4-chloro-2-formyl-N,N-diisopropylbenzamide | 1225544-88-6

• 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-chloro-2-formyl-N,N-diisopropylbenzamide
• 英文别名: 4-chloro-2-formyl-N,N-di(propan-2-yl)benzamide
• CAS: 1225544-88-6
• 化学式: C₁₄H₁₈ClNO₂
• 分子量: 267.755
• InChiKey: OVIVVNQXBHPXQU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  18
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  37.4
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  4-chloro-2-formyl-N,N-diisopropylbenzamide 在 sodium tetrahydroborate 、 盐酸 作用下， 以 甲醇 、 水 为溶剂， 生成 5-氯-1(3h)-异苯并呋喃酮
  参考文献：
  名称：

  动力霉素 A 衍生物通过突变合成作为潜在的癌症化疗药物

  摘要：

  烯二炔抗肿瘤抗生素具有非凡的结构，并表现出强大的 DNA 切割特性，这激发了人们对癌症治疗的持续兴趣。然而，它们复杂的结构和高反应活性对其临床生产和开发提出了巨大的挑战。我们在此报告了概念验证研究，使用变合成策略将化学合成与关键碘蒽-γ-硫内酯中间体的选择性修饰结合起来，用于动力霉素 A 和所有其他已知的蒽醌稠合烯二炔 (AFE) 的生物合成。通过对无法合成这种基本结构单元的突变细菌生产者进行化学互补，我们表明可以制备取代蒽醌基序 A 环的动力霉素衍生物。在没有来自该中间体的天然生产的竞争的情况下，最有效地利用这些外部提供的结构类似物进行前体定向的生物合成成为可能。为了实现这一目标，我们描述了所需的 Δ orf15阻断突变体以及碘蒽结构变体库的一般合成路线。它们的成功掺入为增强 DNA 结合和调节修饰烯二炔的生物还原激活以进行 DNA 切割打开了大门。

  DOI：

  10.1002/hlca.202300123
• 作为产物：
  描述：

  4-氯苯甲酰氯 在 正丁基锂 、 三乙胺 作用下， 以 四氢呋喃 、 正己烷 、 甲苯 为溶剂， 反应 25.5h， 生成 4-chloro-2-formyl-N,N-diisopropylbenzamide
  参考文献：
  名称：

  Manufacturing Synthesis of 5-Substituted Phthalides

  摘要：

  A manufacturing synthesis of 5-chlorophthalide has been elaborated. The key step of the procedure is ortho-lithiation of 4-chloro-N,N-diisopropylbenzamide, followed by formylation with dimethyl formamide. Reduction of the formyl moiety and subsequent ring closure, which can be carried out also in one pot, led to 5-chlorophthalide in high overall yield. The procedure has also been successfully adapted for the synthesis of the 5-fluoro and 5-trifluoromethyl analogues. The compounds thus obtained are useful building blocks in the synthesis of various heterocyclic ring systems.

  DOI：

  10.1021/op100049t

文献信息

• Directed <i>ortho</i>-metalation–nucleophilic acyl substitution strategies in deep eutectic solvents: the organolithium base dictates the chemoselectivity
  作者：Simone Ghinato、Giuseppe Dilauro、Filippo Maria Perna、Vito Capriati、Marco Blangetti、Cristina Prandi

  DOI：10.1039/c9cc03927a

  日期：——

  Directed ortho metalation (DoM) or nucleophilic acyl substitution (SNAc) can be efficiently programmed on the same aromatic carboxylic acid amide, in a choline chloride-based eutectic mixture, by simply switching the nature of the organolithium reagent. Telescoped, one-pot ortho-lithiation/Suzuki–Miyaura cross-couplings have also been demonstrated for the first time in Deep Eutectic Solvents.

  定向邻位金属化（d Ò M）或亲核酰基取代（S Ñ AC）可以有效地设定为在同芳族羧酸酰胺，在基于氯化物胆碱共熔混合物，通过简单地切换有机锂试剂的性质。伸缩式单罐正锂化/铃木-宫浦交叉联结也已在深共晶溶剂中首次得到证明。
• Regioselective Pd-Catalyzed Aerobic Aza-Wacker Cyclization for Preparation of Isoindolinones and Isoquinolin-1(2<i>H</i>)-ones
  作者：Guoqiang Yang、Wanbin Zhang

  DOI：10.1021/ol203043h

  日期：2012.1.6

  A switchable regioselective intramolecular aerobic aza-Wacker cyclization catalyzed by palladium is presented. Isolndollnones or isoquinolin1(2H)-ones could be prepared selectively from the same substrates using different catalysts. The type and steric hindrance of the ligands may be the variables most significant for regiocontrol.
• Intensification of Continuous Ortho-Lithiation at Ambient Conditions—Process Understanding and Assessment of Sustainability Benefits
  作者：Ruili Feng、Sushil Ramchandani、Balamurugan Ramalingam、Song Wei Benjamin Tan、Chuanzhao Li、Soo Khean Teoh、Kamelia Boodhoo、Paul Sharratt

  DOI：10.1021/acs.oprd.7b00142

  日期：2017.9.15

  The feasibility of performing an ortho-lithiation reaction in a T-reactor and a spinning disc reactor (SDR) at ambient temperature has been demonstrated and compared experimentally to a conventional batch stirred tank reactor (STR) process performed at a cryogenic temperature of -70 degrees C. The benefits of significantly improved mixing and much shorter residence times in the flow reactors eliminated the need for cryogenic cooling in batch processing which is a costly requirement. A theoretical evaluation of a scaled up process with a design product output of 3 tons per year highlights that significant process intensification is achievable in the flow reactors which demonstrate higher energy efficiency, better volume efficiency, smaller processing inventory, and smaller equipment footprint. For this reaction, the performance of the T-reactor is the best among the three reactors leading to much lower reactor investment and operating cost. The SDR was also demonstrated to be effective, even though this reaction did not take advantage of its inherent capabilities in solid handling or rapid heat removal through evaporation/gas disengagement, all of which present major challenges in enclosed channel geometries such as the T-reactor.