Zwitter ions

Decomposition of its internal salt (a zwitter-ion) provides a convenient source of benzyne for organic synthesis. 

The presence of certain substituents e.g., the amino group) may markedly affect the solubibty and other properties of the sulphonic acid or carboxylic acid. Thus such sulphonic acids as the aminobenzenesul-phonic acids, pyridine- and quinoline-sulphonic acids exist in the form of inner salts or zwitter-ions that result from the interaction of the basic amino group and the acidic sulphonic acid. Sulphanilic acid, for example, is more accurately represented by formula (I) than by formula (II) ... 

Because it contains amino and carboxylic groups rhodamine B tends to form zwitter ions which easily associate and can accumulate in lipophilic chromatogram zones. 

Irradiation of lomefloxacin 271 in dilute neutral aqueous solution (in which it exists as a zwitter ion) in Pyrex-filtered 500 W medium pressure mercury (Helios Italquartz) at 17°C gave pyrrolo[3,2,l-(/ ]quinoline 272 (99JOC5388). Under this condition, reductive defluorination via a radical anion took place. This study is important because of the phototoxicity of the fluorinated compounds which could be used as antibacterials (Scheme 49). 

Zwistigkeit, /. difference, dispute, discord. Zwitter, m. hermaphrodite hybrid bastard mongrel (Petrog.) zwitter. -ion, n. hybrid ion, amphoteric ion. 

Propanesultone also forms random and alternating copolymers with N-substituted ethylenimines276) and similar mechanisms involving zwitter ions were suggested. The polymerization through zwitter ions was performed with cyclic phosphonite as the Mn monomer and pyruvic acid as the ME monomer250). 

A report (62) has appeared of the reaction of PtCl with one peptide, glycyl-glycine. No reaction takes place when the peptide is in the zwitter-ion form but in KOH the free aminogroup can displace chloride. No cyclic compounds were obtained presumable because of the large ring size demanded. 

However, in a re-investigation of the reaction of benzyne with benzene 39>, it was shown that the original method of isolating benzene-diazonium-2-carboxylate resulted in the contamination of the zwitter-ion with silver salts 40>41). In the absence of silver ions biphenylene, and... 

Benzyne is thought to interact with simple ethers such as diethyl ether to form zwitter-ions. However, simple products analogous to those obtained with for example diethyl sulphide have not been detected 1). Apparently the more basic ether, 1,2-dimethoxyethane is cleaved by benzyne 130>. 

Products derived from intermediate zwitter-ions have been obtained in the reactions of benzynes with tertiary amines 1>. Benzyne generated by the reaction of -butyl-lithium with fluorobenzene interacts with AT.Af-dimethylaniline to yield iV-methyl diphenylamine and AT-ethyl diphenylamine 132,133). Using the reaction of chlorobenzene with n-butyl-lithium to generate benzyne resulted in the formation of increased amounts of 2-A7,AT-dimethylaminobiphenyl 132,133)... 

It is known that benzenediazonium-2-carboxylate decomposes to give benzyne via the zwitter-ion (128) 161>. We therefore checked that benzyne is involved in our reactions by carrying out reactions with cinnamaldehyde using benzyne generated from benzothiadiazole-1,1-dioxide 162), diphenyhodonium-2-carboxylate i 3,164)( weil as fr0m anthranilic acid165). Flavene was isolated from each reaction and hence our reactions do involve aiynes and are not arynoid 13 8). 

J. H., In vitro and in vivo evaluation of intestinal barriers for the zwitter-ions L-767,679 and its carboxyl ester prodrug L-775,318, Drug Metab. Disp. 1998, 26, 520-527. 

Analogs 11-13 are representative of new morphinan-derived zwitter-ions. The orally active 14-substituted ether (11) is 10-fold more potent than 2 in reversing morphine-induced decrease in GI motility in rat [41]. 

The first is called a zwitter ion while the second is a diradical. 

The zwitter ions are formed by a heterolytic cleavage of one of the bonds and the charges are stabilized by resonance. If the bond b—d is reformed, we get back the starting material. 

Dipolar species have been observed in the cycloaddition of polar intermediates. Thus cyclobutanes can be formed by non concerted processes involving zwitter ionic intermediates. The combination of an electron rich alkene (enamimes, enol ethers) and an alkene having electron withdrawing groups (nitro a cyano substituted alkenes) first gives a zwitter ion which can rotate about the newly formed bond before cyclization and gives both a cis and a trans adduct. 

In reactions with tetracyanoethylene, the stereochemistry of the double bond of an enol ether is retained in the cyclobutane product when the reaction is carried out in non polar solvents. In polar solvents, cycloaddition is non stereospecific because of the longer life time of the zwitter ion. 

Two possible courses have been proposed. In one case the intermediate is a four-membered ring, while in the other it is a five membered ring. Both the intermediates decompose to give a carbonyl compound and zwitter ion. 

The carbonyl compound and the zwitter ion can recombine to give the normal ozonide. 

A recently described approach involving zinc dust for eliminating acid allows acylation by 9-fluorenylmethoxycarbonyl chloride without dimer formation. The amino acid is dissolved in acetonitrile with the aid of hydrochloric acid, and zinc dust is added to destroy the acid and deprotonate the zwitter-ion, reducing the protons to gaseous hydrogen (Figure 3.16). Acylation is effected in the presence of zinc dust, which reduces the proton that is liberated by the reaction as soon it is formed. See Section 7.7 for another possible impurity in Fmoc amino acids.34,36-39... 

FIGURE 8.20 Peptides activated at an IV-methylamino-acid residue are postulated to epimer-ize because of the formation of the oxazolonium ion. Evidence for the latter resides in spectroscopic studies,96 and the isolation of a substituted pyrrole that was formed when methyl propiolate was added to a solution of Z-Ala-MeLeu-OH in tetrahydrofuran 10 minutes after dicyclohexylcarbodiimide had been added.95 The acetylenic compound effected a 1,3-dipolar cycloaddition reaction (B), with release of carbon dioxide, with the zwitter-ion that was generated (A) by loss of a proton by the oxazolonium ion. 

COOH group of the neutral acid. The situation is complicated, however, by the coexistence of the zwitter-ion with the neutral acid, so that the observed macroscopic constants K and K2 relate to equilibria as follows ... 

However, the situation for the latter acid was reconsidered in detail by van de Graaf, Hoefnagel and Wepster236. They obtained values of pK and pK2 (water, 25 °C) of 2.419 and 4.877 respectively by spectrophotometric measurements and calculated a value of pKd of 4.83 for the ionization of the neutral acid. (The ratio of zwitter-ion to neutral acid present is 10.5 89.5.) From this pKa value and 4.21 for the pKa value of benzoic acid, ap of NH2 is —0.62. This is the recommended value in the IUPAC report79. 

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