1,2-丙二醇二硝酸酯 | 6423-43-4

• 物质功能分类: 有机原料 - 无机酸酯
• 分子结构分类: 有机化合物 - 有机氧化合物 - 有机含氧阴离子化合物
• 中文名称: 1,2-丙二醇二硝酸酯
• 中文别名: 丙二醇二硝酸酯；1,2-二硝酸丙二醇酯
• 英文名称: 1,2-propyl dinitrate
• 英文别名: propane-1,2-diol dinitrate；propane-1,2-diyl dinitrate；1,2-dinitrooxy-propane；propylene glycol dinitrate；1,2-bis-nitrooxy-propane；nitric acid propanediyl ester；1-nitrooxypropan-2-yl nitrate
• CAS: 6423-43-4
• 化学式: C₃H₆N₂O₆
• mdl: MFCD01698023
• 分子量: 166.09
• InChiKey: PSXCGTLGGVDWFU-UHFFFAOYSA-N

物化性质

• 沸点：
  294.26°C (rough estimate)
• 介电常数：
  26.800000000000001
• 物理描述：
  Propylene glycol dinitrate is a colorless liquid with a disagreeable odor. Mp: -30°C. Density 1.37 g/cm3 at 20°C. Slightly soluble in water (7.97 g/L H2O at 24.85°C).
• 颜色/状态：
  Red-orange liquid
• 熔点：
  18 °F (NIOSH, 2016)
• 溶解度：
  In water, 3,262 mg/L @ 25 °C /Estimated/
• 密度：
  Relative density (water = 1): 1.2 (25 °C)
• 蒸汽密度：
  Relative vapor density (air = 1): 5.73
• 蒸汽压力：
  0.38 mm Hg @ 25 °C /Estimated/
• 大气OH速率常数：
  3.20e-13 cm3/molecule*sec
• 稳定性/保质期：

  It is unstable under ordinary conditions, but it is stabilized by small additions of 2-nitrodiphenylamine and di-n-butyl sebacate... .

• 分解：
  121 °C
• 保留指数：
  1004

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  11
• 可旋转键数：
  3
• 环数：
  0.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  110
• 氢给体数：
  0
• 氢受体数：
  6

ADMET

代谢

/丙二醇, 1,2-二硝酸盐/ (PGDN) 的代谢，在体外血液中以及大鼠体内的实验显示，50% 在 1 小时内分解，剩余的 50% 在接下来的小时内分解。在血液中孵育时产生了少量的无机亚硝酸盐，而有积累的无机硝酸盐。在 3 小时结束时，第一次测量时，发现了大量的丙二醇 2-单硝酸盐 (PGMN-2)，以及少量的 PGMN-1)。单硝酸盐、无机硝酸盐和亚硝酸盐的总和代表了加入血液的初始量的 95%。这种代谢发生在红细胞中。在完整的大鼠体内，与体外血液中的情况不同，单硝酸盐进一步降解为除了单硝酸盐和无机硝酸盐之外的氮化合物。只有 56% 的给药 PGDN 以无机硝酸盐的形式出现在尿液中。因此，从定性上来说，PGDN 的体内外代谢与/乙二醇二硝酸盐/ (EGDN) 的代谢没有太大区别。唯一的区别是 PGDN 产生两种单硝酸盐，且 2-异构体占主导，而 EGDN 只产生/乙二醇单硝酸盐/。从数量上来说，皮下注射 PGDN 后血液中的二硝酸盐和无机亚硝酸盐含量比同等剂量的 EGDN 注射要少。在大鼠皮下注射 65 mg/kg 的 PGDN 后，24 小时内排泄完全。

The metabolism of /propylene glycol, 1,2-dinitrate/ (PGDN), as determined in vitro in blood and in vivo in rats, showed that 50% was broken down in 1 hr, and 50% of the remainder in the following hour. Small concentrations of inorganic nitrite were produced during incubation in blood, whereas inorganic nitrate accumulated. At the end of 3 hr, the first time it was measured, there were large amounts of propylene glycol 2-mononitrate (PGMN-2), together with small amounts of PGMN-1). The summed quantities of mononitrates, inorganic nitrate, and nitrite represented 95% of the initial amount added to blood. this metabolism occurred in the erythrocytes. In the intact rat, in contrast to in vitro in the blood, mononitrates undergo further degradation to nitrogen compounds other than the mononitrates and inorganic nitrate. Only 56% of the administered PGDN appeared in the urine as inorganic nitrate. THus, there is qualitatively little to distinguish the in vitro and in vivo metabolism of PGDN from that of /ethylene glycol dinitrate/ (EGDN). The only difference is that PGDN gives rise to two mononitrates and the 2-isomer is predominant, whereas EGDN gives rise only to /ethylene glycol mononitrate/. Quantitatively, there is less dinitrate and inorganic nitrite in the bloodstream after subcutaneous injection from PGDN than from a comparable injection of EGDN. Excretion was complete in 24 hr following a 65 mg/kg PGDN subcutaneous injection in rats.

