Name: e1 elimination: carbocation stability and rates
Uploaded: 2023-04-30T18:28:36.000Z
Duration: 2 min 46 s
Channel: JoVE

卤代烷通过E1机理发生的消除反应分为两步，类似于其SN1反应。
这两个反应的第一步均为缓慢的速率决定步骤，该步骤伴随着卤素离去基团的脱离，形成一个碳正离子中间体。
E1反应的第二步涉及弱碱夺取β氢，从而形成烯烃。相比之下，SN1反应则生成取代产物。
支持E1机理的证据来自动力学研究，这些研究表明E1反应为单分子反应，遵循一级动力学。这意味着反应速率仅取决于底物的浓度。
氘同位素研究提供了进一步的证据。对于叔丁基氯的脱卤化氢反应，非氘代与氘代类似物的速率常数之比 kH/kD 为 1.1。
由于速率常数几乎相同，这表明在决速步中并未断裂碳-氢键，而是在第二步中断裂，与所提出的反应机理一致。
影响E1消除反应的因素包括碳正离子的稳定性、离去基团的性质以及溶剂的类型。
在E1反应中，决速步骤涉及碳正离子中间体的形成。给电子的烷基可通过将碳-氢σ电子离域到带正电碳原子的空p轨道中，从而稳定正电荷。
这种称为超共轭的稳定作用随着烷基数量的增加而增强。因此，E1反应在叔卤代烷中进行得最快。
然而，伯碳正离子也可以发生1,2-氢负离子迁移生成仲碳正离子，或发生1,2-烷基迁移，形成更稳定的叔碳正离子。
由于碳-卤素键在决速步中断裂，E1反应还取决于离去基团的优劣。与溴化物和氯化物相比，碘化物是较弱的共轭碱，因此是更好的离去基团。
最后，极性质子溶剂（如乙醇）能够稳定反应速率控制步骤中生成的碳正离子和卤素离子，从而有利于E1反应的进行。

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	<li>所罗门斯，G.，& 弗莱尔，C. & 斯奈德，S. （2015）。有机化学.新泽西州新泽西州:Wiley，275-281。</li>
	<li>Loudon， M. 和 Parise， J. （2016）。有机化学.纽约州纽约市:麦克米伦出版社，405-513。</li>
	<li>克莱因，D.（2017 年）。有机化学.新泽西州新泽西州:Wiley，289-308。</li>
	<li>Clayden， J.， & Greeves， N.， & Warren， S. （2012）。有机化学.牛津:牛津大学出版社，383-404。</li>
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e1 反应: 动力学和机理

E1 Reaction: Kinetics and Mechanism

与 E2 反应机理不同，我们在此深入探讨 E1 反应机理的各个方面，它有两个步骤:离去基团的限速损失和弱碱β氢抽取。通常，E1 反应机理的实验证明是通过动力学研究或同位素研究进行的。前者证明了一阶动力学——反应完全依赖于底物浓度，而后者则证明了氢的抽取只发生在第二步。


 <h4>影响 E1 反应的因素:</h4>


 影响 E1 消去反应的三个关键因素是:(a) 碳阳离子的稳定性;(b) 离去基团的性质;(c) 溶剂类型。在这种情况下，超共轭机制会导致碳阳离子的稳定。这是形成碳阳离子的限速步骤的关键，影响着取代烷基卤化物的反应速度。一个有趣的推论是，1,2-酸酐在伯碳阳离子中发生转变，形成仲碳阳离子，或 1,2-烷基发生转变，产生更稳定的叔碳阳离子。随后，由于碳-卤素键的断裂是限速步骤，E1 反应主要受到作为弱共轭碱的离去卤化物基团性质的影响。最后，阐明了质子溶剂的极性，因为它们在稳定限速步骤中的中间碳阳离子/卤化物方面起着至关重要的作用。


 <h4>叔卤化物: SN1 与 E1 反应</h4>


 在这一阶段，有必要对 SN1 和 E1 反应进行比较，因为这两种反应都是通过形成一个共同的中间体进行的，因此对影响反应性的因素的反应类似。通常情况下，很难影响产物的形成是通过 SN1 还是 E1 途径进行的，因为无论哪种情况，从碳阳离子开始的活化自由能都非常小。当温度较低时，SN1 与 E1 相比更有利于单分子反应。不过，一般来说，合成路线并不倾向于叔卤化物的取代反应，因为它们很快就会发生消去反应。反应条件温度的升高会使机理转向 E1。作为一条不成文的规定，当需要从此类叔卤底物中获得消去产物时，应使用强碱来促进 E2 反应机理，以对抗 E1 和 SN1 反应机理的竞争。

