Basicity deuterium exchange

The effects of 5-substituents on basic deuterium exchange at the 2-methyl groups in series of 1,2-dimethyl-5-substituted benzimidazoles appear to be dominated by resonance effects. Donor groups such as amino and methoxy slightly weaken the methyl acidity acceptor groups such as nitro have pronounced acid-strengthening effects <84CHEl0ll>. 

Azaindolizine, 5-chloro-nucleophilic substitution, 4, 458 8-Azaindolizine, 7-chloro-nucleophilic substitution, 4, 458 Azaindolizines basicity, 4, 454 electronic spectra, 4, 445 electrophilic substitution, 4, 453 halogenation, 4, 457 hydrogen/deuterium exchange, 4, 458 NMR, 4, 447, 449 nucleophilic attack, 4, 458 protonation, 4, 453 reaction with isothiocyanates, 4, 513 reactions, 5, 267 reviews, 4, 444 UV spectra, 4, 446, 449 Azaindolizines, amino-tautomerism, 4, 452... 

The condensation reaction in deuterium revealed that up to 92% of the acetone undergoes deuterium exchange to form various states of deuterated acetone, with C3H5DO present as the most populated species at ca. 60%. These results indicate that the exchange process is extremely facile even on a catalyst only containing weakly basic sites. Various deuterated products were observed in all of the reaction products, implying that there is significant H-transfer... 

Ring protons of 1,2,3-thiadiazoles are known to undergo rapid deuterium exchange under basic conditions. It has been reported that even weak bases such as phenolate can extract the proton at the 5-position of 4-phenyl-l,2,3-thiadiazole <1999J(P1)1473>. 

In the aqueous pH region the mechanism for hydrogen-deuterium exchange in pyridine involves attack of deuteroxide ion on the pyridin-ium ion to give an ylide intermediate (Scheme 8). The ylide then reacts with D2O to give the deuterated p30 idine. In more basic media the proposed mechanism involves rate-determining deprotonation from the neutral molecule to give a carbanion intermediate which then abstracts a deuteron from the solvent (Scheme 9). 

Ring protons of 1,2,3-thiadiazoles are known to undergo rapid deuterium exchange under basic conditions, yet to date there have been no published estimates or experiments to determine the pA of these protons. Few attempts have even been made to metalate and alkylate this heterocycle. One study <85S945> found that metalation of 5-phenyl-1,2,3-thiadiazole (25) with methyllithium gives 4-lithio-5-phenyl-l,2,3-thiadiazole, which is stable and reacts with aldehydes and ketones in high yields (Equation (11)). Also, treatment of 4-phenyl-1,2,3-thiadiazole with lithium diisopropylamide, in the presence of TMS-Cl, affords 4-phenyl-5-trimethylsilyl-1,2,3-thiadiazole. 

Thiadiazole is a planar, thermally stable, and weakly basic aromatic ring system. Aromatic forms of the 1,2,5-thiadiazole nucleus are generally stable to concentrated mineral acids and are only slightly sensitive to base. Base-catalyzed deuterium exchange of the ring protons can be effected... 

The intermediate tricyclic ketones 495 and 496 have been transformed to the methoxy-substituted derivative 97284,285) latter ketone is subject to hydrogen-deuterium exchange only under basic conditions and appears to exist entirely in the keto form despite the ready formation of its anion and successful methylation on oxygen . In agreement with the aromatic nature of 490, the hydrocarbon undergoes electrophilic substitution reactions... 

Little work has been reported. From studies of proton/deuterium exchange rates, 2-methylpyrrolo[2,l-6]thiazole (478) was estimated to have a pKa of 6.4,394 a value comparable with that of 2-methylindolizine (pKa = 5.9).394 In the same way, the basicity of 3,4-dimethylimidazo-[l,5-a]benzimidazole (468b) (pA = 6.01) resembles that of imidazo-[l,2-a]pyridines (pA = 5.05-5.96).398 It would seem, therefore, that the basicity of azapentalenes parallels that of related indolizine derivatives [Eq. (40)]. 

Metal-free corrin is stable only in the protonated form and reversibly deprotonates at C-8 and C-l 3 in neutral or basic media (pX mcs 8.6 in dimethyicellosolve- water, 1 l).250 Therefore, deutera-tion under basic conditions (Na0D-KCN/Bul0D-D2O (1 1), r.t., M = H2, CoHI(CN)2, Ni2+) occurs at those positions. The electrophilic proton-deuterium exchange (TFA/Bu 0D-D20 (1 1), r.t., M = H2, Coih(CN)2, Ni2+) is more facile at C-5 and C-15 than at C-10 as predicted from MO calculations.239,250... 

If a carbanion is thermodynamically accessible, but is subject to rapid quenching by internal return of C02 in the case of decarboxylation, or by a proton in carboxylation, or in a hydrogen/deuterium exchange reaction, then the carbanionic intermediate off the enzyme would give the appearance of greater basicity than its thermodynamic value would predict. The localized character of the carbanion at the 6-position of UMP requires that the proton that is removed by a base in solution initially remains closely associated, and therefore, to a great extent be transferred to the carbanion. This reduces the rate of exchange and creates a discrepancy between kinetic and thermodynamic acidities. 

The hydrogen/deuterium exchange has proven to be an extremely valuable tool for the analysis of gas-phase anion structures and reactivity184-187. The data which are reported in Table 25 suggest an absolute gas-phase basicity (AG°) of H2C=CH—S- is 341 ... 

The chemist can adopt a variety of procedures to simplify complex spectra to make them more amenable to first-order analysis or analysis by inspection. A simple example is deuterium exchange which was described in the previous section. Acidic protons attached to carbon may also be exchanged under basic conditions. 

While deuterium exchange between DGeCl3 and benzene and toluene does not occur at room temperature, trichlorogermane behaves as a strong acid with the more basic methylbenzenes, i.e., m-xylene, mesitylene and isodurene, by promoting rapid deuterium exchange. With mesitylene, for example, the equilibrium is established at 20 °C after 60 minutes. 

To the best of our knowledge, there are no published data on the reactions of alkanes with H2 over palladium single crystals. Deuterium exchange reactions with various alkanes over palladium films were extensively investigated by Kemball et al. (39-42). Because those results were already discussed in several excellent review articles (43-46), we do not intend to dwell upon analyzing all the data at greater length. We only specify here the basic characteristics of Pd films exhibited in D2/alkane reactions ... 

By deuterium exchange in basic solution the relative ease of displacement of hydrogen at C-5 and of hydrogen in the methyl group at C-5 has been determined (Table 8). 

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