1 / 67

Reactions of alkyl halides: nucleophilic Substitution and elimination

Reactions of alkyl halides: nucleophilic Substitution and elimination. Dr. Sheppard CHEM 2412 Fall 2014 McMurry (8 th ed.) sections 10.1, 11.1-11.5, 11.7-11.10, 11.12. Alkyl Halides. Contain F, Cl, Br, or I Widely used in:

Download Presentation

Reactions of alkyl halides: nucleophilic Substitution and elimination

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript


  1. Reactions of alkyl halides: nucleophilic Substitution and elimination Dr. Sheppard CHEM 2412 Fall 2014 McMurry (8th ed.) sections 10.1, 11.1-11.5, 11.7-11.10, 11.12

  2. Alkyl Halides • Contain F, Cl, Br, or I • Widely used in: • Synthesis (electrophilic carbon and easy functional group transitions) • Solvents (CCl4, CHCl3, CH2Cl2) • Industrial applications • Structure:

  3. Properties of Alkyl Halides • Bond strength • Measured by bond dissociation energy • Inversely proportional to bond length • Electronegativity and small size of F keep bonding electrons close C-F > C-Cl > C-Br > C-I short long strong weak • Which C-X bond is easier to break, C-Cl or C-Br?

  4. Properties of Alkyl Halides • Polarity • Alkyl halides have substantial dipole moments • Dipole moments depend on: • Electronegativity of X • F > Cl > Br > I • C-X bond length • C-I > C-Br > C-Cl > C-F • Polarizability of electrons (ease of distribution of electron density) • I > Br > Cl > F • Since these trends oppose one another, the trend in molecular dipole moment is not periodic C-Cl > C-F > C-Br > C-I

  5. Summary of Alkyl Halide Properties

  6. Reactions of Alkyl Halides • Carbon bonded to X is electron-poor (electrophilic) • Will react with nucleophiles • Nucleophiles are also bases! So, there are two competing reactions: • Substitution • Nucleophile substitutes for X (the leaving group) • Elimination • Nucleophile/base removes H, eliminates HX to yield an alkene

  7. Substitution vs. Elimination • How do we know which reaction will occur? • In this chapter: • Mechanisms of substitution • Mechanisms of elimination • Substitution vs. elimination

  8. I. Nucleophilic Substitution • Nucleophile substitute for leaving group (X) • Example: CH3CH2CH2Br + NaOCH3→ CH3CH2CH2OCH3 + NaBr • Leaving group = • Nucleophile =

  9. Stereochemistry • When the product has a stereocenter, we must consider stereochemistry • Examples: • How can we explain the observed stereochemistry? • There is more than one possible mechanism • SN2 and SN1 (differ in timing of C-X breaking and C-Nu formation)

  10. The SN2 Reaction • Bimolecular nucleophilic substitution • Bimolecular = two species (RX and Nu) participate in RDS • Rate = k [RX] [Nu] • Mechanism: • Single step • No intermediates • Bonds broken and made simultaneously (concerted) • Same mechanism as acetylide ion and methyl/primary RX

  11. Transition State of SN2 Reaction

  12. CH3Br + NaOH→ • Products: • Mechanism:

  13. SN2 Energy Diagram • One step • Exothermic E Reaction Coordinate

  14. SN2 Stereochemistry • Nucleophile attacks reaction center (electrophilic carbon) from the direction opposite the leaving group • Backside attack • Causes change in configuration • Stereocenter: S↔R • Rings: cis↔trans • Ex: (S)-2-bromobutane + NaOH

  15. SN2 Characteristics • Factors influencing the rate of SN2 reaction: • Alkyl halide structure • Nucleophile • Leaving group • Solvent

  16. SN2 Characteristics: RX Structure • Steric effects • Nucleophile must have access to reaction center • Access is hindered with bulky substituents

  17. SN2 Characteristics: RX Structure • Trends in RX reactivity: • Methyl halide most reactive • Tertiary alkyl halide not likely to react • Branched 1° and 2° alkyl halides react slower than unbranched • Vinyl and aryl halides will not react

  18. SN2 Characteristics: Nucleophile • Nucleophile: contains lone pair • Some nucleophile are better than others • Better nucleophile = faster SN2 reaction • Some common nucleophiles: • What trends do you notice relating nucleophilicity and structure?

