Radicals, anti-Markovnikov mechanism

The mechanism of the addition reaction under these conditions is not an ionic sequence rather, it is a much faster radical chain sequence. The reason is that the activation energies of the component steps of radical reactions are very small, as we observed earlier during the discussion of the radical halogenation of alkanes (Section 3-4). Consequently, in the presence of radicals, anti-Markovnikov hydrobromination simply outpaces the regular addition pathway. The initiation steps are... 

A typical example of a nonpolymeric chain-propagating radical reaction is the anti-Markovnikov addition of hydrogen sulfide to a terminal olefin. The mechanism involves alternating abstraction and addition reactions in the propagating steps ... 

The rate of addition depends on the concentration of both the butylene and the reagent HZ. The addition requires an acidic reagent and the orientation of the addition is regioselective (Markovnikov). The relative reactivities of the isomers are related to the relative stabiUty of the intermediate carbocation and are isobutylene 1 — butene > 2 — butenes. Addition to the 1-butene is less hindered than to the 2-butenes. For hydrogen bromide addition, the preferred orientation of the addition can be altered from Markovnikov to anti-Markovnikov by the presence of peroxides involving a free-radical mechanism. 

The addition of hydrogen halides to simple alkenes, in the absence of peroxides, takes place by an electrophilic mechanism, and the orientation is in accord with Markovnikov s rule. " When peroxides are added, the addition of HBr occurs by a free-radical mechanism and the orientation is anti-Markovnikov (p. 985). It must be emphasized that this is true only for HBr. Free-radical addition of HF and HI has never been observed, even in the presence of peroxides, and of HCl only rarely. In the rare cases where free-radieal addition of HCl was noted, the orientation was still Markovnikov, presumably beeause the more stable product was formed. Free-radical addition of HF, HI, and HCl is energetically unfavorable (see the discussions on pp. 900, 910). It has often been found that anti-Markovnikov addition of HBr takes place even when peroxides have not been added. This happens because the substrate alkenes absorb oxygen from the air, forming small amounts of peroxides... 

In both mechanisms, the regiochemistry is determined by a preference for forming the most stable intermediate possible. For example, in the ionic mechanism, adds to produce a tertiary carbocation, rather than a secondary carbocation. Similarly, in the radical mechanism, Br adds to produce a tertiary radical, rather than a secondary radical, hi this respect, the two reactions are very similar. But take special notice of the fundamental difference. In the ionic mechanism, the proton comes on first. However, in the radical mechanism, the bromine comes on first. This critical difference explains why an ionic mechanism gives a Markovnikov addition while a radical mechanism gives an anti-Markovnikov addition. 

In the photoaddition of 2-pyrrolidone the 5-alkyl isomer (69) always predominates, usually in a ratio of 2 1. The formation of anti-Markovnikov 1 1 adducts, telomers, and dehydrodimers of structure (71) supports a free radical mechanism. Similarly, formamide undergoes olefin addition under... 

Anti-Markovnikov addition of HBr to alkynes occur when peroxides are present. 1) These reactions take place through a free radical mechanism. 

Bromine attaches itself to the less hindered carbon atom by a radical mechanism to form the more stable radical intermediate => anti-Markovnikov addition. Radical addition... 

Similar to the addition of secondary phosphine-borane complexes to alkynes described in Scheme 6.137, the same hydrophosphination agents can also be added to alkenes under broadly similar reaction conditions, leading to alkylarylphosphines (Scheme 6.138) [274], Again, the expected anti-Markovnikov addition products were obtained exclusively. In some cases, the additions also proceeded at room temperature, but required much longer reaction times (2 days). Treatment of the phosphine-borane complexes with a chiral alkene such as (-)-/ -pinene led to chiral cyclohexene derivatives through a radical-initiated ring-opening mechanism. In related work, Ackerman and coworkers described microwave-assisted Lewis acid-mediated inter-molecular hydroamination reactions of norbornene [275]. 

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. 

Kharasch and Mayo in 1933," in the first of many papers on the subject, showed that the addition of HBr to allyl bromide in the presence of light and air occurs rapidly to yield 1,3-dibromopropane, whereas in the absence of air and with purified reagents, the reaction is slow and 1,2-dibromopropane is formed. The latter reaction is the normal addition occurring by an ionic pathway giving the Markovnikov orientation. In 1933 the mechanism of the abnormal process ( anti-Markovnikov addition) was not discussed, and it was only in 1937 that the free radical chain mechanism for this process was proposed by Kharasch and his co-workers. "" The mechanism was extended to propene, for which the role of peroxides in promoting the reaction was demonstrated (equations 30, 31). This mechanism was also proposed... 

Taylor in 1925 demonstrated that hydrogen atoms generated by the mercury sensitized photodecomposition of hydrogen gas add to ethylene to form ethyl radicals, which were proposed to react with H2 to give the observed ethane and another hydrogen atom. Evidence that polymerization could occur by free radical reactions was found by Taylor and Jones in 1930, by the observation that ethyl radicals formed by the gas phase pyrolysis of diethylmercury or tetraethyllead initiated the polymerization of ethylene, and this process was extended to the solution phase by Cramer. The mechanism of equation (37) (with participation by a third body) was presented for the reaction, - which is in accord with current views, and the mechanism of equation (38) was shown for disproportionation. Staudinger in 1932 wrote a mechanism for free radical polymerization of styrene,but just as did Rice and Rice (equation 32), showed the radical attack on the most substituted carbon (anti-Markovnikov attack). The correct orientation was shown by Flory in 1937. In 1935, O.K. Rice and Sickman reported that ethylene polymerization was also induced by methyl radicals generated from thermolysis of azomethane. 

