Starting from commercially available Ni(II)octaethylporphyrin (OEP), an efficient approach for the preparation of a series of fluorinated and nonfluorinated benzochlorins with variable lipophicity has been developed. Their spectroscopic properties, preliminary in vitro photosensitizing efficacy, and tumor selectivity were determined. Our methodology provides a facile approach for the preparation of the free-base and the related Zn(II) benzochlorins containing alkyl and alkyl ether side chains with variable carbon units. For the preparation of benzochlorins containing alkyl groups attached to the exocyclic phenyl ring, the Ni(II) meso-(2-formylvinyl)octaethyl porphyrin 2 was reacted with various reagents such as (trifluoromethyl)trimethylsilane (TMS-CF3) or the Grignard reagents of various fluorinated or nonfluorinated alkyl halides. The corresponding intermediates 3, 6a−6e, and 8 obtained via intramolecular cyclization under acidic conditions afforded the related benzochlorins 5, 7a−d, and 9 in good yield...