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

SN2置換反応と同様に、ハロゲン化アルキルのE2脱離も協調経路を介して進行します。
しかし、求核剤がα炭素を攻撃するSN2反応とは異なり、E2では強塩基として機能し、β水素を排出します。
β水素とハロゲン化物の損失は、炭素-水素結合と炭素-ハロゲン結合が部分的に切断され、αとβ炭素との間に部分的に形成されたπ結合を特徴とする律速遷移状態を通じて同時に発生します。反応が完了すると、アルケンが生成されます。
E2反応は二分子であり、反応速度がハロゲン化アルキルと塩基の濃度に依存する2次速度論に従い、協調メカニズムをサポートします。
重水素同位体研究は、炭素-水素結合が炭素-重水素結合よりも弱いという事実に基づいて、このメカニズムをさらに確認しています。
例えば、臭化プロピルの塩基誘起脱ハロゲン化水素化水素化では、水素化基質kHの速度定数は、水素化基質k Dの6.7倍であり、この律速ステップが遷移状態での炭素-水素結合の切断を含むことが確認されています。
E2メカニズムに影響を与える要因には、塩基の強度、基質と脱離基の性質、溶媒の種類などがあります。
塩基はE2速度方程式に現れるため、塩基の強度を上げると反応速度が増加します。水酸化物イオン、アルコキシドイオン、アミドイオンなどの強塩基は、E2反応に有利に働きます。
炭素-炭素二重結合の安定性は、置換とともに増加します。したがって、塩基が強い場合、より置換された三級ハロアルカンは、二次および一次ハロアルカンよりも速くE2除去を受けます。
理想的には、良好な脱離基は弱い共役塩基です。ハロゲン化アルキルでは、ヨウ化物基は臭化物や塩化物よりも塩基性が低く、好まれます。
E2反応では、水などの極性プロトン性溶媒が強力な水素結合を介して塩基に溶媒和するため、基質に対する反応性が低下します。対照的に、アセトンのような極性非プロトン性溶媒では、塩基は弱溶媒和のみであるため、E2反応により適しています。

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	<li>Brown, W.H., & Iverson, B.L., & Anslyn, V.E., & Foote S.C. (2014).有機化学。オハイオ州メイソン:Cengage Learning、369。</li>
	<li>Solomons, G., & Fryhle, C. & Snyder, S. (2015).有機化学。ニュージャージー州ニュージャージー州:ワイリー、277。</li>
	<li>Loudon, M., & Parise, J. (2016).有機化学。ニューヨーク州ニューヨーク:マクミラン出版社、405。</li>
	<li>クライン、D.(2017)。有機化学。ニュージャージー州ニュージャージー州:ワイリー、289。</li>
	<li>Clayden, J., & Greeves, N., & Warren, S. (2012).有機化学。オックスフォード:オックスフォード大学出版局、382。</li>
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e2 反応: 反応速度論とメカニズム

E2 Reaction: Kinetics and Mechanism

ハロゲン化アルキルの SN2 置換と E2 脱離は、協調的な経路を介して進行します。 求核試薬は SN2 反応でアルファ炭素を攻撃しますが、E2 メカニズムでは強塩基として機能し、ベータ水素を引き抜きます。 E2 脱離反応における律速遷移状態は、部分的に切断された炭素-水素結合および炭素-ハロゲン結合と、アルファ炭素とベータ炭素の間に部分的に形成されたパイ結合によって特徴付けられます。 ベータ水素とハロゲン化物が同時に除去され、共役酸とハロゲン化物とともにアルケンが生成します。

E2 反応は二分子反応であり、二次反応速度論に従い、反応速度はハロゲン化アルキルと塩基の濃度に依存します。 この協調的なメカニズムは、C-H 結合と比較して C-D 結合を切断するのに必要なエネルギーがより高いことに基づいた重水素同位体の研究によってさらに確認されています。 したがって、律速段階で移動する水素 (ベータ水素) が重水素で置換されると、一次速度論的重水素同位体効果が観察されます。

さまざまな脱ハロゲン化水素反応の研究により、水素化された基質の速度定数 (kH) が重水素化された基質の速度定数 (kD) よりも 2.5 ～ 8 倍高いことが明らかになり、律速段階には炭素 - 水素結合の切断が含まれることが確認されています。 遷移状態。

E2 メカニズムは、塩基の強度、基質と脱離基の性質、および溶媒の種類によって影響されます。 塩基は E2 速度式に現れるため、反応速度は塩基の強さとともに増加します。 水酸化物、アルコキシド、アミドアニオンなどの強塩基は、E2 反応を促進します。

炭素間二重結合の安定性は置換により高まるため、より多く置換された第三級ハロアルカンは第一級および第二級ハロアルカンよりも速く E2 脱離を受けます。 理想的には、優れた脱離基は弱い共役塩基です。 ヨウ化物基は、ハロゲン化物の中で最も塩基性が低く、最も優れた脱離基です。

塩基は、極性プロトン性溶媒 (水など) 中で強い水素結合を介して溶媒和される可能性があり、その効果が低下します。 したがって、塩基が弱くしか溶媒和しない極性非プロトン性溶媒 (アセトンなど) は E2 反応に有利です。

E2 反応: 反応速度論とメカニズム

SN2置換とハロゲン化アルキルのE2除去は、協調経路を介して進行します。求核剤はSN2反応でアルファ炭素を攻撃しますが、...

Education

JoVE Core

Organic Chemistry

有機化学

Unit 1

ユニット1

Nucleophilic Substitution and Elimination Reactions of Alkyl Halides

ハロゲン化アルキルの親核置換反応および脱離反応

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

KEY TERMS AND CONCEPTS

主要用語と概念

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 有機化学では、立体化学、反応、メカニズムの基本概念を、簡潔でわかりやすいアニメーション ビデオ レッスンを使用して説明します。さらに、科学者の実際のビデオでは、世界中の今日の研究室で行われている古典的および独自の研究実験における関連概念の適用を示しています。

E2 Elimination: Rate, Base, and Solvent

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