Several potentially bis(alkylating) bis(quinones) (3-5) and 1,4- and 1,3-bis(alkylating) monoquinones (6-13) belonging to general structure 2,2'-ethylenebis[5-[(leaving group)methyl]-1,4-benzoquinone] (3-5) and 2,5- and 2,6-bis[(leaving group)methyl]-1,4-benzoquinone water-soluble and -insoluble classes were prepared by oxidative demethylation of the corresponding tetramethoxydiphenylethanes (17-19) and dimethoxybenzenes (24, 27, 36-39), respectively. Methods employed for the preparation of tetramethoxydiphenylethane intermediates involved (1) arylmethyl bromide coupling and (2) catalytic hydrogenation of stilbene intermediates derived via Wittig reaction of (arylmethyl)phosphonium salts with aryl aldehydes. However, in biological investigations using a subcutaneous B16 (hypoxic) melanoma tumor in BDF1 hybrid mice with cyclophosphamide as positive control the most interesting series of structurally related analogues were the potentially monoalkylating monoquinones of the 2-[(leaving group)methyl]-1,4-benzoquinone type (i.e., 14 and 15) having water-insoluble (acetoxy) and water-solubilizing (succinate) groups. Serial measurements of tumor size, and evaluation of increased life span, in response to drug treatment also revealed potentially 1,4-bis(alkylating) (bromomethyl)-1,4-quinone 7 and 1,3-bis(alkylating) (hydroxymethyl)-1,4-quinone 10 to have variable activity, but none of the potentially bis(alkylating) bis(quinones) showed antitumor properties in this model.

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ChemInform Abstract Treatment of the bicyclic tertiary alcohols (I), (VII), and (VIII) with iodine and mercuric oxide (yellow modification) results in ring cleavage, yielding the iodo ketones as shown in the reaction scheme. The additional product (X) is formed in the case of the unsaturated alcohol (VII). Further examples of this reaction are given in the original paper. The synthesis of the alcohols (VII) and (VIII) is also described. (Intermediates, mechanism).

ChemInform Abstract Wittig reaction of the phosphonium salt (IV) with the aldehyde (V) is the key step in the synthesis of the bisalkylating bisquinones (VIII), (IX), and (XI). The bisalkylating quinones (XIII), (XIV), (XVI), and (XVII) are prepared as outlined in the reaction scheme, the 2,6-disubstituted quinones (XVIII) are produced analogously from the 2,6-disubstituted dimethoxybenzenes. The antitumor activity of the quinones prepared is studied.