Chem
Abstract
In the asymmetric synthesis of (S)-Ibuprofen, the compound is synthesized in nonracemic form directly from an achiral precursor. First, racemic ibuprofen was converted to aN achiral ketene via the acid chloride by adding thionyl chloride followed by triethylamine. Then, ketene was reacted with a chiral and nonracemic (S)-ethyl lactate produces a mixture of diasteromeric esters of ibuprofen derivatives where (S) configuration is predominantly. Finally, hydrolysis of the ester then provides (S)-ibuprofen in a relatively high yield. all reaction were monitored by TLC at room temperature with appropriate solvent system which states in experiment section. IR, 1H-NMR, 13C-NMR, polarimetry and melting point range were used to define the product and its purity.
Introduction
Racemic mixture of ibuprofen is sold in the market, however only the (S)-enantiomer is responsible for the desired therapeutic effects. 1 Although the (R) is converted to the (S) isomer in the body, the (R)- ibuprofen displays toxicity due to its storage in fatty tissue as a glycerol ester, whose long-term effects are not known.2 There are many method to prepare the desired optically pure form, including resolution of diastereomeric salt, resolution of racemic, and asymmetric syntheses using chiral auxiliaries and chiral catalysts.3 In this experiment, asymmetric syntheses has been used to generate (S)-ibuprofen isomer. The experiment part will discuss in the later section.
In McCullag’s paper, resolution of racemic ibuprofen involved adding a resolving agent, (S)-(-)- phenethylamine, to the racemic mixture.4 The resolving agent undergo an acid-base reaction with Ibuprofen and producing two salts that are diastereomers.
Scheme 1: synthesis of (S, S) salt and (R, S) salt- insoluble in aqueous solution
In McCullag’s paper, racemic ibuprofen (1) was dissolved in 0.24 M of KOH and stirring the mixture at temperature between 75C and 85C. Then resolving agent, (S)-(-)- phenethylamine
In the asymmetric synthesis of (S)-Ibuprofen, the compound is synthesized in nonracemic form directly from an achiral precursor. First, racemic ibuprofen was converted to aN achiral ketene via the acid chloride by adding thionyl chloride followed by triethylamine. Then, ketene was reacted with a chiral and nonracemic (S)-ethyl lactate produces a mixture of diasteromeric esters of ibuprofen derivatives where (S) configuration is predominantly. Finally, hydrolysis of the ester then provides (S)-ibuprofen in a relatively high yield. all reaction were monitored by TLC at room temperature with appropriate solvent system which states in experiment section. IR, 1H-NMR, 13C-NMR, polarimetry and melting point range were used to define the product and its purity.
Introduction
Racemic mixture of ibuprofen is sold in the market, however only the (S)-enantiomer is responsible for the desired therapeutic effects. 1 Although the (R) is converted to the (S) isomer in the body, the (R)- ibuprofen displays toxicity due to its storage in fatty tissue as a glycerol ester, whose long-term effects are not known.2 There are many method to prepare the desired optically pure form, including resolution of diastereomeric salt, resolution of racemic, and asymmetric syntheses using chiral auxiliaries and chiral catalysts.3 In this experiment, asymmetric syntheses has been used to generate (S)-ibuprofen isomer. The experiment part will discuss in the later section.
In McCullag’s paper, resolution of racemic ibuprofen involved adding a resolving agent, (S)-(-)- phenethylamine, to the racemic mixture.4 The resolving agent undergo an acid-base reaction with Ibuprofen and producing two salts that are diastereomers.
Scheme 1: synthesis of (S, S) salt and (R, S) salt- insoluble in aqueous solution
In McCullag’s paper, racemic ibuprofen (1) was dissolved in 0.24 M of KOH and stirring the mixture at temperature between 75C and 85C. Then resolving agent, (S)-(-)- phenethylamine
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