Pyridine and Pyrrole

Pyridine was first isolated in a pure state from bone oil by Anderson had earlier obtained picoline from coal tar. He established the molecular 

Later suggestions concerning pyridine followed closely the pattern of the history of benzene structures. Consideration of the conversion of pyrrole to 3-chloropyridine (see p. 88) led Ciamician and Dennstedt to propose a prism formula. Riedel , from the degradation of acridine to quinoline, and thence to pyridine derivatives, supposed the diagonal structure which he had proposed for acridine (9) to persist in pyridine (10), while Bamberger (see below) suggested a centric structure (11), and a Thiele formula was also considered. 

Pyrrole was isolated from bone oil by Runge o and purified and analysed some years later by Anderson i. Following work in the indole series, v. Baeyer and Emmerling22 proposed for pyrrole the structure (12), the nearest analogy to the Kekule structures of the six-membered ring compounds. This 

If Kermack and Robinson srepresentation of benzene (4) restated Thiele s structure in electronic terms, it also re-interpreted Armstrong and Bamberger s ideas which were now transformed into the view that aromatic stability was associated with a sextet of electrons s. Two of nitrogen s five valency electrons were used to link the nitrogen atom to the two adjacent carbon atoms in pyridine, one contributed to the aromatic sextet, and two, 

Lewis s account29 (1916) of the inductive effect and Lowry s idea of electromeric shifts in unsaturated bonds (1923) were combined by Lucas in 1924-5, and developed by Robinson s (1926) and Ingold i 34d (1926) into a comprehensive qualitative theory of reactions. 

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Pyridine and pyrrole are both weak bases but pyridine is much more basic than pyrrole When pyridine is protonated its unshared pair is used to bond to a proton and... 

Nitrogen compounds in crudes may generally be classified into basic and non-basic categories. Basic nitrogen compounds are mainly those having a pyridine ring, and the non-basic compounds have a pyrrole structure. Both pyridine and pyrrole are stable compounds due to their aromatic nature. 

The chemistry of these polycyclic heterocycles is just what you miglu expect from a knowledge of the simpler heterocycles pyridine and pyrrole Quinoline and isoquinoline both have basic, pyridine-like nitrogen atoms, anc both undergo electrophilic substitutions, although less easily than benzene Reaction occurs on the benzene ring rather than on the pyridine ring, and r mixture of substitution products is obtained. 

Aromatic molecules can be polymerized catalytically on clean metal surfaces, or electrochemically to produce oriented polymer films. Initial adsorption of aromatic molecules occurs by electron donation from the aromatic molecule to the surface. This electron donation creates radical cations that can polymerize. Molecular orientation in the films depends on the stable bonding configuration of the radical cation. Thiophene, pyridines, and pyrrole all polymerize with the ring substantially perpendicular to the surface, whereas aniline polymerizes with the phenyl rings parallel to the surface. The catalytically... 

However, pyridine and pyrrole are significantly less basic than either of their saturated analogues. The pyridinium cation has pATa 5.2, making pyridine a much weaker base than piperidine, whereas the pyrrolium cation (pATa - 3.8) can be considered a very strong acid, and thus pyrrole is not at all basic. 

We can draw Frost circles (see Section 2.9.3) to show the relative energies of the molecular orbitals for pyridine and pyrrole. The picture for pyridine is essentially the same as for benzene, six jt electrons forming an energetically favourable closed shell (Figure 11.1). For pyrrole, we also get a closed shell, and there is considerable aromatic stabilization over electrons in the six atomic orbitals. 

Figure 11.1 Relative energies of pyridine and pyrrole molecular orbitals from Frost circles...

Though we shall return to this again, one critical difference between pyridine and pyrrole to note here relates to basicity. Pyridine is a base because its nitrogen still carries a lone pair able to accept a proton. Pyrrole is not basic it has already used up its lone pair in contributing to the aromatic sextet. 

