1.4- Electrophilic addition

Electrophilic addition is an important reaction for alkenes. When you see an alkene on the MCAT, check for electrophilic addition. An electrophile j.s an eiec-LrOn-loving species, so il will have at leas I a partially positive charge, even if it is only from a momentary dipole. The double bond of an alkene is an electron-rich environment and will attract electrophiles, 

When hydrogen halides (HF, HC1, HBr, and HI) are added to alkenes, they follow Markovnikov s rule unless otherwise specified on the MCAT, Markovnikov s rule says the hydrogen will add to the least substituted carbon of the double bond . The reaction takes place in two steps. First, the hydrogen halide, a Bronsted-Lowry acid, creates a positively charged proton, which acts as the electrophile. Second, the newly formed carbocation picks up the negatively charged halide ion. The first step is the slow step and determines the rate. 

Tho reaction follows Markovnikov s rule because the rule dictates the formation of the more stable carbocation. You should be aware that if peroxides (ROOR) are present the bromine, not the hydrogen, will add to the least substituted carbon. This is called an anti-Markovnikov addition. The other halogens will still follow Markovnikov s rule even in the presence of peroxides. 

The most reactive alkenes in electrophilic addition are the most thermodynamically stable. This is because they also have the lowest activation energy when forming carbocations. Hydrogen halides add to alkynes in nearly the same way they add to alkenes. 

Hydration of an alkene also follows Markovnikov s rule. Hydration takes place when water is added to an alkene in the presence of an acid. Tlxis reaction is the reverse of dehydration of an alcohol. Low temperatures and dilute add drive this reaction toward alcohol formation high temperatures and concentrated acid drive the reaction toward alkene formation. 

Electrophilic Addition.—Reactions of androsta-3,5-dienes with MCPBA gave complex mixtures the composition of which was dependent upon the level of peracid used (1 or 2 equivalents). Diepoxides were isolated in low yield only when 2 equivalents were used and in general products were derived from epoxide ring opening.34 In a study of the structures of withanolides G,H,I,J,K, and U which were all shown to possess the 14a-hydroxy-group, it was demonstrated that the 14a-hydroxy-group influenced the epoxidation of the 5,6-double bond.35 Incorporation of ozonizable dyes as internal standards facilitated selective ozonization of 

Kocovsky and V. Cerny, Collect. Czech. Chem. Commun., 1980, 45, 3023. 

Electrophilic Addition.—K detailed kinetic and product analysis of the reaction of 1,2-dimethylcyclohexene with HCl in acetic acid has b n made at 10% conversion, when secondary reactions are unimportant. Addition of HCl takes place by two competing mechanisms a carbonium chloride ion pair (Ad 2) leading to (319) as the major product, and a termolecular 

Addition of antimony pentachloride to cyclohexene gives 1,2-dichloro-cyclohexanes in a cisUrans ratio of 5, whereas chlorination with other metal chlorides gives mainly trans addition, as in the case using elemental chlorine. lodonium nitrate, prepared in situ by addition of ICI to AgNOg in chloroform-pyridine, adds to alkenes at room temperature to form (/) iodonitrate esters (325) (trans addition), (ii) iodoalkane pyridinium nitrates (326), or (Hi) alkene pyridinium iodides (327) depending on the substrate. Compounds (326) and (327) may be formed by nucleophilic displacement of 

The iodocarbamates obtained are easily hydrogenolysed by zinc and acid to provide a synthesis of the carbamates (331) from olefins.  

Anti-Markovnikov addition of HBr to terminal olefins is ected by bromination of the derived organoboranes in the presence of sodium methoxide. Alternatively, alk-l-enes are converted to primary alkyl bromides by the sequence  

The well-known hydroalumination of olefins with dialkylaluminium hydrides can be extended to the addition of diethylaluminium chloride. With diphenylpropene the intermediate (332) is formed, together with ethylene, and yields l,l-diphenylpropan-2-ol in 90% yield on oxidation with H2O2. 

Stoichiometric studies of M-H additions to alkynes also show mixed stereochemical results. The more common cw-addition is typified by the CO-promoted transformation of Cp2Nb(H)(RCECR) to ds-Cp2Nb(CO)(Ti -CR=CHR) [90]. In mononuclear systems where frans-additions have been found, radical-type mechanisms have been implicated [91] or cis/trans isomerization of the intermediate vinyl species [92] has been found. Although the intermediacy of alkyne complexes has not been established, Schwartz s hydrozirconation of alkynes [93] by Cp2ZrHCl represents a general entry to vinyl-metal species which can be transformed stereoselectively to alkenes, vinyl halides, and/or carboxylic acids. 

