Synthesis of N-(2-Hydroxybenzyl)iminodiacetic Acid Ligand Towards the Study of its Complex with Iron(III)

Previous work in this lab has led to evidence that 2-(hydroxybenzyl)aminodiacetic acid (HDA) possibly forms a diiron complex with iron(III). If this is true, the complex could serve as a model for a class of enzymes called purple acid phosphatases. Chapter 1 gives some background information about diiron complexes in nature and the properties of purple acid phosphatases. It also summarizes work in this lab involving the formation of the iron(III)-HDA complex and the study of its stoichiometry. Early experiments with iron(III) and HDA exhausted the supply of HDA that had been synthesized once previously. For this complex to be studied in the future, a reliable and high yielding HDA synthesis procedure would be needed. Chapters 2-4 each outline a different HDA synthesis pathway that was attempted. The first pathway (outlined in chapter 2) involved a 1 step Mannich reaction, where a secondary amine reacts with formaldehyde to form an imminium ion intermediate, and then a nucleophile (in this case phenol) attacks the imminium ion and forms a tertiary amine. This reaction worked well, but the desired product was not able to be isolated from impurities as a crystalline solid. In the second pathway (outlined in chapter 3), a primary amine is alkylated with chloroacetic acid via an SN2 reaction. This pathway was a three-step synthesis, with the first two steps dedicated to forming the desired primary amine, 2-(aminomethyl)phenol, and the third step as the alkylation step. The first two steps were successfully completed, with the third step still needing work. The third reaction pathway (outlined in chapter 4) was another three-step synthesis. The first step in this synthesis used an Appel reaction, where carbon tetrabromide (or chloride) and triphenylphosphine are used to convert an alcohol into an alkyl halide. The second step involved the addition of iminodiacetonitrile to the primary alkyl halide in an SN2 reaction. The carboxyl groups are then added in a hydrolysis reaction in the third step. The first step of the synthesis worked, but the purification methods attempted were not successful. The conditions for the second step of the synthesis were successfully set, and the third step needs to be worked on in the future. All three reaction pathways showed promise and could potentially be used as a reliable HDA synthesis method