438 5. QUINONES 



reduced by any excess thioglycolate present. A variety of products can 

 thus be formed from simple 1,4 addition of thiols and the terminal result 

 will depend on many factors. One important fact emerging from the many 

 reports on such reactions is that the rates are often quite high and in many 

 cases the reactions are complete within a matter of several minutes or less. 

 Substituted groups on the quinone ring exert erratic effects on the 

 rate of thiol addition and the mechanism is often not understood. The occu- 

 pation of a position usually prevents the addition of the thiol to this po- 

 sition. Thus toluquinone, xyloquinone, cumoquinone, and duroquinone 

 add progressively fewer thiol molecules. Cumoquinone, with one free po- 

 sition, reacts readily with one molecule of thioglycolate, but duroquinone, 

 with no free positions, does not (Snell and Weissberger, 1939). However, 

 in neutral solution, duroquinone oxidizes the SH groups, forming duro- 

 hydroquinone. In the same way, menadione adds one thiol at the 3-posi- 

 tion. If menadione and thioglycolate are mixed, a crystalline thionaphtho- 

 quinone: 



is formed (Fieser, 1941; Fieser and Turner, 1947), and similar compounds 

 are found with other thiols. In contrast to some other addition reactions, 

 the presence of certain groups on p-benzoquinone or on the 2-position of 

 1,4-naphthoquinone may actually enhance the 1,4 addition of thiols. Thus 

 menadione reacts with thiols faster than does 1,4-naphthoquinone. On the 

 other hand, a large group, such as a tert-hutyl on the 2-position, sterically 

 prevents the addition (Blackball and Thomson, 1953). It is rather odd 

 that a methoxy group adjacent to an open position is usually able to in- 

 hibit thiol addition (Redfearn and Whittaker, 1962). The important factor 

 was considered to be the state of the electron-deficient position; when the 

 adjacent group is strongly electron-attracting or weakly electron-supply- 

 ing, reactivity increases. Methoxy groups elsewhere do not inhibit; thus 

 2-methyl-5-methoxy-p-Q and 2-methyl-5,6-dimethoxy-2)-Q react readily 

 with cysteine. It is interesting and particularly important in considering 

 the mechanism by which certain compounds inhibit enzymes that not all 

 groups shield a position from reaction with thiols. Thus Col well and McCall 

 (1945) obtained evidence that 2-methyl-3-chloro-l,4-NQ reacts with cys- 

 teine and thioglycolate, and Nickerson et al. (1963) have recently shown 

 that 2,3-dichloro-l,4-NQ reacts readily with glutathione, the chlorine atoms 

 being displaced. On the other hand, no reaction with menadione substitut- 

 ed in the 3-position with methyl, methoxy, or hydroxy groups occurs. 



