23981-80-8

Hazards Identification

Pictogram(s):

Signal:

Danger

GHS Hazard Statements:

H301 (50%): Toxic if swallowed [Danger Acute toxicity, oral]
H302 (50%): Harmful if swallowed [Warning Acute toxicity, oral]
H315 (100%): Causes skin irritation [Warning Skin corrosion/irritation]
H319 (100%): Causes serious eye irritation [Warning Serious eye damage/eye irritation]
H371 (50%): May cause damage to organs [Warning Specific target organ toxicity, single exposure]

Precautionary Statement Codes:

P260, P264, P264+P265, P270, P280, P301+P316, P301+P317, P302+P352, P305+P351+P338, P308+P316, P321, P330, P332+P317, P337+P317, P362+P364, P405, and P501

Hazard Classes and Categories:

Acute Tox. 3 (50%)
Acute Tox. 4 (50%)
Skin Irrit. 2 (100%)
Eye Irrit. 2 (100%)
STOT SE 3 (50%)
Acute Tox. 4 (100%)
STOT SE 3 (100%)

Usage

Uses

Used in Pharmaceutical Industry:
(+/-)-2-(6-METHOXY-2-NAPHTHYL)PROPIONIC ACID is used as an active pharmaceutical ingredient (API) for the development of non-steroidal anti-inflammatory drugs (NSAIDs). Its application is based on its ability to reduce inflammation, alleviate pain, and lower fever, making it a valuable component in the treatment of various conditions such as arthritis, headaches, and other inflammatory disorders.
Used in Research and Development:
In the field of research and development, (+/-)-2-(6-METHOXY-2-NAPHTHYL)PROPIONIC ACID serves as a key compound for studying the structure-activity relationships of NSAIDs. Its unique chemical structure allows scientists to investigate the effects of modifications on its anti-inflammatory, analgesic, and antipyretic properties, potentially leading to the discovery of more effective and safer NSAIDs.
Used in Chemical Synthesis:
(+/-)-2-(6-METHOXY-2-NAPHTHYL)PROPIONIC ACID can also be used as a starting material or intermediate in the synthesis of other related compounds with potential applications in various industries, such as pharmaceuticals, agrochemicals, and materials science. Its versatile chemical structure makes it a valuable building block for the development of novel molecules with improved properties and applications.

InChI:InChI=1/C14H14O3/c1-9(14(15)16)10-3-4-12-8-13(17-2)6-5-11(12)7-10/h3-9H,1-2H3,(H,15,16)

Upstream product

• 70101-36-9 2-Methoxy-6-(1-methyl-2,2-bis-methylsulfanyl-vinyl)-naphthalene 
• 23389-75-5 rac-1-(pyridin-4-yl)ethanol 
• 52344-67-9 2-(6-methoxynaphthalene-2-yl)propionic anhydride 
• 5445-17-0 Methyl 2-bromopropionate 
• 121429-59-2 1,4-dihydro-7-methoxy-N-methylnaphthalene-1-sulfonamide 
• 121429-72-9 1,4-dihydro-7-methoxy-N,N-dimethylnaphthalene-1-sulfonamide 
• 128884-52-6 7-Methoxy-1,4-dihydro-naphthalene-1-sulfonic acid diethylamide 
• 121429-60-5 1,4-dihydro-7-methoxy-N-(1',1'-dimethylethyl)naphthalene-1-sulfonamide 
• 121429-73-0 1,4-dihydro-7-methoxy-N-(1',1'-dimethylethyl)-N-methylnaphthalene-1-sulfonamide 
• 139633-40-2 1,4-dihydro-7-methoxy-N-(1',1'-dimethylpropyl)naphthalene-1-sulfonamide 
• 139633-41-3 7-Methoxy-1,4-dihydro-naphthalene-1-sulfonic acid (1,1,3,3-tetramethyl-butyl)-amide 
• 128884-54-8 7-Methoxy-1,4-dihydro-naphthalene-1-sulfonic acid tert-butyl-methoxymethyl-amide 
• 75-69-4 trichlorofluoromethane 
• 3900-45-6 6-methoxy-2-acetylnaphthalene 

Downstream Products

• 863203-65-0 2-(6-Methoxy-naphthalen-2-yl)-propionic acid 4-nitro-phenyl ester 
• 31220-35-6 (R,S) naproxen ethyl ester 
• 709000-02-2 2-<1-(6-methoxynaphthyl)ethyl>-1H-benzimidazole 
• 140226-03-5 naproxen-L-lactic acid pentamethylbenzyl ester 
• 3900-45-6 6-methoxy-2-acetylnaphthalene 
• 30012-51-2 methyl 2-(6-methoxy-2-naphthyl)propionate 
• 108781-65-3 1-(6-methoxy-2-naphthyl)ethanol 
• 132367-16-9 2-methoxy-6-(1-methoxyethyl)naphthalene 
• 37414-52-1 2-(6-methoxy-2-naphthyl)-propyl alcohol 
• 52079-10-4 6-hydroxy-α-methyl-2-naphthaleneacetic acid 
• 22204-53-1 (+)-2-(6-methoxy-2-naphthyl)propionic acid 
• 22204-53-1 (2S)-2-(6-methoxy(2-naphthyl))propanoic acid 
• 23979-41-1 (R)-2-(6-methoxy-2-naphthyl)propionic acid 

