Quinonemethides

The biosynthesis process, which consists essentially of radical coupling reactions, sometimes followed by the addition of water, of primary, secondary, and phenohc hydroxyl groups to quinonemethide intermediates, leads to the formation of a three-dimensional polymer which lacks the regular and ordered repeating units found in other natural polymers such as cellulose and proteins. 

Substitution Reactions on Side Chains. Because the benzyl carbon is the most reactive site on the propanoid side chain, many substitution reactions occur at this position. Typically, substitution reactions occur by attack of a nucleophilic reagent on a benzyl carbon present in the form of a carbonium ion or a methine group in a quinonemethide stmeture. In a reversal of the ether cleavage reactions described, benzyl alcohols and ethers may be transformed to alkyl or aryl ethers by acid-catalyzed etherifications or transetherifications with alcohol or phenol. The conversion of a benzyl alcohol or ether to a sulfonic acid group is among the most important side chain modification reactions because it is essential to the solubilization of lignin in the sulfite pulping process (17). 

Chemical Properties. Lignin is subject to oxidation, reduction, discoloration, hydrolysis, and other chemical and enzymatic reactions. Many ate briefly described elsewhere (51). Key to these reactions is the ability of the phenolic hydroxyl groups of lignin to participate in the formation of reactive intermediates, eg, phenoxy radical (4), quinonemethide (5), and phenoxy anion (6) ... 

Fig. 3. Reactions at the quinonemethide center during pulping (a) sulfite pulping, and (b) kraft pulping.

In the presence of alkaH, the acidic phenoHc units in lignin are ionized. At temperatures above 120°C, quinonemethides form from the phenoHc units, as shown in equation 1, where Ar is an aryl group. 

In the presence of sulfide or sulfhydryl anions, the quinonemethide is attacked and a benzyl thiol formed. The P-aryl ether linkage to the next phenylpropane unit is broken down as a result of neighboring-group attack by the sulfur, eliminating the aryloxy group which becomes reactive phenolate ion (eq. 2). If sulfide is not present, a principal reaction is the formation of the stable aryl enol ether, ArCH=CHOAr. A smaller amount of this product also forms in the presence of sulfhydryl anion. 

Some cleavage takes place even if the phenoHc hydroxyl is blocked as an ether link to another phenylpropane unit and quinonemethide formation is prevented. If the a- or y-carbon hydroxyl is free, alkaH-catalyzed neighboring-group attack can take place with epoxide formation and P-aryloxide elimination. In other reactions, blocked phenoHc units are degraded if an a-carbonyl group is present. 

The cleavage process occurs by p-quinonemethide formation after acetate hydrol-ysis. 

Estrone (54, Chart 6) contains a full retron for the o-quinonemethide-Diels-Alder transform which can be directly applied to give 55. This situation, in which the Diels-Alder transform is used early in the retrosynthetic analysis, contrasts with the case of ibogamine (above), or, for example, gibberellic acid (section 6.4), and a Diels-Alder pathway is relatively easy to find and to evaluate. As indicated in Chart 6, retrosynthetic conversion of estrone to 55 produces an intermediate which is subject to further rapid simplification. This general synthetic approach has successfully been applied to estrone and various analogs. ... 

This ester, developed for peptide synthesis, is prepared by the standard DCC coupling protocol and is cleaved reductively with SnCl2 (MeOH, 25°, 5 h) followed by treatment with mild base to effect quinonemethide formation with release of the acid in 75-95% yield. ... 

Acyloxybenzyl esters were designed to be released under physiological conditions. Porcine liver carboxyesterase efficiently releases the phosphate by acetate hydrolysis and quinonemethide formation. In a diester, the first ester is cleaved faster than the second. ... 

Other benzyl radicals, including the parent benzyl radical, give reversible formation of quinonemethide derivatives (typically a mixture of a,p- and cqocoupling products) in competition with a,a-coupling (see also Section... 

The kinetic product distribution appears to be determined by steric factors ex-substitution favors quinonemethide formation ring substitution favors a,cx-coupling. However, since quinonemethide formation is reversible, the only iso table product is often that from a,a-coupling. 

Gunatilaka, A. A. L. Triterpenoid quinonemethide and related compound (celastroloids). In Progress in the Chemistry of Organic Natural Products Hertz, W. Kirby, G. W. Moore, R. E. Steglich, W. Tamm, C., Eds. Springer-Verlag New York, 1996 Vol. 67, 1-123. 

Dirsch, V. M. Kiemer, A. K. Wagner, H. Vollmar, A. M. The triterpenoid quinonemethide pristimerin inhibits induction of inducible nitric oxide synthase in murine macrophages. Eur. J. Pharm. 1997, 336, 211-217. 

