E1 Elimination

10 Key excerpts on "E1 Elimination"

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  Organic Chemistry

  A Mechanistic Approach

  • Penny Chaloner(Author)
  • 2014(Publication Date)
  • CRC Press

    (Publisher)

  381 10.1 INTRODUCTION Elimination reactions are those in which we remove two atoms or groups from a molecule to generate a multiple bond. Most of the examples we will discuss involve making a carbon–carbon double bond, but we will also make some triple bonds and a few carbon–heteroatom bonds. We previously saw elimination processes as a “side reaction” of substitution—now, we turn the tables and see substitution as a side reaction of a desired elimination. Although we have good method- ologies for inducing reactions to go in one direction or the other, we should recognize that there may always be some competition. In this chapter, we will concentrate initially on eliminations to give alkenes, turning later to alkynes, and multiple bonds involving heteroatoms. 10.2 MECHANISMS As with substitution, we have two mechanisms that are relatively common and one that is much rarer. The two common mechanisms, E1 and E2, have strong similarities to the S N 1 and S N 2 pro- cesses described in the previous chapter and are generally favored by similar conditions to these analogues. The third mechanism, E1cB, is rather different, with no direct analogy in substitution chemistry. We will initially exemplify all the reactions by removal of hydrogen halides, HX, in the presence of base and then explore the scope of the reactions. 10.2.1 E1 Elimination, UNIMOLECULAR This mechanism (Figure 10.1) has strong similarities to the S N 1 process—indeed, the first RDS is identical. A leaving group is lost, taking the electrons from the bond being broken with it, in a slow step, to give a carbocation. However, the next step is not capture of the carbocation by a nucleophile but a rapid loss of a proton to give an alkene. The observed kinetics of the reaction are first order, with the rate proportional only to the concentration of the alkyl halide, not to any added base. The RDS is unimolecular, hence the name E1. The analogy to S N 1 is clear.

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  Reaction Mechanisms in Organic Chemistry

  • Metin Balcı(Author)
  • 2021(Publication Date)
  • Wiley-VCH

    (Publisher)

  a value is significantly reduced. Then, even a weak base can take the proton, forming a double bond between the carbon atoms bearing the departed groups. As seen from the example above, a common intermediate, a carbocation, is formed in both unimolecular substitution and unimolecular elimination reactions. This cation undergoes substitution or elimination reactions. At this stage, it is important to mention that elimination always competes with substitution.

  3.1.1 E1 Reaction Mechanism

  Remember that the SN 1 reaction proceeds in two steps. The formation of a carbocation is the rate-determining step. Similarly, an E1 reaction also proceeds in two steps, and the rate-determining step is the formation of a carbocation. “E” stands for elimination, while “1” stands for the unimolecular reaction. The carbocation formed must be stable. Furthermore, it is desired to use polar solvents to stabilize the carbocation and to have good leaving groups. Strong nucleophiles attack the carbocation, forming substitution products, while weak nucleophiles form elimination products. Often, both products can occur simultaneously. For example, let us examine the solvolysis of t-butyl bromide in ethanol. Because ethanol is a polar solvent, it both facilitates the removal of bromide and stabilizes the carbocation formed. The t-butyl cation is a common intermediate in E1 and SN 1 reactions. Ethanol attacks the carbocation as a nucleophile and forms the t-butyl ethyl ether. On the other hand, ethanol acts as a base and abstracts a proton from the β-carbon to form an alkene. The nucleophilic substitution product is formed in 81% yield, while the elimination product yield is about 19%.

  The solvolysis of t-butyl bromide proceeds by the E1 mechanism. The first step is the formation of a carbocation by heterolytic cleavage of the C—Br bond. In the second, a more rapid deprotonation step, ethanol removes a proton from the adjacent β-carbon atom. If there is no proton in the β-position, then the carbocation can either undergo rearrangement or react with a nucleophile. In the case of t

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  Reaction Mechanisms in Organic Chemistry

