methyl cubane | 23096-16-4

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 英文名称: methyl cubane
• 英文别名: Methylcubane；1-methylcubane
• CAS: 23096-16-4
• 化学式: C₉H₁₀
• 分子量: 118.178
• InChiKey: UXKDTZFBSHLJOY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  9
• 可旋转键数：
  0
• 环数：
  6.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  0
• 氢给体数：
  0
• 氢受体数：
  0

反应信息

• 作为反应物：
  描述：

  1,1,3,3-tetramethyl-2,3-dihydro-1H-isoindol-2-yloxoyl radical 、 methyl cubane 在 反式-二叔丁基连二次硝酸酯 作用下， 以 苯 为溶剂， 反应 168.0h， 生成 1,1,3,3-tetramethyl-2-(4-methylcuban-1-yl)oxyisoindole 、
  参考文献：
  名称：

  Regiochemical Variations in Reactions of Methylcubane with tert-Butoxyl Radical, Cytochrome P-450 Enzymes, and a Methane Monooxygenase System

  摘要：

  Reactions of methylcubane (1) with the tert-butoxyl radical (t-BuO.), with cytochrome P-450 enzymes, and with a methane monooxygenase (MMO) system have been studied. For the purpose of product characterization, authentic samples of 2-methylcubyl and 4-methylcubyl derivatives were prepared. 2-Methylcubanecarboxylic acid (9b) is a new compound prepared from cubanecarboxylic acid. The key synthetic reactions were (1) metalation and subsequent iodination of the 2-position of (diisopropylcarbamoyl)cubane to effect the initial functionalization, (2) lithium-for-iodine exchange and methylation followed by reduction to give 2-methyl-1-[(diisopropylamino)methyl]-cubane, and (3) dimethyldioxirane oxidation of this amine to give 9b. The known 4-methylcubanecarboxylic acid (9d) was prepared here by a route related to that employed for 9b. Reactions of acids 9b and 9d with methyllithium gave the corresponding methyl ketones which were oxidized by m-chloroperoxybenzoic acid to provide authentic samples of 2- and 4-methylcubanol acetates (3b and 3d). Reaction of 1 with t-BuO(.) in the presence of 2,2,5,5-tetramethylisoindole-N-oxyl radical (TMIO(.)) at 40-55 degrees C gave mainly cube-substituted products in confirmation of the report (Della, E. W.; Head, N. J.; Mallon, P.; Walton, J. C. J. Am. Chem. Sec. 1992, 114, 10730) that hydrogen atom abstraction by the electrophilic alkoxyl radical at low temperature occurs at the cubyl C-H positions. In a competition experiment at 42 degrees C, methylcubane was at least 3.5 times more reactive toward t-BuO(.) than cyclohexane, indicating that the cubyl positions in 1 are greater than or equal to 40 times more reactive than the methyl positions in 1 (per hydrogen) toward the alkoxyl radical. Oxidation of 1 by enzymes gave alcohol products that were converted to their acetate derivatives for identification and quantitation. Microsomal cytochrome P-450 enzymes from rat and the rat purified P-450 isozyme CYP2B1 hydroxylated 1 at all positions, whereas the reconstituted MMO system from Methylococcus capsulatus (Bath) hydroxylated 1 only at the methyl position. The differences in regioselectivity suggest that the transition states for hydrogen abstraction by the alkoxyl radical and for enzyme-catalyzed hydroxylation differ considerably. The results are consistent with a model for concerted enzyme catalyzed hydroxylation of 1 involving ''side-on'' approach to the C-H bond of substrate.

  DOI：

  10.1021/ja952226l
• 作为产物：
  描述：

  在 三乙基硼氢化锂 作用下， 以 四氢呋喃 为溶剂， 生成 methyl cubane
  参考文献：
  名称：

  Regiochemical Variations in Reactions of Methylcubane with tert-Butoxyl Radical, Cytochrome P-450 Enzymes, and a Methane Monooxygenase System

