diethyl 4-bromobenzene-1,3-dicarboxylate | 56984-35-1

• 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: diethyl 4-bromobenzene-1,3-dicarboxylate
• 英文别名: 6-bromo-isophthalic acid diethyl ester；4-bromoisophthalic acid diethyl ester；diethyl 4 bromoisophthalate；diethyl 4-bromoisophthalate；4-bromo-isophthalic acid diethyl ester；4-Brom-isophthalsaeure-diaethylester
• CAS: 56984-35-1
• 化学式: C₁₂H₁₃BrO₄
• 分子量: 301.137
• InChiKey: AMIIIXXHQPWVFM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  17
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  52.6
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  diethyl 4-bromobenzene-1,3-dicarboxylate 在 四(三苯基膦)钯 、 sodium carbonate 、 sodium hydroxide 作用下， 以 乙醇 、 水 、 甲苯 为溶剂， 反应 25.0h， 生成 2'-chlorobiphenyl-2,4-dicarboxylic acid
  参考文献：
  名称：

  Synthesis and structure–activity relationships of new carbonyl guanidine derivatives as novel dual 5-HT2B and 5-HT7 receptor antagonists. Part 2

  摘要：

  We previously reported that the novel dual 5-HT₂B and 5-HT7 receptor antagonist N-(9-hydroxy-9H-fluorene-2-carbonyl)guanidine (4) exerted a suppressing effect on 5-HT-induced dural protein extravasation in guinea pigs. To develop a synthetic strategy, we performed docking studies of lead compound 4 bound to 5-HT₂B and 5-HT₇ receptors, and observed that the carbonyl guanidine group forms a tight interaction network with an active center Asp (D135:5-HT2B, D162:5-HT₇), Tyr (Y370:5-HT₂B, Y374:5-HT₇) and aromatic residue (W131:5-HT2B, F158:5-HT₇). Based on molecular modeling results, we optimized the substituents at the 5- to 8-position and 9-position of the fluorene ring and identified N-(diaminomethylene)-9-hydroxy-9-methyl-9H-fluorene-2-carboxamide (24a) exhibits potent affinity for 5-HT₂B (Ki=4.3 nM) and 5-HT7 receptor (Ki=4.3 nM) with high selectivity over 5-HT₂A, 5-HT₂C, α₁, D₂ and M₁ receptors. Compound 24a reversed the hypothermic effect of 5-carboxamidotryptamine (5-CT) in mice and also showed a suppressing effect on 5-HT-induced dural protein extravasation in guinea pigs when orally administered at 30 mg/kg. Compound 24a is therefore a promising candidate for a novel class of anti-migraine agent without any adverse effects.

  DOI：

  10.1016/j.bmc.2014.05.027
• 作为产物：
  描述：

  2,4-二甲基溴苯 在 potassium permanganate 、 硫酸 作用下， 以 水 为溶剂， 反应 32.0h， 生成 diethyl 4-bromobenzene-1,3-dicarboxylate
  参考文献：
  名称：

  Synthesis, Crystal Structure, and Resolution of [10](1,6)Pyrenophane: An Inherently Chiral [n]Cyclophane

  摘要：

  A synthetic approach to a set of three inherently chiral [n] cyclophanes, [n] (1,6)pyrenophanes (29a-c, n = 8-10) was investigated. Progress toward 29a was thwarted by the failure of the key dithiacyclophane-forming reaction. For the next higher homologue, the synthesis was completed, but the desired [9](1,6)pyrenophane (29b) could only be partially separated from an isomeric pyrenophane, [9](1,8)pyrenophane (28b), and an unidentified byproduct. Work aimed at the synthesis of the next higher homologue resulted in the isolation of a 7:4 mixture of [10](1,8)pyrenophane (28c) and [10](1,6)pyrenophane (29c), which could not be separated by column chromatography or crystallization. However, single-crystal X-ray structures of 28c and 29c were obtained after manual separation of two crystals with different morphologies from the same batch of crystals obtained from the 7:4 mixture of 28c and 29c. The pyrene system of 29c was found to have a gentle end-to-end bend as well as a significant longitudinal twist. Short intermolecular C(sp(3))-H center dot center dot center dot pi contacts (2.64 to 2.76 angstrom) between H-atoms on the bridge and the centroids of three of the four six-membered rings of the pyrene system of a neighboring pyrenophane of like chirality give rise to the formation of single enantiomer columns. From a DNMR study of the mixture of 28c and 29c, the bridge in [10](1,8)pyrenophane (28c) was found to undergo a conformational flip from one side of the pyrene system to the other with Delta G double dagger = 14.9 +/- 0.2 kcal/mol. A two-stage preparative HPLC protocol was subsequently developed for the separation of 28c and 29c (Chiralpalc AD-H column) and then the enantiomers of 29c (Chiralcel OJ-H column). This enabled the measurement of their optical rotations and CD spectra.

