Group Reactivities in Thiophenes

The carbonyl group reactivities in thiophenes and benzenes are very similar, as shown by the similar rates of alkaline hydrolysis of esters and by the great similarity of the thiophenealdehydes to benzaldehyde in numerous carbonyl group reactions. This has been ascribed to the counteracting —I- -M effects of the thienyl group in this kind of reactions.  

Thiophenealdehydes have been condensed with aliphatic aldehydes, methyl ketones,cyclic ketones, benzyl cyanides,and aliphatic nitro compounds to the corresponding vinylthiophenes. By the use of potassium methylate, 2-thiophenealdehyde has been condensed with the reactive methyl groups of iV-heterocyclic compounds. Thiophenealdehydes have 

The primary condensation product of 2-thiophenealdehyde with 2 moles of ethyl acetoacetate (189) has been cleaved with alkali to 

Asinger, M, Thiel, W. Dathe, O. Hampel, E. Mittag, E. Plaschil, and C. Schroder, Ann. Chem. Liebigs 639, 146 (1961). 

Acta 40, 1521 (1957). 

---

The acid cleavage of the aryl— silicon bond (desilylation), which provides a measure of the reactivity of the aromatic carbon of the bond, has been applied to 2- and 3-thienyl trimethylsilane, It was found that the 2-isomer reacted only 43.5 times faster than the 3-isomer and 5000 times faster than the phenyl compound at 50,2°C in acetic acid containing aqueous sulfuric acid. The results so far are consistent with the relative reactivities of thiophene upon detritia-tion if a linear free-energy relationship between the substituent effect in detritiation and desilylation is assumed, as the p-methyl group activates about 240 (200-300) times in detritiation with aqueous sulfuric acid and about 18 times in desilylation. A direct experimental comparison of the difference between benzene and thiophene in detritiation has not been carried out, but it may be mentioned that even in 80.7% sulfuric acid, benzene is detritiated about 600 times slower than 2-tritiothiophene. The aforementioned consideration makes it probable that under similar conditions the ratio of the rates of detritiation of thiophene and benzene is larger than in the desilylation. A still larger difference in reactivity between the 2-position of thiophene and benzene has been found for acetoxymercuration which... 

The ease with which electrophilic substitution occurs in position 4 in thiophenes containing a —I—M-substituent in position 3, if the reactive a-positions are blocked with halogens or methyl groups, in contrast to the difiiculty of achieving such substitution in the 3-position of a —I—M 2-substituted thiophene was noticed already by Steinkopf et They easily dinitrated and disulfonated 2,5-di-... 

Two different sets of experimental conditions have been used. Buu-Hoi et al. and Hansen have employed the method introduced by Papa et using Raney nickel alloy directly for the desulfurization in an alkaline medium. Under these conditions most functional groups are removed and this method is most convenient for the preparation of aliphatic acids. The other method uses Raney nickel catalysts of different reactivity in various solvents such as aqueous ammonia, alcohol, ether, or acetone. The solvent and activity of the catalyst can have an appreciable influence on yields and types of compounds formed, but have not yet been investigated in detail. In acetic anhydride, for instance, desulfurization of thiophenes does not occur and these reaction conditions have been employed for reductive acetylation of nitrothiophenes. Even under the mildest conditions, all double bonds are hydrogenated and all halogens removed. Nitro and oxime groups are reduced to amines. 

The first group consists of monocyclic heteroaromatic compounds with one heteroatom and without strongly electron-donating substitutents (OH, NH2). Pyrrole, furan, and thiophene are better electron donors than benzene. The order of their reactivities in azo coupling is thiophene > pyrrole > furan > benzene. 

The only available data concern the effects of alkyl groups on the trifluoroacetylation reaction (Table XXVI). A methyl group in position 2 increases (taking into account the statistical factor) the reactivity of the other a position by a factor of 23.8 (compared with factors of 380 and 1720 observed in thiophene and furan, respectively).143... 

Protiodeplumbylation (cleavage of PbR3 groups from aromatics) was used in the first demonstration that furan was more reactive than thiophene toward electrophiles (32RTC1054). 

Furane and thiophene derivatives are poorly reactive substrates thiophenes in particular require the presence in the ring of electron donors such as, for example, the methoxy group, in order to undeigo the Mannich reaction successfully. The preferred site of attack is again in the a position with respect to the heteroatom. - -35i,4i6,4i7,427 interestingly, the reaction takes place at position a-2 in the 3-substituted derivatives, rather than at the less hindered a-5 position. - ... 

---