Radicals from Carboxylic Acids

Another way that has potential for the generation of perfluoroalkyl radicals from carboxylic acids is the use of Barton esters. However, unlike the situation for their hydrocarbon analogs, fluorinated thiohydroxamate esters have thus far only been able to be prepared in situ [65]. 

The generation of oxygen-centered radicals from carboxylic acids and alcohols with the tandem reagent, PhI(OAc)2-l2, is an established practice... 

Barton, D. H. R., Crich, D., Motherwell, W. B. The invention of new radical chain reactions. Part VIII. Radical chemistry of thiohydroxamic esters a new method for the generation of carbon radicals from carboxylic acids. Tetrahedron 1985, 41,3901-3924. 

Radicals from Carboxylic Acids. Carboxy radicals appear to be involved in three venerable reactions in preparative carbohydrate chemistry, the Ruff degradation, the Hunsdiecker reaction and the Kolbe electrolysis. 

Although the vast majority of publications involving Barton esters have involved the generation of carbon-centered radicals from carboxylic acids, the 0-acylthiohy-droxamate decarboxylative protocol has also been extended to other substrates. 

Several useful synthetic methodologies are based on the generation of the oxygen-centered radicals from carboxylic acids and the (diacetoxyiodo)benzene-iodine system [613-617]. In particular, a direct conversion of 2-substituted benzoic acids 566 into lactones 567 via oxidative cyclization induced by [bis(acyloxy)iodo]arene/iodine has been reported (Scheme 3.224) [613,614]. 

Startg. selenoimidate, tri-n-butyltin hydride, and AIBN in toluene heated at 110° for 3-6 h - product. Y 84% (after oxidation with DDQ). F.e. and 4-chromanones, also generation of imidoyl radicals from carboxylic acid thioamides via S-stannyl thio-imidates, s. M.D. Bachi, D. Denenmark, J. Am. Chem. Soc. Ill, 1886-8 (1989). 

A hydroxymethyl group can be introduced (ArH —> ArCH20H) by several variations of this method. Alkylation of these substrates can also be accomplished by generating the alkyl radicals in other ways from hydroperoxides and FeS04, from alkyl iodides and H2O2—Fe V from carboxylic acids and lead tetraacetate, or from the photochemically induced decarboxylation of carboxylic acids by iodoso-benzene diacetate. 

A radical tandem cyclization, consisting of two radical carbocyclizations and a heterocoupling reaction, has been achieved by electrolysis of unsaturated carboxylic acids with different coacids. This provides a short synthetic sequence to tricyclic products, for example, triquinanes, starting from carboxylic acids which are accessible in few steps (Scheme 6) [123]. The selectivity for the formation of the tricyclic, bi-cyclic, and monocyclic product depending on the current density could be predicted by applying a mathematical simulation based on the proposed mechanism. 

The generation of radicals from carboxylate ions at the anode (Section 2.17.6, p. 115), and their coupling to form new carbon-carbon bonds is illustrated by the synthesis of hexacosane (Expt 5.11). The method has been usefully applied to the preparation of esters of long-chain carboxylic acids, from which of course the free acids may be prepared by hydrolysis. 

From the practical point of view, alkylation of heteroaromatics with Barton decarboxylation of A-acyloxy-2-thiopyridones (17), prepared from carboxylic acids and Af-hydroxy-2-thiopyridone, is very useful, since it can be used for various kinds of carboxylic acids such as sugars and nucleosides [23-26]. This reaction comprises of the initial homolytic cleavage of the N-0 bond in A-acyloxy-2-thiopyridone to form an acyloxyl radical and PyS , (3-cleavage of the acyloxyl radical to generate an alkyl radical and C02, addition to the electron-deficient position of heteroaromatics by the alkyl radical to form the adduct, and finally, abstraction of a hydrogen atom from the adduct by PyS , as shown in eq. 5.10. 

Treatment of O-acyl esters (2) with l,l-dichloro-2,2-difluoroethylene provides a,a-difluorocarboxylic acids (37) through photolysis, followed by the hydrolysis of the adducts (36) with AgN03 (eq. 8.17) [53]. Eq. 8.18 shows the preparation of a-keto carboxylic acids (40) from carboxylic acids, by means of the radical addition to ethyl acrylate, oxidation to the sulfoxides by mCPBA, the Pummerer reaction with... 

