IV. Reactions of First-Formed Radicals

A. Reactions in Neutral Solution

In discussing the various products arising from reaction in neutral solu­tion of first-formed radi­cals (typically reactions in which the hydroxyl radical is generated by γ-radiolysis), it is con­venient to distin­guish between products with a molecular weight less than or equal to that of the substrate and those with a higher molecular weight. Because first-formed radicals can undergo dimer­ization, dispro­portion­ation, elimination, and rearrangement, the number of possible reaction products is staggering; nevertheless, many of them have been identified.^1,2,24,25

Product yields for reactions begun by γ-radiolysis of water can be expressed in terms of G-values; that is, the molecules or radicals formed per 100 eV of energy absorbed. A G‑value also can be used as a measure of substrate reacted. In the reaction of D-glucose shown in Scheme 2 the G-value for con­sump­tion of starting material is 5.6.² The values for formation of products 11-13 are 0.95, 0.15, and <0.08, respectively. The G-values cited for D‑glucose and com­pounds 11-13 were determined in the presence of N₂O to maximize the formation of the hydroxyl radical.

1. Low-Molecular-Weight Products

Although many low-molecular-weight products are formed in detectable amounts from reac­tions of simple sugars, the yields of most are quite low. Many of these compounds are produced by reac­tions of the first-formed radi­cals; for example, the major, low-molecular-weight product (11) from reac­tion of D-glucose is believed to arise by loss of the elements of water from the first-formed radical 10 (Scheme 2, path a).² Another reaction of 10 that forms a low-mo­lec­ular-weight product is loss of a hydrogen atom to give D-gluc­ono-1,5-lactone (12) (Scheme 2, path b), and a third reaction is opening of the pyranoid ring in 10 by fragmentation of the bond between C-5 and the ring oxygen atom to give, after hydrogen-atom abstraction, a carboxylic acid (13) (Scheme 2, path c).² All of the reactions of the radical 10 shown in Scheme 2 are driven, at least in part, by the stability gained from forming a C–O double bond.

2. High-Molecular-Weight Products

The products 11-13 (Scheme 2) and the other low molecular-weight products (more than twenty identified) account for less than half of the D‑glucose con­sumed during γ-radiolysis because most products formed have high molecular weights. Little is known about either the structure of the high-molecular-weight materials or the mechanism of their formation. One proposal is that dimerization of radicals that have lost the elements of water may be the first step in formation of some high-molecular-weight products (eq 12).²

B. Acid-Catalyzed Reactions

Under strongly acidic conditions (pH = 1) four of the first-formed radicals generated from D-glucose eliminate the elements of water to give in each case a carbonyl-conjugated radical.^6,26 A proposed mechanism for this reaction, shown in Scheme 3, involves protonation of the hydroxyl group adjacent to a radical center in the first-formed radical 1 to produce an inter­mediate (14) with an excel­lent leaving group that departs to form a radical cation (15). This radical cation then depro­tonates to give the carbonyl-conjugated radical 16. Another mech­anistic possibility for forming 16 is a concerted reaction beginning with the protonated radical 14 (Scheme 3). Forming car­bon­yl-con­jugated radicals by acid-catalyzed reaction also has been studied in noncarbohydrate sys­tems.^5,27,28

The acid-catalyzed reactions of three first-formed radicals produced from D-glucose deserve further comment. Two of these radicals, 17 (Scheme 4) and 20 (Scheme 5), do not undergo the carbonyl-group-forming reaction character­istic of the other first-formed radicals (Scheme 3).⁶ Although 17 could start along this pathway by producing the radical cation 18, deproton­ation of 18 to give a carbon-centered radical with an adjacent carbonyl group cannot take place. Formation of a carbonyl-conjugated radical from 18 would require opening of the pyranoid ring (Scheme 4). Evidence against such reaction is that 17 is less reactive than other first-formed radi­cals, and when it does react, no carbonyl-conjugated radical can be detected. The first-formed radical 20 also must undergo ring opening if a carbonyl-conjugated radical is to be produced; in fact, ring opening in this case is neces­sary to form the radical-cation 21 (Scheme 5). The radical 20, which is the least reactive of the first-formed radicals derived from D-glucose, also gives no indication of forming a carbonyl-conjugated radical.6

The radical 22 is the third, first-formed radical produced from D-glucose that deserves further comment. This radical is noteworthy because it is ­the most reactive of the first-formed radicals. Protonation of 22 gives the intermediate 23 in which the leaving group has an axial orientation and, therefore, the p-type orbitals on C‑2 and the ring oxygen atom in 23 begin stabilizing the radical cation 24 as it starts to develop (Scheme 6).⁶

C. Base -Catalyzed Reaction

Proton a­bstraction from O-2 in the first-formed radical 25 begins a process that gen­erates the ring-open radical anion 26 (Scheme 7). (Since an α-hydroxy radical is far more acidic than its parent alcohol,² the proton attached to O-2 should be removed much more readily than any other proton in 25.) The radical anion 26 rapidly undergoes a pro­ton transfer to produce the semi­done 27, one of two semidiones formed from base-catalyzed reaction of a first-formed, D-gluco­pyran­osyl radical.^11,29 The second of these two (30) is proposed to arise from the radical 28 ac­cording to the mechanism outlined in Scheme 8.¹¹ (Semidiones 27 and 30 are readily detected because for each of them the nega­tive charge slows the rates of dimerization and reduction and thus leads to more prominent ESR spectra.¹¹)