  DOI：

  10.1021/jo201013q

文献信息

• Preparation and use of magnesium amides
  申请人：Ludwig-Maximilians-Universität München

  公开号：EP1810974A1

  公开（公告）日：2007-07-25

  The present application relates to mixed Mg/Li amides of the general formula          R1R2N-MgX·zLiY     (I), wherein R1, R2 and R3 independently are selected from substituted or unsubstituted aryl or heteroaryl containing one or more heteroatoms, linear, branched or cyclic, substituted or unsubstituted alkyl, alkenyl, alkynyl, or derivatives thereof, and, for R1 and R2 only, the silyl derivatives thereof; one of R1 and R2 may be H; or R1 and R2 together can be part of a cyclic or polymeric structure; X and Y independently are selected amongst others from the group consisting of F; Cl; Br; I; CN; SCN; NCO; and z > 0, as well as a process for the preparation of the mixed Mg/Li amides and the use of these amides, e.g. as bases.

  本申请涉及一般式为R1R2N-MgX·zLiY（I）的混合Mg/Li胺，其中 R1、R2和R3独立地选择自含有一个或多个杂原子的取代或未取代芳基或杂芳基，线性、支链或环状，取代或未取代的烷基、烯基、炔基或其衍生物，以及仅对于R1和R2，其硅基衍生物；R1和R2中的一个可以是H；或者R1和R2可以共同构成环状或聚合结构的一部分； X和Y独立地从F、Cl、Br、I、CN、SCN、NCO等组中选择，z > 0，以及混合Mg/Li胺的制备方法和这些胺的用途，例如作为碱。
• A Convenient Alumination of Functionalized Aromatics by Using the Frustrated Lewis Pair Et₃Al and TMPMgCl⋅LiCl
  作者：Andreas Unsinn、Stefan H. Wunderlich、Anukul Jana、Konstantin Karaghiosoff、Paul Knochel

  DOI：10.1002/chem.201301869

  日期：2013.10.18

  straightforward and efficient alumination of functionalized arenes by using the frustrated Lewis pair Et3Al and TMPMgCl⋅LiCl (TMP=2,2,6,6‐tetramethylpiperidyl) has been developed. In particular, halogenated electron‐rich aromatics can be smoothly functionalized by using the frustrated Lewis pair Et3Al and TMPMgCl⋅LiCl. Compared with previously described alumination methods, this procedure avoids extensive cooling

  通过使用路易斯受挫的Et一对官能化芳烃的一种直接和高效的脱铝3 Al和TMPMgCl ⋅的LiCl（TMP = 2,2,6,6-四甲基）已经被开发出来。特别地，卤代的富电子的芳族化合物可以顺利地通过使用路易斯受挫的Et一对官能化3 Al和TMPMgCl ⋅的LiCl。与先前描述的铝化方法相比，此过程避免了广泛的冷却，也避免了碱的过量使用。这种原位方法已被证明是最实用的方法，可对具有敏感官能团（CONEt 2，CO 2 Me，CN，OCONMe 2）或卤素（F，Cl，Br，I）。生成的芳族铝酸盐通过NMR光谱进行表征，在金属化成锌后进行烯丙基化，酰化和钯催化的交叉偶联反应。结果表明，用于金属转移的锌盐的性质至关重要。因此，与ZnCl 2（2当量）相比，使用Zn（OPiv）2（2当量； OPiv =新戊酸酯）使得随后的淬灭反应仅需稍微过量的亲电子试剂（1.2当量）即可进行，并提供了有趣的功能化芳烃收率高。
• Direct Pd-Catalyzed Cross-Coupling of Functionalized Organoaluminum Reagents
  作者：Klaus Groll、Tobias D. Blümke、Andreas Unsinn、Diana Haas、Paul Knochel

