Name: sn2 backside attack and inversion
Uploaded: 2023-04-30T18:28:35.000Z
Duration: 2 min 27 s
Channel: JoVE

SN2反应的动力学研究表明，亲核试剂和底物均参与决速步。然而，这些研究并未精确阐明反应过程中分子的排列方式。为了推导出SN2反应的完整机理，需考虑以下理论。
首先，底物含有一个电负性卤素，从而形成一个极化的碳-卤键。这导致碳原子上产生一个亲电中心，吸引带有孤对电子的亲核试剂。
然而，卤素周围存在较高的电子密度，有效阻碍了正面进攻。因此，亲核试剂从离去基团的相反方向接近亲电中心，从而发生背面进攻。
当亲核试剂将其孤对电子提供给亲电试剂时，离去基团则带着与碳原子成键的电子对脱离。这导致形成一个过渡态，在此过渡态中，亲核试剂与底物之间的键形成过程和底物与离去基团之间的键断裂过程同时发生。
过渡态极不稳定。为了恢复稳定性，离去基团以协同方式带着电子对离去，导致底物构型发生翻转。
分子轨道理论进一步支持背面进攻机制。亲核试剂的孤对电子占据最高分子轨道（HOMO）。为了形成化学键，HOMO需要与亲电试剂的最低未占分子轨道（LUMO）发生重叠。
当亲核试剂从离去基团的同一侧接近亲电试剂时，会遇到一个节面，导致HOMO与成键和反键的LUMO发生重叠。然而，由于反键重叠抵消了成键重叠，无法形成化学键。
相比之下，亲核试剂从背面进攻时，其HOMO能有效与亲电试剂的LUMO重叠，从而促进键的形成。
因此，两种理论均支持SN2 反应机理为协同过程，其中亲核试剂从背面进攻，同时取代离去基团，导致构型翻转。

s_n2 反应:机理

SN2 Reaction: Mechanism

S_N2反应的动力学研究表明其机理的一个基本特征:它是一个没有中间体的单步过程。 在这里，亲核试剂和底物都参与速率限制步骤。


 底物中电负性较大的卤素的存在会产生极化的碳卤化物键。 卤化物拉动电子云，在碳原子处产生亲电中心。 因此，碳原子带有部分正电荷，而卤化物带有部分负电荷。 亲电子碳用其孤对电子吸引亲核试剂。


 然而，卤化物周围的高电子密度有效地阻止了亲核试剂的同侧攻击。 因此，亲核试剂从底物的缺电子侧接近亲电试剂，导致背面攻击。 因此，亲核试剂将其孤对电子贡献给亲电子碳，与离去基团成 180° 角。


 当卤化物离开亲电子碳时，它会随着与碳键合的电子对一起移动。 这导致过渡态，其中亲核试剂和底物之间的键部分形成，而底物和离去基团之间的键部分断裂。


 碳上有三个固体键和两个部分键，过渡态非常不稳定。 因此，离去基团与与碳键合的电子对分离，导致底物构型反转。 （图1）


 <img alt="Figure1" src="/files/ftp_upload/11749/11749_PT_Figure%201.svg" style="text-align: center; height: 110px;">

 图1 SN2机制


 此外，分子轨道理论也支持背面攻击。 当亲核试剂的键合轨道，即最高占据分子轨道（HOMO），从与离去基团相同的一侧接近底物的最低未占据分子轨道（LUMO）时，它面临着一个取消成键和反键重叠的节点。 相比之下，亲核试剂的背面攻击有效地与基底的 LUMO 重叠，从而形成键。



因此，当进入的亲核试剂从与被置换的离去基团相反的方向与底物反应时，SN2 机制在一步中发生。

<h4>建议阅读:</h4>

S_N2 反应:机理

SN2反应的动力学研究表明其机理的一个关键特征：这是一个不经过中间体的单步过程。在此过程中，……

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

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, which brings a lone pair of electrons. But the electron-rich halide blocks attack from the same side. For that reason, the nucleophile approaches from the opposite side of the leaving group. This is called a backside attack.

In the transition state, the nucleophile is partly bonded to the carbon while the carbon-halide bond is partly broken. The carbon has three solid bonds and two partial bonds, so this state is very unstable. As the halide leaves with the electron pair, the substrate flips and its configuration inverts.

Molecular orbital theory also supports this path. The nucleophile’s highest occupied molecular orbital, or HOMO, matches poorly with the substrate’s lowest unoccupied molecular orbital, or LUMO, from the same side because of a node. A backside attack gives better overlap and allows bond formation. So the SN2 mechanism is a single-step reaction in which the nucleophile attacks opposite the leaving group and displaces it.

SN2 Backside Attack and Inversion

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 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: 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 how SN2 reactions happen in one step, why nucleophiles attack from the backside, and how inversion of configuration forms in the transition state.

SN2 Backside Attack and Inversion | 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。

SN2 Backside Attack and Inversion

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