An SN2 Reaction

These reactions proceed via a collision between the reactants, with the nucleophilic species attacking the opposite side of the molecule with respect to the ionic substituent that it liberates. Such a process yields a transition structure in which the ion and neutral reactants are weakly bound. 

The potential surface for such a reaction has the following general shape  

The reactants and products are at the two ends of the curve. The transition structure for the reaction connects two minima. These minima are two ion-molecule complexes, intermediate species through which the reaction proceeds. 

Predict the struaure of the transition state and the two intermediate ion-moleculc complexes for the S). 2 reaction  

What are the energies for each species Plot the general shape of the potential energy curve for this reaction. 

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All these reactions of octadecyl p toluenesulfonate have been reported in the chemical literature and all proceed in synthetically useful yield You should begin by identifying the nucleophile in each of the parts to this problem The nucleophile replaces the p toluenesulfonate leaving group in an Sn2 reaction In part (a) the nucleophile is acetate ion and the product of nucleophilic substitution IS octadecyl acetate... 

The Williamson ether synthesis (Sec tion 16 6) An alkoxide ion displaces a halide or similar leaving group in an Sn2 reaction The alkyl halide cannot be one that is prone to elimination and so this reaction is limited to methyl and primary alkyl halides There is no limitation on the alkoxide ion that can be used... 

This IS an example of an Sn2 reaction in a polar aprotic solvent... 

What is the structure of the transition state in an Sn2 reaction In particular-, what is the spatial ariangement of the nucleophile in relation to the leaving group as reactants pass through the transition state on their- way to products ... 

With primary alcohols, the next stage is an Sn2 reaction in which the halide ion, bromide, for exfflnple, displaces a molecule of water from the alkyloxonium ion. 

Nucleophilic ring opening of epoxides has many of the features of an Sn2 reaction. Inversion of configuration is observed at the carbon at which substitution occurs. 

Two processes that are consistent with second-order kinetics both involve hydroxide ion as a nucleophile but differ in the site of nucleophilic attack. One of these processes is an Sn2 reaction in which hydroxide displaces caiboxylate from the alkyl group of the ester. 

The carbon-oxygen bond broken in the process is therefore the one between oxygen and the acyl group. The bond between oxygen and the ethyl group remains intact. An Sn2 reaction at the ethyl group would have broken this bond. 

None of the bonds to the chirality center is broken when hydroxide attacks the carbonyl group. Had an Sn2 reaction occuned instead, inversion of configuration at the chirality center would have taken place to give (.S)-(—)-l-phenylethyl alcohol. 

Williamson ether synthesis (Section 16.6) Method for the preparation of ethers involving an Sn2 reaction between an alkoxide ion and a primary alkyl halide ... 

For each reaction, plot energy (vertical axis) vs. the number of the structure in the overall sequence (horizontal axis). Do reactions that share the same mechanistic label also share similar reaction energy diagrams How many barriers separate the reactants and products in an Sn2 reaction In an SnI reaction Based on your observations, draw a step-by-step mechanism for each reaction using curved arrows () to show electron movements. The drawing for each step should show the reactants and products for that step and curved arrows needed for that step only. Do not draw transition states, and do not combine arrows for different steps. 

Another way to assess nucleophilic reactivity is to examii the shape of the nucleophile s electron-donor orbital (th is the highest-occupied molecular orbital or HOMC Examine the shape of each anion s HOMO. At which ato would an electrophile, like methyl bromide, find the be orbital overlap (Note This would involve overlap of tl the HOMO of the nucleophile and the lowest-unoccupif molecular orbital or LUMO of CH3Br.) Draw all of tl products that might result from an Sn2 reaction wi CHaBr at these atoms. 

One way to generate carbanions is to combine an acidic molecule with one equivalent of a very strong base, such as n-butyl lithium (n-BuLi). For example, reaction of the alkyne shown below with n-BuLi leads to a carbanion of formula CsH, 02 , which then undergoes an Sn2 reaction with n-propyl bromide (n-PrBr),... 

A wide array of substances can be prepared using nucleophilic substitution reactions. In fact, we ve already seen examples in previous chapters. The reaction of an acetylide anion with an alkyl halide (Section 8.8), for instance, is an Sn2 reaction in which the acetylide nucleophile replaces halide. 

