(-)-8-苯基薄荷醇 | 65253-04-5

• 物质功能分类: 分析化学 - 标准品 - 药典标准品和杂质标准品
• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 中文名称: (-)-8-苯基薄荷醇
• 中文别名: (-)-8-苯基(2-丙基)-5-甲基环己醇
• 英文名称: (-)-8-phenylmenthol
• 英文别名: (1R,2S,5R)-(-)-8-phenylmenthol；(-)-phenylmenthol；(-)-(1R,2S,5R)-5-methyl-2-(1-methyl-1-phenylethyl)cyclohexanol；(-)-(1R,2S,5R)-2-(1-Methyl-1-phenylethyl)-5-methylcyclohexanol；(1R,2S,5R)-5-methyl-2-(2-phenylpropan-2-yl)cyclohexan-1-ol
• CAS: 65253-04-5
• 化学式: C₁₆H₂₄O
• mdl: MFCD00010501
• 分子量: 232.366
• InChiKey: WTQIZFCJMGWUGZ-BPLDGKMQSA-N

物化性质

• 比旋光度：
  -26°(20/D, c=2, C2H5OH)
• 沸点：
  130 °C (0.7501 mmHg)
• 密度：
  0.999 g/mL at 20 °C (lit.)
• 闪点：
  >230 °F
• 溶解度：
  可溶于氯仿（轻微）、甲醇（非常轻微）
• 最大波长(λmax)：
  259nm(CH2Cl2)(lit.)
• 稳定性/保质期：

  试剂纯度通过NMR和[α]D检验。

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  17
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.625
• 拓扑面积：
  20.2
• 氢给体数：
  1
• 氢受体数：
  1

安全信息

• 危险品标志：
  Xi
• 危险类别码：
  R36/37/38
• WGK Germany：
  3
• 海关编码：
  2906299090
• 安全说明：
  S26,S36

SDS

Name:	(-)-8-Phenylmenthol 98% Material Safety Data Sheet
Synonym:	None listed
CAS:	65253-04-5

Section 1 - Chemical Product MSDS Name:(-)-8-Phenylmenthol 98% Material Safety Data Sheet
Synonym:None listed

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Section 2 - COMPOSITION, INFORMATION ON INGREDIENTS

CAS#	Chemical Name	content	EINECS#
65253-04-5	(-)-8-Phenylmenthol	98	unlisted

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:
Causes eye irritation. May cause chemical conjunctivitis.
Skin:
Causes skin irritation.
Ingestion:
May cause gastrointestinal irritation with nausea, vomiting and diarrhea.
Inhalation:
Causes respiratory tract irritation. Can produce delayed pulmonary edema.
Chronic:
Effects may be delayed.

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Section 4 - FIRST AID MEASURES
Eyes: Immediately 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:
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. Vapors may be heavier than air. They can spread along the ground and collect in low or confined areas.
Extinguishing Media:
Use water spray, dry chemical, carbon dioxide, or appropriate foam.

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Section 6 - ACCIDENTAL RELEASE MEASURES
General Information: Use proper personal protective equipment as indicated in Section 8.
Spills/Leaks:
Cover with sand, dry lime or soda ash and place in a closed container for disposal. Provide ventilation.

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Section 7 - HANDLING and STORAGE
Handling:
Wash thoroughly after handling. Remove contaminated clothing and wash before reuse. Avoid contact with eyes, skin, and clothing. Keep container tightly closed. Avoid ingestion and inhalation. Use with adequate ventilation. Wash clothing before reuse.
Storage:
Store in a tightly closed container. Store in a cool, dry, well-ventilated area away from incompatible substances.

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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# 65253-04-5: 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:
A respiratory protection program that meets OSHA's 29 CFR 1910.134 and ANSI Z88.2 requirements or European Standard EN 149 must be followed whenever workplace conditions warrant respirator use.

