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

As reações de eliminação de haletos de alquila através de um mecanismo E1 ocorrem em duas etapas análogas à sua contraparte SN1.
O primeiro passo em ambas as reações é um passo lento de limitação de taxa que prossegue com a perda do grupo de saída de haleto formando um intermediário de carbocátion.
A segunda etapa nas reações E1 envolve a abstração de um hidrogênio beta por uma base fraca formando um alceno. Em contraste, uma reação SN1 produz um produto de substituição.
As evidências que apóiam o mecanismo E1 vêm de estudos cinéticos, que mostram que as reações E1 são unimoleculares e seguem a cinética de primeira ordem. Ou seja, a taxa de reação depende apenas da concentração do substrato.
Estudos de isótopos de deutério fornecem mais evidências. Para a desidroalogenação do cloreto de terc-butila, a razão das constantes de taxa dos análogos não deuterados e deuterados, kH / kD é 1,1.
Como as constantes de taxa são quase idênticas, isso sugere que uma ligação carbono-hidrogênio não é quebrada na etapa de limitação de taxa, mas na segunda etapa, consistente com o mecanismo proposto.
Os fatores que influenciam as reações de eliminação de E1 incluem a estabilidade do carbocátion, a natureza do grupo de saída e o tipo de solvente.
Em uma reação E1, a etapa limitante da taxa envolve a formação de um intermediário de carbocátion. Os grupos alquila doadores de elétrons podem estabilizar a carga positiva deslocalizando os elétrons sigma carbono-hidrogênio no orbital p vazio do carbono carregado positivamente.
Essa interação estabilizadora, chamada hiperconjugação, aumenta com o número de grupos alquila. Portanto, as reações E1 são mais rápidas com haletos de alquila terciários.
No entanto, um carbocátion primário também pode sofrer um deslocamento de 1,2 hidreto para formar um carbocátion secundário, ou um deslocamento de 1,2 alquil, para dar um carbocátion terciário mais estável.
Como a ligação carbono-halogênio se rompe na etapa de limitação de taxa, as reações E1 dependem ainda mais da qualidade do grupo de saída. Em comparação com brometos e cloretos, os iodetos são bases conjugadas fracas e, portanto, melhores grupos de saída.
Finalmente, solventes próticos polares, como o etanol, estabilizam o carbocátion e os íons haleto formados na etapa limitante da taxa, favorecendo assim as reações E1.

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	<li>Solomons, G., & Fryhle, C. & Snyder, S. (2015). Química Orgânica. Nova Jersey, NJ: Wiley, 275-281.</li>
	<li>Loudon, M., & Parise, J. (2016). Química Orgânica. Nova York, NY: Macmillan Publishers, 405-513.</li>
	<li>Klein, D. (2017). Química Orgânica. Nova Jersey, NJ: Wiley, 289-308.</li>
	<li>Clayden, J., & Greeves, N., & Warren, S. (2012). Química Orgânica. Oxford: Oxford University Press, 383-404.</li>
</ol>

reação e1: cinética e mecanismo

E1 Reaction: Kinetics and Mechanism

Aqui, em contraste com o mecanismo de reação E2, nos aprofundamos nos aspectos do mecanismo de reação E1, que tem duas etapas: perda do grupo de saída como limitante da velocidade e abstração do hidrogênio beta por uma base fraca. Normalmente, a prova experimental para o mecanismo E1 é através de estudos cinéticos ou estudos de isótopos. Enquanto o primeiro demonstra a cinética de primeira ordem – a dependência da reação apenas na concentração do substrato – o último comprova a abstração do hidrogênio apenas na segunda etapa.

Fatores que Influenciam a Reação E1:

Os três fatores principais que influenciam as reações de eliminação E1 são (a) a estabilidade do carbocátion, (b) a natureza do grupo de saída e (c) o tipo de solvente. Nesse contexto, é demonstrado o mecanismo de hiperconjugação que leva à estabilização dos carbocátions. Isso é fundamental para a etapa limitante da velocidade onde o carbocátion é formado, influenciando a velocidade da reação dos haletos de alquila substituídos. Um corolário interessante é um deslocamento de 1,2-hidreto em um carbocátion primário para formar um carbocátion secundário ou um deslocamento de 1,2-alquil para fornecer um carbocátion terciário mais estável. Posteriormente, como a quebra da ligação carbono-halogênio é a etapa limitante da velocidade, as reações E1 são influenciadas principalmente pela natureza dos grupos haleto que saem como bases conjugadas fracas. Por último, a polaridade dos solventes próticos é elucidada, pois eles desempenham um papel crucial na estabilização dos carbocátions/haletos intermediários na etapa limitante da velocidade.

Haletos Terciários: SN1 versus E1

Nesta fase, é essencial comparar as reações SN1 versus E1, pois ambas as reações ocorrem via formação de um intermediário comum e, como resultado, respondem de forma semelhante aos fatores que afetam a reatividade. Tipicamente, é difícil influenciar se a formação de produtos ocorre através da via SN1 ou E1, pois, em ambos os casos, a energia livre de ativação proveniente do carbocátion é muito pequena. SN1 é frequentemente favorável em comparação com E1 para reações unimoleculares quando as temperaturas são mais baixas. Porém, em geral, as vias sintéticas não preferem reações de substituição por haletos terciários, pois são eliminados muito rapidamente. Um aumento na temperatura da condição de reação desloca o mecanismo para favorecer E1. Como regra não escrita, quando se deseja um produto de eliminação de tais substratos terciários, uma base forte é usada para promover o mecanismo E2 contra os mecanismos concorrentes E1 versus SN1.

Reação E1: Cinética e Mecanismo

Aqui, em contraste com o mecanismo de reação E2, nos aprofundamos nos aspectos do mecanismo de reação E1, que tem duas etapas: perda limitante da taxa do ...

Education

JoVE Core

Organic Chemistry

Química Orgânica

Unit 1

Unidade 1

Nucleophilic Substitution and Elimination Reactions of Alkyl Halides

Reações de Substituição Nucleofílica e Eliminação de Haletos de Alquila

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

KEY TERMS AND CONCEPTS

TERMOS-CHAVE E CONCEITOS

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

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E1 Elimination: Carbocation Stability and Rates

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