1-benzyl-3,3-difluoroindolin-2-one | 221665-91-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: 1-benzyl-3,3-difluoroindolin-2-one
• 英文别名: 1-Benzyl-3,3-difluoro-1H-indole-2(3H)-one；1-benzyl-3,3-difluoroindol-2-one
• CAS: 221665-91-4
• 化学式: C₁₅H₁₁F₂NO
• 分子量: 259.255
• InChiKey: GNUSZEFQDTTWBB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  19
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.13
• 拓扑面积：
  20.3
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1-benzyl-3,3-difluoroindolin-2-one 在 N-溴代丁二酰亚胺(NBS) 、 偶氮二异丁腈 作用下， 以 氯苯 为溶剂， 以69%的产率得到3,3-二氟-1,3-二氢-2H-吲哚-2-酮
  参考文献：
  名称：

  Copper-Mediated Fluoroalkylation Reactions with Iododifluoroacetamides: Controlling the Selectivity among Cross-Coupling, Intramolecular Cyclization, and Homocoupling Reactions

  摘要：

  Cu-mediated fluoroalkylation reactions with iododifluoroacetamides I have been systematically investigated. It was found that three types of reactions may coexist in Cu-mediated reactions between iododifluoroacetamides and aryl/alkenyl iodides: cross-coupling, intramolecular cyclization, and homocoupling reactions. The selectivity among these three types of reactions could be controlled by tuning the substituents on the nitrogen atom of iododifluoroacetamides, and/or by removing the cross-coupling reaction partner (aryl/alkenyl halides). The general rule is as follows: (a) in the presence of proper aryl/alkenyl iodides, the cross-coupling products 2 (or 6) are generally formed as the major products; (b) in the absence of aryl/alkenyl iodides, and when R-1 = alkyl and R-2 = aryl groups, or when R-1 = R-2 = aryl groups, the intramolecular cyclization products 3 can be formed predominantly; and (c) in the absence of aryl/alkenyl iodides, and when R-1 = R-2 = alkyl groups, or when R-1 = H and R-2 = alkyl, aryl groups, the homocoupling products 4 can be formed dominantly. Our experimental results also indicate that in many cases when cross-coupling, homocoupling, and intramolecular cyclization reactions coexist in the Cu-mediated reaction system, the reactivity decreases in the following order: cross-coupling > intramolecular cyclization > homocoupling.

  DOI：

  10.1021/jo1005262
• 作为产物：
  描述：

  1-苄基吲哚 在 叔丁基过氧化氢 、 potassium dihydrogenphosphate 、 N-氟代双苯磺酰胺 作用下， 以 甲苯 、 乙腈 为溶剂， 反应 0.33h， 以60%的产率得到1-benzyl-3,3-difluoroindolin-2-one
  参考文献：
  名称：

  Direct Conversion of Indoles to 3,3-Difluoro-2-oxindoles via Electrophilic Fluorination

  摘要：

  3,3-Difluoro-2-oxindoles can be obtained directly from indoles in moderate yields via electrophilic fluorination using N-fluorobenzenesulfonimide as a mild fluorinating reagent. The presence of tell-butyl hydroperoxide during the reaction, together with additional heating after quenching the reaction with triethylamine, is beneficial to the formation of the desired product.

  DOI：

  10.1021/ol302666d

文献信息

• 一种靛红腙类化合物选择性氟化方法
  申请人：中南大学

  公开号：CN108299137B

  公开（公告）日：2020-04-14

  本发明公开了从靛红腙类化合物选择性氟化方法，该方法是将靛红腙与1‑氯甲基‑4‑氟‑1，4‑二氮杂双环[2.2.2]辛烷二(四氟硼酸)盐及碱性化合物一锅反应，选择性合成相应的3，3‑二氟吲哚酮和3‑氟吲哚酮氟化产物；该方法填补了现有技术中从靛红出发选择性在三位单氟化或双氟化的技术空白，且操作简单、流程短、产物收率高，满足工业生产要求。
• Divergent Regioselective Csp²–H Difluoromethylation of Aromatic Amines Enabled by Nickel Catalysis
  作者：Quan Gou、Qianqiong Chen、Qiujian Tan、Minghong Zhu、Huisheng Huang、Mengjiao Deng、Wei Yi、Shuhua He

