8-甲基苯并[b]菲 | 2381-31-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 菲及其衍生物
• 中文名称: 8-甲基苯并[b]菲
• 中文别名: 8-甲基苯并[A]蒽
• 英文名称: 5-Methyl-1,2-benzanthracen
• 英文别名: 8-Methyl-benzanthracen；8-methylbenzanthracene；8-methylbenz(a)anthracene；8-Methylbenzanthracen；8-Methylbenz[a]anthracene；8-methylbenzo[a]anthracene
• CAS: 2381-31-9
• 化学式: C₁₉H₁₄
• 分子量: 242.32
• InChiKey: IJGWKTGQVIDRLA-UHFFFAOYSA-N

物化性质

• 熔点：
  156.5°C
• 沸点：
  452.14°C (rough estimate)
• 密度：
  1.2310
• 颜色/状态：
  Plates from benzene-alcohol; needles from benzene-ligroin
• 溶解度：
  Insoluble in water
• 蒸汽压力：
  2.05X10-7 mm Hg at 25 °C (est)
• 稳定性/保质期：

  Stable under recommended storage conditions.

• 分解：
  Hazardous decomposition products formed under fire conditions - Carbon oxides.
• 保留指数：
  417.63;417.56;417.57;417.63;417.56;417.56

计算性质

• 辛醇/水分配系数(LogP)：
  6.3
• 重原子数：
  19
• 可旋转键数：
  0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.05
• 拓扑面积：
  0
• 氢给体数：
  0
• 氢受体数：
  0

ADMET

代谢

8-甲基苯[a]蒽 (8-MeBaA) 的反式二氢二醇代谢物通过反向相和正相高效液相色谱法从8-MeBaA与肝脏微粒体或含有纯化细胞色素P-448和环氧化物水解酶的重组系统的孵化中分离出来。无论酶源如何，代谢形成的8-MeBaA反式-3,4-和-5,6-二氢二醇都被发现富含一种对映异构体，并且仅在光学纯度上有所不同。由未经处理或用苯巴比妥处理的鼠肝脏微粒体形成的8-MeBaA反式-8,9-二氢二醇富含(+)-对映异构体。相比之下，由3-甲基胆蒽处理的鼠肝脏微粒体或含有细胞色素P-448和环氧化物水解酶的重组鼠肝酶系统形成的8-MeBaA反式-8,9-二氢二醇则富含(-)对映异构体。这些结果表明，在催化形成3,4-和5,6-环氧化物中间体时，不同形式的细胞色素P-450与8-MeBaA未取代的3,4-和5,6-双键的相互作用主要发生在芳香平面的同一侧，它们仅在立体选择性程度上有所不同。然而，不同形式的细胞色素P-450可能会与8-MeBaA甲基取代的8,9-双键的芳香平面的不同侧面相互作用，导致形成富含不同对映异构体的反式-8,9-二氢二醇。这表明不同形式的细胞色素P-450可能优先在平面多环烃分子的甲基取代双键的不同侧催化环氧化反应。这些特性可以用来进一步分类和理解药物代谢酶系统中不同形式细胞色素P-450的酶-底物相互作用。

8-Methylbenz[a]anthracene (8-MeBaA) transdihydrodiol metabolites were isolated by reversed-phase and normal-phase HPLCs from incubations of 8-MeBaA with liver microsomes or a reconstituted system containing purified cytochrome P-448 and epoxide hydrolase. Regardless of the enzyme source, the metabolically formed 8-MeBaA trans-3,4- and -5,6-dihydrodiols were found to be enriched in one enantiomeric isomer and differed only in the degree of optical purity. The 8-MeBaA trans-8,9-dihydrodiol formed by liver microsomes from either untreated or phenobarbital-treated rats was enriched with the (+)-enantiomer. In contrast, the 8-MeBaA trans-8,9-dihydrodiol formed either by liver microsomes from 3-methylcholanthrene-treated rats or by the reconstituted rat liver enzyme system containing cytochrome P-448 and epoxide hydrolase was enriched with the (-)enantiomer. These results indicate that, in catalyzing the formation of 3,4- and 5,6-epoxide intermediates, the interaction with the unsubstituted 3,4- and 5,6-double bonds of 8-MeBaA by the different forms of cytochrome P-450 occur preferentially on the same face of the aromatic plane and they differ only in the degree of stereoselectivity. However, different forms of cytochrome P-450 may interact with different faces of the aromatic plane at the methyl-substituted 8,9-double bond of 8-MeBaA, resulting in the formation of trans-8,9-dihydrodiols enriched in different enantiomeric forms. This demonstrates that different forms of cytochrome P-450 may catalyze the epoxidation reaction preferentially at different sides of the methyl-substituted double bond of a planar polycyclic hydrocarbon molecule. These properties may be used to further classify and to understand the enzyme-substrate interactions of the different forms of cytochrome P-450 in the drug-metabolizing enzyme systems.

