Mechanistic types

Note in passing that almost all transfers of protons to and from oxygen and nitrogen are fast, and they are almost never rate determining. The stereochemistry at the start, which has disappeared in the products (the wavy bond indicated unspecified stereochemistry), is deliberate— weTl look at the reasons for this in the next section, but for now, think about the shape of the carbocation intermediate and where it will be attacked. 

The other mechanism for nucleophilic substitution is the 5 2 reaction, substitution, nucleophilic, bimolecular. The rate of the reaction is proportional to both the concentrations of the nucleophile and the substrate, and this is a single-step process. The kinetics are given by 

FIGURE 9.1 Prototype substitution reaction at sp carbon atom. R, R, R may be hydrogen, alkyl or aryl no particular stereochemical outcome should be inferred at this point. 

Explain why the rate of disappearance of MejCCl in aqueous solution is unaffected by the presence of Na[Nj, sodium azide, in the solution, but the products include both the azide and the alcohol. 

If the rate of the reaction is unaffected by the concentration of the nucleophile, then the reaction must go by the Sj. mechanism. So in the RDS of the reaction, the carbon-chlorine bond is broken to give the carbocation. This is not surprising as this is a stable tertiary carbocation. The carboca-tion is very reactive, so in the second, fast, step, it will be attacked by both azide ion and water  

---

We will discuss shortly the most important structure-reactivity features of the E2, El, and Elcb mechanisms. The variable transition state theoiy allows discussion of reactions proceeding through transition states of intermediate character in terms of the limiting mechanistic types. The most important structural features to be considered in such a discussion are (1) the nature of the leaving group, (2) the nature of the base, (3) electronic and steric effects of substituents in the reactant molecule, and (4) solvent effects. 

The first three chapters discuss fundamental bonding theory, stereochemistry, and conformation, respectively. Chapter 4 discusses the means of study and description of reaction mechanisms. Chapter 9 focuses on aromaticity and aromatic stabilization and can be used at an earlier stage of a course if an instructor desires to do so. The other chapters discuss specific mechanistic types, including nucleophilic substitution, polar additions and eliminations, carbon acids and enolates, carbonyl chemistry, aromatic substitution, concerted reactions, free-radical reactions, and photochemistry. 

Oxidation and Reduction (Chapter 19). Many oxidation and reduction reactions fall naturally into one of the four types mentioned above, but many others do not. For a description of oxidation-reduction mechanistic types, see page 1507. 

There are basically four ways in which addition to a double or triple bond can take place. Three of these are two-step processes, with initial attack by a nucleophile, an electrophile, or a free radical. The second step consists of combination of the resulting intermediate with, respectively, a positive species, a negative species, or a neutral entity. In the fourth type of mechanism, attack at the two carbon atoms of the double or triple bond is simultaneous. Which of the four mechanisms is operating in any given case is determined by the nature of the substrate, the reagent, and the reaction conditions. Some of the reactions in this chapter can take place by all four mechanistic types. 

Indicate the mechanistic type to which each of these reactions belongs and write out a mechanism showing any intermediates. 

Examples of the three mechanistic types are, respectively (a) hydrolysis of diazonium salts to phenols89 (b) reaction with azide ion to form aryl azides90 and (c) reaction with cuprous halides to form aryl chlorides or bromides.91 In the paragraphs that follow, these and other synthetically useful reactions of diazonium intermediates are considered. The reactions are organized on the basis of the group that is introduced, rather than on the mechanism involved. It will be seen that the reactions that are discussed fall into one of the three general mechanistic types. 

A shift in mechanistic type can also occur with change of nucleophile, thus a displacement that is S l with, for example, H20 , HCO30, MeCO20, etc., may become SN2 with eOH or EtO . 

The two reactions upon which the above comparison was made belong to the Sn2 mechanistic type. There are good indications, however, that the same conclusion applies as well to reactions belonging to different mechanistic types. We have already commented (p. 60) on the close similarity between the EM-profile for intramolecuar fluorescence quenching in... 

Product stereochemistries can be greatly influenced by these chelation control effects. This was first observed by Cram.10 There are many controversies about this topic, and the issue remains a topic of investigative interest.11 Without kinetic data, it has been suggested that it is impossible to distinguish the following two mechanistic types 12... 

As another important mechanistic type, fragmentation into at least three products that are formed more or less simultaneously has to be mentioned. Such [5 - 2 + 2 + 1] reactions were encountered in 2-pyrrolidinones (65, 67), certain pyrazolidine derivatives (68, 72, 73), l,2,4-triazolidine-3-ones (69) and l,2,4-triazolidine-3,5-diones (70), 2//-pyrrol-2-ones (71), 1,3-dithiolane 1-oxides (78), 1,2,3,4-thiatriazoles (74), 1,2,4-oxadiazolines (75), and in several rings containing sulfur in an oxidized state (76-79,82). Most of these molecules have an exocyclic double bond. 