Which compound in each of rhe following pairs will react faster in an Sn2 reaction with OH ... 

Strategy Draw the target ether, identify the two groups attached to oxygen, and recall the limitations of the two methods for preparing ethers. The Williamson synthesis uses an Sn2 reaction and requires that one of the two groups attached to oxygen be either... 

The net effect of the addition/elimination sequence is a substitution of the nucleophile for the -Y group originally bonded to the acyl carbon. Thus, the overall reaction is superficially similar to the kind of nucleophilic substitution that occurs during an Sn2 reaction (Section 11.3), but the mechanisms of the two reactions are completely different. An SN2 reaction occurs in a single step by backside displacement of the Leaving group a nucleophilic acyl substitution takes place in two steps and involves a tetrahedral intermediate. 

Perhaps the single most important reaction of enolate ions is their alkylation by treatment with an alkyl halide or tosylate, thereby forming a new C-C bond and joining two smaller pieces into one larger molecule. Alkylation occurs when the nucleophilic enolate ion reacts with the electrophilic alkyl halide in an SN2 reaction and displaces the leaving group by backside attack. 

Walden inversion (Section 11.1) The inversion of configuration at a chirality center that accompanies an SN2 reaction. 

The stereoselectivity is an important issue here an Sn2 reaction would lead to inversion at Ci, a two-step reaction, with first formation of an adsorbed... 

Eschenmoser and co-workers have provided strong evidence that the transition state in an Sn2 reaction must be linear. Base treatment of methyl a-tosyl-o-toluenesulfonate (4) gives the o-(l-tosylethyl)benzenesulfonate ion (6). The role of... 

It may be noted that the pseudo-first-order rate law for an Sn2 reaction in the presence of a large excess of Y [Eq. (10.2)] is the same as that for an ordinary SnI reaction [Eq. (10.3)]. It is thus not possible to tell these cases apart by simple kinetic... 

In contrast to such systems, substrates of the type RCOX are usually much more reactive than the corresponding RCH2X. Of course, the mechanism here is almost always the tetrahedral one. Three reasons can be given for the enhanced reactivity of RCOX (1) The carbonyl carbon has a sizable partial positive charge that makes it very attractive to nucleophiles. (2) In an Sn2 reaction a cr bond must break in the rate-determining step, which requires more energy than the shift of a pair of n electrons, which is what happens in a tetrahedral mechanism. (3) A trigonal carbon offers less steric hindrance to a nucleophile than a tetrahedral carbon. 

With primary R, the reaction probably goes through the alkyl halide formed initially in an Sn2 reaction ... 

Ladhams-Zieba (2004) has demonstrated that university students working on reaction mechanisms in organic chemistry also operate on the drawings on the page, rather than on what they represent. She asked 18 second year university students to predict and draw the product species most likely to be produced from the substitution reaction of hydroxide ion into 2 bromobutane, represented as in Fig. 1.13(a). Ten of them drew the inverted substitution product that you might expect from backside attack in an Sn2 reaction (Fig. 1.13(b)). 

In an Sn2 reaction, aUcyl groups make it very crowded at the electrophilic center where the nucleophile needs to attack. If there are three alkyl gronps, then it is virtually impossible for the nucleophile to get in and attack (this is an argument based on sterics) ... 

The rate of an Sn2 process is dependent on the strength of the nucleophile. A strong nucleophile will speed up the rate of an Sn2 reaction, while a weak nucleophile will slow down the rate of an Sn2 reaction. In contrast, an SnI process is not affected by... 

Answer This reaction utilizes DMSO, which is a polar aprotic solvent, so we expect an Sn2 reaction even though the substrate is secondary. 

This is not a new reaction. This is just an Sn2 reaction. We are simply using the alkoxide ion (ethoxide in this case) to function as the attacking nucleophile. But notice the net result of this reaction we have combined an alcohol and an alkyl halide to form an ether. This process has a special name. It is called the Williamson Ether Synthesis. This process relies on an Sn2 reaction as the main step, and therefore, we must be careful to obey the restrictions of Sn2 reactions. It is best to use a primary alkyl halide. Secondary alkyl halides cannot be used because elimination will predominate over substitution (as seen in Sections 10.9), and tertiary alkyl halides certainly cannot be used. 

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