N-肉桂基哌嗪 | 18903-01-0

• 物质功能分类: 医药中间体 - 哌嗪类化合物
• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: N-肉桂基哌嗪
• 中文别名: 1-(肉桂)哌嗪；1-肉桂基哌嗪；反式-1-肉桂基哌嗪；苯丙烯基哌嗪；肉桂基哌嗪；1-苯丙烯基哌嗪
• 英文名称: 1-(3-phenyl-2-propenyl)piperazine
• 英文别名: 1-cinnamylpiperazine；1-Cinnamyl-piperazin；N-cinnamylpiperazine；Cinnamylpiperazine；1-(3-phenylprop-2-enyl)piperazine
• CAS: 18903-01-0
• 化学式: C₁₃H₁₈N₂
• 分子量: 202.299
• InChiKey: WGEIOMTZIIOUMA-UHFFFAOYSA-N

物化性质

• 熔点：
  39-44 °C(lit.)
• 沸点：
  129 °C1 mm Hg(lit.)
• 密度：
  0.989 g/mL at 25 °C(lit.)
• 闪点：
  >230 °F

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  15
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  15.3
• 氢给体数：
  1
• 氢受体数：
  2

安全信息

• 危险品标志：
  Xi
• 安全说明：
  S26,S36
• 危险类别码：
  R36/37/38
• WGK Germany：
  3
• 海关编码：
  2933599090
• 危险品运输编号：
  OTH

SDS

Name:	1-Cinnamylpiperazine Material Safety Data Sheet
Synonym:
CAS:	18903-01-0

Section 1 - Chemical Product MSDS Name:1-Cinnamylpiperazine Material Safety Data Sheet
Synonym:

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Section 2 - COMPOSITION, INFORMATION ON INGREDIENTS

CAS#	Chemical Name	content	EINECS#
18903-01-0	1-Cinnamylpiperazine		242-652-0

Hazard Symbols: XI
Risk Phrases: 36/37/38

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Section 3 - HAZARDS IDENTIFICATION
EMERGENCY OVERVIEW
Irritating to eyes, respiratory system and skin.
Potential Health Effects
Eye:
Causes eye irritation.
Skin:
Causes skin irritation. May be harmful if absorbed through the skin.
Ingestion:
May cause irritation of the digestive tract. May be harmful if swallowed.
Inhalation:
Causes respiratory tract irritation. May be harmful if inhaled.
Chronic:
Not available.

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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.
Ingestion:
Get medical aid. Wash mouth out with 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:
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.
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.

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Section 7 - HANDLING and STORAGE
Handling:
Avoid breathing dust, vapor, mist, or gas. Avoid contact with skin and eyes.
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# 18903-01-0: Personal Protective Equipment Eyes: Not available.
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: Solid
Color: colorless - pale yellow
Odor: Not available.
pH: Not available.
Vapor Pressure: Not available.
Viscosity: Not available.
Boiling Point: 129 deg C @ 1 mmHg
Freezing/Melting Point: 39-44 deg C
Autoignition Temperature: Not available.
Flash Point: > 110 deg C (> 230.00 deg F)
Explosion Limits, lower: Not available.
Explosion Limits, upper: Not available.
Decomposition Temperature:
Solubility in water:
Specific Gravity/Density: 0.989
Molecular Formula: C13H18N2
Molecular Weight: 202.1394

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Section 10 - STABILITY AND REACTIVITY
Chemical Stability:
Not available.
Conditions to Avoid:
Incompatible materials, moisture.
Incompatibilities with Other Materials:
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# 18903-01-0 unlisted.
LD50/LC50:
Not available.
Carcinogenicity:
1-Cinnamylpiperazine - Not listed by ACGIH, IARC, or NTP.

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Section 12 - ECOLOGICAL INFORMATION
Other No information available.

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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
No information available.
IMO
No information available.
RID/ADR
No information available.

