天然橡胶 | 78-79-5

• 物质功能分类: 有机原料 - 烃类化合物及其衍生物 - 无环烃
• 分子结构分类: 有机化合物 - 碳氢化合物 - 不饱和烃
• 中文名称: 天然橡胶
• 中文别名: 2-甲基1,3-丁二烯；橡胶,天然；维他可乐波；胶乳；异戊二烯；2-甲基-1,3-丁二烯
• 英文名称: isoprene
• 英文别名: 2-methyl-1,3-butadiene；3-methyl-1,3-butadiene；2-methylbutadiene；isopren；2-methylbuta-1,3-diene
• CAS: 78-79-5；9006-04-6
• 化学式: C₅H₈
• mdl: MFCD00008600
• 分子量: 68.1185
• InChiKey: RRHGJUQNOFWUDK-UHFFFAOYSA-N

物化性质

• 熔点：
  323-329 °C(lit.)
• 沸点：
  34 °C(lit.)
• 密度：
  0.681 g/mL at 25 °C(lit.)
• 蒸气密度：
  2.35 (vs air)
• 闪点：
  −65 °F
• 溶解度：
  0.7克/升
• 最大波长(λmax)：
  231nm(neat)(lit.)
• 介电常数：
  2.1（25℃）
• LogP：
  2.42 at 20℃
• 物理描述：
  Isoprene, stabilized appears as a clear colorless liquid with a petroleum-like odor. Density 5.7 lb / gal. Flash point -65°F. Boiling point 93°F. May polymerize exothermically if heated or contaminated. If polymerization takes place inside a closed container, the container may rupture violently. Less dense than water and insoluble in water. Vapors heavier than air.
• 颜色/状态：
  Colorless volatile liquid
• 气味：
  Petroleum-lke
• 味道：
  Tasteless
• 蒸汽密度：
  2.35 (NTP, 1992) (Relative to Air)
• 蒸汽压力：
  550 mm Hg at 25 °C
• 大气OH速率常数：
  1.01e-10 cm3/molecule*sec
• 稳定性/保质期：
  Stable under recommended storage conditions. Contains the following stabilizer(s): 4-tert-Butylpyrocatechol (>/= 100 to </= 150 ppm)
• 自燃温度：
  743 °F (395 °C)
• 分解：
  Decomposes at 120 °C.
• 粘度：
  0.3 mm²/s at 20-25 °C
• 燃烧热：
  -18,848 Btu/lb = -10,471 cal/g = -438.4X10+5 J/kg
• 汽化热：
  26.39 kJ/mol at 25 °C; 25.87 kJ/mol at 34 °C
• 表面张力：
  16.9 dynes/cm = 0.0169 N/m at 20 °C (liquid)
• 聚合：
  The substance polymerizes due to heating and under the influence of many materials. This generates fire or explosion hazard.
• 折光率：
  Index of refraction: 1.42160 at 20 °C/D
• 保留指数：
  502.2;504;506;504;496;506;508;507;507;504;505;504;508.6;506;502.95;500;503;502;503;504;502;503;503;503;504

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  5
• 可旋转键数：
  1
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  0
• 氢给体数：
  0
• 氢受体数：
  0

ADMET

代谢

异戊二烯（IP）... 在体内被代谢为活性的环氧物，这可能是导致暴露于IP的老鼠观察到肿瘤的原因。通过使用生理毒代动力学（PT）模型，可以获得吸入IP及其中间环氧物在人体和组织的负担的详细知识。为此，开发了一种针对小鼠、大鼠和人类的IP的PT模型。实验确定的分配系数从文献中获取。代谢参数来自气体吸收实验。通过在模型中引入肝脏和肝脏外代谢，可以描述测量数据。在暴露浓度高达50 ppm的情况下，稳态下的代谢速率在小鼠中是人类的14倍，在大鼠中是人类的8倍左右（在空气中50 ppm IP时为2.5 umol/hr/kg）。由于IP的快速代谢和低的热力学分配系数（整体：空气），IP几乎不会积累。IP是内源产生的。与人类相比，在啮齿类动物中这种产生可以忽略不计（0.34 umol/hr/kg）。人类内源性产生的IP大约有90%被代谢，10%未改变地呼出。预测非暴露人类的IP血浓度为9.5 nmol/L。在8小时内暴露于10 ppm IP后，血药浓度-时间曲线下的面积（AUC）是无避免内源性IP在24小时内产生的AUC的大约4倍...