Relevant academic research and scientific papers

Racemization and hydrolysis of (S)-naproxen 2,2,2-trifluoroethyl ester in non-polar solvents by strong neutral bases: Implication for ion-pair kinetic basicity and hydrolysis

By using strong neutral bases as catalyst, a detailed investigation of the racemization of (S)-naproxen 2,2,2-trifluoroethyl ester was conducted in the non-polar solvents isooctane, cyclohexane and n-hexane. The second-order interconversion constant kint* as representing the ion-pair kinetic basicity in isooctane was first estimated and correlated with the equilibrium ion-pair basicity pKip in tetrahydrofuran, giving slopes of 0.768 and 0.689 for non-phosphazene and phosphazene bases, respectively, in the Bronsted correlations. The result was further compared with that for (S)-naproxen 2,2,2-trifluoroethyl thioester, showing about a 1-2 orders of magnitude enhancement of kint* for the corresponding thio-containing analogue. A smaller influence of non-polar solvents (i.e. isooctane, n-hexane and cyclohexane) on kint* was found. Kinetic analysis of the racemization and hydrolysis of (S)-naproxen 2,2,2-trifluoroethyl ester in isooctane and n-hexane containing 7-methyl-1,5,7-triazabicyclo[4.4.0]dec-5-ene and water suggests nucleophilic hydrolysis by the base, where the breakdown of tetrahedral intermediates I R1 and IS1 is the rate-limiting step and the hydrolysis constant khy is in proportion to the product of base and ion-pair concentrations. Copyright 2004 John Wiley & Sons, Ltd.

Photochemically Controlled Drug Dosing from a Polymeric Scaffold

Purpose: To develop the first photoactive biomaterial coating capable of controlled drug dosing via inclusion of synthesised drug-3,5-dimethoxybenzoin (DMB) conjugates in a poly(2-methyoxyethyl acrylate) (pMEA) scaffold. Methods: Flurbiprofen- and naproxen-DMB conjugates were prepared via esterification and characterised via NMR spectroscopy and mass spectrometry following chromatographic purification. Conjugate photolysis was investigated in acetonitrile solution and within the pMEA matrix following exposure to low-power 365?nm irradiation. Photo-liberation of drug from pMEA into phosphate buffered saline was monitored using UV-vis spectroscopy. Results: The synthetic procedures yielded the desired drug conjugates with full supporting characterisation. Drug regeneration through photolysis of the synthesised conjugates was successful in both acetonitrile solution and within the pMEA scaffold upon UV irradiation. Conjugates were retained within the pMEA scaffold with exclusive drug liberation following irradiation and increased drug dose with increasing exposure. Multi-dosing capacity was demonstrated though the ability of successive irradiation periods to generate further bursts of drug. Conclusion: This study demonstrates the first application of photochemically controlled drug release from a biomaterial coating and the feasibility of using pMEA as a scaffold for housing the photoactive drug-DMB conjugates.

Simple synthetic approach to arylacetic NSAIAs via TosMIC procedure

Preparation of 1-methylpyrrole-2-acetonitrile, 1-methyl-5-(4-methylbenzoyl) pyrrole-2-acetonitrile and 2-(6-methoxy-2-naphthyl)propionitrile by treatment of 1-methylpyrrole-2-carboxaldehyde, 1-methyl-5-(4-methylbenzoyl)pyrrole-2-carboxaldehyde and, respectively, 6-methoxy-2-acetylnaphthalene with tosylmethylisocyanide (TosMIC) is described. This one-step synthetic procedure is very useful to obtain the nitrile precursors of tolmetin and naproxen, two clinically important non-steroidal antiinflammatory agents (NSAIAs).

Investigation of lipase-catalysed hydrolysis of naproxen methyl ester: use of NMR spectroscopy methods to study substrate-enzyme interaction.

(+/-)-2-(6-Methoxy-2-naphthyl)propionic acid methyl ester (methyl ester of Naproxen), the precursor of therapeutically important nonsteroidal anti-inflammatory drugs (NSAIDs) was enantioselectively hydrolysed using as biocatalyst Candida rugosa lipase. In research aimed at studying the structure-activity relationship (SAR), NMR spectroscopy methods were employed to identify which Naproxen molecular moiety was essential to the substrate-enzyme interaction. The experimental results, in agreement with previous computer modelling studies and reported kinetic data, gave new information on the enzyme-substrate complex formation in solution.

