The Bimolecular Elimination Reaction

As with the substitution reaction, there are two common mechanisms for the elimination reaction. We have just explored the first-order process, the El reaction. Now let s look at the bimolecular reaction, the E2 reaction. 

9a Rate Law The Sn2 reaction is also complicated by alkene formation. Just as we saw for the Sn2 reaction, the typical rate law for the bimolecular E2 reaction shows that the alkene is formed in a second-order process that is first order in both substrate and nucleophile  

E2 Product Sm2 Product more basic ethoxide ion gives mostly 

E2-Sn2 conditions. The steric requirements for deprotonation are far less severe than for attack at the rear of the carbon-bromine bond of /cr/-butyl bromide (fig. 7.76). 

FIGURE 7.76 For tertiary substrates, the Sn2 reaction does not proceed, but the Ei2 reaction is relatively unhindered. 

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Munk and Kim22 described a new approach to the synthesis of stereoisomeric enamines of known configuration which takes advantage of the well-documented facility and stereospecificity of the bimolecular -elimination reaction. 

The bimolecular elimination reaction (E2) also requires a specific arrangement (B) of four atomic centers. In B, the groups X and Y are coplanar with the two carbon atoms and antiparallel (anti-trans, or true... 

We will now look at the special factors that are involved in the bimolecular -elimination reaction. 

PROBLEM 4.61 Observe the Bimolecular elimination reaction. When the base reacts with the hydrogen in the first step of the reaction, what is the spatial relationship between that hydrogen and the bromide leaving group Do you suppose this relationship is important Why or why not ... 

E2 Reaction (Section 7.9) The bimolecular elimination reaction. The proton and leaving group are lost in a single, base-induced step. The product has a new it bond. 

E2 reaction (Section 11.8) A bimolecular elimination reaction in which both the hydrogen and the leaving group are lost in the same step. 

Notice that there is only one mechanistic step (no intermediates are formed), and that step involves both the substrate and the base. Because that step involves two chemical entities, it is said to be bimolecular. Bimolecular elimination reactions are called E2 reactions, where the 2 stands for bimolecular. ... 

The H02- elimination at reaction (22) is often slow, and at a high concentration of peroxyl radicals this reaction may compete with the bimolecular decay of the peroxyl radicals (leading to chain scission Ulanski et al. 1994). However in the presence of base, deprotonation speeds up the 02 elimination [reactions (23)... 

Under hypoxic conditions, cellular enzymes reduce the benzotriazine di-N-oxide [(reaction (68) P450 reductase Cahill and White 1990 and NADPH may be involved Walton et al. 1992 Wang et al. 1993]. Upon microsomal reduction of tirapazamine the radical formed in reaction (68) has been identified by EPR (Lloyd et al. 1991). Using the pulse radiolysis technique, it has been shown that this radical has a pKd of 6 (Laderoute et al. 1988), and it is the protonated form that undergoes the DNA damaging reaction (Wardman et al. 2003). The rate constants of the bimolecular decay of the radical [reaction (70)] has been found to be 2.7 x 107 dm3 mol-1 s 1. The reaction with its anion is somewhat faster (8.0 x 108 dm3 mol-1 s 1), while the deprotonated radicals do not react with one another at an appreciable rate. From another set of pulse radiolysis data, a first-order process has been extracted (k = 112 s 1) that has been attributed to the water elimination reaction (72), and the tirapazamine action on DNA [reaction (74)] has been considered to be due to the resulting radical (Anderson et al. 2003). 

J. F. Bunnett, The Mechanism of Bimolecular -Elimination Reactions, Angew. Chem. Int. Ed. Engl. 1962,1, 225-235. 

Tertiary alkyl chlorides are easily dehydrochlorinated by base (via the E2, or bimolecular elimination reaction mechanism), but the environment of the degrading resin is not basic. Loss of hydrogen chloride to yield an olefin can occur principally by the El, or monomolecular elimination reaction. This is a slow reaction because, in the rate-determining step, the C—Cl bond is broken to form two separated oppositely charged particles. The reaction rate is not assisted by the acid present. 

