Oxidation of thiophene

Oxidation of thiophene with peracid under carefully controlled conditions gives a mixture of thiophene sulfoxide and 2-hydroxythiophene sulfoxide. These compounds are trapped by addition to benzoquinone to give ultimately naphthoquinone (225) and its 5-hydroxy derivative (226) (76ACS(B)353). The further oxidation of the sulfoxide yields the sulfone, which may function as a diene or dienophile in the Diels-Alder reaction (Scheme 88). An azulene synthesis involves the addition of 6-(A,A-dimethylamino)fulvene (227) to a thiophene sulfone (77TL639, 77JA4199). 

Melles and Backer " found, from a study of the oxidation of substituted thiophenes with perbenzoic or peracetic acid, that sulfones could be obtained from polysubstituted methyl- and phenyl-thiophenes and that the presence of electron-attracting groups, such as nitro, hindered the oxidation. Oxidation of thiophene - led to a product which was formed through a Diels-Alder reaction between the intermediate thiophene sulfoxide (211) and thiophene sulfone (212) and for which two alternative structures, (213) or (214), were suggested. Similar sesquioxides were also obtained from 2- and 3-methylthiophene and 3-phenylthiophene. The structures were not proved. Bailey and Cummins synthesized thiophene-1,1-dioxide... 

Oxidation of thiophene with Fenton-like reagents produces 2-hydroxythiophene of which the 2(570 One isomer is the most stable (Eq. 1) <96JCR(S)242>. In contrast, methyltrioxorhenium (Vn) catalyzed hydrogen peroxide oxidation of thiophene and its derivatives forms first the sulfoxide and ultimately the sulfone derivatives <96107211>. Anodic oxidation of aminated dibenzothiophene produces stable radical cation salts <96BSF597>. Reduction of dihalothiophene at carbon cathodes produces the first example of an electrochemical halogen dance reaction (Eq. 2) <96JOC8074>. 

Oxidative desulfurization of sulfur compounds Oxidation of thiophene and derivatives with hydrogen peroxide using Ti-Beta catalyst... 

Oxidation of thiophene and its derivatives was studied using hydrogen peroxide (H2O2), t-butyl-hydroperoxide and Ti-Beta redox molecular sieve as selective oxidation catalysts. A new reaction pathway was discovered and investigated using C-13 NMR, GC, GC-MS, HPLC, ion chromatography, and XANES. The thiophene oxidized to thiophene-sesquioxide [3a,4,7,7a-tetrahydro-4,7-epithiobenzo[b]-thiophene 1,1.8-trioxide] and the sesquioxide oxidized mostly to sulfate. 2-Methyl-thiophene and 2,5 dimethylthiophene also oxidized to sulfate and sulfone products. The Benzothiophene oxidation product was sulfone. This proposed new reaction pathway is different from prior literature, which reported the formation of thiophene 1,1-dioxide (sulfone ) as a stable oxidation product... 

The oxidation of thiophene and its derivatives with H202 was studied using a Ti-Beta molecular sieve. The oxidation product is very dependent from the aromaticity of model compounds. The thiophene oxidation product was mostly sulfates and the benzothiophene oxidation product was benzothiophene sulfone. Oxidation of mono and di-alkyl thiophenes also produced sulfates and sulfones. The diffusivity and aromaticity of the relevant sulfur compounds, intermediates and stable product, as well as the proposed new mechanism of oxidation will be discussed. This proposed new reaction pathway is different from current literature, which reports the formation of sulfones as a stable oxidation product. 

In methanol, the radical-cation intermediates from oxidation of thiophenes and N-methylpyrroles can be trapped to give low molecular weight products. Reactivity resembles that of furan but with additional consequences because of the properties of thioethers and amines. 

Oxidation of cyclic sulfites to sulfates was accomplished with RuClj/aq. Na(IO )/CH3CN-CCiyO°C and a large-scale oxidation of D-mannitol-l,2 5,6-diacetonide-2,3-cyclic sulfite to the sulfate described (Fig. 5.17) [437]. The system RuO /aq. Na(10 )/CHCl3 converted cyclic sulfite diesters to the sulfates (Fig. 5.18) [438]. Oxidations of thiophene and aUcyl- and aryl-substituted thiophenes by RuCyaq. Na(ClO) were compared with similar reactions effected by stoich. [MnOJ- [439]. 

The by far more common and preparatively valuable dioxirane oxidation of divalent sulfur substrates is that of sulfides, to produce either sulfoxides or sulfones . Since sulfoxides are considerably less reactive than sulfides, the reaction outcome may be conveniently controlled by the stoichiometry of the oxidant For example, in the low-temperature oxidation of thiophene by an excess of DMD, the corresponding 1,1-dioxide (sulfone) has been obtained, albeit in low yield (equation 20). This is the first preparatively useful method for isolating this elusive sulfone, which also accentuates the importance of the neutral and anhydrous conditions under which the oxidations with the isolated DMD may be conducted. 

Oxidation of thiophene with m-chloroperbenzoic acid (MCPBA, 3-chloroperoxobenzoic acid) probably gives first unstable thiophene 1-oxide, and then thiophene 1,1-dioxide (Scheme 6.34a). 2,5-Diarylthio-phenes can be oxidized to the corresponding 1-oxides with 30% aqueous hydrogen peroxide in trifluoroacetic acid and dichloromethane. 

