Pyridine lone pairs

The formal replacement of a CH in benzene by N leads to far-reaching changes in typical reactivity pyridines are much less susceptible to electrophilic substitution than benzene and much more susceptible to nucleophilic attack. However, pyridine undergoes a range of simple electrophilic additions, some reversible, some forming isolable products, each involving donation of the nitrogen lone pair to an electrophile, and thence the formation of pyridinium salts which, of course, do not have a counterpart in benzene chemistry at all. The ready donation of the pyridine lone pair in this way does not destroy the aromatic... 

Figure 5. A possible superposition of pyridyl ether 11 (dark carbon atoms) and (5)-nicotine (light carbon atoms). "Du" represents a point on the receptor that could be interacting with the pyridine lone pair. Conformations were analyzed and overlays were performed using Chem 3D .

The of the conjugate acid of pyridine is 5.25, lower than that of an alkyl amine because the pyridine lone pair is in a relatively electronegative sp orbital. 

Presently, the only known example is azacahx[3]pyridine 8a [19]. In the solid state, it adopts a triangular shape with approximate Cs symmetry (Fig. 2). One pyridine ring is oriented to a different direction from the remaining two pyridine rings to avoid the electrostatic repulsion between the pyridine lone pairs in the cavity. 

Two azacalix[6]pyridines, 7d [ 18] and 8d [ 19], have thus far been investigated. In the solid state, both azacalix[6]pyridines adopt roughly triangular shapes, though the molecular geometries are different from each other to some extent, as shown in Fig. 7. The pyridine rings of 7d and 8d are arranged to minimize the electrostatic repulsion between the pyridine lone pairs, as in the case of azacalix[3]pyridine 8a (Sect. 3.1.1). 

Fig. 1-6). The structure obtained for thiazoie is surprisingly close to an average of the structures of thiophene (169) and 1,3,4-thiadiazole (170) (Fig. 1-7). From a comparison of the molecular structures of thiazoie, thiophene, thiadiazole. and pyridine (171), it appears that around C(4) the bond angles of thiazoie C(4)-H with both adjacent C(4)-N and C(4)-C(5) bonds show a difference of 5.4° that, compared to a difference in C(2)-H of pyridine of 4.2°, is interpreted by L. Nygaard (159) as resulting from an attraction of H(4) by the electron lone pair of nitrogen. 

In all its reactions the lone pair of thiazole is less reactive than that of pyridine. Table 1-61 shows three sets of physicochemical data that illustrate this difference. These are (1) the thermodynamic basicity, which is three orders of magnitude lower for thiazole than for pyridine (2) the enthalpy of reaction with BF3 in nitrobenzene solution, which is 10% lower for thiazole than for pyridine and (3) the specific rate of quaterni-zation by methyl iodide in acetone at 40°C, which is about 50% lower for... 

Bonati has classified the pyrazole complexes into two groups compounds containing neutral pyrazoles (HPz), called 2-monohaptopyrazoles since it is the N-2 pyridinic nitrogen lone pair which confers on them the ligand properties and compounds containing pyrazole anions (Pz) which can act as monodentate or, more often, as exobidentate ligands (72CRV497). 

The more recent results of Scheme 18 can be summarized as follows the less hindered isomer is formed unless the substituent has a lone pair, the electrostatic field of which enhances the nucleophilicity of the adjacent nitrogen atom. This is true not only for pyridine and pyrazole, but probably also for CHO and C02Et. 

The CNDO method has been modified by substitution of semiempirical Coulomb integrals similar to those used in the Pariser-Parr-Pople method, and by the introduction of a new empirical parameter to differentiate resonance integrals between a orbitals and tt orbitals. The CNDO method with this change in parameterization is extended to the calculation of electronic spectra and applied to the isoelectronic compounds benzene, pyridine, pyri-dazine, pyrimidine and pyrazine. The results obtained were refined by a limited Cl calculation, and compared with the best available experimental data. It was found that the agreement was quite satisfactory for both the n TT and n tt singlet transitions. The relative energies of the tt and the lone pair orbitals in pyridine and the diazines are compared and an explanation proposed for the observed orders. Also, the nature of the lone pairs in these compounds is discussed. 

