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Related Concept Videos

E2 Reaction: Kinetics and Mechanism02:45

E2 Reaction: Kinetics and Mechanism

SN2 substitutions and E2 eliminations of alkyl halides proceed via a concerted pathway. While the nucleophile attacks the alpha carbon in SN2 reactions, it functions as a strong base and abstracts a beta hydrogen in the E2 mechanism. The rate-limiting transition state in E2 elimination reactions is characterized by partially broken carbon–hydrogen and carbon–halogen bonds and a partially formed pi bond between the alpha and beta carbons. The beta hydrogen and halide are eliminated...
E2 Reaction: Stereochemistry and Regiochemistry02:43

E2 Reaction: Stereochemistry and Regiochemistry

Elimination reactions of alkyl halides can yield one or more alkenes depending on the specific regiochemical and stereochemical considerations. While the regiochemistry of the reaction governs the location of the double bond in the product, the stereochemical requirements often influence the geometry.
When a substrate with two different β hydrogens undergoes an E2 elimination, the presence of a strong base can yield two regioisomeric alkenes. The more-substituted alkene is the major product and...
E1 Reaction: Kinetics and Mechanism02:46

E1 Reaction: Kinetics and Mechanism

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 leaving group and abstraction of the beta hydrogen by a weak base. Typically, the experimental proof for the E1 mechanism is via kinetic studies or isotope studies. While the former demonstrates the first-order kinetics—the dependence of the reaction solely on substrate concentration—the latter proves the abstraction of hydrogen only in the...
E1 Reaction: Stereochemistry and Regiochemistry02:43

E1 Reaction: Stereochemistry and Regiochemistry

One of the critical aspects of the E1 reaction mechanism, as also observed in E2, is the regiochemistry, with multiple regioisomers obtained as products. In the example discussed, the presence of water as a weak base favors elimination over substitution to generate two alkenes. Given that alkenes’ stability increases with the number of alkyl groups across the double bond, typically, E1 reactions lead to the Zaitsev product, for this is more substituted and stable than the Hofmann product.
Electrophilic 1,2- and 1,4-Addition of HX to 1,3-Butadiene01:17

Electrophilic 1,2- and 1,4-Addition of HX to 1,3-Butadiene

The electrophilic addition of hydrogen halides such as HBr to alkenes and nonconjugated dienes gives a single product as per Markovnikov’s rule.
Electrophilic Addition of HX to 1,3-Butadiene: Thermodynamic vs Kinetic Control01:23

Electrophilic Addition of HX to 1,3-Butadiene: Thermodynamic vs Kinetic Control

The addition of a hydrogen halide to 1,3-butadiene gives a mixture of 1,2- and 1,4-adducts. Since more substituted alkenes are more stable, the 1,4-adduct is expected to be the major product. However, the product distribution is strongly influenced by temperature; low temperature favors the 1,2-adduct, whereas the 1,4-adduct is predominant at high temperature.

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Reply to E. Hindié

Alexander M M Eggermont1, Christian U Blank1, Mario Mandala1

  • 1Alexander M. M. Eggermont, MD, PhD, Princess Máxima Center, Utrecht, the Netherlands; Christian U. Blank, MD, PhD, The Netherlands Cancer Institute-Antoni van Leeuwenhoek, Amsterdam, the Netherlands; Mario Mandala, MD, Azienda Ospedaliera Papa Giovanni XXIII, Bergamo, Italy; Georgina V. Long, BSc, MBBS, Melanoma Institute Australia, The University of Sydney, and Mater and Royal North Shore Hospitals, Sydney, New South Wales, Australia; Victoria G. Atkinson, MBBS, Princess Alexandra Hospital, Brisbane, Queensland, Australia; St 00B4ephane Dalle, MD, PhD, Hospices Civils de Lyon Cancer Institute, Lyon, France; Andrew M. Haydon, MBBS, PhD, Alfred Hospital, Melbourne, Victoria, Australia; Andrey Meshcheryakov, MD, PhD, N.N. Blokhin Cancer Research Center, Moscow, Russian Federation; Adnan Khattak, MD, Fiona Stanley Hospital and Edith Cowan University, Perth, Western Australia, Australia; Matteo S. Carlino, BMedSc, MBBS, Westmead and Blacktown Hospitals, Melanoma Institute Australia, and The University of Sydney, Sydney, New South Wales, Australia; Shahneen Sandhu, MD, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia; James Larkin, PhD, Royal Marsden Hospital, London, United Kingdom; Susana Puig, MD, PhD, Hospital Clinic Universitari de Barcelona, Barcelona, Spain; Paolo A. Ascierto, MD, Istituto Nazionale Tumori IRCCS "Fondazione G. Pascale," Naples, Italy; Piotr Rutkowski, MD, PhD, Maria Skłodowska-Curie National Research Institute of Oncology, Warsaw, Poland; Dirk Schadendorf, MD, PhD, University Hospital Essen, Essen, Germany; German Cancer Consortium, Heidelberg, Germany; Rutger Koornstra, MD, PhD, Radboud University Medical Center Nijmegen, Nijmegen, the Netherlands; Leonel Hernandez-Aya, MD, Washington University School of Medicine, St Louis, MO; Anna Maria Di Giacomo, MD, Center for Immuno-Oncology, University Hospital of Siena, Siena, Italy; Alfonsus J. M. van den Eertwegh, MD, PhD, Amsterdam University Medical Center, location VUMC, Amsterdam, the Netherlands; Jean-Jacques Grob, MD, Aix Marseille University, Hôpital de la Timone, Marseille, France; Ralf Gutzmer, MD, Skin Cancer Center, Hannover Medical School, Hanover, Germany; Rahima Jamal, MD, BSc, Centre Hospitalier de l'Université de Montreal (CHUM), Centre de recherche du CHUM, Montreal, Quebec, Canada; Paul C. Lorigan, MD, Christie NHS Foundation Trust, Manchester, United Kingdom; Alexander C. J. van Akkooi, MD, PhD, The Netherlands Cancer Institute-Antoni van Leeuwenhoek, Amsterdam, the Netherlands; Clemens Krepler, MD, Merck & Co, Inc, Kenilworth, NJ; Nageatte Ibrahim, MD, Merck & Co, Inc, Kenilworth, NJ; Sandrine Marreaud, MD, European Organisation for Research and Treatment of Cancer Headquarters, Brussels, Belgium; Michal Kicinski, PhD, European Organisation for Research and Treatment of Cancer Headquarters, Brussels, Belgium; Stefan Suciu, PhD, European Organisation for Research and Treatment of Cancer Headquarters, Brussels, Belgium; and Caroline Robert, MD, PhD, Gustave Roussy and Paris-Saclay University, Villejuif, France.

Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
|January 25, 2021
PubMed
Summary

No abstract available in PubMed .

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