Sn2 reactions generality

Now let s consider the effect of the substrate on the rate of an E2 process. Recall from the previous chapter that Sn2 reactions generally do not occur with tertiary substrates, because of steric considerations. But E2 reactions are different than Sn2 reactions, and in fact, tertiary substrates often undergo E2 reactions quite rapidly. To explain why tertiary substrates will undergo E2 but not Sn2 reactions, we must recognize that the key difference between substitution and elimination is the role played by the reagent. In a substitution reaction, the reagent functions as a nucleophile and attacks an electrophilic position. In an elimination reaction, the reagent functions as a base and removes a proton, which is easily achieved even with a tertiary substrate. In fact, tertiary substrates react even more rapidly than primary substrates. 

The rates of Sn2 reactions generally are vastly increased when they are carried out in polar aprotic solvents. 

Gas-phase intracomplex substitution in (R)-(- -)-l-arylethanol/CHs OH2 adducts. It is well established that bimolecular Sn2 reactions generally involve predominant inversion of configuration of the reaction center. Unimolecular SnI displacements instead proceed through the intermediacy of free carbocations and, therefore, usually lead to racemates. However, many alleged SnI solvolyses do not give fully racemized products. The enantiomer in excess often, but not always, corresponds to inversion. Furthermore, the stereochemical distribution of products may be highly sensitive to the solvolytic conditions.These observations have led to the concept of competing ° or mixed SNl-SN2 mechanisms. More recently, the existence itself of SnI reactions has been put into question. ... 

The previous study might seem to be a theoretician s amusement, of no practical value. This is not true, as we will see when analyzing why vinylic SN2 reactions generally proceed with retention of configuration. 

In general, Sn2 reactions of alkyl halides show the following dependence of rate on structure ... 

Sn2 reactions with anionic nucleophiles fall into this class, and observations are generally in accord with the qualitative prediction. Unusual effects may be seen in solvents of low dielectric constant where ion pairing is extensive, and we have already commented on the enhanced nucleophilic reactivity of anionic nucleophiles in dipolar aprotic solvents owing to their relative desolvation in these solvents. Another important class of ion-molecule reaction is the hydroxide-catalyzed hydrolysis of neutral esters and amides. Because these reactions are carried out in hydroxy lie solvents, the general medium effect is confounded with the acid-base equilibria of the mixed solvent lyate species. (This same problem occurs with Sn2 reactions in hydroxylic solvents.) This equilibrium is established in alcohol-water mixtures ... 

Now that we have a good picture of how SN2 reactions occur, we need to see how they can be used and what variables affect them. Some SN-2 reactions are fast, and some are slow some take place in high yield and others, in low yield. Understanding the factors involved can be of tremendous value. Let s begin by recalling a few things about reaction rates In general. 

The one general exception to the rule that ethers don t typically undergo Sn2 reactions occurs with epoxides, the three-membered cyclic ethers that we saw in Section 7.8. Epoxides, because of the angle strain in the three-membered ring, are much more reactive than other ethers. They react with aqueous acid to give 1,2-diols, as we saw in Section 7.8, and they react readily with many other nucleophiles as well. Propene oxide, for instance, reacts with HC1 to give l-chloro-2-propanol by Snj2 backside attack on the less hindered primary carbon atom. We ll look at the process in more detail in Section 18.6. 

The rates of SN2 reactions are strongly affected by the solvent. Protic solvents— those that contain an —OH or -NH group—are generally the worst for S j2 reactions, while polar aptotic solvents, which are polar but don t have an -OH or -NH group, are the best. 

We have seen how the polarity of the solvent influences the rates of Sn 1 and Sn2 reactions. The ionic strength of the medium has similar effects. In general, the addition of an external salt affects the rates of SnI and Sn2 reactions in the same way as an increase in solvent polarity, though this is not quantitative different salts have different effects. However, there are exceptions though the rates of SnI reactions are usually increased by the addition of salts (this is called the salt effect), addition of the leaving-group ion often decreases the rate (the common-ion effect, p. 395). 

Sn2 and SN2 Reactions with Halides and Sulfonates. Corey and Posner discovered that lithium dimethylcuprate can replace iodine or bromine by methyl in a wide variety of compounds, including aryl, alkenyl, and alkyl derivatives. This halogen displacement reaction is more general and gives higher yields than displacements with... 