来源:Hazardous Substances Data Bank (HSDB)

代谢

肝脏微粒体中致癌物8-羟基甲基苯并[a]蒽(8-HOCH2-BA)的代谢导致3-甲基胆蒽处理的大鼠产生了12个可识别的代谢物。识别出的代谢物中包括反式-1,2-、3,4-、5,6-、8,9-和10,11-二氢二醇。主要的对映异构体分别具有1R,2R、3R,4R、5R,6R、8S,9S和10R,11R的绝对构型。使用特异性氚标记的[3H-CH2]8-HOCH2-BA作为底物，对未经处理以及用3-甲基胆蒽、苯巴比妥和多氯联苯处理的未成年雄性Sprague-Dawley大鼠的肝脏微粒体形成的代谢物进行了量化。识别出8,9-二氢二醇作为8-HOCH2-BA的代谢物表明，羟基甲基取代基并不阻止8-HOCH2-BA中羟基甲基取代的8,9-双键的酶促氧化...

Metabolism of the carcinogen 8-hydroxymethylbenz[a]anthracene (8-HOCH2-BA) with liver microsomes from 3-methylcholanthrene-treated rats resulted in 12 identifiable metabolites. Trans-1,2-, 3,4-5,6-, 8,9-, and 10,11-dihydrodiols are among the identified metabolites. The major enantiomers of the trans-dihydrodiols have 1R,2R, 3R,4R, 5R,6R, 8S,9S, and 10R,11R absolute configurations, respectively. Metabolites formed by liver microsomes from untreated as well as 3-methylcholanthrene-, phenobarbital-, and polychlorinated biphenyl-treated immature male Sprague-Dawley rats were quantified by using specifically tritium-labeled [3H-CH2]8-HOCH2-BA as the substrate. The identification of an 8,9-dihydrodiol as a metabolite of 8-HOCH2-BA indicates that a hydroxymethyl substituent does not prevent the enzymatic oxidation at the hydroxymethyl-substituted 8,9-double bond of 8-HOCH2-BA. ...

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 毒性总结

识别和使用：8-甲基苯并(a)蒽（8-MBA）是一种固体。它可以由有机材料的不完全燃烧形成。它主要用于生物化学研究。人类暴露和毒性：没有可用的数据。动物研究：在经典的2阶段启动-促进模型中对小鼠皮肤进行了8-MBA和8-羟基甲基苯并(a)蒽（8-OHMBA）的3,4-二氢二醇（二醇）以及其他代谢物的肿瘤启动活性的研究。这些数据表明，8-MBA的3,4-二醇是一个作为8-MBA近端致癌物的良好候选物，并且进一步表明，湾区3,4-二醇-1,2-环氧化物可能是这种化合物在小鼠皮肤上的最终致癌物。在经典的两阶段启动-促进实验中，8-MBA导致每只小鼠产生1.0个乳头状瘤。在其他实验中，小鼠在第一个月接受8-MBA皮下注射3毫克，在3个月和9个月时接受5毫克。在7个月的观察时间内，每只小鼠出现了5.5个肺肿瘤。然而，8-MCA在培养中并未产生转化的动物细胞。这一组化学物质的致癌活性和致突变活性之间似乎没有多少量的相关性。

IDENTIFICATION AND USE: 8-Methylbenz(a)anthracene (8-MBA) is a solid. It can be formed from incomplete combustion of organic materials. It is used mostly in biochemical research. HUMAN EXPOSURE AND TOXICITY: There are no data available. ANIMAL STUDIES: The tumor-initiating activity of the 3,4-dihydrodiols (diols) as well as other metabolites of 8-MBA and 8-hydroxymethylbenz[a]anthracene (8-OHMBA) were examined in the classical 2-stage initiation-promotion model on mouse skin. These data indicate that the 3,4-diol of 8-MBA is a good candidate as a proximate carcinogen of 8-MBA and further suggest that the bay region 3,4-diol-1,2-epoxide is a likely ultimate carcinogen of this compound on mouse skin. in the classical two-stage initiation-promotion experiment, 8-MBA was causing 1.0 papillomas/mouse. In other experiment, mice were administered 8-MBA sc at a dose of 3 mg in the first month and 5 mg at 3 and 9 months. 5.5 lung tumors were present per mouse at the 7-month observation time. However, 8-MCA did not produce transformed animal cells in culture. There appeared to be little quantitative correspondence between carcinogenic and mutagenic potency for this group of chemicals.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 解毒与急救

