3-硝基-4-[N-(2-羟乙基)氨基]-N,N-二(2-羟乙基)苯胺 | 33229-34-4

• 物质功能分类: 生物化工 - 氨基酸及其衍生物 - 氨基醇类衍生物
• 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: 3-硝基-4-[N-(2-羟乙基)氨基]-N,N-二(2-羟乙基)苯胺
• 中文别名: 2,2'-[4-(2-羟基乙氨基)-3-硝基苯亚氨基]二乙醇胺；N1,N4,N4-三(2-羟乙基)-2-硝基-1,4-苯二胺；3-硝基-4-羟乙氨基-N,N-二羟乙基苯胺；2-3-硝基-4-[N-(2-羟乙基)氨基]-N,N-二(2-羟乙基)苯；3-硝基-4-(N-羟乙基氨基)N,N-二(羟乙基)苯胺；N-[4-[(2-羟乙基)氨基]-3-硝基苯基]二乙醇胺；HC 蓝 NO. 2；3-硝基-4-羟乙氨基-N,N-二羟乙基苯胺 (染发剂蓝二号)；染料红 2；HC 蓝 2号；HC蓝2号
• 英文名称: HC blue 2
• 英文别名: HC Blue No.2；HC Blue no. 2；2-[4-[bis(2-hydroxyethyl)amino]-2-nitroanilino]ethanol
• CAS: 33229-34-4
• 化学式: C₁₂H₁₉N₃O₅
• mdl: MFCD00071762
• 分子量: 285.3
• InChiKey: MIWUTEVJIISHCP-UHFFFAOYSA-N

物化性质

• 熔点：
  108-111 °C (lit.)
• 沸点：
  427.73°C (rough estimate)
• 密度：
  1.2263 (rough estimate)
• 溶解度：
  可溶于水
• LogP：
  0.01 at 20℃
• 物理描述：
  Hc blue 2 is a dark blue to dark brown microcrystalline powder. (NTP, 1992)
• 颜色/状态：
  Dark-blue microcrystalline (75% pure) or blackish-blue amorphous powder (98% pure), with a copper cast.

计算性质

• 辛醇/水分配系数(LogP)：
  0.4
• 重原子数：
  20
• 可旋转键数：
  8
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  122
• 氢给体数：
  4
• 氢受体数：
  7

ADMET

代谢

HC Blue No. 2（200微摩尔（57毫克））被从小鼠和大鼠中分离的肝细胞代谢，产生的轮廓与体内所见相似。高效液相色谱分离显示，HC Blue No. 2在小鼠体内被广泛代谢为一个主要代谢物，该代谢物尚未被鉴定。

Metabolism of HC Blue No. 2 (200 uM (57 mg) by hepatocytes isolated from mice and rats yielded profiles similar to those seen in vivo. High performance liquid chromatography separation showed that HC Blue No. 2 is metabolized extensively in mice to one major metabolite, which has not been characterized.

来源:Hazardous Substances Data Bank (HSDB)

代谢

早期研究显示，HC蓝1号能诱导B6C3F1小鼠发生肝细胞癌，而结构相似的硝基芳胺HC蓝2号则不会。...因此进行了比较代谢和遗传毒性研究。在雌性B6C3Fl小鼠口服灌胃（100毫克/千克）18小时后，两种化合物的尿液中放射性物质的回收量相当。通过高效液相色谱（HPLC）分析，HC蓝1号产生了3个主要极性代谢物峰，其中一个是可被葡萄糖醛酸酶水解的。HC蓝2号在体内的代谢产生了单一的主要代谢物峰，该峰不被葡萄糖醛酸酶水解。B6C3Fl小鼠肝细胞对HC蓝1号和HC蓝2号的代谢产生了与体内代谢观察到的轮廓定性地相似的代谢物轮廓。HC蓝1号在肝细胞中的代谢速率大约是HC蓝2号的两倍。对体外处理后的鼠肝细胞进行细胞遗传学评估表明，HC蓝1号在诱导染色体畸变方面比HC蓝2号更有效，而两种化学物质在诱导姐妹染色单体交换方面都显示出较弱的活动。此外，在V79细胞代谢合作试验中，HC蓝1号（而非HC蓝2号）抑制了细胞间的通信，这表明HC蓝1号可能具有非遗传毒性活性。...