Isoprene (IP) ... is metabolized in vivo to reactive epoxides, which might cause the tumors observed in IP exposed rodents. Detailed knowledge of the body and tissue burden of inhaled IP and its intermediate epoxides can be gained using a physiological toxicokinetic (PT) model. For this purpose, a PT-model was developed for IP in mouse, rat, and human. Experimentally determined partition coefficients were taken from the literature. Metabolic parameters were obtained from gas-uptake experiments. The measured data could be described by introducing hepatic and extrahepatic metabolism into the model. At exposure concentrations up to 50 ppm, the rate of metabolism at steady-state is 14 times faster in mice and about 8 times faster in rats than in humans (2.5 umol/hr/kg at 50 ppm IP in air). IP does accumulate only barely due to its fast metabolism and its low thermodynamic partition coefficient whole body:air. IP is produced endogenously. This production is negligible in rodents compared to that in humans (0.34 umol/hr/kg). About 90% of IP produced endogenously in humans is metabolized and 10% is exhaled unchanged. The blood concentration of IP in non-exposed humans is predicted to be 9.5 nmol/L. The area under the blood concentration-time curve (AUC) following exposure over 8 hr to 10 ppm IP is about 4 times higher than the AUC resulting from the unavoidable endogenous IP over 24 hr...

来源:Hazardous Substances Data Bank (HSDB)

代谢

人们常常猜测异戊二烯的毒理学性质必须与丁二烯相似。实际上，异戊二烯的急性毒性非常相似，而且生物转化为单环氧合物和双环氧合物的过程在质量上也是相似的。然而，有一个区别；异戊二烯是不对称的，因此可能有更多代谢上的对映异构体。药代动力学研究已经表明，在最大代谢消除速率上存在物种差异（与丁二烯一样）：在小鼠中，这个速率至少比大鼠高出三倍，这暗示了小鼠对异戊二烯代谢的物种敏感性。

...It is often speculated that the toxicological properties of isoprene must resemble those of butadiene. In fact, the acute toxicity of isoprene is very similar and also the biotransformation to mono- and diepoxides is qualitatively alike. There is however a difference; isoprene is asymmetric and therefore more metabolic enantiomers are possible. Pharmacokinetic studies have demonstrated species differences (as with butadiene) in the maximum metabolic elimination rate: in mice this was determined to be at least three times higher than in rats which implies a species sensitivity in isoprene metabolism in the mouse.

来源:Hazardous Substances Data Bank (HSDB)

代谢

研究了对从表达人CYP1A1、CYP1A2、CYP2A6、CYP2B6、CYP2C9、CYP2D6、CYP2E1或CYP3A4的细胞系中提取的微粒体中异戊二烯的代谢。通过气相色谱分析确定了环氧代谢物的形成。CYP2E1显示出形成异戊二烯单环氧3,4-环氧-3-甲基-1-丁烯（EPOX-I）和3,4-环氧-2-甲基-1-丁烯（EPOX-II）的最高速率，其次是CYP2B6。CYP2E1是唯一显示出可检测到异戊二烯二环氧2-甲基-1,2:3,4-二环氧丁烷形成的酶。两种异戊二烯单环氧都被CYP2E1氧化为二环氧，且酶促速率相似。为了确定CYP2E1在肝脏代谢中的相对作用，异戊二烯以及两种单环氧与十个人类肝脏微粒体制剂一起在存在环氧水解酶抑制剂环己烯氧化物的情况下进行孵化。获得的活动与针对CYP1A2、CYP2A6、CYP2C9、CYP2D6、CYP2E1和CYP3A特定底物的活动进行了相关性分析。结果支持了使用单一人类P450酶获得的结果。异戊二烯（单环氧）代谢显示出与CYP2E1活动显著相关，后者通过氯唑沙宗6-羟基化来确定。因此，CYP2E1是在体外参与异戊二烯及其单环氧代谢的主要酶。为了调查在异戊二烯单环氧代谢中环氧水解酶作用的物种差异，将人类肝脏微粒体对异戊二烯的环氧化与小鼠和大鼠肝脏微粒体的环氧化进行了比较。在存在和不存在环氧水解酶抑制剂环己烯氧化物的情况下，通过孵化测量了作为环氧化和水解平衡形成的单环氧的量。环氧水解酶的抑制导致小鼠、大鼠和人类肝脏微粒体中单环氧形成的速率相似。然而，在没有抑制剂的情况下，孵化期末期存在的单环氧总量是小鼠肝脏微粒体的两倍，是大鼠肝脏微粒体的15倍。因此，物种之间环氧水解酶活性的差异对于各种物种中异戊二烯的毒性可能至关重要。