The fact that the leaving group is chemically identical to the solvent leads to further complications in the relationship between the kinetics and the mechanism of these reactions. All mechanistic types, i.e. A, D, /a and /d, can give rise to the same rate law and the interest lies in the criteria that are needed to make the distinction and, eventually, in the significance of the distinctions that are made. 

A number of reactions do not seem to belong to any of the above mechanistic types. Such processes are referred to as multicenter reactions. The Diels-Alder cycloaddition reaction of 1,3-butadiene with maleic anhydride is an example (Scheme 5). No charged or odd election intermediates seemingly are involved in this reaction. 

Two distinct mechanistic types of sensitization involving the dyes classified by Oster (7) as photoreducible can be... 

Although a substantial number of reactions are described in the text, they belong to a relatively modest number of mechanistic types. The preparation of alkyl halides from alcohols and HX, the cleavage of ethers, and the preparation of amines from alkyl halides and ammonia (and many other reactions) all, for example, occur by a nucleophilic substitution mechanism. The following is a brief review of the main mechanistic pathways discussed in the text. 

Despite the chemical diversity of the several hundred structures representing herbicidal activity, most reactions of herbicides fall within only a limited number of mechanistic types oxidation, reduction, nucleophilic displacements (such as hydrolysis), eliminations, and additions. "Herbicides", after all, are more-or-less ordinary chemicals, and their principal transformations in the environment are fundamentally no different from those in laboratory glassware. Figure 2 illustrates three typical examples which have received their share of classical laboratory study—the alkaline hydrolysis of a carboxylic ester (in this case, an ester of 2,4-dichlorophenoxyacetic acid, IX), the cycloaddition of an alcohol to an olefin (as in the acetylene, VI), and the 3-elimination of a dithiocarbamate which provides the usual synthetic route to an isothiocyanate (conversion of an N.N-dimethylcarbamic acid salt, XI, to methyl isothiocyanate). Allow the starting materials herbicidal action (which they have), give them names such as "2,4-D ester" or "pronamide" or "Vapam", and let soil form the walls of an outdoor reaction kettle the reactions and products remain the same. 

Given the diverse range of catalysts and experimental conditions under which catalytic dehydrocoupling occurs, it is likely that any one, or several, of the mechanistic types described earlier may be important under a particular set of conditions. It is therefore of paramount importance that the particular conditions be carefully considered when making comparisons between different sets of experimental results. 

Nucleophilic aromatic photosubstitution reactions have been divided into five mechanistic categories17 and each of these mechanistic types has its representatives in the class of aryl halides. Which reaction pathway is followed in any particular case depends on a number of factors such as the nature of the leaving group, the presence of electron-donating or electron-withdrawing substituents on the aromatic ring, the solvent, the multiplicity and the lifetime of the reactive excited state and the presence or absence of electron donors or acceptors in the reaction medium. This renders it rather difficult to make predictions about the mechanistic course that will be followed under a given set of circumstances. 

The latter requirement and the concomitant improvement of comfort led to the exploitation of alternative methods to estimate the biomass concentration. All of them have in common (1) that they are indirect measures, and (2) that models are mandatory to relate these measures to biomass concentration. The models are of the descriptive rather than the mechanistic type which means... 

In this chapter, the concepts of organic bases and basicity were presented. These discussions were expanded to define nucleophiles and nucleophilicity. Trends associated with conjugate bases of acids and nucleophilicity were presented and translated to define the concept of leaving groups. As discussions continue, all of these concepts will play important roles in the various organic reaction mechanistic types presented in the following chapters. 

In Chapter 4, Sn2 reactions were defined and presented in the context of the various conditions necessary for such reactions to take place. However, as mentioned in the introductory comments of Chapter 4, there are additional fundamental mechanistic types relevant to organic chemistry that are essential to understand in order to advance in this subject. In this chapter, discussions of organic chemistry reaction mechanisms are advanced to the study of SN1 reactions. While conditions required for SN1 reactions to proceed are quite different from those essential for SN2 reactions, the products of SN1 reactions, in many cases, resemble those derived from SN2 mechanisms. Additionally, unlike SN2 reactions, SN1 reaction mechanisms allow routes for unwanted or, in some planned cases, preferred side reactions. 

In this chapter, SN l reactions were introduced, compared to SN2 reactions and discussed mechanistically. Through these discussions, the involvement of electron orbitals, and their various hybrids, was addressed. Furthermore, complicating side reactions such as hydride and alkyl migrations were presented. As discussions move into more advanced mechanistic types, it is important to maintain awareness of the involvement and orientation of orbitals, the steric environment at reactive centers, and the overall reactivity of nucleophiles and electrophilic centers. 

Presently, several different organic reaction mechanisms have been presented. Keeping all of these in mind, predict all of the possible products of the following reactions and list the mechanistic type or types from which these products result. 

---