Pyridazines protonation, basicity

The pH-independence of Tdhpz at Pt indicates that the driving force for coordination of the nitrogen heteroatom to the Pt surface is much larger than that for protonation even in molar acid. This behavior is in contrast to that of pyridine, where protonation of the nitrogen heteroatom in molar acid hinders N-coordination to the surface (H). Such a difference in chemisorption characteristics may be related to the fact that the basicity of the nitrogen heteroatom in pyridine (pKb =8.8) is much greater than that of the nitrogens in pyridazine (pKb = 11.8) (23.). ... 

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). 

Relative rates have been determined for the competitive methylations and also acetylations of azines. Pyridazine reacts faster than pyridines in both reactions this is interpreted in terms of pair-pair electron repulsion and the a-effect. An additivity approach provides reasonable predictions of isomer ratios of quatemization products of pyridazine and other azines. Reinvestigation of the quatemization of various amino- and diamino-pyridazines with methyl iodide shows that both 1- and 2-methyl derivatives were usually formed. 3-Amino-6-chloropyridazine forms JV2-quateraary salts with a- and -halo esters and 1,4-dibromobutane, but with 1 -dibromo-ethane or 1,3-dibromopropane bicyclic products, are formed. Protonation and quatemization of l,4,S,6-tetrahydropyridazines takes place at position 1, this being the more basic nitrogen. ... 

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... 

Protonation of (benzo)pyridazines has been mentioned in Section 6.01.4.2 and was reviewed in CHEC-I <84CHEC-l(3B)l>. Pyridazine (pA 2.3) is more basic than the other diazines due to reduced lone pair lone pair repulsion on formation of the cation. There is no equivalent to the benzene-like... 

The quaternization of (benzo)pyridazines by alkyl halides (these systems are not readily susceptible to arylation) was reviewed in CHEC-I <84CHEC-l(3B)l>. Monoquaternization of pyridazines occurs more readily than other diazines but less readily than pyridine, reflecting the intermediate basicity/nucleophilicity of pyridazine. Diquaternization of pyridazine can only be achieved with oxonium salts, particularly Me30 BF4 . As with protonation and A-oxidation, mixtures of products are often obtained on quaternization of unsymmetrical pyridazines and have been the subject of theoretical studies. A number of 2-(ribofuranosyl)-3(2//)-pyridazinones have been prepared by stannic chloride catalyzed alkylation of 3-(trimethylsilyloxy)pyridazines with protected 1-0-ace-tylribofuranose <83JHC369>. The quaternization behavior of phthalazines is similar to that of pyridazines, but with cinnolines alkylation usually occurs at N-2, unless there is a particularly bulky substituent at C-3. 

The gas and aqueous-phase basicities of pyrimidine are distinctly smaller by 3.4 and 1.1 pAi units, respectively, than those of pyridazine. A theoretical explanation has been proposed by considering important NH and lone pair electrostatic interactions that act from the 2-position. The proton-transfer equilibrium for the basicity comparison shows that the position of equilibrium is in the direction expected for the dominant effect to be the relief of the destabilization imparted by electrostatic repulsion between lone pair electrons, i.e., to the left in the equation (Equation (1)). Another significant contribution to AG° values is the field inductive effect of the electronegative aza substituent, which is less at the 3- than at the 2-position. This aza substituent effect destabilizes cations. Second-order attractive interactions between the lone pair electrons and the adjacent NH in the conjugate acid of pyridazine are also invoked. The attractive electrostatic interaction in the conjugate acid of pyridazine, and the predominant lone pair repulsion in pyridazine, are opposed by a favorable aza substituent effect. This accounts for the positive AG°(g) value. Solvation by water is expected to preferentially stabilize the neutral species or ion which is internally destabilized. The result is a smaller equilibrium shift in solution compared with the gas phase <86JA3237>. 

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