Acyl radicals, oxidation

Eq. 4.54 shows the reaction of n-heptanol (151) with Pb(OAc)4 under high-pressured carbon monoxide with an autoclave to generate the corresponding 8-lactone (152). This reaction proceeds through the formation of an oxygen-centered radical by the reaction of alcohol (151) with Pb(OAc)4,1,5-H shift, reaction with carbon monoxide to form an acyl radical, oxidation of the acyl radical with Pb(OAc)4, and finally, polar cyclization to provide 8-lactone [142-146]. This reaction can be used for primary and secondary alcohols, while (3-cleavage reaction of the formed alkoxyl radicals derived from tertiary alcohols occurs. 

The reaction starts with the thermal generation of tert-butoxy radicals that subsequently abstract a hydrogen atom from the carbonyl group of the aldehyde. The generated acyl radicals oxidize the palladacycles into either a Pd(IV) complex or a dimeric Pd(III) species which are generated by a rate-determining C-H palladation step. Reductive elimination liberates the product and closes the catal5rtic cycle. 

Reaction 21 is the decarbonylation of the intermediate acyl radical and is especially important at higher temperatures it is the source of much of the carbon monoxide produced in hydrocarbon oxidations. Reaction 22 is a bimolecular radical reaction analogous to reaction 13. In this case, acyloxy radicals are generated they are unstable and decarboxylate readily, providing much of the carbon dioxide produced in hydrocarbon oxidations. An in-depth article on aldehyde oxidation has been pubHshed (43). 

The acyl phosphonates, acyl phosphine oxides and related compounds (e.g. 81. 82) absorb strongly in the near UV (350-400 nm) and generally decompose by rescission in a manner analogous to the benzoin derivatives.381"285 Quantum yields vary from 0.3 to 1.0 depending on structure. The phosphinyl radicals are highly reactive towards unsaturated substrates and appear to have a high specificity for addition v.v abstraction (see 3.4.3.2). 

Phenacyl radicals are produced by photodecomposition of initiators containing the phenone moiety (Scheme 3.74). These initiators include benzoin derivatives and acylphosphine oxides (see 3.3.4.1.1). Acyl radicals can be formed by... 

Phosphinyl radicals (e.g. 103-107) arc generated by photodecomposition of acyl phosphinates or acyl phosphine oxides (see 3.3.4.LI)282,466 474,473 or by hydrogen abstraction from the appropriate phosphine oxide.467... 

Mechanisms of aldehyde oxidation are not firmly established, but there seem to be at least two main types—a free-radical mechanism and an ionic one. In the free-radical process, the aldehydic hydrogen is abstracted to leave an acyl radical, which obtains OH from the oxidizing agent. In the ionic process, the first step is addition of a species OZ to the carbonyl bond to give 16 in alkaline solution and 17 in acid or neutral solution. The aldehydic hydrogen of 16 or 17 is then lost as a proton to a base, while Z leaves with its electron pair. 

These are phosphoacylglycerols containing only one acyl radical, eg, lysophosphatidylcliolme (lysoleci-thin), important in the metabohsm and interconversion of phosphohpids (Figure 14—9).lt is also found in oxidized hpoproteins and has been imphcated in some of their effects in promoting atherosclerosis. 

Figure 22-3. 3-Oxidation of fatty acids. Long-chain acyl-CoA is cycled through reactions 2-5, acetyl-CoA being split off, each cycle, by thiolase (reaction 5). When the acyl radical is only four carbon atoms in length, two acetyl-CoA molecules are formed in reaction 5.

The unexpected formation of cyclopenta[b]indole 3-339 and cyclohepta[b]indole derivatives has been observed by Bennasar and coworkers when a mixture of 2-in-dolylselenoester 3-333 and different alkene acceptors (e. g., 3-335) was subjected to nonreductive radical conditions (hexabutylditin, benzene, irradiation or TTMSS, AIBN) [132]. The process can be explained by considering the initial formation of acyl radical 3-334, which carries out an intermolecular radical addition onto the alkene 3-335, generating intermediate 3-336 (Scheme 3.81). Subsequent 5-erafo-trig cyclization leads to the formation of indoline radical 3-337, which finally is oxidized via an unknown mechanism (the involvement of AIBN with 3-338 as intermediate is proposed) to give the indole derivative 3-339. 

The acyl radicals formed in ketone photolysis are excited and, therefore, rapidly splits into CO and alkyl radical (in the gas phase). Since aldehydes and ketones are products of oxidation, continuous hydrocarbon photooxidation is an autoaccelerated process. 

Aldehydes are oxidized by dioxygen by the chain mechanism in reactions brought about in different ways initiated, thermal, photochemical, and induced by radiation as well as in the presence of transition metal compounds [4-8]. Oxidation chains are usually very long from 200 to 50,000 units [4], Acyl radicals add dioxygen very rapidly with a rate constant of 10s—109 Lmol V1 [4], Therefore, the initiated chain oxidation of aldehyde includes the following elementary steps at high dioxygen pressures [4-7] ... 

The chain unit in the thermal and photochemical oxidation of aldehydes by molecular dioxygen consists of two consecutive reactions addition of dioxygen to the acyl radical and abstraction reaction of the acylperoxyl radical with aldehyde. Experiments confirmed that the primary product of the oxidation of aldehyde is the corresponding peroxyacid. Thus, in the oxidation of n-heptaldehyde [10,16,17], acetaldehyde [4,18], benzaldehyde [13,14,18], p-tolualdehyde [19], and other aldehydes, up to 90-95% of the corresponding peroxyacid were detected in the initial stages. In the oxidation of acetaldehyde in acetic acid [20], chain propagation includes not only the reactions of RC (0) with 02 and RC(0)00 with RC(0)H, but also the exchange of radicals with solvent molecules (R = CH3). 

