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

Analogous to SN2 substitution reactions, E2 eliminations of alkyl halides also proceed via a concerted pathway.
However, unlike SN2 reactions where the nucleophile attacks the &#945; carbon, in E2, it functions as a strong base and abstracts a &#946; hydrogen.
Loss of the &#946; hydrogen and the halide occur simultaneously through a rate-limiting transition state characterized by a partially broken carbon-hydrogen and carbon-halogen bond and a partially formed &#960; bond between the &#945; and &#946; carbons.&#160;Completion of the reaction yields an alkene.
E2 reactions are bimolecular and follow second-order kinetics, where the reaction rate depends on the concentrations of the alkyl halide and the base, supporting a concerted mechanism.
Deuterium isotope studies further confirm this mechanism based on the fact that the carbon-hydrogen bond is weaker than a carbon-deuterium bond.
For example, in the base-induced dehydrohalogenation of propyl bromide, the rate constant for the hydrogenated substrate, kH, is 6.7 times higher than its deuterated counterpart, kD, confirming that the rate-limiting step involves the breaking of a carbon-hydrogen bond at the transition state.
Factors influencing the E2 mechanism include the strength of the base, the nature of the substrate and leaving group, and the type of solvent.
Since the base appears in the E2 rate equation, increasing the strength of the base increases the rate of the reaction. Strong bases like hydroxide, alkoxide, and amide ions favor E2 reactions.
The stability of the carbon-carbon double bond increases with substitution. Therefore, with strong bases, the more substituted tertiary haloalkanes undergo E2 eliminations faster than the secondary and primary counterparts.
Ideally, a good leaving group is a weak conjugate base. In alkyl halides, the iodide group is the least basic and favored over bromide and chloride.
In E2 reactions, polar protic solvents, like water, solvate the base via strong hydrogen bonds, making them less reactive towards the substrate. In contrast, in polar aprotic solvents, like acetone, the base is only weakly solvated, making them more suitable for E2 reactions.

e2 reactie: kinetiek en mechanisme

E2 Reaction: Kinetics and Mechanism

S_N2-substituties en E2-eliminaties van alkylhalogeniden verlopen via een gecoördineerde route. Terwijl het nucleofiel de alfakoolstof aanvalt in S_N2-reacties, functioneert het als een sterke base en abstraheert een bèta-waterstof in het E2-mechanisme. De snelheidsbeperkende overgangstoestand bij E2-eliminatiereacties wordt gekenmerkt door gedeeltelijk verbroken koolstof-waterstof- en koolstof-halogeenbindingen en een gedeeltelijk gevormde pi-binding tussen de alfa- en bèta-koolstofatomen. De bètawaterstof en het halogenide worden gelijktijdig geëlimineerd, waardoor samen met het geconjugeerde zuur en het halogenide een alkeen ontstaat.


 E2-reacties zijn bimoleculair en volgen tweede-ordekinetiek, waarbij de reactiesnelheid afhangt van de concentraties van het alkylhalogenide en de base. Het gecoördineerde mechanisme wordt verder bevestigd door deuteriumisotoopstudies, die gebaseerd zijn op de hogere energie die nodig is om de C-D-binding te verbreken in vergelijking met de C-H-binding. Wanneer de waterstof die wordt overgedragen in de snelheidsbepalende stap (bètawaterstof) wordt vervangen door deuterium, wordt dus een primair kinetisch deuteriumisotoopeffect waargenomen.


 Uit onderzoek naar verschillende dehydrohalogeneringsreacties blijkt dat de snelheidsconstante voor het gehydrogeneerde substraat (k_H) 2,5 tot 8 keer hoger is dan die voor de gedeutereerde tegenhanger (k_D), wat bevestigt dat de snelheidsbeperkende stap het verbreken van een koolstof-waterstofbinding inhoudt. de transitiestaat.


 Het E2-mechanisme wordt beïnvloed door de sterkte van de basis, de aard van het substraat en de vertrekkende groep, en het type oplosmiddel. Omdat de base voorkomt in de E2-snelheidsvergelijking, neemt de reactiesnelheid toe met de sterkte van de base. Sterke basen zoals hydroxide-, alkoxide- en amide-anionen bevorderen E2-reacties.


 Omdat de stabiliteit van de dubbele koolstof-koolstofbinding toeneemt met substitutie, ondergaan meer gesubstitueerde tertiaire haloalkanen sneller E2-eliminaties dan primaire en secundaire haloalkanen. Idealiter is een goede vertrekkende groep een zwakke geconjugeerde base. De jodidegroep is de minst basische en de best vertrekkende groep onder de halogeniden.


 De base kan worden opgelost via sterke waterstofbruggen in polaire protische oplosmiddelen (zoals water), waardoor ze minder effectief worden. Polaire aprotische oplosmiddelen (zoals aceton), waarbij de base slechts zwak is opgelost, bevorderen dus E2-reacties.

E2 Reactie: Kinetiek en mechanisme

SN2 substitutions and E2 eliminations of alkyl halides proceed via a concerted pathway. While the nucleophile attacks the alpha carbon in SN2 reactions, ...

Education

JoVE Core

Organic Chemistry

Organische chemie

Unit 1

Onderdeel 1

Nucleophilic Substitution and Elimination Reactions of Alkyl Halides

Nucleofiele substitutie- en eliminatiereacties van alkylhaliden

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

KEY TERMS AND CONCEPTS

BELANGRIJKE TERMEN EN CONCEPTEN

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 explains basic concepts of stereochemistry, reactions, and mechanisms using concise and easy-to-understand animated video lessons. Additionally, the scientist-in-action videos demonstrate the application of related concepts in classical and original research experiments performed in today's laboratories worldwide.

E2 Elimination: Rate, Base, and Solvent

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