来源:Hazardous Substances Data Bank (HSDB)

代谢

代谢研究表明，在大鼠皮下注射65毫克/千克的1,2-丙二醇二硝酸酯（PGDN）后，无机硝酸盐是其主要代谢物；PGDN和亚硝酸盐几乎检测不到。排泄在24小时内完成。

Metabolic studies show that inorganic nitrate /is/ the major metabolite of propylene glycol dinitrate (PGDN) in rats administered 65 mg/kg subcutaneously; PGDN and nitrite were almost undetectable. Excretion was complete in 24 hours.

来源:Hazardous Substances Data Bank (HSDB)

代谢

努力更好地理解产生体内高铁血红蛋白的氧化过程，并解释血红蛋白在解毒硝基酯方面的作用。该反应是非酶催化的，对二硝基化合物和氧合血红蛋白而言是一级反应。氧化速率与二硝基化合物浓度成正比，并不像酶催化那样趋于极限。氧化速率与氧浓度关系复杂。在零氧浓度下不发生氧化，在非常高的氧浓度下也不会发生。在溶血素中，每断裂一个酯键，认为是1.5个血红素被氧化，而在整个细胞中，每摩尔反应的酯是1.9到2.3个血红素。从这些研究中，可以推断血红蛋白在解毒二硝基化合物引起的效果方面发挥了重要作用。体内的血红蛋白，借助高铁血红蛋白还原酶系统，催化地将二硝基化合物代谢为亚硝酸盐和硝酸盐，而单硝基化合物则由脱硝组织酶进一步降解。

... An effort was made to understand the oxidative process /which produces methemoglobin in vivo/ better and explain the role of hemoglobin in detoxifying nitrate esters. The reaction was nonenzymatic and first-order for dinitrate and O2Hb. The rate of oxidation proceeds linearly with dinitrate concentration and does not approach a limit as would be the case if it were enzymatically driven. The rate of oxidation is related complexly to the oxygen concentration. No oxidation occurs at zero oxygen concentration and none at very high concentrations. The stoichiometry was thought to be 1.5 hemes oxidized per ester bond broken in hemolysates and 1.9 to 2.3 per mole reacted ester in whole cells. From these studies, it was reasoned that hemoglobin would fulfill an important role in detoxifying the effects caused by the dinitrates. Hemoglobin in vivo, with the methemoglobin reductase system, acts catalytically to metabolize dinitrates to nitrite and nitrate, and the mononitrates are further degraded by the denitrifying tissue enzymes.

来源:Hazardous Substances Data Bank (HSDB)

代谢

在大鼠体内，皮下注射65毫克/千克的丙二醇二硝酸酯会导致血液中丙二醇二硝酸酯水平迅速升高。丙二醇二硝酸酯的代谢物在注射后2-4小时达到最高值，在8-12小时后降至几乎为零。血液中观察到的最主要代谢物是硝酸盐，其次是丙二醇2-单硝酸酯，其浓度约为无机硝酸盐的一半。丙二醇1-单硝酸酯和无机亚硝酸盐的水平则不到丙二醇2-单硝酸酯的一半。

Subcutaneous injection of 65 mg/kg propylene glycol dinitrate in rats caused a rapid increase in blood levels of propylene glycol dinitrate. Appearance of metabolites of propylene glycol dinitrate in the blood was maximal 2-4 hours postinjection and had declined to essentially zero by 8-12 hours postinjection. The predominant metabolite observed in the blood was nitrate, with propylene glycol 2-mononitrate observed at approximately one-half the concentration of inorganic nitrate. The levels of propylene glycol 1-mononitrate and inorganic nitrite were less than half that of propylene glycol 2-mononitrate.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 暴露途径

这种物质可以通过吸入、皮肤接触和摄入被身体吸收。

The substance can be absorbed into the body by inhalation, through the skin and by ingestion.

来源:ILO-WHO International Chemical Safety Cards (ICSCs)

毒理性

• 暴露途径

吸入，皮肤吸收，吞食，皮肤和/或眼睛接触

inhalation, skin absorption, ingestion, skin and/or eye contact

来源:The National Institute for Occupational Safety and Health (NIOSH)

毒理性

• 症状

眼睛刺激；结膜炎；高铁血红蛋白血症；头痛，平衡障碍，视觉干扰；在动物中：肝脏，肾脏损害

irritation eyes; conjunctivitis; methemoglobinemia; headache, impaired balance, visual disturbance; In Animals: liver, kidney damage

来源:The National Institute for Occupational Safety and Health (NIOSH)

毒理性

• 吸入症状

蓝色嘴唇、手指甲和皮肤。混乱。抽搐。眩晕。头痛。恶心。昏迷。

Blue lips, fingernails and skin. Confusion. Convulsions. Dizziness. Headache. Nausea. Unconsciousness.