Previous studies indicated that HC Blue 1 induced hepatocellular carcinomas in B6C3F1 mice whereas the structurally similar nitroaromatic amine HC Blue 2 did not. ... Comparative metabolism and genetic toxicity studies were undertaken. Eighteen hour urinary recovery of admin radioactivity was equivalent for both cmpd following oral gavage (100 mg/kg) in female B6C3Fl mice. By HPLC analysis, HC Blue 1 yielded 3 major polar metabolite peaks, one of which was susceptible to glucuronidase. In vivo metabolism of HC Blue 2 yielded a single major metabolite peak which was not hydrolyzed by glucuronidase. Metabolism by B6C3Fl mouse hepatocytes yielded metabolite profiles which were qualitatively similar to the profiles observed after in vivo metabolism. HC Blue 1 was metabolized by hepatocytes at approximately twice the rate of HC Blue 2. Cytogenetic evaluations of mouse hepatocytes after in vitro treatment indicated HC Blue 1 was more potent than HC Blue 2 in inducing chromosomal aberrations while both chemicals showed weak activity for inducing sister-chromatid exchanges. Furthermore, in the V79 cell metabolic cooperation assay, HC Blue 1, but not HC Blue 2, inhibited cell-to-cell communication suggesting a non-genotoxic activity may be present for HC Blue 1. ...

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 致癌性证据

致癌性分类：1）人类证据：不足；2）动物证据：不足。对人类致癌风险的总体评估为第3组：该物质对人类致癌性不可分类。

Classification of carcinogenicity: 1) evidence in humans: inadequate; 2) evidence in animals: inadequate. Overall summary evaluation of carcinogenic risk to humans is Group 3: The agent 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：HC蓝2号

IARC Carcinogenic Agent:HC Blue No. 2

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：对其对人类的致癌性无法分类

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57卷（1993年）：美发师和理发师的职业暴露及个人使用染发剂；一些染发剂、化妆品着色剂、工业染料和芳香胺

IARC Monographs:Volume 57: (1993) Occupational Exposures of Hairdressers and Barbers and Personal Use of Hair Colourants; Some Hair Dyes, Cosmetic Colourants, Industrial Dyestuffs and Aromatic Amines

来源:International Agency for Research on Cancer (IARC)

毒理性

• 非人类毒性摘录

50只雄性和雌性B6C3F1小鼠，七周大，被喂食含0、5000或10,000毫克/千克（ppm）（雄性）或0、10,000或20,000 ppm（雌性）HC蓝2号（约98%纯度）的饲料，持续104周，并在112-113周大时被处死。处理过的雄性小鼠的最终平均体重与对照组相似；然而，处理过的雌性小鼠的体重比对照组低15%（低剂量）和22%（高剂量）。研究结束时存活情况如下：雄性——对照组，50只中的24只；低剂量组，50只中的24只；高剂量组，50只中的34只；雌性——对照组，50只中的35只；低剂量组，50只中的28只；高剂量组，50只中的20只（p< 0.005，生命表测试）。雌性小鼠存活率降低归因于卵巢和子宫被克雷伯氏菌感染。没有观察到任何肿瘤发生率的显著增加。（工作组指出，雌性小鼠存活率降低妨碍了对研究的充分评估。）

Groups of 50 male and female B6C3F1 mice, seven weeks of age, were fed 0, 5000 or 10,000 mg/kg (ppm) (males) or 0, 10,000 or 20,000 ppm (females) HC Blue No. 2 (about 98% pure) in the diet for 104 weeks and were killed at 112-113 weeks of age. Final mean body weights of treated males were similar to those of controls; however, those of treated females were 15% (low-dose) and 22% (high-dose) lower than those of controls. Survival at the end of the study was: males--control, 24/50; low-dose, 24/50; and high-dose, 34/50; females-- control, 35/50; low-dose, 28/50; and high-dose, 20/50 (p< 0.005, life table test). The reduced survival of female mice was attributed to infection of the ovaries and uteri with Klebsiella sp. No significant increase in the incidence in any tumor was observed. (The Working Group noted that the reduced survival of females precluded adequate evaluation of the study.)

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

大约85克含有1.77% HC蓝2号的商业半永久性染发剂配方，其中富含每毫克378.6微居里的(14)C标记的HC蓝2号，被应用于人类志愿者的头发上，轻轻揉搓5-8分钟，并让其在头发和头皮上保持接触额外30分钟。30天后，尿液中的放射性标记物占不到应用的0.1%；一半在52小时后通过尿液排出。（工作组注意到尿液中未识别出代谢物，因此HC蓝2号在人体中的代谢命运仍然未知。）

About 85 g of a commercial semi-permanent hair dye formulation containing 1.77% HC Blue No. 2 enriched with 378.6 uCi/mg (14)C-labelled HC Blue No. 2 was applied to the hair of human volunteers, worked in gently for 5-8 min and allowed to remain in contact with the hair and scalp for an additional 30 min. After 30 days, radiolabel accounting for less than 0.1% of that applied was detected in the urine; half was excreted in urine after 52 hr. (The Working Group noted that urinary metabolites were not identified, so that the metabolic fate of HC Blue No. 2 in humans remains unknown.)

