a two-step protonation. As a check of the method, the pKa of o-iodobenzoic acid was determined concurrently, yielding the value of -7.4 which is in good agreement with previously published data ( 12).
A first protonation of compound I could lead to structures Ib, Id, Ic, or If; loss of water from I b will yield Ic. (Schcme I.) Of these structures for a single protonation, I b and I/ are considered least likely. Protoriation of a conjugated carbonyl function, such as that of benzophenone, occurs a t pKa = -6.41 (16). and protonation of a lactone occurs at the carbonyl rather than the ether oxygen; an electronic shift would convert "structure" If into Ie. Examination of Fig. 2 reveals that protonation of compound I gives rise to a new peak a t 256 mp, while the doublet at 276-284 coalesces to a single peak a t 288 mp. By comparison, o-iodobcnzoic acid shows a peak at 285 mp which, in strong acid, shifts to 328 nip. Thus, the 288 mp peak of mono-protonated 1,3dihydro-l-hydroxy-3-oxo-l,2-benziodoxole could be indicative of thc presence of a carboxylic acid function (Ie). However, not enough is known about the spectral characteristics of iodonium compounds to rule out the possible contribution of structure Id.
The possibility of a sulfonation reaction appears unlikcly, as dilution of the above concentrated sulfuric acid solutions resulted in an absorption spectra identical to that obtained by mild acidification of an aqueous solution.
The second protonation (Ha = -5.75) may be associated with that of a carbonyl group, leading t o structures such as Ig, Th, Ii, Ij, or 11; loss of water could lead to Ik, or Ih. The shift of the absorption band from 288 m p to 296 nip is quite small. Structures I j and I2 would contain a protonated lactone oxygen, and are therefore considered far Journal of Pharmaceulical Sciences less likely than structure Ii, which represents a classically protonated carboxylic acid and is resonance stabilized. Although the pKa observed is significantly less than those recorded for other o-substituted benzoic acids ( -6.78 to -7.78), the effect of an o-iodonium function must be taken into consideration. Thus, no conclusion can be made a t present on the possible significance of these data on deciding bctween structures Ii and I h for the doubly protonated species, or between Ie and Id for the singly protonated molecule.
The ionization properties of l&dihydro-l-hydroxy-3-oxo-1,2-benziodoxole and homologs thus support the heterocyclic nature of thcse compounds.