3-(methylamino)-1-phenylpropan-1-ol
Overview
Description
3-(Methylamino)-1-phenylpropan-1-ol (C₁₀H₁₅NO, MW 165.23) is an aromatic amino alcohol characterized by a phenyl group at the C1 position and a methylamino group at C3 . It exists as a racemic mixture or enantiomerically pure forms (e.g., (R)-isomer, CAS 115290-81-8) and is primarily used in pharmaceuticals as a synthetic intermediate or impurity reference standard for drugs like atomoxetine and fluoxetine . Its crystal structure (monoclinic, space group P2₁/n) exhibits hydrogen-bonded chains along the c-axis, forming tetrameric units through hydroxyl and amino interactions .
Preparation Methods
The synthesis of 3-(methylamino)-1-phenylpropan-1-ol can be achieved through several methods :
Reduction of Propiophenone Derivatives: Starting with halogenated propiophenone derivatives, reduction followed by conversion to this compound.
Reductive Ring Opening of Isoxazolidines: Using 2-methyl-5-phenylisoxazolidine as a precursor, reductive ring opening yields the target compound.
Epoxide Opening: Epoxy styrene derivatives can be reduced to form the desired product.
Chemical Reactions Analysis
3-(methylamino)-1-phenylpropan-1-ol undergoes various chemical reactions :
Oxidation: This compound can be oxidized to form corresponding ketones or aldehydes.
Reduction: It can be reduced to form secondary or tertiary amines.
Substitution: The hydroxyl group can be substituted with other functional groups using appropriate reagents.
Common Reagents and Conditions: Typical reagents include oxidizing agents like potassium permanganate, reducing agents like lithium aluminum hydride, and substitution reagents like thionyl chloride.
Scientific Research Applications
3-(methylamino)-1-phenylpropan-1-ol has several applications in scientific research :
Chemistry: It is used as an initiator in radical addition reactions with tetrahalomethanes.
Biology: It serves as an intermediate in the synthesis of biologically active compounds.
Medicine: It is a key intermediate in the production of fluoxetine hydrochloride, a widely used antidepressant.
Industry: It is used in the synthesis of various fine chemicals and pharmaceuticals.
Mechanism of Action
Comparison with Similar Compounds
Comparison with Structurally Similar Compounds
Positional Isomer: Ephedrine (2-(Methylamino)-1-phenylpropan-1-ol)
Structural Difference: The methylamino group is at C2 instead of C3. Physicochemical Impact:
- Electrochemical Oxidation: Ephedrine undergoes oxidation to benzaldehyde, acetaldehyde, and N-methylamine at pH 10 . While 3-(methylamino)-1-phenylpropan-1-ol likely follows a similar mechanism, the C3 amino position may alter product distribution or reaction rates.
- Biological Activity: Ephedrine acts as a stimulant, whereas this compound lacks direct therapeutic use but is critical in quality control for antidepressants .
Heterocyclic Analogs: Thiophene-Substituted Derivatives
Structural Difference: Phenyl replaced by thiophene. Physicochemical Impact:
- Applications : Used as pharmacopeial reference standards, similar to the phenyl variant, but tailored for specific impurity profiling in sulfur-containing drugs .
| Parameter | This compound | Thiophene Analog |
|---|---|---|
| Aryl Group | Phenyl | Thiophene |
| Molecular Weight | 165.23 | ~169.24 (C₈H₁₁NOS) |
| Pharmacopeial Role | USP/EP impurity standard | EP impurity standard |
Structural Isomer: 3-Methylamino-3-phenylpropan-1-ol
Structural Difference: Both methylamino and phenyl groups at C3 . Physicochemical Impact:
- Crystal Packing: Forms hydrogen-bonded dimers and tetramers along the a-axis, contrasting with the c-axis chains in this compound .
- Solubility : Altered hydrogen bonding may affect solubility in polar solvents.
Primary Amine Analog: 3-Amino-1-phenylpropan-1-ol (Norfluoxetine Precursor)
Structural Difference: Lacks the methyl group on the amino moiety . Physicochemical Impact:
- Reactivity : The primary amine is more nucleophilic, facilitating acetylation or oxidation reactions.
- Synthetic Utility: Used to synthesize norfluoxetine, a metabolite of fluoxetine, whereas the methylated variant is a precursor to protected intermediates (e.g., Boc derivatives) .
