Org415 Alcohols 2020 PDF

Oxidation States of Carbon Rules 1. Bonds to other carbons are zero. 2. Bonds to hydrogen and less electronegative elements are -1. 3. Bonds to more electronegative elements are +1. 4. Multiple bonds count as multiple single bonds. 5. Lone pair of electrons is -1. 6. Carbocation is +1. H H...

Oxidation States of Carbon Rules 1. Bonds to other carbons are zero. 2. Bonds to hydrogen and less electronegative elements are -1. 3. Bonds to more electronegative elements are +1. 4. Multiple bonds count as multiple single bonds. 5. Lone pair of electrons is -1. 6. Carbocation is +1. H H H O H H H C C C OH C C HO C Cl H H H H H -3 -2 -1 +3 -2 -1 1  Alcohols Compounds that have hydroxyl -OH groups attached to sp3 carbons. OH OH CH3CH2OH OH OH OH phenol enol Classification o o o Primary 1 Secondary 2 Tertiary 3 H R R R C OH R C OH R C OH H H R 2 Nomenclature Simple Method Name the group attached to the -OH followed by the word alcohol. CH3 OH CH3 CH2 OH CH3 CH OH ethyl alcohol isopropyl alcohol benzyl alcohol ethanol 2-propanol phenylmethanol IUPAC Method 1. Find the longest chain containing -OH and replace -e with -ol. 2. Number the position of -OH. 3. Number the substituents according to their position on the chain and list them in alphabetical order. OH HO CH3 cis-3-methylcyclobutanol 2-ethyl-4-methylpentanol3 Physical Properties Solubility Alcohols are polar because of -OH group. Low MW alcohols are soluble in water. As hydrocarbon character increases solubility decreases. More -OH groups increase solubility. HO CH2 CH2 OH ethylene glycol (1,2-ethanediol) Boiling Point Alcohols have higher boiling points than alkanes and alkenes. R R R O- O - O - +H H +H H +H + O + O Hydrogen Bonding - - R R 4 Industrial Sources 1. Hydration of alkenes cracking H3O+ Petroleum R CH CH2 R CH CH3 cracking OH TiCl3, AlEt3, air CH2 CH2 Ziegler-Natta CH3(CH2CH2)nCH2OH H3O+ polymerization CH3 CH2 OH 2. Fermentation Grain starch Yeast or Sugars CH3 CH2 OH fermentation Sugar cane molasses 5 Preparation of Alcohols 1. Oxymercuration OH OH Hg(OAc)2 HgOAc NaBH4 H2O 2. Hydroboration H CH3 BH3 CH3 NaOH, H2O2 OH 3. Permanganate Oxidation KMnO4 OH cis NaOH, H2O OH 6 4. Epoxidation/Hydrolysis CH3 CH3 CH3 HCO3H H3O OH O OH trans Mechanism CH3 CH3 H O O H O H H CH3 CH3 H OH -H O H OH OH 7 5. Reduction of Carbonyls O OH C C H 1) NaBH4 H 2) HCl, H2O H Mechanism O O OH C NaBH4 C C H H H H - [ ] H H H O OH 1) NaBH4 2) HCl, H2O 8  6. Reduction of Esters O 1) LiAlH4 CH3CH2 C OCH3 2) HCl, H O CH3CH2 CH2 OH 2 Mechanism O O O LiAlH4 CH3CH2 C OCH3 - CH3CH2 C OCH3 CH3CH2 C H [H ] H [H-] O CH3CH2 CH2 OH H CH3CH2 C H H 9 7. Grignard Synthesis O O MgX OH Mg C H3O R X R MgX R C R C Mechanism O O MgBr OH MgBr H O OH 1) CH3MgBr H 2) HCl, H2O CH3 OH 1) CH3CH2MgBr O 2) HCl, H2O CH2CH3 Limitations Reacts with many functional groups: acids, alcohols, amines,10 carbonyls, nitriles and nitro compounds.  Class Problems #1 1. Draw R-4-ethyl-2-hexanol. 