N,N-bis(trideuteriomethyl)benzamide | 24768-98-7

• 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: N,N-bis(trideuteriomethyl)benzamide
• 英文别名: N,N-di(trideuteriomethyl)benzamide；N,N-dimethylbenzamide-d6；N,N-bis-trideuteriomethyl-benzamide；N-Di-(trideuterio-methyl)benzamid
• CAS: 24768-98-7
• 化学式: C₉H₁₁NO
• 分子量: 155.145
• InChiKey: IMNDHOCGZLYMRO-WFGJKAKNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.39
• 重原子数：
  11.0
• 可旋转键数：
  3.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  20.31
• 氢给体数：
  0.0
• 氢受体数：
  1.0

反应信息

• 作为反应物：
  描述：

  N,N-bis(trideuteriomethyl)benzamide 在 叔丁基过氧化氢 、 iron(III) tetraphenylporphyrin 作用下， 以 二氯甲烷 为溶剂， 生成
  参考文献：
  名称：

  的甲基基团的氧化N，N- -dimethylbenzamides由细胞色素P450单氧化酶系统模型

  摘要：

  的氧化N，N- -dimethylbenzamides到相应Ñ甲酰基Ñ -methylbenzamides使用tetraphenylporphyrinato -铁（III）-Bu吨OOH独立于苯甲酰胺组和受试者的芳基环的取代基的对的氘动力学同位素效应5.6。这些结果与涉及从底物直接提取氢原子的机理是一致的。

  DOI：

  10.1016/s0040-4039(00)97769-4
• 作为产物：
  描述：

  二甲基-D6-胺盐酸盐 、 苯甲酰氯 在 sodium hydroxide 作用下， 以 四氢呋喃 为溶剂， 反应 6.0h， 以80%的产率得到N,N-bis(trideuteriomethyl)benzamide
  参考文献：
  名称：

  Electrochemical models for cytochrome P-450. N-Demethylation of tertiary amides by anodic oxidation

  摘要：

  DOI：

  10.1021/jo00271a040

文献信息

• Oxidation of tertiary benzamides by 5,10,15,20-tetraphenylporphyrinatoiron^IIIchloride–tert-butylhydroperoxide
  作者：Luis Constantino、Jim Iley

  DOI：10.1039/b404169k

  日期：——

  no steric hindrance to oxidation of an isopropyl group. Thus, we propose that these reactions proceed via hydrogen atom abstraction to form an alpha-carbon-centred radical and we attribute the observed diminished reactivity of the N-cyclopropyl group to its known reluctance to form a cyclopropyl radical. Oxidation of N-methyl-N-(2,2,3,3-tetramethylcyclopropyl)methylbenzamide provides preliminary evidence

  叔苯甲酰胺在N-烷基的α-位被5,10,15,20-氯化四苯基卟啉铁（III）-Bu'（t）OOH系统氧化。主要产物是N-酰基酰胺，尽管也会形成少量的仲酰胺，即脱烷基化产物。这些反应的初始速率对初始底物浓度的曲线是弯曲的，表明形成了氧化剂-底物复合物。反应速率对苯甲酰胺部分中的取代基几乎不敏感，但对于N，N-（CH（3））（2）和N，N-（CD（ 3））（2）化合物。比较N-烷基-N-甲基苯甲酰胺的反应产物后发现，对于所有研究的化合物（除N-环丙基-N-甲基苯甲酰胺以外），烷基的氧化是优选的，对于N-烯丙基-N-甲基苯甲酰胺，强烈建议（约为8倍）。与微粒体氧化相反，对异丙基的氧化没有空间位阻。因此，我们提出这些反应是通过氢原子抽象进行的，以形成一个以α-碳为中心的基团，并且我们将观察到的N-环丙基的反应性降低归因于其已知的不愿意形成环丙基的基团。N-甲基-N-（2,2,3,3-四甲基环丙基
• Identification of unexpected unlabeled <i>N,N</i> -dimethylamide formation in the synthesis of deuterated fragment of ribociclib by a HATU-mediated coupling reaction
  作者：Kuo Gai、Baomin Liu、Yinsheng Zhang

  DOI：10.1002/jlcr.3690

  日期：2019.2

  Starting from N,N-dimethylamine and D2O, deuterated fragment of ribociclib was synthesized for use as a mass spectroscopy internal standard. Furthermore, systematic studies on D0 (unlabeled material) formation during the amidation reaction were performed, leading to the identification of a coupling reagent, HATU (O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate), as main cause. Finally, an alternative route was designed using EDCI/HOBT as coupling reagents to produce the desired deuterated compound without D0 residue.

