5-chloro-2-trifluoroacetamidobenzophenone | 69559-40-6

• 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: 5-chloro-2-trifluoroacetamidobenzophenone
• 英文别名: N-(2-benzoyl-4-chlorophenyl)-2,2,2-trifluoroacetamide；2-Trifluoracetamid-5-chlor-benzophenon
• CAS: 69559-40-6
• 化学式: C₁₅H₉ClF₃NO₂
• mdl: MFCD00554963
• 分子量: 327.69
• InChiKey: LASKFGKVOJKTNF-UHFFFAOYSA-N

物化性质

• 熔点：
  126-127 °C
• 沸点：
  461.6±45.0 °C(Predicted)
• 密度：
  1.431±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  22
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.066
• 拓扑面积：
  46.2
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  5-chloro-2-trifluoroacetamidobenzophenone 在 palladium on activated charcoal sodium hydroxide 、 氢气 、 硝酸 、 三氟乙酸 作用下， 以 水 、 乙酸乙酯 为溶剂， 20.0~50.0 ℃ 、310.26 kPa 条件下， 反应 53.0h， 生成 (2,3-Diamino-5-chlorophenyl)-phenylmethanone
  参考文献：
  名称：

  Synthesis and SAR of novel di- and trisubstituted 1,4-dihydroquinoxaline-2,3-diones related to licostinel (Acea 1021) as NMDA/glycine site antagonists

  摘要：

  A series of novel di- and trisubstituted 1,4-dihydroquinoxaline-2,3-diones (QXs) related to licostinel (Acea 1021) was synthesized and evaluated as antagonists for the glycine site of the N-methyl-D-asparate (NMDA) receptor. The in vitro potency of these antagonists was determined by displacement of the glycine site radioligand [H-3]-5,7-dichlorokynurenic acid ([H-3]DCKA) in rat brain cortical membranes. Structure-activity relationship studies indicate that a cyano group is a good replacement for the nitro group in the 5-position of licostinel while 5-carboxy, 5-ester, 5-ketone and 5-amide derivatives showed reduced potency. 5,6-Cyclized analogues of licostinel also showed significantly reduced potency. Among the trisubstituted QXs investigated, 5-cyano-6,7-dichloro QX and 5-cyano-7-chloro-6-methyl QX are the most potent with IC50 values of 32 nM and 26 nM, respectively. (C) 2003 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(03)00059-2
• 作为产物：
  描述：

  2-氨基-5-氯-N-甲氧基-N-甲基苯甲酰胺 在 正丁基锂 、 三乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 1.0h， 生成 5-chloro-2-trifluoroacetamidobenzophenone
  参考文献：
  名称：

  通过α-叔胺​​的动力学拆分不对称合成带有C4-四取代立体中心的氢喹唑啉

  摘要：

  通过手性磷酸催化的分子内脱水环化对 2-酰胺基 α-叔苄胺进行动力学拆分，实现了不对称合成带有 C4-四取代立体中心的氢喹唑啉的新方案。该方法获得了具有广泛范围和高对映选择性的 α-叔苄胺和氢喹唑啉。对于带有 C4-四取代立体中心的氢喹唑啉产物，观察到了有趣的 C-N 键旋转受限。

  DOI：

  10.1021/acs.orglett.1c04039

文献信息

• Synthetic studies on quinazoline derivatives. II. The reactions of 2-trichloro- and 2-trifluoroacetamidobenzophenones with primary amines.
  作者：MICHIHIRO YAMAMOTO、HISAO YAMAMOTO

  DOI：10.1248/cpb.29.2135

  日期：——

  The reaction of 5-chloro-2-trichloroacetamidobenzophenone (2a) with several primary alkylamines in DMSO gave high yields of 3-substituted 6-chloro-3, 4-dihydro-4-phenyl-4-trichloromethyl-2(1H)-quinazolinones 6, which were found to be formed by base-catalyzed and/or thermal cyclization and simultaneous rearrangement of the isomeric 5-chloro-2-trichloroacetamidobenzophenone alkylimines 5. Both compounds 5 and 6 were obtained when the reaction was effected in benzene. Treatment of the compound 2a with bulky amines such as isopropylamine and cyclohexylamine gave, under similar conditions, the corresponding benzophenone imines 5d and 5e exclusively, and these could be transformed into the quinazolinones 6d and 6e, respectively, on heating in pyridine or HMPT. The reaction of N-substituted trichloroacetamidobenzophenones 2m and 3n with N-(2-aminoethyl) morpholine as well as ammonia in DMSO yielded the 1-alkylaminobenzophenone imines 4m-o, which on treatment with trichloroacetyl chloride were readily cyclized to give the corresponding 1-substituted 4-trichloromethylquinazolinones 6m-o. The trichloromethyl group of the 1-unsubstituted quinazolinones 6 was easily displaced by a nucleophile such as hydride, alkoxide or hydroxide under base catalysis to give the 3, 4-dihydro-2 (1H)-quinazolinone derivative 9, 10 or 11 almost quantitatively, whereas the 1, 3-disubstituted quinazolinone 6o was not affected. The sodium borohydride reduction of the methylimine 5a at room temperature mainly afforded the trichloroacetamidobenzhydrylamine 8a, which underwent thermal cyclization to the quinazolinone 9a via split of chloroform. In contrast, the reaction of 5-chloro-2-trifluoroacetamidobenzophenone (2p) with some primary alkylamines in DMSO produced the trifluoroacetamidobenzophenone alkylimines 5p-r, which on treatment with sodium borohydride could be converted only to 3-substituted 6-chloro-3, 4-dihydro-4-phenyl-2-trifluoromethylquinazolines 15. These procedures were successfully utilized in syntheses of the imidazo [1, 2-c] quinazolinone 16, oxazolo [3, 2-c] quinazolinones 17t and 17v, and 1, 3-oxazino [3, 2-c] quinazolinone 17u.

