Based on McMurry’s Organic Chemistry, 7th edition 10. Organohalides Based on McMurry’s Organic Chemistry, 7th edition

What Is an Organohalide? An organic compound containing at least one halogen attached to an sp3 hybridized carbon X (F, Cl, Br, I) replaces H Can contain many C-X bonds Properties and some uses Fire-resistant solvents Refrigerants Pharmaceuticals and precursors

Epibatidine (200X more effective than morphine!)

Vancomycin (antibiotic from amycolatopsis orientalis):

10.1 Naming Alkyl Halides Name is based on longest carbon chain (Contains double or triple bond if present) Number from end nearest any substituent (alkyl or halogen) Halogens have same priority as alkyl groups

Naming with Multiple Halides If more than one of the same kind of halogen is present, use prefix di, tri, tetra If there are several different halogens, number them and list them in alphabetical order

Naming if Two Halides or Alkyl Are Equally Distant from Ends of Chain Begin at the end nearer the substituent whose name comes first in the alphabet

Many Alkyl Halides That Are Widely Used Have Common Names

10.2 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 on carbon and slight negative on halogen

Properties of the Halomethanes

10.3: Radical Halogenation Alkane + Cl2 or Br2, initiated by heat or light; replaces C-H with C-X Hard to control for monosubstitution Reacts via a free radical mechanism See mechanism in Figure 10-1 It is usually not a good idea to plan a synthesis that uses this method

Multiple Substitution

Radical Halogenation of Alkanes If there is more than one type of hydrogen in an alkane, the reaction favors replacing the hydrogen at the most highly substituted carbons: 3o>2o>1o The number of available hydrogens is a factor Methyl hydrogens, for example, often outnumber 2o or 3o hydrogens.

Chlorination is unselective:

Relative Reactivity Based on quantitative analysis of reaction products, relative reactivity is estimated Order parallels stability of radicals (See Figure 10-2)

Bromination is much more selective than chlorination:

10.4 Preparing Alkyl Halides Alkyl halide is formed by the addition of HCl, HBr, HI to alkenes to give the Markovnikov product (see Alkenes chapter) Alkyl geminal dihalide from anti addition of bromine or chlorine

10.5 Allylic Bromination of Alkenes N-bromosuccinimide (NBS) selectively brominates allylic positions Requires light for activation: a source of bromine atoms at very low concentrations

Allylic Bromination of Alkenes

Allylic Stabilization

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

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

Allylic Resonance:

Allylic Radicals as Reaction Intermediates:

Use of Allylic Bromination Allylic bromination with NBS creates an allylic bromide Reaction of an allylic bromide with base produces a conjugated diene, useful in synthesis of complex molecules

Practice Problem 10.1: Products?

Problem 10.5: Draw resonance forms

Problem 10.5

Problem 10.6: Explain?

Problem 10.6: mechanism

10.6 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 tertiary alcohol Primary and secondary alcohols react very slowly and often rearrange, so alternative methods are used

Reactivity of Alcohols with HX

Preparation of Alkyl Halides from Primary and Secondary Alcohols Specific reagents avoid acid and rearrangements of carbon skeleton Thionyl chloride converts alcohols into alkyl chlorides (SOCl2 : ROH to RCl) Phosphorus tribromide converts alcohols into alkyl bromides (PBr3: ROH to RBr)

Problem 10.23: Products?

Prob. 10.8: Synthesize from alcohols?

10.7 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, alkenyl X = Cl, Br, I

François Auguste Victor Grignard Born in Cherbourg, 1871 PhD, University of Lyon, 1901 Nobel Prize in Chemistry, 1912

Grignard Carbon as Nucleophile:

Reactions of Grignard Reagents Many useful reactions RMgX behaves as R- (adds to C=O) RMgX + H3O+ yields R-H

10.8 Organometallic Coupling Reactions Alkyllithium (RLi) forms from RBr and Li metal RLi reacts with copper iodide to give lithium dialkylcopper (Gilman reagents) Henry Gilman (1893-1986)

Lithium dialkylcopper reagents react with alkyl halides to give alkanes:

Problem 10.23 (continued):

Utility of Organometallic Coupling in Synthesis Coupling of two organometallic molecules produces larger molecules of defined structure Aryl and vinyl organometallics also effective Coupling of lithium dialkylcopper molecules proceeds through trialkylcopper intermediate

10.9 Oxidation and Reduction in Organic Chemistry In organic chemistry, 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 easily recognizable 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: loss of H, and/or gain of O, N, X

Reduction: gain of H and/or loss of O, N, X 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: gain of H and/or loss of O, N, X

Oxidation Levels Functional groups are associated with specific oxidation levels

Practice Problem 10.2: Rank in order of increasing oxidation level

Problem 10.13: oxidation or reduction?

Problem 10.33: oxidation or reduction?

Problem 10.39: Identify reagents

Problem 10.39 a = BH3/THF followed by H2O2/OH-1 (hydroboration/oxidation) b = PBr3/ether c = (CH3)2CuLi/ether