1-甲基-1，2，3-苯并三唑-5-羧酸 | 305381-67-3

• 物质功能分类: 医药中间体 - 杂环化合物
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并三唑类
• 中文名称: 1-甲基-1，2，3-苯并三唑-5-羧酸
• 中文别名: 1-甲基-1,2,3-苯并三唑-5-羧酸
• 英文名称: 1-methyl-1H-benzo[d][1,2,3]triazole-5-carboxylic acid
• 英文别名: 1-methyl-1H-benzotriazole-5-carboxylic acid；1-Methyl-1H-benzotriazol-5-carbonsaeure；1-methylbenzotriazole-5-carboxylic acid；1-methyl-1H-1,2,3-benzotriazole-5-carboxylic acid
• CAS: 305381-67-3
• 化学式: C₈H₇N₃O₂
• mdl: MFCD03086163
• 分子量: 177.162
• InChiKey: SGHWYTLJLHVIBQ-UHFFFAOYSA-N

物化性质

• 熔点：
  250 °C
• 沸点：
  432.4±18.0 °C(Predicted)
• 密度：
  1.49±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  13
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  68
• 氢给体数：
  1
• 氢受体数：
  4

安全信息

• 危险品标志：
  Xn
• 危险类别码：
  R20/21/22,R36/37/38
• 海关编码：
  2933990090
• 危险性防范说明：
  P261,P264,P270,P271,P280,P301+P312,P302+P352,P304+P340,P330,P363,P501
• 危险性描述：
  H302,H312,H332
• 安全说明：
  S26,S36/37/39

SDS

Name:	1-Methyl-1h-1 2 3-benzotriazole-5-carboxylic acid 97% Material Safety Data Sheet
Synonym:
CAS:	305381-67-3

Section 1 - Chemical Product MSDS Name:1-Methyl-1h-1 2 3-benzotriazole-5-carboxylic acid 97% Material Safety Data Sheet
Synonym:

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Section 2 - COMPOSITION, INFORMATION ON INGREDIENTS

CAS#	Chemical Name	content	EINECS#
305381-67-3	1-Methyl-1H-1,2,3-benzotriazole-5-carb	97%	unlisted

Hazard Symbols: XN
Risk Phrases: 20/21/22 36/37/38

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Section 3 - HAZARDS IDENTIFICATION
EMERGENCY OVERVIEW
Harmful by inhalation, in contact with skin and if swallowed.
Irritating to eyes, respiratory system and skin.
Potential Health Effects
Eye:
Causes eye irritation.
Skin:
Causes skin irritation. Harmful if absorbed through the skin.
Ingestion:
Harmful if swallowed. May cause irritation of the digestive tract.
Inhalation:
Harmful if inhaled. Causes respiratory tract irritation.
Chronic:
Not available.

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Section 4 - FIRST AID MEASURES
Eyes: Flush eyes with plenty of water for at least 15 minutes, occasionally lifting the upper and lower eyelids. Get medical aid.
Skin:
Get medical aid. Flush skin with plenty of water for at least 15 minutes while removing contaminated clothing and shoes.
Ingestion:
Get medical aid. Wash mouth out with water.
Inhalation:
Remove from exposure and move to fresh air immediately. If not breathing, give artificial respiration. If breathing is difficult, give oxygen. Get medical aid.
Notes to Physician:
Treat symptomatically and supportively.

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Section 5 - FIRE FIGHTING MEASURES
General Information:
As in any fire, wear a self-contained breathing apparatus in pressure-demand, MSHA/NIOSH (approved or equivalent), and full protective gear.
Extinguishing Media:
Use water spray, dry chemical, carbon dioxide, or chemical foam.

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Section 6 - ACCIDENTAL RELEASE MEASURES
General Information: Use proper personal protective equipment as indicated in Section 8.
Spills/Leaks:
Vacuum or sweep up material and place into a suitable disposal container.

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Section 7 - HANDLING and STORAGE
Handling:
Avoid breathing dust, vapor, mist, or gas. Avoid contact with skin and eyes.
Storage:
Store in a cool, dry place. Store in a tightly closed container.

