Acyl compounds tetrahedral intermediate

As a general rule, nucleophilic addition reactions are characteristic only of aldehydes and ketones, not of carboxylic acid derivatives. The reason for the difference is structural. As discussed previously in A Preview of Carbonyl Compounds and shown in Figure 19.14, the tetrahedral intermediate produced by addition of a nucleophile to a carboxylic acid derivative can eliminate a leaving group, leading to a net nucleophilic acyl substitution reaction. The tetrahedral intermediate... 

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 aminolysis of Y-phenyl X-benzoates by piperidine in 20 mol% DMS0-H20 at 25 °C proceeded, on the basis of a curved Brpnsted-type plot, via a zwitterionic tetrahedral intermediate with a change in the RDS the curvature centre of the plots was at p Ka = 6.4 regardless of the electronic nature of the substituent X in thebenzoyl moiety 27 The rates of aminolysis of a series of Y-phenyl benzoates by acylic secondary amines were compared with new results for similar reactions with Y-phenyl diphenylphosphi-nates (discussed further in the section Phosphates and Phosphinates). The results showed that the C=0 compounds were more reactive than the P=0 compounds 28... 

Poor nucleophiles react with acyl isoureas B so slowly that the latter start to decompose. In some sense they acylate themselves. The N atom designated with the positional number 3 intramolecularly substitutes the O-bound leaving group that is attached to the carboxyl carbon Cl. A four-membered cyclic tetrahedral intermediate is formed. When the Cl -Ol bond in this intermediate opens up, the N-acyl urea E is produced. Because compound E is an amide derivative it is no longer an acylating agent (cf. Section 6.2). 

From Figure 6.40 you can see that these particular conditions are fulfilled if the rate-determining step of the acylation—i.e., the formation of the tetrahedral intermediate B—is considerably faster than the further reaction of the carbonyl compound C giving the alkoxide D. In more quantitative terms, it would hence be required that the rate of formation [Pg.307]

The Weinreb amide syntheses in Figure 6.50 proceeding via the stable tetrahedral intermediates B and F are chemoselective SN reactions at the carboxyl carbon atom of carbon acid derivatives that are based on strategy 1 of the chemistry of carboxylic acid derivatives outlined in Figure 6.41. Strategy 2 of the chemistry of carboxylic acid derivatives in Figure 6.41 also has a counterpart in carbon acid derivatives, as is demonstrated by a chemoselective acylation of an organolithium compound with chloroformic acid methyl ester in this chapter s final example ... 

The SN reaction under consideration is not terminated until water, a dilute acid, or a dilute base is added to the crude reaction mixture. The tetrahedral intermediate B is then protonated to give the compound E. Through an El elimination it liberates the carbonyl compound C (cf. discussion of Figure 6.4). Fortunately, at this point in time no overreaction of this aldehyde with the nucleophile can take place because the nucleophile has been destroyed during the aqueous workup by protonation or hydrolysis. In Figure 6.32 this process for chemoselective acylation of hydride donors, organometallic compounds, and heteroatom-stabilized carbanions has been included as strategy 1. ... 

We saw before that both electronic and steric factors make the carbonyl group particularly susceptible to nucleophilic attack at the carbonyl carbon (a) the tendency of oxygen to acquire electrons even at the expense of gaining a negative charge and (b) the relatively unhindered transition state leading from the trigonal reactant to the tetrahedral intermediate. These factors make acyl compounds, loo, susceptible to nucleophilic attack. 

It is in the second step of the reaction that acyl compounds differ from aldehydes and ketones. The tetrahedral intermediate from an aldehyde or ketone gains a proton, and the result is addition. The tetrahedral intermediate from an acyl... 

Thus, nucleophilic acyl substitution proceeds by two steps, with the intermediate formation of a tetrahedral compound. Generally, the overall rate is affected by the rate of both steps, but the first step is the more important. The first step, formation of the tetrahedral intermediate, is affected by the same factors... 

Nucleophilic attack on a flat acyl compound involves a relatively unhindered transition state leading to a tetrahedral intermediate that is actually a compound since the carbonyl group is unsaturated, attachment of the nucleophile requires... 

Because 64 is not a large acceleration, Breslow et al. began searching for more active substrates. They did this by first constructing molecular models of the tetrahedral intermediate for acylation by a variety of esters. They then assessed the quality of the fit within the cavity. This procedure led to the testing of p-nitrophenyl ferrocenylacrylate, a compound whose ferrocene system can enter the cavity and, with a slight tilt, rest its side chain above a P-cyclodextrin hydroxyl ... 

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