Novel reaction products from the hypervalent iodine oxidation of hydroxylated stilbenes and isoflavones

Novel reaction pathways for the hypervalent iodine-mediated oxidation of bioactive phenols containing extended conjugated π-systems are described. Oxidation of 4-hydroxystilbenes in methanol using a hypervalent iodine-based oxidant led to the formal 1,2-addition of methoxy groups across the central stilbene double bond. Treatment of the structurally related 4-hydroxyisoflavone with di(trifluoroacetoxy)iodobenzene leads to the surprising formation of 2,4′-dihydroxybenzil. Potential mechanisms for these new reaction pathways are discussed, and the X-ray crystal structure of 2,4′-dihydroxybenzil is presented. In contrast, oxidation of the corresponding 3-hydroxystilbenes and 3-hydroxyisoflavone led to conventional dienone oxidation products. The antitumour implications of these oxidation processes are briefly highlighted; the novel 4-substituted phenolic oxidation products were found to be inactive in terms of in vitro antitumour cellular activity, whereas the 3-substituted phenol products gave novel agents with potent and enhanced antitumour activity in the HCT 116 cancer cell line. © The Royal Society of Chemistry 2005.

Synthesis of Chromanes and 4H-Chromenes: Exploring the Oxidation of 2H-Chromenes and Dihydro-1-benzoxepines by Hypervalent Iodine(III)

The reaction of various oxygen-containing benzo-fused cycloalkenes were studied with the hypervalent iodine reagent hydroxy(tosyloxy) iodo]benzene [PhI(OH)OTs, HTIB]. 2H-Chromene and 4-methyl-2H-chromene resulted in substituted 4H-chromene and cis-3,4-dialkoxy-4-methyl-3,4-dihydro-2H-chromenes, respectively. Ring contraction to chromanes and benzofurans was observed for dihydrobenzoxepines and 2,2-dimethyl-2H-chromenes, respectively.

Hypervalent iodine in synthesis 92. A facile synthesis of 3-substituted-5,6-dihydroimidazo[2,1-b]thiazoles by cyclocondensation of alkynyl(phenyl)iodonium salts and imidazolidine-2-thione

A simple method for the synthesis of 3-substituted 5,6-dihydroimidazo[2,1-b]thiazoles is achieved by cyclocondensation of alkynyl(phenyl)iodonium salts with imidazolidine-2-thione.

Hypervalent Iodine in Synthesis. 94. A Facile Synthesis of 2-Substituted-imidazo[1,2-a]pyridines by Cyclocondensation of Alkynyl(phenyl) iodonium Salts and 2-Aminopyridine

A facile method for the synthesis of 2-substituted-imidazo[1,2-a]pyridines is achieved by cyclocondensation of alkynyl(phenyl)iodonium salts with 2-aminopyridine.

Hypervalent iodine in synthesis 93. A facile synthesis of 2-substituted imidazo[1,2-a]pyrimidines by cyclocondensation of alkynyl(phenyl)iodonium salts and 2-aminopyrimidine

Simple stirring of a mixture of the alkynyl(phenyl)iodonium salts 1 with 2-aminopyrimidine 2 in chloroform under reflux for two hours in the presence of K2CO3 gave, after workup, the 2-substituted imidazo[1,2-]pyrimidines 3 in moderate to good yields. A possible mechanism for the formation of 3 involves the intramolecular cyclization of the intermediate alkylidenecarbene 6.

Hypervalent iodine in synthesis. 90. A mild and efficient method for the iodination of pyrazoles

The combined reagent of iodobenzene diacetate (or polymer-supported iodobenzene diacetate) with iodine was used as an effective iodinating agent of pyrazoles to the corresponding 4-iodopyrazole derivatives at room temperature with high yields.

Hypervalent iodine in synthesis 91: a mild and efficient method for the halogenation of 6-methyluracil derivatives

The combined reagent of iodobenzene diacetate (or polymer-supported iodobenzene diacetate) with iodine or bromine was used as an effective halogenative agent of 6-methyluracil derivatives to the corresponding 5-halo-6-methyluracil derivatives at room temperature with high yields.