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Section 8 - EXPOSURE CONTROLS, PERSONAL PROTECTION
Engineering Controls:
Facilities storing or utilizing this material should be equipped with an eyewash facility and a safety shower. Use adequate ventilation to keep airborne concentrations low.
Exposure Limits CAS# 305381-67-3: Personal Protective Equipment Eyes: Not available.
Skin:
Wear appropriate protective gloves to prevent skin exposure.
Clothing:
Wear appropriate protective clothing to prevent skin exposure.
Respirators:
Follow the OSHA respirator regulations found in 29 CFR 1910.134 or European Standard EN 149. Use a NIOSH/MSHA or European Standard EN 149 approved respirator if exposure limits are exceeded or if irritation or other symptoms are experienced.

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Section 9 - PHYSICAL AND CHEMICAL PROPERTIES

Physical State: Solid
Color: brown
Odor: Not available.
pH: Not available.
Vapor Pressure: Not available.
Viscosity: Not available.
Boiling Point: Not available.
Freezing/Melting Point: 269 - 272 deg C(decom)
Autoignition Temperature: Not available.
Flash Point: Not available.
Explosion Limits, lower: Not available.
Explosion Limits, upper: Not available.
Decomposition Temperature:
Solubility in water:
Specific Gravity/Density:
Molecular Formula: C8H7N3O2
Molecular Weight: 177.16

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Section 10 - STABILITY AND REACTIVITY
Chemical Stability:
Not available.
Conditions to Avoid:
Incompatible materials.
Incompatibilities with Other Materials:
Strong oxidizing agents, reducing agents, bases, amines.
Hazardous Decomposition Products:
Nitrogen oxides, carbon monoxide, carbon dioxide.
Hazardous Polymerization: Has not been reported.

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Section 11 - TOXICOLOGICAL INFORMATION
RTECS#:
CAS# 305381-67-3 unlisted.
LD50/LC50:
Not available.
Carcinogenicity:
1-Methyl-1H-1,2,3-benzotriazole-5-carboxylic acid - Not listed by ACGIH, IARC, or NTP.

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Section 12 - ECOLOGICAL INFORMATION

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Section 13 - DISPOSAL CONSIDERATIONS
Dispose of in a manner consistent with federal, state, and local regulations.

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Section 14 - TRANSPORT INFORMATION

IATA
No information available.
IMO
No information available.
RID/ADR
No information available.

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Section 15 - REGULATORY INFORMATION

European/International Regulations
European Labeling in Accordance with EC Directives
Hazard Symbols: XN
Risk Phrases:
R 20/21/22 Harmful by inhalation, in contact with
skin and if swallowed.
R 36/37/38 Irritating to eyes, respiratory system
and skin.
Safety Phrases:
S 26 In case of contact with eyes, rinse immediately
with plenty of water and seek medical advice.
S 36/37/39 Wear suitable protective clothing, gloves
and eye/face protection.
WGK (Water Danger/Protection)
CAS# 305381-67-3: No information available.
Canada
None of the chemicals in this product are listed on the DSL/NDSL list.
CAS# 305381-67-3 is not listed on Canada's Ingredient Disclosure List.
US FEDERAL
TSCA
CAS# 305381-67-3 is not listed on the TSCA inventory.
It is for research and development use only.

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SECTION 16 - ADDITIONAL INFORMATION
N/A

制备方法与用途

应用

1-甲基-1,2,3-苯并三唑-5-羧酸是一种有机中间体。其合成过程包括多个步骤：首先由4-氨基-3-硝基苯甲酸制备4-氨基-3-硝基苯甲酸甲酯；然后通过甲基化得到4-甲氨基-3-硝基苯甲酸甲酯；还原硝基获得4-甲氨基-3-氨基苯甲酸甲酯，接着关环形成4-甲氨基-3-氨基苯甲酸甲酯，最后水解甲酯制得1-甲基-1,2,3-苯并三唑-5-羧酸。

制备

（1）4-氨基-3-硝基苯甲酸甲酯的合成

在磁子搅拌下，将4-氨基-3-硝基苯甲酸(3.6g，19mmol)与35mL甲醇混合后，在油浴加热至约75℃并回流反应过夜。冷却后，倾入100mL水中，底部析出黄色固体粉末。搅拌下加入NaHCO₃直至无气泡生成，随后使用乙酸乙酯萃取，并用饱和的NaHCO₃溶液和去离子水洗涤。收集有机层，经过无水硫酸钠干燥、过滤并浓缩后得到3.0g（收率77%）黄色固体。GC/MS：196。

