Zwitterionic form

Some 4,5-disubstituted pyridazines exhibit ring-chain isomerism involving heterospiro compounds. For example, 5-(o-aminophenylcarbamoyl)pyridazine-4-carboxylic acid exists in a zwitterionic form in the solid state, but in a solution of DMSO it is almost exclusively 3, 4 -dihydro-3 -oxospiro[pyridazine-5(2//),2 (l //)-quinoxaline]-4-carboxylic acid (134). The equilibrium is strongly influenced by the nature of the solvent, the substituents on the pyridazine ring and the nucleophilicity of the group attached to the phenyl ring (Scheme 48) <80JCS(P2)1339). 

The 4-substituted analogs can exist in two uncharged tautomeric forms (141) and (142) and, in addition, in the zwitterionic form (143), but all the evidence shows that the compounds all exist predominantly in the NH2 or OH form (141). 

Isoelectric point (Section 27.3) pH at which the concentration of the zwitterionic form of an amino acid is a maximum. At a pH below the isoelectric point the dominant species is a cation. At higher pH, an anion predominates. At the isoelectric point the amino acid has no net charge. 

The electronic spectrum of a compound arises from its 7r-electron system which, to a first approximation, is unaffected by substitution of an alkyl group for a hydrogen atom. Thus, comparison of the ultraviolet spectrum of a potentially tautomeric compound with the spectra of both alkylated forms often indicates which tautomer predominates. For example, Fig. 1 shows that 4-mercaptopyridine exists predominantly as pyrid-4-thione. In favorable cases, i.e., when the spectra of the two alkylated forms are very different and/or there are appreciable amounts of both forms present at equilibrium, the tautomeric constant can be evaluated. By using this method, it was shown, for example, that 6-hydroxyquinoline exists essentially as such in ethanol but that it is in equilibrium with about 1% of the zwitterion form in aqueous solution (Fig. 2). 

Ratio of the Zwitterion Form to the Hydroxy Form (pAy) for /3-Hydroxypyeidines... 

The changes found in the ratio of the zwitterion to the hydroxy form for )9 hydroxypyridines with fused benzene rings have been discussed by Mason. The proportion of the zwitterion form decreases... 

The ultraviolet spectrum of vitamin Be, or pyridoxine, measured in aqueous ethanol varies with the composition of the solvent indicating that this compound is in equilibrium with the zwitterion form 38. The equilibrium constant in pure water was obtained by extrapolation. Prior to this, equilibria which involved tautomers of type 39 had been suggested for vitamin Be, but see Section VI,A. In the case of pyridoxal, an additional equilibrium, 40 41, occurs (cf. Section VIII) other pyridoxal analogs have also been studied (Table II). 

The structure of malonyl-a-aminopyridine (cf. 121) has been discussed by Snyder and Robinson/ who interpreted the infrared and ultraviolet spectra and the fact that it could be converted into a monochloro derivative (122, R = Cl) to indicate that the intra-molecularly hydrogen-bonded hydroxy form 122 (R = OH) was predominant. However, comparison of the basicities of the methoxy compound 122 (R = OMe), the mesomeric betaine 123 (R = Me), and the parent compound indicates that in aqueous solution the last exists mainly in the zwitterion form 123 (R = H), ... 

Sheinker and Pomerantsev one of the protons remains bonded to a hetero nitrogen atom in the monoanion of 127. 2,5-Dihydroxypyra-zines could exist in a dioxo form (128) or in a zwitterion form (129), and, although structure 128 was assigned to the 5-butyl derivative in 1927, the evidence for structure 128 as opposed to 129 is inconclusive. 

The type of extended quinonoid form (cf. 133), if any, which can stabilize the zwitterion form is shown. 

Mercaptopyridine and 3-mercaptoquinoline have been shown to exist predominantly in the zwitterion form (e.g., 204) by ultraviolet spectral comparisons and pK measurements (cf. Table V). 

