间氨基苯乙醚 | 621-33-0

• 物质功能分类: 有机原料 - 氨基化合物
• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 中文名称: 间氨基苯乙醚
• 中文别名: 3-乙氧基苯胺；3-氨基苯乙醚；间乙氧基苯胺
• 英文名称: m-phenetidine
• 英文别名: 3-ethoxyaniline
• CAS: 621-33-0
• 化学式: C₈H₁₁NO
• mdl: MFCD00007785
• 分子量: 137.181
• InChiKey: WEZAHYDFZNTGKE-UHFFFAOYSA-N

物化性质

• 熔点：
  204 °C
• 沸点：
  248 °C(lit.)
• 密度：
  1.032 g/mL at 25 °C(lit.)
• 闪点：
  >230 °F
• 溶解度：
  可溶于氯仿、甲醇（少许）
• 物理描述：
  M-phenetidine is a dark red liquid. (NTP, 1992)
• 蒸汽压力：
  1 mm Hg at 153 °F ; 5 mm Hg at 202.5° F; 760 mm Hg at 442° F (NTP, 1992)
• 保留指数：
  1293;1293
• 稳定性/保质期：
  **避光**

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  10
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  35.2
• 氢给体数：
  1
• 氢受体数：
  2

ADMET

毒理性

• 副作用

高铁血红蛋白血症 - 血液中高铁血红蛋白含量增加；该化合物被归类为次要的毒性效应。

Methemoglobinemia - The presence of increased methemoglobin in the blood; the compound is classified as secondary toxic effect

来源:Haz-Map, Information on Hazardous Chemicals and Occupational Diseases

安全信息

• 危险等级：
  6.1(b)
• 危险品标志：
  T
• 危险类别码：
  R23/24/25,R33
• 危险品运输编号：
  UN 2311 6.1/PG 3
• WGK Germany：
  3
• RTECS号：
  SI5400000
• 海关编码：
  29222200
• 包装等级：
  III
• 危险类别：
  6.1(b)
• 安全说明：
  S28,S28A,S36/37,S36/37/39,S45
• 储存条件：
  存放在密封容器内，并置于阴凉、干燥处。

SDS

Name:	m-Phenetidine 98% Material Safety Data Sheet
Synonym:	3-Ethoxybenzenamine; 3-Ethoxyaniline; Aniline, 3-ethoxy-; Benzenamine, 3-ethoxy-; m-Ethoxyanilin
CAS:	621-33-0

Section 1 - Chemical Product MSDS Name:m-Phenetidine 98% Material Safety Data Sheet
Synonym:3-Ethoxybenzenamine; 3-Ethoxyaniline; Aniline, 3-ethoxy-; Benzenamine, 3-ethoxy-; m-Ethoxyanilin

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Section 2 - COMPOSITION, INFORMATION ON INGREDIENTS

CAS#	Chemical Name	content	EINECS#
621-33-0	m-Phenetidine	98	210-680-2

Hazard Symbols: T
Risk Phrases: 23/24/25 33

---

Section 3 - HAZARDS IDENTIFICATION
EMERGENCY OVERVIEW
Toxic by inhalation, in contact with skin and if swallowed. Danger of cumulative effects.Cancer suspect agent.Light sensitive.Air sensitive.
Potential Health Effects
Eye:
May cause eye irritation. May cause chemical conjunctivitis.
Skin:
May cause skin irritation.
Ingestion:
May be harmful if swallowed. May form methemoglobin which in sufficient concentration causes cyanosis (bluish discoloration of skin due to deficient oxygenation of the blood).
Inhalation:
May be harmful if inhaled. Inhalation of aniline causes anoxia due to the formation of methemoglobin.
Chronic:
Effects may be delayed.

