Thiophenes tautomerism

Examples of the remaining potential 3,4-dihydroxy heterocycles are presently restricted to furan and thiophene. Although the parent 3,4-dihydroxyfuran apparently exists as the dioxo tautomer (86), derivatives bearing 2-alkyl or 2,5-dialkyl substituents prefer the keto-enol structure (87) (71T3839, 73HCA1882). The thiophene analogues also prefer the tautomeric structure (87), except in the case of the 2,5-diethoxycarbonyl derivative which has the fully aromatic structure (88) (71T3839). 

The effect of substituents on the reactivity of heterocyclic nuclei is broadly similar to that on benzene. Thus mem-directing groups such as methoxycarbonyl and nitro are deactivating. The effects of strongly activating groups such as amino and hydroxy are difficult to assess since simple amino compounds are unstable and hydroxy compounds exist in an alternative tautomeric form. Comparison of the rates of formylation and trifiuoroacetylation of the parent heterocycle and its 2-methyl derivative indicate the following order of sensitivity to substituent effects furan > tellurophene > selenophene = thiophene... 

In many cases, substituents linked to a pyrrole, furan or thiophene ring show similar reactivity to those linked to a benzenoid nucleus. This generalization is not true for amino or hydroxyl groups. Hydroxy compounds exist largely, or entirely, in an alternative nonaromatic tautomeric form. Derivatives of this type show little resemblance in their reactions to anilines or phenols. Thienyl- and especially pyrryl- and furyl-methyl halides show enhanced reactivity compared with benzyl halides because the halogen is made more labile by electron release of the type shown below. Hydroxymethyl and aminomethyl groups on heteroaromatic nuclei are activated to nucleophilic attack by a similar effect. 

Pyrrolethiols, readily obtained from the corresponding thiocyanates by reduction or treatment with alkali, rapidly oxidize to the corresponding disulfides. They are converted into thioethers by reaction with alkyl halides in the presence of base. Both furan- and thiophene-thiols exist predominantly as such rather than in tautomeric thione forms. 

This can be achieved by an indirect method. The lithio derivative is first reacted with a borate ester. Sequential acid hydrolysis and oxidation yields the corresponding hydroxy derivative. This procedure is illustrated by the conversion of 2-lithiobenzo[6]thiophene to 2-hydroxybenzo[6]thiophene, which exists predominantly in the 2(3//)-one tautomeric form (200) <70JCS(C)1926). 

The 4- and 5-hydroxy-imidazoles, -oxazoles and -thiazoles (499, 501) and 4-hydroxy-pyrazoles, -isoxazoles and -isothiazoles (503) cannot tautomerize to an aromatic carbonyl form. However, tautomerism similar to that which occurs in hydroxy-furans, -thiophenes and -pyrroles is possible (499 500 503 504 501 502), as well as a zwitterionic... 

Benzo[6]thiophene, 2-acetyl-3-hydroxy-synthesis, 4, 892 Benzo[6]thiophene, 2-acyl-synthesis, 4, 918 Benzo[6]thiophene, 3-acyl-synthesis, 4, 918- 19 Benzo[6]thiophene, acylamino-synthesis, 4, 815 Benzo[6]thiophene, alkenyl-synthesis, 4, 917 Benzo[6]thiophene, 2-alkoxy-synthesis, 4, 929 Benzo[6]thiophene, 3-alkoxy-synthesis, 4, 929 Benzo[6]thiophene, 4-alkoxy-synthesis, 4, 930 Benzo[6]thiophene, 2-alkyl-synthesis, 4, 877-878 Benzo[6]thiophene, 2-alkylthio-synthesis, 4, 931 Benzo[6]thiophene, 2-amino-diazotization, 4, 810 reactivity, 4, 797 stability, 4, 810 synthesis, 4, 869, 924-925 tautomerism, 4, 38 Benzo[6]thiophene, 3-amino-cycloaddition reactions, 4, 68 synthesis, 4, 109, 881, 925 Benzo[6]thiophene, 4-amino-synthesis, 4, 925 Benzo[6]thiophene, 5-amino-synthesis, 4, 925 Benzo[6]thiophene, 7-amino-synthesis, 4, 925 Benzo[6]thiophene, 3-t-amyl-synthesis, 4, 915 Benzo[6]thiophene, 2-aryl-synthesis, 4, 881... 

The mechanism of the Fiesselmann reaction between methylthioglycolate and a,P-acetylenic esters proceeds via consecutive base-catalyzed 1,4-conjugate addition reactions to form thioacetal Enolate formation, as a result of treatment with a stronger base, causes a Dieckmann condensation to occur providing ketone 8. Elimination of methylthioglycolate and tautomerization driven by aromaticity provides the 3-hydroxy thiophene dicarboxylate 9. 

Based on these observations, it is likely that the mechanism involves initial formation of thione 3 (X = O or S), which is followed by tautomerization to 4 and cyclization to 5. Aromaticity drives the facile elimination of either H2O or H2S resulting in the thiophene product. 

The mechanism for the redistribution in oxidation states begins similarly to that of the Paal thiophene synthesis. However, upon formation of dithione 38, nucleophilic addition of one thiocarbonyl into the other produces the intermediate zwitterion 39. A 1,3-tautomerization of hydrogen then gives... 

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 UV spectrum of 5-phenyl-3 hydroxythiophene is very similar to that of its methyl ether in alcoholic solution, indicating that it exists largely in the enol form in this solvent. The same coincidence of the wavelength maxima was also obtained for 5-phenyl-2-hydroxy-thiophene and its methyl ether. In chloroform solution, the maxima were shifted toward longer wavelengths, suggesting that the tautomeric equilibrium in this solvent is displaced more toward the keto form. ... 

The carbanions derived from acylthiophenes have been condensed with aldehydes,and, through the Claisen condensation with esters, thienylsubstituted -diketones have been obtained. 2-Thenoyl trifluoroacetone, first prepared by Reid and Calvin through the Claisen condensation of 2-acetylthiophene with ethyl trifluoracetate, has become an extremely useful chelating agent for the extraction of numerous elements from strongly acidic solutions, The tautomeric form which dominates in aqueous solution is the ketone hy-drate. Other thiophenes have also proved useful for analytical purposes. ... 

Prediction of tautomeric equilibria by a quantum mechanical continuum model of solvation Tautomerism of thiophenes... 

Armulated thiophenes of types 195 and 197 (A benzo, naphtho) were studied concerning keto-enol tautomerism. The ring fusion has a remarkable influence upon these equilibria. Whereas for the c-fused thiophenes 197 only keto tautomers were present, for h-fused derivatives 195 also the enol forms 196 were found (the equilibria are solvent dependent) (82JOC705). 

The second chapter concerns the tautomerism of five-membered ring systems with a single heteroatom concentrating mainly on pyrroles, furans, and thiophenes. It is authored by Professor W. Friedrichsen and Dr. T. Traulsen (University of Kiel, Germany) together with Drs. J. Elguero and A. R. Katritzky. 

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