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

Analog zu SN2-Substitutionsreaktionen verlaufen auch die E2-Eliminierungen von Alkylhalogeniden über einen konzertierten Weg.
Im Gegensatz zu S N 2-Reaktionen, bei denen dasNukleophilden α Kohlenstoff angreift, fungiert es in E2 jedoch als starke Base und abstrahiert einen β Wasserstoff.
Der Verlust des β Wasserstoffs und des Halogenids erfolgt gleichzeitig durch einen geschwindigkeitsbegrenzenden Übergangszustand, der durch eine teilweise gebrochene Kohlenstoff-Wasserstoff- und Kohlenstoff-Halogen-Bindung und eine teilweise gebildete π-Bindung zwischen dem α und dem β Kohlenstoff gekennzeichnet ist. Nach Abschluss der Reaktion entsteht ein Alken.
E2-Reaktionen sind bimolekular und folgen einer Kinetik zweiter Ordnung, bei der die Reaktionsgeschwindigkeit von den Konzentrationen des Alkylhalogenids und der Base abhängt, was einen konzertierten Mechanismus unterstützt.
Deuterium-Isotopenstudien bestätigen diesen Mechanismus weiterhin, da die Kohlenstoff-Wasserstoff-Bindung schwächer ist als eine Kohlenstoff-Deuterium-Bindung.
Bei der baseninduzierten Dehydrohalogenierung von Propylbromid ist beispielsweise die Geschwindigkeitskonstante für das hydrierte Substrat kH 6,7-mal höher als für sein deuteriertes Gegenstück kD, was bestätigt, dass der geschwindigkeitsbegrenzende Schritt das Brechen einer Kohlenstoff-Wasserstoff-Bindung im Übergangszustand beinhaltet.
Zu den Faktoren, die den E2-Mechanismus beeinflussen, gehören die Stärke der Basis, die Art des Substrats und der Abgangsgruppe sowie die Art des Lösungsmittels.
Da die Base in der E2-Geschwindigkeitsgleichung vorkommt, erhöht eine Erhöhung der Stärke der Base die Reaktionsgeschwindigkeit. Starke Basen wie Hydroxid, Alkoxid und Amidionen begünstigen E2-Reaktionen.
Die Stabilität der Kohlenstoff-Kohlenstoff-Doppelbindung nimmt mit der Substitution zu. Daher werden die stärker substituierten tertiären Haloalkane bei starken Basen schneller E2-Eliminierungen durchlaufen als die sekundären und primären Gegenstücke.
Im Idealfall ist eine gute Abgangsgruppe eine schwache konjugierte Basis. Bei Alkylhalogeniden ist die Iodidgruppe die am wenigsten basische und wird Bromid und Chlorid vorgezogen.
Bei E2-Reaktionen solvatisieren polare protische Lösungsmittel wie Wasser die Base über starke Wasserstoffbrückenbindungen, wodurch sie gegenüber dem Substrat weniger reaktiv werden. Im Gegensatz dazu ist bei polaren aprotischen Lösungsmitteln wie Aceton die Base nur schwach solvatisiert, wodurch sie sich besser für E2-Reaktionen eignen.

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

E2 Reaction: Kinetics and Mechanism

SN2-Substitutionen und E2-Eliminierungen von Alkylhalogeniden verlaufen über einen konzertierten Weg. Während das Nukleophil bei SN2-Reaktionen den Alpha-Kohlensubstanz angreift, fungiert es als starke Base und abstrahiert im E2-Mechanismus einen Beta-Wassersubstanz. Der geschwindigkeitsbestimmende Übergangszustand bei E2-Eliminierungsreaktionen ist durch teilweise gebrochene Kohlensubstanz-Wassersubstanz- und Kohlensubstanz-Halogen-Bindungen sowie eine teilweise gebildete Pi-Bindung zwischen den Alpha- und Beta-Kohlensubstanzen gekennzeichnet. Der Beta-Wassersubstanz und das Halogenid werden gleichzeitig eliminiert, wodurch ein Alken zusammen mit der konjugierten Säure und dem Halogenid entsteht.

E2-Reaktionen sind bimolekular und folgen einer Kinetik zweiter Ordnung, wobei die Reaktionsgeschwindigkeit von den Konzentrationen des Alkylhalogenids und der Base abhängt. Der konzertierte Mechanismus wird weiter durch Deuteriumisotopenstudien bestätigt, die auf der höheren Energie basieren, die zum Aufbrechen der C-D-Bindung im Vergleich zur CH-Bindung erforderlich ist. Wenn also der im geschwindigkeitsbestimmenden Schritt übertragene Wassersubstanz (Beta-Wassersubstanz) durch Deuterium ersetzt wird, wird ein primärer kinetischer Deuteriumisotopeneffekt beobachtet.

Untersuchungen verschiedener Dehydrohalogenierungsreaktionen zeigen, dass die Geschwindigkeitskonstante des hydrierten Substrats (kH) 2,5–8-mal höher ist als die des deuterierten Gegenstücks (kD), was bestätigt, dass der geschwindigkeitsbestimmende Schritt das Aufbrechen einer Kohlensubstanz-Wassersubstanz-Bindung beinhaltet der Übergangszustand.

Der E2-Mechanismus wird durch die Stärke der Base, die Art des Substrats und der Abgangsgruppe sowie die Art des Lösungsmittels beeinflusst. Da die Base in der E2-Geschwindigkeitsgleichung vorkommt, erhöht sich die Reaktionsgeschwindigkeit mit der Stärke der Base. Starke Basen wie Hydroxid-, Alkoxid- und Amidanionen fördern E2-Reaktionen.

Da die Stabilität der Kohlensubstanz-Kohlensubstanz-Doppelbindung mit der Substitution zunimmt, durchlaufen stärker substituierte tertiäre Haloalkane schneller E2-Eliminierungen als primäre und sekundäre Haloalkane. Im Idealfall ist eine gute Abgangsgruppe eine schwache konjugierte Base. Die Iodidgruppe ist die am wenigsten basische und beste Abgangsgruppe unter den Halogeniden.

Die Base kann über starke Wassersubstanzbrückenbindungen in polaren protischen Lösungsmitteln (wie Wasser) solvatisiert werden, wodurch sie weniger wirksam werden. Daher begünstigen polare aprotische Lösungsmittel (wie Aceton), in denen die Base nur schwach solvatisiert ist, E2-Reaktionen.

E2-Reaktion: Kinetik und Mechanismus

SN2-Substitutionen und E2-Eliminierungen von Alkylhalogeniden verlaufen über einen konzertierten Weg. Während das Nukleophil den Alpha-Kohlenstoff in SN2-Reaktionen angreift, ...

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Organic Chemistry

Organische Chemie

Unit 1

Einheit 1

Nucleophilic Substitution and Elimination Reactions of Alkyl Halides

Nucleophile Substitutions- und Eliminationsreaktionen von Alkylhalogeniden

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

KEY TERMS AND CONCEPTS

KERNBEGRIFFE UND KONZEPTE

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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