Six 2,5- and 5,6- dihalonicotinic acids in a mixture were converted to their corresponding methyl esters and then analyzed by gas chromatography and gas chromatography-mass spectrometry. Four methods of conversion were compared for their GC sensitivity, efficiency and analysis time. In Method #1, using HC1 and methanol as the reagents, the displacement of the halogens by chlorine (from HC1) at 2- and 6-positions was a common occurrence, rendering the method inefficient. In Method #2 (BF3/methanol), the displacement of halogens by methoxide was evident. Method #3 (dicyclohexylcarbodiimide/methanol) produced a mixture of derivatives with a poor yield. Method #4 (diazomethane) gave a quantitative yield of the corresponding methyl esters without any side reactions and was suitable for analytical method development. The latest method provided short analysis time with all six methyl dihalonicotinates eluting within nineteen minutes. The resolution of the ester peaks was excellent and the detection limit was about 1ng/|Mu L for the dihalonicotinic acids.
Fossler, Cheryl L.; Setliff, Frank L.; and Shaikh, Ali U.
"Analysis of a Mixture of Several Dihalonicotinic Acids by Gas Chromotography and Gas Chromotography-Mass Spectrometry,"
Journal of the Arkansas Academy of Science: Vol. 52
, Article 9.
Available at: http://scholarworks.uark.edu/jaas/vol52/iss1/9