The mechanism shown in Scheme 23 has been suggested The first step involves the transfer of an electron from the acylsilane to produce the cation-radical intermediate. Attack of methanol at the silicon cleaves the C-Si bond to give the acyl radical intermediate, although there is no direct evidence for the acyl radical intermediate. The acyl radical is then oxidized anodically to the acyl cation, which reacts with methanol to give the corresponding methyl ester. 

The reactions of aldehydes at 313 K [69] or 323 K [70] in CoAlPO-5 in the presence of oxygen results in formation of an oxidant capable of converting olefins to epoxides and ketones to lactones (Fig. 23). This reaction is a zeolite-catalyzed variant of metal [71-73] and non-metal-catalyzed oxidations [73,74], which utilize a sacrificial aldehyde. Jarboe and Beak [75] have suggested that these reactions proceed via the intermediacy of an acyl radical that is converted either to an acyl peroxy radical or peroxy acid which acts as the oxygen-transfer agent. Although the detailed intrazeolite mechanism has not been elucidated a similar type IIaRH reaction is likely to be operative in the interior of the redox catalysts. The catalytically active sites have been demonstrated to be framework-substituted Co° or Mn ions [70]. In addition, a sufficient pore size to allow access to these centers by the aldehyde is required for oxidation [70]. 

Two sources of acyl radicals have proved to be useful for the homolytic acylation of protonated heteroaromatic bases the oxidation of aldehydes and the oxidative decarboxylation of a-keto acids. The oxidation... 

Also in this case the acyl radical can be oxidized by the ferric salt, but in the presence of protonated heteroaromatic bases the aromatic attack successfully competes with the oxidation. The process has great versatility and can be carried out with a large variety of aldehydes (aliphatic, a,jS-unsaturated, aromatic, and heteroaromatic). 

The acyl radicals attack the protonated heteroaromatic bases with good results, although the oxidizing medium can lead to the competitive processes of Eqs. (31) and (32). 

The possibility of using other sources of acyl radicals, such as tin hydrides and acyl chlorides, is complicated by the fact that homolytic acylation requires an oxidizing medium for the rearomatization of the... 

The acrolein coordinated with catalyst then gives an acyl radical by abstracting its aldehyde hydrogen. In the general oxidation of aldehydes, the acyl radical is considered to be discontinuing coordination with catalyst, as was described by Bawn (3) and Hoare and Waters (17). However, in the acrolein oxidation, the acyl radical formed by hydrogen abstraction may not conform to this proposal, as described below. 

The formation of carbon monoxide and carbon dioxide during the oxidation of acrolein is shown in Figure 5. The facts that the decomposition of peracrylic acid produced not carbon monoxide but carbon dioxide (28) and that in the initial state of the oxidation of acrolein only carbon monoxide is formed, indicate that the evolution of carbon monoxide during oxidation may be ascribed to the decomposition of the acyl radical. 

In the liquid-phase oxidation of acrolein, the metal ion with higher valence coordinates acrolein to produce an acyl radical by hydrogen abstraction. 

The acyl radical formed from acrolein, maintaining its coordination with a catalyst, may react preferably with oxygen, rather than decompose to produce carbon monoxide, though it is generally believed that a free acyl radical is formed after the abstraction of aldehyde hydrogen by a metal. In such a case, the catalyst metal is considered as behaving as a mononuclear, not a binuclear complex. The molecular weight of the catalyst recovered from the oxidation solution was measured (Table V). 

A novel tandem carbonyiation/cyclization radical process has been developed for the intramolecular acylation of l-(2-iodoethyl)indoles and pyrroles <99TL7153>. In this process, an acyl radical is formed when CO is trapped by an alkyl radical formed from the AIBN-induced radical reaction of l-(2-iodoethyl)indoles 104 with BusSnH. Intramolecular addition of the acyl radical to the C-2 position of the heteroaromatic system presumably affords a benzylic radical which undergoes in situ oxidative rearomatization to the bicycloketones 105. 

Protonated pyridines and derivatives readily undergo acylation at C-2 or C-4 (Table 28) (76MI20503). Acyl radicals are usually generated either by hydrogen abstraction from aldehydes (Scheme 210), or by oxidative decarboxylation of a-keto acids (Scheme 211). In the former case (Scheme 210) with acridine as the substrate, reduction can take place to give a dihydroacridine. 

Steps I and 2 constitute an oxidation by the ionic pathway by Cr(VI), and steps 6 and 7 a similar oxidation by Cr(V), which is produced by an electron-transfer process. Either Cr(VI) (step 3) or Cr(IV) (step 4) (Cr(IV) is produced in step 2] may abstract a hydrogen and the resulting acyl radical is converted to carboxylic acid in step 5. Thus, chromium in three oxidation states is instrumental in oxidizing aldehydes. Still another possible process has... 

Oxidation of acyl radicals by iron (III) has been postulated by Coffman et al (10). 

Acyl radicals obtained by the oxidation of aldehydes or the oxidative decarboxylation of a-keto acids react selectively at the a- or y-position of the protonated heterocyclic nitrogen. Pyridines, quinolines, pyrazines and quinoxalines all react as expected yields are typically 40 to 70%. Similarly, pyridines can be carbamoylated in acid media at C-2 (Scheme 38). 

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