Intermediate tetrahedral

Fig. 1. The rate-determining step in the neutral hydrolysis of paramethoxy-phenyl dichloroacetate. In the reactant state (a) a water molecule is in proximity of the carbonyl carbon after concerted proton transfer to a second water molecule and electron redistribution, a tetrahedral intermediate (b) is formed.

Taft then noted that the tetrahedral intermediates of both reactions differ by only two protons, suggesting that the steric effect in both reactions is expected to be the same. Taking the difference in these reaction rates, thus allowed the quantification of the inductive effect. 

Small amounts of salt-like addition products (85) formed by reaction on the ring nitrogen may be present in the medium. (Scheme 60) but. as the equilibrium is shifted by further reaction on the exocyclic nitrogen, the only observed products are exocyclic acylation products (87) (130. 243. 244). Challis (245) reviewed the general features of acylation reactions these are intervention of tetrahedral intermediates, general base catalysis, nucleophilic catalysis. Each of these features should operate in aminothiazoles reactivity. 

Toth et al. have thoroughly studied the rearrangement their kinetic determinations suggest a general acid-catalyzed mechanism (Scheme 115) (1578). Some points remain unclear, however why is the intermediate (181) written as a transition state when it is known that a tetrahedral intermediate (181b or 181b ) could as well be postulated How does this... 

The lack of examples demonstrating the reactivity on C-2 may be the misleading impression that this atom is not electrophilic, contrary to what is indicated from charge diagrams. Such is not the case as the Cook s rearrangement demonstrates (209, 212). A logical mechanism for this reaction involves the tetrahedral intermediate (88) (Scheme 42). This... 

A mechanism consistent with these facts is presented m Figure 19 7 The six steps are best viewed as a combination of two distinct stages Formation of a tetrahedral intermediate characterizes the first stage (steps 1-3) and dissociation of this tetra hedral intermediate characterizes the second (steps 4-6)... 

Step 3 The oxonium ion formed m step 2 loses a proton to give the tetrahedral intermediate m its neutral form This step concludes the first stage m the mechanism... 

Step 4 The second stage begins with protonation of the tetrahedral intermediate on one of Its hydroxyl oxygens... 

Nucleophilic addition to the protonated carbonyl to form a tetrahedral intermediate... 

Elimination from the tetrahedral intermediate to restore the carbonyl group... 

With regard to the second point we already know a good bit about the acid-base chemistry of the reactants and products that of the tetrahedral intermediate is less famil lar We can for example imagine the following species in equilibrium with the tetrahe dral intermediate (TI)... 

More than one form of the tetrahedral intermediate can be present at a particular pH and the most abundant form need not be the one that gives most of the product A less abundant form may react at a faster rate than a more abundant one... 

In the first stage of the hydrolysis mechanism water undergoes nucleophilic addi tion to the carbonyl group to form a tetrahedral intermediate This stage of the process IS analogous to the hydration of aldehydes and ketones discussed m Section 17 6... 

Second stage Dissociation of the tetrahedral intermediate by dehydrohalogenation... 

FIGURE 20 2 Hydrolysis of an acyl chloride proceeds by way of a tetrahedral intermediate For mationofthe tetrahedral intermediate is rate determining... 

Loss of a proton and of chloride ion from the tetrahedral intermediate yields the mixed anhydride... 

The sp hybridized carbon of an acyl chloride is less sterically hindered than the sp hybridized carbon of an alkyl chloride making an acyl chloride more open toward nude ophilic attack Also unlike the 8 2 transition state or a carbocation intermediate m an Stvfl reaction the tetrahedral intermediate m nucleophilic acyl substitution has a stable arrangement of bonds and can be formed via a lower energy transition state... 

Step 3 The product of step 2 is the conjugate acid of the tetrahedral intermediate It transfers a proton to water giving the neutral form of the tetrahedral intermediate and regenerating the acid catalyst... 

Write the structure of the tetrahedral intermediate formed in each of the reactions given in Problem 20 7... 

FIGURE 20 4 The mecha nism of acid catalyzed ester hydrolysis Steps 1 through 3 show the formation of the tetrahedral intermediate Dissociation of the tetrahe dral intermediate is shown in steps 4 through 6... 

Step 3 Deprotonation of the oxonium ion to give the neutral form of the tetrahedral intermediate... 

Step 4 Protonation of the tetrahedral intermediate at its alkoxy oxygen... 

Step 5 Dissociation of the protonated form of the tetrahedral intermediate to an alcohol and the protonated form of the carboxylic acid... 

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