Pyrrole-type nitrogen

Indole is planar with 10 TT-electrons in a completely conjugated system. The ring is classified as a TT-excessive he tero aromatic compound because of the electron-donating character of the pyrrole-type nitrogen atom. The TT-system is relatively electron-rich, particularly at C-3, as represented by resonance stmcture (lb). 

Benzyl carbamates of pyrrole-type nitrogens can be cleaVfed with nucleophilic reagents such as hydrazine hydrogenation and HF treatment are also effective. ... 

Our definition does not take account of lone pairs on heteroatoms in the ring which do not contribute to the -system we are normally concerned here with pyridinoid nitrogen atoms, and their influence on aromaticity is discussed in Section V,B. It is also noteworthy that for molecules possessing an unsubstituted pyrrole-type nitrogen atom, the aromaticity of the anion produced on deprotonation can be significantly greater than that of the protonated form. This has been found in a number of cases with aromatic annulenes,15-18 and we will meet similar results with certain mesoionic azapentalenes (Section IV,C,l,a). 

Some other data on, 5N chemical shifts, referred to internal MeN02, are recorded in Table 25. Comparison of pyrrole with imidazole demonstrates that the deshielding of the pyrrole-type nitrogen is about 15 ppm. Increased nitrogen shielding is observed for 2,1,3-benzothiadiazole ( + 49 ppm) and the parent 1,2,5-thiadiazole ( + 34 ppm). In contrast, the corresponding oxadiazoles were deshielded, as in 2,1,3-benzooxadiazole ( — 36 ppm) and 1,2,5-oxadiazole (— 34 ppm). 

The Hammett cr+ constant for the 4(5)-position of imidazole is around -1 for C-2 it is of the order -0.8 (86CHE587). The electrophilic substitutions which do occur at the 2-position invariably involve preformation of an anion at that position. The 2-proton, which should be the least active in a conventional SEAr sense, turns out to be the most labile over a wide pH range, and there is a marked rate acceleration on going from imidazole to imidazolium cation. Any negative charge generated at C-2 is stabilized by the adjacent pyrrole-type nitrogen (see Section 3.4.1.8.2). 

Azalene salts 90 and 92 are obtained by quaternization of the corresponding heterocyclic bases with alkyl halides or tosylates. If the heterocyclic base contains several nitrogen atoms, alkylation can produce different quaternary salts. Quaternization, however, is surprisingly selective if certain conditions are met.205 Pyrrolo- and indolopyridines containing one pyridine-and one pyrrole-type nitrogen atom in their molecular lattice are (in aprotic solvents) almost exclusively alkylated at the nitrogen atom of the pyridine... 

If the heterocyclic base contains several pyridine-type nitrogens select can also be observed. Indeno[l,2-b]quinoxalines, for example, are quaternized at the N-10 atom.110 The alkylation of heterocycles conta one pyrrole-type nitrogen and several pyridine-type nitrogens is appar selective (e.g., indolo[2,3-b]quinoxaline).201 The yields of quaternary however, are extremely low,201 even if phenacyl halides or a-halo ester used.207 Perhaps the resultant quaternary salts are dealkylated.200,207... 

Quaternary salts (90) from azalenes obtained from heterocyclic bases and phenacyl halides or derivatives of a-halo carbon acids also contain an acidic exocyclic CH2 group. Therefore, during the deprotonation, mixtures of pseudoazulenes 91 and ylides 98 can be formed, especially if Y = CH. °5 Quaternary salts (90) containing one pyrrole-type nitrogen (Y = N) de-protonate exclusively to pseudoazulenes166 (Scheme 6). Analogous behavior... 

The aromaticity obtained by means of the DE values and their differences in the single pseudoazulene systems are also the result of calculations of the bond orders (Fig. 1). The calculated bond alternations46 57-77-79-82-117118-129 are in line with the heteroaromaticity of the systems. Similar relationships were calculated for azulene.219 The extent of the bond alternation, however, differs from one system to the other (see Fig. 1). In indeno[2.1-f>]-l-benzo-pyran (44a) the bond lengths of the central cyclo[fo]pyran system indicate pronounced bond alternation, and in the opinion of the authors, the systems have little aromatic character.129 Calculations with 1 //-pyrindines (26) and 2//-pyrindines (29) show that 26 is more stable than 29, but both are less aromatic than indole.63 A comparison of SCF calculations for pseudoazulenes 26 and 29 with their aza analogs 68 and 69-73, which contain a pyrrole-type nitrogen, shows only minor perturbations of carbon-carbon bond lengths on replacing a =CH— moiety by =N—.66... 

Only a few investigations of electrophilic substitution reactions of pseudo-azulenes containing a pyrrole-type nitrogen have been reported. There are many examples of alkylations (see Table VI). An alkylation always takes place at the nitrogen of the five-membered ring. For 7H-pyrrolo[2,3-b]-pyridine 68 azocoupling and reaction with dithiolium salts have been reported.166... 

A further chracterization of these pyrrole type nitrogen compounds in the very weak base concentrate can be made by using the colorometric pyrrolic nitrogen value of 6.8% (Table III) as the value for a, -unsub-stituted pyrrole type compounds. This leaves 22.2% of the nitrogen in pyrroles and indoles which have both a- and -substitution. The affi-unsubstituted pyrroles and indoles also have no N-substitution because these N-substituted compounds would titrate as weak bases and not as very weak bases. The lack of N-substitution on the pyrroles and indoles is consistent with the research of Jacobson (18, 19) who reported that N-alkylpyrroles and N-alkylindoles thermally and irreversibly isomerize to give the a and alkyl isomers and therefore would not likely be present in crude shale oil. 

This particular experimental fact allowed Kost [164] to speculate that carbon atoms were more preferable endocyclic reaction centers in reactions with unsaturated ketones than nitrogens. But applying this generalization to other ami-noazoles is not correct because of a dramatic difference of the nucleophilicity of the pyrrole-type nitrogen of indole and pyrimidine-type poly azoles. Indeed, the... 

Pentazoles are extremely sensitive to light. Light exposition leads to quick decomposition or even explosion <2002MI1>. Arylpentazoles are very basic compounds the 1SN NMR spectra of //-chlorophenylpentazole in a 1 1 mixture of trifluoroacetic acid and trifluoroacetic anhydride only show a low percentage of protonation at the N-3 nitrogen atom in /3-position to the pyrrole-type nitrogen atom. In chlorosulfonic acid with a pof about —12 the pentazole is fully protonated. Thus a pof about —9 is estimated experimentally. Chlorosulfonic acid also fully protonates //-methoxyphenylpentazole <2004TL1977>. The protonation is reversible by dilution or neutralization of the solution (Equation 2). 

Pyrrolic-type nitrogen compounds are more sensitive than the corresponding aromatics, while the latter are more sensitive than the pyridinic types. Thus, indole has a higher sensitivity than naphthalene naphthalene a higher one than quinoline. This effect becomes less pronounced as the aromatic condensation increases (6). 

It has to be a pyrrole-type nitrogen as it must have three o bonds, so the lone pair must be in a p orbital. This means that one of the rings must be five-membered and the simplest member of this interesting class is called indolizine—it has pyridine and pyrrole rings fused together along a C-N bond. 

Like pyrrole-type nitrogens, ring oxygen and sulfur atoms also have a deshielding effect on pyridine-type nitrogen atoms with the effect greatest on adjacent atoms. For examples see Table 23b and structures 166-173 in Figure 20. 

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