Addition of bromine to cyclohexene

Addition of bromine to cyclohexene is subject to stereoelectronic control and proceeds via formation of a bromonium ion intermediate. This is followed by spontaneous antiperiplanar (8 2 type), antiparallel opening by the bromide anion via a chairlike TS. Thus, under kinetic control, the predominant or exclusive product formed is via path b resulting from diaxial addition of Br2 to the double bond. 

Bellucci G, Bianchini R, Ambrosetti R (1985) Direct evidence for bromine-olefin charge transfer complexes as essential intermediates of the fast ionic addition of bromine to cyclohexene. J Am Chem Soc 107 2464—2471... 

Addition of bromine to an alkene is highly stereospecific and gives products with stereochemistry consistent with an anti addition mechanism. For example, addition of bromine to cyclohexene produces fraMS-l,2-dibromocyclohexane. Addition of bromine to cis-2-butene produces ( )-2,3-dibromobutane (equation 9.2), while addition to the trans isomer gives the meso product (equation 9.3). ° ... 

One possible mechanism for reactions of Bra" with alkenes involves the dissociation of Bra to Br2 and Br ion before reaction of Bra with the alkene. ° Alternatively, Bra" might act as an electrophile and add directly to the alkene. Bellucci and co-workers used the stopped-flow technique to study the kinetics of addition of bromine to cyclohexene in 1,2-dichloroethane solution. With molecular bromine the kinetics were overall third order, first order in cyclohexene and second order in Bra. 

The addition of bromine and chlorine to a cycloalkene gives a trans dihalocycloal-kane. For example, the addition of bromine to cyclohexene gives trawfrl,2-dibromocyclo-hexane the cis isomer is not formed. Thus, the addition of a halogen to a cycloalkene is stereoselective. A stereoselective reaction is a reaction in which one stereoisomer is formed or destroyed in preference to all others that might be formed or destroyed. We say that addition of bromine to an alkene occurs with anti stereoselectivity. 

The addition of bromine or chlorine to a cycloalkene gives a frans-dihalocydoalkane formed as a racemic mixture. The addition of bromine to cyclohexene, for example, gives Irans-1,2-dibromocydohexane ... 

The trans-addition of bromine to C=C double bonds follows the onium mechanism generally formulated in Figure 3.42. Cyclohexene reacts stereoselectively to give racemic trans-1,2-dibromocyclohexane ... 

Further support for the difference in mechanism for addition with Br2 and Bra" comes from the observation that the two reagents give different stereochemical results upon addition of bromine to 3-substituted cyclohexenes. Bellucci, G. Bianchini, R. Vecchiani, S. /. Org. Chem. 1986,51,4224. Furthermore, the two reagents yield diastereomeric products upon reaction with chiral ketals. Giordano, C. Coppi, L. /. Org. Chem. 1992, 57,2765. 

Addition of bromine to cholesterol inititally produced 5a,6/f-dibromocholestan-3/i-ol (reference 22). Upon standing in methanol solution at room temperature for 3 days, the initial product was converted to a 4 1 mixture of 5/S,6a-dibromocholestan-3/f-ol and the 5a,6j3 isomer. The rate constant for the rearrangement was not affected by a 30-fold molar excess of cyclohexene, suggesting that the rearrangement did not occur by dissociation of the cholesterol dibromide to cholesterol and bromine. 

Syn addition of dichlorocarbene to cyclohexene gives a dichlorocydopropane. Compare this step to the electrophilic addition of bromine and chlorine to an alkene first discussed in Section 6.3D. 

Because only anti addition occurs, addition of Br2 to cyclohexene forms only the enantiomers that have the bromines on opposite sides of the ring. 

The radical addition of halogen to an alkene has been referred to briefly in Section 9.3.2. We saw an example of bromination of the double bond in cyclohexene as an unwanted side-reaction in some allylic substitution reactions. The mechanism is quite straightforward, and follows a sequence we should now be able to predict. 

The silver(I) fluoride/bromine and silver(I) fluoride/iodine systems can be exploited for generation in situ and electrophilic addition of "bromine monofluoride and iodine monofluoride to cyclohexene, mcthylenecyclohcxane, styrene, indene, and acenaphthylene.55... 

Figure 17-8 Apparatus for coulometric titration of cyclohexene with Br2. The solution contains cyclohexene, 0.15 M KBr, and 3 mM mercuric acetate in a mixed solvent of acetic acid, methanol, and water. Mercuric acetate catalyzes the addition of Br2 to the olefin. [Adapted from D. H. Evans, Coulometric Titration of Cyclohexene with Bromine," J. Chem. Ed. 1968,45,88.]... 

Strong differences in the reactivity of the aromatic C=C double bond compared to the reactivity of the C=C double bond of olefins are observed olefinic electrophilic additions are faster than aromatic electrophilic substitutions. For instance, the addition of molecular bromine to cyclohexene (in acetic acid) is about 1014 times faster than the formation of bromobenzene from benzene and bromine in acetic acid113,114. Nevertheless, the addition of halogens to olefins parallels the Wheland intermediate formation in the halogenation of aromatic substrates. 

In addition reactions of bromine to alkenes, Risbood and Ruthven154 have shown that 5A zeolite preadsorbed with bromine can selectively brominate styrene in presence of cyclohexene. By simple alteration of the order of adsorption of reactants to Pentasil zeolites, Smith and Fry155 have been able to add selectively bromine to the double bond of linear alkenes in presence of cyclic and branched alkenes, or to brominate cyclic or branched alkenes in presence of linear ones. An example is shown in equation 9. 

The addition of bromine fluoride to cyclohexene occurs highly stereospecifically to yield the fra/i.v-adduct. Further examples of the bromofluorination of cyclic alkcncs with various reagents are reported in Table 21, and also given by the reactions of norbornene benzo-... 

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