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

SN2반응의 운동 연구는 뉴클레오필과 기질 모두 속도 결정 단계에 참여하는 것으로 나타났습니다. 그러나, 그(것)들은 분자가 반응 도중 배열하는 방법을 정확하게 설명하지 않습니다. SN2 반응의 전체 메커니즘을 도출하려면 다음 이론을 고려하십시오.
첫째, 기판에는 편광 된 탄소 할라이드 결합을 생성하는 전기 음성 할로겐이 포함되어 있습니다. 이것은 전자의 그것의 외로운 쌍으로 뉴클레오필을 유치하는 탄소에 전기 성 센터로 이끌어 냅니다.
그러나, 할라이드 주위에 높은 전자 밀도의 존재는 효과적으로 전면 공격을 차단합니다. 따라서, 뉴클레오필은 반대쪽에서 백사이드 공격으로 이어지는 퇴진군에 대한 전기필에 접근한다.
뉴클레오필이 고독한 쌍을 전기필에게 기부함에 따라, 떠나는 그룹은 탄소에 결합된 전자 쌍으로 멀리 당깁니다. 이는 핵과 기판 사이의 결합 형성과 기판과 퇴사 군 사이의 결합 파손이 동시에 발생하는 전환 상태를 초래한다.
전환 상태는 매우 불안정합니다. 안정성을 회복하기 위해, 떠나는 그룹은 기판 구성의 반전으로 이어지는 공동 방식으로 전자 쌍으로 출발합니다.
분자 궤도 이론은 백사이드 공격을 더욱 지원합니다. 뉴클레오필의 외로운 전자 쌍은 가장 높은 분자 궤도 또는 HOMO를 차지합니다. 결합을 형성하기 위해 HOMO는 전기필의 가장 낮은 비어 있는 분자 궤도 또는 LUMO와 겹쳐야 합니다.
뉴클레오필이 떠나는 그룹과 같은 면에서 전기필에 접근할 때, 그것은 노드에 직면하고, 이는 결합 및 항 본딩 LUMO와 호모가 겹치는 귀착된다. 그러나, 결합 방지 중복으로 채권 형태는 결합 중복을 취소하지 않습니다.
대조적으로, 뉴클레오필의 후면 접근법은 결합 형성으로 이어지는 전기필의 LUMO와 호모를 효율적으로 겹친다.
따라서, 두 이론모두SN2반응 메커니즘이 동시에 이탈그룹을 대체하고 구성의 반전을 일으키면서 뒤에서 뉴클레오필이 공격하는 것을 지지한다.

sn2 반응: 메커니즘

SN2 Reaction: Mechanism

SN2 반응의 동역학 연구는 해당 메커니즘의 필수 특징을 제시합니다. 이는 중간체가 없는 단일 단계 공정입니다. 여기서 친핵체와 기질 모두 속도 결정 단계에 참여합니다.


기판에 전기음성도가 더 높은 할로겐이 존재하면 극성화된 할로겐화 탄소 결합이 생성됩니다. 할로겐화물은 탄소 원자에 친전자성 중심을 생성하는 전자 구름을 끌어당깁니다. 따라서 탄소 원자는 부분적인 양전하를 띠는 반면 할로겐화물은 부분적인 음전하를 띱니다. 친전자성 탄소는 비공유 전자쌍으로 친핵체를 끌어당깁니다.


그러나 할로겐화물 주변의 높은 전자 밀도는 친핵체의 동일한 쪽 공격을 효과적으로 차단합니다. 따라서 친핵체는 기질의 전자가 부족한 쪽에서 친전자체에 접근하여 후면 공격을 일으킵니다. 따라서 친핵체는 이탈기로부터 180° 떨어진 친전자성 탄소에 자신의 고립전자쌍을 제공합니다.


할로겐화물이 친전자성 탄소에서 멀어짐에 따라 탄소에 결합된 전자쌍과 함께 멀어집니다. 이로 인해 친핵체와 기질 사이에 부분적으로 형성된 결합과 기질과 이탈기 사이에 부분적으로 끊어진 결합이 있는 전이 상태가 발생합니다.


탄소에 3개의 고체 결합과 2개의 부분 결합이 있어 전이 상태는 매우 불안정합니다. 따라서 이탈기는 탄소에 결합된 전자쌍과 함께 이탈하여 기질 구성의 반전을 초래합니다. (그림 1)


<img alt="Figure1" src="/files/ftp_upload/11749/11749_PT_Figure%201.svg" style="text-align: center; height: 110px;">

Figure 1. SN2 mechanism

또한 분자 궤도 이론은 후면 공격도 뒷받침합니다. 친핵체의 결합 궤도, 즉 가장 높은 점유 분자 오비탈(HOMO)이 이탈기와 같은 쪽에서 기질의 가장 낮은 비어 있는 분자 오비탈(LUMO)에 접근할 때, 결합과 결합을 모두 취소하는 노드를 향하게 됩니다. 결합 방지 겹침. 대조적으로, 친핵체에 의한 후면 공격은 기판의 LUMO와 효율적으로 중첩되어 결합 형성을 초래합니다.


따라서 SN2 메커니즘은 들어오는 친핵체가 이탈하는 이탈기의 반대 방향에서 기질과 반응할 때 단일 단계에서 발생합니다.


<h4>추천 도서:</h4>

<ol style="display: flex; flex-direction: column; gap: 10px;">
<li>Brown, W.H., &amp; Iverson, B.L., &amp; Anslyn, V.E., &amp; Foote S.C. (2014). Organic Chemistry. Mason, Ohio: Cengage Learning, 344-345.</li>
<li>Solomons, G., &amp; Fryhle, C. &amp; Snyder, S. (2015). Organic Chemistry. New Jersey, NJ: Wiley, 246-248.</li>
<li>Loudon, M., &amp; Parise, J. (2016). Organic Chemistry. New York, NY: Macmillan Publishers, 391-393.</li>
<li>Klein, D. (2017). Organic Chemistry. New Jersey, NJ: Wiley, 277-278.</li>
<li>Clayden, J., &amp; Greeves, N., &amp; Warren, S. (2012). Organic Chemistry. Oxford: Oxford University Press, 340-342.</li>
</ol>

SN2 반응: 메커니즘

SN2 반응에 대한 역학 연구는 그 메커니즘의 본질적인 특징을 시사합니다 : 중간체가없는 단일 단계 공정입니다. 여기서, 둘 다 ...

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Organic Chemistry

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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

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

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SN2 Backside Attack and Inversion

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