3,5-二硝基苄氯 | 74367-78-5

• 物质功能分类: 医药中间体 - 原料药中间体
• 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: 3,5-二硝基苄氯
• 中文别名: α-氯-3,5-二硝基甲苯；3,5-二硝基氯苄
• 英文名称: 3,5-dinitrobenzyl chloride
• 英文别名: 1-(chloromethyl)-3,5-dinitrobenzene
• CAS: 74367-78-5
• 化学式: C₇H₅ClN₂O₄
• mdl: MFCD00007234
• 分子量: 216.581
• InChiKey: SMJODKZAFKWUJG-UHFFFAOYSA-N

物化性质

• 熔点：
  79-82 °C (lit.)
• 沸点：
  373.4±27.0 °C(Predicted)
• 密度：
  1.538±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  14
• 可旋转键数：
  1
• 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

安全信息

• 危险等级：
  8
• 危险品标志：
  C
• 安全说明：
  S26,S36/37/39,S45
• 危险类别码：
  R34,R36/37
• 海关编码：
  2904909090
• 包装等级：
  III
• WGK Germany：
  3
• 危险品运输编号：
  UN 3261 8/PG 2
• 储存条件：
  | 2-8°C |

反应信息

• 作为反应物：
  描述：

  3,5-二硝基苄氯 在 对甲苯磺酸 、 一水合肼 、 sodium iodide 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 2.25h， 生成 3,5-dinitrobenzylamine
  参考文献：
  名称：

  Development of 3,5-Dinitrophenyl-Containing 1,2,4-Triazoles and Their Trifluoromethyl Analogues as Highly Efficient Antitubercular Agents Inhibiting Decaprenylphosphoryl-β-d-ribofuranose 2′-Oxidase

  摘要：

  We report herein the discovery of 3,5-dinitrophenyl 1,2,4-triazoles with excellent and selective antimycobacterial activities against Mycobacterium tuberculosis strains, including clinically isolated multidrug-resistant strains. Thorough structure activity relationship studies of 3,5-dinitrophenyl-containing 1,2,4-triazoles and their trifluoromethyl analogues revealed the key role of the position of the 3,5-dinitrophenyl fragment in the antitubercular efficiency. Among the prepared compounds, the highest in vitro antimycobacterial activities against M. tuberculosis H(37)Rv and against seven clinically isolated multidrug-resistant strains of M. tuberculosis were found with S-substituted 4-alkyl-5-(3,5-dinitrophenyl)-4H-1,2,4-triazole-3-thiols and their 3-nitro-5-(trifluoromethyl)phenyl analogues. The minimum inhibitory concentrations of these compounds reached 0.03 mu M, which is superior to all the current first-line anti-tuberculosis drugs. Furthermore, almost all compounds with excellent antimycobacterial activities exhibited very low in vitro cytotoxicities against two proliferating mammalian cell lines. The docking study indicated that these compounds acted as the inhibitors of decaprenylphosphoryl-beta-D-ribofuranose 2'-oxidase enzyme, which was experimentally confirmed by two independent radiolabeling experiments.

  DOI：

  10.1021/acs.jmedchem.9b00912
• 作为产物：
  描述：

  3,5-二硝基甲苯 在 N-氯代丁二酰亚胺 作用下， 以 丙酮 为溶剂， 以20g的产率得到3,5-二硝基苄氯
  参考文献：
  名称：

  一种他唑巴坦的制备方法

  摘要：

  本发明公开了一种他唑巴坦的制备方法。该方法以3,5‑二硝基苄氯为羧基保护试剂与6α‑溴青霉烷‑3α‑羧酸‑1β‑氧化物进行酯化反应；然后经还原、热裂解、氯甲基化、叠氮化、双氧化、环合加成得到他唑巴坦3,5‑二硝基苄基酯；然后以钯炭作为催化剂，采用氢气脱除他唑巴坦3,5‑二硝基苄基酯的保护，得到他唑巴坦；副产物3,5‑二硝基甲苯与氯化试剂N‑氯代丁二酰亚胺进行反应，制备3,5‑二硝基苄氯，实现保护试剂的循环利用。本发明使用化学性质稳定、反应活性高、价格较低的3,5‑二硝基苄氯作为羧基保护试剂，避免了稳定性差容易导致分解性爆炸的过氧乙酸的使用，实现了工艺的本质安全。

  公开号：

  CN109721617B

文献信息

• 1-Substituted-5-[(3,5-dinitrobenzyl)sulfanyl]-1H-tetrazoles and their isosteric analogs: A new class of selective antitubercular agents active against drug-susceptible and multidrug-resistant mycobacteria
  作者：Galina Karabanovich、Jaroslav Roh、Tomáš Smutný、Jan Němeček、Petr Vicherek、Jiřina Stolaříková、Marcela Vejsová、Ida Dufková、Kateřina Vávrová、Petr Pávek、Věra Klimešová、Alexandr Hrabálek

