Synthesis of enantiopure 2-iodomandelic acid and determination of its absolute configuration by VCD spectroscopy
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Racemic 2-iodomandelic acid 1 was synthesized from commercially available 2-iodobenzoic acid 2. Acyl chloride 3 was reacted with diethyl malonate, then the formed diester was hydrolysed and decarboxylated in a one-pot reaction. The obtained 2-iodoacetophenone 4 was reacted with bromine and the dibromoacetophenone derivative 5 was hydrolysed to give the racemic 2-iodomandelic acid (±)-1. Optical resolution of (±)-1 via diastereomeric crystallization with strychnine afforded enantiopure (R)-(−)-1. Absolute configuration of (−)-1 and of its methyl ester (−)-6 was determined by VCD spectroscopy.
KeywordsMandelic acid derivatives Building block Optical resolution Determination of absolute configuration
The authors thank Professor József Rábai the stimulating discussions and the National Research Development and Innovation Office (K115764), and the Central Hungarian Operational Program (KMOP-4.2.1/B-10-2011-0002) for supporting this work.
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