑N-氧基自由基（BTNO）与一系列4-X- N，N-二甲基苯胺（X = CN，CF 3，CO 2 CH 2 CH 3，CH 3，OC 6 H 5，OCH 3）已在CH 3 CN中进行了研究。产物分析表明，首先形成了自由基4-XC 6 H 4 N（CH 3）CH 2 •，这可能导致生成N-脱甲基产物或与BTNO偶联的产物。发现反应速率通过增加芳基取代基的供电子能力而显着提高（ρ + = -3.8）。使用给电子性取代基（X = CH 3，OC 6 H 5，OCH 3），未观察到分子间氘动力学同位素效应（DKIE）和基本的分子内DKIE。在具有吸电子取代基（X ＝ CN，CF 3，CO 2 CH 2 CH 3）的情况下，观察到分子间和分子内DKIE的实质值。这些结果可以根据N的电子转移机理来解释，N-二甲基苯胺到BTNO自由基，然后使苯胺自由基阳离子去质子化（ET-PT机理）。通过将Marcus方程应用于X
• Isotope effect profiles in the N-demethylation of N,N-dimethylanilines: a key to determine the pK_aof nonheme Fe(<scp>iii</scp>)–OH complexes
  作者：Alessia Barbieri、Martina De Gennaro、Stefano Di Stefano、Osvaldo Lanzalunga、Andrea Lapi、Marco Mazzonna、Giorgio Olivo、Barbara Ticconi

  DOI：10.1039/c5cc00411j

  日期：——

  pK_aof [(N4Py)Fe^III–OH]²⁺is obtained from the kinetic isotope effect profiles in theN-demethylation ofN,N-dimethylanilines promoted by [(N4Py)Fe^IVO]²⁺.

  通过[(N4Py)Fe^III–OH]²⁺在[(N4Py)Fe^IVO]²⁺促进的N,N-二甲基苯胺的N-去甲基化反应动力同位素效应剖面得到

  K_a。

• Sustainable and Affordable Synthesis of (Deuterated) <i>N</i>-Methyl/Ethyl Amines from Nitroarenes
  作者：Akash Mondal、Abhijith Karattil Suresh、Ganesan Sivakumar、Ekambaram Balaraman

  DOI：10.1021/acs.orglett.2c03595

  日期：2022.12.16

  affordable synthesis of (deuterated) N-methyl/ethyl amines directly from nitroarenes is disclosed. The reaction is catalyzed by a single-site manganese catalyst and involves tandem dehydrogenation, transfer hydrogenation, and borrowing hydrogenation. This catalytic protocol is highly selective and provides a facile method for the large-scale synthesis of a series of N-CH3/N-CD3 aniline derivatives with excellent

  公开了直接从硝基芳烃可持续和负担得起的（氘代）N-甲基/乙基胺的合成。该反应由单中心锰催化剂催化，包括串联脱氢、转移氢化和借位氢化。该催化方案具有高选择性，为大规模合成一系列具有优异官能团耐受性的N -CH 3 / N -CD 3苯胺衍生物提供了一种简便的方法。
• Catalytic Amination of Alcohols Using Diazo Compounds under Manganese Catalysis Through Hydrogenative N‐Alkylation Reaction
  作者：Reshma Babu、Subarna Sukanya Padhy、Rohit Kumar、Ekambaram Balaraman

  DOI：10.1002/chem.202302007

  日期：2023.11.2

  N-alkylation of diazo compounds: Value-added to industry waste diazo compounds using feedstock alcohols under earth-abundant manganese catalysis.alcoholdehydrogenative couplingdrug intermediateshydrogenkinetic studiesmanganese

  重氮化合物的N -烷基化：在地球丰富的锰催化下使用原料醇对工业废重氮化合物进行增值。醇氢偶联药物中间体氢动力学研究锰
• A Kinetic Study of the Reaction of <i>N</i>,<i>N</i>-Dimethylanilines with 2,2-Diphenyl-1-picrylhydrazyl Radical: A Concerted Proton−Electron Transfer?
  作者：Enrico Baciocchi、Alessandra Calcagni、Osvaldo Lanzalunga

  DOI：10.1021/jo8001672

  日期：2008.6.1

  The reactivity of the 2,2-diphenyl-1-picrylhydrazyl radical (dpph(center dot)) toward the N-methyl C-H bond of a number of 4-X-substituted-N,N-dimethylanilines (X = OMe, OPh, CH3, H) has been investigated in MeCN, in the absence and in the presence of Mg(ClO4)(2), by product, and kinetic analysis. The reaction was found to lead to the N-demethylation of the N,N-dimethylaniline with a rate quite sensitive to the electron donating power of the substituent (rho(+) = -2.03). With appropriately deuterated N,N-dimethylanilines, the intermolecular and intramolecular deuterium kinetic isotope effects (DKIEs) were measured with the following results. Intramolecular DKIE [(k(H)/k(D))(intra)] was found to always be similar to intermolecular DKIE [(k(H)/k(D))(inter)]. These results suggest a single-step hydrogen transfer mechanism from the N-C-H bond to dpph(center dot) which might take the form of a concerted proton-electron transfer (CPET). An electron transfer (ET) step from the aniline to dpph(center dot) leading to an anilinium radical cation, followed by a proton transfer step that produces an alpha-amino carbon radical, appears very unlikely. Accordingly, a rate-determining ET step would require no DKIE or at least different inter and intramolecular isotope effects. On the other hand, an equilibrium-control led ET is not compatible with the small slope value (-0.22 kcal(-1) K-1) of the log k(H)/Delta G degrees plot. Furthermore, the reactivity increases by changing the solvent to the less polar toluene whereas the reverse would be expected for an ET mechanism. In the presence of Mg2+, a strong rate acceleration was observed, but the pattern of the results remained substantially unchanged: inter and intramolecular DKIEs were again very similar as well as the substituent effects. This suggests that the same mechanism (CPET) is operating in the presence and in the absence of Mg2+. The significant rate accelerating effect by Mg2+ is likely due to a favorable interaction of the Mg2+ ion with the partial negatively charged alpha-methyl carbon in the polar transition state for the hydrogen transfer process.