（2）4-甲氨基-3-硝基苯甲酸甲酯的合成

称量4-氨基-3-硝基苯甲酸(2.0g，10.2mmol)于50mL三口烧瓶中，并加入碘化钾(1.69g，10.2mmol)，随后加入干燥的DMF（25mL）。在磁子搅拌下待原料完全溶解后，分批加入氢化钠(270mg，11.2mmol)。室温搅拌反应15分钟后，缓慢滴加对甲苯磺酸甲酯(MPTS, 2.0g，11.2mmol)，继续室温搅拌0.5h。将反应液倒入去离子水中，乙酸乙酯萃取并用去离子水洗涤两次。收集有机层后经过无水硫酸钠干燥过夜，过滤浓缩得到黄色固体。硅胶柱层析（石油醚：乙酸乙酯=5:1，v/v）分离后得到1.2g（收率56%）黄色固体。GC/MS：210。

（3）4-甲氨基-3-氨基苯甲酸甲酯的合成

在50mL单口烧瓶中称量4-甲氨基-3-氨基苯甲酸甲酯(1.2g，5.4mmol)，加入预先制备好的40mL 2mol/L氢氧化钠溶液，并滴加1mL 1,4-二氧六环助溶。油浴加热至50℃并搅拌反应4小时后，冷却至室温，用稀盐酸调节溶液至酸性，进行乙酸乙酯萃取和浓缩干燥，最终得到600mg（收率53%）白色固体。GC/MS：177。

（4）1-甲基-1,2,3-苯并三唑-5-羧酸的合成

在100mL三口烧瓶中称量1-甲基-5-羧酸甲酯苯并三氮唑(1.2g，5.4mmol)，加入预先制备好的40mL 2mol/L氢氧化钠溶液，并滴加1mL 1,4-二氧六环助溶。油浴加热至50℃继续搅拌反应4小时后，冷却至室温并用稀盐酸调节溶液为酸性，通过乙酸乙酯萃取和浓缩干燥，最终得到600mg（收率53%）白色固体。

该化合物的核磁共振氢谱和碳谱数据如下：

• 1H NMR(400MHz，CDCl₃) δ 8.78(s，1H)，8.19(d，J＝8.8Hz，1H)，7.55(d，J＝8.8Hz，1H)，4.33(s，3H)，3.98(s，3H)
• 13C NMR(100MHz，CDCl₃) δ 166.6，145.6，135.6，128.2，126.3，122.9，109.0，52.4，34.4。
• HRMS(EI/[M]+): C₉H₉N₃O₂ 计算值：191.0695；实验值：191.0693。

反应信息

• 作为反应物：
  描述：

  1-甲基-1，2，3-苯并三唑-5-羧酸 在 草酰氯 作用下， 以 二氯甲烷 为溶剂， 反应 1.0h， 生成 1-甲基-1H-1,2,3-苯并三唑-5-羰基氯
  参考文献：
  名称：

  新型植物活化剂支架的发现：从水杨酸到苯并三唑

  摘要：

  摘要从水杨酸（SA）和相关的商业化植物活化剂开始，基于分子三维形状和药效团相似度比较（SHAFTS），预测了一种新的铅化合物苯并三唑，并设计和合成了一系列苯并三唑衍生物。生物测定表明，苯并三唑在体内对多种疾病（包括真菌和卵菌）具有高活性，但在体外则无活性。并且在1'-位和5'-位引入适当的基团对于该活性是有利的。因此，它们具有被开发为新型植物激活剂的潜力。

  DOI：

  10.1016/j.cclet.2017.02.004
• 作为产物：
  描述：

  4-氟-3-硝基苯甲酸 在 palladium on activated charcoal 氢气 、 溶剂黄146 、 sodium nitrite 作用下， 以 甲醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 27.0h， 生成 1-甲基-1，2，3-苯并三唑-5-羧酸
  参考文献：
  名称：

  HETEROCYCLIC COMPOUNDS FOR THE INHIBITION OF PASK

  摘要：

  本文披露了新的杂环化合物和组合物，以及它们作为药物治疗疾病的应用。还提供了抑制PAS激酶（PASK）在人类或动物主体中活性的方法，用于治疗疾病，如糖尿病。

  公开号：

  US20120277224A1

文献信息

• Substituted Indoles
  申请人：AbbVie Inc.

