3,3-Dimethyl-2-hydroxymethylbutyl 4-bromobenzamide | 174720-51-5

• 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: 3,3-Dimethyl-2-hydroxymethylbutyl 4-bromobenzamide
• 英文别名: 4-bromo-N-[2-(hydroxymethyl)-3,3-dimethylbutyl]benzamide
• CAS: 174720-51-5
• 化学式: C₁₄H₂₀BrNO₂
• 分子量: 314.222
• InChiKey: OZSCMEZJBGACLM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  18
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  49.3
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  3,3-Dimethyl-2-hydroxymethylbutyl 4-bromobenzamide 在 bis-triphenylphosphine-palladium(II) chloride 、 copper(l) iodide 劳森试剂 、 草酰氯 、 二甲基亚砜 、 三乙胺 作用下， 以 二氯甲烷 、 xylene 为溶剂， 反应 7.5h， 生成 5-tert-Butyl-2-(4-trimethylsilanylethynyl-phenyl)-4H-[1,3]thiazine
  参考文献：
  名称：

  Heterocyclic Insecticides Acting at the GABA-Gated Chloride Channel: 5-Alkyl-2-arylpyrimidines and -1,3-thiazines

  摘要：

  5-tert-Butyl-2-(4-ethynylphenyl)pyrimidine and the corresponding 2,5-disubstituted-4H-1,3-thiazine block the GABA-gated chloride channel at c.20 and c.200 nM, respectively, measured as 50% inhibition of the binding of 1-(-4-ethynylphenyl)-4-[H-3]propyl-2,6,7-trioxabicyclo[2.22]octane (4'-ethynyl-4-n-[H-3]propylbicycloorthobenzoate; [H-3]EBOB) in house fly and mouse brain membranes, and they are also toxic to topically-treated dies with LD(50) values of 6-27 mu g g(-1) alone and 2-6 mu g g(-1) with piperonyl butoxide (PB) as synergist. In the pyrimidine series, the general pattern of effectiveness of substituents in the 5-position is tert-butyl > isopropyl approximate to cyclohexyl approximate to cyclopropyl > methyl, phenyl and 3- and 4-fluorophenyl, and in the 2-position is 4-ethynylphenyl much greater than 4-bromophenyl. These planar pyrimidines and nearly-planar 4H-1,3-thiazines with 2-ethynylphenyl or 2-bromophenyl and 5-tert-butyl or 5-isopropyl substituents are more effective than the corresponding 6H-1,3-thiazine, 6-oxo-1,3-thiazines and 4,6-dioxo-1,3-thiazine examined, but they are less active than the analogous conformationally flexible trans-1,3-dioxanes and -1,3-dithianes. The heterocyclic moiety confers a region of high electron density and positions the 2- and 5-substituents in a linear or parallel relationship for optimal affinity at the receptor. Two observations indicate that the new pyrimidines and thiazines probably act as chloride channel blockers. First, the poisoning signs are identical to those of EBOB in both mice and house flies. Second, each of the pyrimidines, thiazines and dioxanes falls on the same correlation line for inhibition of [H-3]EBOB binding and toxicity to house flies (with PB) as that obtained earlier for EBOB analogs, dithianes and polychlorocycloalkanes, suggesting that they all act at the same or closely coupled binding sites in the GABA-gated chloride channel.

  DOI：

  10.1002/(sici)1096-9063(199603)46:3<237::aid-ps359>3.0.co;2-p
• 作为产物：
  描述：

  ethyl t-butylcyanoacetate 在 sodium hydroxide 、 lithium aluminium tetrahydride 作用下， 以 乙醚 为溶剂， 反应 2.5h， 生成 3,3-Dimethyl-2-hydroxymethylbutyl 4-bromobenzamide
  参考文献：
  名称：

  Heterocyclic Insecticides Acting at the GABA-Gated Chloride Channel: 5-Alkyl-2-arylpyrimidines and -1,3-thiazines