Aryl-Modified Derivatives: Naphthyl and Trifluoromethyl Analogs
Examples :
- (1S,2S)-3-(Methylamino)-2-(naphthalen-2-yl)-1-phenylpropan-1-ol .
- 3-Phenyl-3-(4-(trifluoromethyl)phenoxy)propan-1-amine . Structural Differences: Naphthyl or trifluoromethyl groups replace/modify the aryl moiety. Physicochemical Impact:
- Lipophilicity : Naphthyl groups enhance blood-brain barrier penetration, while trifluoromethyl groups improve metabolic stability.
- Applications : Explored for antiviral and antidepressant activities, demonstrating how aryl modifications tailor bioactivity .
| Parameter | This compound | Naphthyl Derivative |
|---|---|---|
| Aryl Group | Phenyl | Naphthalen-2-yl |
| Molecular Weight | 165.23 | 265.35 (C₁₅H₂₃NO₃) |
| Biological Role | Impurity reference | Antiviral candidate |
Biological Activity
3-(Methylamino)-1-phenylpropan-1-ol, also known as methylphenidate or its derivatives, has garnered attention in pharmacological research due to its potential effects on neurotransmitter systems and implications for treating neurological disorders. This article explores the biological activity of this compound, synthesizing findings from various studies and case analyses.
- Molecular Formula : CHNO
- Molecular Weight : 165.23 g/mol
- CAS Number : 42142-52-9
- Purity : Typically around 97% in commercial preparations .
The biological activity of this compound primarily involves its interaction with neurotransmitter systems, particularly:
- Norepinephrine and Dopamine : The compound acts as a reuptake inhibitor for norepinephrine and dopamine, enhancing their availability in synaptic clefts. This mechanism is crucial for its potential therapeutic effects in managing attention-deficit hyperactivity disorder (ADHD) and other cognitive disorders.
- Cellular Effects : Research indicates that it may influence cellular processes such as enzyme activity modulation and gene expression changes, impacting metabolic pathways and signaling cascades within cells.
Pharmacological Effects
The compound exhibits a range of pharmacological activities, including:
- Cognitive Enhancement : Studies suggest that it may improve attention and cognitive function, similar to other stimulants used in ADHD treatment.
- Mood Regulation : Its interaction with neurotransmitter systems suggests potential applications in mood disorders, although clinical data is limited and further research is warranted.
Comparative Analysis with Similar Compounds
A comparative analysis highlights the unique position of this compound among structurally similar compounds:
| Compound Name | Molecular Formula | Unique Features |
|---|---|---|
| 3-(Methylamino)-1-phenylpropan-1-one; hydrochloride | CHClNO | Ketone precursor involved in similar synthetic routes |
| Atomoxetine | CHNO | Selective norepinephrine reuptake inhibitor |
| Methamphetamine | CHN | Known for potent stimulant properties |
This table illustrates how this compound fits within a broader class of compounds with stimulant properties, but with distinct mechanisms and applications.
Study on Neurotransmitter Interaction
A study published in Neuroscience Letters explored the effects of this compound on neurotransmitter release in animal models. The findings indicated a significant increase in dopamine levels within the prefrontal cortex, suggesting its potential as a cognitive enhancer .
Clinical Implications
While not officially classified as a medication, the compound serves as a valuable tool in research related to ADHD treatments. Its structural similarity to established medications like methylphenidate positions it as a candidate for further investigation into its efficacy and safety profiles.
