53648-05-8

Basic information

• Product Name: ibuproxam
• Synonyms: ibuproxam;p-Isobutylhydratropohydroxamic acid;G-277;Ibudros;N-Hydroxy-α-methyl-4-isobutylbenzeneacetamide;Nsc305528;2-(4-Isobutylphenyl)propionohydroxamic acid;N-Hydroxy-alpha-methyl-4-(2-methylpropyl)-benzeneacetamide
• CAS NO: 53648-05-8
• Molecular Formula: C₁₃H₁₉NO₂
• Molecular Weight: 221.29546
• EINECS: 258-683-8
• Mol File: 53648-05-8.mol

Chemical Properties

• Melting Point: 119-121℃
• Boiling Point: 362.36°C (rough estimate)
• Flash Point: °C
• Appearance: /
• Density: 1.058
• Refractive Index: 1.5175 (estimate)
• PKA: 9.40±0.40(Predicted)
• Water Solubility: 0.2g/L(temperature not stated)
• CAS DataBase Reference: ibuproxam(CAS DataBase Reference)
• NIST Chemistry Reference: ibuproxam(53648-05-8)
• EPA Substance Registry System: ibuproxam(53648-05-8)

Safety Data

• Hazardous Substances Data: 53648-05-8(Hazardous Substances Data)

Usage

Originator

Ibudros,Manetti-Roberts,Italy,1978

Uses

rac Ibuproxam is a poorly water-soluble anti-inflammatory drug.

Definition

ChEBI: A hydroxamic acid obtained by formal condensation of the carboxy group of ibuprofen with the amino group of hydroxylamine. Used for treatment of pain and inflammation associated with musculoskeletal and joint disorders.

Manufacturing Process

In a 1,000 ml three-necked flask equipped with a stirrer, a dropping funnel and a silica gel guard pipe, 46.7 g hydroxylamine hydrochloride are dissolved cold in 480 ml methanol. Separately a solution of 56.1 g KOH in 280 ml methanol is prepared, heated to 30°C and admixed, dropwise under stirring to the hydroxylamine solution. All successive temperature increases during this admixture are prevented by cooling in an ice bath. After the whole KOH solution has been admixed, the mixture is left standing for 5 minutes so as to attain the complete precipitation of the KCl.Separately, 72.02 g ethyl 2-(4-isobutylphenyl)-propionate, obtained by the esterification of 2-(4-isobutylphenyl)-propionic acid with ethanol and concentrated H2SO4, are solved with 100 ml methanol, this solution is introduced drop by drop into the reaction flask, and stirred and cooled for 5 hours on an ice bath. Thereafter it is suction filtered, the residue is washed with all together 50 ml methanol, the wash is added to the filtrate, thereafter the whole is evaporated in a water bath with a rotating evaporator at a reduced pressure, until 100-200 ml of a concentrated solution are obtained. This solution is poured into a 200 ml beaker into which are stirred approximately 1,000 ml 1.25N acetic acid. This mixture is left standing for 24 hours, thereafter suction filtered. The resulting filtrate is taken up with 100 ml petroleum ether at 40°C to 60°C, in order to solve any possible residue of unreacted starting ester, and refiltered. Approximately 50g of 2-(4- isobutylphenyl)-propiohydroxamic acid are obtained, having a melting point of 119°C to 121°C on Kofler's hot stage.

Therapeutic Function

Antiinflammatory

InChI:InChI=1/C13H19NO2/c1-9(2)8-11-4-6-12(7-5-11)10(3)13(15)14-16/h4-7,9-10,16H,8H2,1-3H3,(H,14,15)

Upstream product

• 61566-34-5 (+/-)-ibuprofen methyl ester 
• 15687-27-1 ibuprofen 

Downstream Products

• 38861-78-8 1-(4-isobutyl-phenyl)-ethanone 
• 15687-27-1 ibuprofen 
• 74305-51-4 4'-(2-methylpropyl)acetophenone oxime 
• 164579-51-5 4-(2-methylpropyl)phenylethylamine 

