Bromination, radicals reactions

An important radical reaction bromination at benzylic and allylic positions... 

Symmetrical diols can be made by a radical reaction. Radical reactions are rarely much use in carbon-carbon bond formation as they often give poor yields and many products They are of course useful in some FGl reactions in things hke altylic bromination and in functionahsing remote carbon atoms. If rou want to read more about this see Tedder, Part 2, Chapter 11 or Carruthers, Chapter 4. One useful radical reaction is the prnacol reduction ... 

Other nonpolymeric radical-initiated processes include oxidation, autoxidation of hydrocarbons, chlorination, bromination, and other additions to double bonds. The same types of initiators are generally used for initiating polymerization and nonpolymerization reactions. Radical reactions are extensively discussed in the chemical Hterature (3—15). 

Free-radical reactions written in the simplest way imply no separation of charge. The case of toluene bromination can be used to illustrate this point ... 

The major organic reactions of BrCl consist of electrophilic brominations of aromatic compounds. Many aromatic compounds do not react in aqueous solution unless the reaction involves activated aromatic compounds (an example being phenol). Bromine chloride undergoes free-radical reactions more readily than bromine. 

In radical reactions not involving bromine or chlorine on the substrate, rearrangements are much rarer One example is the fluorination of di-tert butyl ketone which produces perfluormated / rt-buty isobutyl ketone [J5] Although isolated yields are poor only the rearranged ketone could be isolated This is perhaps only the second example of a 1,2-acyl shift Low fluorine substrate ratios show that this rearrangement occurs after monofluorination... 

As mentioned in an earlier section (cf. Chapter 1, Section III), allylic positions are subject to attack by free radicals resulting in the formation of stable allyl radicals. A-Bromosuccinimide (NBS) in the presence of free-radical initiators liberates bromine radicals and initiates a chain reaction bromination sequence by the abstraction of allylic or benzylic hydrogens. Since NBS is also conveniently handled, and since it is unreactive toward a variety of other functional groups, it is usually the reagent of choice for allylic or benzylic brominations (7). 

The enhanced selectivity of alkane bromination over chlorination can be explained by turning once again to the Hammond postulate. In comparing the abstractions of an alkane hydrogen by Cl- and Br- radicals, reaction with Br- is less exergonic. As a result, the transition state for bromination resembles the alkyl radical more closely than does the transition state for chlorination, and the stability of that radical is therefore more important for bromination than for chlorination. 

Side-chain bromination at the benzylic position occurs when an alkylbenzene is treated with /V-bromosuccinimide (NBS). For example, propylbenzene gives (l-bromopropyl)benzene in 97% yield on reaction tvith NBS in the presence of benzoyl peroxide, (PhC02)2f as a radical initiator. Bromination occurs exclusively in the benzylic position and does not give a mixture of products. 

It seems that NCS should be involved in free radical reaction generated by NBS. But, the presence of traces of 4 also indicative of the production method unless extremely pure NBS has been used for bromination. Instantly, for the regular preparation of 4 the method with N,2,6-trichloro-4-nitroacetanilide is more successful (ref. 2). 

Thus, this first example of stereoselective radical reaction, initiated with the system based on Fe(CO)5, shows opportunities and prospects of using the metal complex initiators for obtaining the stereomerically pure adducts of bromine-containing compounds to vinyl monomers with chiral substituents. 

The reaction of HBr with dioxygen with the formation of the H02 radical and bromine atom ... 

Also, ferric ion promotes nuclear (ionic) bromination of benzene derivatives at the expense of the radical reaction at the side chain. 

In order to synthesize biologically relevant phosphonylimidazole 73, bromoimidazole 72 was derived from radical-initiated bromination of methyl l-p-methoxybenzyl-2-thiomethyl-5-imidazolylcarboxylate (71) [56]. The thiomethyl group served to block the C(2) position, which would otherwise undergo preferential halogenation under these conditions. As expected, a variety of Arbusov-Michaelis reaction conditions failed even under forcing conditions. On the other hand, Pd-catalyzed phosphorylation of 72 with diethyl phosphite led to methyl-4-diethylphosphonyl-l-p-methoxybenzyl-2-thiomethyl-5-imidazolylcarboxylate (73). After further manipulations, the desired phosphonic acid-linked aminoimidazoles, which resembled intermediates formed during purine biosynthesis, were accessed. 

