Pseudo-first-order rate constants for the decarboxylation of 3-hydroxy- and 3-amino- picolinic acids in aqueous solution at 150 °C were determined and plotted as a function of acidity. Each rate profile has a maximum at an acidity well above the isoelectric point and this is attributed to decarboxylation of an intermediate protonated at the 2-position, analogous to the intermediates involved in the decarboxylation of salicylic and anthranilic acids. There is also a shoulder on each rate profile at a lower acidity corresponding to the isoelectric point where the Hammick ylide mechanism has a rate maximum in most picolinic acid decarboxylations. It is concluded that 3-hydroxy- and 3-aminopicolinic acids decarboxylate by the ylide mechanism at low acidity and by the protonation mechanism at higher acidities. In agreement with this interpretation, the 13C kinetic isotope effect in 3-hydroxypicolinic acid decarboxylation is 2.0% on the ylide part of the curve, 1.3% where decarboxylation of the protonated intermediate is rate determining, and drops to 0.4% in the intermediate region. Comparison of the rate constants for ylide decarboxylation with those for other 3-substituted picolinic acids shows that 3-hydroxy and 3-amino substituents facilitate decarboxylation, probably by their inductive and field effects on the developing negative charge at the 2-position of the transition state.

The mechanism of catalysis of aromatic chlorination by pyridine was investigated by measuring the rates of chlorination of toluene in acetic acid with and without added pyridine, pyridinium nitrate, or lithium chloride. All three increase the rate of chlorination slightly and to about the same extent. The effect on the second-order rate constant for chlorination of p-chloranisole in chloroform was determined for pyridine, pyridinium chloride, N-ethylpiperidinium chloride, tetra-n-butylammonium chloride, and tetra-n-butylammonium perchlorate. Again, all additives increase the rate constant, with the increase being least for pyridine. It is concluded that, for chlorination in dilute solution, pyridine has no specific catalytic effect, but probably increases the rate by increasing the polarity of the medium. Tetra-n-butylammonium chloride was observed to have a decreasing accelerating effect on chlorination in chloroform as its concentration is increased. This was thought to be the result of complexation of chlorine as trichloride. The formation constant for tetra-n-butylammonium trichloride in chloroform was found by the Benesi–Hildebrand spectrophotometric method to be 17 ± 3 M−1. This, together with the previously determined value of 9 × 104 M−1 for the corresponding tribromide, shows that the order of stability of trihalides in nonaqueous solvents is [Formula: see text] contrary to an earlier report.

The first-order rate constants for decarboxylation of picolinic and five substituted picolinic acids in buffered aqueous solution at 150° and ionic strength 1.0 increase as pH increases above 0, go through a maximum at pH near 1, then level off at about half the maximum. For quinolinic acid at 95° the rate maximum occurs at the isoelectric pH. It is therefore concluded that the anion decarboxylates about half as fast as the isoelectric species. Anion and isoelectric species show similar carboxyl-carbon kinetic isotope and substituent effects, so they probably decarboxylate by similar mechanisms. The methyl betaine of picolinic acid decarboxylates about 200 times faster than the anion. From these facts it is concluded that the isoelectric species which decarboxylates is probably zwitterion rather than neutral acid, and that anion and zwitterion decarboxylate by loss of carbon dioxide to form 2-pyridyl carbanion and ylid, respectively. The slower decarboxylation of isoelectric species compared to betaine suggests that only a small fraction of the isoelectric species is zwitterion. However, qualitative estimates from spectra of the fraction of zwitterion present in the isoelectric species at 150° suggest that this cannot be the whole explanation. The relative reactivities of the 2-and 4-positions are similar for decarboxylation and hydrogen exchange in pyridinium ions, but not in the unprotonated species.