CaveU and Chapman made the interesting observation that a difference exists between the orbital involved in the quatemization of aromatic nitrogen heterocycles and aromatic amines, which appears not to have been considered by later workers. The lone pair which exists in an sp orbital of the aniline nitrogen must conjugate, as shown by so many properties, with the aromatic ring and on protonation or quatemization sp hybridization occurs with a presumed loss of mesomerism, whereas in pyridine the nitrogen atom remains sp hybridized in the base whether it is protonated or quaternized. Similarly, in a saturated compound, the nitrogen atom is sp hybridized in the base and salt forms. 

Charton has recently examined substituent effects in the ortho position in benzene derivatives and in the a-position in pyridines, quinolines, and isoquinolines. He concludes that, in benzene derivatives, the effects in the ortho position are proportional to the effects in the para position op). However, he finds that effects of a-sub-stituents on reactions involving the sp lone pair of the nitrogen atoms in pyridine, quinoline, and isoquinoline are approximately proportional to CT -values, or possibly to inductive effects (Taft s a ). He also notes that the effects of substituents on proton-deuterium exchange in the ortho position of substituted benzenes are comparable to the effects of the same substituents in the a-position of the heterocycles. 

It is notable that pyridine is activated relative to benzene and quinoline is activated relative to naphthalene, but that the reactivities of anthracene, acridine, and phenazine decrease in that order. A small activation of pyridine and quinoline is reasonable on the basis of quantum-mechanical predictions of atom localization encrgies, " whereas the unexpected decrease in reactivity from anthracene to phenazine can be best interpreted on the basis of a model for the transition state of methylation suggested by Szwarc and Binks." The coulombic repulsion between the ir-electrons of the aromatic nucleus and the p-electron of the radical should be smaller if the radical approaches the aromatic system along the nodal plane rather than perpendicular to it. This approach to a nitrogen center would be very unfavorable, however, since the lone pair of electrons of the nitrogen lies in the nodal plane and since the methyl radical is... 

Pyridinium ylide is considered to be the adduct car-bene to the lone pair of nitrogen in pyridine. The validity of this assumption was confirmed by Tozume et al. [12J. They obtained pyridinium bis-(methoxycarbonyl) meth-ylide by the photolysis of dimethyl diazomalonate in pyridine. Matsuyama et al. [13] reported that the pyridinium ylide was produced quantitatively by the transylidalion of sulfonium ylide with pyridine in the presence of some sulfides. However, in their method it was not easy to separate the end products. Kondo and his coworkers [14] noticed that this disadvantage was overcome by the use of carbon disulfide as a catalyst. Therefore, they used this reaction to prepare poly[4-vinylpyridinium bis-(methoxycarbonyl) methylide (Scheme 12) by stirring a solution of poly(4-vinylpyridine), methylphenylsulfo-nium bis-(methoxycarbonyl)methylide, and carbon disulfide in chloroform for 2 days at room temperature. 

Figure 15.8 Pyridine and pyrimidine are nitrogen-containing aromatic heterocycles with tt electron arrangements much like that of benzene. Both have a lone pair of electrons on nitrogen in an sp2 orbital in the plane of the ring.

Note that nitrogen atoms have different roles depending on the structure of the molecule. The nitrogen atoms in pyridine and pyrimidine are both in double bonds and contribute only one tt electron to the aromatic sextet, just as a carbon atom in benzene does. The nitrogen atom in pyrrole, however, is not in a double bond and contributes two tt electrons (its lone pair) to the aromatic sextet. In imidazole, both kinds of nitrogen are present in the same molecule— a double-bonded "pyridine-like" nitrogen that contributes one v electron and a pyrrole-like" nitrogen that contributes two. 

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