  DOI：10.1021/acs.orglett.2c01262

  日期：2022.5.20

  bidentate phosphine ligand, offering an invaluable synthesis means to construct extensive p-difluoromethylated products and difluorooxindole derivatives with significant functional fragments. Furthermore, the gram-scale reaction, broad substrate scope, excellent functional-group compatibility, late-stage difluoromethylation of pesticides, and even formal synthesis of HDAC6 inhibitors further demonstrate the

  在此，在二齿膦配体的帮助下，开发了第一个用于镍催化的各种芳族胺的邻位或对位二氟甲基化的催化方案，为构建广泛的对二氟甲基化产物和具有重要功能片段的二氟羟吲哚衍生物提供了宝贵的合成方法。 . 此外，克级反应、广泛的底物范围、优异的官能团相容性、农药的后期二氟甲基化，甚至HDAC6抑制剂的正式合成进一步证明了该方法的实用性。
• Solvent Effects: Syntheses of 3,3-Difluorooxindoles and 3-Fluorooxindoles from Hydrazonoindolin-2-one by Selectfluor
  作者：Qiong Yang、Guo-Li Dai、Yu-Ming Yang、Zhuangzhu Luo、Zhen-Yu Tang

  DOI：10.1021/acs.joc.8b00737

  日期：2018.6.15

  Efficient syntheses of 3,3-difluorooxindoles and 3-fluorooxindoles via fluorination of hydrazonoindolin-2-one with Selectfluor are reported. Under different solvent conditions, this method produced 3,3-difluorooxindoles and 3-fluorooxindoles selectively. The broad substrate scope and mild reaction conditions make this transformation a valuable method in drug discovery and development.
• Nucleophilic Di- and Tetrafluorination of Dicarbonyl Compounds
  作者：Rajendra P. Singh、Utpal Majumder、Jean'ne M. Shreeve

  DOI：10.1021/jo0157674

  日期：2001.9.1

  Reactions of various diketo compounds with Deoxofluor [(CH3OCH2CH2)(2)NSF3] have been investigated. When reacted with Deoxofluor, a-diketones, R1COCOR2 (R-1 = R-2 = Ph; R-1 = R-2 = 4-Me-C6H4; R-1 = Ph, R-2 = Me; R-1 = Me, R-2 = Et) (1a-d) formed difluoro derivatives (2a-d) in the presence of a catalytic amount of HF and/or tetrafluoro (3a-d) products depending on the reaction conditions and stoichiometry used. Reactions of beta -diketones, R3COCH2COR4 (R-3 = R-4 = Ph; R-3 = R-4 = Me; R-3 = Me, R-4 = Ph) (4e-g), with Deoxofluor in the presence of a catalytic amount of HF led to the formation of difluoroalkenones as a mixture of E (5e-g) and Z (6e-g) isomers in good yield. Reaction of other diones, R5CO-X-COR6 (R-5 = R-6 = Ph, X =-CH=CH-; R-5 = R-6 = Me, X = -C6H4C6H4-; R-5 = R-6 = Ph, X = -CH2CH2CH2-; R-5 = R-6 = Me, X = -CH2CH2-) (7h-k) with Deoxofluor produced mainly difluoro products (8h-k) with low yields of tertrafluoro derivatives (9h-k). Acyclic alpha -keto amides react poorly to give the corresponding difluoro derivatives, whereas cyclic (alpha -keto amides (101-p) react smoothly under very mild conditions to produce the corresponding difluoro products (111-p) in > 88% isolated yield.
• A synthesis of 3-fluoroindoles and 3,3-difluoroindolines by reduction of 3,3-difluoro-2-oxindoles using a borane tetrahydrofuran complex
  作者：JoséC. Torres、Simon J. Garden、Angelo C. Pinto、Filipe S.Q. da Silva、Núbia Boechat

  DOI：10.1016/s0040-4020(98)01229-0

  日期：1999.2

  A borane tetrahydrofuran complex has been used to study the reduction of 3,3-difluoro-2-oxindoles and been found to yield either 3-fluoroindoles or 3,3-difluoroindolines. The latter have been found to be reasonably stable when the aromatic nucleus is substituted with an electron withdrawing group and are in these cases the predominant product. The efficient synthesis of the former occurs by elimination of HF in the presence of silica from the latter. The 3,3-difluoro-2-oxindoles were prepared by the reaction of appropriately substituted isatin derivatives with DAST. (C) 1999 Elsevier Science Ltd. All rights reserved.