(S)-4-氯-3-羟基丁腈 | 127913-44-4

• 物质功能分类: 有机原料 - 腈类化合物
• 分子结构分类: 有机化合物 - 有机卤素化合物 - 卤代醇
• 中文名称: (S)-4-氯-3-羟基丁腈
• 中文别名: S(-)-4-氯-3-羟基丁腈(阿伐他汀中间体)；S-4-氯-3-羟基丁腈；S(-)-4-氯-3-羟基丁腈
• 英文名称: (S)-4-chloro-3-hydroxy butyronitrile
• 英文别名: (S)-4-chloro-3-hydroxybutanenitrile；(S)-4-Chloro-3-hydroxybutyronitrile；(3S)-4-chloro-3-hydroxybutanenitrile
• CAS: 127913-44-4
• 化学式: C₄H₆ClNO
• mdl: MFCD00273363
• 分子量: 119.551
• InChiKey: LHBPNZDUNCZWFL-BYPYZUCNSA-N

物化性质

• 沸点：
  110 °C/1 mmHg(lit.)
• 密度：
  1.250 g/mL at 20 °C(lit.)
• 闪点：
  110 °C
• 溶解度：
  氯仿（微溶）、甲醇（微溶）

计算性质

• 辛醇/水分配系数(LogP)：
  -0.1
• 重原子数：
  7
• 可旋转键数：
  2
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.75
• 拓扑面积：
  44
• 氢给体数：
  1
• 氢受体数：
  2

安全信息

• 危险品标志：
  Xi
• 安全说明：
  S28,S36/37,S45
• 危险类别码：
  R23/24/25
• 海关编码：
  2942000000
• 危险性防范说明：
  P261,P305+P351+P338
• 危险性描述：
  H315,H319,H335
• 储存条件：
  室温

SDS

Material Safety Data Sheet

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Section 1. Identification of the substance
Product Name: (S)-4-Chloro-3-hydroxybutyronitrile
Synonyms:

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Section 2. Hazards identification
Harmful by inhalation, in contact with skin, and if swallowed.

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Section 3. Composition/information on ingredients.
Ingredient name: (S)-4-Chloro-3-hydroxybutyronitrile
CAS number: 127913-44-4

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Section 4. First aid measures
Skin contact: Immediately wash skin with copious amounts of water for at least 15 minutes while removing
contaminated clothing and shoes. If irritation persists, seek medical attention.
Eye contact: Immediately wash skin with copious amounts of water for at least 15 minutes. Assure adequate
flushing of the eyes by separating the eyelids with fingers. If irritation persists, seek medical
attention.
Inhalation: Remove to fresh air. In severe cases or if symptoms persist, seek medical attention.
Ingestion: Wash out mouth with copious amounts of water for at least 15 minutes. Seek medical attention.

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Section 5. Fire fighting measures
In the event of a fire involving this material, alone or in combination with other materials, use dry
powder or carbon dioxide extinguishers. Protective clothing and self-contained breathing apparatus
should be worn.

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Section 6. Accidental release measures
Personal precautions: Wear suitable personal protective equipment which performs satisfactorily and meets local/state/national
standards.
Respiratory precaution: Wear approved mask/respirator
Hand precaution: Wear suitable gloves/gauntlets
Skin protection: Wear suitable protective clothing
Eye protection: Wear suitable eye protection
Methods for cleaning up: Mix with sand or similar inert absorbent material, sweep up and keep in a tightly closed container
for disposal. See section 12.
Environmental precautions: Do not allow material to enter drains or water courses.

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Section 7. Handling and storage
Handling: This product should be handled only by, or under the close supervision of, those properly qualified
in the handling and use of potentially hazardous chemicals, who should take into account the fire,
health and chemical hazard data given on this sheet.
Store in closed vessels.
Storage:

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Section 8. Exposure Controls / Personal protection
Engineering Controls: Use only in a chemical fume hood.
Personal protective equipment: Wear laboratory clothing, chemical-resistant gloves and safety goggles.
General hydiene measures: Wash thoroughly after handling. Wash contaminated clothing before reuse.

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Section 9. Physical and chemical properties
Appearance: Not specified
Boiling point: No data
No data
Melting point:
Flash point: No data
Density: No data
Molecular formula: C4H6ClNO
Molecular weight: 119.6

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Section 10. Stability and reactivity
Conditions to avoid: Heat, flames and sparks.
Materials to avoid: Oxidizing agents.
Possible hazardous combustion products: Carbon monoxide, nitrogen oxides, hydrogen chloride.