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Section 4 - FIRST AID MEASURES
Eyes: Immediately flush eyes with plenty of water for at least 15 minutes, occasionally lifting the upper and lower eyelids. Get medical aid immediately.
Skin:
Get medical aid. Flush skin with plenty of water for at least 15 minutes while removing contaminated clothing and shoes.
Ingestion:
Never give anything by mouth to an unconscious person. Get medical aid immediately. Do NOT induce vomiting. If conscious and alert, rinse mouth and drink 2-4 cupfuls of milk or 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:

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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. During a fire, irritating and highly toxic gases may be generated by thermal decomposition or combustion.
Extinguishing Media:
In case of fire, use water, dry chemical, chemical foam, or alcohol-resistant foam.

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Section 6 - ACCIDENTAL RELEASE MEASURES
General Information: Use proper personal protective equipment as indicated in Section 8.
Spills/Leaks:
Absorb spill using an absorbent, non-combustible material such as earth, sand, or vermiculite. Do not use combustible materials such as sawdust. Provide ventilation. Place under an inert atmosphere.

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Section 7 - HANDLING and STORAGE
Handling:
Wash thoroughly after handling. Use with adequate ventilation. Do not get in eyes, on skin, or on clothing. Do not ingest or inhale.
Store protected from light. Handle under an inert atmosphere. Store protected from air. Do not breathe vapor.
Storage:
Keep containers tightly closed. Do not expose to air. Store protected from light. Store under an inert atmosphere. Store in a cool, dry area away from incompatible substances.

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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 general or local exhaust ventilation to keep airborne concentrations below the permissible exposure limits.
Exposure Limits CAS# 621-33-0: Personal Protective Equipment Eyes: Wear appropriate protective eyeglasses or chemical safety goggles as described by OSHA's eye and face protection regulations in 29 CFR 1910.133 or European Standard EN166.
Skin:
Wear appropriate protective gloves and clothing to prevent skin exposure.
Clothing:
Wear appropriate protective clothing to prevent skin exposure.
Respirators:
A respiratory protection program that meets OSHA's 29 CFR 1910.134 and ANSI Z88.2 requirements or European Standard EN 149 must be followed whenever workplace conditions warrant respirator use.

---

Section 9 - PHYSICAL AND CHEMICAL PROPERTIES

Physical State: Clear liquid
Color: clear brown
Odor: None reported.
pH: Not available.
Vapor Pressure: Not available.
Viscosity: Not available.
Boiling Point: 248 deg C @ 760.00mmHg
Freezing/Melting Point: Not available.
Autoignition Temperature: Not applicable.
Flash Point: > 112 deg C (> 233.60 deg F)
Explosion Limits, lower: Not available.
Explosion Limits, upper: Not available.
Decomposition Temperature: Not available.
Solubility in water: Not available.
Specific Gravity/Density: 1.0320g/cm3
Molecular Formula: C8H11NO
Molecular Weight: 137.18

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Section 10 - STABILITY AND REACTIVITY
Chemical Stability:
Stable under normal temperatures and pressures.
Conditions to Avoid:
Incompatible materials, light, exposure to air, excess heat.
Incompatibilities with Other Materials:
Air, acid anhydrides, acid chlorides, acids, chloroformates, direct light, strong oxidizing agents.
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# 621-33-0: SI5400000 LD50/LC50:
Not available.
Carcinogenicity:
m-Phenetidine - Not listed by ACGIH, IARC, or NTP.
Other:
See actual entry in RTECS for complete information.

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Section 12 - ECOLOGICAL INFORMATION
Other No information available.

---

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
Shipping Name: PHENETIDINES
Hazard Class: 6.1
UN Number: 2311
Packing Group: III
IMO
Shipping Name: PHENETIDINES
Hazard Class: 6.1
UN Number: 2311
Packing Group: III
RID/ADR
Shipping Name: PHENETIDINES
Hazard Class: 6.1
UN Number: 2311
Packing group: III

---

Section 15 - REGULATORY INFORMATION

European/International Regulations
European Labeling in Accordance with EC Directives
Hazard Symbols: T
Risk Phrases:
R 23/24/25 Toxic by inhalation, in contact with skin
and if swallowed.
R 33 Danger of cumulative effects.
Safety Phrases:
S 28A After contact with skin, wash immediately with
plenty of water.
S 36/37 Wear suitable protective clothing and
gloves.
S 45 In case of accident or if you feel unwell, seek
medical advice immediately (show the label where
possible).
WGK (Water Danger/Protection)
CAS# 621-33-0: No information available.
Canada
CAS# 621-33-0 is listed on Canada's NDSL List.
CAS# 621-33-0 is not listed on Canada's Ingredient Disclosure List.
US FEDERAL
TSCA
CAS# 621-33-0 is listed on the TSCA inventory.

