(R,R)-(-)-2,5-二(甲氧甲基)吡咯烷 | 90290-05-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯烷类
• 中文名称: (R,R)-(-)-2,5-二(甲氧甲基)吡咯烷
• 中文别名: (R,R)-(-)-2,5-二(甲氧甲基)吡咯烷,97
• 英文名称: (2R,5R)-2,5-bis(methoxymethyl)pyrrolidine
• 英文别名: (R,R)-2,5-bis(methoxymethyl)pyrrolidine；(2R,5R)-bis(methoxymethyl)pyrrolidine；(R,R)-bis(methoxymethyl)pyrrolidine
• CAS: 90290-05-4
• 化学式: C₈H₁₇NO₂
• 分子量: 159.228
• InChiKey: HDXYTIYVVNJFLU-HTQZYQBOSA-N

物化性质

• 沸点：
  106-108°C/18mm
• 密度：
  1.0469 (rough estimate)
• 闪点：
  106-108°C/18mm
• 稳定性/保质期：
  对空气和湿气具有较好的稳定性。

计算性质

• 辛醇/水分配系数(LogP)：
  0.1
• 重原子数：
  11
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  30.5
• 氢给体数：
  1
• 氢受体数：
  3

安全信息

• 危险品标志：
  Xi
• 危险类别码：
  R36/37/38
• 安全说明：
  S24/25,S26,S36
• 储存条件：
  在阴凉处储存以避免阳光直射。

SDS

Name:	(R R)-(-)-2 5-Bis(Methoxymethyl)Pyrrolidine 96% Material Safety Data Sheet
Synonym:	None Known
CAS:	90290-05-4

Section 1 - Chemical Product MSDS Name:(R R)-(-)-2 5-Bis(Methoxymethyl)Pyrrolidine 96% Material Safety Data Sheet
Synonym:None Known

---

Section 2 - COMPOSITION, INFORMATION ON INGREDIENTS

CAS#	Chemical Name	content	EINECS#
90290-05-4	(R,R)-(-)-2,5-Bis(Methoxymethyl)Pyrrol	96%	unlisted

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

---

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.
Ingestion:
May cause irritation of the digestive tract. The toxicological properties of this substance have not been fully investigated.
Inhalation:
May cause respiratory tract irritation. The toxicological properties of this substance have not been fully investigated.
Chronic:
No information found.

---

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. Wash clothing before reuse.
Ingestion:
Never give anything by mouth to an unconscious person. Get medical aid. 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:

---

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. Vapors may be heavier than air. They can spread along the ground and collect in low or confined areas. Runoff from fire control or dilution water may cause pollution.
Extinguishing Media:
Use agent most appropriate to extinguish fire. Use water spray, dry chemical, carbon dioxide, or appropriate foam.

---

Section 6 - ACCIDENTAL RELEASE MEASURES
General Information: Use proper personal protective equipment as indicated in Section 8.
Spills/Leaks:
Absorb spill with inert material (e.g. vermiculite, sand or earth), then place in suitable container. Avoid runoff into storm sewers and ditches which lead to waterways. Clean up spills immediately, observing precautions in the Protective Equipment section. Provide ventilation.

---

Section 7 - HANDLING and STORAGE
Handling:
Wash thoroughly after handling. Remove contaminated clothing and wash before reuse. Use with adequate ventilation. Avoid contact with eyes, skin, and clothing. Keep container tightly closed. Avoid ingestion and inhalation.
Storage:
Keep container closed when not in use. Store in a tightly closed container. Store in a cool, dry, well-ventilated area away from incompatible substances.

---

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# 90290-05-4: 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.

