3-(吡咯烷-2-基)吡啶 | 5746-86-1

• 物质功能分类: 医药中间体 - 吡啶类化合物
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 中文名称: 3-(吡咯烷-2-基)吡啶
• 中文别名: (+/-)-去甲烟碱；DL-降烟碱；2-(3-吡啶)-吡咯烷；2-(吡啶-3)-吡咯烷；(±)-降烟碱；去甲基烟碱
• 英文名称: rac-nornicotine
• 英文别名: 3-pyrrolidin-2-yl-pyridine；nornicotine；(±)-nornicotine；3-pyrrolidin-2-ylpyridine
• CAS: 5746-86-1
• 化学式: C₉H₁₂N₂
• mdl: MFCD00016913
• 分子量: 148.208
• InChiKey: MYKUKUCHPMASKF-UHFFFAOYSA-N

物化性质

• 熔点：
  235-236 °C(Solv: ethanol (64-17-5))
• 沸点：
  107-108°C 2mm
• 密度：
  1,074 g/cm3
• 闪点：
  101°C
• 溶解度：
  H2O:50 mg/mL
• 物理描述：
  Liquid
• 颜色/状态：
  Hygroscopic, somewhat viscous liquid
• 气味：
  Develops a slight amine odor, less pungent than that of nicotine
• 蒸汽压力：
  0.00923 mm Hg at 25 °C (est)
• 旋光度：
  Specific optical rotation: -89 degrees at 22 °C
• 分解：
  When heated to decomposition it emits very toxic fumes of /oxides of nitrogen and hydrochloric acid/.
• 折光率：
  Index of refraction: 1.5378 at 20 °C/D
• 解离常数：
  pKa = 5.25 (est)
• 保留指数：
  1435.4
• 稳定性/保质期：

  在常温常压下保持稳定

计算性质

• 辛醇/水分配系数(LogP)：
  0.2
• 重原子数：
  11
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.444
• 拓扑面积：
  24.9
• 氢给体数：
  1
• 氢受体数：
  2

ADMET

代谢

Nornicotine 是已知的一种尼古丁的第三手烟雾代谢物。

Nornicotine is a known thirdhand smoke metabolite of Nicotine.

来源:NORMAN Suspect List Exchange

毒理性

• 相互作用

... Nornicotine 导致异常蛋白质糖基化并催化某些处方药物，如常用的类固醇泼尼松，的共价修饰。...

... Nornicotine causes aberrant protein glycation and catalyzes the covalent modification of certain prescription drugs such as the commonly used steroid, prednisone. ...

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 人类毒性摘录

/CASE REPORTS/ 脐带组织被研究作为检测产前尼古丁暴露的手段。... 在2009年6月至9月期间，19名有烟草暴露史的女性（孕期直接吸烟或二手烟暴露）同意参与研究。完成了一份问卷，以记录怀孕每个阶段尼古丁的暴露情况。所有婴儿均为足月产（38周或以上），并获得了成对的脐带组织（10厘米或更长的段）和胎粪。... 诺尼克丁仅在胎粪中被检测到，浓度非常低。... 当母亲表示她在怀孕早期就戒烟了或者只有二手烟暴露时，所有分析物的浓度最低，如果暴露仅限于第一或第二孕期间，检测效果则较差。...

/CASE REPORTS/ Umbilical cord tissue was studied as a means of detecting prenatal exposure to nicotine. ... Between June and September 2009, 19 women with a tobacco exposure history (either first- or second-hand tobacco smoke exposure during pregnancy) were consented for the study. A questionnaire was completed to document nicotine exposure during each trimester of pregnancy. All infants were delivered at term (38 weeks or greater) and paired umbilical cord tissue (10-cm segment or greater) and meconium were obtained. ... Nornicotine was detected only in meconium, at very low concentrations. ... All analyte concentrations were lowest when the mother stated she quit smoking early in pregnancy or had only second-hand exposure, and detection was poor if exposure was limited to the first or second trimesters. ...

