Chapter 13: Alcohols and Phenols [ Chapter 9 Sections: 9.10; Chapter 13 Sections: 13.1-13.3, 13.9-13.10] 1. Nomenclature of Alcohols simple alcohols C3 C3C2 Eddie Sachs 1927-1964 larger alcohols find the longest continuous carbon chain that contains the group (hydroxyl group) number the chain to assign the lowest locant value to the takes precedence over C=C and triple bonds in cyclic alcohols, the group is always at the 1-position alcohols are designated as 1, 2 or 3 d on the type of carbon to which the group is attached Glucose phenol (carbolic acid) Joseph Lister 1827-1912 Tetrahydrocannabinol (TC, marijuana) P: 13.1, 13.30
2. Properties of Alcohols A. Boiling Points 3C as with alkyl halides, since oxygen is more electronegative than carbon, carbon takes on a partial positive charge and oxygen a partial negative charge leading to a polar covalent bond similarly, the bond is polarized strongly towards the oxygen the strongly polarized bond results in a very strong dipole-dipole interaction termed a "hydrogen bond" alcohols have higher boiling points than similar weight non-hydrogen bonding compounds as a result of this additional intermolecular "hydrogen bonding" interaction the term "hydrogen bond" is a misnomer since it is NT actually a bond, just a strong interaction (~10-20 kj/mole interaction versus ~300 kj/mol for actual bonds) C 2 Explain the following boiling point observations for a series of compounds with similar molecular weights 30 C 36 C 47 C 118 C "like dissolves like" alcohols are polar compounds and capable of hydrogen bonding low molecular weight alcohols are soluble (i.e., "miscible") in polar solvents and hydrogen bonding solvents (like water) higher molecular weight alcohols are more "alkane like" and are rejected by hydrogen bonding solvents (therefore, they are NT soluble or immiscible) 3C R hexanol heptanol etc. B. Solubility in Water
3. Acidity of Alcohols cyclohexanol pka = phenol pka = 10 hybrid form resonance interactions spread charge over multiple atoms since delocalization of charge stabilizes charge, resonance-stabilized anions are always more stable than non-resonance stabilized anions phenols are more acidic than typical alcohols
Rationalize the following differences in pka pka = 16 pka = 16 pka = 5 pka = 12 pka = 10 pka = 10 N 2 pka = 7 C 3 pka =11 electron-withdrawing substituents close to the site of deprotonation serve to stabilize the negative charge and thereby increase acidity electron-donating substituents close to the site of deprotonation serve to destabilize the negative charge and thereby decrease acidity P: 13.5, 13.33-34 4. Typical Bases Used alcohol alkoxide typical s for deprotonating alcohols are sodium metal (Na ), lithium metal (Li ), sodium hydride (Na), or sodium amide (NaN 2 ) P: 13.4 5. Synthesis of Alcohols A. S N 2 reactions Na Br DMS Ts K DMF hydroxide as a nucleophile will react with methyl, 1 and 2 alkyl halides and tosylates to form alcohols 3 alkyl halides and tosylates cannot react via the SN2 reaction (E2 predominates) a polar aprotic solvent (DMS, DMF) are favored for these reactions P: 13.41
B. SN1 reactions SN1 reactions require a weaker than SN2 reactions to prevent competing elimination reactions 2 is the nucleophile Ts 2 2 and 3 alkyl halides and tosylates react via the SN1 reaction (methyl and 1 substrates are acetone unreactive) typically water itself is used as solvent (and nucleophile) or a mixture of water and an organic solvent such as acetone C. ydration of Alkenes 3 P 4 2 acid-catalyzed hydration Markovnikov addition rearrangements of intermediate carbocationare possible 1. g(ac) 2, 2 2. NaB 4 oxymercuration Markovnikov addition no rearrangements 1. B 3 2. 2 2, K hydroboration anti- Markovnikov addition no rearrangements D. Diol Formation KMn 4 KMn 4 Na, 2 Mn potassium permanganate reacts with alkenes to form vicinal diols the reaction takes place via syn addition Na, 2 NaS 3 / 2 or s 4 tbu, Na 2 Barry Sharpless 1941-2001 Nobel Prize smium tetroxide provides the same product as KMn4 with alkenes, but the s 4 can be used in catalytic amounts if tbu or NM are present to re-oxidize the s 2 byproduct P: 9.33, 13.7-8 s s
E. xidation of Alcohols Na 2 Cr 2 7, 2 S 4, 2 or oxidation of 2 alcohols with strong oxidizing agents (KMn 4 or Jones reagent) results in formation of a ketone KMn 4 Na 2 Cr 2 7, 2 S 4, 2 or oxidation of 1 alcohols with strong oxidizing agents (KMn 4 or Jones reagent) results in formation of a carboxylic acid KMn 4 PCC oxidation of 1 alcohols with the weaker oxidizing agent PCC results in formation of an aldehyde pyridinium chlorochromate Cr 3 N 3 alcohols cannot be oxidized to carbonyl compounds [] [] [] C C C [R] [R] [R] carbon fully reduced reductions are characterized by addition of hydrogen or loss of oxygen oxidations are characterized by addition of oxygen or loss of hydrogen C [] [R] C carbon fully oxidized P: 13.22, 13.48
6. Quick Review of the Reactions of Alcohols A. Conversion of Alcohols to Alkyl alides via the SN1 reaction (3, and some 2 alcohols) via the SN2 reaction (methyl, 1 alcohols) X X X =, Br, I X = Br, I Zn 2 via the SN2 reaction on preformed tosylates (methyl, 1, and some 2 alcohols) R S toluenesulfonyl chloride Ts pyridine S R alkyl toluenesulfonate RTs + N Ts pyridine Ts NaBr N via specialized reagents S 2 PBr 3 Br thionyl chloride phosphorous tribromide B. Elimination Reactions via acid-catalyzed E1 3 P 4 via E2 PBr 3 Br or or Ts as LG heat K, ethanol, heat P: 13.19, 13.21, 13.35, 13.53