2-(Hydroxymethyl)-1-phenylcyclopropanecarbonitrile | 60788-55-8

• 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: 2-(Hydroxymethyl)-1-phenylcyclopropanecarbonitrile
• 英文别名: 2-(hydroxymethyl)-1-phenylcyclopropane-1-carbonitrile
• CAS: 60788-55-8
• 化学式: C₁₁H₁₁NO
• 分子量: 173.214
• InChiKey: YDIYUDSRGPPHKA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  13
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  44
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  2-(Hydroxymethyl)-1-phenylcyclopropanecarbonitrile 在 palladium on activated charcoal 氢氧化钾 、 正丁基锂 、 sodium azide 、 草酰氯 、 四溴化碳 、 氢气 、 二甲基亚砜 、 三乙胺 、 三苯基膦 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 26.5h， 生成 (1R,2S)-1-phenyl-2-<(R)-1-aminoethyl>-N,N-diethylcyclopropanecarboxamide
  参考文献：
  名称：

  Conformational Restriction by Repulsion between Adjacent Substituents on a Cyclopropane Ring:  Design and Enantioselective Synthesis of 1-Phenyl-2-(1-aminoalkyl)-N,N-diethylcyclopropanecarboxamides as Potent NMDA Receptor Antagonists

  摘要：

  Adjacent substituents on a cyclopropane ring mutually exert steric repulsion quite significantly, because they are fixed in eclipsed conformation to each other. Based on this structural feature of the cyclopropane ring, conformationally restricted analogs of milnacipran (1), namely 1-phenyl-2-(1-aminoalkyl)-N,N-diethylcyclopropanecarboxamides (2, 3, ent-2, and ent-3) were designed as potent NMDA receptor antagonists and were synthesized highly enantioselectively. Reaction of (R)epichlorohydrin [(R)-5] and phenylacetonitrile (6) in the presence of NaNH2 in benzene gave a chiral cyclopropane derivative that was isolated as lactone 4 with 96% ee in 67% yield, after alkaline hydrolysis of the cyano group. The nucleophilic addition reaction of Grignard reagents to aldehyde 10, which was readily prepared from 4, proceeded highly selectively from the si-face to afford addition products 11 in high yields. Although hydride reduction of the corresponding ketone 15b, prepared from 11b, with L-Selectride also proceeded highly diastereo selectively, the facial selectivity was reversed to give the re-face addition product 11b. On the other hand, reduction of 15 with DIBAL-H afforded the si-face addition product 12 in high yields. These results suggested that these nucleophilic addition reactions proceeded via either the bisected s-trans or s-cis conformation of the cyclopropylcarbonyl derivatives. From 11 and 12, the target conformationally resticted analogs, 2 and 3, were synthesized, respectively. Starting from (S)-epichlorohydrin [(S)-5], their corresponding enantiomers, ent-a and ent-3, were also synthesized. The structures of the conformationally restricted analogs detected by the X-ray crystallographic analysis suggested that their conformations can be restricted as we hypothesized. Thus, a new method for restricting the conformation of cyclopropane derivatives has been developed.

  DOI：

  10.1021/jo9518056
• 作为产物：
  描述：

  alpha-苯基环氧乙烷丙腈 在 正丁基锂 作用下， 以 四氢呋喃 为溶剂， 反应 1.0h， 以72%的产率得到2-(Hydroxymethyl)-1-phenylcyclopropanecarbonitrile
  参考文献：
  名称：

  Hughes, Simon; Griffiths, Gwerydd; Stirling, Charles J. M., Journal of the Chemical Society. Perkin transactions II, 1987, p. 1253 - 1264

  摘要：

  DOI：

文献信息

• AMINOALKYLCYCLOPROPANE DERIVATIVE
  申请人：Asahi Kasei Kogyo Kabushiki Kaisha

  公开号：EP0747348A1

  公开（公告）日：1996-12-11

  Disclosed are a novel optically active compound represented by formula (1), a racemic modification thereof, and a pharmaceutically acceptable acid addition salt of the optically active compound or racemic modification thereof:    wherein R is a straight chain or branched C1-C5 aliphatic group which is saturated or unsaturated, or a phenyl group which is unsubstituted or substituted with 1 to 3 substituents which are each independently selected from the group consisting of a halogen atom, a C1-C4 alkyl group, a nitro group, an amino group, a hydroxyl group and a C1-C4 alkoxy group; and mark * indicates an asymmetric carbon atom. The novel optically active aminoalkylcyclopropane derivative of the present invention, a racemic modification thereof, and a pharmaceutically acceptable acid addition salt of the optically active aminoalkylcyclopropane derivative or racemic modification thereof have remarkably high antagonistic activity with respect to NMDA receptor, as compared to known aminomethylcyclopropane derivatives and is useful as a preventive agent for cerebral infarction and a protective agent against ischemic diseases.

  本发明公开了一种由式（1）代表的新型光学活性化合物、其外消旋修饰物以及该光学活性化合物或其外消旋修饰物的药学上可接受的酸加成盐： 其中 R 是饱和或不饱和的直链或支链 C1-C5 脂肪族基团，或未被取代或被 1 至 3 个取代基取代的苯基，这些取代基各自独立地选自卤素原子、C1-C4 烷基、硝基、氨基、羟基和 C1-C4 烷氧基组成的组；标记 * 表示不对称碳原子。 与已知的氨基甲基环丙烷衍生物相比，本发明的新型光学活性氨基烷基环丙烷衍生物、其外消旋修饰物以及光学活性氨基烷基环丙烷衍生物或其外消旋修饰物的药学上可接受的酸加成盐对 NMDA 受体具有显著的高拮抗活性，可用作脑梗塞的预防剂和缺血性疾病的保护剂。
• Chemo-, Regio-, and Diastereoselective Synthesis of Functionalized Cyclopropanes by Cyclization of Dilithiated Nitriles with Epibromohydrin
  作者：Peter Langer、Ilia Freifeld

  DOI：10.1021/ol010207c

  日期：2001.11.1

  [GRAPHICS]The cyclization of 1,1-dianions with epibromohydrin results in chemo-, regio-, and diastereoselective formation of functionalized hydroxymethyl cyclopropanes.
• HUGHES, SIMON;GRIFFITHS, GWERYDD;STIRLING, CHARLES J. M., J. CHEM. SOC. PERKIN TRANS.,(1987) N 9, 1253-1264
  作者：HUGHES, SIMON、GRIFFITHS, GWERYDD、STIRLING, CHARLES J. M.

  DOI：——

  日期：——
• CASADIO S.; BONNAUD B.; MOUZIN G.; COUSSE H., BOLL. CHIM. FARM., 1978, 117, NO 6 331-342
  作者：CASADIO S.、 BONNAUD B.、 MOUZIN G.、 COUSSE H.

  DOI：——

  日期：——
• US5621142A
  申请人：——

  公开号：US5621142A

  公开（公告）日：1997-04-15