Reactions of Acid Derivatives

Although quite reliable empirical rules exist for the enantioselectivity of hydrolases for secondary alcohols, such rules are not as reliable for acid derivatives. The rule 

Resolution of branched alkanoic adds. Hydrolase-catalyzed esterification of 2-methylalkanoic acids can be fairly efficient, especially for acids with long chains, provided that the conditions are carefully adjusted by immobilization of the enzyme (in some cases), by control of the water activity, and by proper choice of the appropriate alcohol as nucleophile as well as the correct solvent [134]. The alcohol concentration does also influence the E-value [133]. It is important to note that the esterifications are reversible, thus preventing easy access to the remaining substrate in high ees. Some representative examples are given in Table 4.4. A procedure based on iterative resolutions can be used to provide both enantiomers of 2-methyloctanoic acid in high ees ( 99%) and reasonable yields (25% for S- and 43% for R-acid based on the starting racemic acid) [137]. 

Methyldecanoic acids with remotely located methyl branches have been subjected to esterifications under similar conditions with 1-hexadecanol in cyclohexane at aw = 0.8. Here, R-seleclivi ly is the result for the 3-, 5-, and 7-methyldecanoic acids (E = 21, 58, and 17, respectively), whereas one obtains S-selectivity for the 2-, 

S-selective esterification R-selective esterification Lipozyme IM20, isooctane, Novozyme 435, 

R-selective interesterification Novozyme 435, acetonitrile tri-n-propylorthoformate, trace -propanol, 45 °C Remaining substrate 98% (S) at c - 60%, 

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Reaction of acid derivatives with inorganic acids... 

Reaction of acid derivatives with 2-hydrazinoquinazolines blocked at position 1 (311) gave members of this ring system (312) [84EGP(D)206-... 

We close this section with a somewhat more detailed consideration of ester hydrolysis as an example of the kinds of questions that arise in study of reactions of acid derivatives.123... 

Some reactions of acid derivatives are summarized in Table 10.5. p-Keto esters can be prepared by the Claisen condensation, a reaction analogous to the aldol condensation but involving ester enolates as the reactive intermediates. 

Mechanism 21-13 Hydride Reduction of an Ester 1015 Mechanism 21-14 Reduction of an Amide to an Amine 1016 21-9 Reactions of Acid Derivatives with Organometallic Reagents 1017 Mechanism 21-15 Reaction of an Ester with Two Moles of a Grignard Reagent 1018... 

Reactions of Acid Derivatives with Organometallic Reagents... 

Making other compounds by substitution reactions of acid derivatives... 

WeVe talked at length about the interconversions of acid derivatives, explaining the mechanism of attack of nucleophiles such as ROH, H20, and NH3 on acyl chlorides, acid anhydrides, esters, acids, and amines, with or without acid or base present. We shall now go on to talk about substitution reactions of acid derivatives that take us out of this closed company of compounds and allow us to make compounds containing functional groups at other oxidation levels such as ketones and alcohols. 

There are a number of variations of the condensation reaction of acid derivatives. The reaction between a cyclic ketone having a pendant alkynyl ester unit and tetra-butylammonium fluoride leads to cyclization to a bicyclic alcohol with an exocyclic allene moiety. A chain-extension reaction culminates in acyl addition of an ester enolate. The reaction of a p-keto ester, such as methyl 3-oxobutanote and EtZnCH2k leads to chain extension via a carbenoid-like insertion reaction (p. 803), which reacts with an aldehyde in a second step to give a methyl 3-oxopentanoate derivative with a —CH(OH)R group at C-2 relative to the ester carbonyl. ... 

Hydrazides are normally made by the reaction of acid derivatives, such as esters, acid chlorides, or amides with hydrazine. The interaction of esters and hydrazine hydrate is very straight-forward and gives good yields. If the esters are liquid, simple addition of hydrazine hydrate to the diethyl ether solution of the esters will cause the precipitation of the hydrazide. If the esters are solid or insoluble, solvents such as methanol or ethanol are required. Normally, such reactions take place very rapidly. Diesters normally form dihydrazides if an excess of hydrazine is used. However, we have been able to convert some diesters into monoester-monohydrazide derivatives (e.g., (94) and (95)) by controlling the molar ratio in a highly diluted reaction (for typical examples see Scheme 23).96... 

Reactions of Acid Derivatives Involving Carbanions A. Malonic Ester Synthesis... 

Reactions of acid derivatives with nitrogen compounds... 

When acid derivative 2 reacts with sulfuric acid, the oxygen atom is the base and the conjugate acid product of this acid-base reaction is oxocarbenium ion 3, which is resonance stabilized. When 2 is an acid chloride, anhydride, ester, or amide, a heteroatom is attached to the positive carbon in 3. As in Chapter 18 (Section 18.1), the acid-base reaction of the carbonyl unit in 2 to give 3 facilitates reactions with nucleophiles. The reaction of intermediate 3 with a nucleophile ( Y) gives tetrahedral intermediate 4 contrary to acyl addition, reaction 4 contains an X group that can function as a leaving group. Loss of X leads to the final product of this reaction 5. If the nucleophile ( Y) is hydroxide, compormd 5 is the carboxylic acid (X = OH). If the nucleophile Y is an alcohol, the product 5 is an ester, and if Y is an amine, the product 5 is an amide. This first reaction is therefore the acid-catalyzed acyl substitution reaction of acid derivatives. 

A review has appeared on the analysis, structures, nomenclatures and reactions of acids derived from monosaccharides and polysaccharides. ... 

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