The peroxide- or light-catalyzed reaction has a free-radical mechanism (anti-Markovnikov) ... 

It is possible to obtain anti-Markovnikov products when HBr is added to alkenes in the presence of free radical initiators, e.g. hydrogen peroxide (HOOH) or alkyl peroxide (ROOR). The free radical initiators change the mechanism of addition from an electrophilic addition to a free radical addition. This change of mechanism gives rise to the anh-Markovnikov regiochemistry. For example, 2-methyl propene reacts with HBr in the presence of peroxide (ROOR) to form 1-bromo-2-methyl propane, which is an anh-Markovnikov product. Radical additions do not proceed with HCl or HI. 

Reaction 1 has been postulated both in oxidations of alkanes in the vapor phase (29) and in the anti-Markovnikov addition of hydrogen bromide to olefins in the liquid phase (14). Reaction 2 involves the established mechanism for free-radical bromination of aromatic side chains (2). Reaction 4 as part of the propagation step, established in earlier work without bromine radicals (26), was not invoked by Ravens, because of the absence of [RCH3] in the rate equation. Equations 4 to 6, in which Reaction 6 was rate-determining, were replaced by Ravens by the reaction of peroxy radical with Co2+ ... 

A stereo specific addition of BufOI to /1-methylstyrene was observed in the presence of BF3, yielding Markovnikov products. This result contrasts with the non-stereospecific addition of Bu OCl and Bu OBr. It has been suggested that the bridging in the intermediate chloronium and bromonium ion derived from PhCH=CHMe is not as symmetrical as in the iodonium ion. Consequently, charge develops on the benzylic carbon in the first two cases, and rotation occurs about the C—C bond190. By contrast, a radical mechanism is assumed in the absence of BF3 as anti-Markovnikov products are formed (both in the dark and upon UV irradiation)190. 

Reactions of BufOI/BF3, AcOI, IC1 or IBr with 1,3-butadiene give mixtures of Markovnikov 1,2- and 1,4-addition products no anti-Markovnikov 1,2-products have been detected. A radical mechanism was observed for Bu OI. Greater 1,4-addition occurs with reagents containing an anion of lower basicity (IC1 and IBr). These results have been interpreted as reflecting the charge density and ion-pair stability191. 

C is correct. Anti-Markovnikov alkene free radical addition is demonstrated by reaction mechanisms 1 and 2, both of which rely on peroxides as reagents. Based on tine experimental results provided by the question stem, anti-Markovnikov addition only succeeds using HBr. 

A well-known example of the application of mechanistic understanding to help to control product yields is also of commercial significance - the addition of HBr to alkenes which may occur via cationic or radical mechanisms, Scheme 2.1 [2a]. Very pure alk-l-enes (1), in the absence of peroxides, react to give the 2-bromo-products (2) by Markovnikov addition. In the presence of peroxides or other radical sources, anti-Markovnikov addition gives the 1-bromo-products (3). 

The results obtained57 were explained by competition of ionic and radical mechanisms, which lead to Markovnikov and anti-Markovnikov adducts, respectively. At this competition the nature of the unsaturated compound play an important role in determining the preferred mechanism. Thus, the major formation of Markovnikov adducts and therefore the preference of the ionic mechanism in the series of olefins styrene > 1-methylcyclohexene > 2,3-dimethyl-1-butene > isobutene > 1-heptene correlates with the ability of substituents to stabilize the intermediate carbenium ion. 

Numerous attempts to obtain the Markovnikov adduct by varying the reaction conditions, including its realization in concentrated HC1, had failed. Moreover, in a competitive reaction of a mixture of 1-heptene and styrene only the anti-Markovnikov adducts were formed for both olefins and, surprisingly, 1-heptene was found to be more reactive than styrene. This is also in agreement with the concept of two mechanisms. Here, 1-heptene assists in the formation of GeCl3 radicals and styrene acts as a radical trap, forming selectively only the anti-Markovnikov adduct. 

The addition of J-butyl hypoiodite to selected olefins has been investigated21. In the absence of BF3 and in the dark, /-BuOI reacts with styrene to give the anti-Markovnikov regioisomer (i.e. by a free radical mechanism). In the presence of BF3, /3-t-butoxy-/ -... 

The change in regiochemistry is a result of a change in the mechanism of the reaction, from an ionic mechanism in the Markovnikov reaction to a radical chain mechanism in the anti-Markovnikov reaction. The radical chain mechanism for the addition of hydrogen bromide to 1-butene is outlined in the following equations ... 

In 1933, M. S. Kharasch and F. W. Mayo found that some additions of HBr (but not HC1 or HI) to alkenes gave products that were opposite to those expected from Markovnikov s rule. These anti-Markovnikov reactions were most likely when the reagents or solvents came from old supplies that had accumulated peroxides from exposure to the air. Peroxides give rise to free radicals that initiate the addition, causing it to occur by a radical mechanism. The oxygen-oxygen bond in peroxides is rather weak, so it can break to give two alkoxy radicals. 

Alkoxy radicals (R—O -) initiate the anti-Markovnikov addition of HBr. The mechanism of this free-radical chain reaction is shown in Mechanism 8-3. 

However, in the presence of peroxide the addition of HBr follows anti-Markovnikov s addition to give n-propyl bromide. This is often known as the peroxide effect ° and the addition proceeds by the free radical mechanism (Scheme 2.44). 

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