  摘要：

  Reactions of methylcubane (1) with the tert-butoxyl radical (t-BuO.), with cytochrome P-450 enzymes, and with a methane monooxygenase (MMO) system have been studied. For the purpose of product characterization, authentic samples of 2-methylcubyl and 4-methylcubyl derivatives were prepared. 2-Methylcubanecarboxylic acid (9b) is a new compound prepared from cubanecarboxylic acid. The key synthetic reactions were (1) metalation and subsequent iodination of the 2-position of (diisopropylcarbamoyl)cubane to effect the initial functionalization, (2) lithium-for-iodine exchange and methylation followed by reduction to give 2-methyl-1-[(diisopropylamino)methyl]-cubane, and (3) dimethyldioxirane oxidation of this amine to give 9b. The known 4-methylcubanecarboxylic acid (9d) was prepared here by a route related to that employed for 9b. Reactions of acids 9b and 9d with methyllithium gave the corresponding methyl ketones which were oxidized by m-chloroperoxybenzoic acid to provide authentic samples of 2- and 4-methylcubanol acetates (3b and 3d). Reaction of 1 with t-BuO(.) in the presence of 2,2,5,5-tetramethylisoindole-N-oxyl radical (TMIO(.)) at 40-55 degrees C gave mainly cube-substituted products in confirmation of the report (Della, E. W.; Head, N. J.; Mallon, P.; Walton, J. C. J. Am. Chem. Sec. 1992, 114, 10730) that hydrogen atom abstraction by the electrophilic alkoxyl radical at low temperature occurs at the cubyl C-H positions. In a competition experiment at 42 degrees C, methylcubane was at least 3.5 times more reactive toward t-BuO(.) than cyclohexane, indicating that the cubyl positions in 1 are greater than or equal to 40 times more reactive than the methyl positions in 1 (per hydrogen) toward the alkoxyl radical. Oxidation of 1 by enzymes gave alcohol products that were converted to their acetate derivatives for identification and quantitation. Microsomal cytochrome P-450 enzymes from rat and the rat purified P-450 isozyme CYP2B1 hydroxylated 1 at all positions, whereas the reconstituted MMO system from Methylococcus capsulatus (Bath) hydroxylated 1 only at the methyl position. The differences in regioselectivity suggest that the transition states for hydrogen abstraction by the alkoxyl radical and for enzyme-catalyzed hydroxylation differ considerably. The results are consistent with a model for concerted enzyme catalyzed hydroxylation of 1 involving ''side-on'' approach to the C-H bond of substrate.

  DOI：

  10.1021/ja952226l

文献信息

• Cytochrome P450-Catalyzed Hydroxylation of Mechanistic Probes that Distinguish between Radicals and Cations. Evidence for Cationic but Not for Radical Intermediates
  作者：Martin Newcomb、Runnan Shen、Seung-Yong Choi、Patrick H. Toy、Paul F. Hollenberg、Alfin D. N. Vaz、Minor J. Coon

  DOI：10.1021/ja994106+

  日期：2000.3.1

  Oxidation of the mechanistic probes trans,trans-2-methoxy-3-phenylmethylcyclopropane and methylcubane by six cytochrome P450 isozymes has been studied. The probes differentiate between radical and cationic species in that different structural rearrangements occur for the two types of intermediates. The P450 isozymes are the phenobarbital-inducible hepatic isozymes P450 2B1 (from rat) and P450 2B4 (from

  研究了六种细胞色素 P450 同工酶对反式、反式-2-甲氧基-3-苯基甲基环丙烷和甲基立方烷的氧化机制。探针区分自由基和阳离子物种，因为两种类型的中间体发生不同的结构重排。P450 同工酶是苯巴比妥诱导的肝同工酶 P450 2B1（来自大鼠）和 P450 2B4（来自兔），表达的截短同工酶 P450 Δ2B4 和 P450 Δ2E1（乙醇诱导，来自兔），以及后两者的突变体活性位点苏氨酸被丙氨酸、Δ2B4 T302A 和 Δ2E1 T303A 取代。从两个探针中都发现了阳离子重排产物。反式氧化，反式-2-甲氧基-3-苯基甲基环丙烷产生少量自由基衍生的重排产物，表明羟基化是通过插入反应发生的，过渡态寿命在 80-200 fs 范围内。细胞色素 P450 催化羟基化的机理描述符合...
• Homolytic reactions of cubanes. Generation and characterization of cubyl and cubylcarbinyl radicals
  作者：Ernest W. Della、Nicholas J. Head、Philip Mallon、John C. Walton

