Substituted alkyl halides

Figure 6.10 A plot of dissociation enthalpy versus substitution pattern for the gas-phase dissociation of alkyl chlorides to yield carbocations. More highly substituted alkyl halides dissociate more easily than less highly substituted ones.

Compounds with a low HOMO and LUMO (Figure 5.5b) tend to be stable to selfreaction but are chemically reactive as Lewis acids and electrophiles. The lower the LUMO, the more reactive. Carbocations, with LUMO near a, are the most powerful acids and electrophiles, followed by boranes and some metal cations. Where the LUMO is the a of an H—X bond, the compound will be a Lowry-Bronsted acid (proton donor). A Lowry-Bronsted acid is a special case of a Lewis acid. Where the LUMO is the cr of a C—X bond, the compound will tend to be subject to nucleophilic substitution. Alkyl halides and other carbon compounds with good leaving groups are examples of this group. Where the LUMO is the n of a C=X bond, the compound will tend to be subject to nucleophilic addition. Carbonyls, imines, and nitriles exemplify this group. 

I-or problems II-a through II-c select a properly substituted alkyl halide or alcohol so that the desired alkenc will be the major product of the elimination reaction. (Since there is no limitation as to the number of carbon atoms in the starting material, we do not have to worry about reactions which add... 

Alkylation of / -ketoesters with ( -substituted alkyl halides is an efficient method for the synthesis of cyclic products577-580. In one such reaction sequence, the dianion of a / -ketoester was reacted with 2-(2-bromoethyl)-l,3-dioxolane, the co-substituent in this case being a masked aldehyde. Upon regeneration of the aldehyde functionality, a condensation reaction occurred to give the cyclohexanone as shown in equation 88577. 

Carbocations are common intermediates in organic reactions. Highly substituted alkyl halides can ionize when they are heated in a polar solvent. The strongly electrophilic carbocation reacts with any available nucleophile, often the solvent. 

Some of the same features affect the electrophilicity of tetrahedral electrophiles undergoing SN2 reactions. Thus some donor substituents on the carbon being attacked reduce the electrophilicity of alkyl halides, where the order of reactivity is methyl > ethyl > isopropyl > terf-butyl. The transition structure of an SN2 reaction is inherently electron rich, and donor substituents slow it down. Equally, steric hindrance to attack, the traditional explanation for this reactivity order, is greater for the more substituted alkyl halides. 

A slightly different mechanism has been proposed by Cairncross and Sheppard (37) for the reaction of fluoroarylcopper compounds with substituted alkyl halides. Pentafluorophenylcopper can form a complex with bicyclooctyl bromide by coordination with the halogen atom. Such a complex may go directly to coupled product in a four-center process, or, depending on the nature of the group attached and the nature of the alkyl moiety, may form an ion pair which collapses to the coupled... 

It unites with both halogens in polymethylene halides (two equivalents of sodium amide are required) to form 1-phenyl cycloalkyl cyanides. The action of substituted alkyl halides on phenyl acetonitrile and its horaologs furnishes valuable intermediates for syntheses. ... 

Long-chain halides undergo this reaction at 100°, no C-dialkylated products being formed. In alkylations with aryl-substituted alkyl halides, Ar(CH,) X, n= 1 to 3, yields are improved by performing the reaction rapidly in liquid ammonia (56-9S>%). Also, quinoline methylated in the 2-or 4-position reacts in the same way. A methyl group in the 3-position of pyridine or quinoline is unreactive. 

Like an S l reaction, more substituted alkyl halides yield more substituted (and more stable) car-bocations in the rate-determining step. Increasing the stability of a carbocation, in turn, decreases Eg for the slow step, which increases the rate of the El reaction according to the Hammond postulate. 

Substituted alkyl halides undergo, of course, the reactions characteristic of their other functional groups—nitration of benzyl chloride, oxidation of ethylene bromohydrin, addition to allyl bromide —but as halides they react very much like ethyl or isopropyl or /cr/ butyl halides. 

As mentioned earlier (Sec. 14.1), substituted alkyl halides also undergo the reactions characteristic of their other functional groups. 

In the Williamson synthesis an alkyl halide (or substituted alkyl halide) is allowed to react with a sodium alkoxide or a sodium phenoxide ... 

Like these other nucleophilic substitution reactions, ammonolysis is limited chiefly to alkyl halides or substituted alkyl halides. As with other reactions of this kind, elimination tends to compete (Sec. 14.23) with substitution ammonia can attack... 

An aryl halide is not just any halogen compound containing an aromatic ring. Benzyl chloride, for example, is not an aryl halide, for halogen is not attached to the aromatic ring in structure and properties it is simply a substituted alkyl halide and was studied with the compounds it closely resembles (Chap. 14). 

The alkylation reaction has proved to be more efficient with the softer organometallics of the series and proceeds via an ionic pathway, and via radical species with the most substituted alkyl halides. Although alkyl iodides are usually more reactive than the corresponding bromides and chlorides, the use of the former compounds does not seem to be crucial. 

For S 2, reactions should be designed such that the nucleophile attacks the least highly substituted alkyl halide. ("X" stands for a halide Cl, Br, or I.)... 

The regioselective addition of HX to alkenes produces the more substituted alkyl halide, which is known as the Markovnikov (Markovnikoff) product. Markovnikov s rule states that on addition of HX to an alkene, H attaches to the carbon with fewest alkyl groups and X attaches to the carbon with most alkyl groups . This can be explained by the formation of the most stable intermediate carbocation. 

The addition of HX occurs so as to give the most substituted alkyl halide, following Markovnikov s rule (see Section 6.2.2.1). One or two equivalents of HX can be used to form vinyl halides or dihaloalkanes, respectively. 

Where X is Br or Cl, the free acids may be obtained by acidification of the alkaline solution, but where X is I, the acids must be isolated as salts to avoid reduction of the arsonic acids by HI. Rather than using alkyl halides, alkyl or dialkyl sulfates or alkyl arenesulfonates can be used. Primary alkyl halides react rapidly and smoothly, secondary halides react only slowly, whereas tertiary halides do not give arsonic acids. Allyl halides undergo the Meyer reaction, but vinyl halides do not. Substituted alkyl halides can be used eg, ethylene chlorohydrin gives 2-hydroxyethylarsonic acid [65423-87-2], C2H7As04. Arsinic acids, R sC OH), are also readily prepared by substituting an alkali metal arsonite, RAs(OM)2, for sodium arsenite ... 

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