N-benzoylcytisine | 6202-07-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: N-benzoylcytisine
• 英文别名: (1R,9S)-11-Benzoyl-7,11-diazatricyclo[7.3.1.02,7]trideca-2,4-dien-6-one
• CAS: 6202-07-9
• 化学式: C₁₈H₁₈N₂O₂
• 分子量: 294.353
• InChiKey: HODDQHCNQOBZKP-DZGCQCFKSA-N

物化性质

• 熔点：
  184-188 °C
• 沸点：
  556.6±49.0 °C(Predicted)
• 密度：
  1.30±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  22
• 可旋转键数：
  1
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  40.6
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  N-benzoylcytisine 在 platinum(IV) oxide 、 palladium dihydroxide 氢气 、 甲酸铵 、 三乙胺 作用下， 以 甲醇 、 乙醇 、 二氯甲烷 为溶剂， 反应 46.0h， 生成 (1R,2S,9R)-11-methyl-7,11-diazatricyclo[7.3.1.0^2,7]tridecane 11-carboxylate
  参考文献：
  名称：

  在 O-烷基氨基甲酸酯的对映选择性锂化-亲电捕获中评价类斯巴丁手性二胺

  摘要：

  在二胺介导的 O-烷基氨基甲酸酯的不对称锂化捕获中评估了七种 (+)-sparteine 样二胺和 (-)-sparteine。(+)-sparteine 样二胺（手性位移 NMR 光谱≥98:2 er）由 (-)-金雀花碱（N-苄基金雀花碱的手性 HPLC 得到 >99:1 er）和两个新的 (+)含有 N-CD3 取代基的类sparteine 二胺被包括在本研究中。从配体评估研究中获得了以下结果： (-)-sparteine 在诱导近乎完美的对映选择性 (99 : 1 er) 的能力方面无与伦比；N-甲基二胺和两种 N-CD3-取代的二胺是最佳的 (+)-sparteine 替代物（高达 96 : 4 er）；空间位阻更大的 N-烷基取代基降低了对映选择性（N-异丙基：86：14 er；N-CH2tBu：54：46 er）。从合成的角度来看，

  DOI：

  10.1039/b600032k
• 作为产物：
  描述：

  苯甲酰氯 、 cytisine 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 5.0h， 以85%的产率得到N-benzoylcytisine
  参考文献：
  名称：

  在 O-烷基氨基甲酸酯的对映选择性锂化-亲电捕获中评价类斯巴丁手性二胺

  摘要：

  在二胺介导的 O-烷基氨基甲酸酯的不对称锂化捕获中评估了七种 (+)-sparteine 样二胺和 (-)-sparteine。(+)-sparteine 样二胺（手性位移 NMR 光谱≥98:2 er）由 (-)-金雀花碱（N-苄基金雀花碱的手性 HPLC 得到 >99:1 er）和两个新的 (+)含有 N-CD3 取代基的类sparteine 二胺被包括在本研究中。从配体评估研究中获得了以下结果： (-)-sparteine 在诱导近乎完美的对映选择性 (99 : 1 er) 的能力方面无与伦比；N-甲基二胺和两种 N-CD3-取代的二胺是最佳的 (+)-sparteine 替代物（高达 96 : 4 er）；空间位阻更大的 N-烷基取代基降低了对映选择性（N-异丙基：86：14 er；N-CH2tBu：54：46 er）。从合成的角度来看，

  DOI：

  10.1039/b600032k

文献信息

• 1-Acyldeoxyvasicinone salts as effective intermediate C-and N-acylating agents for alkaloids and amino acids
  作者：Kh. M. Shakhidoyatov、G. P. Genjemuratova、E. Oripov

  DOI：10.1007/s10600-006-0261-9

  日期：2006.11

  The reaction of deoxyvasicinone with acid chlorides of aliphatic (acetylbromide) and aromatic (benzoyl-, o-, p-methoxy-, p-nitrobenzoylchlorides) acids was studied. It was shown that 1-deoxyvasicinone salts were formed at room temperature; α-aroyloxymethylidenedeoxyvasicinones, in the presence of triethylamine at 80–85°C. It was found that acid chlorides cause 1-acyldeoxyvasicinone salts to transform into α-hydroxy-or α-aroyloxyarylidenedeoxyvasicinones, which indirectly confirmed their acylating properties. It was found that 1-acyldeoxyvasicinone salts were effective acylating agents for alkaloids (cytisine, 1,2-dihydrodeoxyvasicinone) and amino acids (glycine, β-alanine, α-aminobutyric acid) and can be used to acylate primary and secondary aliphatic and heterocyclic amines.