TFA) in DCM (dichloromethane). Linkers for carboxylic acids have also been designed to effect cleavage via photolysis (3-nitro-4-hydroxymethylbenzoic acid, ONb 14) [18] and flouridolysis (N-3 or 4) ((4-hydroxymethyl)-phenoxy-t-butylphenylsilyl)phenyl pentanedioic acid monoamide (PBs) 15 [19] and quinonemethide-based handle 16 [20] (Fig. 

The reaction of C60 with o-quinonemethide, prepared from o-hydroxybenzyl alcohol (110) (Scheme 9.32), was performed in a modified domestic oven at 800 W and gave 111 in 27% yield after only 4 min [72], Although Eguchi et al. [83] reported the same reaction with a slightly better yield (31%) by thermolysis in a sealed vessel, the microwave approach to this adduct has the advantage of simplicity, and avoids the risks associated with high-pressure conditions. 

The addition of anionic forms of trivalent phosphorus reagents (diethyl phosphite or diphenylphosphinite) to quinonemethides bearing two phosphoryl linkages on the exocyclic double bond provides a,a,a-triphosphoryl species (Equation 3.32).451... 

Gross, H. and Keitel, I., a-Substituted phosphonates. 58. A direct phosphorylation of 7,7-bisphosphorylated quinonemethide nucleus with trivalent phosphorus-hydrogen compounds via carbon-carbon cleavage, Phosph., Sulf., Silic. Relat. Elem., 62, 35, 1991. 

An alternative route to phenolate-like EGBs is through the cathodic reduction of quinonemethides, (36), [82, 83]. The advantage of these PBs is that they are reduced at modest potentials, which allow EGB formation to take place in situ, and they are ultimately converted into phenols that are easily reoxidized to (36) either by air or by anodic oxidation (60-70% yield) [82]. The radical anion (36a) is expected to have basicity similar to that of (35) , whereas the pK of the conjugate acid of the dianion formed by further reduction can be assumed close to that of triphenylmethane, 30.6. 

One modification that pertains to the present book is the role of anthraquinone (AQ) in the pulping process. Under conditions of alkaline pulping, carbohydrates in the wood reduce AQ into an anion-radical (AQ ). Experiments with lignin quinonemethide as a model compound showed that the AQ anion-radical caused fragmentation of the quinonemethide (Scheme 8.23). 

The bisulfide ion present in the kraft process is even a better nucleophile than hydroxide, so when it is present it attacks the quinonemethide intermediate. An episulfide is formed that then hydrolyzes to a thiol-alcohol. 

Dithiazolidines containing o-quinonemethide structural units in the 3,5-positions (e.g. (99)) are converted by reagents with an activated CHj group into a range of condensed heterocyclic compounds not easily accessible otherwise (Scheme 14) <85S535,86PHA283>. 

There are a number of examples of the synthesis of chromans using o-quinone methides as the heterodiene in a hDA reaction. Both pyrano[3 -c]-benzopyrans and cyclopenta[c][l]benzopyrans result from an intramolecular cycloaddition of a substituted o-quinonemethide generated under mild conditions. In the former case, salicylaldehyde and an unsaturated alcohol yield the rra/is-fused tetrahydropyranobenzopyran (Scheme 10) <99JOC9507>. However, the latter synthesis (Scheme 11) is less selective <99BCJ73>. 

Meanwhile, Freudenberg (17) was the first person who demonstrated the formation of an addition compound from a quinonemethide and sucrose during enzymatic dehydrogenation of coniferyl alcohol in a concentrated sucrose solution. Thereafter, Tanaka (18) observed the formation of a benzyl ester between the quinonemethide of a dilignol and a uronic... 

MW = 1034), biphenyl tetramer hexaol (MW = 782), /3-0-4 tetramer hep-taacetate (C55H66O22, MW = 1078) and /J-O-4 tetramer heptaol (MW = 784). The Igepal (GAF Corp., sold through Aldrich) standards F.W. = 749 and 1982 were also examined. Two synthetic polymers prepared by anion-initiated polymerizations of a quinonemethide according to the procedure of Chum et al. (20) were treated as intermediate MW lignin model polymers. 

Table I illustrates the molecular weight averages found from universal calibration (narrow standards) for four aspen lignins and two quinonemethide-derived polymers using the Unical software. The poly-dispersities were the same within the experimental errors for all lignin samples. In contrast, the polydispersities found for the quinonemethide-derived polymers by universal calibration were near 1.1. The molecular weight averages found for the four acetylated lignins studied by universal calibration were substantially larger than those determined from previous work using conventional GPC (e.g., AESE and BM lignins from refs. 7 and 12 had approximately one-third those values found by HPSEC-DV in the present study).

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