2,4-二硝基甲苯 | 121-14-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 2,4-二硝基甲苯
• 中文别名: 2,4-二硝基甲苯(易制爆)；1-甲基-2,4-二硝基苯
• 英文名称: 2,4-DNt
• 英文别名: 2,4-dinitro-toluene；DNT；1-methyl-2,4-dinitrobenzene；2,6-dinitrotoluene；2,4-Dinitrotoluene
• CAS: 121-14-2；1326-41-6；84029-42-5
• 化学式: C₇H₆N₂O₄
• mdl: MFCD00007172
• 分子量: 182.136
• InChiKey: RMBFBMJGBANMMK-UHFFFAOYSA-N

物化性质

• 熔点：
  71 °C
• 沸点：
  300 °C
• 密度：
  1.3208 g/cm3(Temp: 71 °C)
• 物理描述：
  Heated yellow liquid. Solidifies if allowed to cool. Insoluble in water and more dense than water. Toxic by skin absorption, inhalation and ingestion. Easily absorbed through the skin. Produces toxic oxides of nitrogen during combustion. Used to make dyes and other chemicals.
• 颜色/状态：
  Yellow needles or monoclinic prisms
• 气味：
  SLIGHT ODOR
• 闪点：
  169 °C c.c.
• 溶解度：
  Ethanol, at 15 °C, 30.46 g/L; diethyl ether, at 22 °C, 94 g/L; carbon disulfide, at 17 °C, 21.9 g/L
• 蒸汽密度：
  6.27 (NTP, 1992) (Relative to Air)
• 蒸汽压力：
  1.47X10-4 mm Hg at 22 °C
• 亨利常数：
  5.40e-08 atm-m3/mole
• 分解：
  When heated to decomposition it emits toxic fumes of /nitrogen oxides/. Decomposes when heated to 250 °C. Mixture with sodium carbonate can decompose with significant pressure increase at 210 °C.
• 粘度：
  0.0034553 Pa.s at 342.65 deg K
• 腐蚀性：
  Liquid dinitrotoluene will attack some forms of plastics, rubber, and coatings.
• 燃烧热：
  3.568 MJ/Mol
• 汽化热：
  94.2 kJ/mol
• 表面张力：
  0.050041 N/m at 342.65 deg K
• 折光率：
  Index of refraction: 1.442
• 保留指数：
  1537;1497;1498;1501.2

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  13
• 可旋转键数：
  0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.142
• 拓扑面积：
  91.6
• 氢给体数：
  0
• 氢受体数：
  4

ADMET

代谢

(14)C标记的2,4-DNT到2,4-二硝基苄醇的代谢，通过兔、狗和猴子的肝后线粒体部分转化，比通过小鼠和大鼠的部分转化要大。唯一一致的性别差异是在氮气冲洗后，雄性肝脏形成了更多的氨基甲苯。

METAB OF (14)C-LABELED 2,4-DNT TO 2,4-DINITROBENZYL ALCOHOL BY POSTMITOCHONDRIAL LIVER FRACTION FROM RABBITS, DOGS & MONKEYS WAS GREATER THAN BY FRACTIONS FROM MICE & RATS. ONLY CONSISTENT SEX DIFFERENCE WAS FORMATION OF MORE AMINOTOLUENES BY MALE LIVERS FOLLOWING A NITROGEN FLUSH.

来源:Hazardous Substances Data Bank (HSDB)

代谢

在大鼠尿液中含有2,4-二硝基甲苯的九种代谢物。通过给雄性大鼠重复口服给药，然后使用薄层色谱法（TLC）检测到这些代谢物。这些代谢物包括2-氨基-4-硝基甲苯、4-氨基-2-硝基甲苯、2,4-二氨基甲苯、2,4-二硝基苄醇、2-氨基-4-硝基苄醇、4-氨基-2-硝基苄醇、2-硝基-4-乙酰氨基甲苯、2-氨基-4-乙酰氨基甲苯和2-氨基-4-乙酰氨基苯甲酸。

NINE METABOLITES OF 2,4-DINITROTOLUENE IN RAT URINE WERE DETECTED BY TLC AFTER REPEATED ORAL ADMIN TO MALE RATS. 2-AMINO-4-NITROTOLUENE, 4-AMINO-2-NITROTOLUENE, 2,4-DIAMINOTOLUENE, 2,4-DINITROBENZYL ALC, 2-AMINO-4-NITROBENZYL ALC, 4-AMINO-2-NITROBENZYL ALC, 2-NITRO-4-ACETYLAMINOTOLUENE, 2-AMINO-4-ACETYLAMINOTOLUENE, & 2-AMINO-4-ACETYLAMINOBENZOIC ACID WERE IDENTIFIED.

