Dihydro-m-benzoxazines were prepared by condensation of phenols, /3-naphthol and 7-hydroxycoumarins with formaldehyde and primary amines. The products were quaternized or cleaved hydrolytically to aminophenols which could be condensed with aromatic aldehydes to yield 2-substituted dihydro-1,3-oxazines.From hydroquinone, isomeric pairs of bis-dihydrooxazines were obtained and structures assigned on the basis of dipole measurements. The dihydro-moxazines as a class show inhibition of adenocarcinoma E0771. This activity is retained in the corresponding methiodides and aminophenols as well as nonbenzenoid tetrahydro-m-oxazines.Introduction.-The organic chemist's intensive efforts to synthesize compounds which will inhibit unrestricted neoplastic growth have led to effective agents which may be grouped into three categories: (a) alkylating agents, (b) antimetabolites and (c) diverse unrelated compounds which have been discovered either by random antitumor screening or because of a special therapeutic interest in some other Abbreviations Used in Tables I-X.-Solvents: a, (methylene chloride-) methanol; b, (methylene chloride-) ethanol; c, (methylene chloride-) benzene; d, (methylene chloride-) ethyl acetate; e, (methylene chloride-) cyclohexane; /, (methylene chloride-) heptane; g, chloroform; h, methanol-ether; i, water.Substituent groups: j, 3-picolyl; k, 4-picolyl; l, 3,4-dimethoxyphenethyl; m, 2-picolyl; p, 4-pyridyl; q, 3-pyridyl; r, 2-pyridyl. Other: n, partial destruction on chromatography; o, 0.01 molar in benzene except 0.004 molar for no. 76, 77, 84, 85; s, orally active.
