2-(羟基亚氨基)-2-(4-甲氧基苯基)乙酸乙酯 | 131934-12-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 中文名称: 2-(羟基亚氨基)-2-(4-甲氧基苯基)乙酸乙酯
• 英文名称: Ethyl 2-hydroxyimino-2-(4-methoxyphenyl)acetate
• CAS: 131934-12-8
• 化学式: C₁₁H₁₃NO₄
• 分子量: 223.229
• InChiKey: CFUZFAQNHIPTBV-UHFFFAOYSA-N

物化性质

• 沸点：
  357.7±44.0 °C(Predicted)
• 密度：
  1.16±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  16
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  68.1
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-(羟基亚氨基)-2-(4-甲氧基苯基)乙酸乙酯 在 palladium on activated charcoal 甲酸铵 作用下， 以 甲醇 为溶剂， 反应 5.0h， 以55%的产率得到2-氨基-2-(4-甲氧基苯基)乙酸乙酯
  参考文献：
  名称：

  甲酸铵催化钯催化偶氮苯和肟的转移加氢†

  摘要：

  使用甲酸铵作为氢源的Pd 0已实现了偶氮苯的还原裂解，包括肟的还原为相应的胺。

  DOI：

  10.1039/a705957d
• 作为产物：
  描述：

  硝基乙酸乙酯 、 苯甲醚 在 三氟甲磺酸 作用下， 以30%的产率得到2-(羟基亚氨基)-2-(4-甲氧基苯基)乙酸乙酯
  参考文献：
  名称：

  过酸和硫醇-烯反应，可得到具有HDAC抑制活性的psammaplin类似物

  摘要：

  基于超强酸，微波和S-ene化学的原始方法，提出了一种新颖的类似psammaplin结构的合成方法。新化合物被评估为组蛋白脱乙酰基酶抑制剂。结果突出了使用在还原/氧化条件下活化的二硫键前药时的重要考虑因素，必须根据肿瘤细胞类型仔细选择二硫键前药。

  DOI：

  10.1016/j.tet.2014.10.053

文献信息

• Lewis acid promoted electrophilic aromatic substitution reaction of nitrile oxide: Increase of the electrophilicity of carbon atom of nitrile oxide by Lewis acid complexation
  作者：Jae Nyoung Kim、Eung K. Ryu

  DOI：10.1016/s0040-4039(00)73637-9

  日期：1993.5

  Nitrile oxides complexed with Lewis acid have their increased electrophilic character at the carbon atom and could be used as hydroxynitrilium ion equivalents toward aromatic compounds.

  与路易斯酸络合的腈氧化物在碳原子上具有增强的亲电子特性，可以用作芳族化合物的羟基腈离子当量。
• Oxyiminoalkanoic acid derivatives
  申请人：——

  公开号：US20030186985A1

  公开（公告）日：2003-10-02

  To provide a novel oxyiminoalkanoic acid derivative which has excellent hypoglycemic and hypolipidemic actions and which is used for the prevention or treatment of diabetes mellitus, hyperlipemia, insulin insensitivity, insulin resistance and impaired glucose tolerance. A compound represented by the formula: 1 wherein R 1 is an optionally substituted hydrocarbon group or an optionally substituted heterocyclic group; X is a bond, —CO—, —CH(OH)— or a group represented by —NR 6 — wherein R 6 is a hydrogen atom or an optionally substituted alkyl group; n is an integer of 1 to 3; Y is an oxygen atom, a sulfur atom, —SO—, —SO 2 — or a group represented by —NR 7 — wherein R 7 is a hydrogen atom or an optionally alkyl group; ring A is a benzene ring optionally having additional one to three substituents; p is an integer of 1 to 8; R 2 is a hydrogen atom, an optionally substituted hydrocarbon group or an optionally substituted heterocyclic group; q is an integer of 0 to 6; m is 0 or 1; R 3 is a hydroxy group, OR 8 (R 8 is an optionally substituted hydrocarbon group.) or NR 9 R 10 (R 9 and R 10 are the same or different groups which are selected from a hydrogen atom, an optionally substituted hydrocarbon group, an optionally substituted heterocyclic group or an optionally substituted acyl group or R 9 and R 10 combine together to form a ring); R 4 and R 5 are the same or different groups which are selected from a hydrogen atom or an optionally substituted hydrocarbon group wherein R 4 may form a ring with R 2 ; provided that when R 1 is a ethoxymethyl, a C 1-3 alkyl, phenyl or p-methoxyphenyl and q=m=0, R 3 is NR 9 R 10 ; and provided that O-[2-chloro-4-(2-quinolylmethoxy)phenylmethyl]oxime and a methylpyruvate of [2-chloro-4-(2-quinolylmethoxy)phenylmethyl]-2-iminoxypropionic acid are excluded; or a salt thereof.