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SECTION 16 - ADDITIONAL INFORMATION
N/A

制备方法与用途

化学性质
无色油状液体，沸点248℃，167-169℃（12.93kPa），127-128℃（1.47kPa），相对密度1.032，折光率1.5655。溶于醇和醚，微溶于水，遇光和空气会变成棕黄色。

用途
用于有机合成。

生产方法
由间氨基酚经乙酰化、烷基化、水解、中和而得：

1. 乙酰化：将间氨基酚加入乙酸中，加热回流8小时。回收乙酸后，水析，冷却过滤即得乙酰氨基酚（[621-42-1]）。

2. 烷基化：将乙醇、氢氧化钠、间乙酰氨基酚和溴乙烷加入反应器中，加热回流8小时。倒入水中冷却后过滤，得间乙酰氨基苯乙醚。

3. 水解、中和：将间乙酰氨基苯乙醚与工业盐酸混合，于水浴加热8小时。然后倒入水中，用40%氢氧化钠中和至碱性。分出油层。水溶液用乙醚提取，回收乙醚后，在氮气保护下减压蒸馏，收集140-144℃（2.0kPa）馏分即得间乙氧基苯胺。

类别
有毒物品

毒性分级
中毒

可燃性危险特性
明火可燃；受热会放出有毒的苯胺类气体

储运特性
库房应通风、低温干燥，并与食品原料分开储存和运输

灭火剂
雾状水、二氧化碳、砂土、干粉

反应信息

• 作为反应物：
  描述：

  间氨基苯乙醚 在 diphenyl ether-biphenyl eutectic 、 亚硝酸铵 、 铁粉 、 氯化铵 、 N,N-二异丙基乙胺 、 三氟乙酸酐 、 三氯氧磷 作用下， 以 四氢呋喃 、 甲醇 、 异丙醇 、 甲苯 为溶剂， 反应 27.25h， 生成 4-Morpholin-4-yl-but-2-enoic acid [4-(3-bromo-phenylamino)-3-cyano-7-ethoxy-quinolin-6-yl]-amide
  参考文献：
  名称：

  Synthesis and Structure−Activity Relationships of 6,7-Disubstituted 4-Anilinoquinoline-3-carbonitriles. The Design of an Orally Active, Irreversible Inhibitor of the Tyrosine Kinase Activity of the Epidermal Growth Factor Receptor (EGFR) and the Human Epidermal Growth Factor Receptor-2 (HER-2)

  摘要：

  A series of of 6,7-disubstituted-4-anilinoquinoline-3-carbonitrile derivatives that function as irreversible inhibitors of EGFR and HER-2 kinases have been prepared. These inhibitors have, at the 6-position, butynamide, crotonamide, and methacrylamide Michael acceptors bearing water-solublilizing substituents. These compounds were prepared by acylation of 6-amino-4-(arylamino)quinoline-3-carbonitriles with unsaturated acid chlorides or mixed anhydrides. We performed competitive reactivity studies showing that attaching a dialkylamino group onto the end of the Michael acceptor results in compounds with greater reactivity due to intramolecular catalysis of the Michael addition. This, along with improved water-solubility results in compounds with enhanced biological properties. We present molecular modeling results consistent with the proposed mechanism of inhibition. One compound, 5 (EKB-569), which shows excellent oral in vivo activity, was selected for further studies and is currently in phase I clinical trials for the treatment of cancer.