The ultraviolet spectra of the pyridinecarboxylic acids (334) were initially interpreted assuming that the proportion of the zwitterion structure 335 was not appreciable,and the early pK work was inconclusive. However, Jaffe s calculations based on the Hammett equation indicated that about 95% of nicotinic and isonicotinic acids existed in the zwitterion form, and ultraviolet spectral data showed that the actual percentages of picolinic, nicotinic, and isonieotinie acids existing in the zwitterion form in aqueous solution are 94, 91, and 96%, respectively.This was later confirmed by Stephenson and Sponer, who further demonstrated that the proportion of the zwitterion form decreases in solvents of low dielectric constant, becoming very low in ethanol. Dipole moment data indicate that isonicotinic acid exists as such in dioxane, and 6-hydroxypyridine-3-carboxyiic acid has been shown to exist in form 336 u.sing pK data. ... 

Free nicotinic acid can exist in neutral (21) and in zwitterion forms (22). On reaction with acid either form is converted into the same... 

As shown by an H NMR study (77BSB967), A-methyl derivatives of 5-mercaptoimidazole exist in the thione form 176a in chloroform. According to results obtained in (82KGS957), the zwitterionic form 176b should not be excluded from consideration for the compounds 176 (R" = CONH2, CSNH2). 

The combination of positive and negative charges within the same molecule causes a more complicated situation, which obviously has not been well-defined to date. A quite large number of pyrrolizidine alkaloids are related to Otonecine (8) (Scheme 3). Spectroscopic investigations show that these alkaloids exist in the nonionized form in CDCI3, and in the zwitterionic form in D2O (00JNP857, 71TL3421). The dipolar structure is the result of an intramolecular interaction between a nucleophilic and an electrophilic center. 

Zero order reaction A reaction whose rate is independent of reactant concentration, 289,295-298, 317q Zinc, 86-87,550 Zn-Cn2+ voltaic cell, 481-485 Zwitterion Form of an amino acid in which there is a separation of charge between the nitrogen atom of the NH2 group (+) and one of the oxygen atoms of the COOH group (—), 623-624... 

The problem of the structure of 1,2- and 1,4-quinone diazides was investigated by Le Fevre s group (1949, 1954) by measuring dipole moments. The observed moments in benzene are in the range 2.9 to 5.0 D, compared with calculated values of 1.6 to 4.0 D for the quinone diazide structure and 15.7 and 27.4 D respectively for the 1,2-and 1,4-zwitterionic forms. No attempts were made by Lowe-Ma et al. (1988) to calculate dipole moments for the mesomeric structure 4.4 that they proposed. 

L), the IR spectrum of which indicated that it exists in a zwitterionic form. Thus, reaction of L with one mole, or two moles, or protonic acid produces and L, respectively (XXII). 

Ledaal and co-workers (101-105) have proposed a linear free energy relationship for predicting the percent zwitterion formed at the rth carbon atom in substituted quinones, substituted dibenzoylethylenes, and substituted acetylenes. Fliszar and Granger (106) have proposed the equation... 

On several occasions the product isolated by the submitters was contaminated with L-cystine dihydrochloride, which was not easily removed by recrystallization. In this event the product was converted to the zwitterionic form and recrystallized in the following manner. The pH of a solution of the product in water was adjusted to 6 with aqueous 2.5N potassium hydroxide. The neutralized solution was evaporated to dryness under reduced pressure at ca. 40°. The residue was dissolved in a minimum amount of hot water, and two volumes of 95% ethanol were added to precipitate S-acetamidomethyl-L-cysteine monohydrate, dec. 187°, [a] 9 — 42.5° (c = 1, water). 

The present procedure provides a convenient method for preparing S-acetamidomethyl-L-cysteine hydrochloride." The zwitterionic form may be obtained readily from the hydrochloride by... 

C17-0120. In aqueous solution, amino acids exist as zwitterions (German for double ions ), compounds in which internal proton transfer gives a molecule with two charged functional groups. Use Lewis structures to illustrate the proton transfer equilibrium between the uncharged form of glycine (NH2 CH2 CO2 H) and its zwitterion form. 

The zwitterionic form of monoethyl phosphate is unlikely to have a significant lifetime because loss of a proton from cationic oxygen would be very fast. 

The activation free energies computed both in the gas phase and in aqueous solution (Table 2.6) suggest that the generation of an alkylating QM (QM-NI) becomes a much easier process, passing from the protonated quaternary ammonium salt NI to its zwitterionic form NI. ... 

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