Carbanions deuterium exchange

In theory two carbanions, (189) and (190), can be formed by deprotonation of 3,5-dimethylisoxazole with a strong base. On the basis of MINDO/2 calculations for these two carbanions, the heat of formation of (189) is calculated to be about 33 kJ moF smaller than that of (190), and the carbanion (189) is thermodynamically more stable than the carbanion (190). The calculation is supported by the deuterium exchange reaction of 3,5-dimethylisoxazole with sodium methoxide in deuterated methanol. The rate of deuterium exchange of the 5-methyl protons is about 280 times faster than that of the 3-methyl protons (AAF = 13.0 kJ moF at room temperature) and its activation energy is about 121 kJ moF These results indicate that the methyl groups of 3,5-dimethylisoxazole are much less reactive than the methyl group of 2-methylpyridine and 2-methylquinoline, whose activation energies under the same reaction conditions were reported to be 105 and 88 kJ moF respectively (79H(12)1343). 

Early reports of the persistance of optical activity in nitro-substituted carbanions have since been shown to be erroneous.365 366 The treatment of optically active 2-nitrooctane with sodium ethoxide or hydroxide produces an optically inactive salt.366 Optically active 4-nitropentanoic acid racemizes and enolizes at the same rate in the presence of a base.368 Optically active phenyl sec-butyl ketone racemizes and undergoes deuterium exchange at the same rate in the presence of DQ<-)a 7 Of course this could conceivably be due to the tendency of the... 

The finding that thiamine, and even simple thiazolium ring derivatives, can perform many reactions in the absence of the host apoenzyme has allowed detailed analyses of its chemistry [33, 34]. In 1958 Breslow first proposed a mechanism for thiamine catalysis to this day, this mechanism remains as the generally accepted model [35]. NMR deuterium exchange experiments were enlisted to show that the thiazolium C2-proton of thiamine was exchangeable, suggesting that a carbanion zwitterion could be formed at that center. This nucleophilic carbanion was proposed to interact with sites in the substrates. The thiazolium thus acts as an electron sink to stabilize a carbonyl carbanion generated by deprotonation of an aldehydic carbon or decarboxylation of an a-keto acid. The nucleophilic carbonyl equivalent could then react with other electro-... 

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). 

In the case of peptide complexes (e.g. 37), only the protons on carbon adjacent to the terminal carboxylate group are acidic enough to allow carbanion formation and to undergo deuterium exchange.65... 

Carbanion mechanisms may give either syn or anti elimination. For example, Hunter and Shearing studied the butoxide-catalyzed elimination of methanol from 35 and 36. Since deuterium exchange with solvent is in close competition with elimination, the mechanism is probably (EjcB)b. The ratio ofsyn/anti... 

Evidence for the formation of carbanions from ketoximes and DMSO in the presence of large amounts of KOH is provided by partial deuterium exchange between DMSO-D6 and the a-position of ketoximes (75MI2 76S281) in the synthesis of pyrroles, along with partial deuteration of hydroxyl. 

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 stereochemical course of hydrogen-deuterium exchange in homochiral PhEtHC CF3 has been studied [15] and, like systems containing other carbanion-stabilising groups, the extent of racemisation of the product varies with solvent. 

Recent work [log] casts some doubt on the generality of this interpretation. Evidence from deuterium-exchange experiments on butan-2-one indicates that the transition state for enolisation has little if any carbanion character that weak bases, like acids, favour formation of the more substituted enol, and that even the fairly strong base DO" caused deute-... 

H. F. Leach. Carbenium ion and carbanion mechanisms in deuterium exchange and isomerization became part of the repertoire, and there were often salutary reminders in his admirably clear papers of the interplay between thermodynamic and kinetic control in the catalytic reactions investigated. 

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