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Section 11. Toxicological information
No data.

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Section 12. Ecological information
No data.

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Section 13. Disposal consideration
Arrange disposal as special waste, by licensed disposal company, in consultation with local waste
disposal authority, in accordance with national and regional regulations.

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Section 14. Transportation information
Non-harzardous for air and ground transportation.

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Section 15. Regulatory information
No chemicals in this material are subject to the reporting requirements of SARA Title III, Section
302, or have known CAS numbers that exceed the threshold reporting levels established by SARA
Title III, Section 313.

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SECTION 16 - ADDITIONAL INFORMATION
N/A

制备方法与用途

用途

(S)-4-氯-3-羟基丁腈是阿托伐他汀的侧链中间体。阿托伐他汀钙由美国辉瑞医药研发，能够有效降低血脂，具有高效低毒的优点，备受市场青睐。

制备 方法一：

将200kg (S)-环氧氯丙烷（2.16mol, 1eq）和600kg甲苯投入反应器中，升温至40℃。滴加65kg氢氰酸（2.4mol, 1.11eq）（流量计计量），控制滴加时间为4h。保温反应，直至在线监测显示反应完全。向反应釜中加入100kg 10% 氢氧化钠溶液，搅拌30min后静置分层。有机相减压浓缩，得到234kg (S)-4-氯-3-羟基丁腈，纯度为98.2%。

方法二：

在三口瓶中加入R-环氧氯丙烷（9.25g, 100mmol）、水（100mL），冷却至0℃。滴加30% 氰化钠水溶液（18mL, 110mmol）。用50% 硫酸调节pH值至8.0，搅拌反应3小时。使用二氯甲烷提取反应液（20mL×3），合并有机相并用水洗涤（10mL×3次）。无水硫酸钠干燥后减压浓缩至干，得到黄色固体。

化学性质

(S)-4-氯-3-羟基丁腈为无色至淡黄色液体，在常温下应密封保存。沸点为76-80°C/0.1mmHg。

用途

多种手性医药中间体。 罗素伐他汀的中间体。

反应信息

• 作为反应物：
  描述：

  (S)-4-氯-3-羟基丁腈 生成 tert-butyl (2S,4S)-4-{[tert-butyl(dimethyl)silyl]oxy}-2-phenylpyrrolidine-1-carboxylate
  参考文献：
  名称：

  [EN] MITOTIC KINESIN INHIBITORS
  [FR] INHIBITEURS DE KINESINE MITOTIQUE

  摘要：

  本发明涉及二氢吡唑化合物，用于治疗细胞增殖性疾病，治疗与KSP动力蛋白活性相关的疾病，并抑制KSP动力蛋白。该发明还涉及包含这些化合物的组合物，以及使用它们治疗哺乳动物癌症的方法。

  公开号：

  WO2003106417A1
• 作为产物：
  描述：

  4-氯-3-羟基丁腈 生成 (S)-4-氯-3-羟基丁腈
  参考文献：
  名称：

  A novel generation of optically active ethyl 4-chloro-3-hydroxybutyrate as a C4 chiral building unit using microbial dechlorination

  摘要：

  A novel procedure for the generation of optically active ethyl 4-chloro-3-hydroxybutyrate using bacterial cells was developed. Ethyl (S)-4-chloro-3-hydroxybutyrate was prepared by Pseudomonas sp. OS-K-29, which stereoselectively assimilates 2,3-dichloro-1-propanol. The reaction was based on its kinetic dehalogenation for both enantiomers using the resting cells. The obtained 4-chloro-3-hydroxybutyrate rate had high enantiomeric excess of >98%, with a yield of 33% at the microbial resolution step. Moreover, several C4 compounds having the 4-chloro-3-hydroxyl function were also resolved and gave good enantiomeric purities (>95 %ee). Ethyl (R)-4-chloro-3-hydroxybutyrate was also obtained with high enantiomeric purity (>98 %ee) using the cells of Pseudomonas sp DS-K-NR818. Copyright (C) 1996 Elsevier Science Ltd

  DOI：

  10.1016/0957-4166(96)00410-7

文献信息

• Dicyclopentyl azodicarboxylate (DCpAD): A new alternative azo-reagent for the Mitsunobu reaction
  作者：Jian Hai Yang、Li Yan Dai、Xiao Zhong Wang、Ying Qi Chen

  DOI：10.1016/j.cclet.2011.03.017

  日期：2011.9

  Dicyclopentyl azodicarboxylate is introduced as a new azo-reagent which can be conveniently prepared in two steps and be used in the Mitsunobu reaction. Though there are no distinct difference of reactivity between DCpAD and DEAD, the former is a more preferable azo-reagent for its stability.

