3,4-Dihydroacridine | 37624-10-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: 3,4-Dihydroacridine
• 英文别名: 5,6-Dihydro-acridine
• CAS: 37624-10-5
• 化学式: C₁₃H₁₁N
• 分子量: 181.237
• InChiKey: RGYOVBROWDGEAT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  14
• 可旋转键数：
  0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  12.9
• 氢给体数：
  0
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  3,4-Dihydroacridine 在 4-二甲氨基吡啶 、 氢氧化钾 、 N-溴代丁二酰亚胺(NBS) 、 偶氮二异丁腈 、 sodium methylate 、 N-溴代乙酰胺 作用下， 以 四氢呋喃 、 吡啶 、 四氯化碳 、 水 、 叔丁醇 为溶剂， 反应 12.2h， 生成 (-)-(1R,2R)-trans-1,2-dihydroacridine-1,2-diol
  参考文献：
  名称：

  Chemical synthesis of the (1R,2S) and (1S,2R) arene oxide metabolites of acridine

  摘要：

  Enantiopure samples of (+)-(1R,2S) and (-)-(1S,2R)-1,2-epoxy-1,2-dihydroacridine 4 have been obtained from the corresponding trans-2-bromo-1,2,3,4-tetrahydroacridin-1-ol MTPA esters 7a and b. Absolute configurations were deduced by stereochemical correlation to (+)-(1R,2R)-trans-2-bromo-1-(2-methoxy-2-phenyl-2-trifluoroacetoxy)-1,2,3,4-acridine 7a which was unequivocally assigned by X-ray crystal structure analysis. (-)-(1R,2R)-trans-1,2-Dihydroacridine-1,2-diol 2 was obtained by alkaline hydrolysis of (+)-(1R,2S) -acridine 1,2-oxide 4.

  DOI：

  10.1039/p19940002711
• 作为产物：
  描述：

  2-氨基苯甲醛 在 sodium tetrahydroborate 、 PPA 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 生成 3,4-Dihydroacridine
  参考文献：
  名称：

  Synthesis and Solvolysis of Acridine 1,2- and 3,4-Oxides: Crystal Structure of Acridine 1,2-Oxide

  摘要：

  Acridine 1,2- and 3,4-oxides were synthesized from 3,4- and 1,2-dihydroacridine, respectively, via intermediate bromohydrin acetates. Crystals of acridine 1,2-oxide were sufficiently stable to allow the first determination of X-ray crystallographic structural features of a non-K-region arene oxide. Aqueous alkaline hydrolysis of the acridine 1,2- and 3,4-oxides produced trans-1,2-dihydrorxy-1,2-dihydroacridine and trans-3,4-dihydroxy-3,4-dihydroacridine, respectively. The former dihydrodiol was also obtained by a six-step synthesis from 3,4-dihydroacridine. Acid-catalyzed hydrolysis of acridine 1,2-oxide yielded the corresponding cis- and trans-1,2-dihydrodiols (20%) in addition to 1-hydroxy- (12%) and 2-hydroxyacridine (68%). By contrast, solvolysis of acridine 3,4-oxide under acid conditions gave 4-hydroxyacridine as the exclusive product. pH-rate profiles for hydrolysis of the acridine oxides in 1:9 dioxane-water at 25 degrees C were compared with those for anthracene 1,2-oxide, naphthalene 1,2-oxide, and quinoline 5,6- and 7,8-oxides. Second-order rate constants for the hydronium ion-catalyzed ring opening of anthracene 1,2-, acridine 3,4-, and acridine 1,2-oxide are 585, 7.81, and 0.45 M(-1) s(-2), respectively, and are 3-5 times larger than the rate constants for the corresponding naphthalene 1,2-, quinoline 7,8-, and quinoline 5,6-oxides. Rate constants for uncatalyzed ring opening of anthracene 1,2- and acridine 3,4-oxides (117 x 10(-5) s(-1) and 2.4 X 10(-5) s(-1), respectively) are about two to three times larger than the corresponding rate constants for naphthalene 1,2- and quinoline 7,8-oxides, whereas the rate of nucleophilic ring opening by hydroxide ion to give the trans-dihydrodiols is accelerated by less than a factor of 2 for the acridine oxides as compared with their quinoline analogs. The pH-rate profiles for solvolysis of the acridine oxides, like those of the quinoline oxides, exhibit a pH-independent region at pH values below the pK(a) of the ring nitrogen that is attributed to formation of an unreactive N-protonated species.

