Cyclohexyl radicals reactions

The chain mechanism which describes the perbenzoic decomposition in cyclohexane at the reflux temperature, becomes more complex but easy to understand [20, 29]. First of all, as PhCO 2 slowly loses C02 [41], it can lead (before decarboxylation), by H abstraction from the solvent, to PhC02H and the cyclohexyl radical (reaction (14)). Ph formed by reaction (12), has a low nucleophilic character [34]. Consequently it cannot transfer OH from the peracid but abstracts H from cyclohexane leading to PhH. Finally, Cy obtained by reactions (12)—(13) or (14) gives CyOH via reaction (15). 

The percentage of cyclohexylation is given in Fig. 1-20. (411,412). Hydrogen abstraction from the alkyl side-chain produces, in addition, secondary products resulting from the dimerization of thiazolylalkyl radicals or from their reaction with cyclohexyl radicals (Scheme 68) (411). 

High Peroxide Process. An alternative to maximizing selectivity to KA in the cyclohexane oxidation step is a process which seeks to maximize cyclohexyUiydroperoxide, also called P or CHHP. This peroxide is one of the first intermediates produced in the oxidation of cyclohexane. It is produced when a cyclohexyl radical reacts with an oxygen molecule (78) to form the cyclohexyUiydroperoxy radical. This radical can extract a hydrogen atom from a cyclohexane molecule, to produce CHHP and another cyclohexyl radical, which extends the free-radical reaction chain. 

Radical addition to conjugated systems is an important part of chain propagation reactions. The rate constants for addition of cyclohexyl radical to conjugated amides have been measured, and shown to be faster than addition to styrene. In additions to RCH=C(CN)2 systems, where the R group has a chiral center, the Felkin-Ahn rule (p. 148) is followed and the reaction proceeds with high selectivity. Addition of some radicals, such as (McsSijaSi-, is reversible and this can lead to poor selectivity or isomerization. ... 

The cyclohexadienyl radicals decay by second-order kinetics, as proven by the absorption decay, with almost diffusion-controlled rate (2k = 2.8 x 109 M 1 s 1). The cyclohexyl radicals 3 and 4 decay both in pseudo-first-order bimolecular reaction with the 1,4-cyclohexadiene to give the cyclohexadienyl radical 5 and cyclohexene (or its hydroxy derivative) (equation 15) and in a second order bimolecular reaction of two radicals. The cyclohexene (or its hydroxy derivative) can be formed also in a reaction of radical 3 or... 

The rate data for trapping cyclohexyl radicals depended upon competitive scavenging by tributyltin hydride. In the absence of the hydride, competition for the cylohexyl radicals between the pentamethylnitrosobenzene and the derived nitroxide led to a rate constant of ca. 5 x 1071 mol-1 s 1 for reaction of cyclohexyl radicals with the nitroxide. 

The interaction of alkyl halides with mercaptans or alkaline mercaptides prodnces thioalkyl derivatives. This is a typical nncleophilic substitution reaction, and one cannot tell by the nature of products whether or not it proceeds through the ion-radical stage. However, the version of the reaction between 5-bromo-5-nitro-l,3-dioxan and sodium ethylmercaptide can be explained only by the intermediate stage involving electron transfer. As found (Zorin et al. 1983), this reaction in DMSO leads to diethyldisulfide (yield 95%), sodium bromide (quantitative yield), and 5,5 -bis(5-nitro-l,3-dioxanyl) (yield 90%). UV irradiation markedly accelerates this reaction, whereas benzene nitro derivatives decelerate it. The result obtained shows that the process begins with the formation of ethylthiyl radicals and anion-radical of the substrate. Ethylthiyl radicals dimerize (diethyldisulfide is obtained), and anion-radicals of the substrate decompose monomolecularly to give 5-nitro-l,3-dioxa-5-cyclohexyl radicals. The latter radicals recombine and form the final dioxanyl (Scheme 4.4). 

In the course of the reaction, the nitrite ion leaves the primary anion-radical. This produces the cyclohexyl radical in the pyramidal configuration. The vicinal methyl group sterically hinders the conversion of the pyramidal radical into the planar one. With a high concentration of the nucleophile, the rate of addition exceeds the rate of conversion, that is, Then the entering PhS group... 

Finally, when we are running out of cyclohexane, the process terminates by the interaction of two radical species, e.g. two chlorine atoms, two cyclohexyl radicals, or one of each species. The combination of two chlorine atoms is probably the least likely of the termination steps, since the Cl-Cl bond would be the weakest of those possible, and it was light-induced fission of this bond that started off the radical reaction. Of course, once we have formed cyclohexyl chloride, there is no reason why this should not itself get drawn into the radical propagation steps, resulting in various dichlorocyclohexane products, or indeed polychlorinated compounds. Chlorination of an alkane will give many different products, even when the amount of chlorine used is limited to molar ratios, and in the laboratory it is not going to be a particularly useful process. 

Radical cyclization reactions provide a good example of the situation where kinetic and thermodynamic products appear to differ. Cyclization of hex-5-enyl radical can either yield cyclopentylmethyl radical or cyclohexyl radical. 

We will see in Chapter 19 that calculations show cyclohexyl radical to be about 8 kcal/mol more stable than cyclopentylmethyl radical. Were the reaction under strict thermodynamic control, products derived from cyclopentylmethyl radical should not be observed at all. However, the transition state corresponding to radical attack on the internal double bond carbon (leading to cyclopentylmethyl radical) is about 3 kcal/mol lower in energy than that corresponding to radical attract on the external double bond carbon (leading to cyclohexyl radical). This translates into roughly a 99 1 ratio of major minor products (favoring products derived from cyclopentylmethyl radical) in accord to what is actually observed. The reaction is apparently under kinetic control. 

