Carboxylic acid derivatives equilibrium

By methods analogous to those used for the tetrahedral intermediates related to carboxylic acid derivatives, Guthrie proceeded from the heat of formation of pentaeth-oxyphosphorane to free energies of the P(OEt) (OH)5 species. °° This allowed the calculation of the equilibrium constants for addition of water or hydroxide to simple alkyl esters of phosphoric acid see Table 1.7. 

The reaction involves the transfer of an electron from the alkali metal to naphthalene. The radical nature of the anion-radical has been established from electron spin resonance spectroscopy and the carbanion nature by their reaction with carbon dioxide to form the carboxylic acid derivative. The equilibrium in Eq. 5-65 depends on the electron affinity of the hydrocarbon and the donor properties of the solvent. Biphenyl is less useful than naphthalene since its equilibrium is far less toward the anion-radical than for naphthalene. Anthracene is also less useful even though it easily forms the anion-radical. The anthracene anion-radical is too stable to initiate polymerization. Polar solvents are needed to stabilize the anion-radical, primarily via solvation of the cation. Sodium naphthalene is formed quantitatively in tetrahy-drofuran (THF), but dilution with hydrocarbons results in precipitation of sodium and regeneration of naphthalene. For the less electropositive alkaline-earth metals, an even more polar solent than THF [e.g., hexamethylphosphoramide (HMPA)] is needed. 

Many of these reactions an1 reversible, but equilibrium will prefer the more stable products. In other words, since a strong base makes a poor leaving group, the equilibrium will favor the formation of the compound whose leaving group is a stronger base. This explains the order of reactivity of carboxylic acid derivatives. 

Figure 6.2 shows the standard mechanism of substitution reactions carried out on carboxylic acid derivatives in neutral or basic solutions. The tetrahedral intermediate—formed in the rate-determining step—can be converted to the substitution product via two different routes. The shorter route consists of a single step the leaving group X is eliminated with a rate constant Ad. In this way the substitution product is formed in a total of two steps. The longer route to the same substitution product is realized when the tetrahedral intermediate is proto-nated. To what extent this occurs depends, according to Equation 6.1, on the pH value and on the equilibrium constant Kcq defined in the middle of Figure 6.2 ...

Activation of Carboxylic Acids and Carboxylic Acid Derivatives in Equilibrium Reactions... 

Fig. 6.9. Examples of the activation of carboxylic acid derivatives in equilibrium reactions.

Consider the case of an acyl chloride. The chlorine is an inductive electron with-drawer and a resonance electron donor. As we saw in Chapter 17, the inductive effect is stronger. (Recall that chlorine is not a very strong resonance electron donor because the long C—Cl bond and the size difference between the 3p AO on the Cl and the 2p AO on the C result in poor overlap of these orbitals.) In addition, chloride anion is a very weak base. Overall, acyl chlorides are the most reactive of the carboxylic acid derivatives discussed here and are the least favored at equilibrium. 

Although the rate of reaction of a carboxylic acid derivative depends on the inductive and resonance effects of the leaving group and the position of the equilibrium de-... 

Table 20.1 shows that the amount of enol tautomer that is present at equilibrium in the case of simple aldehydes and ketones is very small. Simple carboxylic acid derivatives, such as esters, have an even smaller enol content. However, 1,3-dicarbonyl compounds... 

To model the moiety of glycoproteins which coimects the protein and carbohydrate parts of the molecule, amino acid - carbohydrate adducts (e.g. V-D-gluconylamino acids, thiazolidine-4-carboxylic acid derivatives of carbohydrates, " D-fructose amino acid derivates, etc.) have been synthetized. The protonation and metal ion (Cu2+, Ni2+, Co ", Zn2+ and Et2Sn2+) coordination equilibria of these model compounds have been studied by means of potentiometric equilibrium measurements. CD, EPR, NMR, EXAFS and MSssbauer investigations (the latter in frozen solutions) have been used to determine the structure and symmetry of the coordination sphere of the complexes. >6... 

Prototropic tautomerism of 4(l//)-quinolone-3-carboxylic acid derivatives 25 has been studied with particular emphasis on the influence of the ring substituents on the equilibrium. The techniques used include UV, H-NMR, 13C-NMR (solution), and 13C-NMR CP/MAS (solid state) (92T6135). 

The equilibrium favors the carboxylic acid derivative that is lower on the reactivity scale (less reactive). 

Both the 1,3-diol of cyclopentene and the carboxylic acid derivative of cyclobutane have formula C5H3O2, yet there is no accessible mechanism for establishing chemical equilibrium with the 2,4-pentanedione or its enol tautomer. The chemical potentials of both molecules would be fixed at negative infinity in the system. There are additional structural isomers for which the equivalent statement can be made. 

