(E)-3-(2,6-Dimethyl-phenyl)-2-methyl-acrylic acid methyl ester | 124317-09-5

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 肉桂酸及其衍生物
• 英文名称: (E)-3-(2,6-Dimethyl-phenyl)-2-methyl-acrylic acid methyl ester
• 英文别名: Methyl 3-(2,6-dimethylphenyl)-2-methylprop-2-enoate；methyl 3-(2,6-dimethylphenyl)-2-methylprop-2-enoate
• CAS: 124317-09-5
• 化学式: C₁₃H₁₆O₂
• 分子量: 204.269
• InChiKey: QOUVNPXQHSOYJQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  15
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  26.3
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (E)-3-(2,6-Dimethyl-phenyl)-2-methyl-acrylic acid methyl ester 在 palladium on activated charcoal 氢气 、 三甲基铝 作用下， 以 四氢呋喃 为溶剂， 反应 3.25h， 生成 4,5-dihydro-2-<1-<(2,6-dimethylphenyl)methyl>ethyl>-1H-imidazole
  参考文献：
  名称：

  Potential antisecretory antidiarrheals. 2. .alpha.2-Adrenergic 2-[(aryloxy)alkyl]imidazolines

  摘要：

  Lofexidine, an alpha 2-agonist, has central hypotensive activity and peripheral intestinal antisecretory activity. Analogues were synthesized with increased polarity in an attempt to prevent penetration of the blood-brain barrier. The compounds were evaluated in the cholera toxin treated ligated jejunum of the rat and in the Ussing chamber with a rabbit ileum preparation. Active compounds were determined to be alpha 2-adrenergic agonists by yohimbine reversals of their Ussing chamber activities. The 2,6-dimethyl derivative of lofexidine, 4a, was as active as lofexidine in vivo, but derivatives with 2,6-substituents larger than ethyl were inactive. (Aryloxy)alkyl derivatives which have an imidazoline and a methyl or larger group as part of the alkyl exhibited the best antisecretory activity. Compounds with substituents in the para position of the phenyl ring were generally inactive. 3-Amino-2,6-dimethyl derivative 21 was twice as active as 4a. A 2-methyl substituent is required in the 3-amino series to retain good activity. 2-Methyl derivative 12a had activity comparable to that of 4a, while 6-methyl derivative 12f was inactive. Substituents on the 3-amino group did not affect the activity, but substituting a hydroxyl for the amino group produced an inactive compound. Replacing the phenyl moiety with a 4-indole resulted in retention of activity, but other heterocycles were inactive. Compound 12a was resolved and d isomer 32 was five times more potent than l isomer 33. The more active compounds in the rat cholera toxin assay (RCTA), when evaluated in the dog, exhibited antisecretory activity but also exhibited central nervous system (CNS) effects, sedation and ataxia, at 10 mg/kg, and in spontaneously hypertensive rats at 50 mg/kg. A measure of polarity, log P, was calculated for the (aryloxy)alkyl groups. Regression analysis showed no correlation of antisecretory ED50 to the calculated log P. The active compounds did not show a separation of the central CNS effects from the peripheral antisecretory activity by increasing the polarity.

  DOI：

  10.1021/jm00164a024
• 作为产物：
  描述：

  2,6-二甲基溴苯 、 甲基丙烯酸甲酯 在 palladium diacetate 、 三乙胺 、 三苯基膦 作用下， 反应 8.0h， 以32%的产率得到(E)-3-(2,6-Dimethyl-phenyl)-2-methyl-acrylic acid methyl ester
  参考文献：
  名称：

  Potential antisecretory antidiarrheals. 2. .alpha.2-Adrenergic 2-[(aryloxy)alkyl]imidazolines

