1-(4-hydroxyphenyl)piperazine hydrobromide | 38869-37-3

• 物质功能分类: 有机原料 - 杂环化合物
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: 1-(4-hydroxyphenyl)piperazine hydrobromide
• 英文别名: 1-(p-hydroxyphenyl)piperazine hydrobromide；4-(Piperazin-1-yl)phenol hydrobromide；4-piperazin-1-ylphenol;hydrobromide
• CAS: 38869-37-3
• 化学式: BrH*C₁₀H₁₄N₂O
• 分子量: 259.146
• InChiKey: XMKFYFNHNMOZHH-UHFFFAOYSA-N

物化性质

• 熔点：
  275 °C (decomp)
• 稳定性/保质期：
  遵照规定使用和储存，则不会分解。

计算性质

• 辛醇/水分配系数(LogP)：
  1.38
• 重原子数：
  14
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  35.5
• 氢给体数：
  3
• 氢受体数：
  3

安全信息

• 危险品标志：
  Xn
• 安全说明：
  S22,S24/25,S26,S36/37/39
• 危险类别码：
  R36/37/38,R20/21/22
• 海关编码：
  2933599090

SDS

Name:	1-(4-Hydroxyphenyl)piperazine dihydrobromide Material Safety Data Sheet
Synonym:	4-Piperazinophenol dihydrobromide
CAS:	38869-37-3

Section 1 - Chemical Product MSDS Name:1-(4-Hydroxyphenyl)piperazine dihydrobromide Material Safety Data Sheet
Synonym:4-Piperazinophenol dihydrobromide

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Section 2 - COMPOSITION, INFORMATION ON INGREDIENTS

CAS#	Chemical Name	content	EINECS#
38869-37-3	1-(4-Hydroxyphenyl)piperazine dihydrob	98	254-164-5

Hazard Symbols: None Listed.
Risk Phrases: None Listed.

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Section 3 - HAZARDS IDENTIFICATION
EMERGENCY OVERVIEW
The toxicological properties of this material have not been fully investigated.
Potential Health Effects
Eye:
May cause eye irritation.
Skin:
May cause skin irritation. May be harmful if absorbed through the skin.
Ingestion:
May cause irritation of the digestive tract. The toxicological properties of this substance have not been fully investigated. May be harmful if swallowed.
Inhalation:
May cause respiratory tract irritation. The toxicological properties of this substance have not been fully investigated. May be harmful if inhaled.
Chronic:
No information found.

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Section 4 - FIRST AID MEASURES
Eyes: In case of contact, immediately flush eyes with plenty of water for at least 15 minutes. Get medical aid.
Skin:
In case of contact, flush skin with plenty of water. Remove contaminated clothing and shoes. Get medical aid if irritation develops and persists. Wash clothing before reuse.
Ingestion:
If swallowed, do not induce vomiting unless directed to do so by medical personnel. Never give anything by mouth to an unconscious person. Get medical aid.
Inhalation:
If inhaled, remove to fresh air. 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. During a fire, irritating and highly toxic gases may be generated by thermal decomposition or combustion. This material in sufficient quantity and reduced particle size is capable of creating a dust explosion.
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. Clean up spills immediately, observing precautions in the Protective Equipment section. Avoid generating dusty conditions.
Provide ventilation.

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Section 7 - HANDLING and STORAGE
Handling:
Wash thoroughly after handling. Remove contaminated clothing and wash before reuse. Use with adequate ventilation. Minimize dust generation and accumulation. Avoid contact with eyes, skin, and clothing. Avoid breathing dust.
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# 38869-37-3: 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 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: Crystalline powder
Color: off-white to light beige - beige pink
Odor: No data
pH: Not available.
Vapor Pressure: Not available.
Viscosity: Not available.
Boiling Point: Not available.
Freezing/Melting Point: 291-292 deg C
Autoignition Temperature: Not available.
Flash Point: Not applicable.
Explosion Limits, lower: Not available.
Explosion Limits, upper: Not available.
Decomposition Temperature:
Solubility in water:
Specific Gravity/Density:
Molecular Formula: C10H14N2O.2HBr
Molecular Weight: 340.04

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Section 10 - STABILITY AND REACTIVITY
Chemical Stability:
Stable under normal temperatures and pressures.
Conditions to Avoid:
Dust generation.
Incompatibilities with Other Materials:
Strong oxidizing agents.
Hazardous Decomposition Products:
Carbon monoxide, oxides of nitrogen, carbon dioxide, hydrogen bromide.
Hazardous Polymerization: Has not been reported

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Section 11 - TOXICOLOGICAL INFORMATION
RTECS#:
CAS# 38869-37-3 unlisted.
LD50/LC50:
Not available.
Carcinogenicity:
1-(4-Hydroxyphenyl)piperazine dihydrobromide - 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
Shipping Name: Not regulated.
Hazard Class:
UN Number:
Packing Group:
IMO
Shipping Name: Not regulated.
Hazard Class:
UN Number:
Packing Group:
RID/ADR
Shipping Name: Not regulated.
Hazard Class:
UN Number:
Packing group:

