Fischer-Rosanoff Convention Before 1951, only relative configurations could be known. Sugars and amino acids with same relative configuration as (+)-glyceraldehyde were assigned D and same as (-)- glyceraldehyde were assigned L. With X-ray crystallography, now know absolute configurations: D is (R) and L is (S). No relationship to dextro- or levorotatory. =>

D and L Assignments * * * =>

Properties of Diastereomers Diastereomers have different physical properties: m.p., b.p. They can be separated easily. Enantiomers differ only in reaction with other chiral molecules and the direction in which polarized light is rotated. Enantiomers are difficult to separate. =>

Resolution of Enantiomers React a racemic mixture with a chiral compound to form diastereomers, which can be separated. =>

Chromatographic Resolution of Enantiomers =>

Chapter 6 Alkyl Halides: Nucleophilic Substitution and Elimination Organic Chemistry, 5 th Edition L. G. Wade, Jr.

Classes of Halides Alkyl: Halogen, X, is directly bonded to sp 3 carbon. => Vinyl: X is bonded to sp 2 carbon of alkene. Aryl: X is bonded to sp 2 carbon on benzene ring. Examples:

Polarity and Reactivity Halogens are more electronegative than C. Carbon-halogen bond is polar, so carbon has partial positive charge. Carbon can be attacked by a nucleophile. Halogen can leave with the electron pair. =>

Classes of Alkyl Halides Methyl halides: only one C, CH 3 X Primary: C to which X is bonded has only one C-C bond. Secondary: C to which X is bonded has two C-C bonds. Tertiary: C to which X is bonded has three C-C bonds. =>

Classify These: =>

Dihalides Geminal dihalide: two halogen atoms are bonded to the same carbon => Vicinal dihalide: two halogen atoms are bonded to adjacent carbons.

IUPAC Nomenclature Name as haloalkane. Choose the longest carbon chain, even if the halogen is not bonded to any of those C’s. Use lowest possible numbers for position. =>

Systematic Common Names Name as alkyl halide. Useful only for small alkyl groups. Name these: =>

“Trivial” Names CH 2 X 2 called methylene halide.. CHX 3 is a haloform. CX 4 is carbon tetrahalide. Examples: –CH 2 Cl 2 is methylene chloride –CHCl 3 is chloroform -CHI 3 is iodoform –CCl 4 is carbon tetrachloride

Preparation of RX Free radical halogenation (Chapter 4) - REVIEW Free radical allylic halogenation –produces alkyl halide with double bond on the neighboring carbon. LATER =>

Substitution Reactions The halogen atom on the alkyl halide is replaced with another group. Since the halogen is more electronegative than carbon, the C-X bond breaks heterolytically and X - leaves. The group replacing X - is a nucleophile. =>

Elimination Reactions The alkyl halide loses halogen as a halide ion, and also loses H + on the adjacent carbon to a base. The alkyl halide loses halogen as a halide ion, and also loses H + on the adjacent carbon to a base. A pi bond is formed. Product is alkene.  Also called dehydrohalogenation (-HX).

Ingold

Sir Christopher Father of Physical Organic Chemistry Coined such names and symbols as: SN1, SN2, E1, E2, nucleophile, electrophile resonance effect, inductive effect/ In print, he often attacked enemies vigorously and sometimes in vitrolic manner. Ingold

S N 2 Mechanism Rate is first order in each reactant Both reactants are involved in RDS Note: one-step reaction with no intermediate Bimolecular nuleophilic substitution. Concerted reaction: new bond forming and old bond breaking at same time INVERSION OF CONFIGURATION

S N 2 Energy Diagram One-step reaction. Transition state is highest in energy. =>

Uses for S N 2 Reactions Synthesis of other classes of compounds. Halogen exchange reaction. =>

S N 2: Nucleophilic Strength Stronger nucleophiles react faster. Strong bases are strong nucleophiles, but not all strong nucleophiles are basic. =>

Trends in Nuc. Strength Of a conjugate acid-base pair, the base is stronger: OH - > H 2 O, NH 2 - > NH 3 Decreases left to right on Periodic Table. More electronegative atoms less likely to form new bond: OH - > F -, NH 3 > H 2 O  Increases down Periodic Table, as size and polarizability increase: I - > Br - > Cl -

Polarizability Effect =>

Bulky Nucleophiles Sterically hindered for attack on carbon, so weaker nucleophiles. =>

Solvent Effects (1) Polar protic solvents (O-H or N-H) reduce the strength of the nucleophile. Hydrogen bonds must be broken before nucleophile can attack the carbon. =>

Solvent Effects (2) Polar aprotic solvents (no O-H or N-H) do not form hydrogen bonds with nucleophile Examples: =>

Crown Ethers Solvate the cation, so nucleophilic strength of the anion increases. Fluoride becomes a good nucleophile. =>

S N 2: Reactivity of Substrate Carbon must be partially positive. Must have a good leaving group Carbon must not be sterically hindered. =>

Leaving Group Ability Electron-withdrawing Stable once it has left (not a strong base) Polarizable to stabilize the transition state. =>

Structure of Substrate Relative rates for S N 2: CH 3 X > 1° > 2° >> 3° Tertiary halides do not react via the S N 2 mechanism, due to steric hindrance. =>

Stereochemistry of S N 2 Walden inversion =>

S N 1 Reaction Unimolecular nucleophilic substitution. Two step reaction with carbocation intermediate. Rate is first order in the alkyl halide, zero order in the nucleophile. Racemization occurs. =>

S N 1 Mechanism (1) Formation of carbocation (slow) =>

S N 1 Mechanism (2) Nucleophilic attack => Loss of H + (if needed)

S N 1 Energy Diagram Forming the carbocation is endothermic Carbocation intermediate is in an energy well. =>

Rates of S N 1 Reactions 3° > 2° > 1° >> CH 3 X –Order follows stability of carbocations (opposite to S N 2) –More stable ion requires less energy to form Better leaving group, faster reaction (like S N 2) Polar protic solvent best: It solvates ions strongly with hydrogen bonding. =>

Stereochemistry of S N 1 Racemization: inversion and retention =>

Rearrangements Carbocations can rearrange to form a more stable carbocation. Hydride shift: H - on adjacent carbon bonds with C +. Methyl shift: CH 3 - moves from adjacent carbon if no H’s are available. =>

Hydride Shift =>

Methyl Shift =>

S N 2 or S N 1? Primary or methyl Strong nucleophile Polar aprotic solvent Rate = k[halide][Nuc] Inversion at chiral carbon No rearrangements Tertiary Weak nucleophile (may also be solvent) Polar protic solvent, silver salts Rate = k[halide] Racemization of optically active compound Rearranged products =>