  从 N,N-二甲胺和 D2O 开始，合成了 ribociclib 的氚代片段，用作质谱内标。此外，还对酰胺化反应过程中 D0（未标记物质）的形成进行了系统研究，从而确定了一种偶联试剂 HATU（O-(7-氮杂苯并三唑-1-基)-N,N,N′,N′-四甲基脲六氟磷酸盐）是主要原因。最后，我们设计了一条替代路线，使用 EDCI/HOBT 作为偶联试剂，生成所需的无 D0 残留的氚代化合物。
• Deoxygenative Cross-Coupling of C(aryl)–O and C(amide)═O Electrophiles Enabled by Chromium Catalysis Using Bipyridine Ligand
  作者：Chao Li、Liang Ling、Zheng Luo、Sha Wang、Xiaoyu Zhang、Xiaoming Zeng

  DOI：10.1021/acscatal.2c06264

  日期：2023.3.3

  analysis and deuterium-labeling experiments indicate that cleavage of ester C–O bonds by Cr and subsequent silylation leads to the formation of arylated silachromate, which regioselectively adds to carbonyls of amides through reductive elimination and deoxygenative hydrogen transfer, resulting in the reductive cross-coupling of C(aryl)–O and C(amide)═O electrophiles.

  未活化的 C–O 和不饱和的 C═O 亲电子试剂之间的脱氧交叉偶联仍然是合成化学中未解决的挑战。在这里，我们报告了 C–O/C=O 亲电子试剂的脱氧交叉偶联，通过未活化的芳基酯与不饱和酰胺的反应，由铬催化实现。廉价且简单的 CrCl 3盐与联吡啶配体、镁还原剂和氯硅烷结合，在促进涉及氢转移的 C-O 和 C=O 键之间的脱氧偶联方面表现出高反应性。该反应提供了一种策略，通过锻造 C(sp 2 )–C(sp 3) 结合阻碍通常在还原条件下发生的竞争性酯自偶联和羰基还原。基于高分辨率质谱分析和氘标记实验的机理研究表明，Cr 对酯 C-O 键的裂解和随后的甲硅烷基化导致芳基硅铬酸盐的形成，它通过还原消除和脱氧氢区域选择性地加到酰胺的羰基上转移，导致 C(aryl)–O 和 C(amide)═O 亲电子试剂的还原交叉偶联。
• Kinetics and mechanism of aliphatic amine oxidation by aqueous (batho)2CuII
  作者：Fengjiang Wang、Lawrence M. Sayre

  DOI：10.1021/ja00027a032

  日期：1992.1

  The kinetics of oxidation of a large series of aliphatic amines by the 'high-potential'' oxidant (batho)2Cu(II) (batho = 2,9-dimethyl-4,7-diphenyl-1,10-phenanthrolinedisulfonate) was studied under pseudo-first-order conditions (excess amine) in water or in 30% aqueous methanol (v/v) at 25-degrees-C over the pH range 7-11. The oxidations follow bell-shaped pH-rate profiles, with the low-pH leg reflecting the fact that only the free amine base is subject to oxidation and the high-pH leg representing conversion of (batho)2Cu(II) to an ineffective oxidant at high pH. The latter is thought to be (batho)Cu(II)(OH2)OH on the basis of the observed effect of [batho] on rate at high pH, and curve fitting of the rate data yielded estimates of the unitless K(eq) values governing this conversion. The variation in rate with degree of N-substitution and other structure-reactivity trends (such as the effect of ring size and the non-rate-retarding effect of 2,4,6-trimethyl substitution on PhCH2NR2) support a mechanism involving initial outer-sphere one-electron transfer, followed by proton transfer to the solvent, and then a rapid second one-electron oxidation to give imine/iminium product. Inner-sphere coordination of chelating amines shuts down the redox reaction, presumably as a consequence of displacement of the batho ligand(s) needed for high oxidant strength. Deuterium kinetic isotope effect (DKIE) measurements (i) comparing PhCD2N(CD3)2 vs PhCH2N(CH3)2 (intermolecular DKIE) and (ii) determining N-dealkylation preference in the case of PhCH2N(CH3)CD2Ph (intramolecular DKIE) suggest that the initial electron transfer is mainly rate-limiting. A rate comparison between erythro and three diastereomers of 1,2-diphenyl-2-piperidinoethanol indicates a stereoelectronic preference for one-electron oxidation at nitrogen when held antiperiplanar to a beta-hydroxyl. Stoichiometry studies using an excess of the Cu(II) oxidant reveal regioselective and chemoselective factors governing the overall amine-to-iminium oxidations.
• Electrochemical models for cytochrome P-450. N-Demethylation of tertiary amides by anodic oxidation
  作者：Larry R. Hall、Reynold T. Iwamoto、Robert P. Hanzlik

  DOI：10.1021/jo00271a040

  日期：1989.5