Carboxylic acids with oxygen

In order to construct the basic skeleton of tetrahydrolipstatin, an aldol addition is virtually predestined. The structure of tetrahydrolipstatin may be regarded formally as an a-branched carboxylic acid with oxygen functions at positions 3 and 5. These ought to be established easily by an anti-selective aldol reaction from a )S-hydroxyaldehyde and an enolate component at the oxidation level of a carboxylic acid. The hydroxy-function on the stereogenic centre at position 5 can be used moreover as a stereodifferentiating structural fragment. 

Howarth oxidized various aromatic aldehydes to the corresponding carboxylic acids with Ni(acac)2 dissolved in [BMIM][PF ] as the catalyst and oxygen at atmospheric pressure as the oxidant [59]. However, this reaction cannot be considered a... 

Esters are named by first identifying the alkyl group attached to oxygen and then the carboxylic acid, with the -ic acid ending replaced by -ate. 

Figure 10-4. The double- and single-site titration models for His and Asp groups [42]. (A) In the double site model, only one X is used for describing the equilibrium between the protonated and deprotonated forms, while the tautomer interversion process is represented by the variable x. (B) In the single-site model, protonation at different sites is represented by different X variables. HSP refers to the doubly protonated form of histidine. HSD and HSE refer to the singly protonated histidine with a proton on the h and e nitrogens, respectively. ASP1 and ASP2 refer to the protonated carboxylic acid with a proton on either of the carboxlate oxygens...

S-Protonated thiophens are not observed even at —90°C. The protonation of 2-thienyl carbonyl compounds [235] in HSO3 F—SbFj—SO2 at —85°C occurs primarily on the carbonyl oxygen, and only the second protonation may occur on the ring (Kaper and de Boer, 1970). Thus the protonated carboxylic acid, with a methyl group in the 5-position, adds a second proton on C-4. 

Don t confuse a carboxylic acid with a ketone or an alcohol. Carboxylic acids have entirely different properties and reactivities than either ketones or alcohols. In particular, the proton (H ) on the oxygen in a carboxylic acid is unusually acidic (hence the name ), for reasons we talk about later in this chapter in the section Reactivity of the Ccirbonyl Group. ... 

A reaction of dibromoacetic acid with different aldehydes promoted by Sml2, followed by an elimination reaction also promoted by samarium diiodide, affords ( > ,/l-unsaturalcd carboxylic acids with total stereoselectivity (Scheme 8).42 A mecha- (g) nism that involves chelation of the Sm(III) centre with the oxygen atom of the alcohol group through a six-membered chair-like transition state has been described. 

An alcohol can be viewed as the product of the first step in the oxidation of a hydrocarbon because there is an oxygen atom inserted between a carbon and a hydrogen. The addition of oxygen (or insertion) is one of the definitions of oxidation. If another oxygen atom is inserted on the same carbon and water is eliminated, the result is an aldehyde (if the carbon is at the end of the chain) or a ketone (if the carbon is in the middle of the chain). Inserting one more oxygen on the carbon of an aldehydes results in an acid—this is a carboxylic acid with the affected carbon often referred to as a carboxylic carbon (—COOH). 

W Adam, W Boland, J Hartmann-Schreier, H-U Humpf, M Lazarus, A Saffert, CR Saha-Moller, P Schreier. a Hydroxylation of carboxylic acids with molecular oxygen catalyzed by the a oxidase of peas (Pisum sativum) a novel biocatalytic synthesis of enantiomerically pure (R)-2-hydroxy acids. J Am Chem Soc 120 11044— 11048, 1998. 

You may already be familiar with one anion very much like the allyl anion—the carboxylate ion formed on deprotonating a carboxylic acid with a base. In this structure we again have a double bond adjacent to a single bond but here oxygen atoms replace two of the carbon atoms. 

For both carbon and hydrogen, a bond to oxygen is stronger than a bond to carbon. Yet we have no hesitation in breaking O-H bonds (of, say, carboxylic acids) with even the weakest of bases and we have spent much of the last chapter showing C-O bonds of protonated alcohols rupturing spontaneously What is going on ... 

OL-Chlorination of carboxylic acids.2 A Hell-Volhard-Zelinsky type of a-chlori-nation of carboxylic acids with chlorosulfonic acid is possible if a competing free radical chlorination is suppressed. For this purpose, 1 is superior to oxygen 3 in addition, the reaction is applicable to both short- and long-chain acids (equation I). 

Acid anhydrides react more easily than the corresponding carboxylic acid with nucleophiles because the electron-withdrawing effect of the second carbonyl group reduces the effect of the lone pairs on the oxygen on the first carbonyl group (see 3.22). 

In the nucleophilic reaction of the carboxylic acid with the cation, 7-28, the carbonyl oxygen, not the C—O oxygen, acts as the nucleophile because only then is the resulting intermediate stabilized by resonance. 

Heumann s Synthesis, Phenyl Glycine Ortho-carboxylic Acid.—The synthesis that has resulted in placing synthetic indigo on the market is that of Heumann by the fusion of phenyl glycine ortho-carboxylic acid with caustic potash. The product of this fusion is indoxyl which by atmospheric oxygen is oxidized to indigo. The industrial success of this synthesis was achieved only when the preparation of the-phenyl glycine ortho-carboxylic acid from a cheap source was accomplished. 

Oxidative cleavage of open-chain ketones or alcohols is seldom a useful preparative procedure, not because these compounds do not undergo oxidation (they do, except for diaryl ketones), but because the result is generally a hopeless mixture. Aryl methyl ketones, such as acetophenone, however, are readily oxidized to aryl carboxylic acids with Re207 and 70% aqueous tert-butyl hydroperoxide. Oxygen with a mixture of manganese and cobalt catalysts give similar oxidative... 

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