The gas-phase base-induced elimination reaction of halonium ions was thoroughly investigated in radiolytic experiments22. Radiolytically generated acids C/JH5+ (n = 1,2) were allowed to react at 760 Torr with selected 2,3-dihalobutanes to form the halonium intermediates which, in the presence of trimethylamine, undergo base-induced bimolecu-lar elimination as shown in Scheme 6. This elimination reaction occurs in competition with unimolecular nucleophilic displacement to the cyclic halonium ion and subsequent rearrangement. Isolation and identification of the neutral haloalkenes formed and kinetic treatment of the experimental results indicated that 3-halo-1 -butene is formed preferentially with respect to the isomeric 2-halo-2-butenes and that the bimolecular elimination process occurs predominantly via a transition state with an anti configuration22. 

E2 reaction or bimolecular elimination reaction (Section 9.2) An elimination reaction that follows a concerted mechanism in which a base removes a proton simultaneously with the departure of the leaving group. 

This is an example of the first step of an E2 (bimolecular elimination) reaction mechanism. Note the base-mediated deprotonation of the diester converting the ferf-butoxide anion to ferf-butanol. For clarity, the anion was repositioned and the bond was lengthened. Arrow pushing is illustrated below ... 

Mixtures of Z and E stereoisomers have been obtained in most syntheses. This undoubtedly holds in the presence of an acid catalyst. The tendency of the E-enamine to isomerize to the Z-enamine was readily observed on numerous occasions under unexpectedly mild conditions. Munk and Kim357 summarized the requirements for the stereospecific synthesis of enamines. First, if the introduction of the double bond is to be the final step of the synthesis, it must be stereospecific in character. Second, once the enamine is formed it must retain its stereochemical integrity under the conditions employed in the double-bond-forming step. The base-induced bimolecular -elimination reaction fulfills both these requirements. Indeed, treatment of the mesitoate esters of ( )-threo- (99) and ( )-erythro- (100) l-(4-morpholino)-l,2-diphenylethanol with... 

Apart from the reactions of diazonium salts, a number of other reactions are known in which the C-N bond is broken. The best known of these is the Hofmann elimination of quaternary ammonium hydroxides (Scheme 2.37). An amine is converted by methylation with methyl iodide to the quaternary ammonium salt ( exhaustive methylation ). The iodide, on treatment with moist silver oxide, forms the quaternary ammonium hydroxide which undergoes a bimolecular elimination to form an alkene. The bimolecular elimination of onium salts yields the least alkylated alkene. This substitution pattern is determined by the ease with which a hydrogen atom can be attacked by the base. 

Sulfones and sulfoxides containing at least one b-hydrogen atom undergo a bimolecular elimination reaction (E2) an treatment with alkoxides, leading preferentially to the formation of the least substituted alkene (Hofmann s rule) (Scheme 37). The reaction resembles the analogous eliminations of quaternary ammonium and sulfonium salts (see Chapter 6, p. 83). 

Instead of performing the one step bimolecular SN2 reaction, alkenes react via two closely related bimolecular pathways. The first of these is called the tetrahedral mechanism and proceeds via a negatively charged intermediate. This mechanism is sometimes called the addition/elimination reaction, which is given the label Adn/E. This alternative name is unfortunate, because the other pathway is called the addition/elimination mechanism and proceeds via a readily detectable neutral intermediate. This latter mechanism will be considered in the chapter on sequential addition/elimination reactions. In this book, in an attempt to reduce the confusion, we will call the mechanism that proceeds via an anionic intermediate the tetrahedral mechanism, and reserve the name addition/elimination mechanism for the mechanism that proceeds via a neutral species. 

Now that we have studied bimolecular elimination reaction in some depth, we will turn our attention to the unimolecular pathway. 

Dehydrohalogenation of aliphatic and attcyctic chlorides. Brown2 noted that the bimolecular elimination of hydrogen halide from alkyl halides shifts to the Hofmann type by increasing the steric requirements of the base. Thus the elimination reaction... 

The leaving groups in the bimolecular elimination mechanism (E2) are essentially the same as those in substitution reactions (that is, halides and tosylate). Alcohols do not usually react by the E2 mechanism, but quaternary ammonium salts, such as RN(CH3)3X and sulfonium salts, such as RS(CH3)2X- do. 

The first mechanism to be classified, the bimolecular elimination (E2), was suggested to account for the Hofmann degradation (1), p. 163, of quaternary ammonium hydroxides to olefins and tertiary amines. A single-step reaction between the substrate and a base is involved and the Q-H and C -X bonds break and the Ca-Q double bond forms in a concerted fashion, viz-... 

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