E1 反应: 动力学和机理

此处，与E2反应机理不同，我们深入探讨E1反应机理的特点，该机理包含两个步骤：决速步中离去基团的脱去……

Education

教育

JoVE Core

Organic Chemistry

有机化学

Unit 1

第一单元

Nucleophilic Substitution and Elimination Reactions of Alkyl Halides

卤代烷烃的亲核取代与消除反应

nucleophilic-substitution-and-elimination-reactions-of-alkyl-halides

KEY TERMS AND CONCEPTS

关键术语与概念

e1 elimination: carbocation stability and rates

E1 elimination depends on carbocation stability and reaction rate. It follows a two-step path. The first step is the rate-limiting loss of the leaving group. The second step is the abstraction of the beta hydrogen by a weak base.

Experimental support for the E1 mechanism comes from kinetic studies and isotope studies. Kinetic studies show first-order kinetics, which means the rate depends only on substrate concentration. Isotope studies show that hydrogen is removed only in the second step.

Three main factors affect E1 elimination reactions. These are carbocation stability, the nature of the leaving group, and the solvent type. Hyperconjugation helps stabilize carbocations, so it is important during the rate-limiting step when the carbocation forms. In substituted alkyl halides, this stability affects how fast the reaction occurs.

Carbocations can also rearrange to form more stable intermediates. A 1,2-hydride shift can change a primary carbocation into a secondary carbocation. A 1,2-alkyl shift can give a more stable tertiary carbocation. Since carbon-halogen bond breaking is the slow step, E1 reactions also depend on the leaving halide group, which acts as a weak conjugate base. Protic solvents matter too, because their polarity helps stabilize the carbocation and halide during the rate-limiting step.

Tertiary halides often show a competition between SN1 and E1 pathways. Both reactions form the same intermediate, so they respond similarly to the same reactivity factors. At lower temperatures, SN1 is often favored in unimolecular reactions. At higher temperatures, E1 becomes more likely. When an elimination product is wanted from a tertiary substrate, a strong base is used to push the reaction toward E2 instead of the competing E1 and SN1 routes.

E1 Elimination: Carbocation Stability and Rates

e1-elimination-carbocation-stability-and-rates

alkyl halides

Alkyl Halides: Structure and Reactivity

Alkyl halides are halogen-substituted alkanes. In these compounds, one or more hydrogen atoms in an alkane is replaced by a halogen atom such as fluorine, chlorine, bromine, or iodine. The carbon bonded to the halogen is sp3-hybridized and has a tetrahedral shape. Not every carbon-halogen compound is an alkyl halide. If the halogen is attached to an sp2-hybridized carbon in a carbon-carbon double bond, the compound is a vinyl halide. If the halogen is attached to an sp2-hybridized carbon in an...

nucleophilic substitution reactions

SN1 and SN2 in Organic Substitution

Nucleophilic substitution reactions replace one group in a molecule with another. In these reactions, a nucleophile, which is a Lewis base, reacts with an electrophile, which is a Lewis acid. The nucleophile takes the place of a halogen atom bonded to carbon and releases a stable ion called the leaving group. This reaction pattern is closely related to Lewis acid-base chemistry. The electron-rich species acts as the nucleophile. The electron-deficient species acts as the electrophile. A key...

nucleophiles

Nucleophilic Strength in Substitution Reactions

Nucleophiles are electron-pair donors that take part in substitution reactions. The word comes from Greek and means nucleus-loving. Because they donate electrons, nucleophiles are also Lewis bases. Many nucleophiles are negatively charged species, such as hydroxide, chloride, and hydrosulfide. Neutral molecules can also act as nucleophiles when they have lone pairs of electrons. Examples include ammonia, amines, water, and alcohols. Some molecules without a lone pair can still behave as...

electrophiles

Electrophile Reactivity in Organic Reactions

Electrophile reactivity in organic reactions depends on how a species attracts electrons. Electrophiles are electron-poor and are key partners in nucleophilic substitution reactions. Their charge and orbital structure help explain why they react the way they do. Electrophiles can be positive or neutral species. A positive electrophile such as a proton reacts because it has a vacant, low-energy 1s orbital. Other positive electrophiles, such as carbocations, are reactive because they have an...