Hypervalent iodine in synthesis 64:Syntheses of diaryl selenides and alkyl aryl selenides by palladium-catalyzed arylation of areneselenyl or alkaneselenyl magnesium bromide with diaryliodonium salt

Areneselenyl or alkaneselenyl magnesium bromide reacts rapidly with diaryliodonium salt to give the corresponding diaryl or alkyl aryl selenide in the presence of catalytic amounts of Pd-(PPh3)4 in good yield.

PIFA-Mediated Oxidative Cyclization of 1-Carbamoyl-1-oximylcycloalkanes: Synthesis of Spiro-Fused Pyrazolin-5-one N-Oxides

convenient and efficient synthesis of spiro-fused pyrazolin-5-one N-oxides starting from readily available 1-carbamoyl-1-oximylcycloalkanes is developed. This general protocol features a novel and facile way for access to the five-membered azaheterocycles by formation of a new N-N single bond. The key cyclization step utilizes the formation of an N-oxonitrenium intermediate, mediated by the hypervalent iodine reagent PIFA, and its subsequent intramolecular trapping by the amide moiety under rather mild experimental conditions.

Iodine(III)-promoted ring expansion of 1-vinylcycloalkanol derivatives: A metal-free approach toward seven-membered rings

A versatile and metal-free approach for the synthesis of molecules bearing seven- and eight-membered rings is described. The strategy is based on the ring expansion of 1-vinylcycloalkanols (or the corresponding silyl or methyl ether) mediated by the hypervalent iodine reagent HTIB (Phl(OH)OTs). The reaction condition can be easily adjusted to give seven-membered rings bearing different functional groups. A route to medium-ring lactones was also developed.

SYNTHESIS AND CHARACTERIZATION OF POLY-ORTHO-METHYLANILINE WITH DIFFERENT DEGREES OF OXIDATION

Poly-ortho-methylanilines (POT) in three states fully oxidized, fully reduced and oxidized in varying degrees were synthesized by the reaction of common POT (C-POT) having nearly equal amounts of benzenediamine and quinonediimine units with iodine or phenyl-hydrazine, and the resulting polymers were characterized by IR, C-13-NMR, SEM and elemental analysis. The results showed that the quinonediimine unit in C-POT could be reduced by phenylhydrazine to the benzenediamine unit, forming the polymer with low OD (oxidation degree) or in a fully reduced state and that iodine-oxidation resulted in the increase of quinonediimine unit and decrease of benzenediamine unit. The solubility and flexibility of the formed polymers depend strongly on the amount of quinonediimine unit in it. It is necessary to reduce the content of quinonediimine structure unit in order to improve the solubility of aniline-class polymers.

Synthesis of Tetrahydrofurans by Cyclization of Homoallylic Alcohols with Iodine/Iodine(III)

Tetrahydrofuran derivatives can be obtained by cyclo-functionalization of homoallylic alcohols bearing a terminal double bound by using [hydroxy(tosyloxy)iodo]benzene (HTIB, Koser`s reagent) in the presence of a catalytic amount of 12 (20 mol %) in MeOH under mild conditions. This transformation is an overall 5-endo-trig cyclization, which occurs by two different pathways. The first is a 4-exo-trig cyclization followed by ring expansion, whereas the second is an electrophilic addition followed by a 5-endo-tet cyclization.

STUDY BY MASS SPECTROMETRY OF SOLUTIONS OF [HYDROXY(TOSYLOXY)IODO]BENZENE: PROPOSED DISPROPORTIONATION MECHANISMS

STUDY BY MASS SPECTROMETRY OF SOLUTIONS OF [HYDROXY(TOSYLOXY)IODO]BENZENE: PROPOSED DISPROPORTIONATION MECHANISMS. Solutions of [hydroxy(tosyloxy)iodo]benzene (HTIB or Koser's reagent) in acetonitrile were analyzed using high resolution electrospray ionization mass spectrometry (ESI-MS) and electrospray ionization tandem mass spectrometry (ESI-MS/MS) under different conditions. Several species were characterized in these analyses. Based on these data, mechanisms were proposed for the disproportionation of the iodine(III) compounds in iodine(V) and iodine(I) species.

