Sn2 mechanism and

These reactions follow first-order kinetics and proceed with racemisalion if the reaction site is an optically active centre. For alkyl halides nucleophilic substitution proceeds easily primary halides favour Sn2 mechanisms and tertiary halides favour S 1 mechanisms. Aryl halides undergo nucleophilic substitution with difficulty and sometimes involve aryne intermediates. 

Allyl chloride is quite reactive toward nucleophilic substitutions, especially those that proceed by the Sn2 mechanism, and is used as a starting material in the synthesis of a variety of drugs and agricultural and industrial chemicals. 

The real world of Sn reactions is not quite as simple as the discussion has so far suggested. The preceding treatment in terms of two clearly distinct mechanisms, SnI and Sn2, implies that all substitution reactions will follow one or the other of these mechanisms. This is an oversimplification. The strength of the dual mechanism hypothesis and its limitations are revealed by these relative rates of solvolysis of alkyl bromides in 80% ethanol methyl bromide, 2.51 ethyl bromide, 1.00 isopropyl bromide, 1.70 /er/-butyl bromide, 8600. Addition of lyate ions increases the rate for the methyl, ethyl, and isopropyl bromides, whereas the tert-butyl bromide solvolysis rate is unchanged. The reaction with lyate ions is overall second-order for methyl and ethyl, first-order for tert-butyl, and first- or second-order for the isopropyl member, depending upon the concentrations. Similar results are found in other solvents. These data show that the methyl and ethyl bromides solvolyze by the Sn2 mechanism, and tert-butyl bromide by the SnI mech-... 

Branching at the a and (3 Carbons. For the Sn2 mechanism, branching at either the a or the (3 carbon decreases the rate. Tertiary systems seldom react by the Sn2 mechanism and neopentyl systems react so slowly as to make... 

To sum up, primary and secondary substrates generally react by the Sn2 mechanism and tertiary by the SnI mechanism. However, tertiary substrates seldom undergo nucleophilic substitution at all. Elimination is always a possible side reaction of nucleophilic substitutions (wherever a P hydrogen is present), and with tertiary substrates it usually predominates. With a few exceptions, nucleophilic substitutions at a tertiary carbon have little or no preparative value. However, tertiary substrates that can react by the SET mechanism (e.g., /i-N02C6H4CMe2Cl) give very good yields of substitution products when treated with a variety of nucleophiles. ... 

Racemization of chiral a-methyl benzyl cation/methanol adducts. The rate of exchange between water and the chiral labeled alcohols as a function of racemization has been extensively used as a criterion for discriminating the Sn2 from the SnI solvolytic mechanisms in solution. The expected ratio of exchange vs. racemization rate is 0.5 for the Sn2 mechanism and 1.0 for a pure SnI process. With chiral 0-enriched 1-phenylethanol in aqueous acids, this ratio is found to be equal to 0.84 0.05. This value has been interpreted in terms of the kinetic pattern of Scheme 22 involving the reversible dissociation of the oxonium ion (5 )-40 (XOH = H2 0) to the chiral intimate ion-dipole pair (5 )-41 k-i > In (5 )-41, the leaving H2 0 molecule does not equilibrate immediately with the solvent (i.e., H2 0), but remains closely associated with the ion. This means that A inv is of the same order of magnitude of In contrast, the rate constant ratio of... 

The prominent role of alkyl halides in formation of carbon-carbon bonds by nucleophilic substitution was evident in Chapter 1. The most common precursors for alkyl halides are the corresponding alcohols, and a variety of procedures have been developed for this transformation. The choice of an appropriate reagent is usually dictated by the sensitivity of the alcohol and any other functional groups present in the molecule. Unsubstituted primary alcohols can be converted to bromides with hot concentrated hydrobromic acid.4 Alkyl chlorides can be prepared by reaction of primary alcohols with hydrochloric acid-zinc chloride.5 These reactions proceed by an SN2 mechanism, and elimination and rearrangements are not a problem for primary alcohols. Reactions with tertiary alcohols proceed by an SN1 mechanism so these reactions are preparatively useful only when the carbocation intermediate is unlikely to give rise to rearranged product.6 Because of the harsh conditions, these procedures are only applicable to very acid-stable molecules. 

If the alcohol originally has the d configuration, what configuration would the resulting chloride have if formed (a) by the SN2 mechanism and (b) by the SN1 mechanism ... 

An IV-heterocyclic carbene (similar to that in Scheme 15) has proved to be an effective catalyst for the nucleophilic ring opening of IV-tosylaziridines by silylated nucleophiles (MesSiX, X = N3, Cl, I).45 Yields range from 89 to 99% for reaction at the least substituted carbon, except when a phenyl group on one of the carbons of the aziridine ring induces predominant attack at the benzyl carbon. The stereochemistry is consistent with the SN2 mechanism and THF was found to be the best solvent for the reaction. 

