(S)-(+)-Ibuprofen-d3

Cat. No.: B1507591

CAS No.: 1329643-44-8

M. Wt: 209.3 g/mol

InChI Key: HEFNNWSXXWATRW-PCXQMPHHSA-N

Attention: For research use only. Not for human or veterinary use.

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Overview

1. Description

8. Properties

2. Scientific research applications

9. Synthesis routes and methods I

3. Mechanism of action

10. Synthesis routes and methods II

4. Safety and hazards

11. Synthesis routes and methods III

5. Preparation methods

12. Synthesis routes and methods IV

6. Chemical reactions analysis

13. Retrosynthesis analysis

7. Comparison with similar compounds

14. Disclaimer

Description

(S)-(+)-Ibuprofen-d3 is a deuterated form of the well-known nonsteroidal anti-inflammatory drug (NSAID) ibuprofen. The deuterium atoms replace the hydrogen atoms in the ibuprofen molecule, which can lead to differences in the pharmacokinetics and metabolic stability of the compound. This modification is often used in scientific research to study the drug’s behavior in the body and to potentially improve its therapeutic profile.

Scientific Research Applications

(S)-(+)-Ibuprofen-d3 has a wide range of scientific research applications, including:

Pharmacokinetic Studies: Used to study the absorption, distribution, metabolism, and excretion of ibuprofen in the body.

Metabolic Stability: Research on how deuteration affects the metabolic stability and half-life of the drug.

Drug Development: Used in the development of new NSAIDs with improved therapeutic profiles.

Biological Studies: Investigating the biological effects of deuterated drugs on various biological systems.

Industrial Applications: Used in the production of deuterated drugs for therapeutic use.

Mechanism of Action

Target of Action

These enzymes play a crucial role in the production of prostaglandins, which are involved in inflammation, pain, and fever .

Mode of Action

(S)-(+)-Ibuprofen D3, like other NSAIDs, likely interacts with its targets (COX-1 and COX-2) by inhibiting their activity. This inhibition results in a decrease in the production of prostaglandins, thereby reducing inflammation, pain, and fever .

Safety and Hazards

“(S)-(+)-Ibuprofen D3” is for research use only and not for human or veterinary use. In case of inhalation, skin contact, eye contact, or ingestion, appropriate first aid measures should be taken, including rinsing with water, removing the victim to fresh air, and seeking medical attention.

Preparation Methods

Synthetic Routes and Reaction Conditions

The synthesis of (S)-(+)-Ibuprofen-d3 typically involves the incorporation of deuterium atoms into the ibuprofen molecule. This can be achieved through various synthetic routes, including:

Hydrogen-Deuterium Exchange: This method involves the replacement of hydrogen atoms with deuterium atoms using deuterated reagents under specific reaction conditions.

Deuterated Precursors: Another approach is to use deuterated starting materials in the synthesis of ibuprofen. This method ensures that the deuterium atoms are incorporated into the final product during the synthesis process.

Industrial Production Methods

Industrial production of this compound involves scaling up the synthetic routes mentioned above. The process typically includes:

Selection of Deuterated Reagents: Choosing appropriate deuterated reagents to ensure efficient incorporation of deuterium atoms.

Optimization of Reaction Conditions: Fine-tuning reaction conditions such as temperature, pressure, and catalysts to maximize yield and purity.

Purification: Using techniques like chromatography to purify the final product and remove any impurities.

Chemical Reactions Analysis

Types of Reactions

(S)-(+)-Ibuprofen-d3 undergoes various chemical reactions, including:

Oxidation: The compound can be oxidized to form corresponding carboxylic acids or other oxidized derivatives.

Reduction: Reduction reactions can convert this compound into its alcohol derivatives.

Substitution: The compound can undergo substitution reactions where functional groups are replaced with other groups.

Common Reagents and Conditions

Oxidation: Common oxidizing agents include potassium permanganate (KMnO4) and chromium trioxide (CrO3).

Reduction: Reducing agents like lithium aluminum hydride (LiAlH4) and sodium borohydride (NaBH4) are commonly used.

Substitution: Reagents such as halogens (e.g., chlorine, bromine) and nucleophiles (e.g., hydroxide ions) are used in substitution reactions.

Major Products Formed

The major products formed from these reactions include:

Oxidation: Carboxylic acids and ketones.