  • Metin Balcı(Author)
  • 2021(Publication Date)
  • Wiley-VCH

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  The product distribution is the same. 3.1 Unimolecular Elimination Reactions, E1 93 C CH 3 CH 3 H 3 C I C OH C C Cl C CH 3 CH 3 H 3 C C CH 3 CH 3 CH 3 CH 3 CH 3 CH 3 CH 3 CH 3 CH 3 H 3 C H 3 C H 2 C OEt E1 S N 1 S N 1 EtOH/H 2 O EtOH/H 2 O –I –Cl The structure of the alkyl group directly affects the ratio of substitution/elimination products. Elimination becomes more competitive with substitution as the branching in the β-position increases. The carbocation formed in the first step has a planar structure. With the removal of the leaving group, the steric repulsion between the groups in the starting material is partially reduced. If the carbocation reacts with a nucleophile, which will be attached to the carbocation, the steric repulsion between the substituents will again increase. However, if elimination occurs, the steric effect will be further reduced because another group will depart from the molecule. The reaction of various branched alkyl chlorides with 80% ethanol at 65 ∘ C shows that the amounts of elimination products increase with the branching, while the amounts of substitution products decrease (Table 3.1) [3]. Table 3.1 The percentages of alkenes formed by solvolysis of branched alkyl chlorides in 80% ethanol. C CH 2 CH 3 CH 3 Cl H 3 C C H 3 C CH 3 CH 3 Cl C CH 2 CH 2 CH 3 CH 2 CH 3 Cl H 3 C C CH CH 3 CH 3 Cl H 3 C CH 3 C C CH 3 CH 3 Cl H 3 C H 3 C H 3 C C CH CH 3 CH Cl H 3 C CH 3 H 3 C CH 3 C CH 2 CH 3 CH 2 CH 3 Cl C H 3 C H 3 C H 3 C C CH 2 CH 3 CH 2 CH 3 Cl H 3 C 16% 34% 41% 40% 62% 61% 78% 90% The slow and rate-determining step in E1 reactions is the removal of the leaving group from the molecule. Therefore, it is desired to have a good leaving group. We have presented examples where the leaving groups were halides and a hydroxyl group. Elimination reactions can also be performed with sulfonium and ammonium salts.

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  Klein's Organic Chemistry

  • David R. Klein(Author)
  • 2020(Publication Date)
  • Wiley

    (Publisher)

  This observation is consistent with a stepwise mechanism, in which the rate-determining step does not involve the base. The rate-determining step is the first step in the mechanism (loss of the leaving group), just as we saw in S N 1 reactions. The base does not participate in this step, and therefore, the concentration of the base does not affect the rate. Because this step involves only one chemical entity, it is said to be unimolecular. Unimolecular elimination reactions are called E1 reactions: E 1 Elimination Unimolecular Conceptual CHECKPOINT 8.26 The following reaction occurs via an E1 mechanistic pathway: EtOH Heat (a) What happens to the rate if the concentration of tert-butyl iodide is doubled and the concentration of ethanol is tripled? (b) What happens to the rate if the concentration of tert-butyl iodide remains the same and the concentration of ethanol is doubled? 8.8 The E1 Mechanism 355 LOOKING BACK For a review of carbocation stability and hyperconjugation, see Section 6.11. FIGURE 8.18 Relative stability of primary, secondary, and tertiary carbocations. Most stable Least stable Primary (1°) H 3 C H H Secondary (2°) H 3 C CH 3 H Tertiary (3°) H 3 C CH 3 CH 3 ⊕ ⊕ ⊕ Recall that tertiary carbocations are more stable than secondary carbocations (Figure 8.18), as a result of hyperconjugation. Compare the energy diagrams for E1 reactions involving sec- ondary and tertiary substrates (Figure 8.19). Tertiary substrates exhibit a lower energy of acti- vation during an E1 process and therefore react more rapidly. Primary substrates are generally unreactive toward an E1 mechanism, because a primary carbocation is too unstable to form. FIGURE 8.19 A comparison of energy diagrams for the E1 reactions of secondary and tertiary substrates. Reaction coordinate E1 2° substrate E1 3° substrate E a E a Reaction coordinate Potential energy Potential energy The first step of an E1 process is identical to the first step of an S N 1 process.

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  Organic Mechanisms

  Reactions, Methodology, and Biological Applications

  • Xiaoping Sun(Author)
  • 2020(Publication Date)
  • Wiley

    (Publisher)

  Fig. 7.6 ).

  Figure 7.21 shows reaction profiles for E1 Elimination of 2‐halo‐2‐methylbutane (RX, X = Cl, Br, or I) [2 ]. The order of standard bond dissociation energies (BDEs ) for C─X bonds is BDE (C–Cl, 327 kJ/mol) > BDE (C–Br, 285 kJ/mol) > BDE (C–I, 213 kJ/mol) (see Section 6.1 ). The relative energy levels of R–Cl, R–Br, and R–I are placed accordingly in their reaction profiles. For each of the haloalkanes, the rate‐determining step of E1 reaction (the formation of a carbocation) has a very late transition state. Its structure greatly resembles the carbocation. Therefore, the transition states for all the haloalkanes have very similar energies. As a result, the activation energy of the rate‐determining step for RX almost solely depends on BDE of the C─X bond as indicated in Figure 7.21 (Ea,RCl  > Ea,RBr  > Ea,RI ). This means that rate of the overall reaction is determined by relative ease of departure for the functional group. A better leaving group makes the reaction faster. This is a general principle governing the elimination reactions. On the other hand, the regiochemistry for the E1 reactions is dictated by the relative stabilities of the alkene products. Alkene (1) is more stable and is formed as the major product, as the product formation step for the more stable alkene (which has a lower energy level) possesses a smaller activation energy and is more productive.