  DOI：

  10.1021/jm020241c
• 作为产物：
  描述：

  间硝基苯酚 在 potassium carbonate 、 溶剂黄146 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 0.33h， 生成 间氨基苯乙醚
  参考文献：
  名称：

  [Cp*RhCl₂]₂-Catalyzed Alkyne Hydroamination to 1,2-Dihydroquinolines

  摘要：

  [Cp*RhCl2](2) catalyzes the formation of 1,2-dihydroquinolines from the reaction of two terminal alkynes and an Aniline. This reaction is believed to proceed via an alkyne hydroamination followed by an alkyne insertion..

  DOI：

  10.1021/om501253v

文献信息

• Mitogen-Activated Protein Kinase-Activated Protein Kinase 2 (MAPKAP-K2) as an Antiinflammatory Target: Discovery and in Vivo Activity of Selective Pyrazolo[1,5-<i>a</i>]pyrimidine Inhibitors Using a Focused Library and Structure-Based Optimization Approach
  作者：Tomomi Kosugi、Dale R. Mitchell、Aiko Fujino、Minoru Imai、Mika Kambe、Shinji Kobayashi、Hiroaki Makino、Yohei Matsueda、Yasuhiro Oue、Kanji Komatsu、Keiichiro Imaizumi、Yuri Sakai、Satoshi Sugiura、Osami Takenouchi、Gen Unoki、Yuko Yamakoshi、Vicky Cunliffe、Julie Frearson、Richard Gordon、C. John Harris、Heidi Kalloo-Hosein、Joelle Le、Gita Patel、Donald J. Simpson、Brad Sherborne、Peter S. Thomas、Naotaka Suzuki、Midori Takimoto-Kamimura、Ken-ichiro Kataoka

  DOI：10.1021/jm300411k

  日期：2012.8.9

  A novel class of mitogen-activated protein kinase-activated protein kinase 2 (MAPKAP-K2) inhibitors was discovered through screening a kinase-focused library. A homology model of MAPKAP-K2 was generated and used to guide the initial SAR studies and to rationalize the observed selectivity over CDK2. An X-ray crystal structure of a compound from the active series bound to crystalline MAPKAP-K2 confirmed

  通过筛选激酶集中的文库，发现了一类新型的促分裂原活化蛋白激酶活化蛋白激酶2（MAPKAP-K2）抑制剂。MAPKAP-K2的同源性模型已生成，可用于指导最初的SAR研究并合理化所观察到的对CDK2的选择性。结合到晶体MAPKAP-K2的活性系列化合物的X射线晶体结构证实了预测的结合模式。这使得能够发现一系列吡唑并[1,5- a ]嘧啶衍生物，它们在抗内毒素休克的小鼠模型中作为抗TNF-α剂具有良好的体外细胞效价和体内功效。
• Studies on antiallergy agents. III. Synthesis of 2-anilino-1,6-dihydro-6-oxo-5-pyrimidinecarboxylic acids and related compounds.
  作者：Kohji OZEKI、Teru ICHIKAWA、Hiroyuki TAKEHARA、Kenjiro TANIMURA、Makoto SATO、Hideya YAGINUMA

  DOI：10.1248/cpb.37.1780

  日期：——

  A series of 2-anilino-1,6-dihydro-6-oxo-5-pyrimidinecarboxylic acids with various substituents was synthesized and evaluated in the rat passive cutaneous anaphylaxis test for antiallergic activity. High activity by intraperitoneal and oral administrations was observed for the 3-trifluoromethyl and 2-alkoxyanilino derivatives (64, 79, 81, 82 and 85). Structure-activity relationships are discussed.

