TOPIC 7. ELIMINATION REACTIONS (Sections 7.1-16; 6.16-20)

OBJECTIVES 1. Describe mechanisms for elimination of a leaving group and adjacent proton to form a pi-bond. 2. Discuss the effect of starting material (“substrate”), leaving group, and reaction conditions on the course and outcome of a reaction. 3. Describe syntheses of alkenes and alkynes.

REVIEW OF ALKENES: STRUCTURE, NOMENCLATURE, AND STABILITY S:7.1-4 Prob:7.18-21,28,29 Structure Preview of Reactivity: Additions (Topic 8)

Systematic Nomenclature e.g., Assign Cahn-Ingold-Prelog priority to substituents on each sp2 carbon Highest priority on same side: Z (zusammen=same) opposite sides: E (entgegen=opposite) Problem: Name the following compound

Problem: Provide IUPAC names for the following alkenes Problem: Determine the E/Z configurations of the double bonds in each of the following alkenes geraniol a-pinene                                       

Heats of Hydrogenation C4H8 + H2 C4H10 Relative Stability Heats of Hydrogenation C4H8 + H2 C4H10 Pt or Pd DHo H

Heats of Combustion C4H8 + 6O2 4CO2 + 4H2O DHo H 4CO2 + 4H2O 2719 kJ/mol 2712 kJ/mol H 2707 kJ/mol 4CO2 + 4H2O

Overall Stability Number of substituents  

Cycloalkenes cyclopropene cyclobutene cyclopentene cyclohexene cycloheptene cyclooctene Chem3D strain energies: 15 kcal/mol 27 kcal/mol

FORMATION OF ALKENES & ALKYNES BY ELIMINATION REACTIONS Preview

AN INTRODUCTION TO ELIMINATIONS: ALKYL HALIDES

The E2 Reaction

The E1 Reaction

FACTORS FAVORING SUBSTITUTION AND ELIMINATION S:6.19 Prob:6.21,23,29 Substitution and elimination mechanisms might be competitive pathways in a reaction mixture. The outcome of a reaction depends on: i. the structure of the substrate, ii. the basicity of the nucleophile

Observations

Summary 3° substrates only undergo substitution with weakly basic nucleophiles (ROH, H2O, RCO2H). Stronger bases promote elimination. 1° substrates generally undergo substitution unless the base itself is sterically crowded (e.g., t-BuO-). substrate nucleophile/base Mechanism 3° 2° 1° Me ROH, H2O, RCO2H Anionic bases, NH3 Less basic than HO – (e.g.., HS –, RS –, NH3, CN, RCO2–) More basic than HO – ROH, H2O All except t-BuO– t-Bu-O– all SN1 (some E1 on heating) E2 SN2

DEHYDROHALOGENATION Base-promoted E2 2° and 3°: 1°: S:7.6 Prob:7.22a-b,23a-b 31,32,36,37 Base-promoted E2 2° and 3°: 1°:

Mechanism ‡

Regiochemistry Zaitsev’s Rule: DG Reaction coordinate

Use of bulky bases can lead to formation of “anti-Zaitsev” products

Stereochemistry: Anti Elimination t-BuOK t-BuOK cis reacts 500 times faster than trans

DEHYDRATION OF ALCOHOLS S:7.7,8 Prob:7.22c-d,23c 26,34,35,38 Acid-Promoted Elimination Ease of dehydration: 3° > 2° >> 1° Proceeds under relatively mild conditions 85 °C 20% aq. H2SO4 Requires relatively harsh conditions 180 °C conc. H2SO4

Mechanism: Dehydration of 3° and 2° alcohols by E1

Stability of Carbocations i-Pr+, H2O t-Bu+, H2O H i-PrOH, H+ t-BuOH, H+ reaction coordinate reaction coordinate

Mechanism: Dehydration of 1° alcohols by E2

Rearrangement during elimination

DEBROMINATION OF VICINAL DIBROMIDES S:7.9,10 Prob:7.22e,23b,46 Problem: How would you convert a 1,2-disubstituted alkene to an alkyne?

Alternate Synthesis of Alkynes: Alkylation of Acetylide Anions (see also 4.18c) S:7.11-12 4.18c Problem: Why is this process only useful when using 1° alkyl bromides?

A REVIEW OF REACTIONS You should prepare a chart of all of the types of reactions that have been covered so far… ….we’ll add more later.

SYNTHETIC STRATEGIES S:4.20 Prob:7.24,27a-c At the end of Topic 6 you were challenged to recognize one-step synthetic transformations. But not all transformations can be achieved in one step. For example, there is no method to dehydrogenate (i.e., remove H2) alkanes. So how would you bring about the following transformation? You need to recognize that there is a single intermediate which can: 1. be made from the starting material, and 2. be transformed into the desired product

This can, of course, be extended to longer sequences of reactions This can, of course, be extended to longer sequences of reactions. How would you prepare decane from bromohexane, bromoethane and ethyne?

Problem: Reaction of trans-1-bromo-2-methylcyclohexane with sodium ethoxide, a non-bulky base, results in formation of 3-methylcyclohexene, the anti-Zaitzev product. Explain.

TOPIC 7 ON EXAM 4 Types of Questions Preparing for Exam 4: - Describe elimination reaction mechanisms - Predict the products of elimination reactions - Describe some simple reactions of alkenes (hydrogenation) and alkynes (acidity, hydrogenation) The problems in the book are good examples of the types of problems on the exam. Preparing for Exam 4: - Work as many problems as possible. - Work in groups. - Do the “Learning Group Problem” at the end of the chapter. - Work through the practice exam