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 非人类毒性摘录

实验动物：神经毒性/ 当前研究表明，S(-)-假尼古丁以浓度依赖性方式增加了大鼠纹状体切片中的多巴胺（DA）释放。DA释放的增加是通过S(-)-假尼古丁诱导内源性3,4-二羟基苯乙酸（DOPAC）在纹状体灌流液中的溢出以及通过S(-)-假尼古丁诱导预先装载了[3H]DA的纹状体切片中氚的溢出来表明的。低浓度的S(-)-假尼古丁（0.01-1.0微M），未能引起内源性DOPAC溢出，也无法调节电刺激引起的DOPAC溢出。S(-)-假尼古丁诱导的DOPAC溢出与S(-)-尼古丁产生的DOPAC溢出进行了比较。比较等摩尔浓度（0.1-100微M）的S(-)-假尼古丁和S(-)-尼古丁，S(-)-假尼古丁的灌流导致了显著更大的DOPAC溢出。与S(-)-尼古丁的作用相反，S(-)-假尼古丁在整个S(-)-假尼古丁暴露期间引起了持续的DOPAC溢出增加。此外，在控制Krebs缓冲液中S(-)-假尼古丁引起的DOPAC溢出被低钙缓冲液的灌流所抑制。而且，在低钙缓冲液中，30和100微M S(-)-假尼古丁诱导的DOPAC溢出与没有S(-)-尼古丁的情况没有差异，烟草产品和S(-)-尼古丁的一个已知代谢物在钙依赖性方式下增加了大鼠纹状体切片中的DA释放。有趣的是，与S(-)-尼古丁不同，似乎对S(-)-假尼古丁的这种作用没有出现脱敏现象。

/LABORATORY ANIMALS: Neurotoxicity/ The present study demonstrates that S(-)-nornicotine evoked a concentration-dependent increase in dopamine (DA) release from superfused rat striatal slices. The increase in DA release was indicated by an S(-)-nornicotine-induced overflow of endogenous 3,4-dihydroxyphenylacetic acid (DOPAC) in the striatal superfusate and by an S(-)-nornicotine-induced increase in tritium overflow from striatal slices preloaded with [3H]DA. Low concentrations (0.01-1.0 microM) of S(-)-nornicotine, which did not evoke endogenous DOPAC overflow, also were unable to modulate electrically evoked DOPAC overflow. The increase in DOPAC overflow induced by S(-)-nornicotine was compared with that produced by S(-)-nicotine. Comparing equimolar concentrations (0.1-100 microM) of S(-)-nornicotine and S(-)-nicotine, superfusion with S(-)-nornicotine resulted in a significantly greater DOPAC overflow. In contrast to the effect of S(-)-nicotine, S(-)-nornicotine evoked a sustained increase in DOPAC overflow for the entire period of S(-)-nornicotine exposure. Furthermore, DOPAC overflow evoked by S(-)-nornicotine in control Krebs buffer was inhibited by superfusion with a low-calcium buffer. Moreover, in the low-calcium buffer, DOPAC overflow induced by 30 and 100 microM S(-)-nornicotine was not different from that with no S(-)-nicotine, tobacco products and a known metabolite of S(-)-nicotine, increases DA release in a calcium-dependent manner in superfused rat striatal slices. It is interesting that unlike S(-)-nicotine, there does not appear to be desensitization to this effect of S(-)-nornicotine.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 非人类毒性摘录

在测试的五种烟草生物碱中，只有安那巴辛导致中国仓鼠卵巢细胞（CHO）姐妹染色单体交换（SCE）数量呈剂量依赖性增加。尼古丁和去甲尼古丁在高浓度下适度增加了SCE的基础频率。而安巴比林和肌醇对SCE的自发频率没有影响。

/GENOTOXICITY/ Of five tobacco alkaloids tested, only anatabine led to a dose-dependent enhancement of the number of sister-chromatid exchanges (SCE) in Chinese hamster ovary cells (CHO). Nicotine and nornicotine at high concentrations increased the baseline frequency of SCEs moderately. Anabasine and myosmine had no influence on the spontaneous frequency of SCEs.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 非人类毒性摘录

/其他毒性信息/ ... 发现诺尼丁可以共价地改变淀粉样β-肽，导致肽聚集减少。这种反应级联的潜在后果包括减少斑块形成和/或肽清除的改变，以及可溶性淀粉样β-肽聚集物的毒性减弱。所描述的发现为尼古丁在阿尔茨海默症中的神经保护作用提供了另一种机制，并基于共价化学事件提供了改变淀粉样折叠的方法。

/OTHER TOXICITY INFORMATION/ ... Nornicotine was found to covalently alter amyloid beta-peptide, leading to reduced peptide aggregation. Potential consequences of this reaction cascade include reduced plaque formation and/or altered clearance of the peptide, as well as attenuated toxicity of soluble amyloid beta-peptide aggregates. The findings described provide an alternative mechanism for nicotine neuroprotection in AD and a means for the alteration of amyloid folding based on a covalent chemical event.