In Section 9.3, we learned about the addition of HX across an alkene. 

We saw that the reaction proceeds via Markovnikov addition, that is, the bromine is positioned at the more substituted carbon. This regiochemical outcome was explained with the following proposed mechanism, comprised of two steps  

The first step of the mechanism controls the regiochemical outcome. Specifically, protonation occurs so as to create the more stable, tertiary carbocation, rather than the less stable, primary carbocation. 

When butadiene is treated with HBr, a similar process takes place, but two major products are observed. 

The formation of these two products can be explained with a similar two-step mechanism protonation to form a carbocation followed by nucleophilic attack. In the first step, protonation creates the more stable, resonance-stabilized, allylic carbocation, rather than an unstabilized primary carbocation. 

The stereochemistry of electrophilic addition to norbornenes and norbomadienes is very interesting . As these reactions form on intermediate carbocations, there arises, just as for the solvolysis of 2-substituted norbornanes and norbornenes, the question of the nature of these ions — classical or nonclassical. The electrophilic addi- 

The main peculiarities of the addition of electrophilic reagents to norbornene are intensive skeletal rearrangements, formation of cis-adducts, exo-addition of both an electrophile and a nucleophile. The unusual process of cis-exo-addition was explained by nonclassical carbocations or rapid equilibrium of classical ions steric 

Later on Brown compared the stereochemical resulte of adding various 

In these reactions Brown pointed out extremely high stereospecificity of formation of exo-norbornyl esters —99.98 % If the sole intermediate were a nonclassical ion 

Neither can the experimental results be explained by the assumption of a rapid equilibrium of classical ions imitating a nonclassical ion since in this case the distribution of deuterium between C and C must be equal. The addition of acetic acid can proceed through two mechanisms ionic addition via a nonclassical ion ( 50%) and simultaneous molecular exo-cis-addition ( 50%). Brown, however, showed that the addition of the acetoxy group when acetic acid acts on 7,7-di-methylnorbomene proceeds with the same stereospecificity (99.98 % of exo isomer) as in the reaction with norbomene i.e. simultaneous addition of acetic acid seem to be highly improbable. 

With both negative nucleophilic—or nucleous seeking) and positive electrophilic—or electron seeking) species present, the double bond could, in principle, be attacked by the nucleophile or the electrophile. Both are known but the latter are much more common and are collectively organized under the rubric electrophilic addition. 

The formalism of Equation 6.25 is common among electrophilic addition reactions. Generally, the curved arrow is drawn from the double bond (showing the movement of a pair of electrons) to the electron-deficient species, thus forging a bond to carbon. The curved arrow then becomes the bond. The consequence is the formation of an electron-deficient intermediate (shown here as a carbocation), which is then attacked by an electron-rich nucleophile. Again, the curved arrow, showing the movement of a pair of electrons, becomes the bond.  

Finally, it is reasonable to ask what might occur as a second step in electrophilic addition should no reasonably reactive nucleophile be present. 

A discussion of all but a few examples is clearly beyond this text. 

The 20 examples in the table are an incomplete (but representative) set of electrophiles and examples of the kinds of products that result from their respective reactions with a representative generic alkene. The representations of product stereochemistry in the table are incomplete. Reactions of double bonds with nucleophilic reagents and electrocyclic and related processes are intentionally excluded and will be considered subsequently. 

Less common addition reactions such as the bromination of trifhioromethyl-substi-tuted butatrienes [30] or the reaction of tetrafluoroallene with boron trifluoride have also been reported [283]. Especially the interaction of phosphorylated allenes with electrophiles was summarized in a review by Alabugin and Brel [8], whereas Smadja [284] published a more general overview about the electrophilic addition to allenic derivatives. 

The ring closure to form butenolides by palladium(O) catalysis can be combined with C,C bond linking, as shown by Ma and co-workers. If using tetrakis (triphenyl -phosphane)palladium(O), the products 272 are obtained from 268 (R1 = alkyl, R2 = H) and vinyl iodides or aryl bromides and iodides R3X [304]. The authors assume that 

By treatment of allenic esters with N-benzylideneaniline and boron trifluoride, ring dosures to but-2-enolides with introduction of a carbon substituent at position 3 are also possible [306], However, both the number of examples and the yields are low. 