New process for synthesizing racemic naproxen based on Heck coupling

The invention discloses a novel process for synthesizing racemic naproxen based on Heck coupling, which comprises the following steps: (1) carrying out Heck coupling reaction on 2-X substituted-6-methoxynaphthalene and crotonamide in an aprotic organic solvent under the action of a palladium catalyst and alkali to generate 3-(6-methoxynaphthyl-2-)-crotonamide; and (2) carrying out Hofmann degradation reaction on the 3-(6-methoxynaphthyl-2-)-crotonamide in an alkaline solution of hypochlorite to generate 2-(6-methoxynaphthyl-2-)-propionaldehyde, directly adding the 2-(6-methoxynaphthyl-2-)-propionaldehyde into chlorite without separation, and conducting oxidizing at room temperature to obtain racemic naproxen. The process provided by the invention does not need to prepare a highly active Grignard reagent, does not need a harsh anhydrous condition, and is relatively high in conversion rate and easy in product purification.

Synthesis of rac-ɑ-aryl propionaldehydes via branched-selective hydroformylation of terminal arylalkenes using water-soluble Rh-PNP catalyst

This work detailed the preparation of a class of water-soluble PNP ligands that differed by the nature of the substitute on phenyl ring of ligands. These ligands were incorporated into water-soluble rhodium-PNP complex catalysts that were used to regioselective hydroformylation of a series of terminal arylalkenes, providing efficient access to rac-α-aryl propionaldehydes in good to excellent yield (up to 97%) and branched-regioselectivity (up to 40:1 b/l ratio). Furthermore, gram-scale and diverse synthetic transformation demonstrated synthetic application of this methodology for non-steroidal antiinflammatory drugs.

Preparation of One-Pot Immobilized Lipase with Fe3O4 Nanoparticles Into Metal-Organic Framework For Enantioselective Hydrolysis of (R,S)-Naproxen Methyl Ester

Immobilization of enzyme to magnetic metal-organic frameworks (MOF) can preserve biological functionality in harsh environments to increase enzymes activity, stability, and improve reusability. The magnetic Fe3O4 nanoparticles were treated with calix[4]arene tetracarboxylic acid (Calix) and Candida rugosa lipase (CRL), and then encapsulated into the zeolitic imidazole framework-8 (Fe3O4@Calix-ZIF-8@CRL). The lipase activity data of Fe3O4@Calix-ZIF-8@CRL was 2.88 times higher than that of the Fe3O4@ZIF-8@CRL (without Calix). The catalytic properties of immobilized lipases were studied on the enantioselective hydrolysis of R/S-naproxen methyl ester. It was also observed that Fe3O4@Calix-ZIF-8@CRL has excellent enantioselectivity (E=371) compared to Fe3O4@ZIF-8@CRL (E=131). Furthermore, Fe3O4@Calix-ZIF-8@CRL was seen to still retain 30 % of the conversion rate after the fifth reuse. This work may also be useful for the pharmaceutical industry due to the increased reusability and stability of enzymes, the enantiomeric selectivity exhibited by MOF-enzyme biocomposites, and the significant differences in the biological activities of the enantiomers.

Visible-Light-Enabled Carboxylation of Benzyl Alcohol Derivatives with CO2 Using a Palladium/Iridium Dual Catalyst

A highly efficient carboxylation of benzyl alcohol derivatives with CO2 using a palladium/iridium dual catalyst under visible-light irradiation was developed. A wide range of benzyl alcohol derivatives could be employed to provide benzylic carboxylic acids in moderate to high yields. Mechanistic studies indicated that the oxidative addition of benzyl alcohol derivatives was possibly the rate-determining-step. It was also found that a switchable site-selective carboxylation between benzylic C?O and aryl C?Cl moieties could be achieved simply by changing the palladium catalyst.

Naproxen impurity and preparation method thereof

The invention provides a naproxen impurity R, and the structural formula of the naproxen impurity R is shown in the specification. The invention also provides a preparation method of the naproxen impurity R. The preparation method comprises the following steps of: demethylating naproxen racemate in an acidic medium, and further reacting the demethylated naproxen racemate with 3-bromo-2, 2-dimethyl-1-propanol in the presence of an acid-binding agent to obtain the naproxen impurity R. The naproxen impurity R disclosed by the invention is suitable for being used as an impurity reference substancefor researching the synthesis quality of naproxen and intermediates thereof.

Method for synthesizing aryl propionic acid by metal-free catalysis of carbon dioxide carboxylation

The invention relates to the field of carbon dioxide immobilization and conversion, and particularly discloses a method for synthesizing aryl propionic acid by metal-free catalysis of carbon dioxide carboxylation. The method comprises the following steps: stirring a mixed solution of a diselenide catalyst and a styrene compound in a carbon dioxide atmosphere, adding hydrogen peroxide, and stirringto react, thereby obtaining the aryl propionic acid. Styrene is directly used as a raw material, diselenide is used as a catalyst to realize a carboxylation reaction of olefin and carbon dioxide, andcompared with metal catalyst residues or halogen-containing byproducts in a traditional synthesis method, the byproducts in the method only contain water, and small molecular diselenide is used as the catalyst to replace the traditional metal catalyst, and metal residuals are avoided.