That the mechanism of bromination by NBS was a free radical one was first suggested by Goldfinger et al (1953, 1956) and later supported by Dauben and Me Coy in 1959 and also by Tedder et al in 1960 and 1961. The strongest point in favour of the reaction being a free radical one is that it is catalysed by free radical initiators like peroxides and is also promoted by light. Indeed new substitution at the allyl position is often used to detect free radicals. Like free radical reactions, it is also retarded by inhibitors. 

There are two other mechanistic possibilities, halogen atom abstraction (HAA) and halonium ion abstraction (EL), represented in Schemes 4.4 and 4.5, respectively, so as to display the stereochemistry of the reaction. Both reactions are expected to be faster than outer-sphere electron transfer, owing to stabilizing interactions in the transition state. They are also anticipated to both exhibit antiperiplanar preference, owing to partial delocalization over the C—C—Br framework of the unpaired electron in the HAA case or the electron pair in the EL case. Both mechanisms are compatible with the fact that the activation entropies are about the same as with outer-sphere electron donors (here, aromatic anion radicals). The bromine atom indeed bears three electron pairs located in two orthogonal 4p orbitals, perpendicular to the C—Br bond and in one s orbital. Bonded interactions in the transition... 

Now, just the same sort of rationalization can be applied to the radical addition, in that the more favourable secondary radical is predominantly produced. This, in turn, leads to addition of HBr in what is the anti-Markovnikov orientation. The apparent difference is because the electrophile in the ionic mechanism is a proton, and bromide then quenches the resultant cation. In the radical reaction, the attacking species is a bromine atom, and a hydrogen atom is then used to quench the radical. This is effectively a reverse sequence for the addition process but, nevertheless, the stability of the intermediate carbocation or radical is the defining feature. The terminologies Markovnikov or anti-Markovnikov orientation may be confusing and difficult to remember consider the mechanism and it all makes sense. 

Many times, multistep synthesis problems start with an alkane. An efficient way of adding a functional group to that alkane is to brominate (or chlorinate) the alkane through a free-radical reaction. 

The 2,3-double bond of compound 145 can be dibrominated with bromine <1982AP761>. The reaction is an analog of the dibromination of 126 described in Section 8.06.5.3. The 2-bromination of 152 to give 153 (Equation 6) was claimed to be a radical reaction, but is more likely to be an electrophilic attack, as a base catalyst was used and the reaction needed the presence of a 2-alkoxycarbonyl group to proceed <1984H(22)2789>. In a similar way, the a-carbons of dihydrooxazin-2-ones and dihydrooxazin-3-ones can also be deprotonated and then reacted with electrophiles these reactions are described in Section 8.06.6.5. 

Addition of bromine to quinolizinium bromide results in formation of the perbromide salt (13). The formation of this salt is reversible, for treatment with an easily brominated solvent like acetone regenerates the original bromide. Van der Plas and coworkers (81H(15)213) have shown that if the perbromide salt (13) is heated at 200 °C it is converted into 1-bromoquinolizinium bromide (Scheme 3). While the high temperature suggests that this may be a radical reaction, the orientation (at a carbon atom of lower positive charge, although not the 3-position predicted above) is consistent with an electrophilic mechanism. 

Direct bromination of toluene and ethylbenzene form the corresponding benzyl bromides in high yield. The observed selectivity in SC-CO2 is similar to that observed in conventional organic solvents. Also, SC-CO2 is an effective alternative to carbon tetrachloride for use in the classical Ziegler bromination with N-bromosuccinimide. Reaction yields are high, side products are minimized, and bromine-atom selectivities are observed. Thus, SC-CO2 must be useful as a viable, environmentally benign substitute for many of the solvents typically used for free-radical reactions (Tanko and Blackert, 1994). 

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