---

Section 9 - PHYSICAL AND CHEMICAL PROPERTIES

Physical State: Liquid
Color: clear, colorless
Odor: Not available.
pH: Not available.
Vapor Pressure: Not available.
Viscosity: Not available.
Boiling Point: Not available.
Freezing/Melting Point: Not available.
Autoignition Temperature: Not applicable.
Flash Point: Not applicable.
Explosion Limits, lower: Not available.
Explosion Limits, upper: Not available.
Decomposition Temperature:
Solubility in water:
Specific Gravity/Density:
Molecular Formula: C8H17NO2
Molecular Weight: 159.23

---

Section 10 - STABILITY AND REACTIVITY
Chemical Stability:
Stable under normal temperatures and pressures.
Conditions to Avoid:
Incompatible materials, excess heat, strong oxidants.
Incompatibilities with Other Materials:
Oxidizing agents.
Hazardous Decomposition Products:
Nitrogen oxides, carbon monoxide, irritating and toxic fumes and gases, carbon dioxide, nitrogen.
Hazardous Polymerization: Has not been reported

---

Section 11 - TOXICOLOGICAL INFORMATION
RTECS#:
CAS# 90290-05-4 unlisted.
LD50/LC50:
Not available.
Carcinogenicity:
(R,R)-(-)-2,5-Bis(Methoxymethyl)Pyrrolidine - Not listed by ACGIH, IARC, or NTP.

---

Section 12 - ECOLOGICAL INFORMATION

---

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

---

Section 14 - TRANSPORT INFORMATION

IATA
Not regulated as a hazardous material.
IMO
Not regulated as a hazardous material.
RID/ADR
Not regulated as a hazardous material.

---

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# 90290-05-4: No information available.
Canada
None of the chemicals in this product are listed on the DSL/NDSL list.
CAS# 90290-05-4 is not listed on Canada's Ingredient Disclosure List.
US FEDERAL
TSCA
CAS# 90290-05-4 is not listed on the TSCA inventory.
It is for research and development use only.

---

SECTION 16 - ADDITIONAL INFORMATION
N/A

制备方法与用途

制备方法

R,R-(–)-2,5-二(甲氧基甲基)吡咯烷是一个具有C₂-对称性的化合物，在有机合成中主要用作手性辅助试剂。根据在氮原子上引入的官能团性质，它可以进行手性烷基化反应或手性环化加成反应。

该分子中的氮原子可以方便地进行酰化反应，生成具有手性的酰胺衍生物。在强碱作用下，羰基α-位生成碳负离子后可发生烷基化反应。呋喃酰胺衍生物首先可通过锂-氨还原 (参考文献[1~3]) 生成中间体，并直接与卤代烃反应得到环状结构的手性烷基化产物（式1）。

若在R,R-(–)-2,5-二(甲氧基甲基)吡咯烷分子中的氮原子引入烯烃或二烯烃，可诱导手性环化加成反应，生成手性碳环（式2）或杂环化合物（式3），亦能发生更广泛的反应 (参考文献[7])，例如二烯烃衍生物与硫代乙酸共轭加成反应生成产物具有高度立体选择性（式4）。

此外，R,R-(–)-2,5-二(甲氧基甲基)吡咯烷还可用于衍生新的手性配体化合物。通过适当的化合物反应可得到手性的N,N-手性配体或N,P-手性配体（式5）。

用途简介 用途

R,R-(–)-2,5-二(甲氧基甲基)吡咯烷是一个具有C₂-对称性的化合物，在有机合成中主要用作手性辅助试剂。根据在氮原子上引入的官能团性质，它可以进行手性烷基化反应或手性环化加成反应。

该分子中的氮原子可以方便地进行酰化反应，生成具有手性的酰胺衍生物。在强碱作用下，羰基α-位生成碳负离子后可发生烷基化反应。呋喃酰胺衍生物首先可通过锂-氨还原 (参考文献[1~3]) 生成中间体，并直接与卤代烃反应得到环状结构的手性烷基化产物（式1）。

若在R,R-(–)-2,5-二(甲氧基甲基)吡咯烷分子中的氮原子引入烯烃或二烯烃，可诱导手性环化加成反应，生成手性碳环（式2）或杂环化合物（式3）。此外，还可发生更广泛的反应 (参考文献[7])，例如二烯烃衍生物与硫代乙酸共轭加成反应生成产物具有高度立体选择性（式4）。

