1,2-二甲基肼 | 540-73-8

• 分子结构分类: 有机化合物 - 有机氮化合物
• 中文名称: 1,2-二甲基肼
• 中文别名: 1,2-二甲肼；1，2-二甲基肼；对称二甲基肼
• 英文名称: 1,2-Dimethylhydrazine
• 英文别名: DMH；N,N’-dimethylhydrazine
• CAS: 540-73-8
• 化学式: C₂H₈N₂
• mdl: MFCD01741277
• 分子量: 60.0989
• InChiKey: DIIIISSCIXVANO-UHFFFAOYSA-N

物化性质

• 稳定性/保质期：

  1. 稳定性：稳定。

  2. 禁配物：氧化剂、铜及其合金、铁、铁盐。

  3. 避免接触的条件：受热。

  4. 聚合危害：不聚合。

计算性质

• 辛醇/水分配系数(LogP)：
  -0.4
• 重原子数：
  4
• 可旋转键数：
  1
• 环数：
  0.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  24.1
• 氢给体数：
  2
• 氢受体数：
  2

ADMET

代谢

人和大鼠的结肠都能激活1,2-二甲基肼（1,2-DMH）成为能与细胞大分子反应的化学物质。当比较人和大鼠的结肠时，1,2-二甲基肼的代谢在性质上是相似的，导致了相同的 主要致癌DNA加合物和代谢轮廓。然而，1,2-二甲基肼与结肠DNA的平均结合水平在大鼠中高于人类。

Both human and rat colon activate 1,2-dimethylhydrazine (1,2-DMH) into chemical species that reacted with cellular macromolecules. When human and rat colons were compared, the metabolism of 1,2-dimethylhyrazine was qualitatively similar, /resulting in/ the same major carcinogen DNA adducts and metabolic profile. However, the mean binding levels of 1,2-dimethylhydrazine to colonic DNA were higher in rats than in humans.

来源:Hazardous Substances Data Bank (HSDB)

代谢

N5-甲基-N5-甲酰基-2,5,6-三氨基-4-羟基嘧啶在用1,2-二甲肼处理的大鼠肝脏DNA中被鉴定出来。

N5-methyl-N5-formyl-2,5,6-triamino-4-hydroxypyrimidine was identified in rat liver DNA after treatment with 1,2-dimethylhydrazine.

来源:Hazardous Substances Data Bank (HSDB)

代谢

人类结肠微粒体催化1,2-二甲肼（1,2-DMH）的代谢。所有结肠段中的1,2-DMH代谢被细胞色素P450依赖的混合功能氧化酶系统的抑制剂显著抑制。

Human colon microsomes catalyze the metabolism of 1,2-dimethylhydrazine (1,2-DMH). 1,2-DMH metabolism in all colonic segments is inhibited significantly by inhibitors of the cytochrome p450 dependent mixed function oxidase system.

来源:Hazardous Substances Data Bank (HSDB)

代谢

1,2-二甲肼通过纯化的鼠肝微粒体混合功能胺氧化酶催化的N-氧化反应如下所示。

The N-oxidation of 1,2-dimethylhydrazine catalyzed by purified mouse liver microsomal mixed function amine oxidase is shown.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 致癌性证据

评估：关于1,2-二甲肼的致癌性，没有可用的流行病学数据。在实验动物中有充分的证据表明1,2-二甲肼具有致癌性。总体评估：1,2-二甲肼可能对人类致癌（2A组）。在进行总体评估时，工作组考虑到1,2-二甲肼在广泛的测试系统中一致地表现出诱变性，并且在体外的人类和动物组织中引起相似的DNA损伤模式。

Evaluation: No epidemiological data relevant to the carcinogenicity of 1,2-dimethylhydrazine were available. There is sufficient evidence in experimental animals for the carcinogenicity of 1,2-dimethylhydrazine. Overall evaluation: 1,2-Dimethylhydrazine is probably carcinogenic to humans (Group 2A). In making the overall evaluation, the Working Group took into account that 1,2-dimethylhydrazine is consistently mutagenic in a wide range of test systems and gives rise to a similar pattern of DNA damage in human and animal tissues in vitro.

