Chapter 10 Organohalides

1. Chapter 10Organohalides

2. What Is an Organohalide? • An organic compound containing at least one carbon-halogen bond (C-X) • X (F, Cl, Br, I) replaces H • Can contain many C-X bonds • Properties and some uses • Fire-resistant solvents • Refrigerants • Pharmaceuticals and precursors

3. Why this Chapter? • Reactions involving organohalides are less frequently encountered than other organic compounds, but reactions such as nucleophilic substitutions/eliminations that they undergo will be encountered • Alkyl halide chemistry is model for mechanistically similar but more complex reactions

4. 10.1 Naming Alkyl Halides • Find longest chain, name it as parent chain • (Contains double or triple bond if present) • Number from end nearest any substituent (alkyl or halogen)

5. Naming if Two Halides or Alkyl Are Equally Distant from Ends of Chain • Begin at the end nearer the substituent having its name first in the alphabet

6. 10.1 Structure of Alkyl Halides • C-X bond is longer as you go down periodic table • C-X bond is weaker as you go down periodic table • C-X bond is polarized with slight positive charge on carbon and slight negative charge on halogen

7. 10.2 Preparing Alkyl Halides from Alkanes: Radical Halogenation • Alkyl halide from addition of HCl, HBr, HI to alkanes

8. Preparing Alkyl Halides from Alkanes: Radical Halogenation • Alkane + Cl2 or Br2, heat or light replaces C-H with C-X but gives mixtures • Hard to control • Via free radical mechanism • It is usually not a good idea to plan a synthesis that uses this method

9. Radical Halogenation of Alkanes • If there is more than one type of hydrogen in an alkane, reactions favor replacing the hydrogen at the most highly substituted carbons (not absolute)

10. Relative Reactivity • Based on quantitative analysis of reaction products, relative reactivity is estimated • Order parallels stability of radicals • Reaction distinction is more selective with bromine than chlorine

11. Chlorination vs. Bromination

12. 10.3 Preparing Alkyl Halides from Alkenes: Allylic Bromination • N-bromosuccinimide (NBS) selectively brominates allylic positions (due to lower E resulting from resonance) • Requires light for activation • A source of dilute bromine atoms

13. Allylic Stabilization • Allyl radical is delocalized • More stable than typical alkyl radical by 40 kJ/mol (9 kcal/mol) • Allylic radical is more stable than tertiary alkyl radical

14. 10.4 Stability of the Allyl Radical: Resonance Revisited • Three electrons are delocalized over three carbons • Spin density surface shows single electron is dispersed

15. Effects of Resonance • Allylicbromination of unsymmetrical alkenes usually produces mixed products. • Rxn at less hindered primary is favored. • Also, in general, more highly-substituted alkenes are more stable.

16. 10.5 Preparing Alkyl Halides from Alcohols • Reaction of tertiary C-OH with HX is fast and effective • Add HCl or HBr gas into ether solution of 3°alcohol • 1°and 2°alcohols react very slowly and often rearrange, so alternative methods are used (Ch. 11)

17. 10.6 Organometallic Reagents for Alcohol Synthesis A covalent bond between carbon (C) and a metal (M) makes the C nucleophilic. C M δ- δ+ C Li δ- δ+ C Mg δ- δ+

18. Types of Organometallic Coupling Reagents/Rxns • Grignard Reagents • Alkyllithium Reagents • Gilman Reagents • Suzuki-Miyaura Reaction

19. 10.6 Reactions of Alkyl Halides: Grignard Reagents • Reaction of RX with Mg in ether or THF • Product is RMgX – an organometallic compound (alkyl-metal bond) • R is alkyl 1°, 2°, 3°, aryl (aromatic), alkenyl (vinylic) • X = Cl < Br < I

20. Reagent Synthesis • Formation of Grignard Reagent: • Formation of Alkyllithium Reagent:

21. Organometallic reagent mechanism • The metals in both Grignard reagents and alkyllithium reagents turn the attached R group into a nucleophile, that can then attack an electrophilic carbon (e.g., carbonyl)

22. Examples *We will return to these reactions after discussing alcohols and carbonyls

23. Limitations/Scope of Grignard and Alkyllithium Reagents • Both are good nucleophiles, but will act as bases if H+ available in solution: • In the presence of multiple bonds with a strong EN atom, will attack as nucleophile: • C=O, C=N, C≡N, S=O, N=O

24. 10.7 Organometallic Coupling Reactions • Alkyllithium (RLi) forms from RBr and Li metal • RLi (primary, secondary or tertiary alkyl, aryl or vinyl R group) reacts with copper iodide to give lithium dialkylcopper (Gilman reagents)

25. Utility of Organometallic Coupling in Synthesis • Lithium dialkylcopper (Gilman) reagents react with alkyl halides to give alkanes • Aryl and vinyl organometallics also effective

26. Suzuki-Miyaura Reaction • Coupling rxn of aromatic or vinyl substituted boronic acid with aromatic or vinyl substituted organohalide in presence of base and palladium catalyst. • Widely used today in pharmaceutical industry.

27. 10.8 Oxidation and Reduction in Organic Chemistry • In organic chemistry, we say that oxidation occurs when a carbon or hydrogen that is connected to a carbon atom in a structure is replaced by oxygen, nitrogen, or halogen • Not defined as loss of electrons by an atom as in inorganic chemistry • Oxidation is a reaction that results in loss of electron density at carbon (as more electronegative atoms replace hydrogen or carbon) • Oxidation: break C–H (or (C–C) and form C–O, C–N, C–X

28. Reduction Reactions • Organic reduction is the opposite of oxidation • Results in gain of electron density at carbon (replacement of electronegative atoms by hydrogen or carbon) • Reduction: form C–H (or C–C) and break C–O, C–N, C–X