来源:ILO-WHO International Chemical Safety Cards (ICSCs)

毒理性

• 皮肤症状

可能会被吸收！请参见吸入部分。

MAY BE ABSORBED! See Inhalation.

来源:ILO-WHO International Chemical Safety Cards (ICSCs)

吸收、分配和排泄

这种物质可以通过吸入、皮肤接触或摄入被身体吸收。

The substance can be absorbed into the body by inhalation, through the skin or by ingestion.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

支持丙二醇二硝酸盐经皮吸收的信息来源于在兔子上进行的经皮暴露后显示全身毒性的研究。例如，在兔子背部涂抹低至1,000 mg/kg/天的丙二醇二硝酸盐剂量，每天2小时，持续20天后，观察到一过性血红蛋白降低。此外，接收4,000 mg/kg/天经皮剂量的兔子尿液中硝酸盐代谢物水平升高，这也支持了丙二醇二硝酸盐经皮暴露后的吸收。

Information supporting the dermal absorption of propylene glycol dinitrate was obtained from studies demonstrating systemic toxicity after dermal exposure in rabbits For example, a transient decrease in hemoglobin was observed following dermal application of doses of propylene glycol dinitrate as low as 1,000 mg/kg/day, 2 hours/day, for 20 days to rabbits. Also, observation of elevated levels of the metabolite nitrate in the urine of rabbits receiving a dermal dose of 4,000 mg/kg/day supported the absorption of propylene glycol dinitrate after dermal exposure.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

猴子暴露于1.6 ppm和4.2 ppm丙二醇二硝酸酯的浓度下，分别持续20天和14天，结果在血浆中检测到少量丙二醇二硝酸酯。在1.6 ppm的暴露下，血浆中检测到35微克/毫升丙二醇二硝酸酯，而在4.2 ppm的暴露下，血浆中检测到170微克/毫升。

Exposure of monkeys to concentrations of 1.6 ppm and 4.2 ppm of propylene glycol dinitrate for 20 and 14 days, respectively, resulted in the detection of small amounts of propylene glycol dinitrate in plasma. During exposures to 1 .6 ppm, 35 ug/mL propylene glycol dinitrate was detected in plasma, and during exposures at 4.2 ppm, 170 ug/mL was detected in plasma.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

使用狗血进行体外研究表明，硝化甘油二丙醇优先与血液中的红细胞结合。

In vitro studies using dog blood have shown that propylene glycol dinitrate preferentially associates with red blood cells in the blood.

来源:Hazardous Substances Data Bank (HSDB)

安全信息

• 职业暴露等级：
  C
• 职业暴露限值：
  TWA: 0.05 ppm (0.3 mg/m3) [skin]
• 危险等级：
  1.1A
• 海关编码：
  2920909090
• 危险类别：
  1.1A

反应信息

• 作为反应物：
  描述：

  1,2-丙二醇二硝酸酯 在 苄胺 作用下， 生成 1,2-丙二醇
  参考文献：
  名称：

  Lur'e, B. A.; Kozhukhova, V. M., Journal of general chemistry of the USSR, 1991, vol. 61, # 12, p. 2532 - 2535

  摘要：

  DOI：
• 作为产物：
  描述：

  2-甲基氮丙啶 在 五氧化二氮 作用下， 以 二氯甲烷 为溶剂， 以18.5%的产率得到1,2-丙二醇二硝酸酯
  参考文献：
  名称：

  氮氧化物硝化，第4部分：某些氮丙啶和氮杂环丁烷与五氧化二氮反应后的意外行为

  摘要：

  在环氮上未取代的或带有N-酰基（N，N-二甲基氨基甲酰基或丙酰基）的七个氮丙啶和氮杂环丁烷在卤化溶剂中与N 2 O 5反应，结果如下：-氮丙啶的行为高度依赖在N-取代基上，分别得到二硝酸酯，硝酸硝胺或主要不具有特征的产物，而氮杂环丁烷在所有情况下均给出N-硝基氮杂环丁烷。据信，不同的行为是由环应变效应引起的。

  DOI：

  10.1016/s0040-4039(00)93514-7

文献信息

• Preparation of Di- and polynitrates by ring-opening nitration of epoxides by dinitrogen pentoxide (N2O5)
  作者：Peter Golding、Ross W Millar、Norman C Paul、David H Richards