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Section 15 - REGULATORY INFORMATION

European/International Regulations
European Labeling in Accordance with EC Directives
Hazard Symbols: XI
Risk Phrases:
R 36/37/38 Irritating to eyes, respiratory system
and skin.
Safety Phrases:
S 26 In case of contact with eyes, rinse immediately
with plenty of water and seek medical advice.
S 37/39 Wear suitable gloves and eye/face
protection.
WGK (Water Danger/Protection)
CAS# 18903-01-0: No information available.
Canada
None of the chemicals in this product are listed on the DSL/NDSL list.
CAS# 18903-01-0 is not listed on Canada's Ingredient Disclosure List.
US FEDERAL
TSCA
CAS# 18903-01-0 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

用途：强痛定的中间体。

生产方法：

1. 将肉桂基氯与甲酰基哌嗪缩合，再经水解可得1-肉桂基哌嗪。
2. 将甲酰基哌嗪、无水乙醇和碳酸氢钠与肉桂基氯一起搅拌，加热至80℃回流5小时。
3. 反应物过滤后，通入干燥的氯化氢生成盐，再进行过滤和干燥，得到N-甲酰基-N'肉桂基哌嗪盐酸盐。
4. 将其溶解于水中，用活性炭脱色。
5. 滤出脱色炭后，在95-100℃下加入氢氧化钠水解15小时。
6. 反应液分层，上层油层即为1-肉桂基哌嗪，收率约为68%。

反应信息

• 作为反应物：
  描述：

  N-肉桂基哌嗪 在 盐酸 、 sodium nitrite 、 溶剂黄146 、 锌 作用下， 以 水 为溶剂， 反应 4.0h， 生成 N1-cinnamyl-N4-amino piperazine
  参考文献：
  名称：

  亚芳基酮和噻唑烷肼对克氏锥虫和利什曼原虫的多重抗寄生虫活性。

  摘要：

  针对婴儿利什曼原虫和巴西利什曼原虫，评估了一系列五十个芳基酮和噻唑亚肼。此外，针对克氏锥虫评估了新的简化的噻唑亚甲基肼衍生物。在体外建立了活性化合物对未感染的成纤维细胞或巨噬细胞的细胞毒性，以评估其抗寄生虫作用的选择性。七个噻唑亚甲基肼衍生物和十个亚芳基酮对三种寄生虫具有良好的活性。T. cruzi和Leishmania spp的IC50值。范围从90 nM-25 µM。八种化合物具有抗锥虫和利什曼原虫的多锥虫活性。（皮肤和内脏形式的病因）。这些活性化合物的选择性优于三种参考药物：苯并咪唑，葡聚糖和米替福星。在斑马鱼体内测试时，它们的毒性也很低。为了理解这些化合物的作用机理，研究了两种可能的分子靶标：磷酸三糖异构酶和克鲁普西汀。我们还使用分子剥离方法阐明了其抗T的最低结构要求。克鲁兹活动。

  DOI：

  10.3390/molecules22050709
• 作为产物：
  描述：

  肉桂基氯 在 sodium hydroxide 、 potassium carbonate 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 86.0h， 生成 N-肉桂基哌嗪
  参考文献：
  名称：

  Synthesis and pharmacological study of new calcium antagonists, analogues of cinnarizine and flunarizine

  摘要：

  Several phosphonic diethyl esters were synthesized and their calcium antagonistic activity evaluated in vitro. The diethyl phosphonate group was condensed on substituted [diphenylmethyl], [(2-benzofuranyl)phenylmethyl], [(4-(diphenylmethyl-1 piperazinyl) methyl], [4-(4-diphenylmethyl-1-piperazinyl methyl) phenylmethyl], and [4-(3-phenyl-2-propenyl)-1-piperazinyl methyl] groups. Despite the presence of the diethyl phosphonate moiety and the benzhydrylpiperazinyl group, both present in potent calcium antagonist structures, only 1 of the 19 synthesized compounds exhibited a calcium antagonistic profile.

