Nucleophilic substitution reactions making

Although nucleophilicity and basicity are interrelated, they are fundamentally different. Basicity is a measure of how readily an atom donates its electron pair to a proton it is characterized by an equilibrium constant Kg in an acid-base reaction, making it a thermodynamic property. Nucleophilicity is a measure of how readily an atom donates its electron pair to other atoms it is characterized by the rate constant, k, of a nucleophilic substitution reaction, making it a kinetic property. 

Now we get to the meaning of 2 in Sn2. Remember from the last chapter that nucleophilicity is a measure of kinetics (how fast something happens). Since this is a nucleophilic substitution reaction, then we care about how fast the reaction is happening. In other words, what is the rate of the reaction This mechanism has only one step, and in that step, two things need to find each other the nucleophile and the electrophile. So it makes sense that the rate of the reaction will be dependent on how much electrophile is around and how much nucleophile is around. In other words, the rate of the reaction is dependent on the concentrations of two entities. The reaction is said to be second order, and we signify this by placing a 2 in the name of the reaction. 

In a one-pot synthesis of thioethers, starting from potassium 0-alkyl dithiocarbonate [36], the base hydrolyses of the intermediate dialkyl ester, and subsequent nucleophilic substitution reaction by the released thiolate anion upon the unhydrolysed 0,5-dialkyl ester produces the symmetrical thioether. Yields from the O-methyl ester tend to be poor, but are improved if cyclohexane is used as the solvent in the hydrolysis step (Table 4.13). In the alternative route from the 5,5-dialkyl dithiocarbonates, hydrolysis of the ester in the presence of an alkylating agent leads to the unsymmetrical thioether [39] (Table 4.14). The slow release of the thiolate anions in both reactions makes the procedure socially more acceptable and obviates losses by oxidation. 

It is important to be able to look at a molecular structure and deduce the possible reactions it can undergo. Take an alkene, for example. It has a 7t bond that makes it electron-rich and able to attack electrophiles such as water, halogens and hydrogen halides in electrophilic addition reactions. Haloalkanes, on the other hand, contain polar carbon-halogen bonds because the halogen is more electronegative than carbon. This makes them susceptible to attack by nucleophiles, such as hydroxide, cyanide and alkoxide ions, in nucleophilic substitution reactions. 

With this exception we can see that the impact of the configuration mixing model on nucleophilic substitution reactions, which constitute the most widely studied organic reaction, is indeed extensive. The model readily rationalizes much available experimental data, relates the entire mechanistic spectrum within a single framework, challenges some fundamental precepts of physical organic chemistry and enables one to make reactivity predictions about reactions yet to be investigated. For such a simple, qualitative theory, this is no mean achievement. 

Oil the MCAT, look for carboxylic acid to behave as an acid or as the substrate in a nucleophilic substitution reaction. Like any carbonyl compound, its stereochemistry makes it susceptible to nucleophiles. When the hydroxyl group is protonated, the good leaving group, water, is formed and substitution results. 

Aryl halides are relatively unreactive toward nucleophilic substitution reactions. This lack of reactivity is due to several factors. Steric hindrance caused by the benzene ring of the aryl halide prevents SN2 reactions. Likewise, phenyl cations are unstable, thus making SN1 reactions impossible. In addition, the carbon-halogen bond is shorter and therefore stronger in aryl halides than in alkyl halides. The carbon-halogen bond is shortened in aryl halides for two reasons. First, the carbon atom in aryl halides is sp2 hybridized instead of sp3 hybridized as in alkyl halides. Second, the carbon-halogen bond has partial double bond characteristics because of resonance. 

Nucleophilic substitution reactions can occur with aryl halides, provided that strong electron-withdrawing groups (deactivators) are located ortho and/or para to the carbon atom that s attached to the halogen. (This arrangement makes the carbon susceptible to nucleophilic attack.)... 