  摘要：

  5-tert-Butyl-2-(4-ethynylphenyl)pyrimidine and the corresponding 2,5-disubstituted-4H-1,3-thiazine block the GABA-gated chloride channel at c.20 and c.200 nM, respectively, measured as 50% inhibition of the binding of 1-(-4-ethynylphenyl)-4-[H-3]propyl-2,6,7-trioxabicyclo[2.22]octane (4'-ethynyl-4-n-[H-3]propylbicycloorthobenzoate; [H-3]EBOB) in house fly and mouse brain membranes, and they are also toxic to topically-treated dies with LD(50) values of 6-27 mu g g(-1) alone and 2-6 mu g g(-1) with piperonyl butoxide (PB) as synergist. In the pyrimidine series, the general pattern of effectiveness of substituents in the 5-position is tert-butyl > isopropyl approximate to cyclohexyl approximate to cyclopropyl > methyl, phenyl and 3- and 4-fluorophenyl, and in the 2-position is 4-ethynylphenyl much greater than 4-bromophenyl. These planar pyrimidines and nearly-planar 4H-1,3-thiazines with 2-ethynylphenyl or 2-bromophenyl and 5-tert-butyl or 5-isopropyl substituents are more effective than the corresponding 6H-1,3-thiazine, 6-oxo-1,3-thiazines and 4,6-dioxo-1,3-thiazine examined, but they are less active than the analogous conformationally flexible trans-1,3-dioxanes and -1,3-dithianes. The heterocyclic moiety confers a region of high electron density and positions the 2- and 5-substituents in a linear or parallel relationship for optimal affinity at the receptor. Two observations indicate that the new pyrimidines and thiazines probably act as chloride channel blockers. First, the poisoning signs are identical to those of EBOB in both mice and house flies. Second, each of the pyrimidines, thiazines and dioxanes falls on the same correlation line for inhibition of [H-3]EBOB binding and toxicity to house flies (with PB) as that obtained earlier for EBOB analogs, dithianes and polychlorocycloalkanes, suggesting that they all act at the same or closely coupled binding sites in the GABA-gated chloride channel.

  DOI：

  10.1002/(sici)1096-9063(199603)46:3<237::aid-ps359>3.0.co;2-p

文献信息

• Heterocyclic Insecticides Acting at the GABA-Gated Chloride Channel: 5-Alkyl-2-arylpyrimidines and -1,3-thiazines
  作者：David A. Pulman、Ian H. Smith、John P. Larkin、John E. Casida

  DOI：10.1002/(sici)1096-9063(199603)46:3<237::aid-ps359>3.0.co;2-p

  日期：1996.3

  5-tert-Butyl-2-(4-ethynylphenyl)pyrimidine and the corresponding 2,5-disubstituted-4H-1,3-thiazine block the GABA-gated chloride channel at c.20 and c.200 nM, respectively, measured as 50% inhibition of the binding of 1-(-4-ethynylphenyl)-4-[H-3]propyl-2,6,7-trioxabicyclo[2.22]octane (4'-ethynyl-4-n-[H-3]propylbicycloorthobenzoate; [H-3]EBOB) in house fly and mouse brain membranes, and they are also toxic to topically-treated dies with LD(50) values of 6-27 mu g g(-1) alone and 2-6 mu g g(-1) with piperonyl butoxide (PB) as synergist. In the pyrimidine series, the general pattern of effectiveness of substituents in the 5-position is tert-butyl > isopropyl approximate to cyclohexyl approximate to cyclopropyl > methyl, phenyl and 3- and 4-fluorophenyl, and in the 2-position is 4-ethynylphenyl much greater than 4-bromophenyl. These planar pyrimidines and nearly-planar 4H-1,3-thiazines with 2-ethynylphenyl or 2-bromophenyl and 5-tert-butyl or 5-isopropyl substituents are more effective than the corresponding 6H-1,3-thiazine, 6-oxo-1,3-thiazines and 4,6-dioxo-1,3-thiazine examined, but they are less active than the analogous conformationally flexible trans-1,3-dioxanes and -1,3-dithianes. The heterocyclic moiety confers a region of high electron density and positions the 2- and 5-substituents in a linear or parallel relationship for optimal affinity at the receptor. Two observations indicate that the new pyrimidines and thiazines probably act as chloride channel blockers. First, the poisoning signs are identical to those of EBOB in both mice and house flies. Second, each of the pyrimidines, thiazines and dioxanes falls on the same correlation line for inhibition of [H-3]EBOB binding and toxicity to house flies (with PB) as that obtained earlier for EBOB analogs, dithianes and polychlorocycloalkanes, suggesting that they all act at the same or closely coupled binding sites in the GABA-gated chloride channel.