The metabolism of isoprene was investigated with microsomes derived from cell lines expressing human CYP1A1, CYP1A2, CYP2A6, CYP2B6, CYP2C9, CYP2D6, CYP2E1, or CYP3A4. The formation of epoxide metabolites was determined by gas chromatographic analysis. CYP2E1 showed the highest rates of formation of the isoprene monoepoxides 3,4-epoxy-3-methyl-1-butene (EPOX-I) and 3,4-epoxy-2-methyl-1-butene (EPOX-II), followed by CYP2B6. CYP2E1 was the only enzyme showing detectable formation of the diepoxide of isoprene, 2-methyl-1,2:3,4-diepoxybutane. Both isoprene monoepoxides were oxidized by CYP2E1 to the diepoxide at similar enzymatic rates. In order to determine the relative role of CYP2E1 in hepatic metabolism, isoprene as well as the two monoepoxides were also incubated with a series of ten human liver microsomal preparations in the presence of the epoxide hydrolase inhibitor cyclohexene oxide. The obtained activities were correlated with activities towards specific substrates for CYP1A2, CYP2A6, CYP2C9, CYP2D6, CYP2E1 and CYP3A. The results were supportive for those obtained with single human P450 enzymes. Isoprene (monoepoxide) metabolism sowed a significant correlation with CYP2E1 activity, determined as chlorzoxazone 6-hydroxylation. CYP2E1 is therefore the major enzyme involved in hepatic metabolism of isoprene and the isoprene monoepoxides in vitro. To investigae species differences with regard to the role of epoxide hydrolase in the metabolism of isoprene monoepoxides, the epoxidation of isoprene by human liver microsomes was compared to that of mouse and rate liver microsomes. The amounts of monoepoxides formed as a balance between epoxidation and hydrolysis, was measured in incubations with and without the epoxide hydrolase inhibitor cyclohexene oxide. Inhibition of epoxide hydrolase resulted in similar rates of monoepoxide formation in mouse, rat and man. Without inhibitor, however, the total amount of monoepoxides present at the end of the incubation period was twice as high for mouse liver microsomes than for rat and even 15 times as high as for human liver microsomes. Thus, differences in epoxide hydrolase activity between species may be of crucial importance for the toxicity of isoprene in the various species.

来源:Hazardous Substances Data Bank (HSDB)

代谢

对异戊二烯在体外代谢的立体化学进行了比较研究，使用了来自大鼠、小鼠、猴子、狗、兔子和人类的肝脏微粒体。同时还研究了不同品系和性别之间的差异。在产生异戊二烯单环氧化物的过程中，来自雄性Sprague-Dawley或Wistar大鼠肝脏的微粒体显示出大约2:1的偏好，形成(S)-2-(1-甲基乙烯基)环氧乙烷，与(R)-对映体相比。在小鼠或兔子的微粒体中没有观察到对映体选择性。相反，来自狗、猴子或男性人类肝脏的微粒体更倾向于形成(R)-2-(1-甲基乙烯基)环氧乙烷。来自女性人类肝脏的微粒体没有观察到对映体选择性。在体外代谢异戊二烯的物种之间存在的显著差异表明，在评估动物实验结果以确定与接触异戊二烯相关的人类致癌风险时，应考虑立体化学和机制学数据。

Comparative studies on the stereochemistry of the metabolism of isoprene in vitro have been carried out using liver microsomes from rats, mice, monkeys, dogs, rabbits and humans. Differences between strains and gender were also investigated. In the production of the isoprene monoepoxides, microsomes from the livers of the male Sprague-Dawley or Wistar rat showed an approximately 2:1 preference for the formation of (S)-2-(1-methylethenyl)oxirane compared with the (R)-enantiomer. No enantioselectivity was observed for mouse or rabbit. In contrast, liver microsomes from dog, monkey or male human preferentially formed (R)-2-(1-methylethenyl)oxirane. There was no enantioselectivity observed with microsomes from female human liver. The significant differences between species in the in vitro metabolism of isoprene indicate that stereochemical and mechanistic data should be taken into account when evaluating the results of animal studies designed to assess the carcinogenic risks to humans that may be associated with exposure to isoprene.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 毒性总结

识别和使用：异戊二烯是一种无色易挥发液体。它用于制造丁基橡胶，并作为合成弹性体生产的共聚物。人体研究：呼吸刺激是过度暴露的潜在症状。在高浓度下，异戊二烯可能作为中枢神经系统抑制剂和窒息剂。在异戊二烯橡胶生产工人中，注意到了鼻腔炎症、上呼吸道亚临床和萎缩过程以及嗅觉退化。流行程度和程度与工龄的增加有关。在彗星试验中，异戊二烯在代谢激活的条件下诱导了外周血单核细胞的DNA损伤。动物研究：每天吸入6小时，每周5天，持续2周，雄性和雌性大鼠分别暴露于0、438、875、1750、3500或7000 ppm异戊二烯蒸气，没有影响。在雄性小鼠中，它降低了体重增加，产生了胸腺和睾丸萎缩（仅在7000 ppm时），嗅觉上皮退化，肝脏细胞质空泡化，和前胃上皮细胞增生。在所有暴露组的雄性和雌性小鼠中，红细胞数量、血红蛋白浓度和红细胞压积体积都有所下降。据报道，在 mice 中，暴露相关肝、肺、哈德氏腺和前胃肿瘤以及血管肉瘤和组织细胞肉瘤的发病率增加。在大鼠中，暴露的雄性和雌性大鼠乳腺纤维腺瘤的发病率增加。处理过的雄性大鼠肾小管腺瘤的发病率增加。一些动物也有肾癌。处理过的雄性大鼠睾丸间质细胞腺瘤的发病率也增加。异戊二烯影响21天大的雌性小鼠的卵巢卵泡。在雄性小鼠中，暴露于7000 ppm的动物睾丸重量减少了35%，20%的动物出现了生精小管萎缩，附睾重量减轻，精细胞头数和浓度降低，700和7000 ppm组的精子活力降低。在发育研究中，除了脊椎骨化减少的发生率略有增加外，没有与处理相关的胎儿畸形或变异的发生。在使用5株鼠伤寒沙门氏菌（TA1535、TA1537、TA97、TA98和TA100）进行代谢激活和不进行代谢激活的沙门氏菌/微粒体预孵化试验中，异戊二烯对诱变性的测试为阴性。异戊二烯不能在中国仓鼠卵巢细胞培养中诱导姐妹染色单体交换或染色体畸变。