  提供一种新型的氧亚胺基脂肪酸衍生物，具有优异的降血糖和降血脂作用，并用于预防或治疗糖尿病、高脂血症、胰岛素不敏感、胰岛素抵抗和糖耐量受损。该化合物的结构式为1，其中R1是可选取的取代的碳氢化合物基团或可选取的取代的杂环基团；X是键，-CO-，-CH（OH）-或由-NR6-表示的基团（其中R6是氢原子或可选取的取代的烷基基团）；n是1到3的整数；Y是氧原子、硫原子、-SO-，-SO2-或由-NR7-表示的基团（其中R7是氢原子或可选取的烷基基团）；环A是苯环，可选取具有1到3个附加取代基团；p是1到8的整数；R2是氢原子、可选取的取代的碳氢化合物基团或可选取的取代的杂环基团；q是0到6的整数；m是0或1；R3是羟基、OR8（其中R8是可选取的取代的碳氢化合物基团）或NR9R10（其中R9和R10是相同或不同的基团，选自氢原子、可选取的取代的碳氢化合物基团、可选取的取代的杂环基团或可选取的取代的酰基，或R9和R10结合形成环）；R4和R5是相同或不同的基团，选自氢原子或可选取的取代的碳氢化合物基团，其中R4可以与R2形成环；但当R1为乙氧甲基、C1-3烷基、苯基或对甲氧基苯基且q=m=0时，R3为NR9R10；且不包括O-[2-氯-4-(2-喹啉基甲氧基)苯甲基]肟和[2-氯-4-(2-喹啉基甲氧基)苯甲基]-2-亚氨基丙酸甲酯；或其盐。
• [EN] OXYIMINOALKANOIC ACID DERIVATIVES WITH HYPOGLYCEMIC AND HYPOLIPIDEMIC ACTIVITY<br/>[FR] DERIVES D'ACIDE OXYMINOALCANOIQUE AYANT UN EFFET HYPOGLYCEMIQUE ET HYPOLIPIDEMIQUE
  申请人：TAKEDA CHEMICAL INDUSTRIES, LTD.

