chloromethyl cyclobutyl ether | 104620-74-8

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: chloromethyl cyclobutyl ether
• 英文别名: (Chloromethoxy)cyclobutane；chloromethoxycyclobutane
• CAS: 104620-74-8
• 化学式: C₅H₉ClO
• mdl: MFCD19233804
• 分子量: 120.579
• InChiKey: UWIJSUXTOPVRSB-UHFFFAOYSA-N

物化性质

• 沸点：
  80-82 °C(Press: 105 Torr)
• 密度：
  1.08±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  7
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  9.2
• 氢给体数：
  0
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  chloromethyl cyclobutyl ether 、 1-methyl-1H-imidazole-2-carbaldehyde oxime 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 以51%的产率得到1-<(cyclobutyloxy)methyl>-2-<(hydroxyimino)methyl>-3-methylimidazolium chloride
  参考文献：
  名称：

  Quaternary salts of 2-[(hydroxyimino)methyl]imidazole. 2. Preparation and in vitro and in vivo evaluaton of 1-(alkoxymethyl)-2-[(hydroxyimino)methyl]-3-methylimidazolium halides for reactivation of organophosphorus-inhibited acetylcholinesterases

  摘要：

  A series of structurally related mono- and bis-1,3-disubstituted 2-[(hydroxyimino)methyl]imidazolium halides were evaluated in vitro for their ability to reactivate electric eel, bovine, and human erythrocyte (RBC) acetylcholinesterases (AChE) inhibited by ethyl p-nitrophenyl methylphosphonate (EPMP) and 3,3-dimethyl-2-butyl methyl-phosphonofluoridate (soman, GD). All new compounds were characterized for (hydroxyimino)methyl acid dissociation constant, nucleophilicity, octanol-buffer partition coefficient, reversible AChE inhibition, and kinetics of reactivation of EPMP-inhibited AChEs. For GD-inhibited AChEs, maximal reactivation was used to compare compounds since rapid phosphonyl enzyme dealkylation "aging" complicated interpretation of kinetic constants. For comparison, we also evaluated three known pyridinium therapeutics, 2-PAM, HI-6, and toxogonin. In vivo evaluation in mice revealed that when selected imidazolium compounds were coadministered with atropine sulfate, they were effective in providing lifesaving protection against both GD and EPMP challenges. This was a major accomplishment in the search for effective anticholinesterase therapeutics--the synthesis and preliminary evaluation of the first new monoquaternary soman antidotes with potencies superior to 2-PAM. Significantly, there was an apparent inverse relationship between in vitro and in vivo results; the most potent in vivo compounds proved to be the poorest in vitro reactivators. These results suggested that an alternative and possibly novel antidotal mechanism of protective action may be applicable for the imidazolium aldoximes. Selected compounds were also evaluated for their inhibition of AChE phosphorylation by GD and antimuscarinic and antinicotinic receptor blocking effects.

  DOI：

  10.1021/jm00122a034
• 作为产物：
  描述：

  Methoxymethoxycyclobutane 在 三氯化硼 作用下， 以 正己烷 、 正戊烷 为溶剂， 以64%的产率得到chloromethyl cyclobutyl ether
  参考文献：
  名称：

  Cleavage of methoxymethyl ethers with boron trichloride. A convenient, versatile preparation of chloromethyl ether derivatives

  摘要：

  DOI：

  10.1021/jo00374a040

文献信息

• GOFF D. A.; HARRIS R. N., III; BOTTARO J. C.; BEDFORD C. D., J. ORG. CHEM., 51,(1986) N 24, 4711-4714
  作者：GOFF D. A.、 HARRIS R. N., III、 BOTTARO J. C.、 BEDFORD C. D.

  DOI：——

  日期：——
• US4124765A
  申请人：——

  公开号：US4124765A

  公开（公告）日：1978-11-07
• Quaternary salts of 2-[(hydroxyimino)methyl]imidazole. 2. Preparation and in vitro and in vivo evaluaton of 1-(alkoxymethyl)-2-[(hydroxyimino)methyl]-3-methylimidazolium halides for reactivation of organophosphorus-inhibited acetylcholinesterases
  作者：Clifford D. Bedford、Ralph N. Harris、Robert A. Howd、Dane A. Goff、Gary A. Koolpe、M. Petesch、Alexi Miller、Harold W. Nolen、H. A. Musallam

  DOI：10.1021/jm00122a034

  日期：1989.2

  A series of structurally related mono- and bis-1,3-disubstituted 2-[(hydroxyimino)methyl]imidazolium halides were evaluated in vitro for their ability to reactivate electric eel, bovine, and human erythrocyte (RBC) acetylcholinesterases (AChE) inhibited by ethyl p-nitrophenyl methylphosphonate (EPMP) and 3,3-dimethyl-2-butyl methyl-phosphonofluoridate (soman, GD). All new compounds were characterized for (hydroxyimino)methyl acid dissociation constant, nucleophilicity, octanol-buffer partition coefficient, reversible AChE inhibition, and kinetics of reactivation of EPMP-inhibited AChEs. For GD-inhibited AChEs, maximal reactivation was used to compare compounds since rapid phosphonyl enzyme dealkylation "aging" complicated interpretation of kinetic constants. For comparison, we also evaluated three known pyridinium therapeutics, 2-PAM, HI-6, and toxogonin. In vivo evaluation in mice revealed that when selected imidazolium compounds were coadministered with atropine sulfate, they were effective in providing lifesaving protection against both GD and EPMP challenges. This was a major accomplishment in the search for effective anticholinesterase therapeutics--the synthesis and preliminary evaluation of the first new monoquaternary soman antidotes with potencies superior to 2-PAM. Significantly, there was an apparent inverse relationship between in vitro and in vivo results; the most potent in vivo compounds proved to be the poorest in vitro reactivators. These results suggested that an alternative and possibly novel antidotal mechanism of protective action may be applicable for the imidazolium aldoximes. Selected compounds were also evaluated for their inhibition of AChE phosphorylation by GD and antimuscarinic and antinicotinic receptor blocking effects.
• Cleavage of methoxymethyl ethers with boron trichloride. A convenient, versatile preparation of chloromethyl ether derivatives
  作者：Dane A. Goff、Ralph N. Harris、Jeffrey C. Bottaro、Clifford D. Bedford

  DOI：10.1021/jo00374a040

  日期：1986.11