Carbon-carbon coupling of 4,6-dinitrobenzofuroxan with 3-aminothiophenes: a kinetic and structural study

Potentiometric measurements carried out in a 50-50 (v/v) H 2 O-Me 2 SO mixture together with 1 H and 13 C NMR studies carried out in pure Me 2 SO-d 6 reveal that 3-aminothiophene (4a), 3-N-(methylamino)thiophene (4b), and 3-N,N-dimethylaminothiophene (4c) undergo protonation exclusively at the amino groups in dilute acid solutions. The pK a values of 4a, 4b, and 4c are equal to 3.38, 3.65, and 3.53, respectively, at 25°C, comparing well with those for related anilines in the same aqueous Me 2 SO mixtures. However, despite this similarity of the nitrogen basicities, compounds 4a, 4b, and 4c are found to behave differently from anilines upon treatment with super-electrophilic 4,6-dinitrobenzofuroxan (DNBF). While anilines react to give first an N-bonded sigma -adduct that subsequently decomposes to afford the thermodynamically more stable C-bonded adduct, the 3-aminothiophenes react only as carbon nucleophiles, giving rise directly to the corresponding C-adducts. Based on 1 H and 13 C NMR data as well as measurements of the rate constants (k 1 DNBF ) for DNBF addition to 4a, 4b, and 4c, it is demonstrated that 3-aminothiophenes possess such high negative charge density at C-2 that they can be regarded as strongly enaminic in nature. Estimates of the pK a values for protonation at C-2 of 4a, 4b, and 4c could be made: pK a 4a approx -0.4; pK a 4b approx 0.2; pK a 4c approx 0.8. Thus, these compounds are more susceptible to electrophilic addition at this position than most of the five-membered ring heterocycles studied so far. Altogether, the results demonstrate the importance of the hyper-ortho relationship in the thiophene systems, accounting for the ease of both electrophilic and nucleophilic reactivity of 3-X-thiophenes in σ -complex formation processes.