  引入偶氮二羧酸二环戊酯作为一种新型的偶氮试剂，可以方便地分两步制备并用于Mitsunobu反应。尽管DCpAD和DEAD之间没有明显的反应性差异，但是前者由于其稳定性是更优选的偶氮试剂。
• Novel Development of Exciton-Coupled Circular Dichroism Based on Induced Axial Chirality
  作者：Shinzo Hosoi、Makiko Kamiya、Tomihisa Ohta

  DOI：10.1021/ol010176l

  日期：2001.11.1

  [reaction--see text] A simple method for determining the absolute configuration of chiral alcohols with a unique chromophoric reagent 1 based on induced exciton chirality has been developed. Practical usefulness of the present method was demonstrated by the determination of the absolute configuration of 17,18-dihydroxybergamottin.

  [反应-见正文]已经开发了一种基于诱导的激子手性，用独特的发色试剂1测定手性醇的绝对构型的简单方法。通过确定17，18-二羟基香柠檬素的绝对构型证明了本方法的实际有用性。
• Di-p-nitrobenzyl azodicarboxylate (DNAD): an alternative azo-reagent for the Mitsunobu reaction
  作者：Jianhai Yang、Liyan Dai、Xiaozhong Wang、Yingqi Chen

  DOI：10.1016/j.tet.2010.12.036

  日期：2011.2

  Di-p-nitrobenzyl azodicarboxylate is prepared in 83.6% yield in two steps as a bright yellow solid, which can be used as an azo-reagent in the Mitsunobu reaction. When a chiral secondary alcohol was used, sufficient configurational inversion of alcohol occurred under Mitsunobu conditions. That the hydrazine produced from DNAD is semisoluble in some solvents such as THF and CH2Cl2 makes it separated

  分两步制备呈亮黄色固体的二对硝基苄基偶氮二羧酸酯，产率为83.6％，可以用作Mitsunobu反应中的偶氮试剂。当使用手性仲醇时，在Mitsunobu条件下发生足够的构型醇转化。由DNAD产生的肼在某些溶剂（如THF和CH 2 Cl 2）中可半溶，因此仅通过过滤即可将其轻松从反应混合物中分离出来。然后可以将回收的肼化合物重新暴露于氧化剂以产生DNAD。由于DNAD在环境温度下比DIAD更稳定并且易于分离，因此它是Mitsunobu反应的良好替代偶氮试剂。
• Efficient Activation of Zinc: Application of the Blaise Reaction to an Expedient Synthesis of a Statin Intermediate
  作者：Hyunik Shin、No-Soo Kim、Bo Seung Choi、Ki Kon Lee、Hyeong-wook Choi、Jay Hyok Chang、Kyu Woong Lee、Do Hyun Nam

  DOI：10.1055/s-2004-831197

  日期：——

  Efficient and practical in situ zinc activation was accomplished by treatment with catalytic amount of an organic acid. The protocol was applied successfully to the Blaise reaction of various nitriles. Noteworthy is the excellent Blaise transformation of (S)-4-chloro-3-trimethylsilyloxybutyronitrile (2b) into tert-butyl (S)-6-chloro-5-hydroxy-3-oxohexanoate (1), a key intermediate for the preparation of HMG-CoA reductase inhibitors (statins).

  高效且实用的原位锌活化方法通过使用少量有机酸处理得以实现。该方案成功应用于多种腈的布莱斯反应。值得注意的是，(S)-4-氯-3-三甲基硅氧基丁腈 (2b) 经优异的布莱斯转化，生成叔丁基 (S)-6-氯-5-羟基-3-氧代己酸酯 (1)，这是制备HMG-CoA还原酶抑制剂（他汀类药物）的关键中间体。
• [EN] HERBICIDAL CINNOLINIUM COMPOUNDS<br/>[FR] COMPOSÉS HERBICIDES À BASE DE CINNOLINIUM
  申请人：SYNGENTA CROP PROTECTION AG

  公开号：WO2020127168A1

  公开（公告）日：2020-06-25

  Compounds of the formula (I) wherein the substituents are as defined in claim 1, useful as a pesticides, especially as herbicides.

  式(I)中的化合物，其中取代基如权利要求1中定义的那样，作为杀虫剂特别是除草剂是有用的。