CHLORINATED PHENYL AZIDES AS PHOTOLABELING REAGENTS - SYNTHESIS OF ANORTHO,ORTHO'-DICHLORINATED ARYLAZIDO PCP RECEPTOR-LIGAND

The enhanced photolabeling properties of chlorinated phenyl azides are demonstrated by the synthesis and photolysis of methyl 4-azido-2,3,5, 6-tetrachlorobenzoate (3) and methyl 4-azido-3,5-dichlorobenzoate (4). Photolysis of azide 3 in 1 M diethylamine/cyclohexane as the trapping medium gave 34% NH-insertion product. Similar photolysis of azide 4 g ave 35% NH insertion product. These results demonstrate that chlorinat ed phenyl azides are significantly better at undergoing NH insertion t han nonhalogenated analogs and suggest that improvement of existing ar yl azide-based photolabels might be achieved by introduction of chlori ne atoms on either side of the azide group. As an application, methano )-10,11-dihydro-5H-dibenzo[a,d]cycloheptene (19), an analog of the pot ent PCP receptor ligand IDDC (14), was synthesized and its affinity fo r the PCP receptor was determined to be 6.3 +/- 0.7 muM (IC50 against [H-3]MK801).