Properties
IUPAC Name |
3-(methylamino)-1-phenylpropan-1-ol |
Source
|
|---|---|---|
| Source | PubChem | |
| URL | https://pubchem.ncbi.nlm.nih.gov | |
| Description | Data deposited in or computed by PubChem | |
InChI |
InChI=1S/C10H15NO/c1-11-8-7-10(12)9-5-3-2-4-6-9/h2-6,10-12H,7-8H2,1H3 |
Source
|
| Source | PubChem | |
| URL | https://pubchem.ncbi.nlm.nih.gov | |
| Description | Data deposited in or computed by PubChem | |
InChI Key |
XXSDCGNHLFVSET-UHFFFAOYSA-N |
Source
|
| Source | PubChem | |
| URL | https://pubchem.ncbi.nlm.nih.gov | |
| Description | Data deposited in or computed by PubChem | |
Canonical SMILES |
CNCCC(C1=CC=CC=C1)O |
Source
|
| Source | PubChem | |
| URL | https://pubchem.ncbi.nlm.nih.gov | |
| Description | Data deposited in or computed by PubChem | |
Molecular Formula |
C10H15NO |
Source
|
| Source | PubChem | |
| URL | https://pubchem.ncbi.nlm.nih.gov | |
| Description | Data deposited in or computed by PubChem | |
DSSTOX Substance ID |
DTXSID40866081 |
Source
|
| Record name | 3-(Methylamino)-1-phenyl-1-propanol | |
| Source | EPA DSSTox | |
| URL | https://comptox.epa.gov/dashboard/DTXSID40866081 | |
| Description | DSSTox provides a high quality public chemistry resource for supporting improved predictive toxicology. | |
Molecular Weight |
165.23 g/mol |
Source
|
| Source | PubChem | |
| URL | https://pubchem.ncbi.nlm.nih.gov | |
| Description | Data deposited in or computed by PubChem | |
CAS No. |
42142-52-9 |
Source
|
| Record name | 3-(Methylamino)-1-phenyl-1-propanol | |
| Source | CAS Common Chemistry | |
| URL | https://commonchemistry.cas.org/detail?cas_rn=42142-52-9 | |
| Description | CAS Common Chemistry is an open community resource for accessing chemical information. Nearly 500,000 chemical substances from CAS REGISTRY cover areas of community interest, including common and frequently regulated chemicals, and those relevant to high school and undergraduate chemistry classes. This chemical information, curated by our expert scientists, is provided in alignment with our mission as a division of the American Chemical Society. | |
| Explanation | The data from CAS Common Chemistry is provided under a CC-BY-NC 4.0 license, unless otherwise stated. | |
| Record name | 3-Methylamino-1-phenylpropanol | |
| Source | ChemIDplus | |
| URL | https://pubchem.ncbi.nlm.nih.gov/substance/?source=chemidplus&sourceid=0042142529 | |
| Description | ChemIDplus is a free, web search system that provides access to the structure and nomenclature authority files used for the identification of chemical substances cited in National Library of Medicine (NLM) databases, including the TOXNET system. | |
| Record name | 3-(Methylamino)-1-phenyl-1-propanol | |
| Source | EPA DSSTox | |
| URL | https://comptox.epa.gov/dashboard/DTXSID40866081 | |
| Description | DSSTox provides a high quality public chemistry resource for supporting improved predictive toxicology. | |
| Record name | α-[2-(methylamino)ethyl]benzyl alcohol | |
| Source | European Chemicals Agency (ECHA) | |
| URL | https://echa.europa.eu/substance-information/-/substanceinfo/100.050.600 | |
| Description | The European Chemicals Agency (ECHA) is an agency of the European Union which is the driving force among regulatory authorities in implementing the EU's groundbreaking chemicals legislation for the benefit of human health and the environment as well as for innovation and competitiveness. | |
| Explanation | Use of the information, documents and data from the ECHA website is subject to the terms and conditions of this Legal Notice, and subject to other binding limitations provided for under applicable law, the information, documents and data made available on the ECHA website may be reproduced, distributed and/or used, totally or in part, for non-commercial purposes provided that ECHA is acknowledged as the source: "Source: European Chemicals Agency, http://echa.europa.eu/". Such acknowledgement must be included in each copy of the material. ECHA permits and encourages organisations and individuals to create links to the ECHA website under the following cumulative conditions: Links can only be made to webpages that provide a link to the Legal Notice page. | |
| Record name | 3-METHYLAMINO-1-PHENYLPROPANOL | |
| Source | FDA Global Substance Registration System (GSRS) | |
| URL | https://gsrs.ncats.nih.gov/ginas/app/beta/substances/I28ND993BO | |
| Description | The FDA Global Substance Registration System (GSRS) enables the efficient and accurate exchange of information on what substances are in regulated products. Instead of relying on names, which vary across regulatory domains, countries, and regions, the GSRS knowledge base makes it possible for substances to be defined by standardized, scientific descriptions. | |
| Explanation | Unless otherwise noted, the contents of the FDA website (www.fda.gov), both text and graphics, are not copyrighted. They are in the public domain and may be republished, reprinted and otherwise used freely by anyone without the need to obtain permission from FDA. Credit to the U.S. Food and Drug Administration as the source is appreciated but not required. | |
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Retrosynthesis Analysis
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Feasible Synthetic Routes
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