Thiophenes 2- -, selective nitration

Thiophene is nitrated by mild nitrating agents such as acetyl or benzoyl nitrate, mainly in the 2-position. The selectivity decreases with increasing vigor of the reagent and up to 15% of the 3-isomer can be obtained. 2-Cyanothiophene is nitrated predominantly at position 4. 

It is thus apparent that the selectivity of a reagent toward thiophene and benzene can differ appreciably, and this difference in selectivity is also strongly noticeable in the proportions of 2- and 3-isomers formed. Although in certain reactions no 3-isomer has been detected, appreciable amounts have been found in other reactions. Thus 0.3% of the 3-isomer has been found in the chlorination of thiophene.- Earlier results indicated that 5-10% 3-nitrothiophene is formed in the nitration of thiophene and a recent gas-chromatographic analysis by Ostman shows that the mononitrothiophene fraction contains as much as 16% of the 3-isomer. It appears that gas-chromatographic analysis should be very useful for the detection of small amounts of 3-isomers in other substitution reactions. However, from routine analyses of IR spectra, it appears to the present author that the amount of 3-isomers formed in acylation, formylation, and bromina-tion of thiophene are certainly less than a few per cent. 

Changes in intramolecular selectivity in the bromination and nitration of alkyl-benzenes in acidic media have been attributed to changes in medium polarity or changes in electrophile solvation. Mass spectrometric studies of the first stage in the gas-phase reactions of halobenzenes, furan, thiophene and pyrrole with alkyl cations have been rationalized in terms of co-existing a- and tt-complexes. The extent of... 

A tetraruthenated porphyrin was electropolymerised onto glassy carbon and used to catalyse the oxidation of nitrite to nitrate, with the resultant current giving a selective measure of the concentration of nitrite ion [81]. As an alternative method, soluble poly(3-octyl thiophene) [82] was cast along with tridodecylmethylammonium chloride onto glassy carbon, to give electrodes with superior selectivity over PVC-based membranes to lipophilic ions such as bromide or nitrate. 

Benzothiophene, like thiophene, is a n-electron rich heterocycle. Unlike thiophene, electrophilic attack occurs selectively at the P-position (or 3-position) [10a, Ila] however, substitution at the a-center (2-position) can also be achieved [11b]. The order of positional reactivity, based on nitration, is 3 > 2 > 6 > 5 > 4 > 7 [1 la, 12a]. Also, halogenation under acidic conditions affords the 3-halobenzothiophene [11c, 13a]. In terms of metalation chemistiy, deprotonation occurs preferentially at the 2-position (a) [lid, 13b] metal-halogen exchange is also favored at the a-center over the P-center [12b]. 

Aromatic alkylation reactions which led to a number of para-selective products have been duplicated on phenols and thiophenes (64-65-66-67). So have halogenation and nitration reactions (68—69). 

Isomer distributions have been determined for several electrophilic substitutions of thiophen, such as bromination by Bra and Br+, chlorination by tin tetrachloride, or iodine-catalysed acetylation by acetic anhydride, trifluoroacetylation, and Vilsmeyer formylation. The a. ratios vary from 100 to over 1000, according to the selectivity of the electrophilic agent. The results obtained, together with other data from the literature, permit a test of the applicability of linear free-energy treatments to electrophilic substitution at the a- and j8-positions of thiophen. Plots of log (Xf and log jSf against p for nine reactions were linear, and from the slopes values of = — 0.79 and 0)3+ = — 0.52 were obtained. Serious deviations were observed for mercuration and protodemercuration, while nitration and protodeboronation were not taken into account, as deviation could be expected for various reasons. The linearity was taken as evidence... 

Ammonium nitrate can be usefully added to NCS for selective aromatic chlorination reactions thus, 2-chlorothiophene (59% yield) and 2,5-dichlorothiophene (10%) were obtained after treatment of thiophene with NCS/NH4NO3 in acetonitrile (Scheme 56) [89],... 

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