THE IONIZATION AND SPECTRA OF PYRAZINES

Ionization constants of heterocyclic substances may be readily determined by potentiometric titration, spectroscopy (ultraviolet or visible), or conductivity (1456) and by p.m.r. spectroscopy (1457, 1458). Estimates of ionization constants may be obtained by calculation (1459-1461). They are essential data in practical heterocyclic chemistry and of immense use in the establishment of structures in potential tautomeric compounds. Albert (1462) gives a simple treatment of ionization constants as applied to heterocyclic chemistry. 

2-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 

Pyrazine Basic pAfl Acidic pAfl Refs. 

2-Methylsulfinyl- and 2-methylsulfonylpyrazines were weaker bases by 2.13 (1080) and 3.12 (1079) pH units, respectively, than pyrazine the electron withdrawal was thought to operate by the inductive and mesomeric mechanism. Protonation occurred at N4. Proton magnetic resonance studies show that 2-methoxycarbonylpyrazine also protonates at N4 (1136). 

As expected, amidinopyrazines (431) and guanidinopyrazines (1060) are relatively strong bases. 2-Carboxypyrazine has pA 3.92 (400) and Brown and Jacobsen (431) remark that the possibility that 2-amino-3-carboxypyrazines are zwitterionic cannot be excluded. 

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Ch. 8 Aminopyrazines, Their N Oxides, and Related Nitrogenous Derivatives Ch. 9 The PyrazinecarboxyUc Acids and Related Derivatives Ch. 10 The Ionization and Spectra of Pyrazines... 

Protonation of pyrazine A-oxides takes place at the unsubstituted ring nitrogen as revealed by examination of their UV spectra and ionization constants in water. The same holds for unsubstituted quinoxaline A-oxide and the 3-amino derivative. Pyrazine and quinoxaline di-A-oxides are protonated at one A-oxide oxygen atom (74KGS1554). 

Example The ionization spectra at the first ionization threshold of pyrazine as obtained by PI, MATI and ZEKE-PES are clearly different (Fig. 2.21). [92] The... 

Proton magnetic resonance measurements in dimethyl sulfoxide indicate that 2-aminopyrazine and its 3-methyl derivative exist predominantly in the amino form (979, 1086), in agreement with theoretical and experimental electronic spectra (1083). Proton magnetic resonance analysis of the methylation of 2-aminopyrazine with methyl iodide in dimethyl sulfoxide at room temperature showed it to be methylated 8.8 times as fast as pyrazine to give both 3-amino-l-methyl- and 2-amino-l -methylpyrazinium iodides in the ratio 2.9 I (666). Proton magnetic resonance spectra of ionized 2-aminopyrazine in liquid ammonia have also been reported (665). 

Ultraviolet spectra of numerous pyrazines have been recorded, but in many cases without regard to the effects of ionization, and in various solvents. All pyrazines are basic and thus have both neutral (e.g., 5) and cationic (e.g., 6) forms. Pyrazines with a substituent containing an ionizable hydrogen, such as a carboxy, hydroxy, or mercapto group, may also exist in the anionic form (e.g., 7), the tautomeric neutral form (e.g., 2, R = H), a potentially zwitterionic form (8, R = H) or an isomeric cationic form (e.g., 9, R = H). Many published spectra are in fact of mixed ionic species to determine the spectrum of each ionic form it is necessary to measure its spectrum in a solution buffered at least two units above or below the pAa value (or values) of the substance. In nonaqueous solvents, the neutral (uncharged) species are favored. The ultraviolet spectra of pure species may then serve to characterize the pyrazine, may permit the correlation of spectra with structure, and may be used in quantitative determinations. 

The photoelectron spectrum of pyridazine is similar to those of pyrazine, pyrimidine, and triazine i.e., the lowest ionization potential corresponds to ionization of a lone-pair electron. The ionization potential is in agreement with the calculated value. These spectra were recorded also of pyridazine 1-oxide and 1,2-dioxide, and it was found that the perturbation of the t-system by the N—O group results in the separation of the lower excited states of the AT-oxide ions. ... 

Laser-induced multiphoton ionization spectroscopy has been applied to the parent, methyl-, and chloro-substituted pyrazines <85ANC29ll). The ions produced by laser photoionization in the supersonic jet are mass-analyzed using a time of flight mass spectrometer, in which the spectra obtained reflect the absorption of the n-n transition. Mass-resolved excitation spectroscopy by laser ionization in the infrared region has also been applied to the conformational analysis of a-alkyl substituted pyrazines <92JA5269). Dynamic and structural properties of electronically excited states of pyrazine have been elucidated from high resolution laser spectroscopy with MHz resolution <88JST(173)201). 

Example The ionization spectra at the first ionization threshold of pyrazine as obtained by PI, MATI, and ZEKE-PES are clearly different (Fig. 2.22) [101]. The PI spectrum is a plot of ion current vs. wavelength of the probe laser. PI spectra show a simple rise of the curve at IE, while MATI and ZEKE yield a sharp peak at ionization threshold plus additional signals from lower vibrational ionization thresholds. 

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