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Section 15 - REGULATORY INFORMATION

European/International Regulations
European Labeling in Accordance with EC Directives
Hazard Symbols: Not available.
Risk Phrases:
Safety Phrases:
S 24/25 Avoid contact with skin and eyes.
WGK (Water Danger/Protection)
CAS# 38869-37-3: No information available.
Canada
None of the chemicals in this product are listed on the DSL/NDSL list.
CAS# 38869-37-3 is not listed on Canada's Ingredient Disclosure List.
US FEDERAL
TSCA
CAS# 38869-37-3 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

概述

1-(4-羟苯基)哌嗪二氰溴化物可用作医药合成中间体，如制备1-乙酰基-4-(4-羟基苯基)哌嗪。酮康唑（Ketoconazole）是一种高效低毒、口服有效的广谱抗真菌药物，其关键中间体之一是1-乙酰基-4-(4-羟基苯基)哌嗪。

制备 1. 合成二溴乙基胺氢溴酸盐

在2000毫升三口烧瓶中加入二乙醇胺194毫升（210克，2.0摩尔）。在冷却搅拌下滴加40% HBr溶液1050毫升（约2.5小时内加完），然后将反应瓶装上高35厘米的分馏柱，并加热至120-130°C。馏出生成的水（40小时收集500毫升）。提高温度至140-150°C，蒸出过量的氢溴酸（沸点124°C）至反应液呈稠状，稍冷后加入丙酮搅拌均匀。冷却后析出晶体，滤集并用丙酮洗涤，抽干得319.7克（收率51.2%），产物熔点为166-170°C。滤液减压浓缩，析出结晶，经丙酮重结晶得二溴乙基胺氢溴酸盐27.5克，其熔点为142-148°C。

2. 合成4-甲氧基苯基哌嗪二氢溴酸盐

在反应瓶中加入二溴乙基胺氢溴酸盐15.6克（0.05摩尔），加少许甲醇，然后加正丁醇40毫升加热溶解。再加入对氨基苯甲醚6.19克（0.05摩尔），于110°C左右搅拌回流6小时。继续加热和搅拌下分次加入无水碳酸钠粉5.2克，并在110°C条件下搅拌反应6小时。稍冷后将溶液倾出，在冰冷中结晶，滤集晶体并用冷丙酮洗涤，得产物4-甲氧基苯基哌嗪二氢溴酸盐7克，其熔点为216-222°C。瓶内固体用水精制除去无机盐也能获得约8克以上（收率60-66%），产品熔点为218-219°C。

3. 合成4-羟基苯基哌嗪二氢溴酸盐

在反应瓶中加入回收的40% HBr溶液300毫升及4-甲氧基苯基哌嗪二氢溴酸盐39克（0.143摩尔），装上高35厘米的分馏柱，并加热回流。缓缓馏出水约88毫升，然后提高温度至124°C持续蒸馏6小时。将反应液减压浓缩至稠状后稍冷加丙酮50毫升，摇匀、冷却，滤集结晶并用丙酮洗涤得产物4-羟基苯基哌嗪二氢溴酸盐38克（收率78.6%），其熔点为280°C（分解）。

反应信息

• 作为反应物：
  描述：

  1-(4-hydroxyphenyl)piperazine hydrobromide 在 ammonium hydroxide 、 sodium hydride 作用下， 以 吡啶 、 甲醇 为溶剂， 反应 19.0h， 生成 (2R,4R)-Ketoconazole
  参考文献：
  名称：

  非对映异构酮康唑类似物的合成

  摘要：

  研究了酮康唑的反式异构体以及相应的去乙酰基，1-甲基-，1-甲酰基和1-甲磺酰基类似物的合成。这些异构体以及相应的顺式-非对映异构体通过其碳13 nmr光谱进行表征。

  DOI：

  10.1002/jhet.5570270739
• 作为产物：
  描述：

  双(2-溴乙基)胺氢溴酸盐 在 水 、 氢溴酸 、 正丁醇 作用下， 生成 1-(4-hydroxyphenyl)piperazine hydrobromide
  参考文献：
  名称：

  Prelog; Blazek, Collection of Czechoslovak Chemical Communications, 1934, vol. 6, p. 211,218

  摘要：

  DOI：

文献信息

• 2-Azolylmethyl-2-aryl-1,3-dioxolanes and the salts thereof, agents
  申请人：Hoechst Aktiengesellschaft

  公开号：US04824846A1

  公开（公告）日：1989-04-25

  Compounds I ##STR1## where A equals CH or N; Ar equals naphthyl, thienyl or phenyl; R.sup.1 equals alkyl, F or Cl; g equals zero, 1 or 2; and Y equals various heterocyclic bases, and the acid-addition salts thereof, are described. Several preparation processes are described. The compounds IIIa ##STR2## where R.sup.1, g and Y are as specified in the case of the formula I, serve as intermediates for the preparation of these compounds. Processes are also specified for the preparation of IIIa. I represent valuable antimycotics.

