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

Analogamente alle reazioni di sostituzione SN2, anche le eliminazioni E2 degli alogenuri alchilici procedono attraverso un percorso concertato.
Tuttavia, a differenza delle reazioni SN2 in cui il nucleofilo attacca il carbonio α, in E2 funziona come una base forte e astrae un β idrogeno.
La perdita dell'idrogeno β e dell'alogenuro avviene simultaneamente attraverso uno stato di transizione limitante caratterizzato da un legame carbonio-idrogeno e carbonio-alogeno parzialmente rotto e da un legame π parzialmente formato tra il carbonio α e β. Il completamento della reazione produce un alchene.
Le reazioni E2 sono bimolecolari e seguono una cinetica del secondo ordine, in cui la velocità di reazione dipende dalle concentrazioni dell'alogenuro alchilico e della base, supportando un meccanismo concertato.
Gli studi sugli isotopi del deuterio confermano ulteriormente questo meccanismo sulla base del fatto che il legame carbonio-idrogeno è più debole di un legame carbonio-deuterio.
Ad esempio, nella deidroalogenazione indotta da basi del bromuro di propile, la costante di velocità per il substrato idrogenato, kH, è 6,7 volte superiore alla sua controparte deuterata, kD, confermando che la fase limitante la velocità comporta la rottura di un legame carbonio-idrogeno allo stato di transizione.
I fattori che influenzano il meccanismo E2 includono la forza della base, la natura del substrato e del gruppo uscente e il tipo di solvente.
Poiché la base appare nell'equazione del tasso E2, l'aumento della forza della base aumenta il tasso di reazione. Basi forti come l'idrossido, l'alcossido e gli ioni ammidici favoriscono le reazioni E2.
La stabilità del doppio legame carbonio-carbonio aumenta con la sostituzione. Pertanto, con basi forti, gli aloalcani terziari più sostituiti subiscono eliminazioni di E2 più velocemente rispetto alle controparti secondarie e primarie.
Idealmente, un buon gruppo uscente è una base coniugata debole. Negli alogenuri alchilici, il gruppo ioduro è il meno basico e favorito rispetto al bromuro e al cloruro.
Nelle reazioni E2, i solventi protici polari, come l'acqua, solvatano la base attraverso forti legami idrogeno, rendendoli meno reattivi nei confronti del substrato. Al contrario, nei solventi aprotici polari, come l'acetone, la base è solo debolmente solvatata, rendendoli più adatti per le reazioni E2.

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	<li>Brown, W.H., & Iverson, B.L., & Anslyn, V.E., & Foote S.C. (2014). Chimica organica. Mason, Ohio: Cengage Learning, 369.</li>
	<li>Salomone, G., & Fryhle, C. & Snyder, S. (2015). Chimica organica. New Jersey, NJ: Wiley, 277.</li>
	<li>Loudon, M., & Parise, J. (2016). Chimica organica. New York, NY: Macmillan Publishers, 405.</li>
	<li>Klein, D. (2017). Chimica organica. New Jersey, NJ: Wiley, 289.</li>
	<li>Clayden, J., & Greeves, N., & Warren, S. (2012). Chimica organica. Oxford: Oxford University Press, 382.</li>
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reazione e2: cinetica e mecanismo

E2 Reaction: Kinetics and Mechanism

Le sostituzioni SN2 e le eliminazioni E2 degli alogenuri alchilici procedono attraverso un percorso concordato. Mentre il nucleofilo attacca il carbonio alfa nelle reazioni SN2, funziona come una base forte ed estrae un idrogeno beta nel meccanismo E2. Lo stato di transizione limitante la velocità nelle reazioni di eliminazione E2 è caratterizzato da legami carbonio-idrogeno e carbonio-alogeno parzialmente rotti e da un legame pi parzialmente formato tra i carboni alfa e beta. L'idrogeno beta e l'alogenuro vengono eliminati simultaneamente, producendo un alchene insieme all'acido coniugato e all'alogenuro.

Le reazioni E2 sono bimolecolari e seguono una cinetica del secondo ordine, dove la velocità di reazione dipende dalle concentrazioni dell'alogenuro alchilico e della base. Il meccanismo concertato è ulteriormente confermato dagli studi sugli isotopi del deuterio, che si basano sulla maggiore energia richiesta per rompere il legame C – D rispetto al legame C – H. Pertanto, quando l'idrogeno trasferito nella fase di determinazione della velocità (idrogeno beta) viene sostituito dal deuterio, si osserva un effetto isotopico cinetico primario del deuterio.

Studi su varie reazioni di deidroalogenazione rivelano che la costante di velocità per il substrato idrogenato (kH) è 2,5–8 volte superiore a quella della controparte deuterata (kD), confermando che la fase di limitazione della velocità comporta la rottura di un legame carbonio-idrogeno allo stato di transizione.

Il meccanismo E2 è influenzato dalla forza della base, dalla natura del substrato e del gruppo uscente e dal tipo di solvente. Poiché la base appare nell'equazione della velocità E2, la velocità della reazione aumenta con la forza della base. Basi forti come anioni idrossido, alcossido e ammide promuovono le reazioni E2.

Poiché la stabilità del doppio legame carbonio-carbonio aumenta con la sostituzione, gli aloalcani terziari più sostituiti subiscono eliminazioni E2 più velocemente degli aloalcani primari e secondari. Idealmente, un buon gruppo uscente è una base coniugata debole. Il gruppo ioduro è il meno basico e il miglior gruppo uscente tra gli alogenuri.

La base può essere solvatata tramite forti legami idrogeno in solventi protici polari (come l'acqua), rendendoli meno efficaci. Pertanto, i solventi polari aprotici (come l'acetone), dove la base è solo debolmente solvatata, favoriscono le reazioni E2.

Reazione E2: cinetica e mecanismo

Le sostituzioni SN2 e le eliminazioni E2 degli alogenuri alchilici procedono attraverso un percorso concertato. Mentre il nucleofilo attacca il carbonio alfa nelle reazioni SN2, ...

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Organic Chemistry

Chimica Organica

Unit 1

Unità 1

Nucleophilic Substitution and Elimination Reactions of Alkyl Halides

Reazioni di sostituzione nucleofila ed eliminazione degli alogenuri alchilici

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

KEY TERMS AND CONCEPTS

TERMINI E CONCETTI CHIAVE

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 spiega i concetti di base della stereochimica, delle reazioni e dei meccanismi usando video-lezioni concise e facili da capire. Inoltre, i video scientist-in-action dimostrano l'applicazione di tali concetti in esperimenti di ricerca classici e originali eseguiti al giorno d'oggi nei laboratori in tutto il mondo.

E2 Elimination: Rate, Base, and Solvent

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