来源:Hazardous Substances Data Bank (HSDB)

安全信息

• 危险等级：
  6.1
• 危险品标志：
  Xn
• 安全说明：
  S26,S36/37
• 危险类别码：
  R20/21/22,R36/37/38
• WGK Germany：
  3
• 海关编码：
  2933990090
• 危险品运输编号：
  2810
• RTECS号：
  QS6350000
• 包装等级：
  III
• 危险类别：
  6.1
• 储存条件：
  请将药品存放在2-8℃的环境中，避光保存于阴凉干燥处，并确保容器密封。

SDS

Material Safety Data Sheet

---

Section 1. Identification of the substance
Product Name: 3-(Pyrrolidin-2-yl)pyridine
Synonyms: DL-Nornicotine

---

Section 2. Hazards identification
Harmful by inhalation, in contact with skin, and if swallowed.
H331: Toxic if inhaled
H302: Harmful if swallowed
H312: Harmful in contact with skin
H315: Causes skin irritation
H319: Causes serious eye irritation
P261: Avoid breathing dust/fume/gas/mist/vapours/spray
P280: Wear protective gloves/protective clothing/eye protection/face protection
P305+P351+P338: IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses if present
and easy to do – continue rinsing
IF INHALED: Remove victim to fresh air and keep at rest in a position comfortable for breathing
P304+P340:
P405: Store locked up

---

Section 3. Composition/information on ingredients.
Ingredient name: 3-(Pyrrolidin-2-yl)pyridine
CAS number: 5746-86-1

---

Section 4. First aid measures
Immediately wash skin with copious amounts of water for at least 15 minutes while removing
Skin contact:
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.

---

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.

---

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.

---

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, refrigerated.
Storage:

---

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.

---

Section 9. Physical and chemical properties
Appearance: Not specified
Boiling point: No data
Melting point: No data
Flash point: No data
Density: No data
Molecular formula: C9H12N2
Molecular weight: 148.2

---

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.

---

Section 11. Toxicological information
No data.

---

Section 12. Ecological information
No data.

---

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.

---

Section 14. Transportation information
UN Number: UN2810 Class: 6.1 Packing group: III
Proper shipping name: TOXIC, LIQUIDS, ORGANIC, N.O.S. OR TOXIC, LIQUIDS, ORGANIC, N.O.S. INHALA-
TION HAZARD, PACKING GROUP I, ZONE A OR B (3-(Pyrrolidin-2-yl)pyridine)

---

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.

---

SECTION 16 - ADDITIONAL INFORMATION
N/A

制备方法与用途

用途：用作标准品

反应信息

• 作为反应物：
  描述：

  3-(吡咯烷-2-基)吡啶 在 O,O'-dibenzoyl-L-tartaric acid 作用下， 以 乙醇 、 水 为溶剂， 反应 13.5h， 生成 烟碱
  参考文献：
  名称：

  一种(S)-烟碱的制备方法

  摘要：

  本发明公开了一种(S)‑烟碱的制备方法，该方法系以3‑吡啶甲胺为反应原料，经相转移烯丙基化、硼氢化氧化、环化及甲基化反应将3‑吡啶甲胺转化为外消旋烟碱，再经L‑酒石酸酯拆分得到高光学纯度的(S)‑烟碱。该方法操作简便易行，试剂廉价易得，反应过程绿色环保，产物烟碱的纯度和收率都较高，适合于工业化生产。

  公开号：

  CN115594662A
• 作为产物：
  描述：

  4-羟基-1-(3-吡啶基)-1-丁酮 在 草酰氯 、 2,3,4,6-四-O-叔戊酰基-beta-D-吡喃半乳糖胺 、 二甲基亚砜 、 三乙胺 作用下， 生成 3-(吡咯烷-2-基)吡啶
  参考文献：
  名称：

  Methods of using QIAPINE

  摘要：

  QIAPINE™的用途包括治疗主观内出血，如硬膜下血肿和蛛网膜下腔出血，以及眼部出血，如虹膜积血和玻璃体出血。还描述了QIAPINE™用于治疗由虹膜积血或玻璃体出血导致的视力丧失。

