Chapter 8

Chapter 8 - Chapter 8 Alcohols R OH O H H O O Water CH3 H...

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Unformatted text preview: Chapter 8: Alcohols R OH + O - H H + + O + + O + Water CH3 H Alcohol CH3 CH3 Ether Names 1. Find the longest chain containing the OH function: alkane alkanol. Note: This may not be the longest chain in the molecule! 2. Number such as to give HO-C lowest # 3. Other rules same as in alkanes 8 7 6 5 4 3 9 2 1 OH Br 7 6 2 5 4 3 1 4,4-Dimethyl-1-nonanol 5-Bromo-3-propyl2-heptanol OH Defined as C1, # is not part of name Cyclic alcohols are called cycloalkanols: OH 1 OH 1 3 HO Cyclohexanol Cis-3-methylcyclohexanol CH3 1-Ethylcyclopentanol -OH as a substituent is called hydroxy -OR is alkoxy: Ethers R-O-R', alkoxyalkanes R' R' RCOH RCHOH RCH2OH R'' Primary Secondary Tertiary alcohol Structure O can be thought of as sp3-hybridized, "tetrahedral", i.e. bent, not linear. DH (O H) = 119 kcal mol-1 O H3C H Most striking: Relatively high melting and boiling points, and water solubility. Why? Hydrogen Bonding R H + O - H O - + R Extensive network: 5 kcalmol-1 Increases intermolecular interactions. Allows for solvation by water. Water hexamer Methanol tetramer Hydrophobic-Hydrophilic R OH Water solubility: Decreases with size of R R is hydrophobic; OH is hydrophilic ROH + H2O H2O CH3OH CH3CH2OH (CH3)2CHOH (CH3)3COH ClCH2CH2OH CF3CH2OH K Acidity RO- + H3O+ 15.7 15.5 15.9 17.1 18 14.3 12.4 Steric effect "Inductive" electronic effect. Tapers off with distance. pKa's Sterics and solvation CF3CH2CH2OH 15.4 Alkoxides RO Preparation: +CH3OH + Na NH2 K + CH3O - Na + NH3 pKa 15.5 +CH3CH2OH + Na OH K = 1019.5 K 35 15.9 K ~ 1 - + CH3CH2O Na + H2O 15.7 When CH3CH2OH is solvent, equilibrium is displaced to the right. Alcohols are also basic: Lone e-pairs can be protonated. Molecules which are both acids and bases are called amphoteric. R-O-H + H2SO4 + H R-O HSO4 H Oxonium ion pKa ~ -3 + R NH3 Compare + R NH2 + H Ammonium ion pKa ~10 Synthesis of Alcohols R-OH 1. R-X R-OH OH Review: SN OH By SN2: Rprim-X I - = base) Problem: -Branching E2 ( OH I OH By SN1: Rsec X, Rtert X Problem: E1 Br H-OH HBr OH + Cl H-OH HCl OH + Minimize at low T Solution for E2 problem: Use a relatively nonbasic, "masked" OHequivalent CH3 C O O Acetate (for Rprim, branched, or Rsec) O Br + O CCH3 OH O - SN2 O O CCH3 "Ester" H2O, OH Hydrolysis + CH3CO, removed in aqueous work up Preview: Ester Hydrolysis (Chapter 20) 2. Reduction of Aldehydes Ketones O R C R' O R C H and . Redox relationship: O C + +2H+ -2H+ O +C HO H O C +2e reduction -2e oxidation O C C 2e + 2H + equals H2. There are two practical ways to add H2: a. as such, or b. as H-, then H+. Ketones Aldehydes red ox Rsec-OH Rprim-OH Reduction What are the reagents? Hydrogenation is possible, but is cumbersome: Needs H2 pressure and catalysts (e.g., Pd, Pt). Better: Use reagent that is equivalent to H:-, but not as basic, such as "complex" hydrides, prepared simply by: Na+H:- + BH3 2 sp Na+BH43 sp Sodium borohydride Lithium aluminum hydride (LAH) Li+H- + AlH3 Li+AlH4- These reagents are still somewhat basic and will undergo hydrolysis. Reactivity differs greatly. NaBH4 is less reactive, more selective: Na+BH - H-OH 4 4H2 + NaB(OH)4 4H2 + LiAl(OH)4 - But: slow, OK to use in CH3OH Li+ AlH4 H-OH - violent, needs aprotic solvents (ethers) LiAlH4 (but not NaBH4) will reduce even halides: RX + LiAlH4 R-H Nucleophilicity: Attack at Hydride O C The resulting alkoxide is protonated by alcohol solvent or on aqueous work up O NaBH4, CH3OH HO H Electrophilic carbonyl carbon H O LiAlH4 ether +H AlO Li 3 H H H + , H2 O work up H HO H The aqueous work-up step is normally not shown in eqns. Mechanisms NaBH4: Termolecular, concerted Simultaneous addition of H- and H+ CH3O H O C H BH3 H O H C + CH3O BH3 LiAlH4: Stepwise delivery of, first, H:-, then, H+ (work-up) Oxidation CrVI reagents +3e CrIII Typically, use Na2Cr2O7 or CrO3 in H2O, H2SO4 Good for Rsec-OH Example: OH + Na2Cr2O7 H2SO4 H 2O O O HO Cr OH Chromic acid O Best for secondary alcohols giving ketones. Primary alcohols are overoxidized in aqueous medium. RprimOH: Use NH CrO3Cl + - Pyridinium chlorochromate : "PCC" N Pyridine Avoids overoxidation with aqueous Cr reagents. PCC H OH OH O O Mechanism: via intermediate chromate ester O O VI RCH2OH HO Cr OH R CH O Cr OH HOH O H E2 O O O IV CrOH goes on to CrIII RCH + O 3. Alcohols from Organometallics: R:- M+ R-X + Li Hexane or ether RLi + LiX Alkyllithium O R-X + Mg O MeLi O O Ether needed R-Mg-X "Grignard reagent" "RMgX" MeMgBr Reverse Polarization RX RM RM are basic and nucleophilic Basicity Hydrolysis: Mg D2O Br MgBr D RM as Nucleophiles Not strong enough for R M+ + R'X R-R' (obviously, since they are made from RX). But: O + + R M - + - + O M R H2O O H R Works with ketones, aldehydes, even formaldehyde, CH2=O Ketones: O + CH3MgBr H2O HO CH3 Aldehydes: O H + Li tert HO H sec MgBr CH2 O Formaldehyde OH + prim Retrosynthetic Analysis Work Backwards! Break up into even pieces! Example: Make HO from starting materials 4 carbons or less Li + H O Li + O HO H Synthetic Planning: Know your reactions, forward and backward (vocabulary) Know your mechanisms, forward and backward (grammar) Problem: Which retrosynthesis is best: a, b, or c? Ethanol Beverage Chemical, Fuel Abuse Cyrrhosis Initial dose causes euphoria, but alcohol is a general, CNS active, depressant drug. Absorption: 20% stomach, 80% gastrointestinal. Food slows it, but what is in, stays in...... Distribution through the body and brain is fast. Intravenous can be lethal: Sudden depression of the respiratory system, brain centers. Excretion: Lungs Alcoholic breath; 5% in urine. Metabolism: Zero order in ROH! Linear with time; 10 mL/h (cocktail/hour); by oxidation: CH3CH2OH Enzyme O CH3CH Poisonous Enzyme CO2 Second step is prevented by antabuse (disulfiram) Effect misconceptions: 1. Not a stimulant 2. Doesn't warm you 3. Doesn't help your sleep 4. Not an aphrodisiac ...
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