  DOI：10.1016/j.ejmech.2014.05.069

  日期：2014.7

  In this work, a new class of highly potent antituberculosis agents, 1-substituted-5-[(3,5-dinitrobenzyl)sulfanyl]-1H-tetrazoles and their oxa and selanyl analogs, is described. The minimal inhibitory concentration (MIC) values reached 1 μM (0.36–0.44 μg/mL) against Mycobacterium tuberculosis CNCTC My 331/88 and 0.25–1 μM against six multidrug-resistant clinically isolated strains of M. tuberculosis

  在这项工作中，描述了一类新型的高效抗结核药，即1-取代的5-[（3,5-二硝基苄基）硫烷基] -1 H-四唑及其氧杂和硒基类似物。最小抑菌浓度（MIC）值达到了1μM（0.36-0.44微克/毫升）对结核分枝杆菌CNCTC我八十八分之三百三十一和0.25-1μM针对六个多药耐药性临床分离菌株的结核分枝杆菌。这些化合物的抗分枝杆菌作用具有高度特异性，因为它们对所研究的所有八种细菌菌株和八种真菌菌株均无效。此外，这些化合物在四种哺乳动物细胞系中均表现出较低的体外毒性（IC 50 > 30μM）。我们还检查了化合物的结构-活性关系，特别是硝基基团的数量和位置，四唑和苄基部分之间的连接基以及四唑本身对抗分枝杆菌活性的影响。在不对分枝杆菌活性产生负面影响的情况下，四唑上取代基R 1的相对较高的变异性可进一步优化毒性，并进一步优化1-取代的5-[（3,5-二硝基苄基）硫烷基]-的ADME性质。 1 H-四唑化合物。
• Development of Photoswitchable Fluorescent Molecules Using Arylazopyrazole
  作者：Kenji Torii、Yuichiro Hori、Keiichiro Watabe、Kazuya Kikuchi

  DOI：10.1246/bcsj.20200077

  日期：2020.7.15

  Photoswitchable fluorescent molecules (PSFMs) are important tools for fluorescence imaging of biomolecules. To date, PSFMs have been applied for pulse-chase experiments and super-resolution imaging. However, most have limitations in that their fluorophores have low photostability or require cytotoxic additives. Here, we have developed PSFMs using a photochromic compound, arylazopyrazole, to overcome these limitations. These molecules showed reversible changes in fluorescence intensity upon photoirradiation and high photostability in aqueous solutions.

  光控荧光分子（Photoswitchable fluorescent molecules，简称PSFMs）是生物分子荧光成像的重要工具。迄今为止，PSFMs已被应用于脉冲追踪实验和超分辨率成像。然而，大多数此类分子存在局限性，其荧光团的光稳定性较低，或需要细胞毒性添加剂。在此，我们利用光致变色化合物——芳基偶氮吡唑开发了新型PSFMs，以克服这些局限。这些分子在光照下表现出可逆的荧光强度变化，在水中展现出高度的光稳定性。
• Phenylmercaptotetrazolo- and nitroindazolo masked development/image
  申请人：E. I. du Pont de Nemours and Company

  公开号：US04501896A1

  公开（公告）日：1985-02-26

  Novel nitrobenzyl compounds are incorporated into a photographic emulsion or developer for controlled release of development/image modifier compounds. This occurs imagewise only after developer oxidation products have been formed in the course of the development process. For example, nitrobenzyl-masked phenylmercaptotetrazole (PMT), incorporated into a silver halide emulsion, reacts with developer oxidation products via an electron transfer mechanism to release the potent development restrainer PMT.

  新型硝基苄基化合物被加入到感光乳剂或显影剂中，用于控制显影/图像修饰化合物的释放。这种释放仅在显影过程中形成显影剂氧化产物后，按图像的方式发生。例如，硝基苄基掩蔽的苯硫基四唑（PMT），被掺入到卤化银乳剂中，通过与显影剂氧化产物的电子转移机制反应，释放出强大的显影抑制剂PMT。
• Synthesis and Antimycobacterial and Antiprotozoal Activities of Some Novel Nitrobenzylated Heterocycles
  作者：Agata Górska、Lidia Chomicz、Justyna Żebrowska、Przemysław Myjak、Ewa Augustynowicz-Kopeć、Zofia Zwolska、Janusz Piekarczyk、Henryk Rebandel、Zygmunt Kazimierczuk

  DOI：10.1515/znb-2006-0120

  日期：2006.1.1

  A series of N-, S-, and O-mononitro- and dinitrobenzyl derivatives of heterocycles was synthesized by alkylation of heterocyclic bases with the respective nitrobenzyl chlorides. Of the newly synthesized compounds, dinitrobenzylsulfanyl derivatives of 1-methyl-2-mercaptoimidazole (2c) and of 5-nitro- and 5,6-dichloro-2-mercaptobenzimidazole (8b and 8c, and 8e and 8f, respectively) showed considerable antimycobacterial activity. On a molar basis, nine of the novel compounds showed also a considerably higher antiprotozoal efficacy than metronidazole that reduced T. hominis viability to 73.5% at 8 μg/ml.

