Cleavage carboxylic acids

A wide range of linker groups are currently used with SynPhase crowns. They accommodate formation of the following functional groups upon cleavage carboxylic acids, primary and secondary amides, sulfonamides, alcohols, phenols, amines, anilines, anilides, hydroxymates, aldehydes, ketones, and thiols. 

Hydroxy-2-methoxybenzylalcohol Cleavage TFA 1 % Product after cleavage Carboxylic acid [95, 96 ... 

Hydroxymethylphenylacetic acid [130] PAM resin Phenylacetamidomethyl resin Cleavage - THF/HjO, LiBr/DBU - MeOH/DBU/ LiBr, EtOH/Ti(OEt), Product after cleavage - Carboxylic acid - Carboxylic acid ester... 

Chloromethyl-3-nitrobenzyl-PS/f)VB Cleavage - Photolysis (350) - Hydrogenolysis Product after cleavage - Carboxylic acid [253] - Carboxylic acid [254]... 

Cleavage - PdCl2 + nBuiSnH + H -donator - (Ph,P)2PdCI Product after cleavage - Carboxylic acid [268, 273] - Amine [274]... 

Cleavage 2 eq. (Ph,P)4Pd + 3 eq. HOBl Product after cleavage Carboxylic acid... 

SuIfonamide-PS/DVB [294] Cleavage - NaOH/H.O - NH3/MeOH - Hydrazinolysis/Dioxan Product after cleavage - Carboxylic acid - Carboxamide - Hydrazide... 

Acetyloxybenzyloxy [332] Cleavage Lipase RB 001-05 pH 5.8, rt Product after cleavage Carboxylic acid Amide Alcohol... 

Epoxide cleavage. Carboxylic acids are obtained from this reaction. It shows chemoselectivity in that alkenes and alcohols are inert. Bismuth(III) acetate and oxide are not effective. In aryl epoxides, the presence of electron-donating groups favor the oxidation. ... 

Acetic acid and other carboxylic acids are protonated in superacids to form stable carboxonium ions at low temperatures. Cleavage to related acyl cations is observed (by NMR) upon raising the temperature of the solutions. In excess superacids a diprotonation equilibrium, indicated by theoretical calculations, can play a role in the ionization process. 

Carbon-carbon triple bonds can be cleaved by ozonolysis The cleavage products are carboxylic acids... 

Mass Spectrometry A prominent peak m the mass spectra of most carboxylic acid derivatives corresponds to an acyhum ion derived by cleavage of the bond to the car bonyl group... 

There is also the possibility of removing the 2-oxo group by ring cleavage and subsequent recyclization. Lumazine can be hydrolyzed by strong alkali to 2-aminopyrazine-3-carboxylic acid (153) which is converted first into the amide (154) and then cyclized by ethyl orthoformate into pteridine-4-one (155 equation 47) (51JCS474). 

Unsubstituted 3-alkyl- or 3-aryl-isoxazoles undergo ring cleavage reactions under more vigorous conditions. In these substrates the deprotonation of the H-5 proton is concurrent with fission of the N—O and C(3)—-C(4) bonds, giving a nitrile and an ethynolate anion. The latter is usually hydrolyzed on work-up to a carboxylic acid, but can be trapped at low temperature. As shown by Scheme 33, such reactions could provide useful syntheses of ketenes and /3-lactones (79LA219). 

Indazole-3-carboxylic acid, 1-aryl-ring cleavage, 5, 246... 

Triazole-4-carboxylic acid, 2-phenyl-cleavage reactions, 5, 697... 

Photolytic cleavage reactions (e.g., of o-nitrobenzyl, phenacyl, nitrophenylsul-fenyl derivatives) take place in high yield on irradiation of the protected compound for a few hours at 254-350 nm. For example, the o-nitrobenzyl group, used to protect alcohols, amines, and carboxylic acids,has been removed by irradiation. Protective groups that have been removed by photolysis are described at the appropriate places in this book in addition, the reader may wish to consult five review articles. 

DMSO, NaCN, 125-180°, 5-48 h, 65-90% yield.This cleavage reaction is successful for aromatic systems containing ketones, amides, and carboxylic acids mixtures are obtained from nitro-substituted aromatic compounds there is no reaction with 5-methoxyindole (180°, 48 h). 

In these papers the carboxylic acid to be protected was a stable, unsubstituted compound. Harsh conditions wei acceptable for both formation and cleavage of the amide. 

A number of studies of the acid-catalyzed mechanism of enolization have been done. The case of cyclohexanone is illustrative. The reaction is catalyzed by various carboxylic acids and substituted ammonium ions. The effectiveness of these proton donors as catalysts correlates with their pK values. When plotted according to the Bronsted catalysis law (Section 4.8), the value of the slope a is 0.74. When deuterium or tritium is introduced in the a position, there is a marked decrease in the rate of acid-catalyzed enolization h/ d 5. This kinetic isotope effect indicates that the C—H bond cleavage is part of the rate-determining step. The generally accepted mechanism for acid-catalyzed enolization pictures the rate-determining step as deprotonation of the protonated ketone ... 

The latter is an exttemely reactive species. Trifluoroacetate is a good leaving group and facilitates cleavage of the O—Br bond. The acyl hypohalites are also the active halogenating species in solutions of the hypohalous acids in carboxylic acids, where they exist in equilibrium. 

Nickel peroxide is a solid, insoluble oxidant prepared by reaction of nickel (II) salts with hypochlorite or ozone in aqueous alkaline solution. This reagent when used in nonpolar medium is similar to, but more reactive than, activated manganese dioxide in selectively oxidizing allylic or acetylenic alcohols. It also reacts rapidly with amines, phenols, hydrazones and sulfides so that selective oxidation of allylic alcohols in the presence of these functionalities may not be possible. In basic media the oxidizing power of nickel peroxide is increased and saturated primary alcohols can be oxidized directly to carboxylic acids. In the presence of ammonia at —20°, primary allylic alcohols give amides while at elevated temperatures nitriles are formed. At elevated temperatures efficient cleavage of a-glycols, a-ketols... 

According to Quinkert, photoexcited cyclic ketones may be transformed to open-chain unsaturated carboxylic acids in the presence of molecular oxygen. This reaction may compete efficiently with a-cleavage and secondary transformations thereof. Thus, both stereo iso meric 17-ketones (109) and (110) yield as much as 20% of the unsaturated acid (111) when irradiated in benzene under a stream of oxygen. This photolytic autoxidation has been used notably for partial syntheses of naturally occurring unsaturated 3,4-seco-acids from 3-oxo triterpenes (for references, see ref. 72). 

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