IDENTIFICATION AND USE: Isoprene is a colorless volatile liquid. It is used in manufacturing butyl rubber, and as copolymer in the production of synthetic elastomers. HUMAN STUDIES: Respiratory irritation is a potential symptom of overexposure. Isoprene may act as a CNS depressant and asphyxiant at high concentrations. Catarrhal inflammation, subtrophic and atrophic processes in the upper respiratory tract, and deterioration of olfaction were noted in isoprene rubber production workers. Prevalence and degree were correlated with increasing length of service. In the comet assay isoprene induced DNA damage in peripheral blood mononuclear cells in the presence of metabolic activation. ANIMAL STUDIES: Exposure of rats of each sex to 0, 438, 875, 1750, 3500 or 7000 ppm isoprene vapors by inhalation for 6 hr a day on 5 days/wk for 2 wk had no effect. In male mice it reduced body weight gain, produced atrophy of the thymus and testis (at 7000 ppm only), olfactory epithelial degeneration, vacuolized liver cytoplasm and forestomach epithelial hyperplasia. In both male and female mice in all exposure groups, there were reductions in erythrocyte numbers, hemoglobin concentration and volume of packed erythrocytes. An exposure-related increased incidence of liver, lung, Harderian gland and forestomach tumors and hemangiosarcomas and histiocytic sarcomas was reported in mice. In rats, exposed males and females had increased incidences of mammary fibroadenomas. The incidence of renal tubule adenomas was increased in treated males. Some animals also had a renal carcinoma. Treated males also had increased incidence of interstitial-cell adenomas of the testis. Isoprene affected ovarian follicles in 21 day old female mice. In male mice, there was reduction of testicular weight by 35% in the animals exposed to 7000 ppm, seminiferous tubular atrophy in 20% of animals studied, reduced epididymal weights, lower spermatid headcounts and concentrations, and reduced sperm motility in the 700 and 7000 ppm groups. In developmental studies, there was no treatment-related effect on the incidence of fetal malformations or variations other than a slight increase in the incidence of reduced vertebral ossification. Isoprene was negative when tested for mutagenicity in the Salmonella/microsome preincubation assay using 5 S. typhimurium strains (TA1535, TA1537, TA97, TA98, & TA100) with and without metabolic activation. Isoprene did not induce either sister chromatid exchanges or chromosomal aberrations in cultures of Chinese hamster ovary cells.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 致癌性证据

评估：没有关于异戊二烯致癌性的相关流行病学数据。在实验动物中有足够的证据表明异戊二烯具有致癌性。总体评估：异戊二烯可能对人类具有致癌性（2B组）。

Evaluation: No epidemiological data relevant to the carcinogenicity of isoprene were available. There is sufficient evidence in experimental animals for the carcinogenicity of isoprene. Overall evaluation: Isoprene is possibly carcinogenic to humans (Group 2B).

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 致癌性证据

异戊二烯被合理预期为一种人类致癌物。

Isoprene is reasonably anticipated to be a human carcinogen

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 致癌物分类

国际癌症研究机构致癌物：异戊二烯

IARC Carcinogenic Agent:Isoprene

来源:International Agency for Research on Cancer (IARC)

毒理性

• 致癌物分类

国际癌症研究机构（IARC）致癌物分类：2B组：可能对人类致癌

IARC Carcinogenic Classes:Group 2B: Possibly carcinogenic to humans

来源:International Agency for Research on Cancer (IARC)

吸收、分配和排泄

对大鼠（Wistar）和小鼠（B6C3F1）进行了异戊二烯吸入药代动力学研究，以探讨这种化合物在不同物种间代谢可能的差异。大鼠和小鼠吸入异戊二烯的药代动力学分析显示，两种物种的异戊二烯代谢都表现出饱和动力学。对于大鼠和小鼠来说，在暴露浓度低于300 ppm异戊二烯时，应用线性药代动力学。在大气浓度约为1000 ppm的大鼠和约为2000 ppm的小鼠中，异戊二烯代谢的饱和几乎是完全的。在应用一级代谢的较低浓度范围内，大鼠和小鼠每千克体重的吸入异戊二烯的代谢清除率（与大气中的浓度相关）分别为6200 mL/hr和12,000 mL/hr。估计的最大代谢消除率分别为大鼠130 umole/hr/kg和小鼠400 umole/hr/kg。这表明小鼠的异戊二烯代谢速率是大鼠的两到三倍。当未经处理的家畜被放置在一个封闭的全玻璃暴露系统中时，可以测量到呼出的异戊二烯进入系统。这表明动物内源产生的异戊二烯在动物体内是系统可利用的。从这样的实验中计算出大鼠和小鼠的内源生产率分别为1.9 umole/hr/kg和0.4 umole/hr/kg。/该/数据表明，在讨论异戊二烯可能的致癌或致突变风险时，应该考虑异戊二烯的内源生产。