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：1,2-二甲肼

IARC Carcinogenic Agent:1,2-Dimethylhydrazine

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：2A组：可能对人类致癌

IARC Carcinogenic Classes:Group 2A: Probably carcinogenic 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4卷：(1974年)一些芳香胺、肼及其相关物质，N-亚硝基化合物和杂类烷化剂 增补第7卷：致癌性的整体评估：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） 第71卷：(1999年)对一些有机化学品、肼和过氧化氢的再评估（第1部分，第2部分，第3部分）

IARC Monographs:Volume 4: (1974) Some Aromatic Amines, Hydrazine and Related Substances, N-Nitroso Compounds and Miscellaneous Alkylating Agents 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) Volume 71: (1999) Re-evaluation of Some Organic Chemicals, Hydrazine and Hydrogen Peroxide (Part 1, Part 2, Part 3)

来源:International Agency for Research on Cancer (IARC)

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)

吸收、分配和排泄

在给予大鼠(3)H-1,2-二甲基肼后15-30分钟，在血液、胆汁、尿液以及整个胃肠道的 content 中发现了显著的放射性。

15-30 min after (3)H-1,2-dimethylhydrazine was admin to rats, marked radioactivity was found in blood, bile, urine, and in contents of all regions of GI tract.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

1,2-二甲基肼在大鼠结肠中被很好地吸收，这一点通过体内灌注技术得到了证实。胆汁酸和羟基脂肪酸显著增强了吸收；而脂肪酸对吸收没有显著影响。

1,2-Dimethylhydrazine is well absorbed from the colon of the rat, as shown by an in vivo perfusion technique. The absorption was enhanced significantly by bile acids and by hydroxy-fatty acids; fatty acids had no significant effect.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

组织分布和3（H）与蛋白质、DNA和RNA的共价结合在大鼠中进行了研究，这些大鼠根据不同的剂量方案给予3（H]1,2-二甲基肼。在肝脏、肾脏、十二指肠、回肠和结肠中广泛存在共价结合，并且当每周给予大剂量时，这种结合比将相同剂量分成每日给予要大。然而，尽管每日给药导致肝微粒体中的细胞色素P450降低到对照组水平的47%，但每周给药没有影响。

The tissue distribution and covalent binding of 3(H ) was examined in rats given 3(H]1,2-dimethylhydrazine according to various dose schedules. There was widespread covalent binding to protein, DNA and RNA of liver, kidney, duodenum, ileum and colon and this was greater when a large dose was given weekly than when the same dose was divided and given daily. However, while daily dosing resulted in a loss of cytochrome P450 in hepatic microsomes to 47% of control levels, weekly dosing had no effect.

来源:Hazardous Substances Data Bank (HSDB)

制备方法与用途

用途

1. 用于有机合成中间体和高能火箭燃料。[21]

反应信息

• 作为反应物：
  描述：

  1,2-二甲基肼 在 mercury(II) oxide 作用下， 以 水 为溶剂， 生成 cis-1,2-dimethyldiazene
  参考文献：
  名称：

  Quantitative Studies of Methyl Radicals Reacting with Metal Oxides

  摘要：

  The reactive sticking coefficients of CH3. radicals, produced by the thermal decomposition of azomethane, were determined over ZnO, CeO2, La2O3, Sr/La2O3, and Li/MgO at 650 degrees C. The intrinsic sticking coefficients ranged from 6 x 10(-8) for La2O3 activated at 900 degrees C to 3 x 10(-5) over ZnO. In the presence of even 0.1 mTorr of O-2 the sticking coefficient for the La2O3 sample increased to 3 x 10(-6). Although the other nonreducibie oxides exhibited similar behaviors, the magnitude of the effect was not as great, Methyl radicals are believed to react via electron transfer at the surface. The electron transfer may be either to metal ions, in the case of reducible oxides, or to O-2, in the case of nonreducible oxides. Reactions of CH3. radicals with several high surface area, porous silicas and zeolites were also studied. The sticking coefficient on a high-purity silica was found to be 1 x 10(-8) at 200 degrees C. An analysis of the stable products indicated that the reaction of CH3. radicals with these surfaces exceeded the coupling reactions that might have occurred at the surfaces. That is, the surfaces did not function as an effective ''third body'' in the coupling reaction.