  公开号：US20170174688A1

  公开（公告）日：2017-06-22

  The invention provides for compounds of formula (I) wherein R 1 , R 2 , R 3 , R 4 , R 5 , and R 6 have any of the values defined in the specification, and pharmaceutically acceptable salts thereof, that are useful as agents in the treatment of diseases and conditions mediated and modulated by SUV420H1. Also provided are pharmaceutical compositions comprised of one or more compounds of formula (I).

  该发明提供了以下式（I）的化合物 其中R 1 ，R 2 ，R 3 ，R 4 ，R 5 和R 6 具有规范中定义的任何值，以及其药学上可接受的盐，这些化合物在治疗由SUV420H1介导和调节的疾病和症状中作为药剂是有用的。还提供了由一个或多个式（I）化合物组成的药物组合物。
• [EN] INHIBITORS OF HISTONE DEACETYLASE<br/>[FR] INHIBITEURS D'HISTONE DEACETYLASE
  申请人：METHYLGENE INC

  公开号：WO2005030704A1

  公开（公告）日：2005-04-07

  The invention relates to the inhibition of histone deacetylase. The invention provides compounds and methods for inhibiting histone deacetylase enzymatic activity. The invention also provides compositions and methods for treating cell proliferative diseases and conditions.

  这项发明涉及抑制组蛋白去乙酰化酶。该发明提供了抑制组蛋白去乙酰化酶酶活性的化合物和方法。该发明还提供了治疗细胞增殖性疾病和症状的组合物和方法。
• NOVEL HETEROCYCLIC DERIVATIVES AS M-GLU5 ANTAGONISTS
  申请人：Leonardi Amedeo

  公开号：US20090042841A1

  公开（公告）日：2009-02-12

  This invention relates to novel heterocyclic compounds having selective affinity for the mGlu5 subtype of metabotropic receptors, pharmaceutical compositions thereof and uses for such compounds and compositions in the treatment of lower urinary tract disorders, such as neuromuscular dysfunction of the lower urinary tract, and in the treatment of migraine and gastroesophagael reflux disease (GERD).

  本发明涉及一种新型杂环化合物，其具有选择性亲和力，适用于代谢型受体mGlu5亚型，以及该类化合物的制药组合物及其在治疗下尿路障碍（例如下尿路神经肌肉功能障碍）、偏头痛和胃食管反流病（GERD）方面的用途。
• [EN] THIAZOLIDINE COMPOUNDS AS OREXIN RECEPTOR ANTAGONISTS<br/>[FR] COMPOSÉS THIAZOLIDINES EN TANT QU'ANTAGONISTES DES RÉCEPTEURS DE L'OREXINE
  申请人：ACTELION PHARMACEUTICALS LTD

  公开号：WO2010004507A1

  公开（公告）日：2010-01-14

  The invention relates to thiazolidine derivatives of the formula (I) wherein A, B, and R1 are as described in the description, to salts, especially pharmaceutically acceptable salts, of such compounds and to their use as medicaments, especially as orexin receptor antagonists.

  这项发明涉及式(I)的噻唑啉衍生物，其中A、B和R1如描述中所述，以及这些化合物的盐，特别是药学上可接受的盐，以及它们作为药物的用途，特别是作为促进睡眠的药物受体拮抗剂。
• THIAZOLIDINE COMPOUNDS AS OREXIN RECEPTOR ANTAGONISTS
  申请人：Aissaoui Hamed

  公开号：US20110105491A1

  公开（公告）日：2011-05-05

  The invention relates to thiazolidine derivatives of the formula (I) wherein A, B, and R 1 are as described in the description, to salts, especially pharmaceutically acceptable salts, of such compounds and to their use as medicaments, especially as orexin receptor antagonists.

  这项发明涉及式(I)的噻唑啉衍生物，其中A、B和R1如描述中所述，以及这些化合物的盐，特别是药用可接受的盐，以及它们作为药物的用途，特别是作为促进睡眠的药物受体拮抗剂。