Our study of heterocyclic compounds is directed primarily to an understanding of their reactivity and importance in biochemistry and medicine. The synthesis of aromatic heterocycles is not, therefore, a main theme, but it is useful to consider just a few examples to underline the application of reactions we have considered in earlier chapters. From the beginning, we should appreciate that the synthesis of substituted heterocycles is probably not best achieved by carrying out substitution reactions on the simple heterocycle. It is often much easier and more convenient to design the synthesis so that the heterocycle already carries the required substituents, or has easily modified functions. We can consider two main approaches for heterocycle synthesis, here using pyridine and pyrrole as targets. 

The circulating electrons in the 7t-system of aromatic hydrocarbons and heterocycles generate a ring current and this in turn affects the chemical shifts of protons bonded to the periphery of the ring. This shift is usually greater (downfield from TMS) than that expected for the proton resonances of alkenes thus NMR spectroscopy can be used as a test for aromaticity . The chemical shift for the proton resonance of benzene is 7.2 ppm, whereas that of the C-1 proton of cyclohexene is 5.7 ppm, and the resonances of the protons of pyridine and pyrrole exhibit the chemical shifts shown in Box 1.12. 

Chemical shifts for the C-H proton resonances of benzene, pyridine and pyrrol e (spectra recorded in CDC13)... 

The structure of pyrrolo[3,4-. X-Ray crystallographic analysis of reduced derivatives of pyrrolo[3,2-3]pyridines, 31, confirms the m-fusion of the pyridine and pyrrole rings <2003JOC5652>. 

Problem 20.22 Compare, and explain the difference between, pyridine and pyrrole with respect to reactivity toward electrophilic substitution. 

Heterocyclic These are compounds having at least one hetero atom (any other atom but carbon, e.g. O, N and S) within the ring, and conforming to Hiickel s rule. The aromaticity of heterocyclic compounds, e.g. pyridine and pyrrole, can be explained as follows. 

N-Heterocyclics. The reaction of primary amines with the carbonyl products derived from lipid oxidation is a major pathway in lipid-protein interactions. Formation of Schiff s base intermediates followed by cyclization and rearrangement can yield imines, pyridines and pyrroles (5,15,30,31). For example, 2-pentylpyridine may result from the reaction of ammonia with 2,4-decadienal, one of the principle aldehydes from the autoxidation of linoleate (5). 

Pyridines and pyrroles can be formed in different pathways by Mail-lard reaction. The formation of 5-methyl pyrrole aldehyde and 6-methyl-3-pyridinole has been observed by Nyhammar et al (17) by the reaction of isotope labelled 3-deoxyosone with glycine. The 3-deoxy-hexosone represents an -dicarbonyl compound and in this way the Strecker degradation occurs. Another pathway is the reaction of fu-rans with ammonia. Under roast conditions, we have obtained primarily the corresponding pyrrole, whereas we found the corresponding py-... 

Pyridine and pyrrole (Figure 5) increase according to the roasting level of the beans and are higher in Arabicas than in Robustas under comparable conditions. 

Polycyclic aromatic nitrogen compounds, such as quinoline, indole, acridine, and carbazole, are the main nitrogen-containing compounds in oil fractions, and monocyclic pyridine and pyrrole as well as anilines are present in coal tar (Scheme 11). Saturated cyclic amines are found as products of ring hydrogenation of the compounds shown in Scheme 11 after HDN. Aliphatic amines are rarely found in fuels and only in low concentrations after HDN since their nitrogen atoms are easily removed. 

Chemistry (CHEC-I), chemical literature references prior to 1980 are included where necessary. An attempt has been made to classify the compounds into categories containing pyridine, pyrrole, and pyran and thiopyran rings. Generally, a large volume of chemical literature is available for the pyridine and pyrrole compounds, but for most of the pyran and thiopyran compounds much less information is available. This is noted in the text where appropriate. 

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. 

Aromatic heterocycles such as thiophene, pyridine, and pyrrole are also able to form arene complexes, for example (7j5-C4H4N)(7j5-CsHs)Fe (azaferrocene), (7j5-C4H4S)Cr(CO)3, and (tj6-CsH5N)W(CO)3. 

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