Heteroaromatic rings protonation

Table 2.5 H chemical shifts (ppm) for heteroaromatic ring protons...

In contrast to H shifts, C shifts cannot in general be used to distinguish between aromatic and heteroaromatic compounds on the one hand and alkenes on the other (Table 2.2). Cyclopropane carbon atoms stand out, however, by showing particularly small shifts in both the C and the H NMR spectra. By analogy with their proton resonances, the C chemical shifts of k electron-deficient heteroaromatics (pyridine type) are larger than those of k electron-rieh heteroaromatic rings (pyrrole type). 

The reversed polarity of the double bond is induced by a n electron-accepting substituent A (A = C=0, C=N, NO2) the carbon and proton in the p-position are deshielded (-A/effect, larger shifts). These substituents have analogous effects on the C atoms of aromatic and heteroaromatic rings. An electron donor D (see above) attached to the benzene ring deshields the (substituted) a-C atom (-/ effect). In contrast, in the ortho and para positions (or comparable positions in heteroaromatic rings) it causes a shielding +M effect, smaller H and C shifts), whereas the meta positions remain almost unaffected. 

In an analogous way heteroaromatic diazonium ions that contain an acidic NH group in the heteroaromatic ring, e. g., the diazole, triazole, and tetrazole derivatives 5.1, 5.2, and 5.3, lose that proton even in weakly to strongly acidic solutions, as... 

Halogen substituents are of course easy to introduce to heteroaromatic rings, and they also enhance the acidity of the ring protons. n-BuLi will, for example, lithiate the tetrafluoropyridine 179 at —60°C in ether ° but with pyridine itself it leads to addition/reoxidation products . Addition to the ring is the major product with 2-fluoropyridine 180, though some metaUation can be detected selectivity in favour of metaUation is complete with LDA in THF at —75 °C or with phenyUithium and catalytic -Pr2NH at —50°C (Scheme 90) . Similar results are obtained with quinolines . 

Chemical shift data for a number of simple pseudoazulenes are listed in Table IV. The signals for the protons of the pseudoazulenic skeleton are in the region of other heteroaromatic compounds. Also the NMR spectrum of 49a shows a peak for the pseudoazulene ring protons at i = 4.26 ppm (<5 = 5.74 ppm)135 and that of70a at r = 3.25 ppm (<5 = 6.75 ppm).175 Many authors argue against substantial aromatic character for these pseudoazulene... 

Table A3.4 Chemical shifts (TMS) of protons attached to aromatic and heteroaromatic rings...

DFT studies on heteroatom diallenes have found, in line with previous experimental data, that biradical cyclization to a five-membered heteroaromatic ring is the preferred reaction pathway, although protonation of the heteroatom has been found to promote a competing cyclization to a six-membered, initially biradical, ring.59... 

Nucleophiles can be introduced at C4 of 1,2-type 64 (Scheme 15) and at C4 or C5 of 1,3-type N-alkoxyazolium salts 67 (Scheme 16) by an allylic displacement of ROH and loss of a proton. This reaction mode competes with the nucleophilic addition followed by elimination of ROH described in Section 1.5.1.3. Consequently all ring protons in 1,2-type and 1,3-type azoles become activated but predictions of product distribution turn difficult. In all cases the net result is replacement of hydrogen at the heteroaromatic nucleus with a nucleophile. The sequence can be performed in one pot. 

TABLE D.5 Chemical Shifts of Protons on Heteroaromatic Rings... 

In the first step, the carbon centered radical is generated. The second step involves the addition of this radical to the protonated ring. The third step consists of the rearomatization of the radical adduct by oxidation. The rates of addition of alkyl and acyl radicals to protonated heteroaromatic bases are much higher than those of possible competitive reactions, particularly those with solvents. Polar effects influence the rates of the radical additions to the heteroaromatic ring by decreasing the activation energy as the electron deficiency of the heterocyclic ring increases. 

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