Studies on inhalation pharmacokinetics of isoprene were conducted in rats (Wistar) and mice (B6C3F1) to investigate possible species differences in metabolism of this compound. Pharmacokinetic analysis of isoprene inhaled by rats and mice revealed saturation kinetics of isoprene metabolism in both species. For rats and mice, linear pharmacokinetics apply at exposure concentrations below 300 ppm isoprene. Saturation of isoprene metabolism is practically complete at atmospheric concentrations of about 1000 ppm in rats and about 2000 ppm in mice. In the lower concentration range where first-order metabolism applies, metabolic clearance (related to the concentration in the atmosphere) of inhaled isoprene per kilogram body weight was 6200 mL/hr for rats and 12,000 mL/hr for mice. The estimated maximal metabolic elimination rates were 130 umole/hr/kg for rats and 400 umole/hr/kg for mice. This shows that the rate of isoprene metabolism in mice is about two or three times that in rats. When the untreated animals are kept in a closed all-glass exposure system, the exhalation of isoprene into the system can be measured. This shows that the isoprene endogenously produced by the animals is systemically available within the animal organism. From such experiments the endogenous production rate of isoprene was calculated to be 1.9 umole/hr/kg for rats and 0.4 umole/hr/kg for mice. /The/ data indicate that the endogenous production of isoprene should be accounted for when discussing a possible carcinogenic or mutagenic risk of this compound.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

B6C3F1雄性小鼠暴露于20、200和2000 ppm异戊烯或(14)C-异戊烯，长达6小时。对于所有暴露情况，异戊烯的稳态水平在暴露开始后迅速达到（即，在15到30分钟内）。20、200和2000 ppm暴露的异戊烯的稳态血药水平（通过顶空分析确定）的平均值（+/- SE）分别为24.8 +/- 3.3、830 +/- 51和6800 +/- 400 ng异戊烯/mL血液。在两个较高的暴露浓度下，血液中异戊烯水平的增加与空气中异戊烯浓度的增加成比例。随着暴露浓度的增加，保留的(14)C/吸入的(14)C比率大约下降了2.3倍。根据暴露浓度，从52%（20 ppm异戊烯）到73%（2000 ppm异戊烯）的代谢物相关的（非异戊烯）放射性在64小时的后暴露期内通过尿液排出。在6小时暴露结束后，20 ppm暴露下的(14)C-O2呼出量最小（2%），在较高的异戊烯暴露浓度下增加到18%。这些数据表明，在本研究中使用的暴露浓度范围内，小鼠对异戊烯的代谢是非线性的。血红蛋白加合物的形成在200到2000 ppm异戊烯暴露浓度之间达到近最大值，这与代谢异戊烯的途径已经饱和的结论一致。吸入异戊烯后，血液中存在异戊烯代谢物，在所有研究的浓度下都是如此。吸入异戊烯的小鼠与大鼠的毒代动力学存在实质性差异。在小鼠中，吸入异戊烯的分数保留，这在一定程度上反映了异戊烯的代谢，在200 ppm的暴露浓度下与暴露浓度线性相关，但在2000 ppm时下降；在大鼠中，吸入异戊烯的分数保留随着暴露浓度的增加而降低，暴露浓度范围从8到1500 ppm。

Male B6C3F1 mice were exposed to nominal concentrations of 20, 200, and 2000 ppm isoprene or (14)C-isoprene for up to 6 hr. For all exposures, steady-state levels of isoprene were reached rapidly (ie, within 15 to 30 min) after the onset of exposure. The mean (+/- SE) steady-state blood levels of isoprene (identified by headspace analysis) for the 20, 200, and 2000 ppm exposures were 24.8 +/- 3.3, 830 +/- 51, and 6800 +/- 400 ng isoprene/mL blood, respectively. At the two higher exposure concentrations, the increases in blood levels of isoprene were proportional to the increases in air concentrations of isoprene. There was approximately a 2.3-fold decrease in the retained (14)C/inhaled (14)C ratio with increasing exposure concentration. Depending on the exposure concentration, from 52% (20 ppm isoprene) to 73% (2000 ppm isoprene) of the metabolite-associated (nonisoprene) radioactivity was excreted in the urine over a 64-hr postexposure period. (14)C-O2 exhalation after the end of the 6-hr exposure was minimal (2%) at the 20 ppm exposure and increased up to 18% at the higher isoprene exposure concentrations. These data suggest that metabolism of isoprene in mice is nonlinear within the range of exposure concentrations used in this study. Hemoglobin adduct formation reached near-maximum between 200 and 2000 ppm isoprene exposure concentration, consistent with /the/ conclusion that pathways for metabolism of isoprene were saturated. Isoprene metabolites were present in blood after inhalation of isoprene at all concentrations studied. There were substantial differences in the toxicokinetics of inhaled isoprene in mice compared to rats. In mice, fractional retention of inhaled isoprene, which reflects, in part, metabolism of isoprene, was linearly related to exposure concentrations up to 200 ppm but decreased at 2000 ppm; in rats, fractional retention of inhaled isoprene decreased with increasing exposure concentration over a range of exposures from 8 to 1500 ppm.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

