1. John E. McMurry www.cengage.com/chemistry/mcmurry Paul D. Adams University of Arkansas Chapter 10 Organohalides

2.  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 What Is an Organohalide?

3.  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 Why this Chapter?

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

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

6.  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 10.1 Structure of Alkyl Halides

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

8.  Alkane + Cl 2 or Br 2, 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 Preparing Alkyl Halides from Alkanes: Radical Halogenation

9.  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) Radical Halogenation of Alkanes

10.  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 Relative Reactivity

11. Chlorination vs. Bromination

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

13.  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 Allylic Stabilization

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

15. Effects of Resonance Allylic bromination 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.  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) 10.5 Preparing Alkyl Halides from Alcohols

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

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

19.  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 10.6 Reactions of Alkyl Halides: Grignard Reagents

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.  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) 10.7 Organometallic Coupling Reactions

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

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.  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 10.8 Oxidation and Reduction in Organic Chemistry

28.  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 Reduction Reactions