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Section 9 - PHYSICAL AND CHEMICAL PROPERTIES

Physical State: Clear liquid
Color: clear, colorless
Odor: None reported.
pH: Not available.
Vapor Pressure: Not available.
Viscosity: viscous
Boiling Point: Not available.
Freezing/Melting Point: Not available.
Autoignition Temperature: Not applicable.
Flash Point: > 110 deg C (> 230.00 deg F)
Explosion Limits, lower: Not available.
Explosion Limits, upper: Not available.
Decomposition Temperature: Not available.
Solubility in water: immiscible
Specific Gravity/Density: 0.999 g/cm3
Molecular Formula: C15H24O
Molecular Weight: 220.35

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Section 10 - STABILITY AND REACTIVITY
Chemical Stability:
Stable at room temperature in closed containers under normal storage and handling conditions.
Conditions to Avoid:
Incompatible materials, excess heat, strong oxidants.
Incompatibilities with Other Materials:
Strong oxidizing agents.
Hazardous Decomposition Products:
Carbon monoxide, irritating and toxic fumes and gases, carbon dioxide.
Hazardous Polymerization: Has not been reported.

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Section 11 - TOXICOLOGICAL INFORMATION
RTECS#:
CAS# 65253-04-5 unlisted.
LD50/LC50:
Not available.
Carcinogenicity:
(-)-8-Phenylmenthol - 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
Not regulated as a hazardous material.
IMO
Not regulated as a hazardous material.
RID/ADR
Not regulated as a hazardous material.

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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# 65253-04-5: No information available.
Canada
None of the chemicals in this product are listed on the DSL/NDSL list.
CAS# 65253-04-5 is not listed on Canada's Ingredient Disclosure List.
US FEDERAL
TSCA
CAS# 65253-04-5 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

制备方法

在碘化亚铜催化下，(1R,2S,5R)-(–)-8-苯基薄荷醇可通过苯基溴化镁与(+)-胡薄荷酮反应制备。

合成制备方法

同样地，在碘化亚铜催化下，(1R,2S,5R)-(–)-8-苯基薄荷醇也可通过苯基溴化镁与(+)-胡薄荷酮反应制备。[1]

用途简介

(–)-8-苯基薄荷醇在合成手性不对称磷配体方面应用广泛，可与三氯化磷和联苯酚衍生物反应生成不对称有机磷配体（式1）。这些配体会与金属钌催化剂共同催化不对称加氢还原反应（式2）。

此外，(–)-8-苯基薄荷醇的衍生物也可作为手性诱导辅剂用于多种不对称化学转化中，如分子间和分子内的狄尔斯-阿尔德反应、双羟化反应以及α,β-不饱和8-苯基薄荷醇酸酯的分子内烯化等。这些反应表现出温和的速度、高度立体选择性和高产率。例如，(–)-8-苯基薄荷醇的α-酮酯（如8-苯基薄荷丙酮酸酯）可用于不对称酮加成，并适用于不对称光催化和亲核烷基化反应；其α-亚胺酯与烯烃的烯化则能够产生高光学纯度的α-亚胺酸。在甲基锌试剂的存在下，(–)-8-苯基薄荷醇还可以诱导炔基锆化合物对α-酮酸酯进行不对称加成（式3）。而在4-芳基取代哌啶的合成中，有机镁试剂对不饱和醛酮的不对称迈克尔加成反应同样受到手性辅剂(–)-8-苯基薄荷醇的诱导作用（式4）。最后，在该手性辅助下进行的不对称狄尔斯-阿尔德环化反应是(–)-Epibatidine全合成中的关键步骤（式5）。

