Derivatives of Carboxylic Acids

A classical way to achieve regioselectivity in an (a -i- d -reaction is to start with a-carbanions of carboxylic acid derivatives and electrophilic ketones. Most successful are condensations with 1,3-dicarbonyl carbanions, e.g. with malonic acid derivatives, since they can be produced at low pH, where ketones do not enolize. Succinic acid derivatives can also be de-protonated and added to ketones (Stobbe condensation). In the first example given below a Dieckmann condensation on a nitrile follows a Stobbe condensation, and selectivity is dictated by the tricyclic educt neither the nitrile group nor the ketone is enolizable (W.S. Johnson, 1945, 1947). 

The conversion of carboxylic acid derivatives (halides, esters and lactones, tertiary amides and lactams, nitriles) into aldehydes can be achieved with bulky aluminum hydrides (e.g. DIBAL = diisobutylaluminum hydride, lithium trialkoxyalanates). Simple addition of three equivalents of an alcohol to LiAlH, in THF solution produces those deactivated and selective reagents, e.g. lithium triisopropoxyalanate, LiAlH(OPr )j (J. Malek, 1972). 

What structural features are responsible for the reactivity order of carboxylic acid derivatives Like the other carbonyl containing compounds that we ve studied they all have a planar arrangement of bonds to the carbonyl group Thus all are about the same in offering relatively unhindered access to the approach of a nucleophile They differ m the degree to which the atom attached to the carbonyl group can stabilize the carbonyl group by electron donation... 

The order of reactivity of carboxylic acid derivatives toward nucleophilic acyl sub stitution can be explained on the basis of the electron donating properties of sub stituent X The greater the electron donating powers of X the slower the rate... 

Thioesters Like chlorine sulfur is a third row element with limited ability to donate a pair of 3p electrons into the carbonyl tt system With an electronegativ ity that IS much less than Cl or O however its destabilizing effect on the carbonyl group IS slight and thioesters he m the middle of the group of carboxylic acid derivatives m respect to reactivity... 

Most methods for their preparation convert one class of carboxylic acid derivative to another and the order of carbonyl group stabilization given m Figure 20 1 bears directly on the means by which these transformations may be achieved A reaction that converts one carboxylic acid derivative to another that lies below it m the figure is pracfical a reacfion fhaf converts if fo one fhaf lies above if is nol This is anofher way of saying fhaf one carboxylic acid derivative can be converted to another if the reaction leads to a more stabilized carbonyl group Numerous examples of reacfions of fhis fype will be pre senfed m fhe secfions fhaf follow... 

The first stage of the mechanism is exactly the same as for nucleophilic addition to the carbonyl group of an aldehyde or ketone Many of the same nucleophiles that add to aldehydes and ketones—water (Section 17 6) alcohols (Section 17 8) amines (Sections 17 10-17 11)—add to the carbonyl groups of carboxylic acid derivatives... 

C NMR The C NMR spectra of carboxylic acid derivatives like the spectra of carboxylic acids themselves are characterized by a low field resonance for the carbonyl... 

UV-VIS The following values are typical for the absorption associated with the C=0 group of carboxylic acid derivatives ... 

Section 20 2 The structure and reactivity of carboxylic acid derivatives depend on how well the atom bonded to the carbonyl group donates electrons to it... 

Acylium ion (Section 12 7) The cation R—C=0 Acyl transfer (Section 20 3) A nucleophilic acyl substitution A reaction in which one type of carboxylic acid derivative IS converted to another... 

Solid esters are easily crystallisable materials. It is important to note that esters of alcohols must be recrystallised either from non-hydroxylic solvents (e.g. toluene) or from the alcohol from which the ester is derived. Thus methyl esters should be crystallised from methanol or methanol/toluene, but not from ethanol, n-butanol or other alcohols, in order to avoid alcohol exchange and contamination of the ester with a second ester. Useful solvents for crystallisation are the corresponding alcohols or aqueous alcohols, toluene, toluene/petroleum ether, and chloroform (ethanol-free)/toluene. Esters of carboxylic acid derived from phenols... 

In the next chapter the three elements of the mechanism just described will be seen again as part of the general theme that unites the chemistry of carboxylic acid derivatives. These elements are... 

When a Br nsted base functions catalytically by sharing an electron pair with a proton, it is acting as a general base catalyst, but when it shares the electron with an atom other than the proton it is (by definition) acting as a nucleophile. This other atom (electrophilic site) is usually carbon, but in organic chemistry it might also be, for example, phosphorus or silicon, whereas in inorganic chemistry it could be the central metal ion in a coordination complex. Here we consider nucleophilic reactions at unsaturated carbon, primarily at carbonyl carbon. Nucleophilic reactions of carboxylic acid derivatives have been well studied. These acyl transfer reactions can be represented by... 

Most acid-catalyzed hydrolyses of carboxylic acid derivatives proceed by the A2 mechanism, as shown for ester hydrolysis ... 

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