Pyrazines protonation, basicity

One of the very few exceptions to the rule that the acidity of the complexed ligand exceeds that of the free ligands involves the Ru(II) complexes shown in Table 6.5. It is believed that back bonding from the filled iig orbitals of Ru(II) to unoccupied tt-antibonding orbitals of the ligands more than compensates for the usual electrostatic effects of the metal that makes the nitrogen less basic. This tt-bonding is less likely with the Ru(III) complex and its is lower than that for the protonated pyrazine (see also Sec. 6.3.3. for the effects of Ru(II) and Ru(III) on hydrolysis of nitriles). ... 

The proton affinities of the pyrido[2,3-/ ]pyrazine system for N-1 = 205.56, N-4 = 212.02, and N-5 = 216.32 kcal moP showed that the most basic site is at N-5, which is in agreement with the formation of the quaternary salt derivatives 16-19 as intermediates for the synthesis of imidazopyridopyrazine fused rings <1994H(38)283, 1991JCC675>. 

Interestingly, the second electronegative heteroatom reduces the capacity of the diazines to tolerate the positive charge resulting from protonation. Pyridazine 10.1 (pKa= 2.24), pyrimidine 10.2 (pAfa = 1.23), and pyrazine 10.3 (pA a = 0.51) are all far less basic than pyridine (pKa - 5.23). 

This section covers primary, secondary, tertiary, and quaternary aminopyrazines (both nuclear and extranuclear) but not (functionally substituted amino)pyrazines such as hydrazino-, hydroxyamino-, or azidopyrazines. General discussions have appeared on the spectra of 2-pyrazinamine,255 257 991 the proton-sponge properties of 2,3,5,6-tetra(pyridin-2-yl)pyrazine in relation to its fine structure,925 the fluorescene properties of 3,6-diamino-2,5-pyrazinedicarboxylic acid derivatives in relation to their fine structures,1646,1659 the basic properties of aminopyrazines and other such azines in relation to their electronic structures,412,928 and the fine structures of 3-amino-2-pyrazinecarboxylic acid1340 and l,4-diacetyl-2,3-diphenylpiperazine.559... 

The 1,2,5-thiadiazole nucleus is extremely weakly basic and exhibits an ultraviolet spectrum in concentrated hydrochloric acid identical to that in water. A bathochromic shift of 9 m a in the spectrum taken in 96 % sulfuric acid indicates some protonation of the ring in that solvent. 1,2,5-Thiadiazole is a much weaker base than pyrazine (piTa 0.6) and probably has a pAa well below zero. The very low basicity of pyrazine was explained by Albert et ai. as being related to the... 

Aminopyrazine is a yellowish crystalline solid with m.p. 118-120 (420). It is a weak base with reported pAj, values of 3.14 (123) and 2.96 (821) (others are recorded in Chapter X). The similarity in the ultraviolet spectra (in water) of the neutral molecules of 2-amino-, 2-methylamino-, and 2-dimethylaminopyrazines, and of their monocations, and their similar basic strengths (2.96,3.42,3.27) (821) supports the conclusion that in aqueous solution 2-aminopyrazine exists mainly in the amino form (20) (821). The ultraviolet spectrum of 2-aminopyrazine cation differs from that of the neutral molecule of pyrazine, thus indicating that protonation does not take place at the extranuclear nitrogen atom (821) 2-aminopyrazine in fact protonates at Ni (see below). 

Aminopyrazine is a stronger base than pyrazine moreover, 2-amino-, 2-methylamino-, and 2-dimethylaminopyrazine have closely similar basic strengths, which supports the conclusion that, in aqueous solution, 2-aminopyrazine exists mainly in the amino form (1) (821). Ultraviolet spectral evidence (see Section VIII. 1C) indicates that the protonation does not take place at the extranuclear amino group (821). This and other evidence (p.m.r.) (1136) are consistent with monoprotonation of 2-aminopyrazine at Ni, and the second protonation at N4. 2,3-Diaminopyrazine (pAg 4.88) is a much stronger base than 2-aminopyrazine, but... 

The diazines, pyridazine (p/faH 2.3), pyrimidine (1.3), and pyrazine (0.65) are essentially mono-basic substances, and considerably weaker, as bases, than pyridine (5.2). This reduction in basicity is believed to be largely a consequence of destabilisation of the mono-protonated cations due to a combination of inductive and mesomeric withdrawal by the second nitrogen atom. Secondary effects, however, determine the order of basicity for the three systems repulsion between the lone pairs on the two adjacent nitrogen atoms in... 

The acidity and basicity, particularly of pyridazine derivatives, has been reviewed in CHEC-I <84CHEC-i(3B)i>. Pyridazine (pA, 2.3) is less basic than pyridine (pAa 5.2) but more basic than the other diazines (pyrimidine 1.3, pyrazine 0.6) perhaps because of repulsion between the adjacent nitrogen lone pairs. For comparison, the pAaS for proton gain by phthalazine and cinnoline are 3.5 and 2.3, respectively. Pyridazin-3(2//)-one is about as acidic as phenol with a pAa of 10.5, while the... 

The proton affinity of (la) has been calculated using ST03-21G-HG, MNDO, and AMI methods, and the results suggested that (la) has almost the same basicity as pyrazine and 1,2,4-triazine, and is more basic than 1,3,5-triazine <88MI 6l0-0l>. 

The aromatic nitrogen atoms of the pyrazine and quinoxaline are only weakly basic. Since neither of the lone pair of electrons are part of the aromaticity of the molecule, either nitrogen can be protonated. Upon protonation the aromatic rings have a higher acidity value than any of the diazine isomers. ... 

One finds that pH influences both the taste and the aroma of a food. In terms of taste, hydrogen ion concentration is generally linked to the tartness of a food the lower the pH, the more tart the food tastes. While the effect of pH on taste is well recognized, pH also influences the release of some aroma chemicals, i.e., those that act as acids or bases. For example, one would expect the contribution of volatile acids to aroma to be enhanced in aqueous solution at lower pHs, i.e., those below the pKa of the acid. At low pHs, the acid would be in its protonated form (not ionized) and thus be less soluble in the aqueous phase. This would tend to drive the acid into the sample headspace, increasing its contribution to aroma. Basic odorants (e.g., amines or pyrazines) would behave in an opposite manner. These compounds would become more soluble in the aqueous phase below their pKa since they would be ionized and thus more soluble. This would decrease their contribution to aroma at low pHs. The effect of pH on aroma is obvious when one increases the pH of a traditional acidic food or tries to produce a good chocolate flavor in low pH foods (typically neutral or slightly basic). 

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