吸入异戊二烯的百分比随着暴露浓度和蒸汽浓度的增加而代谢减少。大约75%的总代谢物通过尿液排出，这与吸入异戊二烯的浓度无关。在暴露于8200 ppm之后，比在暴露于较低浓度后，更大百分比的代谢物通过粪便排出。在所有检查的组织中，暂时确定了一种致突变代谢物，即异戊二烯二环氧物。血液中存在的代谢物的相对量在吸入异戊二烯的浓度较低和暴露时间较短时最高。身体脂肪似乎是异戊二烯代谢物和异戊二烯本身的储存库。

The percent of the inhaled isoprene that was metabolized decreased with increasing exposure concn & vapor concn. About 75% of the total metabolites was excreted in urine. This was independent of inhaled isoprene concn. After exposure to 8200 ppm, a larger percent of the metabolites was excreted in feces than after exposure to lower concns. A mutagenic metabolite, isoprene diepoxide, was tentatively identified in all tissues examined. The relative amount of the metabolites present in blood was highest for low concns of inhaled isoprene & for shorter exposure durations. Body fat appeared to be a reservoir for both isoprene metabolites & isoprene itself.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

异戊二烯在大鼠和小鼠体内的内生形成速率是每小时1.9微摩尔/千克。

Isoprene is formed endogenously at the rate of 1.9 umol/kg per hour in both rats and mice.

来源:Hazardous Substances Data Bank (HSDB)

安全信息

• TSCA：
  Yes
• 危险等级：
  3
• 危险品标志：
  F+,T
• 安全说明：
  S45,S53,S61
• 危险类别码：
  R68,R45,R52/53,R12
• WGK Germany：
  1
• 海关编码：
  4002601000
• 危险品运输编号：
  UN 1218 3/PG 1
• 危险类别：
  3
• RTECS号：
  NT4037000
• 包装等级：
  I
• 危险标志：
  GHS02,GHS08,GHS09
• 危险性描述：
  H224,H341,H350,H411
• 危险性防范说明：
  P201,P210,P280,P308 + P313,P370 + P378,P403 + P235

制备方法与用途

理化性质

异戊二烯常温下是一种无色易挥发、刺激性油状液体，不溶于水，溶于苯，易溶于乙醇、乙醚和丙酮。它与空气形成爆炸性混合物，爆炸极限大于1.6%。由于含有共轭双键，异戊二烯的化学性质活泼，容易自身聚合或与其他不饱和化合物共聚合，能与许多物质发生反应生成新的化合物。

高纯异戊二烯用途

高纯异戊二烯主要用于生产异戊二烯橡胶、丁基橡胶、SIS（苯乙烯-异戊二烯-苯乙烯共聚物）和SEPS（SIS的加氢产品），也可用于制造专用化学品，如维生素、医药、香料、环氧固化剂。

化学性质

无色易挥发、刺激性油状液体。不溶于水，溶于苯，并且易溶于乙醇、乙醚、丙酮。

用途 主要用途

异戊二烯是合成橡胶的重要单体，其用量占异戊二烯总产量的95%。主要用于合成异戊橡胶，产量仅次于丁苯橡胶和顺丁橡胶而居合成橡胶的第三位。此外，还用于合成丁基橡胶的一种共聚单体，以改进丁基橡胶的硫化性能，但用量很少。异戊二烯还用于合成树脂、液体聚异戊二烯橡胶等，并用于制造农药、医药、香料及黏结剂。

合成用途

主要用于生产性能接近天然橡胶的聚异戊二烯橡胶，也是丁基橡胶和SIS热塑性弹性体的第二单体。合成橡胶的重要单体，用量占异戊二烯总产量的95%，主要用于合成异戊橡胶。还用作合成丁基橡胶的一种共聚单体，以改进丁基橡胶的硫化性能。用于合成树脂、液体聚异戊二烯橡胶等。近年来，还用于合成里那醇、角鲨烯等，这些是进一步合成香料、药品、农药等的中间体。