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

在给B6C3F1小鼠和Fischer 344/N大鼠口服灌胃100 mg/kg bw (14)C标记的HC蓝No. 2（0.1 mCi/mmol (35 uCi/mg); 98%纯度）后，高达40%的放射性标记物在尿液中回收。

Up to 40% of radiolabel was recovered in the urine of B6C3F1 mice and Fischer 344/N rats after oral administration by gavage of 100 mg/kg bw (14)C-labelled HC Blue No. 2 (0.1 mCi/mmol (35 uCi/mg); 98% pure).

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

HC蓝2号作为染发剂中色素的安全性已根据现有数据进行了评估。... 在B6C3F1小鼠体内进行的代谢放射性分析显示，不到5%的初始放射性以母化合物形式排出；其余以更具极性的代谢物形式排出，大部分集中在一个峰。体外代谢研究表明，产生了β-葡萄糖醛酸酶代谢物。...

The safety of HC Blue No 2 for use as a colorant in hair dyes was evaluated, based on a review of available data. ... An in vivo metabolic radioassay with B6C3F1 mice indicated less than 5% of the initial radioactivity was excreted as the parent cmpd; the remainder was excreted as more polar metabolites, with the majority in one peak. An in vitro metabolic study indicated the production of a beta-glucuronidase metabolite. ...

来源:Hazardous Substances Data Bank (HSDB)

安全信息

• 危险品标志：
  Xi
• 安全说明：
  S26,S36
• 危险类别码：
  R36/37/38
• WGK Germany：
  1
• 海关编码：
  2922199090
• RTECS号：
  KL2880000
• 危险性防范说明：
  P261,P305+P351+P338
• 危险性描述：
  H315,H319,H335

制备方法与用途

化学性质：深蓝紫色的结晶粉末。

用途：主要用于医药和染料中间体。

反应信息

• 作为反应物：
  描述：

  3-硝基-4-[N-(2-羟乙基)氨基]-N,N-二(2-羟乙基)苯胺 在 ammonium hydroxide 、 sodium sulfite 作用下， 以 甲醇 为溶剂， 反应 144.0h， 以80%的产率得到N-(4-氨基-3-硝基苯基)二乙醇胺
  参考文献：
  名称：

  Unusual reaction of 1,4-diamino-2-nitrobenzene derivatives toward nucleophiles: Catalysis by sodium sulphite

  摘要：

  Unusual substitution of amino group occurs by reactions of some 1,4-diamino-2-nitrobenzenes (semipermanent hair dyes) and nucleophiles (NH3, H2O). The reaction is catalyzed by sodium sulfite. The obtained products are suspected of being toxic substances which may he present in cosmetic matrices. Apparently, this reaction is a nucleophilic aromatic substitution hut it may be explained by a mechanism involving a tautomeric form of substrate. (C) 1998 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0040-4020(98)00181-1

文献信息

• [EN] NEW COSMETIC COMPOSITIONS COMPRISING CATIONIC DYES AND PROCESS FOR DIRECT DYEING OF KERATIN FIBERS<br/>[FR] NOUVELLES COMPOSITIONS COSMÉTIQUES COMPRENANT DES COLORANTS CATIONIQUES, ET PROCÉDÉ DE COLORATION DIRECTE DE FIBRES DE KÉRATINE
  申请人：ALFA PARF GROUP S P A

  公开号：WO2014202152A1

  公开（公告）日：2014-12-24

  The present invention relates to new compositions for dyeing keratin fibers comprising, in a medium suitable for dyeing, one or more cationic dye of general formula (I) or (II), or a physiologically tolerated adduct thereof with an acid: (II), as well as to a process for dyeing keratin fibers comprising one or more cationic dye of general formula (I) or (II), or a physiologically tolerated adduct thereof with an acid.

  本发明涉及用于染色角蛋白纤维的新组合物，所述组合物包括适用于染色的介质中的一个或多个阳离子染料，其具有一般式(I)或(II)，或其与酸的生理耐受加合物：(II)，以及一种用于染色角蛋白纤维的方法，包括使用一个或多个具有一般式(I)或(II)的阳离子染料，或其与酸的生理耐受加合物。
• COLORING AGENTS AND METHODS OF USE THEREOF
  申请人：Living Proof, Inc.

  公开号：US20160106648A1

  公开（公告）日：2016-04-21

  Dyes, compositions comprising dyes and methods for using the same are provided.