来源:Hazardous Substances Data Bank (HSDB)

代谢

2,4-二硝基甲苯（2,4-DNT）处理对大鼠某些肝脏外源化合物代谢酶的活性影响很小，并且在大鼠肝脏体外实验中容易被代谢。体外代谢途径取决于氧分压。这种体外代谢产物主要是极性代谢物，它们与微粒体大分子的结合不明显。

2,4-DNT TREATMENT HAD LITTLE EFFECT ON THE ACTIVITY OF SOME HEPATIC XENOBIOTIC METABOLIZING ENZYMES IN RATS, AND WAS READILY METABOLIZED BY LIVER PREPN IN VITRO. THE PATHWAYS OF IN VITRO METABOLISM WERE DEPENDENT ON OXYGEN TENSION. THIS IN VITRO METAB PRODUCED MOSTLY POLAR METABOLITES WHICH DID NOT BIND APPRECIABLY TO MICROSOMAL MACROMOLECULES.

来源:Hazardous Substances Data Bank (HSDB)

代谢

在大鼠中，盲肠内容物的还原代谢能力按每克体重计算超过肝脏微粒体的1000倍，这表明盲肠是DNT还原代谢的主要场所。肝脏和盲肠微生物群共同作用，是二硝基甲苯代谢物形成的主要场所，这些代谢物可能是其致癌活性的原因。

IN RATS, THE REDUCTIVE METABOLIC CAPACITY OF CECAL CONTENTS ON PER G WT BASIS EXCEEDS THAT BY LIVER MICROSOMES BY FACTOR OF 1000, SUGGESTING THAT CECUM REPRESENTS MAJOR SITE OF REDUCTIVE METABOLISM OF DNT. LIVER & CECAL MICROFLORA ACTING IN CONCERT REPRESENT MAJOR SITES FOR FORMATION OF DINITROTOLUENE METABOLITES WHICH MAY BE RESPONSIBLE FOR ITS CARCINOGENIC ACTIVITY.

来源:Hazardous Substances Data Bank (HSDB)

代谢

2,4-二硝基甲苯可以通过吸入烟雾或尘埃、摄入或接触皮肤后被吸收。2,4-DNT的生物活化被认为通过以下过程发生：甲基团通过细胞色素P-450依赖途径被氧化成醇；苯甲基醇与葡萄糖醛酸结合并随胆汁排出。肠道微生物群将葡萄糖苷酸水解并还原一个硝基团，形成可以重新从肠道吸收的氨基硝基苯甲醇。氨基团通过肝酶氧化成羟胺，并通过磺基转移酶与硫酸盐结合。硫酸酯的分解产生了一个高度亲电子的硝基正离子（或碳正离子），它可以与DNA和其他生物亲核物质反应。人类尿液中发现的主要代谢物是2,4-二硝基苯甲醇或其葡萄糖苷酸结合物。其他尿液代谢物包括2,4-二硝基苯甲酸、4-(N-乙酰)氨基-2-硝基苯甲酸和2-氨基-4-硝基苯甲酸。后两者明显是氧化还原代谢的产物。代谢还被认为是涉及O-乙酰转移酶（将2,4-DNT的乙酰基转移）和胞浆黄嘌呤氧化酶（还原2,4-DNT）。尿液中也可以观察到少量未代谢的2,4-DNT。（L276, A169, T47, A170, A177, A178）

2,4-Dinitrotoluene can be inhalated as fumes or dust, ingested, or absorbed after contact with the skin. Bioactivation of 2,4-DNT is thought to occur by the following processes: The methyl group is oxidized to an alcohol by a cytochrome P-450 dependent pathway; the benzyl alcohol is conjugated with glucuronic acid and excreted in the bile. Intestinal microflora hydrolyzes the glucuronide and reduces one nitro group, forming an aminonitrobenzyl alcohol which can be readsorbed from the intestine. The amino group is oxidized to an hydroxylamine by hepatic enzymes and conjugated with sulfate, by sulfotransferase. Decomposition of the sulfate ester yields a highly electrophilic nitrenium (or carbonium) ion which can react with DNA and other biological nucleophiles. The major metabolite found in human urine is 2,4-dinitrobenzyl alcohol or its glucuronide conjugate. Other urinary metabolites include 2,4-dinitrobenzoic acid, 4-(N-acetyl)amino-2nitrobenzoic acid, and 2-amino-4-nitrobenzoic acid. The latter two are clearly the product of both oxidative and reductive metabolism. Metabolism is also believed to involve O-acetyltransferase (which transfers the acetyl group of 2,4-DNT) and cytosolic xanthine oxidase (which reduces 2,4-DNT). Small traces of unmetabolized 2,4-DNT can be observed in the urine too. (L276, A169, T47, A170, A177, A178)