  DOI：10.1002/anie.201205987

  日期：2012.10.29

  A handsome couple: Through the use of the simple Pd catalyst [Pd(tmpp)2Cl2] (tmpp=tris(2,4,6‐trimethoxyphenyl)phosphine) and THF/DMF as solvent, various aryl‐, heteroaryl‐, benzyl‐ and alkylaluminum reagents can be readily cross‐coupled with aryl or heteroaryl iodides, bromides, and nonaflates, and in special cases even with chlorides and triflates. This cross‐coupling tolerates free NH2 groups, aldehydes

  一对英俊的夫妇：通过使用简单的Pd催化剂[Pd（tmpp）2 Cl 2 ]（tmpp = tris（2,4,6-三甲氧基苯基）膦）和THF / DMF作为溶剂，各种芳基，杂芳基，苄基和烷基铝试剂可以很容易地与芳基或杂芳基碘化物，溴化物和壬二酸酯交叉偶联，在特殊情况下甚至与氯化物和三氟甲磺酸酯交叉偶联。这种交叉偶联可耐受游离的NH 2基团，醛，酮，酯和硝基官能团。
• Cobalt-Catalyzed Cross-Coupling Reactions of Heterocyclic Chlorides with Arylmagnesium Halides and of Polyfunctionalized Arylcopper Reagents with Aryl Bromides, Chlorides, Fluorides and Tosylates
  作者：Paul Knochel、Tobias Korn、Matthias Schade、Murthy Cheemala、Stefan Wirth、Simon Guevara、Gérard Cahiez

  DOI：10.1055/s-2006-950290

  日期：2006.11

  A range of aromatic organocopper or organomagnesium compounds undergo smooth cross-coupling reactions with aryl bromides, chlorides, fluorides and tosylates, leading to polyfunctionalized aromatics or heterocycles in the presence of cobalt salts (5-7.5 mol%) as catalysts. Very mild reaction conditions are needed and, in the case of cross-coupling with organocopper compounds, Bu4NI (1 equiv) and 4-fluorostyrene (20 mol%) are essential as promoters for successful couplings.

  一系列芳香族有机铜或有机镁化合物与芳基溴、氯、氟及托烯磺酸酯进行平滑的交叉偶联反应，在钴盐（5-7.5 mol%）作为催化剂的情况下，产生多功能化的芳香族化合物或杂环化合物。反应条件非常温和，且在与有机铜化合物交叉偶联的情况下，四丁基氮化铵（1当量）和4-氟苯乙烯（20 mol%）是成功偶联所必需的促进剂。
• A Novel Class of Inhibitors for Human Steroid 5.ALPHA.-Reductase. Phenoxybenzoic Acid Derivatives. I.
  作者：Susumu IGARASHI、Takenori KIMURA、Ryo NAITO、Hiromu HARA、Masahiro FUJII、Hiroshi KOUTOKU、Hiroyuki ORITANI、Toshiyasu MASE

  DOI：10.1248/cpb.47.1073

  日期：——

  In a search for novel nonsteroidal inhibitors of human prostatic 5 alpha-reductase, we found a new series of phenoxybenzoic acid derivatives to be potent human prostatic 5 alpha-reductase inhibitors. Among them, 4-(biphenyl-4-yloxy)benzoic acid derivatives (2n, YM-31758), 2o and 2s showed more potent inhibitory activities than finasteride with IC50 values of 0.87, 0.67 and 0.56 nM, respectively. The

  在寻找人类前列腺5α-还原酶的新型非甾体抑制剂时，我们发现了一系列新的苯氧基苯甲酸衍生物是有效的人类前列腺5α-还原酶抑制剂。其中，4-（联苯-4-基氧基）苯甲酸衍生物（2n，YM-31758），2o和2s显示出比非那雄胺更有效的抑制活性，IC50值分别为0.87、0.67和0.56 nM。通过分子建模分析计算出苯氧基苯甲酸衍生物2d-2i的优化结构，发现羧基碳原子与苯基质心（苯环C）之间的合适距离为9-11一个范围。