With catalysis by tetrakis(triphenylphosphane)palladium(0), the reaction of allenic amides 275 and aryl or vinyl iodides afforded Z-configured iminolactones 277 

Recently, the highlights of new transition metal catalyzed reactions of allenes were summarized by Hashmi [315], and Zimmer et al. published a comprehensive review of palladium-catalyzed reactions of allenes [316]. 

As a zero-electron reagent, an electrophile such as H or Me can attack the ligand, or the M-L bonds, or the metal—even in an 18e complex. Particularly in the case of the proton, initial attack may occur at one site, followed by rearrangement with transfer to a second site, so the location of the electrophile in the final product may be misleading. Electrophilic addition to metal complexes can therefore be mechanistically complexit is also less easily controllable and less often used than nucleophilic addition. 

Oxidative addition by the Sn2 or by the ionic mechanisms involves electrophilic additicHi to the metal (Eq. 8.33 and Sections 6.2 and 6.4) in the first step  

In some cases the second step does not take place, and the counterion never binds to the metal. This makes the reaction an electrophilic addition, rather than an oxidative addition to the metal, although the latter term is sometimes seen in the literature to describe this type of reaction. An example is the reaction of the highly nucleophilic Co(I) anion, Co(dmg)2py] , with an alkyl triilate, a reaction known to go with inversion. Protonation of metal complexes to give metal hydrides is also very common (Eqs. 3.30-3.31). 

Chung and co-workers result of Eq 8.34 shows how a conventional deprotonation, followed by a nucleophilic attack, leaves the metal t n to electrophilic attack by the carbonyl carbon in the last step. 

Protonaiion reactions are the most common. For example, a hydride can give a dihydrogen complex.  

In this case, no stereochemistry is implied. The distribution of the products depends on the reaction conditions shown in Table 4-1. The information in the last column of the table indicates the process is reversible and an equilibrium results upon heating. The equilibrium leads to the production of the more stable product. 

Examining the mechanism can help you understand the different results. 

The bromide has an equal probability of attacking either carbon atom two or carbon atom four, so why is the product mixture not 50 percent of each At low temperatures, the bromine doesn t move very ftir after giving up its H, so it s near Ccirbon two (1,2-addition). At high temperatures, the bromine donates an H and can move, so it s able to form the more stable product (a disubstituted C=C). 

2-addition is rate controlled, which leads to the formation of the kinetic product (fastest formed). This formation is especially noticeable at low temperatures because they always favor the kinetic product, which is the reaction product with the lower activation energy barrier. In addition, few molecules have sufficient energy to surmount the barrier in the reverse direction to allow the establishment of an equilibrium. 

4-addition is thermodynamically controlled. This reaction forms the thermodynamic product. At higher temperatures, more molecules have sufficient energy to cross the second barrier in the reverse direction and establish an equilibrium. The equilibrium allows the less stable 1,2-addition product to convert to the more stable 1,4-addition product. 

Kamano and M. Tozawa, Yuki Gosei Kagaku Kyokai Shi, 1976, 34, 118. 

A detailed examination of OSO4 reactions with A -steroids has been reported. The A-ring conformation of the reactant or derived complex is important in determining the stereoselectivity of these reactions, and the major role of the proximate substituents is to anchor the appropriate conformation favouring a- or /3-attack. Studies on the stereochemistry of electrophilic attack on cholest-5-en-3-one continue. As with bromine chloride, appreciable /3-attack occurs and the 5/3,6j8-epoxide was isolated along with the previously reported 5a,6a-epoxide and the Baeyer-Villiger product, the A-homo-enol lactone (58). Base-catalysed 

Peracid oxidation of the D-homo-oestrone derivative (59) gave the C-ring aromatic compound (60). ° Mono- or tri-formylation with DMF-POCI3 of 17-methylene-steroids led to the unsaturated aldehydes (61) or the dimethylamino-bisaldehydes (62) which were readily converted with NHa-EtOH into the heterocycles (63). 14-Azidopregnanes are available from the reactions of A - 

Hydrogen fluoride adds on to cholest-4-en 7a-ol (143) at — 60°C to give the 5a-fluoro-compound (144) almost quantitatively, but reaction with the 4-en-7) -ol 

Two distinct reactions are described between 9(ll)-enes (148) and nitrosyl fluoride. Reaction at 3°C in dichloromethane gave the 9a-fluoro-ll-nitrimino-derivative (149), hydrolysed on passage through alumina to give the fluoro-ketone 

Nitrosyl chloride, being a powerful oxidant, affords chloro-nitro-compounds by oxidation at the initial chloro-nitroso stage. frons-Addition of nitrosyl chloride seems to be usual, but an exceptional ds-addition occurred with methyl 3a,7a-diacetoxy-5)3-chol-ll-enoate, giving the lla-chloro-12a-nitro-compound. The rate of reaction was increased in the presence of nitrogen dioxide a free-radical mechanism is thought likely.  