Reduction: Alcohols and alkanes.

Substitution: Halogenated derivatives and other substituted compounds.

Comparison with Similar Compounds

Similar Compounds

Ibuprofen: The non-deuterated form of (S)-(+)-Ibuprofen-d3.

Naproxen: Another NSAID with similar anti-inflammatory and analgesic properties.

Ketoprofen: An NSAID used for pain relief and inflammation reduction.

Uniqueness

This compound is unique due to the presence of deuterium atoms, which can lead to differences in pharmacokinetics and metabolic stability compared to its non-deuterated counterpart. This makes it a valuable tool in scientific research and drug development.

Properties

IUPAC Name	(2S)-3,3,3-trideuterio-2-[4-(2-methylpropyl)phenyl]propanoic acid	Source
Source	PubChem
URL	https://pubchem.ncbi.nlm.nih.gov
Description	Data deposited in or computed by PubChem

InChI	InChI=1S/C13H18O2/c1-9(2)8-11-4-6-12(7-5-11)10(3)13(14)15/h4-7,9-10H,8H2,1-3H3,(H,14,15)/t10-/m0/s1/i3D3	Source
Source	PubChem
URL	https://pubchem.ncbi.nlm.nih.gov
Description	Data deposited in or computed by PubChem

InChI Key	HEFNNWSXXWATRW-PCXQMPHHSA-N	Source
Source	PubChem
URL	https://pubchem.ncbi.nlm.nih.gov
Description	Data deposited in or computed by PubChem

Canonical SMILES	CC(C)CC1=CC=C(C=C1)C(C)C(=O)O	Source
Source	PubChem
URL	https://pubchem.ncbi.nlm.nih.gov
Description	Data deposited in or computed by PubChem

Isomeric SMILES	[2H]C([2H])([2H])[C@@H](C1=CC=C(C=C1)CC(C)C)C(=O)O	Source
Source	PubChem
URL	https://pubchem.ncbi.nlm.nih.gov
Description	Data deposited in or computed by PubChem

Molecular Formula	C13H18O2	Source
Source	PubChem
URL	https://pubchem.ncbi.nlm.nih.gov
Description	Data deposited in or computed by PubChem

Molecular Weight	209.30 g/mol	Source
Source	PubChem
URL	https://pubchem.ncbi.nlm.nih.gov
Description	Data deposited in or computed by PubChem

