SN1 and El Reactions

The ratio of substitution and elimination remains constant throughout the reaction, which means that each process has the same kinetic order with respect to the concentration of terf-butyl halide. The SN1 and El reactions have a common rate-determining step, namely, slow ionization of the halide. The solvent then has the choice of attacking the intermediate carbocation at the positive carbon to effect substitution, or at a /3 hydrogen to effect elimination ... 

Increasing the temperature of the reaction shifts the balance from the SN2 reactions to the elimination reaction. This is because the elimination reaction has a higher activation energy because of more bonds being broken. The SN1 and El reactions do not occur for primary alkyl halides. 

Under ideal conditions, one of these first-order reactions provides a good yield of one product or the other. Often, however, carbocation intermediates react in two or more ways to give mixtures of products. For this reason, SN1 and El reactions of alkyl halides are not often used for organic synthesis. They have been studied in great detail to learn about the properties of carbocations, however. 

Secondary and tertiary alkyl halides can undergo SN1 or El reactions. Ally lie and benzylic halides can also undergo SN1 or El reactions. (Tertiary halides usually undergo E2 elimination in the presence of strong bases.) Both SN1 and El reactions can occur when using weakly basic or non-basic nucleophiles in protic solvents. 

It would appear from the foregoing that there is a class of gas-phase reactions for which the transition state is best represented as having an essentially carbonium-ion pair character. In this way the effect of substitution at or near the centre of reaction can be interpreted, and the vast body of theory in the literature of physical organic chemistry used for the purpose of predicting rates of gas-phase reactions. In addition, the known properties of carbonium ions, as determined by the mass-spectrometer, can be invoked—as indeed they were in discussions of the SN1 and El reactions in polar solvents (Evans, 1946)—to correlate the effects of substituents in gas-phase eliminations. The advantage of studies in the gas-phase lies in the fact that the behaviour of a single molecule can be observed, without the added complication of the cooperative effect of the solvent. But gas-phase studies may, in turn,... 

As indicated in Table 13.7,1,2-dibromoethane (BrCH2-CH2Br) and 1,1,1-trichloro-ethane (CH3-CC13) are examples in which both hydrolysis and elimination are important. If in such cases the reactions occur by SN2 and E2 mechanisms, respectively, the ratio of the hydrolysis versus elimination products should vary with varying pH and temperature, since the two competing reactions likely exhibit different pH and temperature dependencies. On the other hand, if the reaction mechanisms were more SN1- and El-like, a much less pronounced effect of temperature or pH on product formation would be expected, since the rate-determining step in aqueous solution may be considered to be identical for both reactions ... 

Tertiary alcohols react with sulfuric acid at much lower temperatures than do most primary or secondary alcohols. The reactions typically are SN1 and El by way of a tertiary carbocation, as shown here for ferf-butyl alcohol and sulfuric acid ... 

Rearrangements are possible when carbocations are intermediates in a reaction. Thus reactions occurring by the SN1 and El mechanisms are most likely to have a rearranged carbon skeleton. 

A tertiary alkyl halide when treated with sodium methoxide forms an ether or an alkene (Above fig.). A protic solvent is used here and this favours both the SN1 and El mechanisms. However, a strong base is also being used and this favours the E2 mechanism. Therefore, the alkene would be expected to be the major product with only a very small amount of substitution product arising from the SN2 reaction. Heating the same alkyl halide in methanol alone means that the reaction is being done in a protic solvent with a non-basic nucleophile (MeOH). These conditions would yield a mixture of substitution and elimination products arising from the SN1 and El mechanism. The substitution product would be favoured over the elimination product. 

Until now, discussions have focused only on how carbanions and carbocations behave under conditions favorable for nucleophilic substitutions. However, these species may undergo other types of reactions in which unsaturation is introduced into the molecule. Such reactions are called elimination reactions and should be considered whenever charged species are of importance to the mechanistic progression of a molecular transformation. In previous chapters, SN1 and SN2 reactions were discussed. In this chapter, the corresponding El and E2 elimination mechanisms are presented. 

The mechanistic subtypes presented throughout this book include those related to the acid-base properties of organic molecules. These are protonations, deprotonations, and proton transfers. Mechanistic types based on solvation effects include solvolysis reactions, SN1, and El processes. Additional mechanisms utilizing ionic interactions include SN2, SN2, E2, 1,2-additions, 1,4-additions, and addition-elimination processes. Finally, those mechanistic types dependent upon the presence of cationic species include alkyl shifts and hydride shifts. 

The next stage was the observation by Maccoll and Thomas (1955) that there existed an analogy between the effect of substitution upon the gas-phase elimination reaction (Eg) and the effect of similar substitution upon the SN1 or El reaction of the corresponding compounds... 

The text summarizes the preferences for El, E2, SN1, and SN2 reactions for 1°, 2°, and 3° haloalkanes, as a function of reaction conditions, in quite a bit of detail. The chart that follows repeats the same material, again somewhat oversimplified for clarity (solvent effects are not included, for instance). 

SnI and El reactions both have the same rate-determining step—dissociation of the alkyl halide to form a carbocation. This means that any alkyl halide that reacts under Sn1/E1 conditions will form both substitution and elimination products. Remember that primary and secondary alkyl halides do not undergo these reactions because they form relatively unstable carbocations (page 467). 

