Reactivity values pyridines

A systematic and intensive theoretical study of reactivity has been reported by Brown and his colleagues,8,115,139-142 who discussed the reactivity of pyridine, quinoline, and isoquinoline in terms of localization energies. They investigated the values of these indices, first of all for electrophilic substitution, with regard to the value of the Coulomb integral of the heteroatom orbital and the orbitals adjacent to it (auxiliary inductive parameters). They demonstrated that the course of electrophilic substitution can be estimated from theoretical reactivity indices if 77-electron densities are used for reactions that occur readily and localization energies for those occurring only reluctantly. 

This gas-phase reaction provides the only method currently available for determining hydrogen-bonded pyridine free base. The method requires neither assumptions, extrapolations, nor approximations the p factor of the reaction is sufficiently small that the reactivities of the pyridine and benzene derivatives can be compared directly. The method was first introducted for determining the electrophilic reactivity of pyridine [62JCS4881 71JCS(B)2382] using 1-arylethyl acetates (9.109). Subsequent determinations used I-aryl-l-methylethyl acetates. (9.110) and i-arylethyl methyl carbonates (9.111) [79JCS(P2)228],... 

Hydrogen bonding substantially reduces the reactivity of pyridine N-oxide so that o+ values determined for the 2- and 4-positions from solvol-... 

Pyridine N-oxide. A special case of aromatic electrophilic substitution is provided by the ambident reactivity of pyridine /V-oxidc 4.55. Klopman used Equation 3.4 to calculate the relative reactivity (AE values) for electrophilic attack at the 2-, 3- and 4-positions as it is influenced by the energy of the LUMO of the electrophile. He obtained a graph (Fig. 4.8) which shows that each position in turn can be the most nucleophilic. At high values of / , - Es (hard electrophiles), attack should take place at C-3 at lower values of / , - Es, it should take place at C-4 and, with the softest electrophiles, it should take place at C-2. Attack at each of these sites is known the hardest electrophile SO3 does attack the 3-position, the next hardest (NC>2+) the 4-position, and the softest (HgOAc+) the 2-position. 

Kruszewski and Krygowski36 have calculated the value of DEsp (Section II,A,3a) to be 0.350 (benzene = 0.333) and the Ai value (Section II,B) to be 1.0 Julg65 reports a value for A of 0.97 (benzene = 1). At the same time they showed that the KK values (Section II,E) for both benzene and pyridine are 3.53. The decreased reactivity of pyridine (relative to benzene) towards electrophiles is reflected in the value of +23 for Balaban and Simon s aromaticity constant169 (Section II,F, 1). Finally, Berezin162 has calculated the coefficient of influence (Section II,F, 3) of pyridine to be 1.987 (benzene 2.130) but the interpretation here seems somewhat difficult. 

The precise numerical values of the calculated electron densities are unimportant, as the most important feature is the relative electron density thus, the electron density at the pyrazine carbon atom is similar to that at an a-position in pyridine and this is manifest in the comparable reactivities of these positions in the two rings. In the case of quinoxaline, electron densities at N-1 and C-2 are proportionately lower, with the highest electron density appearing at position 5(8), which is in line with the observation that electrophilic substitution occurs at this position. 

Relative reactivity wiU vary with the temperature chosen for comparison unless the temperature coefficients are identical. For example, the rate ratio of ethoxy-dechlorination of 4-chloro- vs. 2-chloro-pyridine is 2.9 at the experimental temperature (120°) but is 40 at the reference temperature (20°) used for comparing the calculated values. The ratio of the rate of reaction of 2-chloro-pyridine with ethoxide ion to that of its reaction with 2-chloronitro-benzene is 35 at 90° and 90 at 20°. The activation energy determines the temperature coefficient which is the slope of the line relating the reaction rate and teniperature. Comparisons of reactivity will of course vary with temperature if the activation energies are different and the lines are not parallel. The increase in the reaction rate with temperature will be greater the higher the activation energy. 

From the relative reactivities, together with the isomer ratios for the phenylation of pyridine, it is possible to calculate the reactivity of each position in the pyridine ring compared with that of any one position in benzene (the partial rate factor). Thus, using the value of 1.04 for the relative reactivities obtained by Augood et al and the isomer ratios (2-, 58 3-, 28 4-, 14) obtained by Dannley and Gregg, the partial rate factors for the three positions in pyridine are 2-, 1.8 3-, 0.87 4-, 0.87. It is doubtful, however, whether much... 

However, an evaluation of the observed (overall) rate constants as a function of the water concentration (5 to 25 % in acetonitrile) does not yield constant values for ki and k2/k i. This result can be tentatively explained as due to changes in the water structure. Arnett et al. (1977) have found that bulk water has an H-bond acceptor capacity towards pyridinium ions about twice that of monomeric water and twice as strong an H-bond donor property towards pyridines. In the present case this should lead to an increase in the N — H stretching frequency in the o-complex (H-acceptor effect) and possibly to increased stabilization of the incipient triazene compound (H-donor effect). Water reduces the ion pairing of the diazonium salt and therefore increases its reactivity (Penton and Zollinger, 1971 Hashida et al., 1974 Juri and Bartsch, 1980), resulting in an increase in the rate of formation of the o-complex (ik ). 

Nucleophilic reactivity toward Pt(II) complexes may be conveniently systematized via linear free energy relationships established between reactions of trans Ptpy2Cl2 (py = pyridine) with various nucleophiles and reactions of other Pt(II) complexes with the same nucleophiles. First, each nucleophile is characterized by a nucleophilicity parameter, derived from its reactivity toward the common substrate, trans Ptpy2Cl2. Reactivity toward other Pt(II) substrates is then quite satisfactorily represented by an equation of the form (21), wherein ky is the value of in the reaction with nucleophile Y... 

One may reliably assume that the elusive nature of borabenzene cannot be attributed to insufficient aromaticity which, according to HSE values, amounts to 78% of benzene s aromaticity. Rather, it will be explained by high reactivity due tp the tr-acceptor properties of a low-lying complexes with tr-donors. Note that, apart from pyridine, even dinitrogen may act as a o--donor [88AG(E)(27)295]. 

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