  公开号：WO1999058510A1

  公开（公告）日：1999-11-18

  (EN) To provide a novel oxyiminoalkanoic acid derivative which has excellent hypoglycemic and hypolipidemic actions and which is used for the prevention or treatment of diabetes mellitus, hyperlipemia, insulin insensitivity, insulin resistance and impaired glucose tolerance. A compound represented by formula (a) wherein R1 is an optionally substituted hydrocarbon group or an optionally substituted heterocyclic group; X is a bond, -CO-, -CH(OH)- or a group represented by -NR6- wherein R6 is a hydrogen atom or an optionally substituted alkyl group; n is an integer of 1 to 3; Y is an oxygen atom, a sulfur atom, -SO-, -SO2- or a group represented by -NR7- wherein R7 is a hydrogen atom or an optionally alkyl group; ring A is a benzene ring optionally having additional one to three substituents; p is an integer of 1 to 8; R2 is a hydrogen atom, an optionally substituted hydrocarbon group or an optionally substituted heterocyclic group; q is an integer of 0 to 6; m is 0 or 1; R3 is a hydroxy group, OR8 (R8 is an optionally substituted hydrocarbon group) or NR9R10 (R9 and R10 are the same or different groups which are selected from a hydrogen atom, an optionally substituted hydrocarbon group, an optionally substituted heterocyclic group or an optionally substituted acyl group or R9 and R10 combine together to form a ring); R4 and R5 are the same or different groups which are selected from a hydrogen atom or an optionally substituted hydrocarbon group wherein R4 may form a ring with R2; provided that when R1 is a ethoxymethyl, a C1-3 alkyl, phenyl or p-methoxyphenyl and q=m=0, R3 is NR9R10; and provided that O-[2-chloro-4-(2-quinolylmethoxy)phenylmethyl]oxime and a methyl pyruvate of [2-chloro-4-(2-quinolylmethoxy)phenylmethyl]-2-iminoxypropionic acid are excluded; or a salt thereof.(FR) On décrit un composé de la formule (a), ou un sel dudit composé, qui donne un nouveau dérivé d'acide oxyminoalcanoïque ayant un excellent effet hypoglycémique et hypolipidémique, et s'utilise pour la prévention ou le traitement du diabète sucré, de l'hyperlipémie, de l'insensibilité à l'insuline, de la résistance à l'insuline et de l'intolérance au glucose. Dans ladite formule, R1 est un groupe hydrocarbure éventuellement substitué ou un groupe hétérocyclique éventuellement substitué; X est une liaison -CO-, -CH(OH)- ou un groupe représenté par -NR6- (R6 étant un atome d'hydrogène ou un groupe alkyle éventuellement substitué); n est un entier compris entre 1 et 3; Y est un atome d'oxygène, un atome soufre, -SO-, -SO2- ou un groupe représenté par -NR7- (R7 étant un atome d'hydrogène ou un groupe alkyle éventuellement substitué; le noyau A est un noyau benzénique ayant éventuellement un à trois substituants complémentaires; p est un entier compris entre 1 et 8; R2 est un atome d'hydrogène, un groupe hydrocarbure éventuellement substitué ou un groupe hétérocyclique éventuellement substitué; q est un entier compris entre 0 et 6; m est 0 ou 1; R3 est un groupe hydroxy, OR8 (R8 étant un groupe hydrocarbure éventuellement substitué) ou NR9R10 (R9 et R10 étant des groupes identiques ou différents sélectionnés dans le groupe constitué par un atome d'hydrogène, un groupe hydrocarbure éventuellement substitué, un groupe hétérocyclique éventuellement substitué ou groupe acyle éventuellement substitué, ou R9 et R10 forment ensemble un noyau); R4 et R5 sont des groupes identiques ou différents sélectionnés dans le groupe constitué par un atome d'hydrogène ou un groupe hydrocarbure éventuellement substitué (R4 pouvant former un noyau avec R2); à condition que, d'une part, si R1 est éthoxyméthyle, un alkyle C1-3, phényle ou p-méthoxyphényle et que q=m=0, R3 soit NR9R10; et, d'autre part que O-[2-chloro-4-(2-quinolylméthoxy)phénylméthyl]oxime et un pyruvate de méthyle d'acide [2-chloro-4-(2-quinolylméthoxy)phénylméthyl]-2-iminoxypropionique soient exclus.

  提供一种新型的氧亚胺基脂肪酸衍生物，具有优异的降血糖和降血脂作用，可用于预防或治疗糖尿病、高脂血症、胰岛素不敏感、胰岛素抵抗和糖耐量受损。该化合物由公式(a)表示，其中R1是可选取代的碳氢化合物基团或可选取代的杂环基团；X是键合，-CO-，-CH（OH）-或由-NR6-表示的基团，其中R6是氢原子或可选取代的烷基基团；n是1至3的整数；Y是氧原子、硫原子、-SO-，-SO2-或由-NR7-表示的基团，其中R7是氢原子或可选取代的烷基基团；环A是苯环，可选具有1至3个补充取代基团；p是1至8的整数；R2是氢原子、可选取代的碳氢化合物基团或可选取代的杂环基团；q是0至6的整数；m是0或1；R3是羟基、OR8（其中R8是可选取代的碳氢化合物基团）或NR9R10（其中R9和R10是从氢原子、可选取代的碳氢化合物基团、可选取代的杂环基团或可选取代的酰基基团中选择的相同或不同基团，或R9和R10结合形成一个环）；R4和R5是从氢原子或可选取代的碳氢化合物基团中选择的相同或不同基团，其中R4可以与R2形成环；前提是当R1是乙氧甲基、C1-3烷基、苯基或对甲氧基苯基且q=m=0时，R3为NR9R10；并且排除O-[2-氯-4-(2-喹啉基甲氧基)苯甲基]肟和[2-氯-4-(2-喹啉基甲氧基)苯甲基]-2-亚氨基丙酸的甲酯；或其盐。
• Oxyiminoalkanoic acid derivatives with hypoglycemic and hypolipidemic activity
  申请人：TAKEDA CHEMICAL INDUSTRIES, LTD.