  DOI：10.1021/ja00053a008

  日期：1992.12

  A series of 4-substituted cubyl radicals was generated by bromine atom abstraction from 1-bromo-4-substituted cubanes. EPR observations showed that the cubyl radicals abstracted secondary hydrogen atoms from the ethyl groups of triethylsilane and decayed mainly by second-order combination reactions. tert-Butoxyl radicals abstracted hydrogen atoms from cubane at least 26 times more rapidly than from

  通过从 1-bromo-4-取代的立方烷中提取溴原子，产生了一系列 4-取代的立方自由基。EPR 观察表明，cubyl 自由基从三乙基硅烷的乙基中提取二级氢原子，主要通过二级组合反应衰变。在-90 o C 时，叔丁氧基从立方烷中提取氢原子的速度至少比环丙烷快26 倍。立方烷上的吸电子取代基大大降低了这一速度。叔丁氧基自由基选择性地从甲基立方烷中提取笼氢而不是伯甲基氢
• Picosecond radical kinetics. Bond cleavage of the cubylcarbinyl radical
  作者：Seung Yong Choi、Philip E. Eaton、Martin Newcomb、Yu Chi Yip

  DOI：10.1021/ja00042a008

  日期：1992.7

  Rate constants for the initial ond clevages of the cubylcarbinyl radical (1) were determined by competition kinetics using benzeneselenol as a trapping agent. Measurements over the temperature range -78 to 25 o C gave a temperature-dependent function of log (k r .s) = 13.16-3.72/2.3RT. The rate constant for the initial ring opening of radical 1 at 25 o C is 2.9×10 10 s -1 , which ranks this reaction

  cubylcarbinyl 自由基 (1) 的初始和裂解的速率常数是通过使用苯硒醇作为捕获剂的竞争动力学确定的。在 -78 到 25 o C 温度范围内的测量给出了 log (kr .s) = 13.16-3.72/2.3RT 的温度相关函数。自由基 1 在 25 o C 下初始开环的速率常数为 2.9×10 10 s -1 ，这将该反应列为已知最快的自由基重排之一。初始裂解反应的推定产物，亚甲基仲仲基自由基 2，显然经历了更快的键裂解反应，估计在 250 * C 下 >1.5×10 11 s -1
• The preparation and fate of cubylcarbinyl radicals
  作者：Philip E. Eaton、Yu Chi Yip

  DOI：10.1021/ja00020a035

  日期：1991.9

  The cubylcarbinyl radical has been generated from cubylcarbinyl bromide and from the N-hydroxy-2-pyridinethione ester of cubylacetic acid under various conditions favoring hydrogen-atom transfer to the radical. Only when selenophenol in high concentration is used as the hydrogen donor is any methylcubane formed. Otherwise the cubylcarbinyl radical rearranges. There is no evidence of a 1,2-shift into the homocubyl system. Instead, one, two, or three bonds of the cubane nucleus cleave, leading to a variety of olefinic products. For the most part, these have been characterized. A mechanistic scheme accounting for their formation is presented; sequential sigma-bond breaking occurs regioselectively, favoring processes in which there is good overlap between the radical orbital and that of the breaking bond. The distribution of products is shown to depend qualitatively on the time the radical intermediates are let live, that is, on the concentration and effectiveness of the hydrogen atom transfer agent. From product distributions, the rate constant for ring cleavage of cubylcarbinyl radical is calculated to be at least 2 X 10(10) s-1, substantially greater than that of any radical derived to date from a saturated hydrocarbon system. Methodology is given for the synthesis of cubylcarbinol, cubylacetic acid, 1,4-bis(hydroxymethyl)cubane, methylcubane, and a variety of other new cubane compounds.
• Synthesis of Methylcubane and Cyclopropylcubane. The Cubane-1,4-diyl Route
  作者：Philip E. Eaton、Jianchang Li、Subhash P. Upadhyaya

  DOI：10.1021/jo00109a030

  日期：1995.2

  Details for preparation of 1,4-diiodocubane from cubane-1,4-dicarboxylic acid are given. The diiodide is used to generate cubane-1,4-diyl, a nonisolable intermediate. Additions to the diyl are shown to provide for the ready synthesis in good yield of methylcubane, 1,4-dimethylcubane, cyclopropylcubane, etc.