The calculated energy difference is 7.5 kcal/mol in favor of cyclohexyl radical according to the 6-31G calculations. Including the entropy contribution lowers this number to around 5 kcal/mol. Were the reaction under thermodynamic control, only cyclohexane would be observed, and interpretations (b) and (c) cannot be correct. 

The H atom detachment in Eq. (6) is followed by H atom abstraction from another cyclohexane molecule in Eq. (8) and the cyclohexyl radicals disappear in disproportionation and combination reactions giving in nearly equal amounts cyclohexene and dicyclohexyl end products. In the liquid phase, the secondary decomposition of the primarily formed energy-rich reaction products is of minor importance because of the effective collisional deactivation. This is in contrast to the gas phase reaction, where the primarily formed products readily undergo decomposition in the absence of deactivation (at low pressures), e.g. ... 

The reaction (equation 76) of the hexenyl radical 47 forming cyclopentyl-methyl radical was discovered independently in several laboratories and has been of pervasive utility in both synthetic and mechanistic studyThe competition between formation of cyclopentylcarbinyl and cyclohexyl radicals favors the former even though the latter is more stable, and this kinetic preference is explained by more favourable transition state interaction. The effects of substituents on the double bond, heteroatoms in the chain, and many other factors on the partitioning between these two paths have been examined. In the gas phase above 300°C, methylcyclopentane has been observed to form cyclohexane via isomerization of cyclopentylmethyl radicals into the more stable cyclohexyl radicals. ... 

An experiment in the absence of oxygen is summarized in Table II (Run 5). Bicyclohexyl, 3-cyclohexylcyclohexene, and 3,3 -bicyclohexenyl were the main products small amounts of 1,3-cyclohexadiene and cyclohexane was also formed. The dimeric products may be formed by coupling reactions between cyclohexyl radicals and allylic cyclohexenyl... 

The first step of the reaction may be the formation of cyclohexyl radicals and cyclohexenyl radicals from cyclohexene by silent discharge. These free radicals might be formed by a cyclohexenyl radical and a hydrogen atom s being generated by electron impact, and the hydrogen atom may add to cyclohexene to give a cyclohexyl radical. 

The simple addition reaction in Scheme 19 illustrates how the notation is used. Ester (1) can be dissected into synthons (2), (3) and (4). Synthons for radical precursors (pro-radicals) possess radical sites ( ) A reagent that is an appropriate radical precursor for the cyclohexyl radical, such as cyclohexyl iodide, is the actual equivalent of synthon (2). By nature, alkene acceptors have one site that reacts with a radical ( ) and one adjacent radical site ( ) that is created upon addition of a radical. Ethyl acrylate is a reagent that is equivalent to synthon (3). Atom or group donors are represented as sites that react with radicals ( ) Tributyltin hydride is a reagent equivalent of (4). In practice, such analysis will usually focus on carbon-carbon bond forming reactions and the atom transfer step may be omitted in the notation for simplicity. 

Ultraviolet irradiation markedly accelerates the reaction, while benzene nitro derivatives decelerate it. The result obtained shows that the process begins with the formation of ethylthiyl radicals and anion radicals of the substrate. Ethylthiyl radicals dimerize (diethyldisulfide is obtained), and anion radicals of the substrate decompose monomolecu-larly to give 5-nitro-l,3-dioxa-5-cyclohexyl radicals. The latter radicals recombine and form the final dioxanyl (Scheme 4-4). 

A syn displacement of the bromine by benzylamine in the presence of triethylamine led, by a Sn2 reaction, to the a and p amino compounds which were separated into 326 (18%) and 327 (81%) respectively. The dichloroacetamide 328 derived from the latter, when subjected to the action of tri-n-butyltinhydride (2eq) and 2,2 -azobisisobutyronitrile underwent a 5-ero ring closure to furnish via the radical 329, the hydrooxindole 330 (51%) and significant amount of the rearrangement product 331 (30%). The latter is believed to be formed by fragmentation of the cyclohexadienyl radical 332 generated from the cyclohexyl radical 329. On diborane reduction, 330 provided the cis hydroindole 333, which on 0,N-debenzylation afforded ( )-c -fused bicyclic aminoalcohol 334, a compound that had been previously cyclised with formaldehyde to ( )-elwesine (320) by Stevens et al [85]. 

The latter, on reaction with methylamine yielded via the P-epoxide 373, the trans-a aminoalcohol 374, which was N-acylated to the amide 375. Acid-catalysed dehydration of the tertiary alcohol 375, led to the olefin 375, from which the key radical precursor, the chlorothioether377 was secured in quantitative yield by reaction with N-chlorosuccinimide. In keeping with the earlier results recorded for structurally related compounds, 377 on heating in the presence of ruthenium dichloride and triphenylphosphine also underwent a 5-exo radical addition to generate the cyclohexyl radical 378 which recaptured the chlorine atom to furnish the a-chloro-c/5-hydroindolone 379. Oxidation of thioether 379 gave the corresponding sulfoxide 380, which on successive treatment with trifluoroacetic anhydride and aqueous bicarbonate led to the chloro-a-ketoamide 381. The olefin 382 resulting from base induced dehydrochlorination of 381, was reduced to the hydroxy-amine 383, which was obtained as the sole diastereoisomer... 

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