  摘要：

  Lofexidine, an alpha 2-agonist, has central hypotensive activity and peripheral intestinal antisecretory activity. Analogues were synthesized with increased polarity in an attempt to prevent penetration of the blood-brain barrier. The compounds were evaluated in the cholera toxin treated ligated jejunum of the rat and in the Ussing chamber with a rabbit ileum preparation. Active compounds were determined to be alpha 2-adrenergic agonists by yohimbine reversals of their Ussing chamber activities. The 2,6-dimethyl derivative of lofexidine, 4a, was as active as lofexidine in vivo, but derivatives with 2,6-substituents larger than ethyl were inactive. (Aryloxy)alkyl derivatives which have an imidazoline and a methyl or larger group as part of the alkyl exhibited the best antisecretory activity. Compounds with substituents in the para position of the phenyl ring were generally inactive. 3-Amino-2,6-dimethyl derivative 21 was twice as active as 4a. A 2-methyl substituent is required in the 3-amino series to retain good activity. 2-Methyl derivative 12a had activity comparable to that of 4a, while 6-methyl derivative 12f was inactive. Substituents on the 3-amino group did not affect the activity, but substituting a hydroxyl for the amino group produced an inactive compound. Replacing the phenyl moiety with a 4-indole resulted in retention of activity, but other heterocycles were inactive. Compound 12a was resolved and d isomer 32 was five times more potent than l isomer 33. The more active compounds in the rat cholera toxin assay (RCTA), when evaluated in the dog, exhibited antisecretory activity but also exhibited central nervous system (CNS) effects, sedation and ataxia, at 10 mg/kg, and in spontaneously hypertensive rats at 50 mg/kg. A measure of polarity, log P, was calculated for the (aryloxy)alkyl groups. Regression analysis showed no correlation of antisecretory ED50 to the calculated log P. The active compounds did not show a separation of the central CNS effects from the peripheral antisecretory activity by increasing the polarity.

  DOI：

  10.1021/jm00164a024

文献信息

• Process for producing phosponium borate compound, novel phosphonium borate compound, and method of using the same
  申请人：Masaoka Shin

  公开号：US20070098616A1

  公开（公告）日：2007-05-03

  The invention relates to a phosphonium borate compound represented by Formula (I) (hereinafter, the compound (I)). The invention has objects of providing (A) a novel process whereby the compound is produced safely on an industrial scale, by simple reaction operations and in a high yield; (B) a novel compound that is easily handled; and (C) novel use as catalyst. Formula (I): (R 1 )(R 2 )(R 3 )PH.BAr 4 (I) wherein R 1 , R 2 , R 3 and Ar are as defined in the specification. The process (A) includes reacting a phosphine with a) HCl or b) H 2 SO 4 to produce a) a hydrochloride or b) a sulfate; and reacting the salt with a tetraarylborate compound. The compound (B) has for example a secondary or tertiary alkyl group as R 1 and is easily handled in air without special attention. The use (C) is characterized in that the compound (I) is used instead of an unstable phosphine compound of a transition metal complex catalyst for catalyzing C—C bond, C—N bond and C—O bond forming reactions and the compound produces an effect that is equal to that achieved by the transition metal complex catalyst.

  本发明涉及一种磷酸盐硼化合物，其由式(I)表示（以下简称化合物(I)）。本发明的目的是提供（A）一种新的工艺，通过简单的反应操作和高产率安全地在工业规模下生产化合物；（B）一种易于处理的新化合物；以及（C）新的用途作为催化剂。式(I)：（R1）（R2）（R3）PH.BAr4（I），其中R1，R2，R3和Ar如规范中所定义。工艺（A）包括将磷化物与a）HCl或b）H2SO4反应，以产生a）盐酸盐或b）硫酸盐；然后将盐与四芳基硼酸盐化合物反应。化合物（B）例如具有二级或三级烷基作为R1，在空气中易于处理而不需要特殊注意。用途（C）的特点是，化合物（I）代替过渡金属复合催化剂的不稳定磷化物化合物，用于催化C-C键，C-N键和C-O键形成反应，并且该化合物产生与过渡金属复合催化剂相同的效果。
• Process for producing phosphonium borate compound, novel phosphonium borate compound, and method of using the same
  申请人：Masaoka Shin

  公开号：US20090305877A1

  公开（公告）日：2009-12-10

  The invention relates to a phosphonium borate compound represented by Formula (I) (hereinafter, the compound (I)). The invention has objects of providing (A) a novel process whereby the compound is produced safely on an industrial scale, by simple reaction operations and in a high yield; (B) a novel compound that is easily handled; and (C) novel use as catalyst. Formula (I): (R 1 )(R 2 )(R 3 )PH.BAr 4 (I) wherein R 1 , R 2 , R 3 and Ar are as defined in the specification. The process (A) includes reacting a phosphine with a) HCl or b) H 2 SO 4 to produce a) a hydrochloride or b) a sulfate; and reacting the salt with a tetraarylborate compound. The compound (B) has for example a secondary or tertiary alkyl group as R 1 and is easily handled in air without special attention. The use (C) is characterized in that the compound (I) is used instead of an unstable phosphine compound of a transition metal complex catalyst for catalyzing C—C bond, C—N bond and C—O bond forming reactions and the compound produces an effect that is equal to that achieved by the transition metal complex catalyst.