  FIGURE 7.21

  Reaction profiles for E1 reactions of haloalkanes.

  7.7 THE E1 Elimination OF ETHERS

  Analogous to acid‐catalyzed dehydration of alcohols (ROH), in the presence of a strong acid, elimination can also occur to secondary or tertiary alkyl ethers (ROR′). Especially interesting is the acid‐catalyzed elimination for tertiary butyl ethers (

  t

  BuOR, R is a primary or secondary alkyl group) (Fig. 7.22 ) [1

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  Organic Chemistry

  • T. W. Graham Solomons, Craig B. Fryhle, Scott A. Snyder(Authors)
  • 2022(Publication Date)
  • Wiley

    (Publisher)

  E1 reactions are favored with substrates that can form stable carboca- tions (i.e., tertiary halides); they are also favored by the use of poor nucleophiles (weak bases), and they are generally favored by the use of polar solvents. It is usually difficult to influence the relative partition between S N 1 and E1 products because the free energy of activation for either reaction proceeding from the carbocation (loss of a proton or combination with a molecule of the solvent) is very small. In most unimolecular reactions, the S N 1 reaction is favored over the E1 reaction, especially at lower temperatures. In general, however, substitution reactions of tertiary halides do not find wide use as synthetic methods. Such halides undergo eliminations much too easily. Increasing the temperature of the reaction favors reaction by the E1 mechanism at the expense of the S N 1 mechanism. • If an elimination product is desired from a tertiary substrate, it is advisable to use a strong base so as to encourage an E2 mechanism over the competing E1 and S N 1 mechanisms. Let us examine several sample exercises that will illustrate how we apply these principles. A summary of these principles can be found in Table 7.1 at the end of the chapter. 7.9 Elimination and Substitution Reactions Compete With Each Other 309 Give the product (or products) that you would expect to be formed in each of the following reactions. In each case, give the mechanism (S N 1, S N 2, E1, or E2) by which the product is formed, and predict the rela- tive amount of each (i.e., would the product be the only product, the major product, or a minor product?). t-BuOH, 50 °C t-BuO − Br CH 3 OH, 25 °C CH 3 OH, 50 °C HS − CH 3 OH, 50 °C HO − CH 3 OH, 50 °C CH 3 O − Br Br Br r H B (c) (e) (b) (d) (a) Strategy and Answer: (a) The substrate is a 1° halide. The base/nucleophile is CH 3 O − , a strong base (but not a hindered one) and a good nucleophile.

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  Organic Chemistry

  • David R. Klein(Author)
  • 2021(Publication Date)
  • Wiley

    (Publisher)

  • Bimolecular elimination reactions are called E2 reactions. SECTION 7.6 • A cis alkene will generally be less stable than its stereoiso- meric trans alkene. This can be verified by comparing heats of combustion for isomeric alkenes. • A trans π bond cannot be incorporated into a small ring. When applied to bicyclic systems, this rule is called Bredt’s rule, which states that it is not possible for a bridgehead car- bon of a bicyclic system to possess a CC double bond if it involves a trans π bond being incorporated in a small ring. SECTION 7.7 • E2 reactions are regioselective and generally favor the more substituted alkene, called the Zaitsev product. • When both the substrate and the base are sterically hindered, an E2 reaction can favor the less substituted alkene, called the Hofmann product. • If the β position has two different protons, the resulting E2 reaction can be stereoselective, because the trans isomer will be favored over the cis isomer (when applicable). • If the β position has only one proton, an E2 reaction is said to be stereospecific, because the proton and the leaving group must be anti-periplanar to one another. SECTION 7.8 • When a tertiary alkyl halide is dissolved in a polar solvent that is both a weak base and a weak nucleophile (such as ethanol, EtOH), substitution and elimination products are both observed. • Unimolecular nucleophilic substitution reactions are called S N 1 reactions. An S N 1 mechanism is comprised of two core steps: 1) loss of a leaving group to give a carbocation intermediate; and 2) nucleophilic attack. • When a solvent molecule functions as the attacking nucleo- phile, the resulting S N 1 process is called solvolysis. • Unimolecular elimination reactions are called E1 reactions. • S N 1 processes are favored by polar protic solvents. • S N 1 and E1 processes are observed for tertiary alkyl halides, as well as allylic and benzylic halides.

