E1cb Elimination

10 Key excerpts on "E1cb Elimination"

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  eBook - ePub

  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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  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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  Organic Mechanisms

  Reactions, Methodology, and Biological Applications

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

    (Publisher)

  Symmetry analysis and theoretical studies using the MO model for the α‐elimination are presented in the chapter. The mechanism for the related rearrangement of carbenes to alkenes via a C─H bond elimination will be discussed.

  Electronegative group facilitated E1cb reactions also possess important synthetic utility and mechanistic significance. They will be presented as well. Elimination reactions have found many applications in biological systems. In this chapter, mechanisms for a few selected enzyme‐catalyzed biological eliminations are reviewed.

  7.1 E2 ELIMINATION: BIMOLECULAR β‐ELIMINATION OF H/LG AND ITS REGIOCHEMISTRY AND STEREOCHEMISTRY

  7.1.1 Mechanism and Regiochemistry

  The E2 reaction is a concerted, bimolecular β‐elimination of a functionalized alkane (R–LG, commonly, LG = Cl, Br, I, MsO, TsO, and TfO) induced by a strong base (B:− ). Usually, the reaction requires a staggered conformation in the functionalized alkane substrate, namely that the departing LG group and the β‐hydrogen to be cleaved should be anti‐coplanar (Fig. 7.1 ) in order for the reaction to be the most kinetically favorable [1 –4 ]. This stereochemistry feature for the reaction is called anti‐elimination. Figure 7.1 shows the general mechanism for the strong‐base induced E2 reaction of a functionalized alkane. In the staggered conformation (reactive conformer), the β‐hydrogen which is anti‐coplanar to a functional group is activated by the LG group and becomes slightly acidic. Under certain conditions, the acidic β‐hydrogen can be effectively attacked by a strong base (B:− ) along the direction of the H─Cβ bond to initiate a bimolecular elimination via a single transition state. In the transition state, the H─Cβ and C─LG bonds are being partially broken, coincident with the partial formation of a C=C π bond. As the transition state collapses, the alkene product is formed, together with the formation of the BH molecule and the LG− ion. Clearly, the stereochemistry of the reaction is determined by the structure of the transition state which correlates to the staggered conformation of the substrate. The relative orientations of all the groups attached to the Cα and Cβ (a, b, c, and d) are retained during the reaction. The reaction follows a second‐order rate law (Eq. 7.3 ) with first order in the base (B−

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  Chemical Kinetics and Mechanism

  • M Mortimer, P G Taylor, Lesley E Smart, Giles Clark(Authors)
  • 2007(Publication Date)
  • Royal Society of Chemistry

    (Publisher)

  192 Elimination reactions involve the removal of two atoms or groups from a molecule. When the eliminated groups are on adjacent carbon atoms, the degree of unsaturation is increased; for example This type of elimination is known as p-elimination. P-eliminations often involve the elimination of H and X from a molecule, where X is a good leaving group. The reaction is brought about by treating the ubstrate with a base X H / P-eliminations usually proceed by either the E2 or the El mechanism. The more common E2 mechanism is a concerted, one-step process. The El mechanism involves two steps, a carbocation intermediate being formed in the low (rate-limiting) first step. Use curly arrows to illustrate the mechanisms of the following reactions. (a> ClCH2CH2Cl + Na+-OH - ClCH=CH2 + Na+Cl- + H20 by an E2 mechanism (b) OS02C6H4CH3 + Na+-OCH3 n-. by an E2 mechanism (c) (CH&CBr + Na+-OCH2CH3 by an El mechanism . ___) + CH30H + Na'-OSO*C6H4CH3 0 (CH3)2CXCH2 + Na'Br- + CH3CH20H 193 We have said that the most commonly encountered mechanism of elimination is the concerted, one-step, E2 mechanism Table 2.1 Leaving groups (X) in E2 reactions The leaving groups commonly employed in E2 reactions are listed in Table 2.1. As you can see, they are essentially the same as those displaced in nucleophilic substitution reactions (see Part 2), with two exceptions. First, protonated alcohols are not listed as substrates RX in Table 2.1, because they usually react by the El mechanism (as we shall see later) rather than the E2 mechanism. Secondly, the trimethylammonium and dimethylsulfonium groups have limited importance as leaving groups in substitution reactions, although they are particularly important in elimination reactions.

