(Z)-1-<(3,4-Dimethoxyphenyl)methylene>-2-formyl-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline | 61348-95-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 四氢异喹啉
• 英文名称: (Z)-1-<(3,4-Dimethoxyphenyl)methylene>-2-formyl-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline
• 英文别名: (Z)-6,7-dimethoxy-1-(3,4-dimethoxyphenylmethylene)-2-formyl-1,2,3,4-tetrahydroisoquinoline；1-(3,4-dimethoxybenzylidene)-3,4-dihydro-6,7-dimethoxy-2(1H)-isoquinolinecarboxaldehyde；(1Z)-1-[(3,4-dimethoxyphenyl)methylidene]-6,7-dimethoxy-3,4-dihydroisoquinoline-2-carbaldehyde
• CAS: 61348-95-6
• 化学式: C₂₁H₂₃NO₅
• 分子量: 369.417
• InChiKey: MTADPZUGZBBVDA-MFOYZWKCSA-N

物化性质

• 沸点：
  572.0±50.0 °C(Predicted)
• 密度：
  1.240±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  27
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  57.2
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (Z)-1-<(3,4-Dimethoxyphenyl)methylene>-2-formyl-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline 在 (S)-Ru(OAc)₂-BINAP sodium hydroxide 、 氢气 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 24.0~80.0 ℃ 、405.3 kPa 条件下， 反应 58.0h， 生成 S-四氢罂粟碱
  参考文献：
  名称：

  General asymmetric synthesis of isoquinoline alkaloids. Enantioselective hydrogenation of enamides catalyzed by BINAP-ruthenium(II) complexes

  摘要：

  In the presence of a small amount of RuX(2)[(R)- or (S)-BINAP] (X = anionic ligand) a wide range of (Z)-2-acyl-1-benzylidene-1,2,3,4-tetrahydroisoquinolines are hydrogenated to give the saturated products in nearly quantitative yields and in high (up to 100 %) optical yields. The enamide substrates are selectively prepared by N-acylation of the corresponding 1-benzylated 3,4-dihydroisoquinolines under suitable acylation conditions; some crystalline materials having low solubility are obtained by a second-order Z/E stereomutation technique utilizing the double-bond photolability and lattice energy effects. This asymmetric hydrogenation sets the key stereogenic center in a predictable manner, either R or S flexibly, at the C(1) position of the benzylated tetrahydroisoquinolines. The chiral products are converted by standard functional group modification to tetrahydropapaverine, laudanosine, tretoquinol, norreticuline, etc. Hydrogenation of the simple 1-methylene substrate is used fbr synthesis of salsolidine. This enantioselective hydrogenation is applied to the synthesis of morphine and its artificial analogues such as morphinans and benzomorphans of either chirality. A mnemonic device is presented for predicting the reactivity and enantiofacial selection of the BINAP-Ru catalyzed hydrogenation. Reaction with BINAP-Rh catalyst proceeds with a lower enantioselectivity and an opposite sense of asymmetric induction.

  DOI：

  10.1021/jo00081a007
• 作为产物：
  描述：

  trimethylacetic formic anhydride 、 3,4-二氢罂粟碱 在 吡啶 作用下， 以 二氯甲烷 为溶剂， 反应 3.0h， 以90%的产率得到(Z)-1-<(3,4-Dimethoxyphenyl)methylene>-2-formyl-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline
  参考文献：
  名称：

  General asymmetric synthesis of isoquinoline alkaloids. Enantioselective hydrogenation of enamides catalyzed by BINAP-ruthenium(II) complexes

  摘要：

  In the presence of a small amount of RuX(2)[(R)- or (S)-BINAP] (X = anionic ligand) a wide range of (Z)-2-acyl-1-benzylidene-1,2,3,4-tetrahydroisoquinolines are hydrogenated to give the saturated products in nearly quantitative yields and in high (up to 100 %) optical yields. The enamide substrates are selectively prepared by N-acylation of the corresponding 1-benzylated 3,4-dihydroisoquinolines under suitable acylation conditions; some crystalline materials having low solubility are obtained by a second-order Z/E stereomutation technique utilizing the double-bond photolability and lattice energy effects. This asymmetric hydrogenation sets the key stereogenic center in a predictable manner, either R or S flexibly, at the C(1) position of the benzylated tetrahydroisoquinolines. The chiral products are converted by standard functional group modification to tetrahydropapaverine, laudanosine, tretoquinol, norreticuline, etc. Hydrogenation of the simple 1-methylene substrate is used fbr synthesis of salsolidine. This enantioselective hydrogenation is applied to the synthesis of morphine and its artificial analogues such as morphinans and benzomorphans of either chirality. A mnemonic device is presented for predicting the reactivity and enantiofacial selection of the BINAP-Ru catalyzed hydrogenation. Reaction with BINAP-Rh catalyst proceeds with a lower enantioselectivity and an opposite sense of asymmetric induction.

