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

E1 메커니즘을 통해 알킬 할라이드의 제거 반응은 SN1 대응과 유사한 두 단계로 발생합니다.
두 반응의 첫 번째 단계는 흡입 중간을 형성하는 할라이드 의 손실로 진행되는 느린 속도 제한 단계입니다.
E1 반응의 두 번째 단계는 알케인을 형성하는 약한 염기에 의한 베타 수소의 추상화를 포함한다. 대조적으로, SN1 반응은 대체 제품을 산출합니다.
E1 메커니즘을 지원하는 증거는 E1 반응이 단분자이며 1 차 역학을 따르는 운동 연구에서 비롯됩니다. 의미, 반응 속도는 기판의 농도에 만 의존한다.
신두리움 동위원소 연구는 추가 증거를 제공합니다. 테르트부틸 염화물의 탈수로겐화의 경우, 비증자 및 중음 유사체의 속도 상수의 비율은 1.1이다.
금리 상수는 거의 동일하기 때문에, 이것은 탄소 수소 결합이 금리 제한 단계에서 깨지지 않고 제안된 메커니즘과 일치하는 두 번째 단계에서 깨지는 것을 시사합니다.
E1 제거 반응에 영향을 미치는 요인에는 카보케이션의 안정성, 이탈 군의 특성 및 용매의 종류가 포함됩니다.
E1 반응에서, 속도 제한 단계는 카보션 중간의 형성을 포함한다. 전자 기증 알킬 그룹은 탄소 수소 시그마 전자를 양전하 탄소의 빈 p-궤도로 탈포시킴으로써 양전하를 안정시킬 수 있다.
하이퍼 컨설션이라고 하는 이 안정화 상호 작용은 알킬 그룹의 수와 함께 증가합니다. 따라서, E1 반응은 삼차 알킬 할리드로 가장 빠릅니다.
그러나, 1차 환암은 또한 보다 안정적인 삼차 탄수화물을 주기 위해 이차 적인 carbocation, 또는 1,2 alkyl 교대를 형성하기 위하여 1,2-수화물 교대를 겪을 수 있습니다.
탄소 할로겐 채권이 금리 제한 단계에서 중단되기 때문에 E1 반응은 탈퇴 그룹의 품질에 더욱 의존합니다. 브로마이드와 염화물에 비해 요오드는 약한 컨쥬게이트 기지이므로 그룹을 더 잘 떠나는 것이 좋습니다.
마지막으로, 극성 용매는 에탄올과 같이 속도 제한 단계에서 형성된 카보션 및 할라이드 이온을 안정화시켜 E1 반응을 선호한다.

<ol>
	<li>Brown, W.H., & Iverson, B.L., & Anslyn, V.E., & Foote S.C. (2014). 유기 화학. 오하이오주 메이슨: Cengage Learning, 369-376.</li>
	<li>Solomons, G., & Fryhle, C. & Snyder, S. (2015). 유기 화학. 뉴저지, 뉴저지: 와일리, 275-281.</li>
	<li>Loudon, M., & Parise, J. (2016). 유기 화학. 뉴욕, NY: Macmillan Publishers, 405-513.</li>
	<li>클라인, D. (2017). 유기 화학. 뉴저지, 뉴저지: 와일리, 289-308.</li>
	<li>Clayden, J., & Greeves, N., & Warren, S. (2012). 유기 화학. 옥스포드 : Oxford University Press, 383-404.</li>
</ol>

e1 반응: 동역학 및 메커니즘

E1 Reaction: Kinetics and Mechanism

여기서는 E2 반응 메커니즘과 달리 이탈기의 속도 제한 손실과 약한 염기에 의한 베타 수소의 추출이라는 두 단계로 구성된 E1 반응 메커니즘의 측면을 탐구합니다. 일반적으로 E1 메커니즘에 대한 실험적 증거는 동역학 연구 또는 동위원소 연구를 통해 이루어집니다. 전자는 1차 동역학(반응이 기질 농도에만 의존함)을 보여주는 반면, 후자는 두 번째 단계에서만 수소가 추출된다는 것을 증명합니다.

E1 반응에 영향을 미치는 요인:

E1 제거 반응에 영향을 미치는 세 가지 핵심 요소는 (a) 탄수화물의 안정성, (b) 이탈기의 특성, (c) 용매 유형입니다. 이러한 맥락에서 탄수화물의 안정화를 유도하는 과접합 메커니즘이 입증되었습니다. 이는 탄소양이온이 형성되는 속도 제한 단계의 핵심이며, 치환된 알킬 할라이드의 반응 속도에 영향을 미칩니다. 흥미로운 결과는 1차 탄소 양이온에서 2차 탄소 양이온을 형성하기 위한 1,2-수소화물 이동 또는 보다 안정적인 3차 탄소 양이온을 제공하기 위한 1,2-알킬 이동입니다. 이어서, 탄소-할로겐 결합 파괴가 속도 제한 단계이기 때문에 E1 반응은 약한 짝염기로서 이탈하는 할로겐화물 그룹의 특성에 의해 주로 영향을 받습니다. 마지막으로, 속도 제한 단계에서 중간 탄소 양이온/할로겐화물을 안정화하는 데 중요한 역할을 하는 양성자성 용매의 극성이 밝혀졌습니다.

3차 할로겐화물: SN1 대 E1

이 단계에서는 SN1 반응과 E1 반응을 비교하는 것이 중요한데, 이 두 반응은 공통 중간체의 형성을 통해 진행되며 결과적으로 반응성에 영향을 미치는 요인에 유사하게 반응하기 때문입니다. 일반적으로 생성물의 형성이 SN1 또는 E1 경로를 통해 진행되는지 여부에 영향을 미치는 것은 어렵습니다. 두 경우 모두 카보양이온에서 진행되는 활성화의 자유 에너지가 매우 작기 때문입니다. 온도가 더 낮을 때 단분자 반응에서는 SN1이 E1에 비해 유리한 경우가 많습니다. 그러나 일반적으로 합성 경로는 3차 할로겐화물이 매우 빠르게 제거되기 때문에 치환 반응을 선호하지 않습니다. 반응 조건의 온도가 증가하면 메커니즘은 E1을 선호하게 됩니다. 이러한 3차 기질에서 제거 생성물이 필요한 경우, 불문율로, 경쟁하는 E1 대 SN1 메커니즘에 대해 E2 메커니즘을 촉진하기 위해 강력한 염기가 사용됩니다.

E1 반응: 동역학 및 메커니즘

여기에서는 E2 반응 메커니즘과 달리 E1 반응 메커니즘의 측면을 탐구하며, 이는 두 단계가 있습니다.

Education

교육

JoVE Core

Organic Chemistry

유기 화학

Unit 1

제1단원

Nucleophilic Substitution and Elimination Reactions of Alkyl Halides

알킬 할라이드의 친핵성 치환 및 제거 반응

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

KEY TERMS AND CONCEPTS

주요 용어 및 개념

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 Organic Chemistry explains basic concepts of stereochemistry, reactions, and mechanisms using concise and easy-to-understand animated video lessons. Additionally, the scientist-in-action videos demonstrate the application of related concepts in classical and original research experiments performed in today's laboratories worldwide.

E1 Elimination: Carbocation Stability and Rates

Description

Transcript

Tags