  化合物I ##STR1## 中，其中A等于CH或N；Ar等于萘基、噻吩基或苯基；R.sup.1等于烷基、F或Cl；g等于零、1或2；Y等于各种杂环碱基，以及它们的酸盐，已经描述。描述了几种制备过程。化合物IIIa ##STR2## 中，其中R.sup.1、g和Y如公式I中所述，用作制备这些化合物的中间体。还指定了制备IIIa的过程。I代表有价值的抗真菌药物。
• 一种泊沙康唑中间体1-（4-羟基苯基）-4-（4-氨基苯基）-哌嗪的制备工艺
  申请人：张家口市格瑞高新技术有限公司

  公开号：CN108003118A

  公开（公告）日：2018-05-08

  本发明涉及化学药物的合成技术领域，具体地说是一种泊沙康唑中间体1‑（4‑羟基苯基）‑4‑（4‑氨基苯基）‑哌嗪的制备工艺。本发明的制备工艺是a.对甲氧基苯基哌嗪盐酸盐的制备；b.对羟基苯基哌嗪氢溴酸盐的制备；c.1‑（4‑羟基苯基）‑4‑（4‑硝基苯基）‑哌嗪的制备；d.1‑（4‑羟基苯基）‑4‑（4‑氨基苯基）‑哌嗪粗品的制备；e.产品纯化。本发明选用价廉的溶剂和活性高的镍催化剂，采取低压加氢反应，大大降低了原材料成本；后处理经除镍离子、铝离子等重要环节，产品质量达到含量99.2%、单个最大杂峰值<0.1%、总杂峰值<1.0%；极大地增强了产品的国内外市场竞争力。
• Novel 1-(1,3-dioxolan-2-ylmethyl)-1H-imidazoles
  申请人：Janssen Pharmaceutica N.V.

  公开号：US04144346A1

  公开（公告）日：1979-03-13

  Novel 1-(1,3-dioxolan-2-ylmethyl)-1H-imidazoles and 1H-1,2,4-triazoles useful as antifungal and antibacterial agents.

  新型1-(1,3-二氧杂环戊烷-2-基甲基)-1H-咪唑和1H-1,2,4-三唑，可用作抗真菌和抗菌剂。
• Heterocyclic derivatives of
  申请人：Janssen Pharmaceutica, N.V.

  公开号：US04287195A1

  公开（公告）日：1981-09-01

  Novel heterocyclic derivatives of [4-(piperazin-1-yl-phenloxymethyl)-1,3-dioxolan-2-ylmethyl]-1H-imidazoles and 1H-1,2,4-triazoles, useful as antifungal and antibacterial agents.

  新型杂环衍生物，包括[4-(哌嗪-1-基苯氧甲基)-1,3-二噁烷-2-基甲基]-1H-咪唑和1H-1,2,4-三唑，作为抗真菌和抗菌剂具有用途。
• Antibacterial and Antifungal Agents, XV: Synthesis and Antifungal Activity of Structural Analogues of Bifonazole and Ketoconazole
  作者：Giorgio Stefancich、Marino Artico、Giorgio Ortar、Romano Silvestri、Giovanna Simonetti、Germana Apuzzo、Marco Artico

  DOI：10.1002/ardp.19923251102

  日期：——

  The synthesis and antifungal activities of the cis‐ and trans‐1‐acetyl‐4‐4‐[[2‐(1,1′‐biphenyl‐4‐yl)‐2‐(1H‐imidazol‐1‐ylmethyl)‐1,3‐dioxolan‐4‐yl]‐methoxy]phenyl}piperazines 3 and 4 are reported. Stereochemical assignments to diastereomeric pairs of cis/trans isomers were made on the basis of 1H‐ and 13C‐NMR data. Among test derivatives the best activity was shown by the benzoyl esters of the cis‐

  顺式和反式 1-乙酰基-4-4-[[2-(1,1'-联苯-4-基)-2-(1H-咪唑-1-基甲基)-的合成和抗真菌活性报道了 1,3-二氧戊环-4-基]-甲氧基]苯基}哌嗪 3 和 4。基于 1H- 和 13C-NMR 数据对非对映异构体的顺式/反式异构体对进行立体化学分配。在测试衍生物中，顺-和反-[2-(1,1'-联苯-4-基)-2-(1H-咪唑-1-基甲基)-1,3 -dioxolan-4-yl]甲醇 9 和 10。