  DOI：

  10.1021/jo00081a007

文献信息

• Process for preparing N-acyltetrahydroisoquinoline
  申请人：Takasago Perfumery Co., Ltd.

  公开号：EP0245960A2

  公开（公告）日：1987-11-19

  A process for preparing an N-acyltetrahydro­isoquinoline represented by formula (II) wherein A repesents a phenylene ring substituted with a hydroxyl group, a Cl-4 alkoxy, acetoxy, or benzyloxy group; R represents a hydrogen atom, a Cl-1 alkyl, or phenyl group; and X represents a hydrogen atom, a phenyl group, or a phenyl group substituted with a hydroxyl group, a lower alkoxy group or an acetoxy group, which comprises asymmetrically hydrogenating a solution of an N-acyl-1-­methylenetetrahydroisoquinoline or N-acyl-1-benzylidene­tetrahydroisoquinoline represented by formula (I) wherein A, R, and X are as defined above, in solution at a H₂ pressure of 1 to 10 kg/cm² at 10 to 40°C for 10 to 160 hours, in the presence as catalyst of an optically active ruthenium-phosphine complex, of which several examples are given. The process exclusively and efficiently provides a useful isomer of the N-actyltetrahydroisoquinoline of high purity which is useful as an intermediate for synthesizing isoquinoline type alkaloids as pharmaceuticals without involving optical resolution of a racemate.

  一种制备由式(II)代表的N-酰基四氢异喹啉的工艺 其中 A 代表被羟基、Cl-4 烷氧基、乙酰氧基或苄氧基取代的苯基环；R 代表氢原子、Cl-1 烷基或苯基；X 代表氢原子、苯基或被羟基、低级烷氧基或乙酰氧基取代的苯基、 其中包括不对称地氢化由式（I）代表的 N-酰基-1-亚甲基四氢异喹啉或 N-酰基-1-亚苄基四氢异喹啉的溶液 其中 A、R 和 X 如上定义，在光学活性钌膦络合物作为催化剂存在下，于 10 至 40°C 下，在 1 至 10 kg/cm² 的 H₂ 压力下，在溶液中进行 10 至 160 小时。 该工艺独家有效地提供了一种有用的高纯度 N-内酰四氢异喹啉异构体，该异构体可用作合成异喹啉类生物碱的中间体，而不涉及外消旋体的光学解析。
• Asymmetric synthesis of isoquinoline alkaloids by homogeneous catalysis
  作者：Ryoji. Noyori、Masako. Ohta、Yi. Hsiao、Masato. Kitamura、Tetsuo. Ohta、Hidemasa. Takaya

  DOI：10.1021/ja00282a054

  日期：1986.10
• Lead tetraacetate mediated oxidation of the enamides derived from 1-benzyl-3,4-dihydroisoquinolines
  作者：George R. Lenz、Carl Costanza

  DOI：10.1021/jo00241a011

  日期：1988.3
• US4851537A
  申请人：——

  公开号：US4851537A

  公开（公告）日：1989-07-25
• General asymmetric synthesis of isoquinoline alkaloids. Enantioselective hydrogenation of enamides catalyzed by BINAP-ruthenium(II) complexes
  作者：Masato Kitamura、Yi Hsiao、Masako Ohta、Masaki Tsukamoto、Tetsuo Ohta、Hidemasa Takaya、Ryoji Noyori

  DOI：10.1021/jo00081a007

  日期：1994.1

  In the presence of a small amount of RuX(2)[(R)- or (S)-BINAP] (X = anionic ligand) a wide range of (Z)-2-acyl-1-benzylidene-1,2,3,4-tetrahydroisoquinolines are hydrogenated to give the saturated products in nearly quantitative yields and in high (up to 100 %) optical yields. The enamide substrates are selectively prepared by N-acylation of the corresponding 1-benzylated 3,4-dihydroisoquinolines under suitable acylation conditions; some crystalline materials having low solubility are obtained by a second-order Z/E stereomutation technique utilizing the double-bond photolability and lattice energy effects. This asymmetric hydrogenation sets the key stereogenic center in a predictable manner, either R or S flexibly, at the C(1) position of the benzylated tetrahydroisoquinolines. The chiral products are converted by standard functional group modification to tetrahydropapaverine, laudanosine, tretoquinol, norreticuline, etc. Hydrogenation of the simple 1-methylene substrate is used fbr synthesis of salsolidine. This enantioselective hydrogenation is applied to the synthesis of morphine and its artificial analogues such as morphinans and benzomorphans of either chirality. A mnemonic device is presented for predicting the reactivity and enantiofacial selection of the BINAP-Ru catalyzed hydrogenation. Reaction with BINAP-Rh catalyst proceeds with a lower enantioselectivity and an opposite sense of asymmetric induction.