Oxidation effects on tetrahydropterin metabolism

The susceptibility of tetrahydropterins to oxidation was investigated in vitro and related to in vivo metabolism. At physiological pH, tetrahydrobiopterin (BH4) was oxidized, with considerable loss of the biopterin skeleton, by molecular oxygen. The hydroxyl radical (.OH) was found to increase this oxidation and degradation, whilst physiological concentrations of glutathione (GSH) retarded both the dioxygen and .OH mediated oxidation. Nitrite, at acid pH, oxidized BH4 to biopterin and tetrahydrofolates to products devoid of folate structure. Loss of dietary folates, from the stomach, due to nitrite mediated catabolism is suggested. The in vivo response of BH4 metabolism to oxidising conditions was examined in the rat brain and liver. Acute starvation depressed brain biopterins and transiently BH4 biosynthetic and salvage (dihydropteridine reductase, DHPR) pathways. Loss of biopterins, in starvation, is suggested to arise primarily from catabolism, due to oxygen radical formation and GSH depletion. L-cysteine administration to starving rats was found to elevate tissue biopterins, whilst depletion of GSH in feeding rats, by L-buthionine sulfoximine, decreased biopterins. An in vivo role for GSH to protect tetrahydropterins from oxidation is suggested. The in vivo effect of phenelzine dosing was investigated. Administration lowered brain biopterins, in the presence of dietary tyrosine. This loss is considered to arise from p-tyramine generation and subsequent DHPR inhibition. Observed elevations in plasma biopterins were in line with this mechanism. In conditions other than gross inhibition of DHPR or BH4 biosynthesis, plasma total biopterins were seen to be poor indicators of tissue BH4 metabolism. Evidence is presented indicating that the pterin formed in tissue samples by acid iodine oxidation originates from the tetrahydrofolate pool and 7,8-dihydropterin derived from BH4 oxidation. The observed reduction in this pterin by prior in vivo nitrous oxide exposure and elevation by starvation and phenelzine administration is discussed in this light. The biochemical importance of the changes in tetrahydropterin metabolism observed in this thesis are discussed with extrapolation to the situation in man, where appropriate. An additional role for BH4 as a tissue antioxidant and reductant is also considered.

Fast hole surface conduction observed for indoline sensitizer dyes immobilized at fluorine-doped tin oxide - TiO2 surfaces

The indoline dyes D102, D131, D149, and D205 have been characterized when adsorved on fluorine-doped tin oxide (FTO) and TiO2 electrode surfaces. Adsorption from 50:50 acetonitrile - tert-butanol onto flourine-doped tin oxide (FTO) allows approximate Langmuirian binding constants of 6.5 x 10(4), 2.01 x 10(3), 2.0 x 10(4), and 1.5 x 10(4) mol-1 dm3, respectively, to be determined. Voltammetric data obtained in acetonitrile/0.1 M NBu4PF6 indicate reversible on-electron oxidation at Emid = 0.94, 0.91, 0.88, and 0.88 V vs Ag/AgCI(3 M KCI), respectively, with dye aggregation (at high coverage) causing additional peak features at more positive potentials. Slow chemical degradation processes and electron transfer catalysis for iodine oxidation were observed for all four oxidezed indolinium cations. When adsorbed onto TiO2 nanoparticle films (ca. 9nm particle diameter and ca.3/um thickness of FTO0, reversible voltammetric responses with Emid = 1.08, 1.156, 0.92 and 0.95 V vs Ag/AgCI(3 M KCI), respectively, suggest exceptionally fast hole hopping diffusion (with Dapp > 5 x 10(-9) m2 s-1) for adsorbed layers of four indoline dyes, presumably due to pie-pie stacking in surface aggregates. Slow dye degradation is shown to affect charge transport via electron hopping. Spectrelectrochemical data for the adsorbed indoline dyes on FTO-TiO2 revealed a red-shift of absorption peaks after oxidation and the presence of a strong charge transfer band in the near-IR region. The implications of the indoline dye reactivity and fast hole mobility for solar cell devices are discussed.