Optimization of the Synthesis of n-Phthalimidoalkylthiols as Precursors for w-Aminoalkylthiols as Prepared by Undergraduate Chemistry Students

The synthesis of n-phthalimidoalkylthiols from phthalimide and n,m-dibromoalkane was demonstrated as a general approach to short and medium chain (x = 1 to 12) functional alkylthiols in an undergraduate laboratory setting. The reaction conditions were demonstrated to be mild enough to directly synthesize nphthalimidoalkylthiols with a carbon chain containing either double or triple bonds. The syntheses of each of these alkylthiols can be completed in less than 24 h (over a few laboratory periods) with at least a 50% overall yield. Reactivity of n,m-dibromoalkane with phthalimide was monitored with 1 H-NMR to determine the length of time needed for the reaction to reach completion avoiding the inaccurate use of thin layer chromatography. Based on this result, reaction times were reduced by two-thirds from those previously reported in the literature, which was necessary to prepare a method that will accommodate the duration of second year introductory organic or organic spectroscopy courses.