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  Reaction Mechanisms in Organic Chemistry

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

    (Publisher)

  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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  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)

  CHAPTER 9 Elimination Reactions M. L. Birsa Faculty of Chemistry, “Al. I. Cuza” University of Iasi, Iasi, Romania E1cB and E2 Mechanisms . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 423 Pyrolytic Reactions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 424 Acid Derivatives . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 424 Halogen Derivatives . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 425 Oxygen Derivatives . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 426 Other Pyrolytic Reactions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 427 Elimination Reactions in Synthesis . . . . . . . . . . . . . . . . . . . . . . . . . . . 427 Other Reactions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 431 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 433 E1cB and E2 Mechanisms Density functional theory (DFT) and a mixed implicit/explicit solvation model have indicated that base-catalysed dehydration of benzene cis-1,2-dihydrodiols takes place by producing an aromatic product and by-products potentially stabilized by hyperaromaticity. 1 Experiments show unusual shifts in isotope effects, indicating an uncommon mechanistic balance on the E2–E1cB continuum. The computational data help unravel hidden by-products in the reaction coordinate and provide a novel conceptual framework for distinguishing between competing pathways in this and any other system with borderline reaction mechanisms. Ketene-forming elimination from 2-X-4-nitrophenyl furylacetates promoted by R 2 NH–R 2 NH + 2 in 70 mol% aqueous MeCN has been studied kinetically. 2 When X = Cl and NO 2 , the reactions exhibited second-order kinetics, the Brönsted  decreased with a poor leaving group, and | lg| increased with a weak base.

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  Organic Reaction Mechanisms 1990

  An annual survey covering the literature dated December 1989 to November 1990

  • A. C. Knipe, W. E. Watts, A. C. Knipe, W. E. Watts(Authors)
  • 2008(Publication Date)
  • Wiley

    (Publisher)

  The authors expected a mixture for an ElcB reaction. However, this assignment may be questioned. The protonated base should be hydrogen-bonded to the p-carbon and it is likely that the rearrangement of the localized hydrogen- 12 Elimination Reactions 371 bonded carbanion is slow compared with expulsion of the leaving-group, as has been shown in other ElcB reactions.16 Also, 1P-elimination may occur from allylic ethers with the same reagents (eq. 2 and 3).17 High stereo- and regio-selectivity are usually seen in these reactions. Conjugated trienes are formed as the final products in base-promoted elimina- tions of HI and HF in aqueous ethanol from (15).18 The initial products from the two parallel reaction routes were isolated. A mechanism of a-substitution reactions of acrylic derivatives has been proposed (Scheme l).I9 The final step is assumed to be an E2 reaction. Formation of a Double or Triple Bond to a Heteroatom It has been reported recently that base-promoted sulphine formation from methyl methanesulphinates, Ar,CHS(O)OMe, takes place by an E 1 cB, mechanism. The 372 Organic Reaction Mechanisms 1990 R~G - base, -HI / / H H F I (15) base, -HI I H ' F+ base, -HF ~ H F H F base, -HF I F + CN fast . )-OH CN SCHEME 1 + same group has now studied sulphine formation from a substrate (16) with an even poorer leaving-group. Observation of H-D exchange indicates that the mechanism is of ElcB, type. The leaving group departs presumably as R,NH rather than R,N-. A reversible ElcB mechanism has also been assigned to the 12 Elimination Reactions 373 MeO- / MeOH - / H S-NPr’; II SAr H O fast pk A HOCH=CHCONH2 0 SCHEME 2 base-promoted elimination of para-substituted thiophenoxides from 4-(ary1thio)- azetidin-2-ones in water (Scheme 2).,l Phenoxides leave 4-7 times more quickly than thiophenoxides.

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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 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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