Exchange, of acidic protons

Exchange of acidic protons is revealed in proton NMR spectra... 

In the ESl-MS analysis of ohgonucleotides, the adduct formation with Na", Mg ", and NH/ and exchange of acidic protons may result in very complicated mass spectra with poor signal-to-noise ratios (S/N). It may seriously compromise the mass determination of especially larger nucleotides. Sample pretreatment procedures directed at the reduction of the cation concentration are therefore of utmost importance in nucleic acid analysis by LC-MS. 

Scheme 5.6 Exchange of acidic protons by deuterons or copper(l) cations...

This process is referred to as internal return, i.e., the base returns the proton to the carbanion faster than exchange of the protonated base with other solvent molecules occurs. If internal return is important under a given set of conditions, how would the correlation between kinetics of exchange and equilibrium acidity be affected How could the occurrence of internal return be detected experimentally ... 

The exchange of aromatic protons can be effected in the absence of any -OH or —NH2 activating group during the course of a Clemmensen reduction in deuteriochloric and deuterioacetic acid mixture (see section Ill-D). This reaction has been carried out with various tricyclic diterpenes and is best illustrated by the conversion of dehydroabietic acid into its 12,14-d2-labeled analog (40 -+ 41).Amalgamated zinc is reportedly necessary for the exchange reaction since the results are less satisfactory when a zinc chloride-mercuric chloride mixture is used. 

A solution of estradiol (38, 15 mg) in methanol-OD (4 ml) and one drop of 10% deuteriosulfuric acid in deuterium oxide is heated under reflux for 5 days. After cooling the reaction mixture is diluted with ether, washed with dilute sodium bicarbonate solution and water, then dried over anhydrous sodium sulfate. Evaporation of the ether gives crystalline 2,4-d2-estradiol (39, 15 mg, 99%), mp 173-175° (ether-hexane), exhibiting 82% isotopic purity and only one aromatic hydrogen by NMR. (For an experimental procedure describing the exchange of aromatic protons under Clemmensen conditions, see section III-D.)... 

The sequential reactions 4.1 and 4.2 represent the self-dissociation of water as the exchange of a proton between water molecules, where hydration of the proton according to reaction 4.2 is the driving force for its separation (reaction 4.1) although the proton hydration is not limited to one H20 (hydration number 1), nor is the occurrence of unhydrated OH ion realistic, the overall reaction 4.3 is generally written as the simplest form to show the principle of proton acidity. 

As free proton cannot exist alone in solution, reactions in which a proton is split off from an acid to form a conjugate base cannot occur in an isolated system (in a homogeneous solution although this is possible in electrolysis (Section 5.7.1)). The homogeneous solution must contain another base Bn that accepts a proton from the acid HAr (acid HA is, of course, not conjugate with base Bn). It will be seen that this second base can even be the solvent molecule, provided it has protophilic properties. Acid-base reactions thus depend on the exchange of a proton between an acid and a base that are not mutually conjugate ... 

The mechanism of alkyl hydrogen exchange was not clarified, but a possible mechanism was postulated. Partial hydride abstraction by a Lewis acid site may have occured forming a carbocation-like species followed by exchange of a proton at a R-carbon. Such a mechanism predicts exchange to occur preferentially at methyl groups adjacent to the most stable carbocations (benzylic > 3° > 2° > 1°). This is consistent with the observed relative rates of epimerization of steranes during thermal maturation of sediments (83). 

Hydrolysis of 2,2,2-trifluoroethanesulfonyl chloride has been found to proceed via intermediate sulfene (CF3CH=S02) formed by iilcB reaction. At pH 1.8-5.0 the (ElcB) mechanism applies, whereby water and hydroxide ion act, respectively, as the carbanion-forming base at low and high pH extremes. The ( lcB)rev reaction applies in dilute acid and is accompanied by the expected H-D exchange of substrate protons when D2O is used as solvent. 

In a study of acid catalysed proton exchange in aqueous urea solutions, much faster rates have been found (A j = 9 x 10 M s ) (Void et al., 1970). This was ascribed to N-protonation. A higher rate is expected for a stronger base [pATg for urea is 0-8 or 1 6, according to Arnett (1963) and 0 18, according to Parry et al. (1969)]. The exchange of NH-protons of thiourea is acid-catalysed about 60 times as efficiently as that of N-methylacetamide (Void and Correa, 1970). 

O-Protonated cations of eimides in concentrated and anhydrous acids are now well characterized by nmr spectroscopy. O-Protonated cations of N,N-dimethyl amides are most easily observed, even in 72% perchloric acid which has a water activity of about 10 , because for tertiary amides the N-protonated forms is relatively less stabilized by hydration (Liler, 1972a). O-Protonated cations of N-alkyl amides show considerable exchange of NH-protons with the solvent in 72% perchloric acid owing to the intervention of the N-protonated form. For primary amides (acetamide), however, O-protonated cations are not observable in that solvent (Liler, 1972b),... 

The d or L configuration of the two en rings about the Co atom then decides which optical isomer of the N—CH3en coordinates stereospecific-ally. The detection of optical forms of this type has been accomplished by the resolution of the fCo(NH3)4sarcosine]2+ ion (29), In dilute acid the rate of exchange of the proton on the coordinated sarcosine N atom is very slow, and the optical configuration of the asymmetric N moiety is preserved. In... 

Exchange of nuclei between different environments affects spin-spin couplings. An example is ethanol. When a small amount of aqueous HC1 is added to pure CH3CH2OH, the OH triplet becomes a single line and the CH2 multiplet becomes a quartet. This removal of the coupling between OH and CH2 protons results from the rapid, acid-catalyzed exchange of OH protons between different ethanol molecules. 

The increase in acidity of methylene protons adjacent to coordinated carbonyl and imine groups is further reflected in the rapid deuterium exchange of such protons compared with rates of... 

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