生产方法 来源

异戊二烯是碳五馏分的重要组分。主要来自炼厂催化裂化汽油得到的异戊烷脱氢和异戊烯脱氢，以及各种石油原料经裂解制乙烯时的副产物。碳五馏分沸点为27.9-49.3℃。

提纯方法

碳五馏分组成复杂，直接精馏难以得到纯度较高的异戊二烯产品，通常采取萃取精馏及共沸精馏法由裂解碳五馏分中分离高纯度异戊二烯。已经工业化的萃取精馏溶剂有乙腈、二甲基甲酰胺和N-甲基吡咯烷酮。除碳五馏分分离得到异戊二烯外，工业上还采用合成法生产。

安全分类 分类

易燃液体

毒性分级

低毒

急性毒性

吸入 - 大鼠 LC50: 180克/立方米/4小时；吸入 - 小鼠 LC50: 139克/立方米/2小时

爆炸物危险特性

与空气混合可爆

可燃性危险特性

遇明火、高温、氧化剂易燃；燃烧产生刺激烟雾

储运特性

库房通风低温干燥；与氧化剂、酸类分开存放

灭火剂

干粉、干砂、二氧化碳、泡沫

职业标准

TWA 100 毫克/立方米

反应信息

• 作为反应物：
  描述：

  天然橡胶 在 mercury dichloride 作用下， 以 水 、 乙腈 为溶剂， 反应 12.0h， 生成 2,2,5-三甲基-4-环庚烯-1-酮
  参考文献：
  名称：

  硫代苯酚在烯基亚环丙烷中的加成反应。卡拉哈那酮的新型合成

  摘要：

  发现将硫酚加到链烯基亚烷基环丙烷（例如3、14）具有很高的区域选择性和立体选择性，从而导致-（或-起始原料中1,4-双键的添加导致乙烯基硫化物加成物（例如4、15）。。向（1）中加入硫酚导致硫化乙烯（16）和（17）的混合物经历Cope重排，产生环庚二烯（18）；水解（18），然后使卡拉哈那酮（19）成为日本啤酒花的有臭成分。和柏树油。

  DOI：

  10.1016/s0040-4039(00)87118-x
• 作为产物：
  描述：

  2-甲基-1-丁烯-3-酮 生成 天然橡胶
  参考文献：
  名称：

  DE267040

  摘要：

  公开号：
• 作为试剂：
  描述：

  茴香烯 、 methyl 6-cyano-9-phenanthrenecarboxylate 在 天然橡胶 作用下， 以 苯 为溶剂， 反应 2.5h， 生成 (Z)-茴香脑 、 methyl (1S,2R,10bS)-8-cyano-1-(4-methoxyphenyl)-2-methyl-2,2a-dihydro-1H-cyclobuta[l]phenanthrene-10b-carboxylate 、
  参考文献：
  名称：

  (E)-3-(4-Methoxyphenyl)-3-pentenyl 6-Cyano-9-phenanthrenecarboxylate 的分子内光环加成。温度和溶剂影响

  摘要：

  (E)-3-(4-Methoxyphenyl)-3-pentenyl 6-cyano-9-phenanthrenecarboxylate 以及相应的 9-phenanthrenecarboxylate 表现出激发态发射，并产生 [2+2] 与菲 9 双键的光环加合物， 10键（环丁烷）和酯羰基（氧杂环丁烷）。基于荧光和环加成的量子效率的温度和溶剂依赖性以及激基复合物中间体的猝灭剂的影响，提出了多个激基复合物中间体对这些现象的参与。

  DOI：

  10.1246/bcsj.67.1434

文献信息

• Boron Lewis Acid-Catalyzed Regioselective Hydrothiolation of Conjugated Dienes with Thiols
  作者：Gautam Kumar、Zheng-Wang Qu、Soumen Ghosh、Stefan Grimme、Indranil Chatterjee

  DOI：10.1021/acscatal.9b04647

  日期：2019.12.6

  tris(pentafluorophenyl)borane, B(C6F5)3, and BF3·Et2O are shown to catalyze the regioselective hydrothiolation of a wide range of terminal 1-aryl-1,3-dienes. In the case of internal 1,3-dienes, B(C6F5)3 is by far the better catalyst than BF3·Et2O. The process features mild reaction conditions, broad scope, and low catalyst loading, and it can be scaled up quickly over a short reaction time. The reactions are rate-limited

  报道了用于合成仲和叔烯丙基硫醚的无过渡金属的1,3-二烯氢硫醇化反应。硼路易斯酸三（五氟苯基）硼烷，B（C 6 F 5）3和BF 3 ·Et 2 O已显示出催化范围广泛的末端1-芳基-1,3-二烯的区域选择性氢硫醇化反应。在内部1,3-二烯的情况下，与BF 3 ·Et 2相比，B（C 6 F 5）3是更好的催化剂。O.该工艺的特点是反应条件温和，适用范围广，催化剂用量低，并且可以在较短的反应时间内迅速扩大规模。如高水平DFT计算所示，反应是通过1，3-二烯与硫醇-硼路易斯酸配合物的1-芳基定向质子化，然后将硫化物阴离子转移到所得的烯丙基阳离子上来进行的，从而限制了反应的速率。
• Convergent Synthesis of Menaquinone-7 (MK-7)
  作者：Aneta Baj、Piotr Wałejko、Andrzej Kutner、Łukasz Kaczmarek、Jacek W. Morzycki、Stanisław Witkowski