Synthesis routes and methods I

Procedure details

Surprisingly, only a few methods for a stereospecific chemical synthesis for 2-aryl-alkanoic acids, especially 2-aryl-propionic acids, are known. Piccolo et al. (J. Org. Chem. 50, 3945-3946, 1985) describe a stereospecific synthesis by the alkylation of benzene or isobutylbenzene with (S)-methyl-2-(chlorosulfonyl)-oxy or 2-(mesyloxy) propionate in the presence of aluminum chloride yielding (S)-methyl-2-phenyl-propionate in good chemical yield (50-80%) and excellent optical yield of >97% as determined by rotation through inversion of configuration at the attacking carbon atoms. The reaction conditions are very similar as described in some patents (Jpn. Kokai Tokkyo Koho 5808045; Chem. Abstracts, 1983, 98; 143138 k; Jpn. Kokai Tokkyo Koho 7979246; Chem. Abstracts, 1980, 92, 6253 f) where racemic reagents have been used. Extensions of this type of reactions to other aromatic substrates, e.g. toluene, isobutylbenzene, tetraline, anisole, naphthalene, 2-methoxy-naphthalene are described in Jpn. Kokai Tokkyo Koho 7971932; Chem. Abstracts 1979, 91, 20125 b; Jpn. Kokai Tokkyo Koho 78128327; Chem. Abstracts 1978, 89, 23975 y; Jpn. Kokai Tokkyo Koho 81145241; Chem. Abstracts 1982, 96, 68650 z; Jpn. Kokai Tokkyo Koho 78149945; Chem. Abstracts 1979, 90, 168303 h; Jpn. Kokai Tokkyo Koho 7844537; Chem. Abstracts 1978, 89, 108693 h; Jpn. Kokai Tokkyo 77131551; Chem. Abstracts 1978, 88, 104920 h. In a recent paper Piccolo et al. (J. Org. Chem. 52. 10, 1987) describe a synthesis leading to R-(-) ibuprofen, whereas Tsuchihashi et al. (Eur. Pat. Appl. EP 67,698, (1982); Chem. Abstracts 98, 178945 y, (1983) report a stereospecific synthesis of the R-(-) ibuprofen-methylester with excellent yields of about 75.0% and high optical purity (>95%) in contrast to Piccolo et al. (J. Org. Chem. 32, 10, 1987) having an optical purity of 15% only for the R-(-) ibuprofen. However, the same authors have reported chemical yields of 68% of S (+) ibuprofen having an optical purity of 75-78%, only. Hayashi, et al. (J. Org. Chem. 48, 2195, 1983; in: Asymmetric Reactions and Processes In Chemistry; eds E. L. Eliel and S. Otsuka, ACS-Symposium Ser. 1985, 1982, 177) describe a stereospecific synthesis of S-(+) ibuprofen through asymmetric Grignard cross-coupling which are catalyzed by chiral phosphine-nickel and phosphine-palladium complexes. The enantiomeric excess of the coupling products with various alkenyl halides under the influence of the above-mentioned metal phosphine complexes, including amino acids, depends strongly on the ligand and ranges up to 94% with enantiomeric excesses in the 60-70% range. A very useful ligand has been found in chiral 2-aminoalkyl phosphines achieving reasonable chemical yields and high optical purity. Furthermore, optically active 2-aryl-alkonates have been synthesized via a Friedel-Crafts synthesis by Sato and Murai (Jpn. Kokai Tokkyo Koho JP 61,210,049 t 86,210,049, 1986) yielding 46% S-(+) ibuprofen. Giordano et al. (EP application 0 158 913, 1985) have reported a process for the preparation of optically active 2-aryl-alkanoic acids and intermediates thereof by halogenation on the aliphatic carbon atom to the ketal group and rearrangements of the haloketals yielding pharmacologically active 2-aryl-alkanoic acids. A stereochemical synthesis of 2-aryl-propionic acids is described by Robertson et al. (EP application 0 205 215 A2, 1986) using 2-(R1)-alkane as the carbon source for the fungi Cordyceps in particular for Cordiceps militaris, yielding enantiomeric S-(+) products of high optical purity.

[Compound]

Name

aromatic substrates

Quantity

0 (± 1) mol

Type

reactant

Reaction Step One

Name

toluene

Quantity

0 (± 1) mol

Type

solvent

Reaction Step Two

Name

isobutylbenzene

Quantity

0 (± 1) mol

Type

reactant

Reaction Step Three

Name

tetraline

Quantity

0 (± 1) mol

Type

reactant

Reaction Step Four

Name

anisole

Quantity

0 (± 1) mol

Type

reactant

Reaction Step Five

Name

naphthalene

Quantity

0 (± 1) mol

Type

reactant

Reaction Step Six

Name

2-methoxy-naphthalene

Quantity

0 (± 1) mol

Type

reactant

Reaction Step Seven

[Compound]

Name

R-(-) ibuprofen

Quantity

0 (± 1) mol

Type

reactant

Reaction Step Eight

[Compound]

Name

R-(-) ibuprofen-methylester

Quantity

0 (± 1) mol

Type

reactant

Reaction Step Nine

[Compound]

Name

R-(-) ibuprofen

Quantity

0 (± 1) mol

Type

reactant

Reaction Step Ten

Name

(+) ibuprofen

Details

Synthesis routes and methods II

Procedure details

To a solution of benzyl 2-p-isobutylphenylpropionate (3 g) in methylene chloride (18 ml) are added a solution of aluminum chloride (4 g) in nitromethane (50 ml) and anisole (3 ml) at 0° C., and the mixture is stirred at room temperature for 6 hours. The reaction mixture is diluted with ethyl acetate, washed with hydrochloric acid and water, dried and evaporated. The residue is recrystallized with n-hexane to give 2-p-isobutylphenylpropionic acid (186 mg) melting at 75°-77.5° C. Yield 91%.