Finally, radicals can fragment to a smaller radical and a normal molecule in a process that is the reverse of addition. As an example, radicals derived from carboxylic acids eliminate carbon dioxide very rapidly. 

Radical nucleophile oxidation based on one-electron oxidation, known as the Minisci reaction, is employed for the functionalization of /V-heterocycles with acidic hydrogen peroxide in the presence of iron(II) salts (Figure 3.112).472 A range of A-heterocycles (pyridines, pyrazines, quinolines, etc.) which are activated towards attack by nucleophilic radicals when protonated are suited to this chemistry. The Minisci reaction is suitable for the preparation of carboxylic amides (from formamide), carboxylic esters (from pyruvic esters via a hydroxyhydroperoxide), aldehydes (from 1,3,5-trioxane) and alkylated pyridines (either from carboxylic acids or from alkyl iodides in dimethyl sulfoxide).473 The latter reaction uses dimethyl sulfoxide as the source of methyl radical (Figure 3.112). 

In the organic field the experiments using the rotating cryostat have been aimed at the preparation of the radical anions of some aliphatic compounds which had not been prepared previously namely, the radical anions from carboxylic acids and ketones. 

The present results confirm that the doublets observed in the e.s.r. spectra of several carboxylic acids immediately after X- or y-irradiation at 77°K are due to the radical anions of the acid. Further it is reasonable to assume that a similar sequence of reactions to that postulated above occurs in the formation of radicals in carboxylic acids by high energy irradiation. Thus the radical anion is the primary product and the more stable free radicals are formed subsequently by hydrogen abstraction by the anion from a neighbouring acid molecule. 

Photolysis at lower temperatures and in the solid state decreases the extent of the hydrogen atom abstraction due to its higher activation energy compared to radical dimerization. Additionally, the lower mobility of the radicals in the solid state increases the cage reaction of the pairwise generated radicals. This way unsymmetrical diacylperoxides form unsymmetrical dimers with less than 1% of the symmetrical product [29]. Peroxides from carboxylic acids, being optically active at the a-carbon, couple photochemically in the solid with only a minor loss of optical activity [30]. 

Determination of the residual antioxidant content in polymers by HPLC and MAE is one way to determine the amoimt needed for reasonable stabilization of a material, and also to compare different antioxidants and their individual efficiencies. During ageing and oxidation of PE, carboxyhc acids, dicarboxylic acids, alcohols, ketones, aldehydes, n-alkanes and 1-alkenes are formed [86-89]. The carboxyhc acids are formed as a result of various reactions of alkoxy or peroxy radicals [90]. The oxidation of polyolefins is generally monitored by various analytical techniques. GC-MS analysis in combination with a selective extraction method is used to determine degradation products in plastics. ETIR enables the increase in carbonyls on a polymer chain, from carboxylic acids, dicarboxyhc acids, aldehydes, and ketones, to be monitored. It is regarded as one of the most definite spectroscopic methods for the quantification and identification of oxidation in materials, and it is used to quantify the oxidation of polymers [91-95]. Mechanical testing is a way to determine properties such as strength, stiffness and strain at break of polymeric materials. 

The introduction of 0-acyl thiohydroxamates (mixed anhydrides of carboxylic acids with thiohydroxamic acids) by the Barton group in 1983 [1] has provided one of the mildest and most convenient and versatile sources of carbon-centered radicals which fulfill the above criteria, and can hence, in Sir Derek s own words, be described as disciplined . Since their preparation from carboxylic acids is extremely straightforward, and since they have demonstrated a rapacious radicophilicity in a wide variety of very useful transformations, it is no surprise that these derivatives are commonly named either as Barton esters or by the acronym PTOC (pyridine thiocarbonyl) esters. The ongoing development of this chemistry has been summarized over the years in several useful reviews [2], and some of the tried and tested experimental procedures have also been collated [3]. 

Kita and coworkers have developed a simple and reliable method for the direct constmction of biologically important aryl lactones 573 from carboxylic acids 572 using a combination of PhI(OAc)2 with NaBr (Scheme 3.226). The mechanism of this reaction includes initial generation of carbonyloxy radical followed by intramolecular benzylic hydrogen abstraction and cycUzation [618]. 

Mercaptans from carboxylic acid chlorides via S-acylxanthates and xanthates A new method for the production of acyl radicals... 

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