Hydroquinone instability

In the presence of nucleophilic solvents, a racemization is observed too in less than one hour, in the presence or in the absence of hydroquinone, compound (12) is fully racemized in methanol44. A mechanism analogous to that proposed to rationalize the optical instability of triorganotin halides can be given here 44). 

In contrast to their instability free in solution, flavin semiquinones bound to proteins are generally (although there are exceptions) quite stable and can be generated in nearly quantitative yields. This stability results from thermodynamic considerations in which the oxidized/semiquinone oxidation-reduction couple is usually more positive and well separated from the semiquinone/hydroquinone couple. In addition to thermodynamic stabilization, kinetic stabilization of protein-bound semiquinones has also been observed and will be discussed in more detail in subsequent portions of this article. 

Although stable as a solid, rifampin has certain predictable instabilities in solution. For example, in alkaline solution the hydroquinone hydroxyls (C-24 and 27) would be expected to readily oxidize.36 The acetates at C-l 1 and C-22 are likely to hydrolyze slowly with time. Most important, acidic solutions would hydrolyze the C-25 hydrazone, regenerating the inactive, and also unstable, rifaldehyde. 

Crystals of the y-form of hydroquinone are monoclinic, space group Plylc, with a = 807. b = 520, c = 1320 pm, (3 = 107". and Z = The structure is built from sheets of H-bonded hydroquinone molecules (Fig. 4b). There are no H-bonded hexameric units, and the inclusion properties are still not well-linown. In accord with the instability and pronounced cleavage of the y-form, these sheets are apparently held together only by van der Waals forces. 

Reduction back to the hydroquinones was possible with Sml2/CH30H. The same reagent reduced nitrobenzene to A-hydroxyl aniline. Surprisingly, aniline, which is the product in the liquid phase, is not formed. The latter result—the high yields and the instability of free <2-quinones—suggests that all reduction/oxidation took place inside 6 rather than... 

Choice of Base Although the early work was done by preparing the dial kali metal salts of the bisphenol in situ, dehydrating them and then adding the dihalo compounds, it was evident that the insolubility and instability of some of the disalts precluded successful reactions, especially on a commercial scale. This has already been alluded to above in reference to the disalt of hydroquinone. Hence, alternatives were examined early in the polyether research program. 

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