Name

benzyl 2-p-isobutylphenylpropionate

Quantity

3 g

Type

reactant

Reaction Step One

Name

aluminum chloride

Quantity

4 g

Type

reactant

Reaction Step One

Name

methylene chloride

Quantity

18 mL

Type

solvent

Reaction Step One

Name

nitromethane

Quantity

50 mL

Type

solvent

Reaction Step One

Name

anisole

Quantity

3 mL

Type

solvent

Reaction Step One

Name

ethyl acetate

Quantity

0 (± 1) mol

Type

solvent

Reaction Step Two

Name

2-p-isobutylphenylpropionic acid

Yield

91%

Details

Synthesis routes and methods III

Procedure details

Three grams of flurbiprofen and 30 g of poloxamer 237 were heated at 110° C. for 10 minutes to obtain a liquified mixture and cooled to 60° C. Into this mixture, 5 g of polyethylene glycol 300, 10 g of ethanol and 52 g of pH 4 buffer solution were added at 60° C. to obtain an ibuprofen gel.

Name

flurbiprofen

Quantity

0 (± 1) mol

Type

reactant

Reaction Step One

[Compound]

Name

poloxamer 237

Quantity

30 g

Type

reactant

Reaction Step One

[Compound]

Name

polyethylene glycol 300

Quantity

5 g

Type

reactant

Reaction Step Two

[Compound]

Name

buffer solution

Quantity

0 (± 1) mol

Type

reactant

Reaction Step Two

Name

ethanol

Quantity

10 g

Type

reactant

Reaction Step Two

Name

ibuprofen

Details

Synthesis routes and methods IV

Procedure details

The process according to claim 1, wherein 3-isobutyl-cyclohexanone and sodium pyruvate are heated in a HCl and acetic acid solution to give a mixture of condensation products and said condensation products are heated for 4 to 5 hours with pyridine hydrochloride to give p-isobutylhydratropic acid.

Name

3-isobutyl-cyclohexanone

Quantity

0 (± 1) mol

Type

reactant

Reaction Step One

Name

sodium pyruvate

Quantity

0 (± 1) mol

Type

reactant

Reaction Step Two

Name

HCl

Quantity

0 (± 1) mol

Type

reactant

Reaction Step Three

Name

acetic acid

Quantity

0 (± 1) mol

Type

solvent

Reaction Step Three

Name

pyridine hydrochloride

Quantity

0 (± 1) mol

Type

reactant

Reaction Step Four

Name

p-isobutylhydratropic acid

Details

Retrosynthesis Analysis

AI-Powered Synthesis Planning: Our tool employs the Template_relevance Pistachio, Template_relevance Bkms_metabolic, Template_relevance Pistachio_ringbreaker, Template_relevance Reaxys, Template_relevance Reaxys_biocatalysis model, leveraging a vast database of chemical reactions to predict feasible synthetic routes.

One-Step Synthesis Focus: Specifically designed for one-step synthesis, it provides concise and direct routes for your target compounds, streamlining the synthesis process.

Accurate Predictions: Utilizing the extensive PISTACHIO, BKMS_METABOLIC, PISTACHIO_RINGBREAKER, REAXYS, REAXYS_BIOCATALYSIS database, our tool offers high-accuracy predictions, reflecting the latest in chemical research and data.

Strategy Settings

Precursor scoring	Relevance Heuristic
Min. plausibility	0.01
Model	Template_relevance
Template Set	Pistachio/Bkms_metabolic/Pistachio_ringbreaker/Reaxys/Reaxys_biocatalysis
Top-N result to add to graph	6

Feasible Synthetic Routes

Reactant of Route 1

(S)-(+)-Ibuprofen-d3

Reactant of Route 2

(S)-(+)-Ibuprofen-d3

Reactant of Route 3

(S)-(+)-Ibuprofen-d3

Reactant of Route 4

(S)-(+)-Ibuprofen-d3

Reactant of Route 5

(S)-(+)-Ibuprofen-d3

Reactant of Route 6

(S)-(+)-Ibuprofen-d3

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Please be aware that all articles and product information presented on BenchChem are intended solely for informational purposes. The products available for purchase on BenchChem are specifically designed for in-vitro studies, which are conducted outside of living organisms. In-vitro studies, derived from the Latin term "in glass," involve experiments performed in controlled laboratory settings using cells or tissues. It is important to note that these products are not categorized as medicines or drugs, and they have not received approval from the FDA for the prevention, treatment, or cure of any medical condition, ailment, or disease. We must emphasize that any form of bodily introduction of these products into humans or animals is strictly prohibited by law. It is essential to adhere to these guidelines to ensure compliance with legal and ethical standards in research and experimentation.

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