2. Draw the product(s) of the following reactions. O a) 1) LiAlH4 b) BH3 2) HCl, H2O NaOH, H2O2 O Br 1) Mg c) H3PO4 d) 2) H2CO H2O 3) HCl, H2O 1) Hg(OAc)2, H2O O e) f) 1) NaBH4 2) NaBH4 + 2) H / H2O 3. Make each diol shown from CH3 CH3 Z-2-butene and E-2-butene. H OH H OH There are four pathways. H OH H CH3 CH3 OH 4. In the reduction of methyl propanoate (slide 9), what other alcohol is produced other than propanol? 11 Reactions of Alcohols 1. Dehydration- E1 CH3 CH3 H3PO4 OH Rearrangement can occur. 2. Dehydration- E2 CH3 CH3 POCl3 pyridine OH Mechanism CH3 H N CH3 POCl3 CH3 Cl OH O P Cl 12 O 3. Halogen Substitution- SN1 OH Cl HCl Cannot be primary alcohol. 4. Halogen Substitution- SN2 OH Br PBr3 OH Cl SOCl2 Cannot be tertiary alcohol. 13 5. Tosylates OH O O pyridine + CH3 S Cl CH3 S O O O Mechanism Tos-Cl H O O N O Cl S CH3 O O O CH3 S O CH3 S O O O Cl OH CN CH3 CH3 14 6. Alkoxides Na CH3CH2 OH CH3CH2 O Na e- trans NaH CH3CH2 OH CH3CH2 O Na o o o Reactivity of alcohols: CH3OH > 1 > 2 > 3 7. Oxidation PCC PCC OH O O OH Cl Cr O H2Cr2O7 O OH or O H2CrO4 HN or KMnO4, H2O 15 Mechanism H OH H Cl H Cr O B O O O O O Cl Cr O O H H O O H OH Cl H B Cr O OH O O OH OH O Cl Cr O O H O OH O K2Cr2O7 H2SO4 OH CrO3 No Reaction H2SO4 16  8. Oxidation of 1,2 Diols HIO4 O O HO OH H H Mechanism O O - H2O I HO O O OH HO O O O H O I O H O I O O OH O H O O O O I OH H H O 17 O 9. Ester Formation A) Carboxylic Acids O O CH3CH2OH CH3 C OH CH3 C OCH2CH3 H Mechanism H H O O O H CH3 C OH CH3 C OH CH3 C O H CH3CH2OH O CH3CH2 H H O O - H2O H CH3 C OCH2CH3 CH3 C O -H H O CH3CH2 18  B) Acid Chlorides O O CH3CH2OH CH3 C Cl CH3 C OCH2CH3 NaOH Mechanism OH CH3CH2 O H CH3CH2 O H3C C Cl O O O -Cl CH3 C OCH2CH3 CH3 C OCH2CH3 Cl Alcohol Synthesis Alkyl Halide Simple Grignard Alcohol Reagent Complex Aldehyde or Alcohol 19 Ketone  OH only carbon source OH O PBr3 1) Mg 2) HCl, H2O Br MgBr NaNH2 H3O O K2Cr2O7 H2SO4 OH 20  Class Problems #2 1. Why are ketones and tertiary alcohols not oxidized? 2. Draw the product(s) for the following reactions. a) OH HIO 4 b) HI HO CH3OCH3 HO POCl3 O c) OH pyridine d) C HCl OH CH3OH OH HBr e) f) OH PCC 3. Explain the trend of reactivity of alcohols to form alkoxides. 4. Synthesize the following. a) OH b) OH 21  Sulfur Compounds Nomenclature Name the group attached to the -SH followed by the word thiol. CH3SH SH Methanethiol Cyclohexanethiol Name the groups attached to the S followed by the word sulfide. CH3SCH3 S Dimethyl sulfide t-Butyl i-propyl sulfide 22 Reactions 1. Thiols (Mercaptans) SN2 HS + CH3CH2 Br CH3CH2 SH 2. Thioethers (Sulfides) NaOCH3 SH S S N2 S + CH3 Br S CH3 23 3. Disulfides Br2 H S S KHCO3 S Mechanism O O C OH H S S Br Br S S S S Br 24 4. Oxidation O O S H2O2 Ph CH3 S S H2O Ph CH3 Ph CH3 Mechanism sulfoxide OH O H O O S H OH Ph CH3 S S Ph CH3 Ph CH3 O O O O CH3CO3H O S S +2 S Ph CH3 Ph CH3 Ph CH3 sulfone 25 5. Methylation CH3 SN2 CH3 S CH3 + CH3I S CH3 CH3 sulfonium ion NH3 CO2 CH3 S N O NH2 N N N HO OH (S)-Adenosylmethionine 26  Class Problems #3 1. What is more stable, RO- or RS-? Explain. 2. Is RS- a good or poor nucleophile? Explain. 3. Draw 2-propanethiol and benzyl methyl sulfide. 4. What is the difference between sulfoxide, sulfone and sulfonium compounds? 5. Draw the product(s) for the following reactions. a) OCH3 1) PBr 3 b) 2) NaSH HO Ph c) d) 6. Synthesize the following. a) 27