  染料、包含染料的组合物以及使用这些染料的方法。
• Symmetrical diazo compounds containing 2-pyridinium groups and a cationic or non-cationic linker, compositions comprising them, method of coloring, and device
  申请人：David Herve

  公开号：US20060156488A1

  公开（公告）日：2006-07-20

  The present disclosure relates to symmetrical cationic diazo compounds of formula (I), the resonance forms, and also the acid addition salts and/or the solvates thereof: The present disclosure further relates to dyeing compositions comprising such compounds as a direct dye in a medium appropriate for the dyeing of keratin fibers, and also to a method of coloring keratin fibers that employs this composition, and a multi-compartment kit containing such compositions.

  本公开涉及公式（I）的对称阳离子重氮化合物，其共振式形式，以及其酸盐和/或溶剂化合物：本公开还涉及包含此类化合物作为直接染料的染料组合物，在适用于染色角蛋白纤维的介质中，以及使用该组合物进行染色角蛋白纤维的方法，以及包含这种组合物的多室套件。
• [DE] NEUE THIAZOLYLMETHYL-PYRAZOLE, VERFAHREN ZU DEREN HERSTELLUNG SOWIE DEREN VERWENDUNG IN FÄRBEMITTELN FÜR KERATINFASERN<br/>[EN] NOVEL THIAZOLYLMETHYL PYRAZOLES, METHOD FOR THE PRODUCTION THEREOF, AND USE THEREOF IN DYES FOR KERATIN FIBERS<br/>[FR] NOUVEAUX THIAZOLYLMETHYLE-PYRAZOLES, PROCEDE DE REALISATION ET UTILISATION DANS DES COLORANTS POUR FIBRES DE KERATINE
  申请人：WELLA AG

  公开号：WO2004106332A1

  公开（公告）日：2004-12-09

  4,5-Diaminopyrazole der allgemeinen Formel (I), worin R eine geradkettige oder verzweigte eine Cl -C6-Alkylgruppe, eine unsubstituierte Phenylgruppe oder eine einfach oder mehrfach substituierte Phenylgruppe darstellt, worin die Substituenten an der Phenylgruppe unabhängig voneinander ausgewählt werden können aus einem Halogenatom, einer C1-C6-Carbonsäureestergruppe, einer geradkettigen oder verzweigten Cl -C6-Alkoxygruppe, einer durch ein oder zwei Heteroatome unterbrochenen geradkettigen oder verzweigten C1-C6-Alkoxygruppe, einer Hydroxyethoxygruppe, einer Dihydroxypropoxygruppe oder einer Nitrilgruppe; diese Verbindungen enthaltende Oxidationsfärbemittel für Keratinfasern sowie Verfahren zur Herstellung dieser Verbindungen.

  通用式（I）的4,5-二氨基吡唑衍生物，其中R代表一条直链或支链的Cl-C6烷基基团，一个未取代的苯基团或一个简单或多取代的苯基团，其中苯基团上的取代基可以独立地选择为卤素原子、一条直链或支链的Cl-C6烷氧基基团、一条被一个或两个杂原子中断的直链或支链的C1-C6烷氧基基团、羟基乙氧基基团、二羟基丙氧基基团或腈基；含有这些化合物的角蛋白纤维氧化染料以及制备这些化合物的方法。
• Dyeing processes comprising at least one multi-carbosite, multi-group coupling agent for wash-protecting the color of artificially dyed keratin fibers
  申请人：Lalleman Boris

  公开号：US20080313821A1

  公开（公告）日：2008-12-25

  Disclosed herein is a cosmetic process for wash-protecting the color of artificially dyed keratin fibers, comprising applying to the keratin fibers at least one composition comprising at least one multi-carbosite, multi-group coupling agent, the coupling agent being an electrophilic hydrocarbon-based compound comprising neither an aldehyde group, nor a carboxylic acid group, nor a formol-generating group, the coupling agent comprising at least two identical reactive groups, the reactive groups not being carried by the same atom, if said atom is a carbon atom, and the coupling agent having a molecular weight of less than 500 g/mol.

  本文揭示了一种用于保护人工染色角蛋白纤维颜色的化妆过程，包括将至少一种包含至少一种多羟基化合物的组合物应用于角蛋白纤维，该耦合剂是一种电泳烃基化合物，既不包含醛基，也不包含羧酸基，也不包含甲醛生成基团，该耦合剂包括至少两个相同的反应基团，这些反应基团不由同一原子携带，如果该原子是碳原子，则该耦合剂的分子量小于500克/摩尔。

表征谱图