立即急救：确保已经进行了充分的中和。如果患者停止呼吸，开始人工呼吸，最好使用需求阀复苏器、袋阀面罩装置或口袋面罩，按训练进行操作。如有必要，执行心肺复苏。立即用缓慢流动的水冲洗受污染的眼睛。不要催吐。如果患者呕吐，让患者向前倾或将其置于左侧（如果可能，头部向下）以保持呼吸道畅通，防止吸入。保持患者安静，维持正常体温。寻求医疗救助。/芳香烃及其相关化合物/

Immediate First Aid: Ensure that adequate decontamination has been carried out. If patient is not breathing, start artificial respiration, preferably with a demand-valve resuscitator, bag-valve-mask device, or pocket mask, as trained. Perform CPR if necessary. Immediately flush contaminated eyes with gently flowing water. Do not induce vomiting. If vomiting occurs, lean patient forward or place on left side (head-down position, if possible) to maintain an open airway and prevent aspiration. Keep patient quiet and maintain normal body temperature. Obtain medical attention. /Aromatic hydrocarbons and related compounds/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 解毒与急救

基本治疗：建立专利气道（如有需要，使用口咽或鼻咽气道）。必要时进行吸痰。观察呼吸不足的迹象，并在必要时协助通气。通过非循环呼吸面罩以10至15升/分钟的速度给予氧气。监测肺水肿，并在必要时进行治疗……。监测休克，并在必要时进行治疗……。预期可能出现癫痫，并在必要时进行治疗。对于眼睛污染，立即用水冲洗眼睛。在转运过程中，用0.9%的生理盐水（NS）持续冲洗每只眼睛……。不要使用催吐剂。对于误食，如果患者能够吞咽、有强烈的咳嗽反射且不流口水，则用水冲洗口腔，并给予5毫升/千克，最多200毫升的水进行稀释。给予活性炭……。/芳香烃及其相关化合物/

Basic treatment: Establish a patent airway (oropharyngeal or nasopharyngeal airway, if needed). Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if necessary. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary. ... For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with 0.9% saline (NS) during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 mL/kg up to 200 L of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool. Administer activated charcoal ... . /Aromatic hydrocarbons and related compounds/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 解毒与急救

高级治疗：对于昏迷、严重肺水肿或严重呼吸困难的病人，考虑进行口咽或鼻咽气管插管以控制气道。使用气囊面罩装置的正压通气技术可能有益。考虑使用药物治疗肺水肿……。对于严重的支气管痉挛，考虑给予β激动剂，如沙丁胺醇……。监测心率和必要时治疗心律失常……。开始静脉输注5%葡萄糖水（D5W），保持通路开放，最低流速……。如果出现低血容量的迹象，使用0.9%生理盐水（NS）或乳酸钠林格氏液（LR）。对于伴有低血容量迹象的低血压，谨慎给予液体。注意液体过载的迹象……。用安定（地西泮）或劳拉西泮（阿蒂凡）治疗癫痫……。使用丙美卡因氢氯化物协助眼部冲洗……。/芳香烃及其相关化合物/

Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in severe respiratory distress. Positive-pressure ventilation techniques with a bag-valve-mask device may be beneficial. Consider drug therapy for pulmonary edema ... . Consider administering a beta agonist such as albuterol for severe bronchospasm ... . Monitor cardiac rhythm and treat arrhythmias if necessary ... . Start IV administration of D5W TKO /SRP: "To keep open", minimal flow rate/. Use 0.9% saline (NS) or lactated Ringer's (LR) if signs of hypovolemia are present. For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam (Valium) or lorazepam (Ativan) ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Aromatics hydrocarbons and related compounds/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 非人类毒性摘录

实验室动物：慢性暴露或致癌性 / 正常胚胎细胞暴露于致癌烃类时体外转化的特异性在仓鼠和小鼠中被研究。将金色仓鼠或SWR小鼠胚胎切碎，并将细胞悬浮液接种到含有大鼠胚胎饲养层的辐射培养皿上。用于克隆的细胞播种7到10天。在显微镜下检查培养物。测试的化合物通过微孔盘过滤器或通过生长培养基中的胶体悬浮液施加在细胞培养上。转化的培养物用胰蛋白酶处理，并皮下接种到成年动物中。在肿瘤发育过程中进行触诊，然后将其移除并进行组织学检查。转化的细胞显示出遗传性随机生长模式，具有持续生长的能力，并在培养中测试时对苯并(a)芘（50328）（BP）具有抗性。在培养中获得了3-甲基胆蒽（56495）（MCA），7,12-二甲基苯并(a)蒽（57976）和10-甲基苯并(a)蒽（2381159）的转化细胞，而在体内没有用8-甲基苯并(a)蒽（2381319），屈曲（218019）和芘（129000）。致癌烃在体外直接将正常细胞转化为肿瘤细胞。在培养物转化过程中，成纤维细胞和上皮型细胞的出现频率很高。BP在加入致癌物后1到2天内诱导了25.6%的克隆转化。BP和MCA产生了转化的细胞，这些细胞在未处理的对照组的培养中未被发现。在培养物中长时间培养后，未经处理的和处理过的小鼠细胞在接种到成年SWR小鼠中后逐渐生长为肿瘤。作者得出结论，转化的表达取决于细胞分裂。

/LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity/ The specificity of in-vitro transformation of normal embryonic cells exposed to carcinogenic hydrocarbons was investigated in hamsters and mice. Golden-hamster or SWR-mice embryos were minced and cell suspensions inoculated onto irradiated dishes containing rat embryo feeder layers. Cells for cloning were seeded for 7 to 10 days. Cultures were examined microscopically. Compounds tested were applied on cell cultures by millipore disc filters or by colloidal suspension in growth medium. Transformed cultures were trypsinized and inoculated subcutaneously into adult animals. Tumors were palpated during development, then removed and examined histologically. The transformed cells displayed a hereditary random pattern of growth, ability to grow continuously, and were resistant to benz(a)pyrene (50328) (BP) when tested in culture. Transformed cells in culture were obtained with 3-methylcholanthrene (56495) (MCA), 7,12-dimethylbenzo(a)anthracene (57976) and 10-methylbenz(a)anthracene (2381159), in-vivo, but not with 8-methylbenz(a)anthracene (2381319), chrysene (218019), and pyrene (129000). Carcinogenic hydrocarbons induced direct transformation of normal cells to tumor cells in-vitro. Fibroblasts and epithelial type cells were found with high frequency during transformation in culture. BP induced 25.6 percent transformation of clones, 1 to 2 days after addition of the carcinogen. BP and MCA produced transformed cells, which were not found in cultures of untreated controls. After long periods in culture both untreated and treated mouse cells grew progressively as tumors after inoculation into adult SWR-mice. The authors conclude that expression of transformation is dependent on cell division.

来源:Hazardous Substances Data Bank (HSDB)

安全信息

• 海关编码：
  2902909090

反应信息

• 作为反应物：
  描述：

  8-甲基苯并[b]菲 在 sodium dichromate 、 溶剂黄146 作用下， 生成 8-methyl-7,12-benzanthraquinone
  参考文献：
  名称：

  378.多环芳烃。第十二部分。1：2-苯并蒽的衍生物的取向，并记录了一些新同系物的制备，以及3：4：5：6-二苯并菲的分离

  摘要：

  DOI：

  10.1039/jr9330001592
• 作为产物：
  描述：

  2,3-二甲基苯胺 在 盐酸 、 乙醚 、 锌 、 苯 作用下， 生成 8-甲基苯并[b]菲
  参考文献：
  名称：

  Synthesis of 1′,9-Methylene-1,2-benzanthracene and Related Hydrocarbons

  摘要：

  DOI：

  10.1021/ja01876a031

文献信息

• Cascade reaction for the synthesis of polycyclic aromatic hydrocarbons via transient directing group strategy
  作者：Ziqi Wang、Wendan Dong、Bing Sun、Qinqin Yu、Fang-Lin Zhang

  DOI：10.1016/j.tet.2019.06.036

  日期：2019.7

  A Pd(II)-catalyzed cascade synthesis of diverse polycyclic aromatic hydrocarbons via transient directing group strategy has been developed, involving the consecutive arylation, cyclization and aromatization. The efficiency and practicality were demonstrated by wide substrate range, concise synthetic pathway and mild reaction conditions. The subsequent transformations of the benz[a]anthracene core accessed

  已经开发了一种通过Pd（II）催化的通过瞬态导向基团策略级联的多种多环芳烃，涉及连续的芳基化，环化和芳构化。广泛的底物范围，简明的合成途径和温和的反应条件证明了其效率和实用性。苯并[ a ]蒽核心的后续转化获得了天然的生物活性PAH分子。
• Phenanthrene Derivatives. IX. 1-Alkyl-1-hydroxytetrahydrophenanthrenes and Related Compounds
  作者：W. E. Bachmann、A. L. Wilds

  DOI：10.1021/ja01270a038

  日期：1938.3
• Coördination of Polycyclic Aromatic Hydrocarbons with Silver Ion; Correlation of Equilibrium Constants with Relative Carcinogenic Potencies¹
  作者：Robert E. Kofahl、Howard J. Lucas

  DOI：10.1021/ja01644a020

  日期：1954.8
• Gmelin Handbuch der Anorganischen Chemie, Gmelin Handbook: Ag: MVol.B5, 1.3.3.17, page 114 - 116
  作者：

  DOI：——

  日期：——
• Newman; Otsuka, 1958, vol. 21, p. 721,724
  作者：Newman、Otsuka

  DOI：——

  日期：——

表征谱图