Isobenzofurans, oxidation

Photolysis of 1,4-diphenylphthalazine 2-oxide in various solvents gives 1,3-diphenyl-isobenzofuran (52) as the primary product. In the presence of oxygen, deoxygenation to 1,4-diphenylphthalazine and oxidation of the initially formed 1,3-diphenylisobenzofuran (52) to 1,2-dibenzoylbenzene also take place (Scheme 17). 

A study of the electrochemical oxidation and reduction of certain isoindoles (and isobenzofurans) has been made, using cyclic voltammetry. The reduction wave was found to be twice the height of the oxidation wave, and conventional polarography confirmed that reduction involved a two-electron transfer. Peak potential measurements and electrochemiluminescence intensities (see Section IV, E) are consistent vidth cation radicals as intermediates. The relatively long lifetime of these intermediates is attributed to steric shielding by the phenyl groups rather than electron delocalization (Table VIII). 

Diarylthioketones are converted in good yields into orthometallated complexes by diiron enneacarbonyl.141 These in turn can be transformed oxidatively (Ce4+) or photochemically into isobenzothiophenes (see Section IV,C,2), or by reaction with mercuric trifluoroacetate into isobenzofurans (Scheme 78)142 the formation of methoxy esters is a competing process in... 

Diaryl thioketones are converted by diiron enneacarbonyl into products of orthometallation.141 Oxidative or photochemically induced deligation of these complexes provides an unusual and valuable synthetic entry into compounds in the uncommon isobenzothiophene category142,151 (Scheme 84). Moreover, the photochemical procedure provides the novel complex, (tetracyanoethylene)tetracarbonyl iron. The orthometallated complexes (68) can also be used to prepare isobenzofurans (see Section IV,B,5). 

In contrast with the reaction of 4-yn-l-ols, both 6-endo-dig and 5-exo-dig cyclization modes were observed in the Pdl2/KI-catalyzed oxidative car-bonylation of2-(l-alkynylbenzyl)alcohols (Eq. 43) [120]. The preferential formation of the lH-isochromene or the 1,3-dihydroisobenzofuran derivative turned out to be dependent on the substitution pattern of the substrate. In particular, lH-isochromenes were obtained as the main reaction products when the triple bond was substituted with an alkyl group and with a primary alcoholic group, while the isobenzofurans were preferentially formed with a tertiary alcoholic group and when the triple bond was terminal or conjugated with a phenyl group. 

Indenopyrene, see Indeno[l,2,3-crf pyrene l//-Indole, see Indole Indolene, see Indoline Inexit, see Lindane Inhibisol, see 1,1,1-Trichloroethane Insecticide 497, see Dieldrin Insecticide 4049, see Malathion Insectophene, see a-Endosulfan, p-Endosulfan Intox 8, see Chlordane Inverton 245, see 2,4,5-T lodomethane, see Methyl iodide IP, see Indeno[l,2,3-crf pyrene IP3, see Isoamyl alcohol Ipaner, see 2,4-D IPE, see Isopropyl ether IPH, see Phenol Ipersan, see Trifluralin Iphanon, see Camphor Isceon 11, see Trichlorofluoromethane Isceon 122, see Dichlorodifluoromethane Iscobrome, see Methyl bromide Iscobrome D, see Ethylene dibromide Isoacetophorone, see Isophorone a-Isoamylene, see 3-Methyl-l-butene Isoamyl ethanoate, see Isoamyl acetate Isoamylhydride, see 2-Methylbutane Isoamylol, see Isoamyl alcohol Isobac, see 2,4-Dichlorophenol Isobenzofuran-l,3-dione, see Phthalic anhydride 1,3-Isobenzofurandione, see Phthalic anhydride IsoBuAc, see Isobutyl acetate IsoBuBz, see Isobutylbenzene Isobutane, see 2-Methylpropane Isobutanol, see Isobutyl alcohol Isobutene, see 2-Methylpropene Isobutenyl methyl ketone, see Mesityl oxide Isobutyl carbinol, see Isoamyl alcohol Isobutylene, see 2-Methylpropene Isobutylethylene, see 4-Methyl-l-pentene Isobutyl ketone, see Diisobutyl ketone Isobutyl methyl ketone, see 4-Methyl-2-pentanone Isobutyltrimethylmethane, see 2,2,4-Trimethylpentane Isocumene, see Propylbenzene Isocyanatomethane, see Methyl isocyanate Isocyanic acid, methyl ester, see Methyl isocyanate Isocyanic acid, methylphenylene ester, see 2,4-Toluene-diisocyanate... 

A novel route to anthracyclinones is based on the chemistry of quinone-isobenzofuran adducts (77TL3537). The 3-methoxybenzyne-furan adduct (1) was reacted with a-pyrone to give a mixture of lactones (2). Thermolysis of this intermediate in the presence of quinone (3) gave in 93% yield the tetracyclic adduct (4) as a stereoisomeric mixture. Aromatization with sodium acetate in acetic acid gave quinone (5) which was subjected to reduction, C-ring oxidation and mild acid hydrolysis to afford a mixture of ( )-7-deoxydaunomycinone (6) and its 1-methoxy regioisomer (Scheme 1). 

This compound with hydriodic acid in acetic acid in the presence of red phosphorous at reflux yielded 5,7-dihydroxy-4-methyl-3H-isobenzofuran-l-one. Condensation of 6-bromo-4-methylhex-4-enoic acid methyl ester and 5,7-dihydroxy-4-methyl-3H-isobenzofuran-l-one with silver oxide in dioxane at room temperature yielded 6-(4,6-dihydroxy-7-methyl-3-oxo-l,3-dihydro-isobenzofuran-5-yl)-4-methylhex-4-enoic acid methyl ester (36% yield). At last, monomethylation with diazomethane yield 6-(4-hydroxy-6-methoxy-7-methyl-3-oxo-l,3-dihydro-isobenzofuran-5-yl)-4-methylhex-4-enoic acid... 