  19. Trends in Nucleophile Structure • Anions are stronger nucleophiles than neutral molecules HO > H2O RO > ROH

  20. Trends in Nucleophile Structure • Less stable anions are stronger nucleophiles than more stable anions RO > RCO2 • Generally, nucleophilicity increases down a group I > Br , Cl > F • Bulky anions are more likely to act as a base, rather than a nucleophile (CH3)3CO vs. CH3O base nucleophile

  21. Nucleophile Structure • Some common good nucleophiles are also strong bases • HO- • RO- • H2N- • Some common good nucleophiles are weak bases • I- • -CN • RCO2- • This will be important later when comparing substitution and elimination

  22. SN2 Characteristics: Leaving Group • Better LG = faster reaction • Better LG = more stable anion

  23. SN2 Characteristics: Solvent • Dissolves reactants, creates environment of reaction, can affect outcome of reaction • Solvents are either protic or aprotic • Polar protic • H-bond donor • Contain NH or OH • Alcohols, carboxylic acids, amines, water • Polar aprotic • Cannot donate H-bond • Dimethyl sulfoxide (DMSO) • Acetone • Acetonitrile • N,N-Dimethylformamide (DMF)

  24. SN2 Characteristics: Solvent • Polar aprotic solvents solvate cations, but not anions • Anions shielded from d+ by methyl groups • Less solvated • More available to react as nucleophiles • Good for SN2!

  25. SN2 Characteristics: Solvent • Polar protic solvents solvate both cations AND anions • Anion is well-solvated • Less available to react as nucleophiles • Not good for SN2!

  26. The SN1 Reaction • Unimolecularnucleophilic substitution • Unimolecular= one species (RX) participates in RDS • Rate = k [RX] • Mechanism: • Multiple steps • Carbocation intermediate • C-X bon broken before C-Nu bond formed • Which step is RDS?

  27. Mechanism of SN1 Reaction

  28. SN1Energy Diagram

  29. SN1 Stereochemistry • Racemic mixture • 50% inversion of configuration • 50% retention of configuration • Why? Look at intermediate…

  30. (R)-3-chloro-3-methylhexane + NaOAc → • Products: • Mechanism:

  31. SN1 Stereochemistry • Sometimes slightly more than one enantiomer is observed • 55-60% inversion • 40-45% retention • Why? Association of leaving group with carbocation

  32. SN1 Characteristics • Factors influencing the rate of SN1 reaction: • Alkyl halide structure • Nucleophile • Leaving group • Solvent

  33. SN1 Characteristics: RX Structure • Electronic effects • More stable carbocation = faster reaction • Remember carbocation stability

  34. SN1 Characteristics: RX Structure • Trends in RX reactivity: • Tertiary alkyl halides most reactive • Primary alkyl halides will not form unless allylic or benzylic

  35. SN1 Characteristics: Nucleophile • Nucleophile is not important for SN1 reactions • Not in the rate equation • Even poor nucleophiles are OK for SN1 • H2O, ROH, etc.

  36. SN1 Characteristics: Leaving Group • Better LG = faster reaction

  37. SN1 Characteristics: Leaving Group • SN1 on alcohols • Need strong acid to protonate –OH and form a better LG

  38. SN1 Characteristics: Solvent • Polar protic solvents = faster reaction • Solvate both cations AND anions • Speed up RDS by solvating and separating carbocation intermediate and leaving group anion • Good for SN1! • Commonly SN1 nucleophile = solvent • Solvolysis reaction

  39. Summary of SN2 vs. SN1

  40. Predict the substitution mechanism and products for the following reactions…

  41. Carbocation Rearrangements • Carbocation intermediates can rearrange to form a more stable carbocation structure • Types of rearrangements: • Hydride shift • Alkyl shift (methyl or phenyl) • Can SN2 reactions undergo rearrangement?

  42. Draw the Mechanism…

  43. Outline • In this chapter: • Mechanisms of substitution • SN2 • SN1 • Mechanisms of elimination • E2 • E1 • Substitution vs. elimination

  44. II. Elimination Reactions • Alkyl halide + base → alkene • X eliminated from one carbon • H eliminated from adjacent carbon • Compete with substitution reactions

  45. 1-Bromobutane + t-BuOK→

  46. Elimination Regiochemistry • Multiple products can be formed if there is more than one adjacent H • How do we know the major product?

  47. Zaitsev’s Rule • In the elimination of HX from an alkyl halide, the more highly substituted alkene product predominates • This alkene is more stable • There are some exceptions, but this rule is generally true • Example: • Which product is major?

  48. The E2 Reaction • Bimolecular elimination • Rate = k [RX] [Base] • Mechanism: • Single step • Concerted • No intermediates • Needs a strong base (NaOH, NaOR, NaNH2)

More Related