  一系列N-、S-和O-单硝基和二硝基苯基杂环衍生物通过用相应的硝基苯基氯化物烷基化杂环碱合成。在新合成的化合物中，1-甲基-2-巯基咪唑（2c）和5-硝基-和5,6-二氯-2-巯基苯并咪唑（8b和8c，以及8e和8f，分别）的二硝基苯基硫醚衍生物显示出相当大的抗分枝杆菌活性。按摩尔计算，九种新化合物的抗原虫效力也比甲硝唑高得多，将T. hominis的存活率降低到8 μg/ml时的73.5%。
• Synthesis and antimicrobial and nitric oxide synthase inhibitory activities of novel isothiourea derivatives
  作者：Zygmunt Kazimierczuk、Malgorzata Chalimoniuk、Agnieszka Ewa Laudy、Rosa Moo-Puc、Roberto Cedillo-Rivera、Bohdan Jerzy Starosciak、Stanislaw J. Chrapusta

  DOI：10.1007/s12272-010-0604-8

  日期：2010.6

  The reaction of substituted benzylhalides, or of halomethyl derivatives of thiophene or furane, with thiourea or its derivatives yielded the respective isothioureas as hydrohalide salts. The products (a total of 17, including 16 novel compounds) were tested for activity against five Gram-positive and nine Gram-negative bacterial strains, six yeast species and two protozoan species. The most active against Gram-positive bacteria were S-(2,4-dinitrobenzyl)isothiourea hydrochloride (MIC range for four out of five strains tested: 12.5–25 μg/mL) and S-(2,3,4,5,6-pentabromobenzyl)isothiourea hydrobromide (MIC range: 12.5–50 μg/mL). The lowest MICs of novel isothioureas for yeast and Gram-negative bacteria ranged between 50 and 100 μg/mL. Nine novel isothioureas showed appreciable genotoxicity in the Bacillus subtilis ‘rec-assay’ test, the most potent being S-2-(5-nitrofuran-2-ylmethyl)isothiourea and S-(2-nitrobenzyl) isothiourea. At 10 μM concentration, S-(3,4-dichlorobenzyl)isothiourea hydrochloride and S-(2,3,4,5,6-pentabromobenzyl)isothiourea hydrobromide inhibited Ca2+/calmodulin-dependent (non-inducible) nitric oxide synthase activity in normal rat brain homogenates stronger (p < 0.05) than the reference drug 7-nitroindazole (by 78, 76 and 60%, respectively); ten other new isothiourea derivatives significantly inhibited the activity to a lower extent (by 28–60%). These results extend the list of promising isothioureas with substantial activity in vitro and suggest that an in-depth study of toxicity, antimicrobial properties in vivo and nitric oxide synthase isoform selectivity of selected novel compounds is warranted.

  取代苄基卤化物或噻吩或呋喃的卤甲基衍生物与硫脲或其衍生物的反应生成相应的异硫脲盐酸盐。产品（总共17个，包括16个新颖化合物）对五种革兰氏阳性细菌、九种革兰氏阴性细菌、六种酵母菌和两种原生动物进行了活性测试。对革兰氏阳性细菌最活跃的是S-(2,4-二硝基苄基)异硫脲盐酸盐（MIC范围为四株测试菌株：12.5–25 μg/mL）和S-(2,3,4,5,6-五溴苄基)异硫脲氢溴酸盐（MIC范围：12.5–50 μg/mL）。新颖的异硫脲对酵母和革兰氏阴性细菌的最低MIC范围在50至100 μg/mL之间。九个新颖的异硫脲在枯草芽孢杆菌“rec-assay”测试中显示出显着的遗传毒性，其中最强烈的是S-2-(5-硝基呋喃-2-基甲基)异硫脲和S-(2-硝基苄基)异硫脲。在10 μM浓度下，S-(3,4-二氯苄基)异硫脲盐酸盐和S-(2,3,4,5,6-五溴苄基)异硫脲氢溴酸盐比参比药物7-硝基吲唑更强（p < 0.05），抑制正常大鼠脑匀浆中的Ca2+/钙调蛋白依赖性（非诱导性）一氧化氮合酶活性（分别抑制78%、76%和60%）；其他十个新的异硫脲衍生物显著抑制活性，但程度较低（抑制28–60%）。这些结果扩展了具有显著体外活性的有希望的异硫脲列表，并表明有必要深入研究所选新颖化合物的毒性、体内抗菌特性和一氧化氮合酶亚型选择性。

表征谱图