In water the intermediate carbonyls are in equilibrium with carboxylic acid derivatives, which are isolated as salts. Acidity function studies indicate carboxyl proton ionization constants of about 10 (305). 

Notice that salt formation, though very favorable, is nonetheless reversible. Upon heating, a slower but thermodynamically favored reaction between the acid and the amine can take place. The acid and the amine are removed from the equilibrium, and eventually salt formation is completely reversed. In this second mode of reaction, the nitrogen acts as a nucleophile and attacks the carbonyl carbon. Completion of an addition-elimination sequence leads to the amide. Although it is convenient, this method suffers from the high temperatures required to reverse ammonium carboxylate formation. Therefore, better procedures rely on the use of activated carboxylic acid derivatives, such as acyl chlorides (Chapter 20). 

Trihydroxypteridine exists predominantly in the dioxo-mono-hydroxy form 191(R = H), its ultraviolet spectrum closely resembling those of both the 1- and the 3-methyl derivatives and that of l,3-dimethyl-7-methoxypteridine-2,4-dione (191, R = Me). These spectra are quite different from those of 8-methyl- (192, R = H) and l,3,8-trimethyl-pteridine-2,4,7-trione (192, R = Me), which are similar to each other and to those of other 8-substituted pteridine-2,4,7-triones. However, the ultraviolet spectrum of 2,4,7-trihydroxypteri-dine does, indeed, show that a small proportion of the trioxo form is present at equilibrium. A somewhat larger proportion of the 6-methyl derivative exists in the trioxo form, although structure 193 predominates. The trioxo form (194) of 2,4,7 trihydroxy-l,3,6-trimethyl-pteridine is the most important tautomer, but the corresponding 6-carboxylic acid exists entirely in the monohydroxy-dioxo form 195. 

Differences in solubility of the reactants may for example be utilized as follows. Sodium iodide is much more soluble in acetone than are sodium chloride or sodium bromide. Upon treatment of an alkyl chloride or bromide with sodium iodide in acetone, the newly formed sodium chloride or bromide precipitates from the solution and is thus removed from equilibrium. Alkyl iodides can be conveniently prepared in good yields by this route. Alkyl bromides are more reactive as the corresponding chlorides. Of high reactivity are a-halogen ketones, a-halogen carboxylic acids and their derivatives, as well as allyl and benzyl halides. 

In the following the reaction is outlined for an a-bromination. The reaction mechanism involves formation of the corresponding acyl bromide 3 by reaction of carboxylic acid 1 with phosphorus tribromide PBr3. The acyl bromide 3 is in equilibrium with the enol derivative 4, which further reacts with bromine to give the a -bromoacyl bromide 5 ... 

Brdnsted-Lowry theory, 194 contrast definitions, 194 indicators, 190 reactions, 188 titrations, 188 Acids, 183 aqueous, 179 carboxylic, 334 derivatives of organic, 337 equilibrium calculations, 192 experimental introduction, 183 names of common, 183 naming of organic, 339 properties of, 183 relative strengths, 192, 451 strength of, 190 summary, 185 weak, 190, 193 Actinides, 414 Actinium... 

Polar C=Y double bonds (Y = NR, O, S) with electrophilic carbon have been added to suifinic acids under formation of sulfones. As in the preceding section one must distinguish between carbonyl groups and their derivatives on the one hand, and carboxylic acids (possessing leaving groups at the electrophilic carbon) on the other. Aldehydes " of sufficient reactivity—especially mono-substituted glyoxals - —and their aryl or arylsulfonyl imines have been added to suifinic acids (in a reversible equilibrium) to yield a-hydroxy or a-amino sulfones the latter could also be obtained from the former in the presence of primary amines (equation 26). 

In contrast to the reactions of the cycloamyloses with esters of carboxylic acids and organophosphorus compounds, the rate of an organic reaction may, in some cases, be modified simply by inclusion of the reactant within the cycloamylose cavity. Noncovalent catalysis may be attributed to either (1) a microsolvent effect derived from the relatively apolar properties of the microscopic cycloamylose cavity or (2) a conformational effect derived from the geometrical requirements of the inclusion process. Kinetically, noncovalent catalysis may be characterized in the same way as covalent catalysis that is, /c2 once again represents the rate of all productive processes that occur within the inclusion complex, and Kd represents the equilibrium constant for dissociation of the complex. 

Reactions with Carboxylic Acid Esters Alkyl nitrones can be metallized upon treatment with phenyl lithium in ether solution. The Li-derivatives react with carboxylic acid esters to give 3-oxo nitrones (305)- the analogs of 3-diketones and j3-keto esters (545). With the help of the 13C NMR method it has been found that 3-oxo nitrones (305) exist as an equilibrium mixture... 

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