Thienyliodomium salts (e.g., 28, 29) can be made by direct oxidation of thiophene with iodine in either the +5 or the +3 oxidation states (58JA4279), or by iodination of thienyl-lithium species (77JHC281 80CS(15)135). Such compounds are, however, of limited use only for the synthesis of halogenated thiophenes (Scheme 11). 

The organization of material in this chapter follows closely that set down in Chapter 3.02. The only points of departure are in the inclusion of a small section on photosubstitution (3.14.2.11) and in the bifurcation of the section on the oxides of thiophene the reactions of thiophene 1-oxides are described in Section 3.14.4.1 and those of thiophene 1,1-dioxides in Section 3.14.4.2. 

Fluorination of tetrachlorothiophene with potassium tetrafluorocobaltate(III) gave 3,4-dichlorotetrafluoro-3-thiolene (156). Similar fluorination of thiophene yielded the 3-thiolene (157) and the thiolan (158) <71JCS(C)346, 72T43). It has been suggested that the fluorination proceeds by initial oxidation of thiophene to the cation-radical by the metal ion, and subsequent quenching of this by atomic fluorine (Scheme 30). 

Electrochemical oxidation of thiophene and its derivatives in Me0H/H2S04 leads in many instances to ring-opened products (70CCC2635,68CRV449). The general reaction can be represented as in Scheme 33. 

Oxidation of thiophene with perbenzoic acid,373,376 or peracetic acid,377, 378 affords the adduct (111), or its isomer (112) (the available evidence supports structure ni 377-378), by a Diels-Alder reaction between the intermediates thiophene-1,1-dioxide and thiophene-1-oxide. Similar reactions have been observed with substituted thiophenes.376 When a solution of thiophene-1,1-dioxide is allowed to stand, the adduct (113), or its isomer (114), is formed.373 378... 

The oxidation chemistry of methylrhenium trioxide (MTO) has been reviewed.72 The oxidation of thiophenes by hydrogen peroxide has also been studied, using MTO as a catalyst.73 The latter reacts with H2O2 to generate 1 1 and 1 2 rhenium peroxides, which are able to transfer an oxygen atom to the sulfur of the substrate, to give first the sulfoxide and then the sulfone. Whilst electron-donating substituents accelerate the first oxidation, the reverse trend is observed for oxidation of the sulfoxide. 

Sulfur oxidation of the thiophene ring leading to thiophene-1-oxides or thiophene-1,1-oxides is useful for modifying the chemistry of the thiophene ring and this subject has been reviewed <02CHC632>. The structure and physical properties of quinquethiophene-1,1-dioxides have been studied in detail <02T10151>. The mechanism for the oxidation of thiophene to a mixture of thiophene-l-oxide (trapped as a Diels-Alder adduct) and thiophen-2-one was studied using... 

Unsubstituted thiophene 1,1-dioxide is highly unstable and difficult to isolate. It was prepared for the first time by oxidation of thiophene with dimethyldioxirane at 20C under neutral conditions <1997JA9077, 1999BCJ1919>. The compound has a very short half-life and undergoes [2 + 4] dimerization followed by S02 extrusion to give dihydroben-zothiophene 1,1-dioxide, which reacts further by cycloaddition with thiophene 1,1-dioxide. 

Stable sulfones have been obtained from oxidation of 2,5-dimethylthiophene and benzo[A]thiophene with dimethyldioxirane. Trifluoroperacetic acid in MeCN in the absence of water is an effective reagent for the oxidation of thiophenes bearing electron-withdrawing groups to the corresponding thiophene 1,1-dioxides <2001TL4397>. 

The thiophene and the 3-substituted thiophenes 233 have been found to undergo ring dihydroxylation yielding the as fraar-dihydrodiol metabolites 234. Evidence is provided for a dehydrogenase-catalyzed desaturation of a heterocyclic dihydrodiol 234-< /234-rraas (R= Me) to yield the corresponding 2,3-dihydroxythiophene 235 as its preferred thiolac-tone tautomer 236. A simple model to allow prediction of the structure of metabolites, formed from Toluene dioxygenase (TDO)-catalyzed bacterial oxidation of thiophene substrates, has been presented (Scheme 17) <20030BC984>. 

Three major topics have dominated research activity on thiophenes since 1996 the design and synthesis of dithienylethene molecules for application as photochromic systems (Section 3.10.2.1.3) reactions brought about under transition metal catalysis (Section 3.10.2.11) and the synthesis, characterization, and reactivity of a plethora of transition metal complexes of thiophenes (Section 3.10.6). All three had received brief mention in CHEC-11(1996) (Sections 2.10.2.2.3, 2.10.4.7.3, and 2.10.6, respectively), but together account for almost one-third of the chapter now. In addition, shorter sections have been introduced to cover the following topics one-electron oxidation of thiophenes (Section 3.10.2.2) electrochemical reactions at cathodes (Section 3.10.2.7.5) sulfur-extrusion and sulfur-transfer reactions (Section 3.10.2.10) and reactivity of silicon-linked substituents (Section 3.10.4.5). 

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