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 毒性总结

2,4-二硝基甲苯（2,4-DNT）可能通过其代谢物将铁(II)氧化为铁(III)，从而将氧合血红蛋白转化为高铁血红蛋白。高水平的高铁血红蛋白通过分解代谢被去除，导致贫血的发展。2,4-DNT的一些代谢物也从胆汁返回到肝脏，在那里通过细胞色素P-450的氮羟基化形成不稳定的硫酸盐结合物。硫酸盐结合物降解为碳正离子或硝renium离子。这些离子与肝大分子（DNA、RNA）共价结合，导致突变，随后发展为肝癌。它们还与肺和肠道的DNA结合。（L276, T45, A171, L280）

2,4-DNT may cause conversion of oxyhemoglobin to methemoglobin via oxidation of iron(II) to iron(III) by its metabolites. High levels of methemoglobin are removed by catabolism, leading to the development of anemia. Some metabolites of 2,4-DNT are also transported back from the bile to the liver, where the amine group is N-hydroxylated by cytochrome P-450 to form an unstable sulfate conjugate. The sulfate conjugate is degraded into carbonium or nitrenium ions. These ions covalently bind to hepatic macromolecules (DNA, RNA), leading to mutations and subsequently liver tumors. They also bind to DNA of the lung and the intestine. (L276, T45, A171, L280)

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 致癌性证据

评估：对于2,4-二硝基甲苯对人类致癌性的证据不足。... 对于2,4-二硝基甲苯对实验动物致癌性的证据是充分的。... 总体评估：2,4-二硝基甲苯... /可能/ 对人类具有致癌性（2B组）。

Evaluation: There is inadequate evidence in humans for the carcinogenicity of 2,4-dinitrotoluene. ... There is sufficient evidence in experimental animals for the carcinogenicity of 2,4-dinitrotoluene. ... Overall evaluation: 2,4-Dinitrotoluene ... /is/ possibly carcinogenic to humans (Group 2B).

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 致癌性证据

这种物质/试剂尚未在美国环保局（EPA）的IRIS计划下进行完整评估，以查看其是否具有人类致癌潜力。

This substance/agent has not undergone a complete evaluation under U.S. EPA's IRIS program for evidence of human carcinogenic potential.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 致癌性证据

A3：已确认对动物有致癌性，但对人类的相关性未知。/二硝基甲苯/

A3: Confirmed animal carcinogen with unknown relevance to humans. /Dinitrotoluene/

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：2,4-二硝基甲苯

IARC Carcinogenic Agent:2,4-Dinitrotoluene

来源:International Agency for Research on Cancer (IARC)

吸收、分配和排泄

单次口服给药后，大鼠血液中的放射性在给药后6小时达到最高值，半衰期约为22小时，肝脏中的最高浓度出现在6小时后。大约有10%在24小时内排入胆汁。粪便排泄在给药后6-9小时达到最大值，尿液排泄在给药后6小时达到最大值。

AFTER SINGLE ORAL ADMIN OF (3)H 2,4-DNT TO RATS, RADIOACTIVITY IN BLOOD REACHED MAX 6 HR AFTER ADMIN WITH A HALF-LIFE OF APPROX 22 HR, MAX LEVEL IN LIVER OCCURRED AFTER 6 HR. ABOUT 10% EXCRETED INTO BILE WITHIN 24 HR. FECAL EXCRETION MAX 6-9 HR & URINARY WAS MAX 6 HR AFTER ADMIN.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

在A型小鼠中，尿液是2,4-二硝基甲苯（2,4-DNT）的主要排泄途径，1、10和100毫克/千克的腹腔注射剂量分别有52.5%、60.1%和70.0%在给药后4小时内排出。在所有剂量下，肝脏和小肠对其进行了快速而广泛的代谢。