  公开号：EP1428531A1

  公开（公告）日：2004-06-16

  The invention relates to use of a compound or a salt thereof for the manufacture of a pharmaceutical composition for prevention or treatment of syndrome X, which compound is represented by the formula:    wherein R1 is an optionally substituted hydrocarbon group or an optionally substituted heterocyclic group; X is a bond, -CO-, -CH(OH)- or a group represented by -NR6- wherein R6 is a hydrogen atom or an optionally substituted alkyl group; n is an integer of 1 to 3; Y is an oxygen atom, a sulfur atom, -SO-, -SO2- or a group represented by -NR7- wherein R7 is a hydrogen atom or an optionally substituted alkyl group; ring A is a benzene ring optionally having additional one to three substituents; p is an integer of 1 to 8; R2 is a hydrogen atom, an optionally substituted hydrocarbon group or an optionally substituted heterocyclic group; q is an integer of 0 to 6; m is 0 or 1; R3 is a hydroxy group, OR8 (R8 is an optionally substituted hydrocarbon group) or NR9R10 (R9 and R10 are the same or different groups which are selected from a hydrogen atom, an optionally substituted hydrocarbon group, an optionally substituted heterocyclic group and an optionally substituted acyl group or R9 and R10 combine together to form a ring); R4 and R5 are the same or different groups which are selected from a hydrogen atom and an optionally substituted hydrocarbon group wherein R4 may form a ring with R2.

  本发明涉及一种化合物或其盐用于制造预防或治疗X综合征的药物组合物，该化合物由式表示： 其中 R1 是任选取代的烃基或任选取代的杂环基；X 是键、-CO-、-CH(OH)- 或由 -NR6- 代表的基团，其中 R6 是氢原子或任选取代的烷基；n 是 1 至 3 的整数；Y 是氧原子、硫原子、-SO-、-SO2- 或由 -NR7- 表示的基团，其中 R7 是氢原子或任选取代的烷基；环 A 是苯环，可任选附加 1 至 3 个取代基；p 是 1 至 8 的整数；R2 是氢原子、任选取代的烃基或任选取代的杂环基；q 是 0 至 6 的整数；m 是 0 或 1；R3 是羟基、OR8（R8 是任选取代的烃基）或 NR9R10（R9 和 R10 是相同或不同的基团，它们选自氢原子、任选取代的烃基、任选取代的杂环基和任选取代的酰基，或 R9 和 R10 结合在一起形成环）；R4 和 R5 是相同或不同的基团，它们选自氢原子和任选取代的烃基，其中 R4 可与 R2 形成环。
• Friedel-Crafts-type reactions involving di- and tricationic species. Onium-allyl dications and O,O-diprotonated aci-nitro species bearing a protonated carbonyl group
  作者：Tomohiko Ohwada、Naoko Yamagata、Koichi Shudo

  DOI：10.1021/ja00004a044

  日期：1991.2

  Stable carbocations do not react with nonactivated benzenes. For example, acetophenone does not react with benzene in the presence of trifluoromethanesulfonic acid (TFSA), while trifluoroacetophenone does do so under acidic conditions owing to activation of the electrophilicity of the hydroxycarbenium cation by the trifluoromethyl group. This and other studies suggest that an electron-withdrawing substituent on the cationic center increases the reactivity toward benzenes. In this paper, involvement of multiply positively charged (dicationic and tricationic) species, which have sufficient electrophilicity toward benzene, is demonstrated in the acid-catalyzed reactions of cinnamaldehyde and its derivatives and also in the acid-catalyzed reactions of nitromethanes. The species formed from cinnamaldehyde, cinnamaldimine, cinnamaldoxime, and their derivatives in TFSA or TFSA-SbF5 have an adequate reactivity toward benzene. O-Protonated cinnamaldehyde and its derivatives, N-protonated cinnamaldimine, and N,N-dimethylcinnamaldiminium salt do not react with benzene. Since a strong acid catalyst is required for the reactions, participation of doubly protonated species, onium-allyl dications, is proposed. Ab initio calculations of (1) the donor-acceptor interaction energies of a neutral donor (such as water and ammonia) and a doubly charged allyl dication and (2) proton affinities demonstrated that the ammonium-allyl dication is more stable than the oxonium-allyl dication, in accordance with the experimental observation. Nitronic acids also react with benzene at the ipso position with respect to the nitro group to give the phenylated oximes in the presence of TFSA. The reaction with benzene is not catalyzed by trifluoroacetic acid, which is sufficiently acidic to monoprotonate a nitronic acid to the protonated aci-nitro form. The reaction requires a stronger acid, trifluoromethanesulfonic acid, suggesting intervention of the dication formed by O,O-diprotonation of aci-nitroalkanes rather than the monoprotonated aci-nitroalkane. As a result of further study on the phenylation reactions, we found a facile phenylation reaction of nitromethanes substituted with an electron-withdrawing group, catalyzed by TFSA, to give phenylated alpha-carbonyloximes in high yields. A triply positively charged cation, an O,O-diprotonated aci-nitro species bearing a protonated ethoxycarbonyl group, which can react with nonactivated benzene, is proposed to be an intermediate in this reaction.