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  Organic Chemistry

  • David R. Klein(Author)
  • 2016(Publication Date)
  • Wiley

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  • Unimolecular elimination reactions are called E1 reactions. • S N 1 processes are favored by polar protic solvents. • S N 1 and E1 processes are observed for tertiary alkyl halides, as well as allylic and benzylic halides. • When the α position is a chiral center, an S N 1 reaction gives nearly a racemic mixture. In practice, there is generally a slight prefer- ence for inversion over retention of configuration, as a result of the effect of ion pairs. SECTION 7.10 • If a C − H bond is being broken in the rate-determining step, then a primary isotope effect will be observed. If, however, the C − H bond is broken during a step that is not rate-deter- mining, then any measureable effect is said to be a secondary isotope effect. • For E2 processes, a primary isotope effect is observed, indi- cating that the C − H bond is broken in the rate-determining step. For E1 processes, the lack of a primary isotope effect supports the fact that the C − H bond is broken in a step other than the rate-determining step. SECTION 7.11 • Substitution and elimination reactions often compete with each other. To predict the products, three steps are required: 1) determine the function of the reagent; 2) analyze the substrate and determine the expected mechanism(s); and 3) consider any relevant regiochemical and stereochemical requirements. SECTION 7.12 • Alkyl halides and alkyl sulfonates undergo similar reactions. • Alcohols react with HBr to give alkyl halides, either via an S N 2 pathway (for primary and secondary substrates) or via an S N 1 pathway (for tertiary substrates). • When treated with concentrated sulfuric acid, tertiary alcohols are converted into alkenes via an E1 process. Primary alcohols are also converted into alkenes, likely via an E2 process. SECTION 7.13 • A retrosynthetic analysis shows the product first, followed by reagents that can be used to make that product. A wavy line indicates a disconnection, which identifies the bond that can be made by the reaction.

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  Organic Reaction Mechanisms 2016

  An annual survey covering the literature dated January to December 2016

  • A. C. Knipe(Author)
  • 2019(Publication Date)
  • Wiley

    (Publisher)

  CHAPTER 9 Elimination Reactions M. L. Birsa Faculty of Chemistry, ‘Al. I. Cuza’ University of Iasi, Iasi, Romania E1cB and E2 Mechanisms . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 449 Solvolytic Reactions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 450 Pyrolytic Reactions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 450 Cycloreversion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 450 Acid Derivatives . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 451 Oxygen Derivatives . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 452 Elimination Reactions in Synthesis . . . . . . . . . . . . . . . . . . . . . . . . . . . 452 Other Reactions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 459 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 461 E1cB and E2 Mechanisms The synthesis of ketone-derived enamides by elimination of HCN from cyanoamides has been reported. 1 An E1cB mechanism consistent with the Z configuration of the de  resulting enamide has been proposed. The E2 mechanism has been proposed for the dehydrochlorination of 2,2-diaryl-1,1,1-trichloroethanes with nitrite ion, leading to 2,2-diaryl-1,1-dichloroethenes, on the basis of experimental kinetic study and quantum chemical simulation. 2 The elimination reactions of (E)-2,4,6-trinitrobenzaldehyde O-benzoyloximes pro- moted by R 2 NH/R 2 NH 2 + in 70 mol% MeCN (aq) have been investigated. 3 The reaction proceeded via a cyclic transition state, which is insensitive to the reactant structure variations and favours the E1cB irr mechanism. A regioselective approach to trifluoromethylated diarylethanes and ethenes has been described.

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  Organic Reaction Mechanisms 2014

  An annual survey covering the literature dated January to December 2014

  • A. C. Knipe(Author)
  • 2017(Publication Date)
  • Wiley

    (Publisher)

  Although no E1cB transition state was located, the electron-withdrawing carboxylate group of the substrates seems to be partially responsible for stabilizing the E2 anti- transition state. The competition between elimination and substitution pathways in two related model systems, H 2 O + C 2 H 5 OH 2 + and OH − + C 2 H 5 OH, that represent, in a generic manner, the same reaction under acidic and basic conditions, has been quantum chemically investigated. 4 It has been found that substitution is favoured in acidic conditions, while elimination prevails in basic conditions. In particular, the elimination pathway in model systems shifts from an E1-like E2 mechanism that is dominated by S N 2 substitution to an E1cB mechanism that prevails over S N 2 substitution. The reactivity of microsolvated fluoride ions, F − (CH 3 OH) 0-2 , with methyl, ethyl, n-propyl, and t-butyl bromide has been evaluated over a broad range of temperatures. 5 Significant decreases in reactivity were observed as either solvation or temperature increases. Increasing solvation increases sensitivity to the reaction barrier as revealed by a larger temperature dependence. These reactions are dominated by an S N 2 mechanism for the methyl bromide reaction, while the S N 2 and E2 mechanisms compete for the reactions with ethyl and n-propyl bromide reactions, respectively. The elimination mechanism, with some association, predominates the t-butyl bromide reactions. The multichannel reactions of CH 3 OCl/CD 3 OCl with chloride anion have been investigated by electronic structure calculations and dynamic studies. 6 The theoretical de  study reveals the presence of three channels (anti-E2, syn-E2, and S N 2@O) for the reaction.

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