Transcript Chapter 6
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 CHO H * CHO OH H CH2OH D-(+)-glyceraldehyde HO H COOH H2N * H => CH2CH2COOH L-(+)-glutamic acid OH H OH H * OH CH2OH D-(+)-glucose 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 => Organic Chemistry, 5th Edition L. G. Wade, Jr. Chapter 6 Alkyl Halides: Nucleophilic Substitution and Elimination Classes of Halides • Alkyl: Halogen, X, is directly bonded to sp3 carbon. •Vinyl: X is bonded to sp2 carbon of alkene. •Aryl: X is bonded to sp2 carbon on benzene ring. • Examples: H H H C C Br H H alkyl halide I H H => C C H Cl vinyl halide aryl halide 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. => H + H C Br H Classes of Alkyl Halides • Methyl halides: only one C, CH3X • 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: CH3 CH CH3 CH3CH2F Cl (CH3)3CBr CH3I => Dihalides • Geminal dihalide: two halogen atoms are bonded to the same carbon •Vicinal dihalide: two halogen atoms are bonded to adjacent carbons. H H H C C H H Br H Br geminal dihalide H C C Br Br H vicinal dihalide => 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. CH3 CH CH2CH3 Cl 2-chlorobutane CH2CH2Br CH3(CH2)2CH(CH2)2CH3 4-(2-bromoethyl)heptane => Systematic Common Names • Name as alkyl halide. • Useful only for small alkyl groups. • Name these: (CH3)3CBr CH3 CH CH2CH3 Cl CH3 CH3 CH CH2F => “Trivial” Names • CH2X2 called methylene halide. . •CHX is a haloform. 3 •CX4 is carbon tetrahalide. •Examples: –CH2Cl2 is methylene chloride –CHCl3 is chloroform -CHI3 is iodoform –CCl4 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 C C H X + Nuc: - C C + X: - H Nuc • 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 C C + - B: C C + X: - + HB H X • 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 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. SN2 Mechanism H H H O H C Br H HO C Br H H H HO C • 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 H - + Br H SN2 Energy Diagram • One-step reaction. • Transition state is highest in energy. => Uses for SN2 Reactions • Synthesis of other classes of compounds. • Halogen exchange reaction. Nucleophile Product R-I Class of Product akyl halide - R-OH alcohol R-X + OR' - R-OR' ether - R-SH thiol - R-SR' thioether amine salt R-NH3+X R- N3 R-X + CC-R' - R-CC-R' alkyne - R-CN R-COO-R' nitrile R-X + I - R-X + OH R-X + SH R-X + SR' R-X + NH3 - R-X + N3 R-X + CN R-X + R-COO - - azide ester => SN2: 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- > H2O, NH2- > NH3 •Decreases left to right on Periodic Table. More electronegative atoms less likely to form new bond: OH- > F-, NH3 > H2O 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. CH3 CH2 O ethoxide (unhindered) weaker base, but stronger nucleophile CH3 H3C C O CH3 => t-butoxide (hindered) stronger base, but weaker nucleophile 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: O CH3 C N acetonitrile H C N CH3 CH3 dimethylformamide (DMF) O C H3C CH3 acetone => Crown Ethers • Solvate the cation, so nucleophilic strength of the anion increases. • Fluoride becomes a good nucleophile. O O O K+ O O O 18-crown-6 CH2Cl CH2F KF, (18-crown-6) CH3CN => SN2: 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 SN2: CH3X > 1° > 2° >> 3° • Tertiary halides do not react via the SN2 mechanism, due to steric hindrance. => Stereochemistry of SN2 Walden inversion => SN1 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. => SN1 Mechanism (1) Formation of carbocation (slow) (CH3)3C Br + (CH3)3C - + Br => SN1 Mechanism (2) • Nucleophilic attack + (CH3)3C + H O H (CH3)3C O H H • Loss of H+ (if needed) (CH3)3C O H + H O H H (CH3)3C O H + + H3O => SN1 Energy Diagram • Forming the carbocation is endothermic • Carbocation intermediate is in an energy well. => Rates of SN1 Reactions • 3° > 2° > 1° >> CH3X – Order follows stability of carbocations (opposite to SN2) – More stable ion requires less energy to form • Better leaving group, faster reaction (like SN2) • Polar protic solvent best: It solvates ions strongly with hydrogen bonding. => Stereochemistry of SN1 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: CH3- moves from adjacent carbon if no H’s are available. => Hydride Shift H Br H CH3 CH3 C C CH3 C C CH3 H CH3 H CH3 H H CH3 CH3 C C CH3 C C CH3 H CH3 H CH3 H CH3 C C CH3 H CH3 H Nuc Nuc CH3 C C CH3 H CH3 => Methyl Shift CH3 Br CH3 CH3 CH3 C C CH3 H CH3 H CH3 CH3 CH3 CH3 C C CH3 CH3 C C CH3 C C CH3 H CH3 H CH3 CH3 CH3 C C CH3 H CH3 Nuc CH3 CH3 Nuc C C CH3 H CH3 => SN2 • Primary or methyl • Strong nucleophile • Polar aprotic solvent • Rate = k[halide][Nuc] • Inversion at chiral carbon • No rearrangements or SN1? • Tertiary • Weak nucleophile (may also be solvent) • Polar protic solvent, silver salts • Rate = k[halide] • Racemization of optically active compound • Rearranged products =>