另外，R,R-(–)-2,5-二(甲氧基甲基)吡咯烷还可用于衍生新的手性配体化合物。通过适当的化合物反应可得到手性的N,N-手性配体或N,P-手性配体（式5）。

反应信息

• 作为反应物：
  描述：

  (R,R)-(-)-2,5-二(甲氧甲基)吡咯烷 在 盐酸 、 三氟乙酸 作用下， 以 乙醚 、 二氯甲烷 、 水 、 乙腈 为溶剂， 生成 5-{[(2R,5R)-2,5-bis(methoxymethyl)-1-pyrrolidinyl]carbonyl}-2-methylpyridine
  参考文献：
  名称：

  Substituted pyridines having antiangiogenic activity

  摘要：

  具有以下化学式的化合物是抑制血管生成的抑制剂。还公开了含有这些化合物的组合物、制备这些化合物的方法以及使用这些化合物进行治疗的方法。

  公开号：

  US20040014744A1
• 作为产物：
  描述：

  (1'R,2R,5R)-2,5-bis(methoxymethyl)-1-(1-phenylethyl)-pyrrolidine 在 palladium on activated charcoal 氢气 作用下， 以 乙醇 为溶剂， 以100%的产率得到(R,R)-(-)-2,5-二(甲氧甲基)吡咯烷
  参考文献：
  名称：

  Wittland, Claudia; Risch, Nikolaus, Journal fur Praktische Chemie (Weinheim), 2000, vol. 342, # 3, p. 311 - 315

  摘要：

  DOI：

文献信息

• Design of optically active selenium reagents having a chiral tertiary amino group and their application to asymmetric inter- and intramolecular oxyselenenylations
  作者：Ken-ichi Fujita、Kazuhisa Murata、Michio Iwaoka、Shuji Tomoda

  DOI：10.1016/s0040-4020(96)01166-0

  日期：1997.2

  class of chiral selenium reagents 4–7 was synthesized on the basis of the concept that the strong intramolecular interaction between an electrophilic selenium and an optically modified tertiary amine (Se…N interaction) would induce asymmetric induction in the reaction between the selenium reagent and olefins. When 7, which showed the most powerful asymmetric induction, was applied to asymmetric methoxyselenenylation

  基于这样的概念，合成了一类新的手性硒试剂4-7：亲电硒与光学修饰的叔胺之间的强分子内相互作用（Se…N相互作用）会在硒试剂之间的反应中诱导不对称诱导和烯烃。当在最适反应条件下将表现出最强不对称诱导作用的7应用于（E）-苯基丙烯的不对称甲氧基硒基化反应时，反式最高的非对映异构体过量（de）获得了另外的产物（97％de）。在各种烯烃的不对称甲氧基硒烯化反应中（高达97％de），末端烯烃（不超过59％de的不对称分子）和内烯烃的不对称分子内氧硒烯化（不超过98％的de）也采用了相同的反应条件。结果表明，这类具有强Se…N相互作用的硒试剂可用于不对称有机合成。
• Preparation of (+)-nemorensic acid and approaches to nemorensine using the partial reduction of electron deficient furans
  作者：Timothy J. Donohoe、Jean-Baptiste Guillermin、Daryl S. Walter

  DOI：10.1039/b202514k

  日期：2002.5.23

  commercially available furoic acid, the synthesis of (+)-nemorensic acid is described in nine steps, and in 32% overall yield. Key steps in our sequence are a chiral auxiliary controlled, stereoselective, Birch reduction of 3-methyl-2-furoic acid and the stereoselective reaction of an oxonium ion generated within a tetrahydrofuran ring. Attempts to complete the synthesis of nemorensine did not succeed because

