Substitution and Elimination as Competing Reactions

We have seen that a Lewis base can react with an alkyl halide by either substitution or elimination. 

How can we predict whether substitution or elimination will predominate The two most important factors are the structure of the alkyl halide and the basicity of the anion. It is useful to approach the question from the premise that the characteristic reaction of alkyl halides with Lewis bases is elimination, and that substitution predominates only under certain special circumstances. In a typical reaction, a secondary alkyl halide such as isopropyl bromide reacts with a Lewis base such as sodium ethoxide mainly by elimination  

As crowding at the carbon that bears the leaving group decreases, the rate of nucleophilic substitution becomes faster than the rate of elimination. A low level of steric hindrance to approach of the nucleophile is one of the special circumstances that permit substitution to predominate, and primary alkyl halides react with alkoxide bases by an 8 2 mechanism in preference to E2  

When a Lewis base reacts with an alkyl halide, either substitution or elimination can occur. Substitution (8 2) occurs when the Lewis base acts as a nucleophile and attacks carbon to displace bromide. Elimination (E2) occurs when the Lewis base abstracts a proton from the 3 carbon. The alkyl halide shown is isopropyl bromide, and elimination (E2) predominates over substitution with alkoxide bases. 

however, the base itself is crowded, such as potassium tert-butoxide, even primary alkyl halides undergo elimination rather than substitution  

We have seen that an alkyl halide and a Lewis base can react together in either a substitution or an elimination reaction. 

The large rate enhancements observed for bimolecnlar nncleophilic snbstitutions in polar aprotic solvents are nsed to advantage in synthetic apphcations. An example can be seen in the preparation of alkyl cyanides (nitriles) by the reaction of sodinm cyanide with alkyl hahdes  

Hexyl halide Sodium cyanide Hexyl cyanide Sodium halide 

When the reaction was carried ont in aqueous methanol as the solvent, hexyl bromide was converted to hexyl cyanide in 71% yield by heating with sodium cyanide. Although this is a perfectly acceptable synthetic reaction, a period of over 20 hours was required. Changing the solvent to dimethyl sulfoxide brought about an increase in the reaction rate sufhcient to allow the less reactive substrate hexyl chloride to be used instead, and the reaction was complete (91% yield) in only 20 minutes. 

The rate at which reactions occur can be important in the laboratory, and understanding how solvents affect rate is of practical value. As we proceed through the text, however, and see how nucleophilic substitution is applied to a variety of functional group transformations, be aware that it is the nature of the substrate and the nucleophile that, more than anything else, determines what product is formed. 

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The acetylide ion, then, can react with an alkyl halide in two ways by attack at carbon to give substitution, or by attack at hydrogen to give elimination. We have seen that the order of reactivity of alkyl halides toward elimination (Sec. 5.14) is 3 > 2° > 1°. In subslitution (of the present kind), we shall find (Sec. 14.11) the order of reactivity is just the opposite 1° > 2° > 3°. It is to be expected, then, that where substitution and elimination are competing reactions, the proportion of elimination increases as the structure of an alkyl halide is changed from primary to... 

The same considerations hold for the reactions of alkyl halides with other nucleophiles. Where substitution and elimination are competing reactions, the proportion of elimination increases as the structure of an alkyl halide is changed from primary to secondary to tertiary. Many tertiary halides yield exclusively alkenes under these conditions. 

Chapters 11 and 12 discuss reactions of alkyl halides to give either substitution or elimination products. It is clear from Chapter 12 that elimination occurs when the nucleophile is also a strong base and when substitution is inhibited due to steric hindrance. There are many cases in which substitution and elimination compete, particularly when the substrate is a secondary alkyl halide. The solvent plays an important role in these reactions, and solvent identification is a key parameter for distinguishing bimolecular versus unimolecu-lar (ionization) processes. The nature of the alkyl halide (1°, 2°, or 3°) is important, as is the strength of the nucleophile and whether or not that nucleophile can also react a strong base. This chapter will discuss those factors that influence both substitution and elimination, as well as introduce several assumptions that will help make predictions as to the major product. 

In the case of an 1 reaction (e.g. HY elimination) a two-step process is involved (see Scheme 2). In the first step (slow, rate-determining) the leaving group Y departs from the substrate as an anion and a carbocation is formed. Since the latter is also the intermediate of an SnI reaction, the SnI substitution may be a competing reaction. In the second step (fast) the positively charged substrate molecule will lose a proton from C-3 to a base (e.g. the solvent). 

Of course, no attacking species acts purely as a hard or soft base, but rather each has a character that is somewhere along a continuum between one extreme and the other. Accordingly, in any given reaction mixture, substitution and elimination reactions usually compete with each other. 

