Name: e2 elimination: rate, base, and solvent
Uploaded: 2023-04-30T18:28:36.000Z
Duration: 2 min 45 s
Channel: JoVE

SN2대체 반응과 유사하게, 알킬 할리드의 E2 제거도 공동 통로를 통해 진행된다.
그러나, 뉴클레오필이 α 탄소를 공격하는 SN2반응과는 달리, E2에서는 강력한 염기로서 기능하고 β 수소를 추상화한다.
β 수소와 할라이드의 손실은 부분적으로 깨진 탄소 수소 및 탄소 할로겐 결합과 α β 탄소 사이의 부분적으로 형성된 π 결합을 특징으로 하는 속도 제한 전이 상태를 통해 동시에 발생합니다. 반응의 완료는 알케인을 낳는다.
E2 반응은 이중 분자이며 반응 속도가 알킬 할라이드와 염기의 농도에 따라 달라지며 공동 메커니즘을 지원하는 2차 운동학을 따릅니다.
Deuterium 동위원소 연구는 탄소 수소 결합이 탄소 중수소 결합보다 약하다는 사실에 근거하여 이 메커니즘을 추가로 확인합니다.
예를 들어, 프로필 브로마이드의 기저 유도 탈수로게네이션에서, 수소기판에 대한 상수속도, kH는, 그 유족대응국인kD보다6.7배 높으며, 속도제한 단계는 전이 상태에서 탄소수소 결합의 파괴를 포함한다는 것을 확인한다.
E2 메커니즘에 영향을 미치는 인자는 기지의 강도, 기판 및 방치 그룹의 특성 및 용매의 유형을 포함한다.
기지가 E2 속도 방정식에 나타나기 때문에, 베이스의 강도를 증가시켜 반응의 속도를 증가시킨다. 수산화, 알산화수소 및 아마이온과 같은 강한 염기는 E2 반응을 선호합니다.
탄소 탄소 이중 결합의 안정성은 대체와 함께 증가합니다. 따라서, 강한 기지와 함께, 더 대체 된 삼차 할로칼은 보조 및 기본 대응보다 빠른 E2 제거를 받아야합니다.
이상적으로, 좋은 떠나는 그룹은 약한 컨쥬게이트 기지입니다. 알킬 할라이드에서 요오드 군은 가장 기본적이며 브로마이드와 염화물보다 선호됩니다.
E2 반응에서, 극성 용매는 물과 같이 강한 수소 결합을 통해 기지를 졸라서 기판쪽으로 덜 반응하게 합니다. 대조적으로, 아세톤과 같은 극성 아프로틱 용매에서는 베이스가 약하게 솔바킹되어 E2 반응에 더 적합합니다.

<ol>
	<li>Brown, W.H., & Iverson, B.L., & Anslyn, V.E., & Foote S.C. (2014). 유기 화학. 오하이오주 메이슨: Cengage Learning, 369쪽.</li>
	<li>Solomons, G., & Fryhle, C. & Snyder, S. (2015). 유기 화학. 뉴저지, 뉴저지: 와일리, 277.</li>
	<li>Loudon, M., & Parise, J. (2016). 유기 화학. 뉴욕, NY: Macmillan Publishers, 405쪽.</li>
	<li>클라인, D. (2017). 유기 화학. 뉴저지, 뉴저지: 와일리, 289.</li>
	<li>Clayden, J., & Greeves, N., & Warren, S. (2012). 유기 화학. 옥스포드 : Oxford University Press, 382.</li>
</ol>

e2 반응: 동역학 및 메커니즘

E2 Reaction: Kinetics and Mechanism

할로겐화 알킬의 SN2 치환과 E2 제거는 공동 경로를 통해 진행됩니다. 친핵체는 SN2 반응에서 알파 탄소를 공격하는 반면, E2 메커니즘에서는 강력한 염기로 기능하고 베타 수소를 추출합니다. E2 제거 반응의 속도 제한 전이 상태는 부분적으로 끊어진 탄소-수소 및 탄소-할로겐 결합과 부분적으로 형성된 알파 탄소와 베타 탄소 사이의 파이 결합을 특징으로 합니다. 베타 수소와 할로겐화물이 동시에 제거되어 짝산 및 할로겐화물과 함께 알켄이 생성됩니다.