  DOI：

  10.1021/jo00084a013

文献信息

• Utilisation de 1,2,3,4-tétrahydro-acridines pour le traitement du SIDA, et composés
  申请人：STE CIVILE DE RECHERCHE NEWPHARM

  公开号：EP0375471A3

  公开（公告）日：1992-07-08

  L'invention se rapporte au domaine de la chimie thérapeutique.Elle a pour objet des compositions pharmaceutiques assurant la regénération des lymphocytes T4 ou l'augmentation de leur nombre chez des sujets présentant un syndrome immuno-déficitaire qui renferment, à titre de principe actif, la 9-amino 1,2,3,4-Tétrahydro acridine ou un de ses sels ou un de ses précurseurs biologiques.L'invention concerne aussi, à titre de produits nouveaux, les précurseurs biologiques de la 9-amino 1,2,3,4-Tétrahydro acridine.

  本发明涉及治疗化学领域，涉及确保免疫缺陷综合征患者 T4 淋巴细胞再生或增加其数量的药物组合物，其活性成分为 9-氨基-1,2,3,4-四氢吖啶或其盐类之一或其生物前体之一。
• Synthesis and Solvolysis of Acridine 1,2- and 3,4-Oxides: Crystal Structure of Acridine 1,2-Oxide
  作者：Derek R. Boyd、R. Jeremy H. Davies、Lynne Hamilton、John J. McCullough、John F. Malone、H. Patricia Porter、Allison Smith、John M. Carl、Jane M. Sayer、Donald M. Jerina

  DOI：10.1021/jo00084a013

  日期：1994.3

  Acridine 1,2- and 3,4-oxides were synthesized from 3,4- and 1,2-dihydroacridine, respectively, via intermediate bromohydrin acetates. Crystals of acridine 1,2-oxide were sufficiently stable to allow the first determination of X-ray crystallographic structural features of a non-K-region arene oxide. Aqueous alkaline hydrolysis of the acridine 1,2- and 3,4-oxides produced trans-1,2-dihydrorxy-1,2-dihydroacridine and trans-3,4-dihydroxy-3,4-dihydroacridine, respectively. The former dihydrodiol was also obtained by a six-step synthesis from 3,4-dihydroacridine. Acid-catalyzed hydrolysis of acridine 1,2-oxide yielded the corresponding cis- and trans-1,2-dihydrodiols (20%) in addition to 1-hydroxy- (12%) and 2-hydroxyacridine (68%). By contrast, solvolysis of acridine 3,4-oxide under acid conditions gave 4-hydroxyacridine as the exclusive product. pH-rate profiles for hydrolysis of the acridine oxides in 1:9 dioxane-water at 25 degrees C were compared with those for anthracene 1,2-oxide, naphthalene 1,2-oxide, and quinoline 5,6- and 7,8-oxides. Second-order rate constants for the hydronium ion-catalyzed ring opening of anthracene 1,2-, acridine 3,4-, and acridine 1,2-oxide are 585, 7.81, and 0.45 M(-1) s(-2), respectively, and are 3-5 times larger than the rate constants for the corresponding naphthalene 1,2-, quinoline 7,8-, and quinoline 5,6-oxides. Rate constants for uncatalyzed ring opening of anthracene 1,2- and acridine 3,4-oxides (117 x 10(-5) s(-1) and 2.4 X 10(-5) s(-1), respectively) are about two to three times larger than the corresponding rate constants for naphthalene 1,2- and quinoline 7,8-oxides, whereas the rate of nucleophilic ring opening by hydroxide ion to give the trans-dihydrodiols is accelerated by less than a factor of 2 for the acridine oxides as compared with their quinoline analogs. The pH-rate profiles for solvolysis of the acridine oxides, like those of the quinoline oxides, exhibit a pH-independent region at pH values below the pK(a) of the ring nitrogen that is attributed to formation of an unreactive N-protonated species.
• Chemical synthesis of the (1R,2S) and (1S,2R) arene oxide metabolites of acridine
  作者：Derek R. Boyd、Michael R. J. Dorrity、Lynne Hamilton、John F. Malone、Allison Smith

  DOI：10.1039/p19940002711

  日期：——

  Enantiopure samples of (+)-(1R,2S) and (-)-(1S,2R)-1,2-epoxy-1,2-dihydroacridine 4 have been obtained from the corresponding trans-2-bromo-1,2,3,4-tetrahydroacridin-1-ol MTPA esters 7a and b. Absolute configurations were deduced by stereochemical correlation to (+)-(1R,2R)-trans-2-bromo-1-(2-methoxy-2-phenyl-2-trifluoroacetoxy)-1,2,3,4-acridine 7a which was unequivocally assigned by X-ray crystal structure analysis. (-)-(1R,2R)-trans-1,2-Dihydroacridine-1,2-diol 2 was obtained by alkaline hydrolysis of (+)-(1R,2S) -acridine 1,2-oxide 4.