Pseudo-first-order rate constants for the decarboxylation of pyrimidine-2-carboxylic acid have been determined at 65 °C in aqueous solution over the acidity range pH = 2 to H0 = −9.5. Rate constants increase rapidly from pH = 2 to H0 = −3, then remain constant. This behaviour can be accounted for by a Hammick-type mechanism in which monoprotonated pyrimidine-2-carboxylic acid loses carbon dioxide to form an ylide (stabilized by the adjacent positively charged nitrogens) which rapidly converts to pyrimidine.

The mechanism of catalysis of aromatic bromination by pyridine was investigated by measuring the rates of bromination of mesitylene in acetic acid and in chloroform with and without added pyridinium or other substituted ammonium salts. Most salts increased both the second- and third-order rate constants for bromination, and pyridinium salts were no more effective than others. Bromide salts decreased the rate and sometimes the order of the bromination reaction by complexing bromine as tribromide. The formation constants of pyridinium tribromide and tetra-n-butylammonium tribromide in chloroform at 25.0° were found to be 2 × 102 and 9 × 104 M−1 respectively. It is concluded that in dilute solution pyridine catalysis of bromination is simply a salt effect which can be accounted for by the commonly accepted mechanism of bromination.

The composition and melting points of the bromine adducts of pyridinium bromide have been determined. Differential scanning calorimetry has been found to be particularly well suited to this type of phase study because it uses small, enclosed samples and responds rapidly to small heat changes. The adducts are described in terms of stoichiometric mixtures of pyridinium bromide and pyridinium tribromide, or in terms of a general formula PyHBr(Br2)n where n equals 1/3, 1/2, 2/3, 1, 3, 6, 18. When pyridinium bromide is allowed to pick up bromine isothermally in an apparatus for thermogravimetric analysis it does so in a stepwise manner with a plateau for each of the above adducts plus one with n equal to 3/2. This provides valuable confirmation of the compositions of adducts deduced from conventional phase diagrams.

The mass spectra of acylanhydronucleosides suggested that the acyl groups undergo a thermal rearrangement. This was confirmed by studying the melting profiles of these compounds in a differential scanning calorimeter. The results have led to a convenient synthesis of 5′-acetylanhydrouridine.

The decarboxylation of pyrrole-2-carboxylic acid in aqueous buffers at 50° and ionic strength 1.0 has been found to be first order with respect to substrate at a fixed pH. As the pH is decreased, the rate constant increases slightly in the pH range 3–1, then rises rapidly from pH 1 to 10 M HCl. The 13C-carboxyl kinetic isotope effect is 2.8% in 4 M HClO4 and negligible at pH ~ 3. These observations can be accounted for by a mechanism, previously proposed for the decarboxylation of anthranilic acid, in which the species undergoing decarboxylation is the carboxylate ion protonated at the 2-position of the pyrrole ring. This intermediate can be formed both by ring-protonation of the carboxylate anion and by ionization of the ring-protonated acid. At low acidities ring-protonation is rate determining, but at higher acidities the rate of protonation exceeds that of decarboxylation.

Chemischer Informationsdienst. Organische ChemieVolume 2, Issue 8 Heterocyclic Compounds ChemInform Abstract: MECHANISMUS DER DECARBOXYLIERUNG VON SUBSTITUIERTEN ANTHRANILSAEUREN BEI HOHER ACIDITAET (4-METHYL-, 4-METHOXY- UND UNSUBSTITUIERTE ANTHRANILSAEURE IM PH-BEREICH 2,5-3,8, KINETIK, ISOTOPENEFFEKTE) G. E. DUNN, G. E. DUNNSearch for more papers by this authorS. K. DAYAL, S. K. DAYALSearch for more papers by this author G. E. DUNN, G. E. DUNNSearch for more papers by this authorS. K. DAYAL, S. K. DAYALSearch for more papers by this author First published: February 23, 1971 https://doi.org/10.1002/chin.197108189AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. Volume2, Issue8February 23, 1971 RelatedInformation

Protonation of 20 α,β-unsaturated ketosteroids by sulfuric acid was studied by ultraviolet spectrophotometry. Plots of log [B]/[BH+] from spectral data against the amide acidity function, HA, gave straight lines with unit slope. The pKBH+ values thus obtained show the same additive effects of substituents as that reported previously for simple α,β-unsaturated alicyclic ketones.

