Thiophene oxides, aromaticity

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 addition to the sulfur compounds listed above, hydrogen sulfide has been found in many crude petroleums. Elemental sulfur has been definitely found in several crude petroleums by API Research Project 48 (23). Although Birch and Norris (5) isolated several disulfides from the spent caustic used in treating gasoline from Iranian petroleum, these compounds may have resulted from the oxidation of the thiols and their presence in the original petroleum is regarded as doubtful. Other types of sulfur compounds, such as thiophenes and aromatic thiols, have been identified in cracked petroleum products, but the presence of such compounds in naturally occurring petroleums has not yet been established. 

Heteroatoms such as nitrogen or sulfur are oxidized on their free peripheric electrons (Fig. 32.12) as described for thiophene. Halogenated aromatic compounds, may also be oxidized by cytochrome P-450 monooxygenases, yielding hypervalent halogenated compounds. 

This 1,3-migration of hydrogen was also observed when 40 reacted with Lawesson s reagent to produce the dithiolactone 41. However, when y-hydroxy-a,P-unsaturated aldehyde 42 was reacted under similar conditions, thiophene 43 was prepared efficiently. These results are not surprising considering that the oxidation state of 42 is equivalent to the traditional saturated 1,4-dicarbonyl substrates of the Paal thiophene reaction via tautomerization of the double bond, and aromaticity is reestablished in the fully conjugated 43. 

The thiophene sulfur atom shows very few of the reactions expected of a sulfide. The oxidation to a sulfone is difficult to achieve, but is of special interest, as knowledge of its aromatic character or lack of it would give information about the ability of sulfur to expand its valence shell beyond eight electrons. 

Our recent studies on effective bromination and oxidation using benzyltrimethylammonium tribromide (BTMA Br3), stable solid, are described. Those involve electrophilic bromination of aromatic compounds such as phenols, aromatic amines, aromatic ethers, acetanilides, arenes, and thiophene, a-bromination of arenes and acetophenones, and also bromo-addition to alkenes by the use of BTMA Br3. Furthermore, oxidation of alcohols, ethers, 1,4-benzenediols, hindered phenols, primary amines, hydrazo compounds, sulfides, and thiols, haloform reaction of methylketones, N-bromination of amides, Hofmann degradation of amides, and preparation of acylureas and carbamates by the use of BTMA Br3 are also presented. 

It has been known that aromatic heterocycles such as furan, thiophene, and pyrrole undergo Diels-Alder reactions despite their aromaticity and hence expected inertness. Furans have been especially used efficiently as dienes due to their electron-rich properties. Thiophenes and pyrroles are less reactive as dienes than furans. But pyrroles with A-elecIron-withdrawing substituents are efficient dienes. There exists a limited number of examples of five-membered, aromatic heterocycles acting as dienophiles in Diels-Alder reactions. Some nitro heteroaromatics serve as dienophiles in the Diels-Alder reactions. Heating a mixture of l-(phenylsulfonyl)-3-nitropyrrole and isoprene at 175 °C followed by oxidation results in the formation of indoles (see Eq. 8.22).35a A-Tosyl-3-nitroindole undergoes high-yielding Diels-Alder reactions with... 

Also as noted above any substituents present have little effect upon such oxidations. In 2,2 -methylenedifuran (118) the rings are attacked simultaneously giving a tetramethoxy derivative.297 Even the bulk of the fert-butyl group has little effect.298 The only marked substituent effect is that exerted by an aromatic (benzene, thiophene, furan) residue which, if directly attached at the 2-position, promotes elimination instead of the addition of another methoxy group. The net process then becomes one of arylation, as when 2-(2-thienyl)furan (119) is oxidized to 120.298 There are reports that acetyl and carboxy groups can be ejected during oxidation, but that ester groups are usually retained.287... 

Thiophene-1-oxide and 1 -substituted thiophenium salts present reduced aromaticity.144 A variety of aromaticity criteria were used in order to assess which of the 1,1-dioxide isomers of thiophene, thiazole, isothiazole, and thiadiazole was the most delocalized (Scheme 46).145 The relative aromaticity of those molecules is determined by the proximity of the nitrogen atoms to the sulfur, which actually accounts for its ability to participate in a push-pull system with the oxygen atoms of the sulfone moiety. The relative aromaticity decreases in the series isothiazole-1,1-dioxide (97) > thiazole-1,1 -dioxide (98) > thiophene-1-dioxide (99) then, one has the series 1,2,5 -thiadiazole-1,1 -dioxide (100) > 1, 2,4-thiadiaz-ole-1,1-dioxide (101) > 1,2,3-thiadiazole-1,1 -dioxide (102) > 1,3,4-thiadiazole-l,1-dioxide (103) in the order of decreasing aromaticity. As 1,2,5-thiadiazole-1,1-dioxide (100) was not synthesized, the approximations used extrapolations of data obtained for its 3,4-dimethyl-substituted analogue 104 (Scheme 46). 

Several aromaticity indices (bond lengths, bond orders, Jug and Francois s aromaticity index) indicate that, despite the nonplanarity of the five-membered ring in 2,5-diphenylthiophene-l-oxide (108), this compound is intermediate in aromaticity between the corresponding thiophene 107 and the nonplanar 1,1-dioxide 109 (Scheme 48).149 The theoretical calculations were supported by experimental electrochemical data.150... 

Acetylenic dienophiles have also been used in conjunction with a different type of diene (150) for the combinatorial synthesis of isoindolones 151 fused with furan, pyrrole or thiophene rings (Fig. 30) [129]. In this case, the diene involved in IMDA is not the 5-membered heterocycle itself, but the one including the exocyclic double bond. The resulting dihydrobenzene is easily aromatized by oxidation with DDQ or C/O2. The synthetic protocol is accomplished in a one-pot process. 

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