  DOI：

  10.1021/j100039a042
• 作为产物：
  描述：

  cis-1,2-dimethyldiazene 在 sodium hydroxide 、 锌 作用下， 生成 1,2-二甲基肼
  参考文献：
  名称：

  Thiele, Chemische Berichte, 1909, vol. 42, p. 2580

  摘要：

  DOI：
• 作为试剂：
  描述：

  Bis-(1,1-dimethyl-2-phenethyl)-diaziridinon 在 1,2-二甲基肼 作用下， 以 苯 为溶剂， 生成 N,N'-bis-(1,1-dimethyl-2-phenyl-ethyl)-urea
  参考文献：
  名称：

  Diaziridinones. III. Reactions with hydrazines. Isomerization of diaziridinones to aziridinecarboxamides by hydrazine catalysis

  摘要：

  DOI：

  10.1021/jo01260a006

文献信息

• Nucleophilic Reactivities of Hydrazines and Amines: The Futile Search for the α-Effect in Hydrazine Reactivities
  作者：Tobias A. Nigst、Anna Antipova、Herbert Mayr

  DOI：10.1021/jo301497g

  日期：2012.9.21

  groups increase the reactivities of the α-position of hydrazines, they decrease the reactivities of the β-position. Despite the 102 times lower reactivities of amines and hydrazines in water than in acetonitrile, the relative reactivities of differently substituted amines and hydrazines are almost identical in the two solvents. In both solvents hydrazine has a reactivity similar to that of methylamine.

  胺，肼，酰肼和羟胺与苯甲酸铵离子和醌甲基化物的反应动力学通过紫外可见光谱法，在乙腈和水中，使用常规光谱仪，定流和激光闪光技术进行了研究。从这些反应的二阶速率常数k 2，根据线性自由能关系log k 2＝s N（N + E）确定亲核参数N和s N。尽管甲基增加了肼的α-位置的反应性，但它​​们却降低了β-位置的反应性。尽管10 2胺和肼在水中的反应性比乙腈低两倍，不同取代的胺和肼的相对反应性在两种溶剂中几乎相同。在两种溶剂中，肼的反应性都与甲胺类似。这一观察结果暗示，如果考虑到肼具有两个反应中心，Me取代氨中的一个氢比引入氨基更能增加亲核性。log k 2与相应的平衡常数（log K）或布朗斯台德碱度（p K aH）的关系图未显示相对于烷基胺而言，肼或羟胺的亲核性（α效应）增强。
• Synthesis of Ring-Substituted Phenyl Hydrazinecarboxylates and Study of Their Protonation in Dimethyl Sulfoxide Solutions
  作者：Petr Vlasák、Patrik Pařík、Jiří Klicnar、Jaromír Mindl

  DOI：10.1135/cccc19980793

  日期：——

  The pK_a values of nineteen phenyl hydrazinecarboxylate hydrochlorides R-C₆H₄OCONHNH₂·HCl (R = H, 3- and 4-Cl, 3- and 4-O₂N, 4-Me) and their 1-methyl or 2-methyl derivatives were determined by potentiometric titration with tetrabutylammonium hydroxide in DMSO. IR spectra of the hydrazinecarboxylates and their hydrochlorides revealed that the hydrazinecarboxylate protonation occurs at N². The methods of synthesis of phenyl hydrazinecarboxylate and their N-methyl derivatives were optimized.