  公开号：

  US09668969B1
• 作为试剂：
  描述：

  对硝基苯甲醛 、 丙酮 在 phosphate buffer 、 3-(吡咯烷-2-基)吡啶 作用下， 以 二甲基亚砜 为溶剂， 生成 1-(4-硝基苯基)-3-氧代-1-丁醇
  参考文献：
  名称：

  Kinetic isotope and thermodynamic analysis of the nornicotine-catalyzed aqueous aldol reaction

  摘要：

  A series of kinetic isotope effects and thermodynamic studies were performed to test key predictions of a computationally derived model for a nornicotine-catalyzed aqueous aldol reaction. The relative energies of the two computationally-derived transition states were challenged using the proton inventory, which demonstrated that a single water molecule from the solvent is involved in, or before, the rate-limiting step. These results suggest the importance of proton transfer in the aqueous aldol reaction and may assist the development of other aqueous organocatalytic processes. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tet.2005.09.094

文献信息

• [EN] MICROBIOCIDAL OXADIAZOLE DERIVATIVES<br/>[FR] DÉRIVÉS D'OXADIAZOLE MICROBIOCIDES
  申请人：SYNGENTA PARTICIPATIONS AG

  公开号：WO2017157962A1

  公开（公告）日：2017-09-21

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

  式(I)的化合物，其中取代基如权利要求1所定义，作为杀虫剂特别是杀菌剂有用。
• [EN] INSECTICIDAL TRIAZINONE DERIVATIVES<br/>[FR] DÉRIVÉS DE TRIAZINONE INSECTICIDES
  申请人：SYNGENTA PARTICIPATIONS AG

  公开号：WO2013079350A1

  公开（公告）日：2013-06-06

  Compounds of the formula (I) or (I'), wherein the substituents are as defined in claim 1, are useful as pesticides.

  式(I)或(I')的化合物，其中取代基如权利要求1所定义的那样，可用作杀虫剂。
• Novel insecticides
  申请人：Syngenta Participations AG

  公开号：EP2540718A1

  公开（公告）日：2013-01-02

  Compounds of formula I wherein the substituents are as defined in claim 1, and the agrochemically acceptable salts and all stereoisomers and tautomeric forms of the compounds of formula I can be used as insecticides and can be prepared in a manner known per se.

  式I的化合物 其中取代基如权利要求1所定义，并且式I化合物的农药可接受盐以及所有立体异构体和互变异构形式可用作杀虫剂，并且可以按照已知的方法制备。
• Molecules having pesticidal utility, and intermediates, compositions, and processes, related thereto
  申请人：Dow AgroSciences LLC

  公开号：US20180279612A1

  公开（公告）日：2018-10-04

  This disclosure relates to the field of molecules having pesticidal utility against pests in Phyla Arthropoda, Mollusca, and Nematoda, processes to produce such molecules, intermediates used in such processes, pesticidal compositions containing such molecules, and processes of using such pesticidal compositions against such pests. These pesticidal compositions may be used, for example, as acaricides, insecticides, miticides, molluscicides, and nematicides. This document discloses molecules having the following formula (“Formula One”).

  这份披露涉及具有对节肢动物门、软体动物门和线虫门害虫具有杀虫效用的分子领域，用于生产此类分子的过程，用于此类过程的中间体，含有此类分子的杀虫组合物，以及使用此类杀虫组合物对抗此类害虫的过程。这些杀虫组合物可以用作螨虫剂、杀虫剂、螨虫剂、软体动物杀虫剂和线虫杀虫剂。本文件披露了具有以下式（“式一”）的分子。
• PROCESS FOR THE RESOLUTION OF (R,S)-NICOTINE
  申请人：Divi Murali Krishna Prasad

  公开号：US20120197022A1

  公开（公告）日：2012-08-02

  (R,S)-Nicotine was resolved through diastereomeric salt formation using dibenzoyl-d-tartaric acid and dibenzoyl-l-tartaric acid to obtain enantiomerically pure (S)-nicotine and (R)-nicotine.

  (R,S)-尼古丁通过使用二苯乙酰-d-酒石酸和二苯乙酰-l-酒石酸形成对映异构盐来分离，以获得对映纯的(S)-尼古丁和(R)-尼古丁。

表征谱图