In all cases where substitution and elimination compete, higher reaction temperatures lead to greater proportions of elimination products. Thus, the amount of elimination accompanying hydrolysis of 2-bromo-2-methylpropane doubles as the tenpCTature is raised from 25 to 65"C, and that from reaction of 2-bromopropane with ethoxide rises from 80% at 25"C to nearly 100% at 55"C. Explain. 

In a comparative study of fluorination of l,2 3,4-di-0-isopropyli-dene-6-O-p-tolylsulfonyl-a-D-galactopyranose with tetrabutylammonium fluoride in a variety of dipolar, aprotic solvents (as well as 1,2-eth-anediol, in which no reaction was observed), acetonitrile was found to give the highest proportion of substitution of the sulfonic esters relative to their elimination.106 Elimination is the major, competing reaction in these nucleophilic-substitution reactions, because of the high basicity and low nucleophilicity of the fluoride ion or, in terms of the... 

A chemical reaction Is the result of competition It Is a race that Is won by the fastest runner. A collection of molecules tend to do, by and large, what Is easiest for them. An alkyl halide with p-hydrogen atoms when reacted with a base or a nucleophile has two competing routes substitution (Sj,jl and Sj,j2) and elimination. Which route will be taken up depends upon the nature of alkyl halide, strength and size of base/nucleophile and reaction conditions. Thus, a bulkier nucleophile will prefer to act as a base and abstracts a proton rather than approach a tetravalent carbon atom (steric reasons) and vice versa. 

The method is suitable for the preparation of ethers having primary alkyl groups only. The alkyl group should be unhindered and the temperature be kept low. Otherwise the reaction favours the formation of alkene. The reaction follows S l pathway when the alcohol is secondary or tertiary about which you will learn in higher classes. However, the dehydration of secondary and tertiary alcohols to give corresponding ethers is unsuccessful as elimination competes over substitution and as a consequence, alkenes are easily formed. 

As the term suggests, a substitution reaction is one in which one group is substituted for another. For nucleophilic substitution, the reagent is a suitable nucleophile and it displaces a leaving group. As we study the reactions further, we shall see that mechanistically related competing reactions, eliminations and rearrangements, also need to be considered. 

Active methylene and methine compounds bearing a leaving group (X) on the y-carbon atom can afford cyclopropyl derivatives via 1,3-elimination of HX. 1,2-Elimination to give alkenes and direct nucleophilic substitution by base may compete with the 1,3-elimination, particularly in the preparation of excessively strained cyclopropyl derivatives. The preferred reaction course is, however, highly dependent on reaction conditions, especially on the nature of the base and solvent employed, as exemplified by the reactions of 4 (equation 7) 4. 

An attempt to study resolved (( )-18) as a probe for the detailed mechanism of the Adn—E vinylic substitution reaction has been complicated by intervention of a competing reaction route this is believed to involve a competing (ElcB elimination-addition, for which antiperiplanar orientation of H and Cl is not a requirement.7 a-Deuterated (ca 50%) E- and Z-substitution products (which do not themselves exchange deuterium) are obtained on reaction with MeS in 9 1 CD3CN-D2O but no incorporation of deuterium in unreacted ((/r)-18) occurs and neither does isomerism to ((Z)-18) precede elimination. 

Scheme 7.15] or S -type mechanism [Equation (7.9)]. Depending on the nature of the nucleophile and catalyst employed, the subsequent nucleophilic substitution of the metal can follow either via a-elimination [path A, Equations (7.8) and (7.9), Scheme 7.15], via an SN2 reaction (path B) or via an SN2 -type reaction (path C). For reasons of clarity, only strictly concerted and stereospecific SN2- or SN2 -anti-type mechanistic scenarios are shown in Scheme 7.15. The situation might, however, be complicated if, e.g., the initial S l -anti ionization event is competing with an Sn2 -syn reaction. Erosion in stereo- and regioselectivity can be the result of these competing reactions. Furthermore, fluxional intermediates such as 7t-allyl Fe complexes are not shown in Scheme 7.15 for reasons of clarity. These intermediates are known for a variety of late transition metal allyl complexes and will be referred to later. Moreover, apart from these ionic mechanisms, radicals might also be involved in the reaction. So far no distinct mechanistic study on allylic substitutions has been published.

The substrates are secondary alkyl -toluene sulfonates, and so we expect elimination to compete with substitution. Compound B is formed in both reactions and has the molecular formula of 4-ferf-butylcyclohexene. Because the two p-toluenesulfonates are diastereomers, it is likely that compounds A and C, especially since they have the same molecular formula, are also diastereomers. Assuming that the substitution reactions proceed with inversion of configuration, we conclude that the products are as shown. 

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