Two suitably positioned nitro groups make the halogen-bearing carbon atom in 2,4-dinitro-halobenzenes a favored point of reaction for nucleophilic substitution reactions. Thus, 2,4-dinitrophenyl hydrazine is produced from the reaction of 2,4-dinitrochlorobenzene with hydrazine ... 

Substituted bicycloalkyl halides are very unreactive toward nucleophilic substitution reactions. The low reactivity in S l reactions has been attributed to the fact that a planar configuration at the bridgehead carbon cannot be obtained without the introduction of considerable strain119. On the other hand, the S 2 reaction is precluded because a backside approach of the nucleophile cannot occur at a bridgehead position for a steric reason. The lack of reactivity of 1 -halobicycloalkanes toward nucleophiles by polar mechanisms makes them attractive substrates for the S l mechanism. 

Chapter 8 begins the treatment of organic reactions with a discussion of nucleophilic substitution reactions. Elimination reactions are treated separately in Chapter 9 to make each chapter more manageable. Chapter 10 discusses synthetic uses of substitution and elimination reactions and introduces retrosynthetic analysis. Although this chapter contains many reactions, students have learned to identify the electrophile, leaving group, and nucleophile or base from Chapters 8 and 9. so they do not have to rely as much on memorization. Chapter 11 covers electrophilic additions to alkenes and alkynes. The behavior of carbocations, presented in Chapter 8, is very useful here. An additional section on synthesis has been added to this chapter as well. 

Although they really belong in Chapter 17 with other nucleophilic substitution reactions, we included the last few examples of epoxide-opening reactions here because they have many things in common with the reactions of bromonium ions. Now we are going to make the analogy work the other way when we look at the stereochemistry of the reactions of bromonium ions, and hence at the stereoselectivity of electrophilic additions to alkenes. We shall first remind you of an epoxide reaction from Chapter 17, where you saw this. 

Aromatization with bromine gives the aromatic pyridazolone by bromination and dehydro-bromination and now we invoke the nucleophilic substitution reactions introduced in Chapter 43. First we make the chloride with POCI3 and then displace with methanol. 

The study of reactions of isolated ions and molecules in the gas phase without interference from solvents has led to very surprising results. Gas-phase studies of proton-transfer and nucleophilic substitution reactions permit the measurement of the intrinsic properties of the bare reactants and make it possible to distinguish these genuine properties from effects attributable to solvation. Furthermore, these studies provide a direct comparison of gas-phase and solution reactivities of ionic reactants. It has long been assumed that solvation retards the rates of ion-molecule reactions. Now, using these new techniques, the dramatic results obtained make it possible to show the extent of this retardation. For example, in a typical Sn2 ion-molecule reaction in the gas phase, the substrates react about 10 times faster than when they are dissolved in acetone, and about 10 ( ) times faster than in water cf. Table 5-2 in Section 5.2). 

These Hughes-Ingold rules can be used for making qualitative predictions about the effect of solvent polarity on the rates of all heterolytic reactions of known mechanisms. For nucleophilic substitution reactions of types (5-11) and (5-12)... 

The preceding discussion has generated two possible mechanisms for nucleophilic substitution a one-step mechanism in which bond breaking and bond making are simultaneous, and a two-step mechanism in which bond breaking comes before bond making. In Section 7.10 we look at data for two specific nucleophilic substitution reactions and see if those data fit either of these proposed mechanisms. 

Because sulfonate anions are such weak bases, they make good leaving groups in nucleophilic substitution reactions, as we learned in Section 9.13. 

These reactions are used to make anhydrides, carboxylic acids, esters, and amides, but not acid chlorides, from other acyl compounds. Acid chlorides are the most reactive acyl compounds (they have the best leaving group), so they are not easily formed as a product of nucleophilic substitution reactions. They can only be prepared from carboxylic acids using special reagents, as discussed in Section 22.10A. 

Steps [3] and [4] result in a nucleophilic substitution reaction of a ketone. Because ketones normally undergo nucleophilic addition, this two-step sequence makes the haloform reaction unique. Substitution occurs because the three electronegative halogen atoms make CX3 (CI3 in the example) a good leaving group. 

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