Radical chain reactions substitution

The hydrogenolyaia of cyclopropane rings (C—C bond cleavage) has been described on p, 105. In syntheses of complex molecules reductive cleavage of alcohols, epoxides, and enol ethers of 5-keto esters are the most important examples, and some selectivity rules will be given. Primary alcohols are converted into tosylates much faster than secondary alcohols. The tosylate group is substituted by hydrogen upon treatment with LiAlH (W. Zorbach, 1961). Epoxides are also easily opened by LiAlH. The hydride ion attacks the less hindered carbon atom of the epoxide (H.B. Henhest, 1956). The reduction of sterically hindered enol ethers of 9-keto esters with lithium in ammonia leads to the a,/S-unsaturated ester and subsequently to the saturated ester in reasonable yields (R.M. Coates, 1970). Tributyltin hydride reduces halides to hydrocarbons stereoselectively in a free-radical chain reaction (L.W. Menapace, 1964) and reacts only slowly with C 0 and C—C double bonds (W.T. Brady, 1970 H.G. Kuivila, 1968). 

Mixed aryl selenides have also proven to be excellent ree ents for group transfer reactions.Photolysis of selenides in an inert solvent such as benzene can initiate chain reactions. Substituted radicals can be generated in this manner, from a-selenoe-... 

Structurally simple alJkyl halides can sometimes be prepared by reaction of an alkane with Cl2 or Br2 through a radical chain-reaction pathway (Section 5.3). Although inert to most reagents, alkanes react readily with Cl2 or Br2 in the presence of light to give alkyl halide substitution products. The reaction occurs by the radical mechanism shown in Figure 10.1 for chlorination. 

The ability of a nitro group in the substrate to bring about electron-transfer free radical chain nucleophilic substitution (SrnI) at a saturated carbon atom is well documented.39 Such electron transfer reactions are one of the characteristic features of nitro compounds. Komblum and Russell have established the SrnI reaction independently the details of the early history have been well reviewed by them.39 The reaction of p-nitrobenzyl chloride with a salt of nitroalkane is in sharp contrast to the general behavior of the alkylation of the carbanions derived from nitroalkanes here, carbon alkylation is predominant. The carbon alkylation process proceeds via a chain reaction involving anion radicals and free radicals, as shown in Eq. 5.24 and Scheme... 

Cu(II) EPR signal in nitriles as solvent as well as by polarographic measurements 144>. Similarly, the EPR signal disappeared when Cu(OTf)2 was used for catalytic cyclo-propanation of olefins with diazoesters 64). In these cases, no evidence for radical-chain reactions has been reported, however. The Cu(acac)2- or Cu(hfacac)2-eatalyzed decomposition of N2CHCOOEt, N2C(COOEt)2, MeCOC(N2)COOEt and N2CHCOCOOEt in the presence of cyclopropyl-substituted ethylenes did not furnish any products derived from a cyclopropylcarbinyl - butenyl rearrangement128. These results rule out the possible participation of electron-transfer processes and radical intermediates which would arise from interaction between the olefin and a radical species derived from the diazocarbonyl compound. 

It is assumed that all similar fluorination reactions proceed via an intricate radical chain-reaction mechanism. The overall reactions for the substitution of hydrogen by fluorine (RH + F2 - RF + HF, AH298 -430 kJ/mol per carbon atom) are more exothermic than the reactions for adding fluorine to the double bonds... 

Interestingly, homolytic substitution at boron does not proceed with carbon centered radicals [8]. However, many different types of heteroatom centered radicals, for example alkoxyl radicals, react efficiently with the organoboranes (Scheme 2). This difference in reactivity is caused by the Lewis base character of the heteroatom centered radicals. Indeed, the first step of the homolytic substitution is the formation of a Lewis acid-Lewis base complex between the borane and the radical. This complex can then undergo a -fragmentation leading to the alkyl radical. This process is of particular interest for the development of radical chain reactions. 

A free radical chain reaction is also called a radical substitution reaction, because radicals are involved as intermediates, and the end result is the substitution of a halogen atom for one of the hydrogen atoms of alkane. 

It was previously mentioned1 that cinnoline and 3-substituted cinnolines (94) could be prepared from the condensation products (95) between an o-nitrobenzaldehyde and a nitroalkane by electrochemical reduction. The reaction has been further studied,138 and it was noticed that when the reduction was carried out stepwise, anthranils (96) were formed, especially at elevated temperatures. The final ring closure was catalyzed by traces of oxygen, whereas too much oxygen produced the cinnoline JV-oxide (97) the ring closure was believed to be a radical chain reaction where the formation of the aromatic cinnoline was part of the driving force [Eq. (76)]. 

CH2CO)2NBr. The a substitution of alkylbenzenes is the result of radical-chain reactions (Section 14-3C). 