用途 手性不对称磷配体的合成

(–)-8-苯基薄荷醇与三氯化磷和联苯酚衍生物反应可生成不对称有机磷配体（式1）。这些配体会与金属钌催化剂协同作用催化不对称加氢还原反应（式2）[2]。

作为手性诱导辅剂

(–)-8-苯基薄荷醇的衍生物可用于多种不对称化学转化中，包括分子间和分子内的狄尔斯-阿尔德反应、双羟化反应及α,β-不饱和8-苯基薄荷醇酸酯的分子内烯化等。这些过程具有温和的反应速率、高度的选择性和高的产率。例如，(–)-8-苯基薄荷醇的α-酮酯（如8-苯基薄荷丙酮酸酯）可用于不对称酮加成，并适用于不对称[2+2]光催化和亲核烷基化反应；其α-亚胺酯与烯烃的烯化可产生高光学纯度的α-亚胺酸。当甲基锌试剂存在时，(–)-8-苯基薄荷醇能诱导炔基锆化合物对α-酮酸酯进行不对称加成（式3）[3]。

在4-芳基取代哌啶的合成过程中，有机镁试剂可以被不饱和醛酮的不对称迈克尔加成反应所利用，并受到手性辅剂(–)-8-苯基薄荷醇的调节作用（式4）[4]。此外，在这种手性辅助下的不对称狄尔斯-阿尔德环化反应是合成(–)-Epibatidine的关键步骤（式5）[8]。

反应信息

• 作为反应物：
  描述：

  (-)-8-苯基薄荷醇 在 4-二甲氨基吡啶 N-溴代丁二酰亚胺(NBS) 、 2,3-二脱氧胞啶 作用下， 以 四氯化碳 、 二氯甲烷 为溶剂， 生成 (1R,2S,5R)-2-(1-methyl-1-phenylethyl)-5-methylcyclohexyl<(tert-butoxycarbonyl)amino>bromoacetate
  参考文献：
  名称：

  n-boc-α-氨基醇和α-氨基酸的立体选择性合成

  摘要：

  描述了N-Boc-α-氨基醇和α-氨基酸的立体选择性合成，向手性亲电甘氨酸当量α-溴-N-Boc-甘氨酸（-）苯基薄荷基酯中添加了格氏试剂。

  DOI：

  10.1016/s0040-4039(00)80272-5
• 作为产物：
  描述：

  长叶薄荷酮 在 sodium 、 异丙醇 、 potassium hydroxide 、 copper(I) bromide 作用下， 以 乙醚 、 乙醇 、 水 、 甲苯 为溶剂， 反应 27.75h， 生成 (-)-8-苯基薄荷醇
  参考文献：
  名称：

  双不对称感应作为机械探针：对映纯α，β-不饱和酯和对映纯α，β-不饱和异羟肟酸酯的双非对映选择性共轭加成对映体纯的锂酰胺

  摘要：

  将N-苄基-N-（α-甲基苄基）锂的对映体双非对映选择性共轭加成到一系列对映纯α，β-不饱和酯[源自Corey's 8-苯基薄荷醇手性助剂]和对映纯α，β-不饱和异羟肟酸盐[源自我们的“手性Weinreb酰胺”辅助（小号） - ñ -1-（1'-萘基）乙基- ø -叔-butylhydroxylamine]已被用作一种机械探针，以确定这些受体的活性构象。

  DOI：

  10.1016/j.tet.2011.05.102
• 作为试剂：
  描述：

  methyl(phenyl)(o-tolyl)phosphine 在 六氯丙酮 、 (-)-8-苯基薄荷醇 作用下， 以 苯 为溶剂， 反应 168.0h， 生成 o-tolylphenylmethylphosphine oxide 、 (S)-methyl(phenyl)(o-tolyl)phosphine oxide
  参考文献：
  名称：

  [EN] CHIRAL PHOSPHORUS COMPOUNDS
  [FR] COMPOSES PHOSPHORES CHIRAUX

  摘要：

  一种立体选择性制备P-手性四配位磷化合物的方法，该方法包括将来自手性醇，手性胺或手性硫醇的第一反应物与包含P-手性三配位磷化合物的第二反应物在亲电试剂的存在下反应。