leaving groups

How Leaving Groups Affect Substitution

Leaving groups affect how nucleophilic substitution reactions happen. In this type of reaction, a nucleophile replaces a functional group on a substrate. The group that leaves is called the leaving group, and it departs when the bond breaks by heterolytic cleavage, taking both electrons with it. A good leaving group is usually a stable weak base. It can leave as an anion or as a neutral molecule. The easier it is for the leaving group to leave, the more it can influence the reaction rate. <br...

carbocations

Carbocation Structure and Stability

Carbocations are reactive carbon species formed during some nucleophilic substitution and elimination reactions. They are electron-deficient intermediates, with the central carbon holding only six electrons and three bonded atoms. Because they are short-lived and highly reactive, they play an important role in many organic reaction pathways. The central carbon in a carbocation is sp2 hybridized and has a trigonal planar shape. It also contains an empty p orbital that sits perpendicular to the...

sn2 reaction: kinetics

SN2 Rate Law and Reaction Mechanism

SN2 reaction kinetics links reaction rate to the concentration of reactants. In a chemical reaction, kinetic studies measure how fast reactants disappear or products appear under fixed conditions such as temperature, pressure, and solvent. These studies help chemists find the rate law, which can give clues about the species involved in the rate-determining step and the reaction mechanism. The rate of a reaction is found experimentally. Scientists withdraw small samples, called aliquots, at...

sn2 reaction: mechanism

SN2 Backside Attack and Inversion

SN2 reactions happen in one step and end with inversion of configuration. The nucleophile and the substrate both take part in the rate-determining step, and no intermediate forms. The substrate contains a polarized carbon-halide bond. The more electronegative halogen pulls the electron cloud toward itself. That leaves the carbon atom electrophilic, or electron-poor, with a partial positive charge. The halide has a partial negative charge. The electrophilic carbon attracts the nucleophile,...

sn2 reaction: transition state

SN2 Reaction: Reactivity and Steric Effects

An SN2 reaction of an alkyl halide happens in one step. The nucleophile forms a bond with the electrophilic carbon while the halide leaves at the same time. No intermediate forms during this process. As the nucleophile approaches with its lone pairs, the leaving group moves away with the electron pair that was bonded to carbon. The transition state is shown with dotted partial bonds and square brackets. This state is very unstable, so it quickly changes into the more favored product state. <br...

sn2 reaction: stereochemistry

SN2 Inversion of Configuration

SN2 reactions cause inversion of configuration at the carbon being substituted. The nucleophile attacks from the back side, while the leaving group departs at the same time. This happens through a transition state, where the carbon changes from tetrahedral to trigonal bipyramidal and then back to tetrahedral. The change in shape helps explain the product stereochemistry. If the substrate is achiral at the alpha-carbon, the inversion is not seen. When the alpha-carbon is chiral, the reversal is...

sn1 reaction: kinetics

SN1 Reaction Rate and Unimolecular Step

SN1 reaction rate depends on the substrate, not the nucleophile. This pattern was identified by Sir Christopher Ingold and Edward D. Hughes while they studied nucleophilic substitution reactions of tertiary alkyl halides. A tertiary alkyl halide can still undergo substitution even when the nucleophile is weak. In their kinetic studies, the rate of product formation stayed the same when the nucleophile concentration changed, as long as the substrate concentration remained constant. That means...

sn1 reaction: mechanism

SN1 Reaction Steps and Carbocation Formation

The SN1 reaction follows a step-by-step pathway that begins with carbocation formation. In a polar protic solvent, a tertiary haloalkane can ionize so that only the substrate takes part in the rate-determining step, which is the slow step. First, the haloalkane undergoes heterolytic cleavage to form a carbocation intermediate and a halide ion. This bond break is highly endothermic and has a large activation energy. The polar protic solvent helps stabilize the ions by solvation, and that makes...

sn1 reaction: stereochemistry

SN1 Pathway and Product Chirality

SN1 reactions can change the chirality of a product because the reaction goes through a carbocation intermediate. First, the bond between the electrophilic carbon and the leaving group ionizes. Then the nucleophile attacks the carbocation. The carbocation formed in an SN1 reaction is sp2 hybridized and has a trigonal planar shape. Its three substituents lie in the same plane, which creates a plane of symmetry. That makes the carbocation achiral, so the nucleophile can approach from either side...