To be effective as autoxidation inhibitors radical scavengers must react quickly with peroxyl or alkyl radicals and lead thereby to the formation of unreactive products. Phenols substituted with electron-donating substituents have relatively low O-H bond dissociation enthalpies (Table 3.1 even lower than arene-bound isopropyl groups [68]), and yield, on hydrogen abstraction, stable phenoxyl radicals which no longer sustain the radical chain reaction. The phenols should not be too electron-rich, however, because this could lead to excessive air-sensitivity of the phenol, i.e. to rapid oxidation of the phenol via SET to oxygen (see next section). Scheme 3.17 shows a selection of radical scavengers which have proved suitable for inhibition of autoxidation processes (and radical-mediated polymerization). 

Know the meaning of substitution reaction, halogenation, chlorination, bromination, free-radical chain reaction, chain initiation, propagation, termination, combustion. 

As mentioned before, alkyl radicals and acyl radicals have a nucleophilic character therefore, radical alkylation and acylation of aromatics shows the opposite reactivity and selectivity to polar alkylation and acylation with the Friedel-Crafts reaction. Thus, alkyl radicals and acyl radicals do not react with anisole, but may react with pyridine. Eq. 5.1 shows the reaction of an alkyl radical with y-picoline (1). The nucleophilic alkyl radical reacts at the 2-position of y-picoline (1), where electron density is lower than that of the 3-position. So, 2-alkyl-4-methylpyridine (2) is obtained with complete regioselectivity. When pyridine is used instead of y-picoline, a mixture of 2-alkylpyridine and 4-alkylpyridine is obtained. Generally, radical alkylation or radical acylation onto aromatics is not a radical chain reaction, since it is just a substitution reaction of a hydrogen atom of aromatics by an alkyl radical or an acyl radical through the addition-elimination reaction. Therefore, the intermediate adduct radical (a complex) must be rearomatized to form a product and a hydrogen atom (or H+ and e ). Thus, this type of reactions proceeds effectively under oxidative conditions [1-6]. 

A. Studer, S. Amrein, Tin Hydride Substitutes in Reductive Radical Chain Reactions, Synthesis 2002, 835-849. 

Russell and coworkers62,109,110 have shown that simple enolates undergo free radical-chain nucleophilic substitution reactions with a-chloronitroalkanes by an SRN2 rather than an S l mechanism, and competition with a chain dimerization process was also observed. Using two equivalents of the enolate anion in the reaction allows complete elimination of HN02 to yield a,/i-unsaturated ketones. The synthetic potential of these reactions has also been reported110. 

NBS provides a fairly constant, low concentration of Br2 because it reacts with HBr liberated in the substitution, converting it back into Br2. This reaction also removes the HBr by-product, preventing it from adding across the double bond by its own free-radical chain reaction. 

The ability of radicals to propagate by abstraction is a key feature of radical chain reactions, which we shall come to later. There is an important difference between homolysis and abstraction as a way of making radicals homolysis is a reaction of a spin-paired molecule that produces two radicals abstraction is a reaction of a radical with a spin-paired molecule that produces one new radical and a new spin-paired molecule. Radical abstractions like this are therefore examples of your first radical reaction mechanism they are in fact substitution reactions at H and can be compared with proton removal or even with an Sfj2 reaction. 

The best known reaction implying anions and photoinduced electron transfer is the S l reaction. In this synthetically useful process a radical chain reaction (steps (9) to (11)) is running ArX is an electron accepting substrate, Nu is the nucleophile and ArNu is the substituted product ... 

The electrophilic PhCOCH2 radical generated by photolysis of PhCOCH2HgCl in DMSO adds readily to enamine 10b to form the substituted enamine 18, which upon hydrolysis gives the 1,4-diketone 19 in 60% overall yield29. In this free radical chain reaction (Scheme 2), the electron transfer from the easily oxidizable adduct radical 17 to PhCOCH2HgCl is facilitated by the fact that the irreversible half-wave reduction potentials of alkylmercury halides are typically more positive than — 0.6 V30. 

Visible light irradiation of l,2-dihydro-2-thioxo-l-pyridinyl jV-(4-alkenyl)-A-alkylcarbamates (PTOC carbamates) produces substituted pyrrolidines by a radical chain reaction (see Section 7.2.5.1). In the absence of hydrogen donors, the intermediate pyrrolidinylmethyl radical reacts with the PTOC carbamate itself to afford 2-[(2-pyridinylthio)methyl]pyrrolidines, e.g., 1, 2, 4 and 521,22. On the other hand, in the presence of a good transfer reagent, another functionality can be introduced. In the presence of diphenyl diselenide, the phenylseleno-sub-stituted products were obtained in good yield, e.g., 3 and 622. In every case, however, a low degree of diastereoselectivity of the cyclization products is observed. 

Clearly, the ArS group had become separated from the rest of the molecule and the most likely explanation was a radical chain reaction (Chapter 39) with the light producing a small amoimt of ArS to initiate the chain. The para-methyl group acts as a label. The whole system is in equilibrium and the more highly substituted alkene is the product. 

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