E2 반응은 이분자 반응이며 2차 동역학을 따릅니다. 여기서 반응 속도는 할로겐화 알킬과 염기의 농도에 따라 달라집니다. 이러한 일치된 메커니즘은 C-H 결합에 비해 C-D 결합을 끊는 데 필요한 더 높은 에너지를 기반으로 하는 중수소 동위원소 연구를 통해 추가로 확인되었습니다. 따라서 속도결정단계에서 이동된 수소(베타수소)가 중수소로 치환되면 1차 운동중수소 동위원소 효과가 관찰됩니다.

다양한 할로겐화수소화 반응에 대한 연구에 따르면 수소화된 기질의 속도 상수(kH)는 중수소화된 기질의 속도 상수(kD)보다 2.5~8배 더 높으며, 이는 속도 제한 단계가 전이 상태에서 탄소-수소 결합이 끊어지는 것을 포함한다는 것을 확인시켜 줍니다.

E2 메커니즘은 염기의 강도, 기질의 성질, 이탈기, 용매의 종류에 의해 영향을 받습니다. 염기가 E2 속도 방정식에 나타나기 때문에 염기의 강도에 따라 반응 속도가 증가합니다. 수산화물, 알콕시드 및 아미드 음이온과 같은 강한 염기는 E2 반응을 촉진합니다.

탄소-탄소 이중 결합의 안정성은 치환에 따라 증가하기 때문에 더 많이 치환된 3차 할로알칸은 1차 및 2차 할로알칸보다 더 빠르게 E2 제거를 겪습니다. 이상적으로 좋은 이탈기는 약한 짝염기입니다. 요오드화물 그룹은 할로겐화물 중에서 가장 기본적인 이탈 그룹이며 가장 좋은 이탈 그룹입니다.

염기는 극성 양성자성 용매(예: 물)에서 강한 수소 결합을 통해 용해될 수 있으므로 효율성이 떨어집니다. 따라서 염기가 약하게만 용해되는 극성 비양성자성 용매(예: 아세톤)는 E2 반응을 선호합니다.

E2 반응: 동역학 및 메커니즘

할로겐화알킬의 SN2 치환 및 E2 제거는 조화로운 경로를 통해 진행됩니다. 친핵체가 SN2 반응에서 알파 탄소를 공격하는 동안 ...

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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

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 reaction gives an alkene, the conjugate acid, and the halide.

E2 reactions are bimolecular and follow second-order kinetics. That means the reaction rate depends on both the alkyl halide and the base. Deuterium isotope studies support this concerted pathway because breaking a C-D bond needs more energy than breaking a C-H bond. When the beta hydrogen in the rate-determining step is replaced by deuterium, a primary kinetic deuterium isotope effect appears.

For many dehydrohalogenation reactions, the rate constant for the hydrogenated substrate, k H, is 2.5 to 8 times higher than for the deuterated one, k D. This shows that carbon-hydrogen bond breaking is part of the rate-limiting transition state. The reaction rate also increases with stronger bases. Hydroxide, alkoxide, and amide anions are strong bases that promote E2 reactions.

Substrate structure also matters. Because more substituted carbon-carbon double bonds are more stable, tertiary haloalkanes usually undergo E2 elimination faster than primary and secondary haloalkanes. The leaving group is important too. A good leaving group is a weak conjugate base, and iodide is the least basic and best leaving group among the halides.

Solvent choice can change the reaction rate as well. Polar protic solvents, such as water, solvate the base strongly through hydrogen bonds and make it less effective. Polar aprotic solvents, such as acetone, weakly solvate the base and therefore favor E2 reactions.

E2 Elimination: Rate, Base, and Solvent

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 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: 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. <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 E2 elimination in alkyl halides, including concerted bond breaking, second-order rate laws, deuterium isotope effects, strong bases, and solvent effects.

E2 Elimination: Rate, Base, and Solvent | 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.

E2 Elimination: Rate, Base, and Solvent

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