IN STRAIN A MICE, THE URINE WAS THE MAJOR ROUTE OF ELIMINATION FOR 2,4-DINITROTOLUENE (2,4-DNT), WITH 52.5, 60.1, AND 70.0% OF IP DOSES OF 1, 10, AND 100 MG/KG, RESPECTIVELY, EXCRETED WITHIN 4 HR AFTER ADMIN. AT ALL DOSES RAPID AND EXTENSIVE METAB BY THE LIVER AND SMALL INTESTINE WAS OBSERVED.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

尿和粪便排泄以及摄入0.5% 2,4-DNT饮食4个月的大鼠体内(3)H标记的2,4-DNT的分布进行了研究。排泄和分布研究显示，肝脏、皮肤和脂肪组织积累了未改变的2,4-DNT和/或其代谢物。

THE CHANGE IN THE URINARY AND FECAL EXCRETIONS AND DISTRIBUTION OF (3)H LABELED 2,4-DNT IN RATS INGESTING A 0.5% 2,4-DNT DIET FOR 4 MO WAS STUDIED. EXCRETION AND DISTRIBUTION STUDIES SHOWED THAT THE LIVER, SKIN, AND THE ADIPOSE TISSUE ACCUMULATED THE UNCHANGED 2,4-DNT AND/OR ITS METABOLITES.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

二硝基甲苯排泄量超过25毫克/升，表明在工业暴露人群中吸收显著。/二硝基甲苯/

Excretion of dinitrotoluene in excess of 25 mg/L indicates significant absorption /in industrial exposed populations/. /Dinitrotoluene/

来源:Hazardous Substances Data Bank (HSDB)

安全信息

• 危险品标志：
  T,N
• 安全说明：
  S45,S53,S61
• 危险类别码：
  R51/53,R48/22,R45,R23/24/25,R62,R68
• WGK Germany：
  3
• RTECS号：
  XT1575000
• 海关编码：
  2904203000
• 包装等级：
  II
• 危险类别：
  6.1
• 危险品运输编号：
  UN 2038/1600/3454

反应信息

• 作为反应物：
  描述：

  2,4-二硝基甲苯 在 吡啶 、 甲醇 、 碘 作用下， 生成 2,2',4,4'-tetranitrostilbene
  参考文献：
  名称：

  Green; Baddiley, Journal of the Chemical Society, 1908, vol. 93, p. 1724

  摘要：

  DOI：
• 作为产物：
  描述：

  4-硝基甲苯 在 甲烷磺酸 、 二氧化氮 、 臭氧 作用下， 以 二氯甲烷 为溶剂， 生成 2,4-二硝基甲苯
  参考文献：
  名称：

  A non-acid methodology for polynitration of arenes at low temperatures

  摘要：

  在臭氧和适当催化剂的存在下，氮氧化物在低温下作为强硝化剂，将芳香烃高效地转化为多硝基衍生物。

  DOI：

  10.1039/c39910001049
• 作为试剂：
  描述：

  4-硝基甲苯 、 硝酸 、 硫酸 、 二氯甲烷 在 二氯甲烷 、 水 、 2,4-二硝基甲苯 作用下， 反应 3.0h， 以leaving 90.2 g of dinitrotoluene containing 99% of 2,4-dinitrotoluene (98% of the的产率得到二硝基甲苯
  参考文献：
  名称：

  Process for the production of nitro derivatives of aromatic compounds

  摘要：

  若要获得难以硝化的芳香族化合物的硝基衍生物，则可以通过硝化处理来轻松地获得，只要在硝酸或其他硝化试剂的存在下，用卤素单取代或多取代的脂肪或环烷烃作为反应介质，然后分离出形成的硝基衍生物。

  公开号：

  US04036838A1

文献信息

• Compositions for Treatment of Cystic Fibrosis and Other Chronic Diseases
  申请人：Vertex Pharmaceuticals Incorporated

  公开号：US20150231142A1

  公开（公告）日：2015-08-20

  The present invention relates to pharmaceutical compositions comprising an inhibitor of epithelial sodium channel activity in combination with at least one ABC Transporter modulator compound of Formula A, Formula B, Formula C, or Formula D. The invention also relates to pharmaceutical formulations thereof, and to methods of using such compositions in the treatment of CFTR mediated diseases, particularly cystic fibrosis using the pharmaceutical combination compositions.