  DOI：10.1016/s0040-4020(01)87978-3

  日期：1993.8

  hydrocarbon solvents (principally CH2Cl2) to give vicinal nitrate ester products by a novel ring-opening nitration reaction. The procedure offers easier temperature control and simpler isolation procedures compared with conventional mixed acid nitrations; it also enables selective nitration reactions to be carried out on polyfunctional substrates. The scope and limitations of the reaction, as well as

  通过新颖的开环硝化反应，使十八种各种环氧化合物与N 2 O 5在氯化烃溶剂（主要为CH 2 Cl 2）中反应，得到邻位硝酸酯产物。与传统的混合酸硝化方法相比，该方法提供了更轻松的温度控制和更简单的分离步骤。它还可以在多官能底物上进行选择性硝化反应。讨论了反应的范围和局限性，以及利用N 2 O 4与硝酸亚硝酸酯原位进行原位氧化的替代方法的范围和局限性。
• Clean nitrations: Novel syntheses of nitramines and nitrate esters by nitrodesilylation reactions using dinitrogen pentoxide (N 2 O 5 )
  作者：Ross W. Millar、Simon P. Philbin

  DOI：10.1016/s0040-4020(97)00093-8

  日期：1997.3

  with conventional substrates (amines or alcohols). These nitrodesilylation reactions proceed cleanly and in good yield, and the scope of the reaction is illustrated by. 29 examples, some of which produce high energy compounds, notably plasticisers and an energetic polymer precursor. These reactions are therefore potentially clean nitrations for the manufacture of energetic compounds which will minimise

  在这种新型的硝化方法中，使用惰性溶剂中的五氧化二氮（N 2 O 5）作为硝化剂，从而无需使用强酸作为反应介质。N 2 O 5分别在甲硅烷基胺和甲硅烷基醚中裂解杂原子-硅键，得到所需的高能基团（分别为硝胺或硝酸酯），而不会释放常规底物（胺或醇）会发生的酸。这些氮代甲硅烷基化反应清洁且收率良好，反应范围如下所示。29个实例，其中一些可以生产高能化合物，尤其是增塑剂和高能聚合物前体。因此，这些反应是潜在的清洁硝化反应，可用于生产高能化合物，这将在将来最大程度地降低这种活性对环境的影响。
• Severe Prolonged Tacrolimus Overdose with Minimal Consequences
  作者：Laura L. Hardwick、Thomas D. Batiuk

  DOI：10.1592/phco.22.12.1063.33604

  日期：2002.8

  A 59-year-old man inadvertently received a 10-fold increase in his twice-daily oral dose of tacrolimus 1 mg that resulted in trough blood levels above 90 ng/ml for over a week. The patient had end-stage renal disease secondary to diabetes mellitus and had received a kidney transplant from his daughter 3 months earlier. Despite the numerous adverse effects commonly reported with tacrolimus, such as mild nephrotoxicity, nausea, tremors, and elevated liver enzyme levels, our patient's acute but prolonged overdose resulted in minimal signs and symptoms of toxicity. Nevertheless, education regarding the importance of accurate dosing, close monitoring, potential drug interactions, and the various capsule colors should be provided to all patients who receive tacrolimus, as well as their physicians, nurses, and pharmacists, in order to prevent as many errors as possible.

  一名59岁的男性偶然间将每日两次口服的他克莫司剂量从1毫克增加到了10倍，导致其血药浓度在一周内超过90 ng/ml。该患者因糖尿病导致终末期肾病，并在3个月前接受了来自女儿的肾脏移植。尽管他克莫司常见的不良反应包括轻度肾毒性、恶心、震颤和肝酶水平升高，但我们的患者在急性但长期的过量情况下，仅出现了轻微的毒性迹象和症状。然而，应该向所有接受他克莫司治疗的患者及其医生、护士和药剂师提供关于准确剂量、密切监测、潜在药物相互作用以及各种胶囊颜色的重要性教育，以尽量减少错误的发生。
• Practical catalytic nitration directly with commercial nitric acid for the preparation of aliphatic nitroesters
  作者：Jichao An、Peipei Liu、Mengyuan Si、Wenhao Li、Pan He、Bo Yang、Guanyu Yang

  DOI：10.1039/d0ob01519a

  日期：——

  To pursue a sustainable and efficient approach for aliphatic nitroester preparation from alcohol, europium-triflate-catalyzed nitration, which directly uses commercial nitric acid, has been successfully developed. Gram scalability with operational ease showed its practicability.

  为了寻求一种可持续且高效的酒精制备脂肪族硝基酯的方法，已经成功开发了直接使用商业硝酸的三氟甲磺酸铕催化硝化反应。Gram 可扩展性和操作简便性显示了它的实用性。
• Gmelin Handbuch der Anorganischen Chemie, Gmelin Handbook: N: MVol.4, 7.7, page 1006 - 1013
  作者：

  DOI：——

  日期：——

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