  DOI：10.1021/acs.oprd.6b00037

  日期：2016.6.17

  A practical synthesis of menaquinone-7 (MK-7, vitamin K2) in the all-trans form was designed. Stereoselective synthesis of MK-7 was achieved through a “1 + 6” convergent strategy by condensation of two building blocks, menadione monoprenyl derivative (fragment “1”) with hexaprenyl bromide (fragment “6”, 82%). Pd-catalyzed desulfonation with LiEt3BH (78%) was followed by oxidation of the hydroquinone

  设计了一种实用的全反式甲萘醌7（MK-7，维生素K 2）合成方法。MK-7的立体选择性合成是通过“ 1 + 6”会聚策略实现的，该策略通过将两个组成部分，甲萘醌单异戊二烯基衍生物（片段“ 1”）与六异戊烯基溴化物（片段“ 6”，82％）缩合而实现。用LiEt 3 BH（78％）进行Pd催化的脱硫，然后使用硝酸铈（IV）铵（72％）氧化对苯二酚部分。我们方法学中的主要挑战是通过偶联两个由反式，反式衍生的三烯基单元来制备全反式六异戊烯基溴化物-法尼醇。通过我们的方法完成了中试规模的制造。这种可扩展的方法是专门为从易于获得的中间体进行大规模公斤级生产而设计的。此外，所提出的方法避免了许多色谱纯化，并且允许相对成本有效的制造。此外，我们的合成产生了高纯度（99.9％）的最终产品MK-7，可将其用作膳食补充剂以及活性药物成分。
• DESIGN, SYNTHESIS AND FUNCTIONAL CHARACTERIZATION OF ROTTLERIN ANALOGS
  申请人：KANTHASAMY ANUMANTHA G.

  公开号：US20110112182A1

  公开（公告）日：2011-05-12

  A method of synthesizing rottlerin analogs is described. The synthesis methods described are the first known method of synthesizing rottlerin analogs from commercially-available materials to produce cost effective analogs. Rottlerin analog structures made by the synthesis methods and methods of use for treating a neurological or inflammatory response mediated by protein kinase C (PKC) are further described.

  描述了一种合成罗特林类似物的方法。所描述的合成方法是从商业可获得的材料中合成罗特林类似物的首个已知方法，以生产具有成本效益的类似物。通过这些合成方法制备的罗特林类似物结构以及用于治疗由蛋白激酶C（PKC）介导的神经或炎症反应的方法也进一步描述了。
• TBAHF₂ and TBAH₂F₃ as Activating Agents of Organosilanes
  作者：Atsunori Mori、Akinori Fujita、Kazutaka Ikegashira、Yasushi Nishihara、Tamejiro Hiyama

  DOI：10.1055/s-1997-3276

  日期：1997.6

  The fluoride reagents, TBAH2F3 and TBAHF2 (TBA: tetrabutylammonium), are found to catalyze the reactions of hexamethyldisilane with 1,3-dienes, aliphatic aldehydes, and aromatic aldehydes to give 1,4-disilyl-2-butenes, α-silyl alcohols and pinacols, respectively. Using an equimolar amount of TBAHF2 and disilanes, reduction of carbonyl compounds occurs in place of the silyl group addition.

  氟化剂TBAH2F3和TBAHF2（TBA：四丁基铵）被发现能够催化六甲基二硅烷与1,3-二烯、脂肪醛和芳香醛的反应，分别生成1,4-二硅基-2-丁烯、α-硅基醇和频哪醇。在使用等摩尔量的TBAHF2和二硅烷时，会发生羰基化合物的还原反应，取代硅基加成反应。
• Catalytic regio- and stereoselective intermolecular [5+2] cycloaddition <i>via</i> conjugative activation of oxidopyrylium
  作者：Ling Zhang、Qiu Shi、Tongxiang Cao、Shifa Zhu

  DOI：10.1039/d0cc04309e

  日期：——

  A catalytic stereodivergent intermolecular [5+2] cycloaddition of maltol-type oxidopyrylium through conjugative activation was reported, which featured high stereoselectivity, good compatibility and mild conditions, providing a convenient access route to various seven-membered heterocycles in moderate to excellent yields. In addition, a discrete mechanism was proposed to illustrate the stereoselectivity

  据报道，麦芽酚型氧化性霉菌通过共轭激活催化立体发散的分子间[5 + 2]环加成反应，具有高立体选择性，良好的相容性和温和的条件，为中等至优异的收率提供了方便的途径通往各种七元杂环。此外，提出了一种离散机制来说明立体选择性。

表征谱图