2-硝基-1,4-苯二胺 | 183870-67-9

• 物质功能分类: 有机原料 - 氨基化合物 - 环烷胺、芳香单胺、芳香多胺及其衍生物和盐
• 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-硝基-1,4-苯二胺
• 中文别名: 2-硝基-P-苯二胺；硝基对苯基二胺；1,4-二氨基-2-硝基苯；2-硝基对苯二胺；邻硝基对苯二胺；2-硝基对苯基二胺；2-硝基对亚苯基二胺
• 英文名称: 2-nitro-1,4-phenylenediamine
• 英文别名: 2-nitrobenzene-1,4-diamine；1,4-diamino-2-nitrobenzene；2-Nitro-P-phenylenediamine
• CAS: 183870-67-9；5307-14-2
• 化学式: C₆H₇N₃O₂
• mdl: MFCD00007903
• 分子量: 153.14
• InChiKey: HVHNMNGARPCGGD-UHFFFAOYSA-N

物化性质

• 熔点：
  135-138 °C (lit.)
• 沸点：
  276.04°C (rough estimate)
• 密度：
  1.3682 (rough estimate)
• 溶解度：
  水中的溶解度0.2克/升
• LogP：
  0.53
• 物理描述：
  Almost black needles with dark-green luster or black powder. (NTP, 1992)
• 颜色/状态：
  Almost black needles with dark-green luster
• 蒸汽压力：
  5.60X10-5 mm Hg at 25 °C (est)
• 稳定性/保质期：

  常温常压下稳定，黑色针状并带有深绿色光泽。

计算性质

• 辛醇/水分配系数(LogP)：
  0.5
• 重原子数：
  11
• 可旋转键数：
  0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  97.9
• 氢给体数：
  2
• 氢受体数：
  4

ADMET

代谢

雄性和雌性大鼠成对通过插管或腹腔注射0.5毫升的/2-硝基-p-苯二胺/(2NPPD) (14C)，溶解在5%的吐温80中。... 尿液中检测到六种代谢物和微量的未改变的2NPPD；这些代谢物包括乙酰化的2NPPD、2NPPD及其乙酰化产物的亚硫酸盐和/或葡萄糖醛酸苷共轭物，以及与含硫氨基酸形成的两种共轭物。在粪便中也发现了类似的代谢物。

Pairs of male and female rats were intubated or injected intraperitoneally with 0.5 mL of /2-nitro-p-phenylenediamine/ (2NPPD) (14C) in 5 percent Tween 80. ... There were six metabolites and a trace of unchanged 2NPPD in the urine; the metabolites were acetylated 2NPPD, sulfite and/or glucuronide conjugates of 2NPPD and of acetylated 2NPPD, and two conjugates with sulfur-containing amino acids. Similar metabolites were found in the feces.

来源:Hazardous Substances Data Bank (HSDB)

代谢

在人鼠皮肤中，2-硝基对苯二胺（2NPPD）被代谢为三氨基苯和N4-乙酰-2NPPD。在大鼠皮肤中，2NPPD还代谢为硫酸化2NPPD代谢物，但在人皮肤中不会。当使用乙醇时，2NPPD在人鼠皮肤中广泛代谢；使用半永久染发剂配方时，代谢并不广泛。在大鼠肠组织中，62%的2NPPD在吸收后被代谢为三氨基苯和N4-乙酰-2NPPD。在皮肤和肠组织之间，代谢谱（形成每种代谢物的比例）存在差异。这些结果表明，2NPPD在皮肤和肠组织中迅速吸收并广泛代谢。代谢程度和代谢谱取决于物种、组织和给药载体。

... In human and rat skin, 2-nitro-p-phenylenediamine (2NPPD) was metabolized to triaminobenzene and N4-acetyl-2NPPD. 2NPPD was also metabolized to a sulfated 2NPPD metabolite in rat skin, but not in human skin. 2NPPD was extensively metabolized in both human and rat skin with ethanol application; metabolism was not as extensive with a semipermanent /hair dye/ formulation application. In rat intestinal tissue, 62% of 2NPPD was metabolized upon absorption to triaminobenzene and N4-acetyl-2NPPD. Differences in the metabolic profiles (proportion of each metabolite formed) were found between the skin and intestinal tissue. These results suggest that 2NPPD is rapidly absorbed and extensively metabolized in both skin and intestinal tissue. The extent of metabolism and the metabolic profile were found to be species-, tissue-, and dosing vehicle-dependent. ...

