Ortho-Hydroxylation of Phenols: With an Addendum on the Cyclisation of 2-Aryloxy-5-Nitrobenzaldehydes

In the method of ortho-hydroxylation studied, phenol, its derivatives or homologues, are condensed with 2-chloro-5-nitrobenzophenone, (Ph.CO.C6H3.NO2.Cl or, for convenience, RCl ) giving aryloxy-nitrobenzophenones of type 1. These, on successive treatment with concentrated sulphuric acid, acetic acid, and hydrogen peroxide, afford o-hydroxyaryloxy-nitrobenzophenones of type 2, which undergo scission in boiling piperidine to give simple derivatives or homologues of catechol. Methylation of type 2 affords compounds of type 3 which on scission yield guaiacol derivatives. Diazomethane is the most reliable methylating agent since it is shown that in suitable compounds of type 2 and in alkaline media, the group R may migrate from one to the other oxygen atom. A preliminary investigation into the possible advantages of 2-chloro-3:5-dinitrobenzophenene over the nono-nitro compound gave promising results. 1. R.O.C6H5; 2. R.O.C6H4.OH; 3. R.O.C6H4.CMe; 4. R O.C6H3.(OH)2; 5. R.O.C6H3.OH.OMe. Renewed hydroxylation, applied to compounds of types 2 and 3, yields those of types 4 and 5 respectively. When heated with piperidine compounds of type 4 in general were not cleaved to pyrogallols, but underwent rearrangement followed by cyclisation, the products finally isolated being derivatives of 4-hydroxy-7-nitro-9-phenylfluorone. The latter process was blocked by the presence of methyl substituents in the positions flanking the two free hydroxyl groups, and in this case with piperidine normal scission to 4:6-dimethylpyrogallol took place. The presence of bromo substituents in these positions did not prevent fluorone formation which was attended by expulsion of one bromine atom. Methylation or tosylation of the hydroxyl groups before treatment with piperidine resulted in normal scission, affording partial O-derivatives of pyrogallol. In one case 1:2:3:4-tetramethoxybenzene was synthesised from phenol by a combination of three hydroxylations and one rearrangement. In an addendum the cyclisation by concentrated sulphuric acid of 2-aryloxy-5-nitrobenzaldehydes is described and is shown to take a different course from that of the 2-arylthio- analogues