Another efficient method is the electrochemical oxidation of NADH at 0.585 V vs Ag/AgCl by means of ABTS2- (2,2,-azinobis(3-ethylbenzothiazoline-6-sulfonate)) as an electron transfer mediator [96]. Due to the unusual stability of the radical cation ABTS, the pair ABTS2 /ABTS is a useful mediator for application in large-scale synthesis even under basic conditions. Basic conditions are favorable for dehydrogenase catalyzed reactions. This electrochemical system for the oxidation of NADH using ABTS2 as mediator was successfully coupled with HLADH to catalyze the oxidation of a meso-diol (ws >-3,4-dihydroxymethylcyclohex-l-ene) to a chiral lactone ((3aA, 7aS )-3a,4,7,7a-tetrahydro-3//-isobenzofurane- l-one) with a yield of 93.5% and ee >99.5% (Fig. 18). 

Voltammetric studies in DMF [189] of aryl-substituted isobenzofurans like 1,3,4,7-tetraphenylisobenzofuran show that it gives two, one-electron reduction waves and one, one-electron oxidation wave. By cyclic voltammetry (CV) it was shown that the first reduction product was stable, whereas the first oxidation product and the second reduction product were unstable. 

Beak has reported an aromatic ring anneladtm using ortho lithiatitm to regioselectively introduce an aldehyde, which is then converted to a carbene. Subsequent Diels-Alder cycloaddition of the resultant isobenzofurans result in adducts that may be oxidized to n q>hthalenes or reduced to tetralins. A typical example is shown in Scheme 9. 

Cycloaddition reactions of the C(3)=N bond of azirines are common (Scheme 45) <71AHC(13)45, B-83MI 101-03,84CHEC-I(7)47>. Azirines can participate in [4 + 2] cycloadditions with dienes including cyclopentadienones, isobenzofurans, triazines, and tetrazines. They also participate in 1,3-dipolar cycloadditions with azomethine ylides, nitrile oxides, mesoionic compounds, and diazomethane. Cycloadditions with heterocumulenes, benzyne, and carbenes are known. Azirines also participate in other pericyclic reactions, such as ene reactions. 

There are general reviews on heterocyclic syntheses by cycloaddition reactions of isocyanates and on the use of heterocyclic cations in preparative organic chemistry. More specific topics are 5-hydroxymethylfuran-2-carb-aldehyde, isobenzofurans and related ort/io-quinonoid systems, the conversion of 2//-cyclohepta[Zj] furan-2-one (1) into derivatives of azulene, the synthesis of indoles from o-alkylphenyl isocyanides, and abnormal Fischer indolization reactions of o-methoxyphenylhydrazones. Two reviews on isoindoles have appeared and a lecture on highly conducting charge-transfer complexes that are based on heterocyclic selenium and tellurium donors has been reprinted.Recent advances in the chemistry of imidazole and in the use of nitro-imidazoles as radiosensitizers have been summarized. There have been reviews on benzimidazole A -oxides and on dihydrobenzimidazoles, benzimidazolones, benzimidazolethiones, and related compounds. Other topics are synthetic applications of 1,3-dithiolium and 1,3-oxathiolium salts and of isoxazoles, the chemistry of benzisoxazoles, 2-amino-oxazoles, 5-oxazolones (2), furoxans, benzofuroxans, and related systems, the synthesis of five-membered meso-ionic compounds, and tetrazoles. ... 

Formation of the 17/-[2]benzopyran system by a 6-endo-dig cyclisation is favoured over the 5-exo-dig route to isobenzofurans in the Pd-catalysed oxidative carbonylation of... 

The role of exciplexes in self-sensitized photo-oxidations has been further investigated by Stevens and co-workers.273 - Photoperoxidation of 1,3-diphenyl-isobenzofuran in solution proceeds at a rate which is independent of acceptor concentration when this is very low, and this observation has been interpreted in terms of a re-encounter of x02 and ground-state acceptor molecules generated in the same triplet-triplet annihilation act. This interpretation accounts for the failure of tetramethylethylene to inhibit the reaction completely. Processes 1—3 in Scheme 8 account for the observations if re-encounter effects are included,... 

This same oxidation level situation - a disubstituted benzene with aldehyde (ketone) ortho to carbinol ready for cyclisation and dehydration to an isobenzofuran - can be achieved in alternative ways phthalaldehyde can be mono-acetalised, then the remaining aldehyde reduced, or lithiation technology can be utilised, as shown below. 

Partial oxidation of 1,2-bishydroxymethylbenzene produces l-methoxy-1,3-dihydroisobenzofuran, from which methanol can be eliminated, using LDA, giving isobenzofuran. Subsequently, conditions have been defined whereby this elimination can be run in such a way as to allow immediate ring lithiation this species then can be further reacted. ... 

The Elbs persulfate oxidation procedure was used by Bach and cowoikers at an early stage of their synthesis of model compounds related to ftedericamycin A. Thus the phenol (59) gave 2,S-dihydroxy-4-methoxybenzoic acid (60) in modest yield (30%). This was then transformed in several steps to the isobenzofutanone (61). Gmeration of the isobenzofuran (62) in situ and Diels-Alder reaction of this with the enedione (63) gave, after loss of die trimethylsilyl group, the desired compound (64 Schone 23) in 62% yield from the isobenzofiiranone (61). 

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