  DOI：

  10.1016/0223-5234(93)90049-k
• 作为试剂：
  描述：

  N-(2-chloroethyl)-3-(5-nitrofuran-2-yl)prop-2-enamide 在 potassium carbonate 、 N-肉桂基哌嗪 作用下， 以 丙酮 为溶剂， 反应 3.0h， 以10%的产率得到N-(2-hydroxyethyl)-3-(5-nitro-2-furyl)propenamide
  参考文献：
  名称：

  5-Nitrofuranes and 5-nitrothiophenes with anti-Trypanosoma cruzi activity and ability to accumulate squalene

  摘要：

  Chagas disease represents a serious public health problem in South America. The first line of treatment is Nifurtimox and Benznidazole which generate toxic effects in treated patients. We have recently shown that a number of 5-nitrofuranes possess activity against Trypanosoma cruzi through oxidative stress and inhibition of parasite ergosterol biosynthesis, specifically at the level of squalene epoxidase. Here, we identify new 5-nitrofuranes and the thia-analogues with excellent effects on the viability of T. cruzi and adequate parasite/mammal selectivity indexes. Analysis of the free sterols from parasite incubated, during 120 h, with the compounds showed that some of them accumulated squalene suggesting the squalene epoxidase activity inhibition of the parasite. Nifurtimox was able to accumulate squalene only at lower incubation times. Due to this fact some derivatives were also tested as antifungal agents. Quantitative structure-activity relationship studies were also performed showing relevant features for further new derivatives design. Taken together, the results obtained in the present work point to a more general effect of 5-nitrofuranes and 5-nitrothiophenes in trypanosomatids, opening potential therapeutic possibilities of them for these infectious diseases. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2009.09.013

文献信息

• Catalyst-Free Synthesis of Chromane-Type N,O-Acetals via Intramolecular Addition of Phenols to Enamines
  作者：Vitaly A. Osyanin、Dmitry V. Osipov、Irina V. Melnikova、Kirill S. Korzhenko、Irina A. Semenova、Yuri N. Klimochkin

  DOI：10.1055/s-0040-1707209

  日期：2020.12

  Abstract A new strategy to 2-aminochromanes through catalyst-free cascade reaction of 3-trifluoroacetyl-4H-chromenes and 4H-chromene-3-carbaldehydes with cyclic secondary amines is presented. The reaction proceeds through subsequent 1,4- and 1,2-additions of amine, bimolecular elimination of trifluoroacetamide or formamide, and 6-exo-trig cyclization. The latter stage is a very rare example of addition

  摘要 通过3-三氟乙酰基-4-不含催化剂的级联反应的新策略，以2-氨基苯并二氢吡喃ħ -chromenes和4 ħ色烯-3- carbaldehydes与环状仲胺被呈现。反应通过随后的胺的1,4-和1,2-加成，三氟乙酰胺或甲酰胺的双分子消除以及6- exo - trig环化来进行。后期是将苯酚加到烯胺中的非常罕见的例子。将获得的半环N，O-缩醛用作合成其他色烷的有用前体。
• 新型钳形金属络合物及其应用
  申请人：中国科学院上海有机化学研究所

  公开号：CN109553641B

  公开（公告）日：2023-05-12

  本发明公开了一种制备新型钳形络合物的方法以及此类络合物在羧酸酯类化合物催化氢化生成相应醇的反应和二氧化碳催化氢化制备甲酰胺类化合物的两个反应中的应用，该应用是以羧酸酯，氢气为原料或者以二氧化碳、氢气和胺类化合物为原料，以上述过渡金属络合物为催化剂，在有机溶剂中或者无溶剂条件下反应，分别形成相应的醇类化合物和/或相应的甲酰胺类化合物。本发明的方法具有反应效率高、选择性好、条件温和、经济环保和操作简便等优点，具有良好的推广和应用前景。
• [EN] NEUROACTIVE COMPOUNDS AND METHODS OF USING THE SAME<br/>[FR] COMPOSÉS NEUROACTIFS ET LEURS PROCÉDÉS D'UTILISATION
  申请人：GEN HOSPITAL CORP

  公开号：WO2015200674A1

  公开（公告）日：2015-12-30

  The invention described herein relates generally to neuroactive compounds and compositions for the treatment psychotic disorders, methods for treating psychosis using these neuroactive compounds, and methods for screening for novel neuroactive compounds. Certain aspects are directed to a family of compounds called "finazines." Certain aspects are directed to in vivo screening methods using high-throughput behavioral assays in zebrafish.