  研究了脱氧紫堇酮与脂肪族（乙酰溴）和芳香族（苯甲酰、邻、对甲氧基、对硝基苯甲酰氯）羧酸酰氯的反应。结果表明，在室温下形成1-脱氧紫堇酮盐；在三乙胺存在下，80-85°C时形成α-芳酰氧甲叉脱氧紫堇酮。研究发现，酰氯引起1-酰基脱氧紫堇酮盐转化为α-羟基或α-芳酰氧芳叉脱氧紫堇酮，间接证实了它们的酰化性质。发现1-酰基脱氧紫堇酮盐对生物碱（金雀花碱、1,2-二氢脱氧紫堇酮）和氨基酸（甘氨酸、β-丙氨酸、α-氨基丁酸）是有效的酰化剂，并可用于酰化脂肪族和杂环的一级和二级胺。
• Thionation of quinolizidine alkaloids and their derivatives via Lawesson’s reagent
  作者：Alena V. Koval’skaya、Polina R. Petrova、Dmitry O. Tsypyshev、Alexander N. Lobov、Inna P. Tsypysheva

  DOI：10.1080/14786419.2020.1868460

  日期：2022.7.18

  Abstract Direct thionation of quinolizidine alkaloids (-)-cytisine, methylcytisine, thermopsine and some of their carbonyl derivatives was realized. It was established that carrying out of the reaction in the boiling toluene with 0.5 eq. of Lawesson’s reagent (LR) is most effective for synthesis of thio analogues of methyl-, allyl-, benzylcytisine and thermopsine. It was found, that formation of thioamides

  摘要 实现了喹尼西啶生物碱(-)-金雀花碱、甲基金雀花碱、嗜热霉素及其一些羰基衍生物的直接硫化。确定在沸腾的甲苯中以0.5当量进行反应。Lawesson 试剂 (LR) 对合成甲基、烯丙基、苄基胞嘧啶和嗜热霉素的硫代类似物最有效。已发现，在起始(-)-金雀花碱的3-甲酰胺或甲基金雀花碱的2-氧代和4-氧代衍生物的情况下，优选形成硫代酰胺；并且它们的彻底硫化需要过量的 LR。结果表明，在这种方法的基础上，“金雀花碱取代的”脲和硫脲以及甲基枸橼酸与苯基马来酰亚胺的 Diels-Alder 加合物的硫代作用并不十分成功：仅发生了 2-吡啶酮核的硫代作用。
• Structural features of N-acylcytisines
  作者：N. P. Abdullaev、U. S. Makhmudov、B. Tashkhodzhaev、G. Genzhemuratova、M. G. Levkovich、Kh. M. Shakhidoyatov

  DOI：10.1007/s10600-010-9495-7

  日期：2009.11

  N-Acyl cytisine derivatives were synthesized by acylation with acetic anhydride; benzoyl and o-bromo- and p-nitrobenzoyl chlorides; and crotonyl and cinnamoyl chlorides. The structures of the synthesized compounds were studied using IR, PMR, and x-ray structure analysis (XSA). PMR spectra of the N-acylcytisines in solution typically had two rotational isomers around the N12–CO bond. Conformational analysis was performed using XSA for the position of the acyl group relative to the cytisine core. Bond lengths and angles of the acyl groups involved in the conjugation were analyzed.

  乙酸酐酰化合成N-酰基金雀花碱衍生物；苯甲酰氯、邻溴苯甲酰氯和对硝基苯甲酰氯；以及巴豆酰氯和肉桂酰氯。使用IR、PMR和X射线结构分析（XSA）研究了合成化合物的结构。溶液中 N-酰基金雀花碱的 PMR 光谱通常在 N12-CO 键周围有两种旋转异构体。使用 XSA 对酰基相对于金雀花碱核心的位置进行构象分析。分析了参与共轭的酰基的键长和角度。
• Regio- and diastereoselective functionalization of (−)-cytisine: an unusual N–C acyl migration
  作者：Jacques Rouden、Alexis Ragot、Sonia Gouault、Dominique Cahard、Jean-Christophe Plaquevent、Marie-Claire Lasne

  DOI：10.1016/s0957-4166(02)00271-9

  日期：2002.7

  In order to test (-)-cytisine as a potential chiral inductor, N-propionyl cytisine was treated with LDA and then with benzyl bromide. Instead of the expected alpha-benzyl substituted propionamide, (-)-N-benzyl 6alpha-propionyl cytisine was formed, arising from an unusual diastereoselective nitrogen to carbon acyl migration. Using LDA in the presence of an excess of LiCl, the 6-substituted cytisine was isolated in yields of up to 79%. The efficiency of the N-C acyl transfer was shown to be dependent on the nature of the N-acyl group. Complete epimerization of the newly created stereocenter was observed under basic conditions. This methodology allows the stereoelective functionalization of the C-6 position of cytisine, an important agonist of nicotinic receptors. (C) 2002 Elsevier Science Ltd. All rights reserved.
• The amide protonation of (–)-N-benzoylcytisine in its perchlorate salts
  作者：Anna K. Przybył、Maciej Kubicki、Marcin Hoffmann

  DOI：10.1016/j.saa.2014.02.192

  日期：2014.8

  The C-13 NMR spectrum of (-)-N-benzoylcytisine perchlorate does not show a double set of signals typical of amide compounds, although this effect has been observed for the other diamine derivatives of cytisine. This observation means that in solution there must be the state of equilibrium between two forms of the cation with the protonated amide groups. DFT calculations have indeed indicated two preferred tautomeric forms with protonated oxygen atoms of amide groups. In the solid state however, according to X-ray analysis of perchlorate and perchlorate hydrate of N-benzoylcytisine the oxygen atom of the amide group in the six-membered ring A is preferred protonation site as compared with the oxygen in benzoic moiety. (-)-N-benzoylcytisine salt is the first compound from among the known derivatives of quinolizidine alkaloids that are not N-oxides, in which in solid state only the oxygen atom at cyclic amide is protonated instead of nitrogen atom or oxygen in benzoic moiety. (C) 2014 Elsevier B.V. All rights reserved.