  本发明涉及一种磷酸铵硼酸盐化合物，其化学式表示为（I）（以下简称化合物（I））。本发明的目的是提供（A）一种新的工艺，能够通过简单的反应操作和高产率安全地在工业规模上生产化合物；（B）一种易于处理的新化合物；以及（C）作为催化剂的新用途。 化学式（I）：（R1）（R2）（R3）PH·BAr4（I） 其中，R1、R2、R3和Ar的定义如规范中所述。 工艺（A）包括将磷化物与a）HCl或b）H2SO4反应，以产生a）盐酸盐或b）硫酸盐；然后将盐与四芳基硼酸盐化合物反应。 化合物（B）例如具有R1为次级或三级烷基，可以在空气中轻松处理，无需特别注意。 用途（C）的特点是，化合物（I）用于催化C-C键、C-N键和C-O键形成反应，而不是不稳定的过渡金属配合物催化剂中的磷化物化合物，其产生的效果与过渡金属配合物催化剂相当。
• Process for Producing Phosphonium Borate Compound, Novel Phosphonium Borate Compound, and Method of Using the Same
  申请人：MASAOKA Shin

  公开号：US20110166389A1

  公开（公告）日：2011-07-07

  The invention relates to novel phosphonium borate compounds represented by the Formula: (R 1 )(R 2 )(R 3 )PH.BAr 4 , wherein R 1 , R 2 , R 3 and Ar 4 are as defined herein, and compositions including such phosphonium borate compounds in combination with a transition metal, transition metal salt, transition metal oxide or transition metal complex for use in carbon-carbon bond forming reactions, carbon-nitrogen bond forming reactions and carbon-oxygen bond forming reactions.

  本发明涉及一种新型的磷酸盐硼酸盐化合物，其化学式表示为：（R1）（R2）（R3）PH.BAr4，其中R1、R2、R3和Ar4如本文所定义，并包括这种磷酸盐硼酸盐化合物与过渡金属、过渡金属盐、过渡金属氧化物或过渡金属配合物的组合物，用于碳-碳键形成反应、碳-氮键形成反应和碳-氧键形成反应。
• PROCESS FOR PRODUCING PHOSPHONIUM BORATE COMPOUND, NOVEL PHOSPHONIUM BORATE COMPOUND, AND METHOD OF USING THE SAME
  申请人：HOKKO CHEMICAL INDUSTRY CO. LTD.

  公开号：EP1688424A1

  公开（公告）日：2006-08-09

  The invention relates to a phosphonium borate compound represented by Formula (I) (hereinafter, the compound (I)). The invention has objects of providing (A) a novel process whereby the compound is produced safely on an industrial scale, by simple reaction operations and in a high yield; (B) a novel compound that is easily handled; and (C) novel use as catalyst.         Formula (I) : (R1)(R2)(R3)PH·BAr4     (I) wherein R1, R2, R3 and Ar are as defined in the specification. The process (A) includes reacting a phosphine with a) HCl or b) H2SO4 to produce a) a hydrochloride or b) a sulfate; and reacting the salt with a tetraarylborate compound. The compound (B) has for example a secondary or tertiary alkyl group as R1 and is easily handled in air without special attention. The use (C) is characterized in that the compound (I) is used instead of an unstable phosphine compound of a transition metal complex catalyst for catalyzing C-C bond, C-N bond and C-O bond forming reactions and the compound produces an effect that is equal to that achieved by the transition metal complex catalyst.

  本发明涉及一种由式（I）表示的硼酸鏻化合物（以下简称化合物（I））。本发明的目的是：(A)提供一种新的工艺，通过简单的反应操作和高产率，在工业规模上安全地生产该化合物；(B)提供一种易于处理的新化合物；(C)提供作为催化剂的新用途。 式 (I) : (R1)(R2)(R3)PH-BAr4 (I) 其中 R1、R2、R3 和 Ar 如说明书中所定义。 工艺 (A) 包括将膦与 a) HCl 或 b) H2SO4 反应生成 a) 盐酸盐或 b) 硫酸盐；并将该盐与四芳基硼酸盐化合物反应。 化合物(B)的 R1 例如是仲烷基或叔烷基，在空气中容易处理，无需特别注意。 用途(C)的特点是用化合物(I)代替过渡金属络合催化剂中不稳定的膦化合物来催化C-C键、C-N键和C-O键形成反应，并且该化合物产生的效果与过渡金属络合催化剂产生的效果相同。
• PHOSPHONIUM BORATE COMPOUND AND METHOD OF USING THE SAME
  申请人：Hokko Chemical Industry Co., Ltd.

  公开号：EP1688424B1

  公开（公告）日：2016-01-13