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 致癌性证据

评估：对人类没有数据。1,4-二氨基-2-硝基苯对动物致癌性的证据不足。总体评估：第3组：1,4-二氨基-2-硝基苯对人类致癌性不可分类。

Evaluation: There is no data for humans. There is inadequate evidence of the carcinogenicity of 1,4-diamino-2-nitrobenzene in animals. OVERALL EVALUATION: Group 3: 1,4-diamino-2-nitrobenzene is not classifiable as to its carcinogenicity to humans.

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：1,4-二氨基-2-硝基苯

IARC Carcinogenic Agent:1,4-Diamino-2-nitrobenzene

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：第3组：无法归类其对人类致癌性

IARC Carcinogenic Classes:Group 3: Not classifiable as to its carcinogenicity to humans

来源:International Agency for Research on Cancer (IARC)

毒理性

• 致癌物分类

国际癌症研究机构专著：第7卷补充：致癌性的总体评估：更新国际癌症研究机构专著第1至42卷，1987年；440页；ISBN 92-832-1411-0（已绝版）

IARC Monographs:Volume Sup 7: Overall Evaluations of Carcinogenicity: An Updating of IARC Monographs Volumes 1 to 42, 1987; 440 pages; ISBN 92-832-1411-0 (out of print)

来源:International Agency for Research on Cancer (IARC)

毒理性

• 暴露途径

这种物质可以通过皮肤被吸收进身体。

The substance can be absorbed into the body through the skin.

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

吸收、分配和排泄

在一个实验中，将2到3只大鼠分组，每只大鼠的10平方厘米皮肤上涂抹了含有0.025%到0.48%对硝基对苯二胺（2NPPD）（14C）的200微升50%染发剂基质，持续五分钟。之后冲洗掉基质，并贴上一个48小时的非封闭型贴片。随着2NPPD浓度的增加，皮肤渗透也增加，并且与2NPPD浓度成正比；在0.025% 2NPPD时为0.01微克/平方厘米，而在0.48% 2NPPD时为3.2%。

/In an/ ... experiment conducted with groups of 2 to 3 rats, each rat was treated with 200 uL of 50 % hair colorant base containing 0.025 to 0.48 % /2-nitro-p-phenylenediamine/ (2NPPD) (14C) on 10 sq cm of skin for five minutes. The base was rinsed off, and a 48-hour nonocclusive patch was applied. Skin penetration increased with increasing 2NPPD concentration and was proportional to 2NPPD concentration; it was 0.01 ug/sq cm with 0.025 % 2NPPD and 3.2% with 0.48 % 2NPPD.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

雄性和雌性大鼠成对进行插管或腹腔注射0.5毫升的2-硝基对苯二胺（2NPPD）(14C)在5%的吐温80中。呼出的空气在24小时内进行放射性检测，尿液和粪便也进行了检测。呼出的空气中没有放射性。在3天后，应用的放射性中有1到2%在尸体中。排泄速率很快；在24小时内，85到90%的应用的放射性在尿液和粪便中被回收。在3天内，48到68%在粪便中被回收，27到41%在尿液中。尿液中发现了六种代谢物和微量的未改变的2NPPD；这些代谢物包括乙酰化的2NPPD，2NPPD及其乙酰化产物的亚硫酸盐和/或葡萄糖醛酸苷共轭物，以及两种含硫氨基酸的共轭物。在粪便中也发现了类似的代谢物。

Pairs of male and female rats were intubated or injected intraperitoneally with 0.5 mL of /2-nitro-p-phenylenediamine/ (2NPPD) (14C) in 5 percent Tween 80. Expired air was assayed for radioactivity for 24 hours, and urine and feces were assayed. No radioactivity was in expired air. At 3 days, 1 to 2 percent of the applied radioactivity was in the carcass. The rate of excretion was rapid; 85 to 90 percent of the applied radioactivity was recovered in the urine and the feces within 24 hours. Over 3 days, 48 to 68 percent was recovered in the feces and 27 to 41 percent in the urine. There were six metabolites and a trace of unchanged 2NPPD in the urine; the metabolites were acetylated 2NPPD, sulfite and/or glucuronide conjugates of 2NPPD and of acetylated 2NPPD, and two conjugates with sulfur-containing amino acids. Similar metabolites were found in the feces.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

/2-硝基-p-苯二胺/(2NPPD) (14C) 以2.6毫克/千克的剂量通过腹腔注射给大鼠...并监测其排泄。在24小时内，几乎92%的放射性被排出；37.4%在尿液中，54.3%在粪便中。4天后，96%的放射性已被排出。...

/2-nitro-p-phenylenediamine/ (2NPPD) (14C) was administered intraperitoneally in a dose of 2.6 mg/kg to rats ... and excretion was monitored. Within 24 hours, almost 92 percent of the radioactivity was excreted; 37.4 percent was in the urine and 54.3 percent was in the feces. After 4 days, 96 percent of the radioactivity had been excreted. ...

