Alkyl halides from carbocations

How does addition of AICI3 promote formation of carbocations from alkyl halides ... 

The second example of this Section shows instead an opposite behaviour. In this example, the dissociation of the methyl fluoride (CH3F) CF bond in methanol (CH3OH) solution is illustrated. Similar reactions, namely the production of carbocations in polar solvents from alkyl halides, are important in organic synthesis where very often they are favoured by the presence of a catalyst, normally a metal cation. Methanol is a polar solvent the dielectric constant e is 32.6 at 298 K, about half of that of water, but the ratio (e — l)/e is close to unity, showing a strong capability to polarize in a static external electric field. Nevertheless this dissociation is energetically unfavourable. 

The investigations described in this chapter show that nature and concentration of the negative counterion has a great influence on the outcome of carbocationic telomerizations because of the different rates of ion-pair collapse and because of reionization of eventually produced 1 1 adducts from alkyl halides and alkenes. On the other hand, it was found that the rate of attack of a carbocation at an alkene is generally independent of the nature of the complex counterion and that free and paired carbocations react with equal rates. If this conclusion also holds for carbocationic polymerizations, a reinterpretation of many polymerization kinetics becomes necessary. 

The alkyl carbocations formed from alkyl halides, aikenes and alcohols act as an electrophile in Friedel-Crafts alkylation reactions. ... 

Carbonium ions can be generated at a variety of oxidation levels. The alkyl carbocation can be generated from alkyl halides by reaction with a Lewis acid (RCl + AICI3) or by protonation of alcohols or alkenes. The reaction of an alkyl halide and aluminium trichloride with an aromatic ring is known as the Friedel-Crafts alkylation. The order of stability of a carbocation is tertiary > secondary > primary. Since many alkylation processes are slower than rearrangements, a secondary or tertiary carbocation may be formed before aromatic substitution occurs. Alkylation of benzene with 1-chloropropane in the presence of aluminium trichloride at 35 °C for 5 hours gave a 2 3 mixture of n- and isopropylbenzene (Scheme 4.5). Since the alkylbenzenes such as toluene and the xylenes (dimethylbenzenes) are more electron rich than benzene itself, it is difficult to prevent polysubsiitution and consequently mixtures of polyalkylated benzenes may be obtained. On the other hand, nitro compounds are sufficiently deactivated for the reaction to be unsuccessful. 

My first contact with Meerwein was in 1954 when I received, while still working in isolated Hungary, a letter from him. He had read a paper of ours, and offered useful comments, even pointing out that we had missed a relevant reference. We subsequently kept up correspondence. He continued to be interested in our early efforts to obtain long lived carbocations from alkyl (and acyl) fluorides in liquid boron trifluoride (and other Lewis acid halides) at low temperature, as well as via metathetic reactions of organic halides with silver tetrafluoroborate (a reagent we introduced in 1955 for the ionization of bromocyclohexadienes to form benzenium ions and which Meerwein developed to a wide utility akylation method). 

Tertiary carbocations may be conveniently prepared in such media from alkyl halides, alcohols, and alkenes. Secondary cations can be observed at low temperatures, but they rearrange readily to more stable tertiary ions. For such cases, special techniques of mixing the reactants, e.g. cocondensation on a cold surface ( molecular beam technique ), have been developed43. Attempts to prepare primary ions in the same manner have not been successful. Methyl and ethyl fluorides exchange halogen but do not generate observable concentrations of cations. All other simple... 

Lewis superacid-catalyzed direct alkylation of alkanes is also possible with alkyl cations prepared from alkyl halides and SbFs in sulfuryl chloride fluoride solution. " Typical alkylation reactions are those of propane and butanes by 2-butyl and ZerZ-butyl cations. The ClfU-Sbfs and C2H5F-SbF5 complexes acting as incipient methyl and ethyl cations besides alkylation preferentially cause hydride transfer. Since intermolecular hydride transfer between different carbocations and alkanes are faster than alkylation, a complex mixture of alkylated products is usually formed. A significant amount of 2,3-dimethylbutane was, however, detected when propane was propylated with the 2-propyl cation at low temperature [Eq. (6.36)]. No 2,2-dimethylbutane, the main product of conventional acid-catalyzed alkylation, was detected, which is a clear indication of predominantly nonisomerizing reaction conditions. 