  公开号：

  WO2005118603A1

文献信息

• EPOTHILONE DERIVATIVES, METHOD FOR PRODUCING SAME AND THEIR PHARMACEUTICAL USE
  申请人：——

  公开号：US20030144523A1

  公开（公告）日：2003-07-31

  This invention relates to the new epothilone derivatives of general formula I, 1 in which substituents Y, Z R 2a , R 2b , R 3 , R 4a , R 4b , D—E, R 5 , R 6 , R 7 , R 8 and X have the meanings that are indicated in more detail in the description. The new compounds interact with tubulin by stabilizing microtubuli that are formed. They are able to influence the cell-splitting in a phase-specific manner and are suitable for treating malignant tumors, for example, ovarian, stomach, colon, adeno-, breast, lung, head and neck carcinomas, malignant melanomas, acute lymphocytic and myelocytic leukemia. In addition, they are suitable for anti-angiogenesis therapy as well as for treatment of chronic inflammatory diseases (psoriasis, arthritis). To avoid uncontrolled proliferation of cells and for better compatibility of medical implants, they can be applied or introduced into polymer materials. The compounds according to the invention can be used alone or to achieve additive or synergistic actions in combination with other principles and classes of substances that can be used in tumor therapy.

  本发明涉及具有通式I的新埃波替隆衍生物，其中取代基Y、Z、R2a、R2b、R3、R4a、R4b、D—E、R5、R6、R7、R8和X的含义在描述中更详细地指出。这些新化合物通过与微管蛋白的相互作用来稳定形成的微管。它们能够以阶段特异性的方式影响细胞分裂，并适用于治疗恶性肿瘤，例如卵巢、胃、结肠、腺体、乳腺、肺、头颈癌、恶性黑色素瘤、急性淋巴细胞和骨髓细胞白血病。此外，它们还适用于抗血管生成治疗以及治疗慢性炎性疾病（银屑病、关节炎）。为了避免细胞的不受控制的增殖以及提高医疗植入物的相容性，它们可以应用于或引入到聚合物材料中。根据发明的化合物可以单独使用，也可以与其他可用于肿瘤治疗的原理和物质类别结合使用，以实现相加或协同作用。
• Novel epothilone derivatives, method for the preparation thereof and their pharmaceutical use
  申请人：——

  公开号：US20040058969A1

  公开（公告）日：2004-03-25

  The invention relates to novel epothilone derivatives of general formula (1), wherein R 5 represents a halogen atom or a cyano group and the other substituents have the meanings as cited in the description. The novel compounds interact with tubulin by stabilizing formed microtubules. They are capable of influencing the cell division in a phase-specific manner and are well-suited for the treatment of malignant tumors, for example, ovarian, stomach, colon, adeno, breast, lung, head and neck carcinomas, malignant melanoma, acute lymphocytic and myelocytic leukemia. In addition, they are well-suited for anti-angiogenesis therapy and for the treatment of chronic inflammable medical disorders (psoriasis, arthritis). In order to prevent uncontrolled cell growths as well as to improve the compatibility of medical implants, the inventive epothilone derivatives can be applied to or introduced into polymeric materials. The inventive compounds can be used alone or in order to obtain additive or synergistic effects, in conjunction with additional principles and substance classes that can be used in tumor therapy. 1

  本发明涉及一类通式（1）的新埃博霉素衍生物，其中R 5 代表卤素原子或氰基，其他取代基的含义如描述中引用。这些新颖化合物通过与微管蛋白作用稳定形成的微管。它们能够以特定阶段的方式影响细胞分裂，非常适合治疗恶性肿瘤，例如卵巢癌、胃癌、结肠癌、腺癌、乳腺癌、肺癌、头颈癌、恶性黑色素瘤、急性淋巴细胞和骨髓细胞白血病。此外，它们还非常适合用于抗血管生成治疗和慢性炎症性医疗疾病（银屑病、关节炎）的治疗。为了防止不受控制的细胞生长以及提高医疗植入物的相容性，本发明的埃博霉素衍生物可以施加或引入到聚合物材料中。本发明的化合物可以单独使用，或者为了获得添加剂或协同效应，与肿瘤治疗中可用的其他原理和物质类别联合使用。 1
• Novel Isomerically Pure Tetrasubstituted Allylboronates:  Stereocontrolled Synthesis of α-Exomethylene γ-Lactones as Aldol-Like Adducts with a Stereogenic Quaternary Carbon Center
  作者：Jason W. J. Kennedy、Dennis G. Hall