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

... 在体外研究中，对2-硝基-p-苯二胺（2NPPD）在人及模糊大鼠皮肤和大鼠空肠组织中的吸收和代谢进行了测量。... 在人皮肤中，24小时内吸收的总施用剂量百分比（受体液+皮肤）为9.2 +/- 5.7（平均值 +/- 标准差）和9.5 +/- 3.2，分别对应于乙醇和半永久性染发剂载体，大约有3%残留在皮肤中。在大鼠皮肤中，24小时内吸收的总施用剂量百分比为9.3 +/- 1.2（平均值 +/- 标准误）、6.9 +/- 1.2和4.2 +/- 0.1，分别对应于乙醇、半永久性和永久性配方载体，大约有3%残留在皮肤中。在大鼠肠组织中，24小时内吸收的总施用剂量百分比为10.9 +/- 1.2，大约有5%残留在组织中。...

... In vitro studies /were conducted/ to measure absorption and metabolism of 2-nitro-p-phenylenediamine (2NPPD) in human and fuzzy rat skin and rat jejunal tissue. ... In human skin, the percentages of total applied dose absorbed (receptor fluid + skin) over 24 hr were 9.2 +/- 5.7 (mean +/- SD) and 9.5 +/- 3.2 for ... ethanol and semipermanent /hair dye/ vehicles, respectively, with approximately 3% remaining in skin. In rat skin, the percentages of total applied dose absorbed over 24 hr were 9.3 +/- 1.2 (mean +/- SE), 6.9 +/- 1.2, and 4.2 +/- 0.1 for the ethanol, semipermanent, and permanent formulation vehicles, respectively, with approximately 3% remaining in skin. In rat intestinal tissue, the percentage of total applied dose absorbed over 24 hr was 10.9 +/- 1.2, with approximately 5% remaining in the tissue. ...

来源:Hazardous Substances Data Bank (HSDB)

安全信息

• TSCA：
  Yes
• 储存条件：
  避光，存放在阴凉干燥处，并密封保存。

制备方法与用途

用途

2-硝基对苯二胺，又称2-硝基-1,4-苯二胺，是一种重要的医药原料。它可用于合成瑞替加滨、艾普拉唑和依佐加滨等药物。

制备

制备过程分为三个步骤：

1. 第一步：将0.5摩尔（约103.1克）1,4-对苯二胺硫酸盐I、1.1摩尔（约231克）分析纯三氟乙酸酐、1.6摩尔（约162克）三乙基胺和250毫升分析纯二氯甲烷加入反应器中。在室温下充分搅拌1小时后，过滤得到142.5克N1,N4-二三氟乙酰基-对苯二胺II。

2. 第二步：将60.3克（0.2摩尔）的N1,N4-二三氟乙酰基-对苯二胺II加入到300毫升分析纯乙酸酐中，充分搅拌形成悬浮液。室温下向反应体系滴加25毫升分析纯浓硝酸，继续搅拌6小时后过滤。滤饼用200毫升水和200毫升分析纯乙酸乙酯各洗涤一次，干燥后得到36.3克N1,N4-二三氟乙酰基-2-硝基-对苯二胺III。

3. 第三步：将36.3克N1,N4-二三氟乙酰基-2-硝基-对苯二胺III、53克碳酸钠和400毫升水加入反应器中，加热回流1小时。室温下抽滤得到16.1克2-硝基对苯二胺。总产率为50%；产物为红黑色固体，熔点为136-137℃。

类别

有毒物品

毒性分级

中毒

急性毒性

• 口服：大鼠LD50: 2100毫克/公斤
• 腹腔注射：大鼠LD50: 348毫克/公斤

可燃性危险特性

可燃；燃烧时会产生有毒氮氧化物烟雾

储运特性

库房通风、低温干燥保存

灭火剂

干粉、泡沫、砂土、二氧化碳，或使用雾状水

反应信息

• 作为反应物：
  描述：

  2-硝基-1,4-苯二胺 在 palladium on activated charcoal 盐酸 、 氢气 、 sulfur 、 2,3-二甲基苯胺 作用下， 以 甲醇 、 异丙醇 、 乙腈 、 xylene 为溶剂， 25.0 ℃ 、101.33 kPa 条件下， 反应 11.0h， 生成 尿激酶
  参考文献：
  名称：

  Rajappa, S.; Sreenivasan, R., Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 1980, vol. 19, # 7, p. 539 - 541

  摘要：

  DOI：
• 作为产物：
  描述：

  4-amino-2-nitro-benzoyl azide