N,N'-diethyl-N,N'-ditolyl-dipicolin

N,N'-diethyl-N,N'-ditolyl-dipicolinamidesweresynthe-sized by reaction of thionyl chloride with 2,6-pyridinedi-carboxylic acid (dipicolinic acid) forming acyl chlorides.Acyl chloride was then reacted with either ortho, meta, orpara isomers of N-ethyltoluidine to produce the desiredEtTDPA molecule [19]. Chemicals used in the synthesis ofEtTDPA obtained from TCI Co. LTDwere of analyticalgrade and used without further purification. The purity of theligand was checked by using elemental analysis and NMRPiguet and co-worl-kers22published an elegant solution to thesynthesis of functionalized Bip derivatives from an N-alkyl-o-nitroaniline derivative and 2,6-pyridine dicarboxylic acid chloride.An example of this is shown in Scheme 1. Targeting Bip1, ethyl-amine wasreacted with the commercially available 4-chloro-3-nitroanisole (1) yielding the desired N-ethyl-2-nitroaniline (2).2,6- Pyridine dicarboxylic acid (3)was then activated with thionylchloride to produce 2,6-pyridine dicarboxylic acid chloride (4),which was subsequently reacted with 2 in the presence of triethylamine in chloroform to yield 5 in 60% yield after purification viacolumn chromatography. The desired Bip derivative could then beaccessed under relatively milder conditions compared to the pre-viously described method by reduction of the nitro group andsubsequent ring- -closing with activated iron and hydrochloric acidin aqueous ethanol at 80 'C. Excess iron was removed using a sat-urated aqueous ethylenediaminetetraacetic acid (EDTA) solutionand the crude reaction mixture was neutralized using aqueousammonium hydroxide. The derivative Bip1 was isolated in 75%