In general, azides are more easily available than nitro compounds by SN2 reaction of the corresponding halides. Thus, the direct conversion of an azide into a nitro group is useful for the synthesis of nitro compounds. Corey and coworkers have reported the easy conversion of azides to nitro compounds via ozonolysis of phosphine imines (Eq. 2.70).139... 

Simple nitroalkanes such as nitroethane, 1-nitropropane, or 2-nitropropane are generally bad electrophiles for the SN2 reactions.14 In contrast, nitro groups at allylic positions are readily displaced by thiolate ions (Eq. 7.13)15 or lithium dialkylcuprates (Eq. 7.14).16... 

As pyramidal amides5,32 their Sn2 reactivity with neutral nucleophiles like /V-methylaniline parallels that of a-haloketones with amines, which, as described in an earlier section, are also strongly affected by steric effects on the a -carbon.183 SN2 reactions are in general strongly and adversely influenced by steric effects and branching / to the reactive centre and the same appears to be true for /V-acyloxy-/V-alkoxyamides 30b and 29a-e. Broadly speaking, their mutagenic activity is affected similarly. 

Although the reaction of a titanium carbene complex with an olefin generally affords the olefin metathesis product, in certain cases the intermediate titanacyclobutane may decompose through reductive elimination to give a cyclopropane. A small amount of the cyclopropane derivative is produced by the reaction of titanocene-methylidene with isobutene or ethene in the presence of triethylamine or THF [8], In order to accelerate the reductive elimination from titanacyclobutane to form the cyclopropane, oxidation with iodine is required (Scheme 14.21) [36], The stereochemistry obtained indicates that this reaction proceeds through the formation of y-iodoalkyltitanium species 46 and 47. A subsequent intramolecular SN2 reaction produces the cyclopropane. 

Concerted bond-forming/bond-breaking processes at tetrahedral carbon (the familiar SN2 reaction) are not easily studied by the crystal structure correlation method. The preferred approach of a nucleophile is sterically more encumbered than the approach to a singly or doubly bonded centre, and the transition states involved are generally of high energy. Intramolecular displacements, such as those described on pages 117-118, are a possible way round this problem, but no systematic study is available. 

The syntheses of a variety of "multi-site" phase-transfer catalysts (PTCs) and the determination of their catalytic activity toward some simple Sn2 reactions and some weak nucleophile-weak electrophile SnAr reactions are described. In general, at the same molar ratio, the "multi-site" PTCs are as or more effective than similar "single-site" PTCs. Thus, the "multi-site" PTCs offer an economy of scale compared to "single-site" PTCs. 

The exact mechanism of silanization depends on the reaction conditions. It is generally accepted that silanization in a Uquid solution is a three-step process [20]. In a first step, the silanes mentioned before form silanetriols by hydrolyzation in the presence of water on the surface or in the solvent. These silanetriols attach themselves by physiosorption via hydrogen bonds onto the substrate surface. Subsequently, the silanol groups react with the free hydroxyl groups on the surface according to a Sn2 reaction mechanism (see Fig. 5). 

In general terms then, the Sn2 reaction is only important for primary and secondary substrates, and the rate of reaction for primary substrates is considerably greater than that for secondary substrates. Should a reaction be attempted with tertiary substrates, one does not usually get substitution, but alternative side-reactions occur (see Section 6.4). 

As we have just seen, SnI reactions are highly favoured at tertiary carbon, and very much disfavoured at primary carbon. This is in marked contrast to Sn2 reactions, which are highly favoured at primary carbon and not at tertiary carbon. With Sn2 reactions, consideration of steric hindrance rationalized the results observed. This leads to the generalizations for nucleophilic substitutions shown in Table 6.8, with secondary substrates being able to participate in either type of process. 

The C—bond strength renders the aliphatic fluorides much less reactive than the corresponding chlorides in S l or Sn2 reactions (from 10 to 10 ). In fluoroalkenes, the C—bond is also strong the more fluorine atoms there are, the stronger the n double bond is. In general, the reactivity of these double bonds decreases with electrophiles while it increases with nucleophiles. 

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