Bromine addition to ergost-7-en-3-one (152) gave mainly a 7,1 l-dibromo-8-ene (153), with a little of the 7,8-dibromo-14-ene (154). Sodium iodide converted the 7,11-dibromide into the 7,9(ll)-diene (155), giving a slightly better over-all yield than dehydrogenation of the 7-ene with mercuric acetate, although neither route was really satisfactory. 

The 9(ll)-dehydro-8) -methyloestrane analogue (156) adds hypobromous acid in the abnormal cis sense, to give the 11 )3-bromo-9j8-alcohol (157), in contrast to most 9(ll)-enes which give 9a-bromo-ll) -alcohols. An ll) -substi-tuent in the 9a-series would be acutely compressed by the 8)3- and 13/3-methyl 

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Markovnikov s rule like Zaitsev s organizes experimental observations in a form suitable for predicting the major product of a reaction The reasons why it works will appear when we examine the mechanism of electrophilic addition m more detail... 

The second mechanism is the one followed when addition occurs opposite to Markovmkov s rule Unlike electrophilic addition via a carbocation intermediate this alternative mechanism is a chain reaction involving free radical intermediates It is pre sented m Figure 6 7... 

Among the hydrogen halides only hydrogen bromide reacts with alkenes by both electrophilic and free radical addition mechanisms Hydrogen iodide and hydrogen chlo ride always add to alkenes by electrophilic addition and follow Markovmkov s rule Hydrogen bromide normally reacts by electrophilic addition but if peroxides are pres ent or if the reaction is initiated photochemically the free radical mechanism is followed... 

Markovmkov s rule is obeyed because the mechanism of sulfuric acid addition to alkenes illustrated for the case of propene m Figure 6 8 is analogous to that described earlier for the electrophilic addition of hydrogen halides... 

We can extend the general principles of electrophilic addition to acid catalyzed hydration In the first step of the mechanism shown m Figure 6 9 proton transfer to 2 methylpropene forms tert butyl cation This is followed m step 2 by reaction of the car bocation with a molecule of water acting as a nucleophile The aUcyloxomum ion formed m this step is simply the conjugate acid of tert butyl alcohol Deprotonation of the alkyl oxonium ion m step 3 yields the alcohol and regenerates the acid catalyst... 

In contrast to the free radical substitution observed when halogens react with alkanes halogens normally react with alkenes by electrophilic addition... 

Neither bromine nor ethylene is a polar molecule but both are polarizable and an induced dipole/mduced dipole force causes them to be mutually attracted to each other This induced dipole/mduced dipole attraction sets the stage for Br2 to act as an electrophile Electrons flow from the tt system of ethylene to Br2 causing the weak bromine-bromine bond to break By analogy to the customary mechanisms for electrophilic addition we might represent this as the formation of a carbocation m a bimolecular elementary step... 

Thus the mechanism for electrophilic addition of Bi2 to ethylene as presented m Figure 6 12 IS characterized by the direct formation of a cyclic bromonium ion as its... 

FIGURE 6 12 Mechanism of electrophilic addition of bromine to ethylene... 

When formulating a mechanism for the reaction of alkynes with hydrogen halides we could propose a process analogous to that of electrophilic addition to alkenes m which the first step is formation of a carbocation and is rate determining The second step according to such a mechanism would be nucleophilic capture of the carbocation by a halide ion... 

FIGURE 9 5 (a) Curved arrow notation and (b) transition state for electrophilic addition of a hydrogen halide HXto an alkyne... 

For further discussion of this topic see the article The Electrophilic Addition to Alkynes in the November 1993 edition of theVourna/ of Chemical Education (p 873) Additional common tary appeared in the Novem ber 1996 issue... 

Furthermore kinetic studies reveal that electrophilic addition of hydrogen halides to alkynes follows a rate law that is third order overall and second order in hydrogen halide... 

Both resonance forms of the allylic carbocation from 1 3 cyclopentadiene are equivalent and so attack at either of the carbons that share the positive charge gives the same product 3 chlorocyclopentene This is not the case with 1 3 butadiene and so hydrogen halides add to 1 3 butadiene to give a mixture of two regioisomeric allylic halides For the case of electrophilic addition of hydrogen bromide at -80°C... 