  从市售开始 糠酸，（+）-nemorensic acid的合成描述为9个步骤，总产率为32％。我们序列中的关键步骤是手性辅助控制，立体选择性，减少桦木 的 3-甲基-2-糠酸和在四氢呋喃环中产生的氧鎓离子的立体选择反应。由于神经核素的低亲核性，未能完成新的神经氨酸的合成尝试。铂炔， 这 生物碱 天然产物的基础部分。
• C2-Symmetrical Pyrrolidine Derivatives Chiral Auxiliaries in Radical Chemistry
  作者：Andres Veit、Roman Lenz、Martin E. Seiler、Markus Neuburger、Margareta Zehnder、Bernd Giese

  DOI：10.1002/hlca.19930760128

  日期：1993.2.10

  5-dideoxy-2,5-imino-L-idit (2c), respectively, as a chiral auxiliary lead to high diastereoselectivities in radical reactions (‘tin method’;Scheme 1). Removal of the chiral auxiliaries affords the corresponding alkylated fumaric acids Scheme 2. Single-crystal X-ray structures of 3b and 3c support arguments that lead to the model of 1,4-stereoinduction.

  Fumaramides图3b和3c中轴承Ç 2 -symmetrical吡咯烷部分（2 - [R，5 - [R）-2,5-双（甲氧基甲基）吡咯烷（图2b）或1,3：4,6-二- ø -亚苄基-2,5- -dideoxy-2,5-imino-L-idit（2c）作为手性助剂分别导致自由基反应中的非对映选择性高（“锡法”；方案1）。除去手性助剂得到相应的烷基化富马酸方案2。3b和3c的单晶X射线结构支持导致形成1,4-立体感应模型的论点。
• [EN] DUAL NK1/NK3 ANTAGONISTS FOR TREATING SCHIZOPHRENIA<br/>[FR] ANTAGONISTES DOUBLES DES RECEPTEURS NK1/NK3 POUR TRAITER LA SCHIZOPHRENIE
  申请人：HOFFMANN LA ROCHE

  公开号：WO2005002577A1

  公开（公告）日：2005-01-13

  The use of compounds of the general formula wherein the substituents are as described in claim 1 or pharmaceutically active acid-addition salts thereof for the preparation of medicaments for the treatment of schizophrenia.

  使用一般式化合物，其中取代基如权利要求1中所述，或其药用活性酸盐，用于制备治疗精神分裂症的药物。
• Chiral C2-symmetric 2,5-disubstituted pyrrolidine derivatives as catalytic chiral ligands in the reactions of diethylzinc with aryl aldehydes
  作者：Min Shi、Yukihiro Satoh、Yukio Masaki

  DOI：10.1039/a803336f

  日期：——

  Two kinds of chiral C2-symmetric 2,5-disubstituted pyrrolidine derivatives having a β-aminoalcohol moiety have been successfully synthesized and their catalytic abilities of chiral induction have been examined in the reactions of diethylzinc with aryl aldehydes. The production of sec-alcohols having R-absolute configuration could be achieved in very high chemical yield (85–95%) and very high enantiomeric

  已经成功地合成了两种具有β-氨基醇部分的手性C 2对称的2，5-二取代的吡咯烷衍生物，并且在二乙基锌与芳基醛的反应中研究了它们的手性诱导催化能力。当N-（2'，2'-二苯基）时，可以以很高的化学收率（85-95％）和很高的对映体过量（ee）（70-96％）来生产具有R-绝对构型的仲醇。-2'-羟乙基）-（2 R，5 R）-双（甲氧基甲基）吡咯烷用作手性配体。另一方面，当N-甲基-（2 R，5 R） -双（diarylhydroxymethyl）吡咯烷被用作催化剂的配体，相应的EE秒-醇降低至20-45％，并且对映体选择性的一个有趣的反转的加成反应中观察到米氯代，p -氯-和米氟-苯甲醛与在相同反应条件下的二乙基锌。同时，我们还合成了一些手性C 2对称N-（β在相同的反应条件下，还研究了在吡咯烷环的2，5-位上具有不同空间大小的大体积取代基的β-羟乙基）吡咯烷衍生物及其手性诱导能力。此外，我们制备了简单的手性C