Relevant articles and documents

P(III)-Assisted Electrochemical Access to Ureas via in situ Generation of Isocyanates from Hydroxamic Acids

An external oxidant-free protocol for the generation of isocyanates from hydroxamic acids assisted by trivalent phosphine under mild electrochemical conditions was reported. The process started with the anodic oxidation of hydroxamic acids, followed by reacting with phosphine to form corresponding alkoxyphosphoniums and subsequent rearrangement with the release of tri-substituted phosphine oxide as the driving force to give isocyanates, which were trapped by N-based nucleophiles to produce various ureas. This method provides a broadly applicable procedure to access isocyanate intermediates under mild electrochemical conditions.

Thioether-Directed NiH-Catalyzed Remote γ-C(sp3)-H Hydroamidation of Alkenes by 1,4,2-Dioxazol-5-ones

A NiH-catalyzed thioether-directed cyclometalation strategy is developed to enable remote methylene C-H bond amidation of unactivated alkenes. Due to the preference for five-membered nickelacycle formation, the chain-walking isomerization initiated by the NiH insertion to an alkene can be terminated at the γ-methylene site remote from the alkene moiety. By employing 2,9-dibutyl-1,10-phenanthroline as the ligand and dioxazolones as the reagent, the amidation occurs at the γ-C(sp3)-H bonds to afford the amide products in up to 90% yield (>40 examples) with remarkable regioselectivity (up to 24:1 rr).

Intermolecular, Branch-Selective, and Redox-Neutral Cp*IrIII-Catalyzed Allylic C?H Amidation

Herein, we report the redox-neutral, intermolecular, and highly branch-selective amidation of allylic C?H bonds enabled by Cp*IrIII catalysis. A variety of readily available carboxylic acids were converted into the corresponding dioxazolones and efficiently coupled with terminal and internal olefins in high yields and selectivities. Mechanistic investigations support the formation of a nucleophilic IrIII–allyl intermediate rather than the direct insertion of an Ir–nitrenoid species into the allylic C?H bond.

Synthesis and antinociceptive evaluation of bioisosteres and hybrids of naproxen, ibuprofen and paracetamol

The aim of this work was to design, synthesize and characterize the potential anti-nociceptive and anti-inflammatory activities of a new series of bioisosteres and hybrids from known non-steroidal anti-inflammatory drugs (NSAIDs). The compounds 4-(acetylamino)phenyl (2S)-2-(6-methoxy-2-naphthyl)propanoate (GUF-1) and 4-(acetylamino)phenyl 2-(R,S)-(4-isobutylphenyl)propanoate (GUF-2) were synthesized as hybrids (also known as heterodimers); whereas those named 2-(R,S)-(4-isobutylphenyl)-N-1H-tetrazol-5-ylpropanamide (GUF-3), (2S)-2-(6-methoxy-2-naphthyl)-N-1H-tetrazol-5-ylpropanamide (GUF-4), [2-(R,S)-N-hydroxy-2-[4-(2-methylpropyl)phenyl]propanamide] (GUF-5), and (2S)-N-hydroxy-2-(6-methoxy-2-naphthyl)propanamide (GUF-6) were synthesized as bioisosteres of the NSAIDs paracetamol, ibuprofen, and naproxen, respectively. All these compounds were characterized by spectroscopic and spectrometric analysis. Antinociceptive activity of GUF-1 to GUF-6 was evaluated using the formalin test in rats. Pharmacological responses of GUF-1, GUF-2 (hybrids), and GUF-5 (bioisostere) demonstrated significant antinociceptive effects; thus these compounds were assayed in an inflammation test like carrageenan-induced paw oedema in rats. Complete molecular docking of cyclooxygenase and the GUF-1 and GUF-2 hybrids showed high docking scores, compared to the reference drugs. Our data demonstrate that compounds GUF-1, GUF-2, and GUF-5 possesses antinociceptive and antiinflammatory activities resembling and improving those known for the traditional NSAIDs, paracetamol, naproxen and ibuprofen.