  本发明描述的内容一般涉及用于治疗精神病态障碍的神活性化合物和组合物，使用这些神活性化合物治疗精神病的方法，以及筛选新型神活性化合物的方法。某些方面涉及一种称为“芬氮杂”的化合物家族。某些方面涉及使用斑马鱼高通量行为分析的在体筛选方法。
• A Nickel(II)‐Mediated Thiocarbonylation Strategy for Carbon Isotope Labeling of Aliphatic Carboxamides
  作者：Simon S. Pedersen、Aske S. Donslund、Jesper H. Mikkelsen、Oskar S. Bakholm、Florian Papp、Kim B. Jensen、Magnus B. F. Gustafsson、Troels Skrydstrup

  DOI：10.1002/chem.202005261

  日期：2021.4.26

  pharmaceutically relevant small molecules and biopharmaceuticals bearing aliphatic carboxamides have been successfully labeled with carbon‐13. Key to the success of this novel carbon isotope labeling technique is the observation that 13C‐labeled NiII‐acyl complexes, formed from a 13CO insertion step with NiII‐alkyl intermediates, rapidly react in less than one minute with 2,2’‐dipyridyl disulfide to quantitatively

  一系列带有脂族羧酰胺的药学上相关的小分子和生物药物已成功用碳13标记。这项新颖的碳同位素标记技术成功的关键在于，观察到13 C标记的Ni II-酰基络合物是由13 CO插入步骤与Ni II-烷基中间体形成的，在不到一分钟的时间内迅速与2,2反应'-二吡啶基二硫化物定量形成相应的2-吡啶基硫酯。使用13 C-SilaCOgen还是使用13C-COgen允许化学计量添加同位素标记的一氧化碳。随后一系列结构多样的胺的单罐酰化反应可提供所需的13 C标记的羧酰胺，收率很高。建议在Ni II-酰基配合物和二硫化物之间形成单电子转移途径，以提供反应性Ni III-酰基硫化物中间体，该中间体迅速经历还原性消除反应，形成所需的硫酯。通过进一步优化反应参数，可以确定仅11分钟的反应时间，从而为探索该化学方法进行碳11同位素标记开辟了可能性。最后，这种同位素标记策略可以适应13的合成C标记的利拉鲁肽和地格曲胰岛素，代表两种抗糖尿病药。
• Selective N-alkylation of amines using nitriles under hydrogenation conditions: facile synthesis of secondary and tertiary amines
  作者：Takashi Ikawa、Yuki Fujita、Tomoteru Mizusaki、Sae Betsuin、Haruki Takamatsu、Tomohiro Maegawa、Yasunari Monguchi、Hironao Sajiki

  DOI：10.1039/c1ob06303k

  日期：——

  the one-pot hydrogenation of the nitro group and the reductive alkylation of the amines. While aliphatic amines were effectively converted to the corresponding tertiary amines under Pd/C-catalyzed conditions, Rh/C was a highly effective catalyst for the N-monoalkylation of aliphatic primary amines without over-alkylation to the tertiary amines. Furthermore, the combination of the Rh/C-catalyzed N-monoalkylation

  发现腈是在催化氢化条件下用于胺的选择性N-烷基化的高效烷基化试剂。对于芳族伯胺，相应的仲胺是在以下条件下有选择地获得的：钯/ C催化的氢化条件。尽管使用电子贫乏的芳族胺或庞大的腈显示出对还原烷基化反应的较低反应性，但添加NH 4 OAc增强了反应活性，从而以优异的产率获得了芳族仲胺。在相同的反应条件下，芳族硝基化合物代替芳族伯胺可以通过多胺反应直接转化为仲胺，该反应涉及硝基的一锅加氢和胺的还原烷基化。脂族胺在以下条件下有效地转化为相应的叔胺钯/ C催化的条件， 铑/ C是用于脂族伯胺的N-单烷基化而不会过度烷基化成叔胺的高效催化剂。此外，铑/ C催化的脂肪族伯胺的N-单烷基化反应及其他钯所得仲脂族胺的/ C催化烷基化可以选择性地制备具有三个不同烷基的脂族叔胺。根据机理研究，似乎可以合理地得出以下结论：在反应的第一步中，在胺发生亲核攻击之前，腈被还原为醛亚胺。