Five-membered rings thiophene derivatives

The enormous literature of five-membered ring systems containing sulfur primarily describes the synthesis, properties and chemistry of thiophene and its derivatives . 

Examples of reactions involving replacement and cyclization are the long-known preparation of thiophenes (89) from 1,4-diketones, and the formation of l,2-dithiole-3-thione (90) from the salicylate ester analog (91).120 In the latter instance, oxidative cyclization with formation of an S—S bond has occurred this is a common feature of these reactions, particularly if such a link is needed to complete a five-membered ring. Another example of this aspect is afforded by the reaction of the propane-1,3-dione derivatives (92) which yield 3,5-diaryl-1,2-dithiolylium salts (93) when heated with phosphorus pentasulfide in carbon disulfide, followed by perchloric acid.121... 

The reactivity of five-membered rings with one heteroatom to electrophilic reagents has been quantitatively compared. Table 1 shows that the rates of substitution for (a) formylation by phosgene and V,iV-dimethylformamide, (b) acetylation by acetic anhydride and tin(IV) chloride, and (c) trifluoroacetylation with trifluoroacetic anhydride (71AHC(13)235) are all in the sequence furan > tellurophene > selenophene > thiophene. Pyrrole is still more reactive as shown by the rate for trifluoroacetylation, by the relative rates of bromination of the 2-methoxycarbonyl derivatives (pyrrole > furan > selenophene > thiophene), and by the rate data on the reaction of the iron tricarbonyl-complexed carbocation [C6H7Fe(CO)3]+ (Scheme 5) (2-methylindole ss V-methylindole > indole > pyrrole > furan > thiophene (73CC540)). 

It is convenient to consider heteroaromatic ligands in two classes - 7t-excessive, five membered rings typified by pyrrole, furan and thiophen, and TC-deficient six-membered rings typified by pyridine. The 7i-excessive heterocycles are usually extremely reactive towards electrophilic attack and, with the exception of thiophen, do not exhibit the chemical inertness often associated with aromatic benzene derivatives. Conversely, the TT-deficient heterocycles are extremely inert with respect to electrophilic attack. Paradoxically, it is the high reactivity of the five-membered rings and the inertness of the six-membered rings that give rise to common synthetic problems. The usual methods for the... 

The fact remains that selenophene and its derivatives have aromatic character. This statement is, however, not easy to substantiate with quantitative data mainly because there are too many ambiguities for parent five-membered ring heterocycles. Some aromaticity indices for five-membered rings with one heteroatom, among them selenophene, were summarized and estimated values for thiophene and selenophene were similar [26], The data obtained from photoelectron ionization energies show that the aromatic stabilization in thiophene is slightly larger than for selenophene [27],... 

Pyrrole 2.1, thiophene 2.2, and furan 2.3, are five-membered ring heteroaromatic compounds containing one heteroatom. They derive their aromaticity from delocalisation of a lone pair of electrons from the... 

Thiophene is an aromatic compound. Its structure can be assumed to be derived from benzene by replacement of two annular CH groups with sulfur. The sulfur atom in this five-membered ring acts as an electron-donating heteroatom by contributing two electrons to the aromatic sextet and thiophene is thus considered to be an electron-rich heterocycle. 

The NICS of each ring, as a criterion of aromaticity, has been used to explain the stability order of benzo[/)]thio-phene and its isomer. The results indicate that the benzene ring is aromatic in all the systems. The five-membered ring of benzo[. ]thiophene is also aromatic, whereas in benzo[r]thiophene it is nonaromatic. This could be an explanation of the stability of the former molecule. The MOS and the condensed Fukui functions derived from the electronic-structure calculations explain the expected electrophilic substitution of these compounds. The theoretical structure, ionization energies, order of aromaticity, stability, and reactivity are in good agreement with the experimental results <2003T6415>. 

It can be concluded that the B3LYP/6-31G will produce high-quality structural parameters for the five-membered rings and their benzo derivatives. Based on the structural uniformity principle and magnetic susceptibility anisotropies, the predicted relative aromaticity of these systems is found to be reliable. From the computed values, the relative stability of thiophene, benzo[ ]thiophene, and benzo[f]thiophene is accurately predicted. 

Secondary steric effects could become significant in aromatic nucleophilic substitution in activated halogenoben-zenes. This can be ascribed to steric inhibition of resonance. In contrast, secondary steric effects are not important in SNAr reactions of thiophene derivatives this is due to the geometry of five-membered ring derivatives, which strongly lowers the steric interactions between the substituents on the thiophene ring. This has been reconfirmed by kinetic data in methanol on SNAr reactions of the two pairs of substrates 210 and 211 with different nucleophiles (piperidine and sodium benzenethiolate) <1997J(P2)309>. 

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