Carboxylate protonation

The first four values are for the carboxyl protons, and the remaining two values are for the ammonium protons. A ladder diagram for EDTA is shown in figure 9.26. The species Y becomes the predominate form of EDTA at pH levels greater than 10.17. It is only for pH levels greater than 12 that Y becomes the only significant form of EDTA. 

Maleic and fiimaric acids have physical properties that differ due to the cis and trans configurations about the double bond. Aqueous dissociation constants and solubiUties of the two acids show variations attributable to geometric isomer effects. X-ray diffraction results for maleic acid (16) reveal an intramolecular hydrogen bond that accounts for both the ease of removal of the first carboxyl proton and the smaller dissociation constant for maleic acid compared to fumaric acid. Maleic acid isomerizes to fumaric acid with a derived heat of isomerization of —22.7 kJ/mol (—5.43 kcal/mol) (10). The activation energy for the conversion of maleic to fumaric acid is 66.1 kJ/mol (15.8 kcal/mol) (24). 

In the 1H NMR spectrum, the acidic -C02H proton normally absorbs as a singlet near 12 5. As with alcohols (Section 17.11), the -C02H proton can be replaced by deuterium when D20 is added to the sample tube, causing the absorption to disappear horn the NMR spectrum. Figure 20.6 shows the H NMR spectrum of phenylacetic acid. Note that the carboxyl proton absorption occurs at 12.0 8. 

Species 3 and 4 in Scheme 4 are key intermediates in the demetalation of la and lm, respectively. Picolinic acid binds to the axial site of Fem and then delivers the carboxylic proton to a Fe-N bond. This is more difficult in the case of lm where the amidato-N donor atoms are less basic. Therefore, the second py... 

Radicals similar to carbamoyl are the alkoxycarbonyl radicals, ROCO. Also, these radicals were successfully used to carboxylate protonated heteroaromatic bases with good yields and selectivity. " ... 

Note that acids, and primary and secondary amides cannot be employed to generate enolate anions. With acids, the carboxylic acid group has pATa of about 3-5, so the carboxylic proton will be lost much more easily than the a-hydrogens. In primary and secondary amides, the N-H (pATa about 18) will be removed more readily than the a-hydrogens. Their acidity may be explained because of resonance stabilization of the anion. Tertiary amides might be used, however, since there are no other protons that are more acidic. 

Breaking of bond b accounts for PLP-dependent decarboxylations. Decarboxylation of the intermediate aldimine is facilitated in the same way as loss of a proton in the transamination sequence. The pro-tonated nitrogen acts as an electron sink, and the conjugated system allows loss of the carboxyl proton. 

Tartaric acid is dibasic (H2tart), carboxyl protons being ionized by pH 5. The hydroxyl groups are not ionized (p/Ca3 14 and pK 15.6).622 The formation constants of ( + )-,(-)-, ( )- and meso-tartaric acids with V02+ confirm binuclear complexes of optically active and, to a lesser extent, meso acids with V02+.623... 

The first four pAi values apply to carboxyl protons, and the last two are for the ammonium protons.11 The neutral acid is tetraprotic, with the formula H4Y. A commonly used reagent is the disodium salt, Na2H2Y 2H20.12... 

In the nuclear magnetic resonance spectra of carboxylic acids, the carboxyl proton is seen to absorb at unusually low magnetic fields. This is illustrated in Figure 18-3 by the spectra of phenylethanoic acid (C6H5CH2C02H)... 

The solvent deuterium isotope effect in the reaction of 359 with glyoxylate decreases from ( H2o/ D2o) °f 1-66 to ( H2o/ D2o) °f 1-12 with increasing pH from 1.25 to 6.43, respectively. 361 probably decarboxylates via a cyclic transition state. Transfer of the carboxylic proton takes place simultaneously with heavy-atom reorganization as indicated by small solvent DIE in the acid-catalysed reaction. The solvent DIE h2o/ D20 °f 1-20 at 1. M H+, observed in the reaction of 359 with pyruvic acid, is similar to the reaction of pyruvic acid with nitrosobenzene for which nucleophilic attack of nitroso nitrogen has been proposed395. 

The carboxylic proton is not visible in the above spectrum due to exchange broadening involving the water in the solvent. 

Carboxylic Acids Carboxylic acids exist as stable hydrogen-bonded dimers in nonpolar solvents even at high dilution. The carboxylic proton therefore absorbs in a characteristic range 8 — 13.2-S —10.0 and is affected only slightly by concentration. Polar solvents partially disrupt the dimer and shift the peak accordingly. 

Fig. 4.15 (CH3)2C(OCH3)2. Fig. 4.16 CH3OCH2COOH.The COOH line is more intense than it should be because the hygroscopic sample has absorbed water, which is in rapid exchange with the carboxyl proton. 

The NMR spectrum of pure pymvic acid consists of two resonances—one due to the carboxyl proton at 8.67 ppm and another due to methyl protons at 2.55 ppm (relative to tetramethylsilane as the reference). The separation between these two peaks is dependent on the purity of the sample— the greater the purity, the greater is the separation. Taking the spectmm of pymvic acid will allow a qualitative check on sample purity and will also provide practice with shinuning a sample for optimal resolution (narrow lines). 

Embedded within this list of DPE of the amino acids are two unexpected results concerning what is the most acidic proton. The first case is cysteine, where one might ask which is more acidic, the carboxylate proton or the thiol proton Kass and Poutsma" note that, in general, the gas-phase acidity of carboxylic acids is greater than thiols the DPE of propanoic acid (CH3CH2CO2H) is 347.7 kcal mol at G3B3 (347.2 expt about 6 kcal mol less than that of ethanethiol (CH2CH2SH ... 

Both the cysteine and tyrosine acidities point out the importance of solvation in solution, the carboxylate proton is lost exclusively for each compound. 

The rate of exchange of protons between carboxylic acids and water solvent is too fast to observe directly by NMR. In the NMR spectrum of aqueous acetate buffer, for example, the carboxyl protons and the water protons give a single line, the average of the lines for the individual species. The rate can be measured indirectly, however, since proton exchange between water and carboxyl necessarily involves transfers of protons between water molecules. The total rate of exchange of protons on water in aqueous acetate buffers is given by... 

P-Elimination of phosphate and concomitant formation of pyruvate from the terminal aci-carbanion (VI) of PGA also occurs (36). Abstraction of a hydroxyl proton from the gew-diol carboxylated intermediate (III) promotes C2 - C3 scission with liberation of PGA derived from C3, C4, and C5 of RuBP. The resulting aci-carbanion of PGA (derived from Cl and C2 of RuBP and from CO2) must undergo inversion of configuration at C2 and protonation prior to its release as the D-isomer of PGA. The status of this final step of carboxylation (protonation of the PGA carbanion) is reflected by the ratio of protonation (PGA formation) to p-elimination (pyruvate formation). 

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