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

Elimination reactions of alkyl halides through an E1 mechanism occur in two steps analogous to its SN1 counterpart.
The first step in both reactions is a slow rate-limiting step which proceeds with the loss of the halide leaving group forming a carbocation intermediate.
The second step in E1 reactions involves the abstraction of a beta hydrogen by a weak base forming an alkene. In contrast, an SN1 reaction yields a substitution product.
Evidence supporting the E1 mechanism comes from kinetic studies, which show that E1 reactions are unimolecular and follow first-order kinetics. Meaning, the reaction rate depends only on the concentration of the substrate.
Deuterium isotope studies provide further evidence. For the dehydrohalogenation of tert-butyl chloride, the ratio of the rate constants of the non-deuterated and deuterated analogs, kH/kD is 1.1.
Since the rate constants are almost identical, this suggests that a carbon-hydrogen bond is not broken in the rate-limiting step but in the second step, consistent with the proposed mechanism.
Factors that influence E1 elimination reactions include the stability of the carbocation, the nature of the leaving group, and the type of solvent.
In an E1 reaction, the rate-limiting step involves the formation of a carbocation intermediate. Electron donating alkyl groups can stabilize the positive charge by delocalizing the carbon-hydrogen sigma electrons into the empty p-orbital of the positively charged carbon.
This stabilizing interaction, called hyperconjugation, increases with the number of alkyl groups. Therefore, E1 reactions are fastest with tertiary alkyl halides.
However, a primary carbocation can also undergo a 1,2-hydride shift to form a secondary carbocation, or a 1,2-alkyl shift, to give a more stable tertiary carbocation.
Since the carbon-halogen bond breaks in the rate-limiting step, E1 reactions further depend on the quality of the leaving group. Compared to bromides and chlorides, iodides are weak conjugate bases, and therefore, better leaving groups.
Finally, polar protic solvents, like ethanol, stabilize the carbocation and the halide ions formed in the rate-limiting step, thereby favoring E1 reactions.

e1 reactie: kinetiek en mechanisme

E1 Reaction: Kinetics and Mechanism

Hier verdiepen we ons, in tegenstelling tot het E2-reactiemechanisme, in de aspecten van het E1-reactiemechanisme, dat twee stappen kent: snelheidsbeperkend verlies van de vertrekkende groep en abstractie van de bèta-waterstof door een zwakke base. Het experimentele bewijs voor het E1-mechanisme vindt doorgaans plaats via kinetische studies of isotopenstudies. Terwijl de eerste de kinetiek van de eerste orde demonstreert - de afhankelijkheid van de reactie uitsluitend van de substraatconcentratie - bewijst de laatste de abstractie van waterstof pas in de tweede stap.


 Factoren die de E1-reactie beïnvloeden:


 De drie sleutelfactoren die de El-eliminatiereacties beïnvloeden zijn (a) de stabiliteit van de carbokation, (b) de aard van de vertrekkende groep en (c) het type oplosmiddel. In deze context wordt het mechanisme van hyperconjugatie dat leidt tot stabilisatie van carbokationen gedemonstreerd. Dit is de sleutel tot de snelheidsbeperkende stap waarbij het carbokation wordt gevormd, waardoor de snelheid van de reactie van gesubstitueerde alkylhalogeniden wordt beïnvloed. Een interessant gevolg hiervan is een 1,2-hydrideverschuiving in een primaire carbokation om een secundaire carbokation te vormen, of een 1,2-alkylverschuiving om een stabielere tertiaire carbokation te geven. Aangezien het verbreken van de koolstof-halogeenbinding de snelheidsbeperkende stap is, worden El-reacties voornamelijk beïnvloed door de aard van de vertrekkende halogenidegroepen als zwakke geconjugeerde basen. Ten slotte wordt de polariteit van protische oplosmiddelen opgehelderd, omdat ze een cruciale rol spelen bij het stabiliseren van de tussenliggende carbokationen/halogeniden in de snelheidsbeperkende stap.


 Tertiaire halogeniden: S_N1 versus E1


 In dit stadium is het essentieel om S_N1- versus E1-reacties te vergelijken, omdat beide reacties verlopen via de vorming van een gemeenschappelijk tussenproduct en als gevolg daarvan op dezelfde manier reageren op factoren die de reactiviteit beïnvloeden. Doorgaans is het moeilijk te beïnvloeden of de vorming van producten via de S_N1- of El-route verloopt, omdat in beide gevallen de vrije activeringsenergie die voortkomt uit de carbokation zeer klein is. S_N1 is vaak gunstig in vergelijking met E1 voor unimoleculaire reacties wanneer de temperaturen lager zijn. Over het algemeen geven synthetische routes echter niet de voorkeur aan substitutiereacties voor tertiaire halogeniden, aangezien deze zeer snel worden geëlimineerd. Een verhoging van de temperatuur van de reactieomstandigheden verschuift het mechanisme en bevoordeelt in plaats daarvan E1. Als een ongeschreven regel wordt, wanneer een eliminatieproduct uit zulke tertiaire substraten gewenst is, een sterke base gebruikt om het E2-mechanisme te bevorderen tegen de concurrerende E1 versus S_N1-mechanismen.

E1 Reactie: Kinetiek en mechanisme

Here, in contrast to the E2 reaction mechanism, we delve into the aspects of the E1 reaction mechanism, which has two steps: rate-limiting loss of the ...

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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

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

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.

E1 Elimination: Carbocation Stability and Rates

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