  合成了一系列具有各种取代基的2-苯胺基-1,6-二氢-6-氧代-5-嘧啶羧酸，并在大鼠被动皮肤过敏反应试验中评估了其抗过敏活性。对于3-三氟甲基和2-烷氧基苯胺基衍生物（64、79、81、82和85），观察到腹膜内和口服给药具有高活性。讨论了构效关系。
• Adenosine Kinase Inhibitors. 5. Synthesis, Enzyme Inhibition, and Analgesic Activity of Diaryl-<i>erythro</i>-furanosyltubercidin Analogues
  作者：Serge H. Boyer、Bheemarao G. Ugarkar、Joel Solbach、Joseph Kopcho、Michael C. Matelich、Kristin Ollis、Jorge E. Gomez-Galeno、Rohan Mendonca、Megumi Tsuchiya、Atsushi Nagahisa、Masami Nakane、James B. Wiesner、Mark D. Erion

  DOI：10.1021/jm0503650

  日期：2005.10.1

  lyxo-furanosyltubercidin analogues as well as the newly discovered erythro-furanosyltubercidin analogues, designed to prevent 5'-O-phosphorylation and associated toxicities, were tested for their analgesic activity in the rat formalin paw model. Described herein are the synthesis, enzyme inhibition structure-activity relationships (SARs) of erythro-furanosyltubercidin analogues, and SARs of analgesic activity of various

  腺苷是一种内源性神经调节剂，当在中枢和周围神经系统中产生时，具有抗惊厥，抗炎和镇痛作用。然而，剂量限制的心血管副作用困扰着使用腺苷受体激动剂的努力。作为替代方案，我们探索了腺苷激酶抑制剂（AKIs）作为潜在的抗癫痫药的用途，并证明了在没有明显的心血管副作用的情况下腺苷受体介导的治疗作用。这些活性与以部位和事件特异性方式抑制AK导致的细胞外腺苷浓度升高有关。几种基于结核菌素的AKI，包括核糖和呋喃呋喃糖基结核病类似物，以及新近发现的赤呋喃呋喃糖基结核病类似物，旨在预防5' 在大鼠福尔马林爪模型中测试了-O-磷酸化作用和相关的毒性。在此描述的是赤型-呋喃糖基tubercidin类似物的合成，酶抑制结构-活性关系（SAR），以及各种类型的AKI的镇痛活性。还报道了AKI铅19d（GP3966）的表征，这是一种口服生物利用化合物（狗中F％= 60％），具有广谱镇痛活性（ED50 <或= 4 mg /
• Substituted 3-cyano quinolines
  申请人：American Cyanamid Company

  公开号：US06002008A1

  公开（公告）日：1999-12-14

  This invention provides compounds having the formula: ##STR1## wherein: X is cycloalkyl which may be optionally substituted; or is a pyridinyl, pyrimidinyl, or phenyl ring; wherein the pyridinyl, pyrimidinyl, or phenyl ring may be optionally substituted; n is 0-1; Y is --NH--, --O--, --S--, or --NR--; R is alkyl of 1-6 carbon atoms; R.sub.1, R.sub.2, R.sub.3, and R.sub.4 are each, independently, hydrogen, halogen, alkyl, alkenyl, alkynyl, alkenyloxy, alkynyloxy, hydroxymethyl, halomethyl, alkanoyloxy, alkenoyloxy, alkynoyloxy, alkanoyloxymethyl, alkenoyloxymethyl, alkynoyloxymethyl, alkoxymethyl, alkoxy, alkylthio, alkylsulphinyl, alkylsulphonyl, alkylsulfonamido, alkenylsulfonamido, alkynylsulfonamido, hydroxy, trifluoromethyl, cyano, nitro, carboxy, carboalkoxy, carboalkyl, phenoxy, phenyl, thiophenoxy, benzyl, amino, hydroxyamino, alkoxyamino, alkylamino, dialkylamino, aminoalkyl, N-alkylaminoalkyl, N,N-dialkylaminoalkyl, phenylamino, benzylamino, ##STR2## R.sub.5 is alkyl which may be optionally substituted, or phenyl which may be optionally substituted; R.sub.6 is hydrogen, alkyl, or alkenyl; R.sub.7 is chloro or bromo R.sub.8 is hydrogen, alkyl, aminoalkyl, N-alkylaminoalkyl, N,N-dialkylaminoalkyl, N-cycloalkylaminoalkyl, N-cycloalkyl-N-alkylaminoalkyl, N,N-dicycloalkylaminoalkyl, morpholino-N-alkyl, piperidino-N-alkyl, N-alkyl-piperidino-N-alkyl, azacycloalkyl-N-alkyl, hydroxyalkyl, alkoxyalkyl, carboxy, carboalkoxy, phenyl, carboalkyl+, chloro, fluoro, or bromo; Z is amino, hydroxy, alkoxy, alkylamino, dialkylamino, morpholino, piperazino, N-alkylpiperazino, or pyrrolidino; m=1-4,q=1-3, and p=0-3; any of the substituents R.sub.1, R.sub.2, R.sub.3, or R.sub.4 that are located on contiguous carbon atoms can together be the divalent radical --O--C(R.sub.8).sub.2 --O--; or a pharmaceutically acceptable salt thereof with the proviso that when Y is --NH--, R.sub.1, R.sub.2, R.sub.3, and R.sub.4 are hydrogen, and n is 0, X is not 2-methylphenyl, which are inhibitors of protein tyrosine kinase.

