Reactions of polyphenols with α-keto acids

[摘要] English: Novel methods of carbon-carbon bond formation are of considerable theoretical andpractical interest to synthetic organic chemists. This work investigates the formationand synthetic potential of a methine bond (one carbon link) between two aromaticmoieties to form diphenylmethane derivatives.This methine link is of industrial importance when the aromatic moiety ishydroxylated. The colour stability of red wine is attributed to a methine bond that isthe result of condensation between glyoxylic or pyruvic acid and an anthocyanidin.This bond may be formed spontaneously during the ageing of wine. Wattle extractbased adhesives rely on the reaction between formaldehyde and polyphenols to formmethine linked polymers. Patented antioxidants rely on the availability of a benzylicproton on a methine link, ortho to a hydroxy group (Irganox®HP-136).The proximity of the two carbonyl double bonds in α-dicarbonyl compounds enhancesthe reactivity of each other towards nucleophiles. In the case of α-keto acids the α-keto group is more electrophilic than the carboxylic group and susceptible to attack bynucleophiles.The hydroxy groups of phloroglucinol and other polyhydroxybenzenes donateelectrons to the aromatic ring to increase the nucleophilicity of the aromatic carbons.Polyphenols thus become ambident nucleophiles that can react either via oxygen orcarbon and have the ability to form new carbon-carbon bonds with suitableelectrophiles.As part of our ongoing investigation into the importance of p-quinone methides inflavonoid chemistry the reaction of a variety of polyhydroxyphenols with α-keto acidswere investigated.Addition of an aromatic ring to a carbonyl group creates a benzylic hydroxy group.With strongly nucleophilic aromatic rings this benzylic substituent is replaced with asecond aromatic ring to yield the anticipated methine linked biaryl compound.Phloroglucinol reacts with pyruvic acid to give 4,6-dihydroxy-3-methyl-3-(2,4,6-trihydroxyphenyl)-1-benzofuran-2(3H)-one and with glyoxylic acid to yield 4,6-dihydroxy-3-(2,4,6-trihydroxyphenyl)-1-benzofuran-2(3H)-one. These products arelactones between the phenolic- and carboxylic acid moiety of an intermediate biarylorganic acid. With oxaloacetic acid a 4,5�?6,7�?tetrahydroxy-2H-spiro[benzofuran-3,4�?chroman]-2,2�?dione is isolated.With unreactive aromatic nucleophiles the benzylic hydroxy group is eliminatedbefore substitution can take place if hydrogen is available in the α-position. Tri-omethylphloroglucinolreacts with pyruvic acid to give methyl-2-(2,4,6-trimethoxyphenyl)-acrylate via the elimination of water. This acrylic acid reacts withozone to form methyloxo-(2,4,6-trimethoxyphenyl)-acetate and with diazomethane toform 2-methoxy(2,4,6-trimethoxyphenyl)-4,5-dihydrofurane.To demonstrate the potential of this reaction we reacted resorcinol with phydroxyphenylpyruvicacid and obtained both the Z and E isomers of 6-hydroxy-3-(4-hydroxybenzylidene)-3H-benzofuran-2-one. This isoaurone synthesis represents animprovement on the recently published synthesis of this natural product.We have developed a novel reaction to form carbon-carbon bonds and synthesizemethine linked diaryl compounds. We have developed this reaction into a newprocedure to synthesize free phenolic 3-substituted benzofuran-2-ones. We adaptedthis reaction to improve a recently published method to synthesize a free phenolicisoaurone. We can use our reaction to synthesize acrylic acids with a phenolicsubstitutuent in the α-position and have started to explore the potential of this α,β-unsaturated carboxylic acid as intermediates for various synthetic procedures.

[发布机构] University of the Free State