  本发明涉及含有上皮钠通道活性抑制剂与至少一种ABC转运蛋白调节剂化合物（A式、B式、C式或D式）的药物组合物。该发明还涉及这些药物配方，以及使用这些组合物治疗CFTR介导的疾病，特别是囊性纤维化的方法。
• Efficient Palladium(0) supported on reduced graphene oxide for selective oxidation of olefins using graphene oxide as a ‘solid weak acid’
  作者：Xi Gao、Jianhao Zhou、Xinhua Peng

  DOI：10.1016/j.catcom.2019.01.020

  日期：2019.3

  Selective oxidation of olefin derivatives to ketones has made innovative development over palladium(0) supported on reduced graphene oxide. Compared to traditional Wacker oxidation, the novel method offers an economical and environment-friendly option by using graphene oxide (GO) as a ‘solid weak acid’ instead of classical homogeneous catalysts like H2SO4 and CF3COOH. X-ray diffraction, X-ray photoelectron

  烯烃衍生物选择性氧化为酮的方法已在还原性氧化石墨烯上负载的钯（0）上取得了创新性的发展。与传统的Wacker氧化相比，该新方法通过使用氧化石墨烯（GO）作为“固体弱酸”，而不是像H 2 SO 4和CF 3 COOH这样的经典均相催化剂，提供了一种经济且环保的选择。Pd 0 / RGO的X射线衍射，X射线光电子能谱，扫描电子显微镜和透射电子显微镜图像表明，在还原的氧化石墨烯的薄片结构上产生了纳米级的Pd颗粒。在最佳条件下，最多可以制备44种结构不同的酮，并具有优异的收率。
• COMPOSITIONS FOR TREATMENT OF CYSTIC FIBROSIS AND OTHER CHRONIC DISEASES
  申请人：Van Goor Fredrick F.

  公开号：US20110098311A1

  公开（公告）日：2011-04-28

  The present invention relates to pharmaceutical compositions comprising an inhibitor of epithelial sodium channel activity in combination with at least one ABC Transporter modulator compound of Formula A, Formula B, Formula C, or Formula D. The invention also relates to pharmaceutical formulations thereof, and to methods of using such compositions in the treatment of CFTR mediated diseases, particularly cystic fibrosis using the pharmaceutical combination compositions.

  本发明涉及包含上皮钠通道活性抑制剂与至少一种ABC转运蛋白调节剂化合物（A式、B式、C式或D式）的药物组合物。该发明还涉及这些药物配方，以及使用这些组合物治疗CFTR介导的疾病，特别是囊性纤维化的方法。
• Synthesis of Indoles by Reductive Cyclization of Nitro Compounds Using Formate Esters as CO Surrogates
  作者：Manar Ahmed Fouad、Francesco Ferretti、Dario Formenti、Fabio Milani、Fabio Ragaini

  DOI：10.1002/ejoc.202100789

  日期：2021.9.14

  A very efficient, general and scalable protocol for the preparation of indoles and other N-heterocycles from suitably substituted nitroarenes using alkyl and phenyl formates as CO surrogates was described. Using phenyl formate, the products were isolated in yields often higher than those previously achieved by using gaseous CO. The mechanism of both the decarbonylation reaction of phenyl formate and

  描述了使用烷基和苯基甲酸酯作为 CO 替代物从适当取代的硝基芳烃制备吲哚和其他N-杂环的非常有效、通用和可扩展的方案。使用甲酸苯酯，产物的分离产率通常高于以前使用气态 CO 实现的产率。通过动力学和机理研究阐明了甲酸苯酯的脱羰反应和环化反应的机理。
• Non-pollutional process for producing aromatic nitro compounds without
  申请人：Nippon Kayaku Kabushiki Kaisha

  公开号：US05237077A1

  公开（公告）日：1993-08-17

  The present invention relates to a process for producing an aromatic nitro compound by introducing a nitrogen oxide gas and ozone-containing oxygen or air into a halogenated organic solvent dissolving or suspending therein an aromatic compound, thereby subjecting the aromatic compound to nitration. By the use of a system comprising the nitrogen oxide and ozone-containing oxygen or air as the nitrating agent, the aromatic nitro compound can be produced under mild conditions without using any mineral acid. In addition, the various disadvantages due to the use of mineral acid in the conventional process can be avoided by the process of the present invention.

  本发明涉及一种通过将一氧化氮气体和含臭氧的氧气或空气引入卤代有机溶剂中溶解或悬浮的芳香化合物，从而使芳香化合物经受硝化的生产芳香硝基化合物的方法。通过使用包含一氧化氮和含臭氧的氧气或空气作为硝化剂的系统，可以在不使用任何矿酸的温和条件下生产芳香硝基化合物。此外，通过本发明的方法可以避免传统工艺中使用矿酸所带来的各种缺点。

表征谱图