Here is the bottom line a strong nucleophile suggests an SN2 mechanism, and a weak nucleophile suggests an SnI mechanism. What do we do if the nucleophile is moderate Move on to factor 3. 

Substitutions by the SRn 1 mechanism (substitution, radical-nucleophilic, unimolecular) are a well-studied group of reactions which involve SET steps and radical anion intermediates (see Scheme 10.4). They have been elucidated for a range of precursors which include aryl, vinyl and bridgehead halides (i.e. halides which cannot undergo SN1 or SN2 mechanisms), and substituted nitro compounds. Studies of aryl halide reactions are discussed in Chapter 2. The methods used to determine the mechanisms of these reactions include inhibition and trapping studies, ESR spectroscopy, variation of the functional group and nucleophile reactivity coupled with product analysis, and the effect of solvent. We exemplify SRN1 mechanistic studies with the reactions of o -substituted nitroalkanes (Scheme 10.29) [23,24]. 

Primary and secondary alkyl halides react with potassium iodide in acetone by an SN2 mechanism, and the rate depends on steric hindrance to attack on the alkyl halide by the nucleophile. 

Further support for this interpretation can be found by considering the data for the hydrolysis of isopropyl compounds in Table 28. The values of r are calculated from (112). It can be seen that the transition states for the isopropyl transfers are much looser than those for the methyl transfers. The solvolysis of isopropyl compounds is closer to the borderline between the SN1 and SN2 mechanisms and therefore we may expect the SN2 transition state to be looser. As discussed above there is supporting evidence from Ko and Parker s (1968) measurements of transfer activity coefficients for the transition state. 

An example of a forbidden 6-endo-tet process would be the intramolecular alkylation of a carbanion via a six-membered transition state (Scheme 9.2). Because such an alkylation would proceed via the Sn2 mechanism and would require a linear... 

Explain whether these reactions would follow the SN1 or the SN2 mechanism and then explain which reaction is faster ... 

Be able to use these factors to predict whether a particular reaction will proceed by an SN1 or an SN2 mechanism and to predict what effect a change in reaction conditions will have on the reaction rate. (Problems 8.28, 8.36, 8.37, and 8.38)... 

When an alkoxide ion is used as the nucleophile, the reaction is called a Williamson ether synthesis. Because the basicity of an alkoxide ion is comparable to that of hydroxide ion, much of the discussion about the use of hydroxide as a nucleophile also applies here. Thus, alkoxide ions react by the SN2 mechanism and are subject to the usual Sn2 limitations. They give good yields with primary alkyl halides and sulfonate esters but are usually not used with secondary and tertiary substrates because elimination reactions predominate. 

Cyanide ion reacts by the SN2 mechanism and aprotic solvents are often employed to increase its reactivity. Yields of substitution products are excellent when the leaving group is attached to a primary carbon. Because of competing elimination reactions, yields are lower, but still acceptable, for secondary substrates. As expected for an SN2 process, the reaction does not work with tertiary substrates. Substitution with cyanide ion adds one carbon to the compound while also providing a new functional group for additional synthetic manipulation. Some examples are given in the following equations ... 

Among simple alkyl groups, methyl and primary alkyl groups always react by the Sn2 mechanism and never by S l. This is partly because the cations are unstable and partly because the nucleophile can push its way in easily past the hydrogen atoms. 

You might ask a very good question at this point. How do we know that these reactions really take place by Sn2 and Sn2 mechanisms and not by an S l mechanism via the stable allyl cation Well in the case of prenyl bromide, we don t In fact, we suspect that the cation probably is an intermediate, because prenyl bromide and its allylic isomer are in rapid equilibrium in solution at room temperature. 

Fig. 4. The reaction steps during nucleophilic substitution in the dilute gas phase. The upper route corresponds to backside displacement (the traditional SN2 mechanism) and the lower route is the frontside displacement mechanism. The latter is possible in weakly bonded RX+...

Because the bond to the leaving group is partially broken in the transition state of the only step of the Sn2 mechanism and the slow step of the SnI mechanism, a better leaving group increases the rate of both reactions. The better the leaving group, the more willing it is to accept the electron pair in the C - X bond, and the faster the reaction. 

We have proposed that, under the conditions we have described, methyl bromide reacts with hydroxide ion by the Sn2 mechanism, and that ferf-butyl bromide reacts by the SnI mechanism. Since 5ec-alkyl bromides are intermediate in structure between these two halides, it is not surprising to find that they can react by either or both mechanisms. 

Nevertheless, from the nine different routes to form the key intermediate of the homologation reaction set out in Scheme 1, three remain the most convincing the insertion mechanism the Sn2 mechanism and the phosphonium ion mechanism (cf. Schemes 2 and 3). 

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