The rates of decarboxylation of 4-methyl-, 4-methoxy-, and unsubstituted anthranilic acids have been determined in aqueous buffers over the pH range 2.5–3.8. Electron-releasing substituents increase the rates of ring-protonation about equally for an acid and its anion, and decrease the ratio of decarboxylation to deprotonation of the protonated acid. Rates, 13C-carboxyl kinetic isotope effects, and deuterium solvent isotope effects have been determined for the decarboxylation of anthranilic acid in aqueous sulfuric acid up to 10 M. No evidence for decarboxylation by cleavage of the unionized carboxyl group was obtained.

AbstractDie CO‐Valenzschwingungsbanden der Benzoate (I) (41 Verbindungen) ergeben mit den entsprechenden Hammett‐Substituentenkonstanten keine eindeutige Relation.

AbstractDie Protonierung von 20 α,β‐ungesättigten Oxosteroiden, z.B. Testosteron (Ia), Progesteron (Ib), Cortison (II) bzw. verschiedenen ihrer Derivate durch Schwefelsäure wird UV‐spektrometrisch untersucht.

The protonation of 14 α,β-unsaturated alicyclic ketones, B, by sulfuric acid leads to values of log [B]/[BH + ] which, when plotted against the amide acidity function, H A , give straight lines of unit slope. The [Formula: see text] values thus obtained show substituent effects which are additive and can be interpreted in terms of polar and resonance effects.

Infrared spectra in the frequency region 1300–1760 cm−1 are reported for 41 substituted sodium benzoates and 10 substituted sodium salicylates in deuterium oxide solution, and for 9 substituted salicylic acids in chloroform and carbon tetrachloride solutions. Carboxylate stretching frequencies of benzoates and salicylates correlate poorly with substituent constants, but the asymmetric frequencies of benzoates and salicylates correlate well with each other, and the asymmetric frequencies of benzoates correlate well with the asymmetric frequencies of the corresponding nitrobenzenes. It is suggested that, among substituted aromatic compounds, group vibrations which couple with the ring vibrations may correlate well with similar vibrations of other groups, but not with coupled vibrations of different symmetry, uncoupled vibrations, or substituent constants. Chelation in chloroform solutions of salicylic acid dimers can be detected by its influence on substituent effects, but infrared spectra provide no good evidence for chelation in aqueous sodium salicylates.

The 13C-carboxyl kinetic isotope effect on decarboxylation of 4-methoxyanthranilic acid has been determined in aqueous solutions of ionic strength 0.50 at 60 °C. The isotope effect, 100(k12/k13 −1), is found to be 4.2% at pH −0.3, 1.4% at pH 1.3, and zero at pH 4.0. This information makes it possible to decide between two mechanisms previously proposed in favor of the one in which both anion and neutral acid are protonated at carbon-1 of the aromatic ring but only the protonated anion decarboxylates.

First-order rate constants for the decarboxylation of fourteen 4- and 5-substituted salicylic acids have been determined in quinoline solution in the temperature range 90–230 °C. Substituents have almost no effect on the rate constants, except those with large negative σ-constants: p-amino, p-hydroxy, p-ethoxy. The enthalpies and entropies of activation do not fit the isokinetic relationship, with the same three substituents deviating. It is suggested that the decarboxylation involves a preliminary ionization of the carboxyl group, followed by protonation of the aromatic ring of the anion so formed, and then loss of carbon dioxide. The isokinetic relationship fails because substituents affect all three steps differently, and the Hammett relationship fails because the substituent effect on the ionization is related to σ while that on the other two steps follows σ+. The three substituents which deviate are those for which σ and σ+ differ widely.

The protonation of a number of aromatic and α,β-unsaturated aliphatic aldehydes, ketones, and carboxylic acids in sulfuric acid has been found to obey the HA acidity function, rather than H0.