Other terms that he invented include the system of classification for mechanisms of aromatic and aliphatic substitution and elimination reactions, designated SN1, SN2, El, and E2. "S" and "E" refer to substitution and elimination, respectively, "N" to nucleophilic, and "1" and "2" to "molecularity," or the number of molecules involved in a reaction step (not kinetic order, having to do with the equation for reaction rate and the concentration of reactants). Ingold first introduced some of these ideas in 1928 in a... 

We note that in Eq. 13-11 we have introduced the El (elimination, unimolecular) reaction, which commonly competes with the SN1 reaction provided that an adjacent carbon atom carries one or several hydrogen atoms that may dissociate. We also note that similar to what we have stated earlier for nucleophilic substitution reactions, elimination reactions may occur by mechanisms between the E2 and El extremes. 

These are best regarded as SN1 reactions, in which the leaving group is the carboxylate anion. The point is brought out very well by Moffat and Hunt s comparison79 of the solvolyses of /-alkyl trifluoroacetates in 70% aqueous acetone with the reactions of the corresponding /-alkyl halides (Table 26). The activation parameters, and the fate of the carbonium ion, as measured by the percentage of olefin formed by the parallel El reaction, are closely similar for the two types of substrate. 

Factors influencing the El reactions are expected to be similar to those for the SN1 reactions. An ionizing solvent is necessary, and for easy reaction the RX compound must have a good leaving group and form a relatively stable R cation. Therefore the El orders of reaction rates are X = I>Br>Cl>F and tertiary R > secondary R > primary R. 

Another feature of El reactions (and also of SN1 reactions) is the tendency of the initially formed carbocation to rearrange, especially if a more stable car-bocation is formed thereby. For example, the very slow SN1 solvolysis of neopentyl iodide in methanoic acid leads predominantly to 2-methyl-2-butene ... 

Bimolecular reactions are generally faster than unimolecular reactions. So, all things being equal, Sn2 will be faster than SN1, and E2 will be faster than El. 

The substrate is a tertiary alkyl bromide and can undergo SN1 substitution and El elimination under these reaction conditions. Elimination in either of two directions to give regioisomeric alkenes can also occur. 

The E2 reaction is the most effective for the synthesis of alkenes from alkyl halides and can be used on primary, secondary, and tertiary alkyl halides. The El reaction is not so useful from a synthetic point of view and occurs in competition with the SN1 reaction of tertiary alkyl halides. Primary and secondary alkyl halides do not generally react by this mechanism. 

The conditions that favour El are the same which that favour the SN1 reaction (i.e. a protic solvent and a non-basic nucleophile). Therefore, the El reaction normally only takes place with tertiary alkyl halides and will be in competition with the SN1 reaction. 

Aldehydes and ketones react with aromatic compounds in the presence of Bransted or Lewis acids. The actual electrophile is the carboxonium ion formed in an equilibrium reaction by protonation or complexation, respectively. The primary product is a substituted benzyl alcohol, which, however, is not stable and easily forms a benzyl cation. The latter continues to react further, either via an SN1 or an El reaction. Thereby, the following overall functionalizations are realized Ar—H —> Ar—C-Nu or Ar—H — Ar—C=C. 

Only three heteroatom nucleophiles add to a significant extent to carbonyl compounds without being followed by secondary reactions such as SN1 reactions (Section 9.2) or El reactions (Section 9.3) H20, alcohols, and, should the substitution pattern be suitable, the carbonyl compound itself. 

The survey in Figure 9.23 shows that N nucleophiles can react with carbonyl compounds in the following ways (1) An addition to the C=0 double bond followed by an SN1 reaction leads to the formation of AW-acetals (details Section 9.2.4). (2) An addition to the C=0 double bond is followed by an El reaction by which, amongst others, enamines are formed (details Section 9.3). (3) Imines are produced. We still need to discuss whether the reaction of O nucleophiles with carbonyl compounds also gives us two options—parallel to the two possibilities (1) and (2) mentioned above. According to Figure 9.12 alcohols and carbonyl compounds always afford 0,0-acetals—through an addition and an SN1 reaction (details Section 9.2.2). 

When regioisomers are possible in an El reaction, the product distribution is found to follow Zaitsev s rule. The reaction of 2-bromo-2-methylbutane under Sn1/E1 conditions (in a polar solvent mixture of ethanol and water with no good base or nucleophile present) gives 64% of the substitution products (water acts as the nucleophile to give an alcohol, or ethanol acts as a nucleophile to give an ether), 30% of the more highly substituted alkene, and 6% of the less highly substituted alkene. 

The bromine is bonded to a tertiary carbon and there is not a strong base present, so the reaction will proceed by an SN1 /E1 mechanism. The substitution product should predominate. The El reaction follows Zaitsev s rule, so more 1-methylcyclohexene should be formed than methylenecyclohexane. 

Predict whether the major pathway that will be followed under a particular set of reaction conditions will be SN1, SN2, El, or E2. (Problems 9.18, 9.25, and 9.26)... 

Follow the steps listed in the preceding Visual Summary of Key Reactions section. Identify the leaving group, the electrophilic carbon, and the nucleophile (or base). Then determine which mechanism is favored (see Section 9.7). Watch out for stereochemistry where important, regiochemistry in elimination reactions, and carbocation rearrangements when the mechanism is SN1 or El. 

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