  DOI：10.1021/ja016391e

  日期：2002.2.1

  1-alkoxycarbonyl vinylcopper(I) intermediates from the conjugate addition of organocuprates onto acetylenic esters were trapped with very high cis-addition selectivity with iodomethylboronic esters in the presence of HMPA. The resulting isomerically pure 3,3-disubstituted allylboronates react with aldehydes in a highly diastereo- and enantioselective manner, providing α-exomethylene γ-lactones with a stereogenic

  尽管它们固有的异构化倾向和低反应性，1-烷氧基羰基乙烯基铜 (I) 中间体在 HMPA 存在下与碘甲基硼酸酯以非常高的顺式加成选择性捕获了有机铜酸盐与炔酸酯的共轭加成。所得的异构纯 3,3-二取代烯丙基硼酸酯以高度非对映选择性和对映选择性方式与醛反应，提供具有立体异构四元 β-碳中心的 α-外亚甲基 γ-内酯。
• Lewis Acid Catalyzed Allylboration:  Discovery, Optimization, and Application to the Formation of Stereogenic Quaternary Carbon Centers
  作者：Jason W. J. Kennedy、Dennis G. Hall

  DOI：10.1021/jo049773m

  日期：2004.6.1

  A full account of the development of the first catalytic manifold for the additions of allylboronates to aldehydes is described. The thermal additions (both diastereospecific and enantioselective) of 2-carboxyester 3,3-disubstituted allylboronates 1 to both aromatic and aliphatic aldehydes give biologically and synthetically important exo-methylene butyrolactones 2 containing a β-quaternary carbon

  描述了将烯丙基硼酸酯加成到醛中的第一催化歧管的发展的完整说明。将2-羧酸酯3,3-二取代的烯丙基硼酸酯1热加成（非对映体特异性和对映体选择性）对芳香族和脂肪族醛均具有生物学和合成意义的外亚甲基丁内酯2包含一个β-季碳中心。尽管热反应在室温下需要14 d才能完成，但是某些金属盐的存在可以使反应12-16 h，同时保留未催化过程中观察到的非对映特异性。描述了对催化作用起源的初步机理研究，以及内酯2立体选择性转化为环状和非环状的立体三单元体，具有潜在的合成中间体用途。
• Exceptionally Mild, High-Yield Synthesis of α-Fluoro Acrylates
  作者：Barbara Zajc、Shivani Kake

  DOI：10.1021/ol0616236

  日期：2006.9.1

  chiral alkyl alpha-(1,3-benzothiazol-2-ylsulfonyl)-alpha-fluoroacetates can be readily synthesized by metalation-fluorination of (1,3-benzothiazol-2-ylsulfonyl)acetates. DBU-mediated condensations of these fluorinated synthons with aldehydes proceed in a facile manner at 0 degrees C or at room temperature giving high yields of alpha-fluoro acrylates. Ketones are unreactive under these conditions. The

  新的非手性和手性烷基α-（1,3-苯并噻唑-2-基磺酰基）-α-氟乙酸盐可以通过（1,3-苯并噻唑-2-基磺酰基）乙酸盐的金属氟化反应容易地合成。这些氟化合成子与醛的DBU介导的缩合反应可在0摄氏度或室温下轻松进行，从而获得高产率的α-氟代丙烯酸酯。在这些条件下，酮不起作用。与未氟化的类似物相比，氟的存在使合成子具有更大的反应性。还比较了α-（1,3-苯并噻唑-2-基磺酰基）-α-氟乙酸盐与Horner-Wadsworth-Emmons试剂（EtO）2P（O）CHFCOOEt的反应性。