In addition to reacting with carbocations generated from alkyl halides, benzene can react with carbocations generated from the reaction of an alkene (Section 4.1) or an alcohol (Section 12.1) with an acid. 

Reaction of an aromatic compound with a carbocation (called the Friedel-Crafts alkylation) affixes an alkyl group onto the aromatic ring. In this electrophilic aromatic substitution reaction, there are several methods for generating the carbocation, including from alkyl halides (RX plus FeXs, or AICI3), alcohols (ROH, BF3) and alkenes (alkene, acid). 

Carbocation Generation from Alkyl Halides. Alkyl chlorides, fluorides, and bromides are convenient and frequently used precursors for generation of alkyl cations in HSOsF-SbFs systems.It should be noted, however, that the HSOsF-SbFs system is less suitable than SbFs for the generation of alkyl, especially secondary alkyl, cations from the corresponding alkyl halides. Ionization of cyclohexyl chloride In Magic Acid Is accompanied by Isomerization, 3deldlng the 1-methyl- 1-cyclopentyl cation (eq 3). ... 

Like alcohol dehydrations El reactions of alkyl halides can be accompanied by carbocation rearrangements Eliminations by the E2 mechanism on the other hand nor mally proceed without rearrangement Consequently if one wishes to prepare an alkene from an alkyl halide conditions favorable to E2 elimination should be chosen In prac tice this simply means carrying out the reaction m the presence of a strong base... 

Dehydrohalogenation of alkyl halides (Sections 5 14-5 16) Strong bases cause a proton and a halide to be lost from adjacent carbons of an alkyl halide to yield an alkene Regioselectivity is in accord with the Zaitsev rule The order of halide reactivity is I > Br > Cl > F A concerted E2 reaction pathway is followed carbocations are not involved and rearrangements do not occur An anti coplanar arrangement of the proton being removed and the halide being lost characterizes the transition state... 

Section 5 15 Dehydrohalogenation of alkyl halides by alkoxide bases is not compli cated by rearrangements because carbocations are not intermediates The mechanism is E2 It is a concerted process m which the base abstracts a proton from the p carbon while the bond between the halogen and the a carbon undergoes heterolytic cleavage... 

Figure 6 4 shows the complementary nature of the electrostatic potentials of an alkene and a hydrogen halide We also know (from Section 4 8) that carbocations when gen erated m the presence of halide anions react with them to form alkyl halides... 

Partial but not complete loss of optical activity m S l reactions probably results from the carbocation not being completely free when it is attacked by the nucleophile Ionization of the alkyl halide gives a carbocation-hahde ion pair as depicted m Figure 8 8 The halide ion shields one side of the carbocation and the nucleophile captures the carbocation faster from the opposite side More product of inverted configuration is formed than product of retained configuration In spite of the observation that the products of S l reactions are only partially racemic the fact that these reactions are not stereospecific is more consistent with a carbocation intermediate than a concerted bimolecular mechanism... 

Unbranched primary alcohols and tertiary alcohols tend to react with hydrogen halides without rearrangement The alkyloxonmm ions from primary alcohols react rap idly with bromide ion for example m an Sn2 process Tertiary alcohols give tertiary alkyl halides because tertiary carbocations are stable and show little tendency to rearrange... 

Carbocations usually generated from an alkyl halide and aluminum chloride attack the aromatic ring to yield alkylbenzenes The arene must be at least as reactive as a halobenzene Carbocation rearrangements can occur especially with primary alkyl hal ides... 