predicting products: sn1 vs. sn2

SN1 and SN2 Reaction Factors

Nucleophilic substitution of alkyl halides can follow an SN1 or SN2 pathway. In an SN2 reaction, the nucleophile attacks as the leaving group leaves at the same time. In an SN1 reaction, the substrate first splits to form a carbocation, which is a positively charged intermediate. The structure of the alkyl halide helps decide which mechanism is more likely. As alkyl substitution increases, steric hindrance also increases, which makes backside attack harder for SN2. More substituted alkyl...

elimination reactions

E2 vs E1 in Alkyl Halide Elimination

Elimination reactions of alkyl halides form alkenes by removing groups from adjacent carbons. A base can act on the substrate instead of causing substitution. It deprotonates the neighboring carbon, and the reaction creates at least one pi bond. The carbon bonded to the halogen is the alpha carbon, and the adjacent carbon is the beta carbon. These are also called beta elimination or 1,2-elimination reactions. Strong bases help drive this process. Common examples include hydroxides, alkoxides,...

e2 reaction: kinetics and mechanism

E2 Elimination: Rate, Base, and Solvent

E2 elimination is a concerted reaction of alkyl halides that forms an alkene. In this mechanism, the base removes a beta hydrogen as the halide leaves from the alpha carbon. The two bonds change at the same time, so the products are formed in one step. The rate-limiting transition state has partially broken carbon-hydrogen and carbon-halogen bonds. It also has a partially formed pi bond between the alpha and beta carbons. Because the beta hydrogen and the halide are eliminated together, the...

e2 reaction: stereochemistry and regiochemistry

e2-reaction-stereochemistry-and-regiochemistry

E2 Elimination: Major and Minor Products

E2 elimination reactions of alkyl halides can form one or more alkenes, and the product mix depends on regiochemistry and stereochemistry. Regiochemistry controls where the double bond appears. Stereochemistry controls the shape of the alkene that forms. When a substrate has two different beta hydrogens, a strong base can remove either one. That can give two regioisomeric alkenes. The more substituted alkene is the major product and is called the Zaitsev product. The less substituted alkene is...

e1 reaction: kinetics and mechanism

E1 elimination depends on carbocation stability and reaction rate. It follows a two-step path. The first step is the rate-limiting loss of the leaving group. The second step is the abstraction of the beta hydrogen by a weak base. Experimental support for the E1 mechanism comes from kinetic studies and isotope studies. Kinetic studies show first-order kinetics, which means the rate depends only on substrate concentration. Isotope studies show that hydrogen is removed only in the second step. <br...

e1 reaction: stereochemistry and regiochemistry

e1-reaction-stereochemistry-and-regiochemistry

E1 Elimination: Zaitsev Product and Carbocation

E1 elimination often gives the most substituted alkene, called the Zaitsev product. In the example, water acts as a weak base and favors elimination over substitution, so two alkene products can form. The Zaitsev alkene is usually more stable than the Hofmann product because it has more alkyl groups attached to the double bond. The lower-energy pathway also helps explain why the Zaitsev product is favored. Its transition state has lower energy, so this product is both thermodynamically stable...

predicting products: substitution vs. elimination

predicting-products-substitution-vs-elimination

Choosing Products in Substitution and Elimination

Substitution and beta-elimination compete when a nucleophile reacts with an alkyl halide. The major product depends on the substrate, the nucleophile, the temperature, and the solvent. Because more than one pathway can happen at once, a reaction often gives a product mixture. The structure of the alkyl halide helps predict which mechanism is more likely. Methyl halides and 1° halides usually favor bimolecular reactions, especially SN2. SN1 and E1 are disfavored for 1° halides because the 1°...

key terms and concepts

Explore how E1 elimination works, including carbocation stability, leaving groups, protic solvents, isotope studies, and why temperature affects SN1 versus E1.

E1 Elimination: Carbocation Stability and Rates | JoVE K12

organic chemistry

JoVE Core 有机化学（Organic Chemistry）使用简明易懂的动画视频课程解释立体化学、反应和机制的基本概念。 此外，科学家在行动视频展示了相关概念在当今世界各地实验室进行的经典和原创研究实验中的应用。

E1 Elimination: Carbocation Stability and Rates

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