Tetrahedral intermediates anionic

Step 2 Proton transfer to anionic form of tetrahedral intermediate... 

In base the tetrahedral intermediate is formed m a manner analogous to that pro posed for ester saponification Steps 1 and 2 m Figure 20 8 show the formation of the tetrahedral intermediate m the basic hydrolysis of amides In step 3 the basic ammo group of the tetrahedral intermediate abstracts a proton from water and m step 4 the derived ammonium ion dissociates Conversion of the carboxylic acid to its corresponding carboxylate anion m step 5 completes the process and renders the overall reaction irreversible... 

Step 2 Nucleophilic addition of the ester enolate to the carbonyl group of the neutral ester The product is the anionic form of the tetrahedral intermediate... 

Aminolysis of esters often reveals general base catalysis and, in particular, a contribution to the reaction rate fi om terms that are second-order in the amine. The general base is believed to function by deprotonating the zwitterionic tetrahedral intermediate. Deprotonation of the nitrogen facilitates breakdown of the tetrahedral intermediate, since the increased electron density at nitrogen favors expulsion of an anion ... 

When the leaving group is better, breakdown can occur directly from A. This is the case when R"0 is a phenolate anion. The mechanism also depends upon the pH and the presence of general acids and bases because the position of the equilibria among the tetrahedral intermediates and their rates of breakdown are determined by these factors. 

The difference in behavior between aldehydes/ketones and carboxylic acic derivatives is a consequence of structure. Carboxylic acid derivatives have ai acyl carbon bonded to a group -Y that can leave as a stable anion. As soon a the tetrahedral intermediate is formed, the leaving group is expelled to general- a new carbonyl compound. Aldehydes and ketones have no such leaving grouj however, and therefore don t undergo substitution. 

The importance of displacement reactions on carbonyl compounds in chemistry and biochemistry has resulted in numerous mechanistic studies. In solution, there is general acceptance of the following mechanism for addition of anionic nucleophiles which features a tetrahedral intermediate, 1, and is designated (1). However, recent experimental (2 10) and theoretical (11-17)... 

Uncatalyzed mechanisms for the breakdown of a tetrahedral intermediate are relatively rare because they require generation of a cation and an anion ... 

Parts A and B of the procedure correspond to preparation of lithium tetramethylpiperidide, and its use in the in situ preparation and addition of dibromomethyllithium to the ester 1 producing tetrahedral intermediate 2. In Part C a mixture of lithium hexamethyldisilazide and lithium ethoxide is prepared for addition in Part D to the solution of 2. The silazide base serves to deprotonate the mono and dibromo ketones that are formed on initial warming of the reaction to -20°C, thus protecting them as the enolate anions 4 and 3. Addition of the sec-butyllithium in Part... 

A theoretical investigation of iV-methylmethanephosphonamidate (300), N-methylmethanephosphamide (302), and A-methylmethanesulfonamide (301) as protease transition-state isosteres has revealed that the anionic phosphonamidate (300) is the best mimic of the tetrahedral intermediate for base-catalysed A-methylacetamide (299) hydrolysis. " ... 

Breslow and co-workers elucidated the currently accepted mechanism of the benzoin reaction in 1958 using thiamin 8. The mechanism is closely related to Lapworth s mechanism for cyanide anion catalyzed benzoin reaction (Scheme 2) [28, 29], The carbene, formed in situ by deprotonation of the corresponding thiazolium salt, undergoes nucleophilic addition to the aldehyde. A subsequent proton transfer generates a nucleophilic acyl anion equivalent known as the Breslow intermediate IX. Subsequent attack of the acyl anion equivalent into another molecule of aldehyde generates a new carbon - carbon bond XI. A proton transfer forms tetrahedral intermediate XII, allowing for collapse to produce the a-hydroxy ketone accompanied by liberation of the active catalyst. As with the cyanide catalyzed benzoin reaction, the thiazolylidene catalyzed benzoin reaction is reversible [30]. 

The authors proposed mechanism involves initial attack of an in sitn formed carbene onto the aldehyde to produce tetrahedral intermediate LXXIII (Scheme 47). Proton transfer wonld produce an acyl anion eqnivalent, bnt is inconsistent with product formation. Instead S 2 displacement to produce ring opened intermediate LXXIV is proposed, followed by proton transfer. At this point, molecular oxygen apparently becomes involved to oxidize nncleophilic alkene LXXV. The active catalyst is then regenerated and observed prodnct is formed. 

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