Carbonyl group, reaction mechanism

Reactions of carboxylic acids can be grouped into the four categories indicated in Figure 15.2. Of the four, we ve already discussed the acidic behavior of carboxylic acids in Sections 15.2 and 15.3, and we mentioned reduction by reaction of the acid with LiAlH4 in Section 13.3. The remaining two categories are examples of fundamental carbonyl-group reaction mechanisms— nucleophilic acyl substitution and a substitution—that will he discussed in detail in Chapters 16 and 17. 

The following reaction, called the benzilic acid rearrangement, tajkes place by typical carbonyl-group reactions. Propose a mechanism fPh = phenyl). 

The reaction takes place in two steps, both of which are typical carbonyl-group reactions. The first step is the reaction between the aldehyde and the amine to jneld an intermediate iminium ion (R2C=NRa ) plus water. The second step is the reaction between the iminium ion intermediate and the ketone to yield the final product. Propose mechanisms for both steps, and show the structure of the intermediate iminium ion. 

Cyanohydrin Formation. The rate-determining step in the formation of cyanohydrins is the addition of cyanide ion to the carbonyl group. The mechanism of the reaction can be illustrated by the following equations ... 

Dialkyl cyanomethylphosphonates are routine reagents readily accessible on laboratory scale and also available from a number of chemical suppliers. Since the review by Pudovik and Yastrebova published in 1970, ° the use of dialkyl cyanomethylphosphonates in Homer-Wadsworth-Enunons reactions has been covered in several comprehensive and excellent reviews. AU the factors governing the reaction (nature of the carbanions and carbonyl group, reaction conditions, mechanism, and stereochemistry) have been studied in depth. We invite the reader to refer to these papers. In contrast, we discuss here the synthetic applications resulting directly from the use of dialkyl cyanomethylphosphonate, which is the pathway of choice for the preparation, via a,p-unsaturatcd nitriles, of a,P-unsaturated aldehydes, cyanoethyl compounds, allylamines, and saturated amines. 

The overall reaction proceeds in two stages. The hemiacetal is formed in the hrst stage by nucleophilic addition of the alcohol to the carbonyl group. The mechanism of hemiacetal formation is exactly analogous to that of acid-catalyzed hydration of aldehydes and ketones (Section 17.6) ... 

The second alternative to the Grignard addition is enolization, which requires a hydrogen a to the carbonyl group. The mechanism has a six-centre cyclic transition state and like the reduction process has fewer steric requirements than does addition. [82,83], Scheme 1.9 (c). Branching at the carbons or to carbonyl slows the addition reaction and therefore increases the extent of enoliza-tion and reduction. Preparative additions to such ketones requires the use of alkyllithium reagents. The cnols may be useful for synthetic purposes since they may add to the carbonyl group in added reactants or in the substrate itself. 

What is certain is that proton transfers between oxygen atoms are very last and are reversible, and for that reason we don t need to be concerned with the details—the proton can always get to where it needs to be for the next step of the mechanism. As with all these carbonyl group reactions, what is really important is the addition step, not what happens to the... 

Carbonyl Group Reactions, Simple, Mechanism and Catalysis of... 

The chemical reactivity displayed by the cuprate reagents is powerful nu-cleophilicity toward carbon, but with a strong preference for reaction at alkene or halide sites over carbonyl groups. The mechanism(s) of the reactions have not been established with certainty. A leading proposal " for the conjugate addition is that reaction is initiated by a one-electron transfer from the copper-lithium species. The... 

W. P. Jencks, Mechanism and Catalysis of Simple Carbonyl Group Reactions in Progress in Physical Organic Chemistry, Vol. 2 (Eds. S. G. Cohen, A. Streitwieser, Jr. and R. W. Taft), Interscience Publishers, New York, 1963, p. 70. 

In a carbonylation reaction applied to polymer synthesis, a number of cationic Pd(II) complexes, such as [Pd(dipy)Me(CO)][BAr 4], convert ethylene—CO mixtures to a perfectly alternating copolymer (-C0-CH2-CH2-) that allows for easy subsequent functionalization of the carbonyl group. The mechanism involves alternating insertions of CO and ethylene, to account for which, the alkyl must prefer to insert CO and the acyl must prefer to insert ethylene. We have already seen that multiple insertion of CO is not favored (Section 7.2), but multiple insertion of ethylene is seen for Zr(IV) in cases where there is no CO to compete (Section 12.2). As expected, if alternation is to occur, the reaction barrier for the CO insertion into Pd-alkyl must be the lowest (calculated as 15 kcal/mol), followed by ethylene into a Pd-acyl (17 kcal/mol), followed by ethylene into a Pd-alkyl (19 kcal/mol). 

The minor process (VII) may occur from the subsequent reaction of an intermediate diradical CH2CH2CH2CH( )OH, formed by H-atom abstraction by the excited carbonyl group. The mechanisms of the two processes (IE) and (VII) do not appear to involve alternative pathways of decay of the same diradical intermediate. 

Perhaps the most extensively studied catalytic reaction in acpreous solutions is the metal-ion catalysed hydrolysis of carboxylate esters, phosphate esters , phosphate diesters, amides and nittiles". Inspired by hydrolytic metalloenzymes, a multitude of different metal-ion complexes have been prepared and analysed with respect to their hydrolytic activity. Unfortunately, the exact mechanism by which these complexes operate is not completely clarified. The most important role of the catalyst is coordination of a hydroxide ion that is acting as a nucleophile. The extent of activation of tire substrate througji coordination to the Lewis-acidic metal centre is still unclear and probably varies from one substrate to another. For monodentate substrates this interaction is not very efficient. Only a few quantitative studies have been published. Chan et al. reported an equilibrium constant for coordination of the amide carbonyl group of... 

Chemistry of the Carbonyl Group, A Programmed Approach to Organic Reaction Mechanisms , Stuart Warren, Wiley 1974. This programme leads up to the present one. 

Wc can t protect the carbonyl group without stopping the reaetion, so we activate one position by adding a COiEt group and using the ester A below, the synthetic equivalent of acetone, instead of acetone itself Here is the reaction draw a mechanism for it. 

So far in this section we have combined enolate anions with other carbonyl compounds by direct attack at the carbonyl group. We can expand the scope of this reaction by using a,p-unsaturated carbonyl compounds as the electrophiles. This is the Michael reaction. Remind yourself of tliis by writing out the mechanism of a Michael reaction such as ... 

The mechanisms of the Fischer esterification and the reactions of alcohols with acyl chlorides and acid anhydrides will be discussed m detail m Chapters 19 and 20 after some fundamental principles of carbonyl group reactivity have been developed For the present it is sufficient to point out that most of the reactions that convert alcohols to esters leave the C—O bond of the alcohol intact... 

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