  这项发明提供了具有以下结构的化合物：##STR1## 其中：X是环烷基，可以选择性地被取代；或者是吡啶基、嘧啶基或苯环；其中吡啶基、嘧啶基或苯环可以选择性地被取代；n为0-1；Y为--NH--、--O--、--S--或--NR--；R为1-6个碳原子的烷基；R.sub.1、R.sub.2、R.sub.3和R.sub.4分别独立地是氢、卤素、烷基、烯基、炔基、烯氧基、炔氧基、羟甲基、卤甲基、烷酰氧基、烯酰氧基、炔酰氧基、烷酰氧甲基、烯酰氧甲基、炔酰氧甲基、烷氧甲基、烷氧基、烷基硫、烷基亚砜基、烷基磺酰基、烷基磺酰胺基、烯基磺酰胺基、炔基磺酰胺基、羟基、三氟甲基、氰基、硝基、羧基、羧基烷氧基、羧基烷基、苯氧基、苯基、噻吩氧基、苄基、氨基、羟氨基、烷氧氨基、烷基氨基、二烷基氨基、氨基烷基、N-烷基氨基烷基、N,N-二烷基氨基烷基、苯基氨基、苄氨基、##STR2## R.sub.5是可以选择性取代的烷基，或者是可以选择性取代的苯基；R.sub.6是氢、烷基或烯基；R.sub.7是氯或溴；R.sub.8是氢、烷基、氨基烷基、N-烷基氨基烷基、N,N-二烷基氨基烷基、N-环烷基氨基烷基、N-环烷基-N-烷基氨基烷基、N,N-二环烷基氨基烷基、吗啉-N-烷基、哌啶-N-烷基、N-烷基-哌啶-N-烷基、氮杂环烷基-N-烷基、羟基烷基、烷氧基烷基、羧基、羧基烷氧基、苯基、羧基+、氯、氟或溴；Z是氨基、羟基、烷氧基、烷基氨基、二烷基氨基、吗啉基、哌嗪基、N-烷基哌嗪基或吡咯烷基；m=1-4，q=1-3，p=0-3；任何位于相邻碳原子上的R.sub.1、R.sub.2、R.sub.3或R.sub.4取代基可以共同形成二价基团--O--C(R.sub.8).sub.2 --O--；或其药学上可接受的盐，但当Y为--NH--时，R.sub.1、R.sub.2、R.sub.3和R.sub.4为氢，n为0时，X不是2-甲基苯基，这些化合物是蛋白酪氨酸激酶的抑制剂。
• Method of treating or inhibiting colonic polyps
  申请人：American Cyanamid Company

  公开号：US06384051B1

  公开（公告）日：2002-05-07

  This invention provides a method of treating or inhibiting colonic polyps which comprises providing a compound of formula 1 wherein: R1, R2, R3, R4, X, Y, and n are as defined hereinbefore, or a pharmaceutically acceptable salt thereof.

  本发明提供了一种治疗或抑制结肠息肉的方法，包括提供如下公式1的化合物： 其中： R1、R2、R3、R4、X、Y和n如前文所定义，或其药用可接受的盐。

表征谱图