  十九种苯基肼羧酸盐盐酸盐R-C6H4OCONHNH2·HCl（R = H，3-和4-Cl，3-和4-O2N，4-Me）及其1-甲基或2-甲基衍生物的pKa值通过在DMSO中与四丁基铵氢氧化物进行电位滴定确定。肼羧酸盐及其盐酸盐的红外光谱表明肼羧酸盐的质子化发生在N2处。苯基肼羧酸盐及其N-甲基衍生物的合成方法已经优化。
• Synthesis of tetrahydrophthalazine and phthalamide (phthalimide) derivatives via palladium-catalysed carbonylation of iodoarenes
  作者：Diána Marosvölgyi-Haskó、Andrea Petz、Attila Takács、László Kollár

  DOI：10.1016/j.tet.2011.09.095

  日期：2011.11

  4-Tetrahydrophthalazin-1-one and 1,2,3,4-tetrahydrophthalazin-1,4-dione derivatives were synthesised in high (up to 85%) and low yields using 2-iodobenzyl bromide and 1,2-diiodobenzene as bifunctional substrates, respectively. Iodoarenes, carbon monoxide and various hydrazine derivatives as N-nucleophiles were used in a three-component palladium-catalysed cascade hydrazinocarbonylation. A similar palladium-catalysed

  1,2,3,4-四氢酞嗪-1-酮和1,2,3,4-四氢酞嗪-1,4-二酮衍生物是使用2-碘代苄基溴和1的高产率（高达85％）和低产率合成的，2-二碘苯分别作为双功能底物。碘芳烃，一氧化碳和各种作为N-亲核试剂的肼衍生物被用于三组分钯催化的级联肼羰基化反应中。类似的钯催化反应，即1,2-二碘苯的氨基羰基化反应，主要导致形成两种主要产物，具体取决于胺N-亲核试剂：使用伯胺可产生N取代的邻苯二甲酰亚胺进行双羰基化，同时仲胺与碘芳烃官能团之一反应，得到相应的2-碘代苯甲酰胺。由于在一个或两个碘代芳烃官能团处插入一氧化碳两次，可以通过改变反应条件来分离出酮羧酰胺-羧酰胺或双酮羧酰胺衍生物。还讨论了闭环反应的一些机理细节和导致副产物的条件。
• Implementation of a combinatorial cleavage and deprotection scheme. 1. Synthesis of phthalhydrazide libraries
  作者：John Nielsen、Palle H. Rasmussen

  DOI：10.1016/0040-4039(96)00544-8

  日期：1996.5

  Phthalhydrazide libraries are synthesized in solution from substituted hydrazines and phthalimides in several different library formats including single compounds, indexed sub-libraries and a full library. When carried out during solid-phase synthesis, this combinatorial cleavage and deprotection scheme offers the possibility for generating a diverse library of substituted phthalhydrazides.

  邻苯二甲酰肼库是由取代的肼和邻苯二甲酰亚胺以几种不同的库格式在溶液中合成的，包括单一化合物，索引子库和完整的库。当在固相合成过程中进行时，这种组合的裂解和脱保护方案为生成取代的邻苯二甲酰肼的多样化文库提供了可能性。
• Über die Carbamoylierung von Hydrazin-Derivaten
  作者：G. Zinner、K. Dörschner

  DOI：10.1002/ardp.19733060107

  日期：——

  Die Bildung von Semicarbaziden bzw. 1.2‐Biscarbamoylhydrazinen aus Methylhydrazin, 1.2‐Dialkylhydrazinen, 3‐Methylpyrazolidin, 3.3‐Pentamethylendiaziridin und seinem 1‐Methyl‐Derivat mit verschiedenen Isocyanaten wird vergleichend untersucht und die Synthese der direkt nicht zugänglichen 4‐subst. 1‐Methylsemicarbazide beschrieben. 1‐Phenylcarbamoyl‐3.3‐pentamethylen‐diaziridin lagert sich beim Schmelzen

  比较了由甲基肼、1.2-二烷基肼、3-甲基吡唑烷、3.3-五亚甲基二氮丙啶及其1-甲基衍生物与各种异氰酸酯形成氨基脲或1.2-双氨基甲酰肼的过程，并比较了直接无法获得的4-subst的合成。1-甲基氨基脲已被描述。1-苯基氨基甲酰基-3.3-五亚甲基-二氮丙啶在熔化时重排为环己酮-（4-苯基-氨基脲）。

表征谱图