One-electron oxidation of carboxylate ions generates acyloxy radicals, which undergo decarboxylation. Such electron-transfer reactions can be effected by strong one-electron oxidants, such as Mn(HI), Ag(II), Ce(IV), and Pb(IV) These metal ions are also capable of oxidizing the radical intermediate, so the products are those expected from carbocations. The oxidative decarboxylation by Pb(IV) in the presence of halide salts leads to alkyl halides. For example, oxidation of pentanoic acid with lead tetraacetate in the presence of lithium chloride gives 1-chlorobutane in 71% yield ... 

One way of determining carbocation stabilities is to measure the amount of energy required to form the carbocation by dissociation of the corresponding alkyl halide, R-X - R+ + X . As shown in Figure 6.10, tertiary alkyl halides dissociate to give carbocations more easily than secondary or primary ones. As a result, trisubstituted carbocations are more stable than disubstituted ones, which are more stable than monosubstituted ones. The data in Figure 6.10 are taken from measurements made in the gas phase, but a similar stability order is found for carbocations in solution. The dissociation enthalpies are much lower in solution because polar solvents can stabilize the ions, but the order of carbocation stability remains the same. 

Note that in the S l reaction, which is often carried out under acidic conditions, neutral water can act as a leaving group. This occurs, for example, when an alkyl halide is prepared from a tertiary alcohol by reaction with HBr or HC1 (Section 10.6). The alcohol is first protonated and then spontaneously loses H2O to generate a carbocation, which reacts with halide ion to give the alkyl halide (Figure 11.13). Knowing that an SN1 reaction is involved in the conversion of alcohols to alkyl halides explains why the reaction works well only for tertiary alcohols. Tertiary alcohols react fastest because they give the most stable carbocation intermediates. 

The mechanism of these reactions is usually Sn2 with inversion taking place at a chiral RX, though there is strong evidence that an SET mechanism is involved in certain cases, ° especially where the nucleophile is an a-nitro carbanion and/or the substrate contains a nitro or cyano group. Tertiary alkyl groups can be introduced by an SnI mechanism if the ZCH2Z compound (not the enolate ion) is treated with a tertiary carbocation generated in situ from an alcohol or alkyl halide and BF3 or AlCla, or with a tertiary alkyl perchlorate. ... 

Apart from the alkyl halide-Lewis acid combination, two other sources of carbo-cations are often used in Friedel-Crafts reactions. Alcohols can serve as carbocation precursors in strong acids such as sulfuric or phosphoric acid. Alkylation can also be effected by alcohols in combination with BF3 or A1C13.37 Alkenes can serve as alkylating agents when a protic acid, especially H2S04, H3P04, and HF, or a Lewis acid, such as BF3 and A1C13, is used as a catalyst.38... 

Addition of hydroxide occurs as a rapid follow-up reaction. Even if the alkyl halide was chiral before the carbocation formed, racemization occurs about the central carbon atom because the hydroxide can bond to the planar central carbon from either side (see Figure 8.17(b)). Statistically, equal numbers of each racemate are formed, so the angle through which the plane polarized light rotated during reaction will, therefore, decrease toward 0°, when reaction is complete. 

We have seen that substitution in secondary and tertiary alkyl halides proceeds by an SN1 mechanism in which there is first slow ionisation resulting in the formation of a flat carbocation and hence the attack by the nucleophilic reagent can take place equally well from either side, i.e., equal amounts of (+) and (-)- forms are likely to be produced giving a racemic product ... 

To be really satisfactory, a Friedel-Crafts alkylation requires one relatively stable secondary or tertiary carbocation to be formed from the alkyl halide by interaction with the Lewis acid, i.e. cases where there is not going to be any chance of rearrangement. Note also that we are unable to generate carboca-tions from an aryl halide - aryl cations (also vinyl cations, see Section 8.1.3) are unfavourable - so that we cannot nse the Friedel-Crafts reaction to join aromatic gronps. There is also one further difficulty, as we shall see below. This is the fact that introduction of an alkyl substitnent on to an aromatic ring activates the ring towards fnrther electrophilic substitution. The result is that the initial product from Friedel-Crafts alkylations is more reactive than the... 

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