A regio and stereospecific synthesis of monoarylimino ortho-quinones derived from β-lapachone (1) was achieved by treatment of the quinone with a slight excess of an arylamine in the presence of an excess of triethylamine/titanium tetrachloride 4:1. Imine formation occurred exclusively at position 6 giving the Z diastereomer, as determined by single crystal X-ray analysis. In vitro tests for cytotoxicity in 55 human cancer cell cultures showed a substantial loss in activity for the p-nitrophenylimine (5) while the phenylimine (2), p-methylphenylimine (3) and p-methoxyphenylimine (4), retained (or bettered) most of the cytotoxicity and selectivity of the parent quinone. Preliminary in vivo testing in hollow fiber assays against a standard panel of 12 human tumor cell lines showed that while -lapachone failed, compounds 2 and 3 had a good score with a net cell kill.