  5-氯-2-三氯乙酰氨基苯并酮(2a)与几种初级烷基胺在DMSO中反应，得到了高产率的3取代的6-氯-3, 4-二氢-4-苯基-4-三氯甲基-2(1H)-喹唑啉酮 6，这些化合物被发现是通过碱催化和/或热环化以及异构体5-氯-2-三氯乙酰氨基苯并酮烷基亚胺的同时重排形成的。两种化合物5和6在苯中反应时均可获得。用体积较大的胺如异丙胺和环己胺处理化合物2a，在类似条件下，得到了相应的苯并酮亚胺5d和5e，经过加热于吡啶或HMPT中，这些亚胺分别可以转化为喹唑啉酮6d和6e。N-取代的三氯乙酰氨基苯并酮2m和3n与N-(2-氨基乙基)吗啉和氨在DMSO中反应，生成了1-烷基氨基苯并酮亚胺4m-o，经过与三氯乙酸酰氯的处理后，这些亚胺可以被迅速环化，得到相应的1-取代的4-三氯甲基喹唑啉酮6m-o。1-未取代的喹唑啉酮6中的三氯甲基基团在碱催化下可以很容易地被氢负离子、烷氧基或氢氧根等亲核试剂取代，几乎定量地产生3, 4-二氢-2(1H)-喹唑啉酮衍生物9、10或11，而1, 3-二取代的喹唑啉酮6o则没有受到影响。在室温下，甲基亚胺5a的钠硼氢化物还原主要产生了三氯乙酰氨基苯基胺8a，该物质经过热环化通过氯仿分解生成喹唑啉酮9a。相比之下，5-氯-2-三氟乙酰氨基苯并酮(2p)与一些初级烷基胺在DMSO中反应，生成了三氟乙酰氨基苯并酮烷基亚胺5p-r，经过与钠硼氢化物的处理后，仅能转化为3取代的6-氯-3, 4-二氢-4-苯基-2-三氟甲基喹唑啉15。这些程序成功应用于合成咪唑[1, 2-c]喹唑啉酮16、噁唑[3, 2-c]喹唑啉酮17t和17v，以及1, 3-噁唑啉[3, 2-c]喹唑啉酮17u。
• Broadening the catalyst and reaction scope of regio- and chemoselective C–H oxygenation: a convenient and scalable approach to 2-acylphenols by intriguing Rh(ii) and Ru(ii) catalysis
  作者：Gang Shan、Xuesong Han、Yun Lin、Shanyou Yu、Yu Rao

  DOI：10.1039/c3ob27457h

  日期：——

  catalyzed C–H oxygenation of aryl ketones and other arenes has been developed for the facile synthesis of diverse functionalized phenols. The reaction demonstrates excellent reactivity, regio- and chemoselectivity, good functional group compatibility and high yields. The practicality of this method has been proved by gram-scale synthesis of a few different 2-acylphenols. Its utility has been well exemplified

  已开发出一种独特的Rh（II）和Ru（II）催化的芳基酮和其他芳烃的CH氧化反应，可以轻松合成各种功能化的酚。该反应显示出优异的反应性，区域和化学选择性，良好的官能团相容性和高产率。该方法的实用性已通过克级合成几种不同的2-酰基酚得到了证明。它的效用已在杂环合成和药物的直接修饰中的进一步应用中得到很好的例证非诺贝特。
• Palladium-Catalyzed Tandem Intramolecular Oxy/Amino-Palladation/Isocyanide Insertion: Synthesis of α-Benzofuranyl/Indolylacetamides
  作者：Nuligonda Thirupathi、Madala Hari Babu、Vikas Dwivedi、Ruchir Kant、Maddi Sridhar Reddy

  DOI：10.1021/ol501048x

  日期：2014.6.6

  A novel palladium-catalyzed approach to 2-benzofuranyl/indolylacetamides from 1-(o-hydroxy/aminophenyl)propargylic alcohols and isocyanides is described. The reaction proceeds through a cascade that includes oxy/aminopalladation, isocyanide insertion, and 1,4-hydroxyl migration. No oxidant or ligand is needed to promote the cascade, and the reactions are carried out under mild conditions to afford the products through high functional tolerance.
• OKLOBDZIJA M.; FAJDIGA T.; KOVAC T.; ZONNO F.; SEGA A.; SUNJIC V., ACTA PHARM. JUGOSL., 1980, 30, NO 3, 121-133
  作者：OKLOBDZIJA M.、 FAJDIGA T.、 KOVAC T.、 ZONNO F.、 SEGA A.、 SUNJIC V.

  DOI：——

  日期：——
• YAMAMOTO, MICHIHIRO;YAMAMOTO, HISAO, CHEM. AND PHARM. BULL., 1981, 29, N 8, 2135-2156
  作者：YAMAMOTO, MICHIHIRO、YAMAMOTO, HISAO

  DOI：——

  日期：——