When the major product of a reaction is the one that is formed at the fastest rate we say that the reaction is governed by kinetic control Most organic reactions fall into this category and the electrophilic addition of hydrogen bromide to 1 3 butadiene at low temperature is a kmetically controlled reaction... 

The regioselectivity of electrophilic addition is governed by the ability of an aro matic ring to stabilize an adjacent carbocation This is clearly seen m the addition of hydrogen chloride to mdene Only a single chloride is formed... 

Section 11 16 Addition reactions to alkenylbenzenes occur at the double bond of the alkenyl substituent and the regioselectivity of electrophilic addition is governed by carbocation formation at the benzylic carbon See Table 11 2... 

Electrophilic addition (Section 11 16) An aryl group stabilizes a benzylic carbocation and con trols the regioselectivity of addition to a double bond involving the benzylic carbon Markovni kov s rule is obeyed... 

Recall from Chapter 6 the general mechanism for electrophilic addition to alkenes... 

The diminished rr electron density m the double bond makes a p unsaturated aide hydes and ketones less reactive than alkenes toward electrophilic addition Electrophilic reagents—bromine and peroxy acids for example—react more slowly with the carbon-carbon double bond of a p unsaturated carbonyl compounds than with simple alkenes... 

Isoprene has sometimes been used as a starting matenal in the laboratory synthesis of ter penes In one such synthesis the first step is the electrophilic addition of 2 moles of hydrogen bromide to isoprene to give 1 3 dibromo 3 methylbutane... 

Electrophile (Section 4 8) A species (ion or compound) that can act as a Lewis acid or electron pair acceptor an elec tron seeker Carbocations are one type of electrophile Electrophilic addition (Section 6 4) Mechanism of addition in which the species that first attacks the multiple bond is an electrophile ( electron seeker )... 

The aromatic ring of a phenoxy anion is the site of electrophilic addition, eg, in methylolation with formaldehyde (qv). The phenoxy anion is highly reactive to many oxidants such as oxygen, hydrogen peroxide, ozone, and peroxyacetic acid. Many of the chemical modification reactions of lignin utilizing its aromatic and phenoHc nature have been reviewed elsewhere (53). 

Electrophilic Addition. Electrophilic reagents attack the electron-deficient bond of maleic anhydride (25). Typical addition reagents include halogens, hydrohaHc acids, and water. 

Electrophilic Addition. In the following example, an a-olefin reacts with a Lewis acid to form the most stable intermediate carbocation. This species, in turn, reacts with the conjugate base to produce the final product. Thus electrophilic addition follows Markovnikov s rule. 

Electrophile Addition Reactions. The addition of electrophilic (acidic) reagents HZ to propylene involves two steps. The first is the slow transfer of the hydrogen ion (proton) from one base to another, ie, from Z to the propylene double bond, to form a carbocation. The second is a rapid combination of the carbocation with the base, Z . The electrophile is not necessarily limited to a Lowry-Briiinsted acid, which has a proton to transfer, but can be any electron-deficient molecule (Lewis acid). 

Electrophilic addition to quinones, eg, the reaction of 2-chloro-l,4-ben2oquinones with dia2onium salts, represents a marked contrast with acetoxylation in product distribution (58). Phenyldia2onium chloride (Ar = C H ) yields 8% 2,3-substitution [80632-59-3] 75% 2,5-substitution [39171-11-4] and 17% 2,6-substitution [80632-60-6]. Fory)-chlorophenyldia2onium chloride, the pattern is 28% 2,3-substitution [80632-61-7], 35%... 

Direct Chlorination of Ethylene. Direct chlorination of ethylene is generally conducted in Hquid EDC in a bubble column reactor. Ethylene and chlorine dissolve in the Hquid phase and combine in a homogeneous catalytic reaction to form EDC. Under typical process conditions, the reaction rate is controlled by mass transfer, with absorption of ethylene as the limiting factor (77). Ferric chloride is a highly selective and efficient catalyst for this reaction, and is widely used commercially (78). Ferric chloride and sodium chloride [7647-14-5] mixtures have also been utilized for the catalyst (79), as have tetrachloroferrate compounds, eg, ammonium tetrachloroferrate [24411-12-9] NH FeCl (80). The reaction most likely proceeds through an electrophilic addition mechanism, in which the catalyst first polarizes chlorine, as shown in equation 5. The polarized chlorine molecule then acts as an electrophilic reagent to attack the double bond of ethylene, thereby faciHtating chlorine addition (eq. 6) ... 

Initiation is an electrophilic addition of a cation across the double bond, but because of the poor nucleophilicity of the initiator s counterion. 

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