Exam 4 - Alcohols, Epoxides, Ethers

Introduction 

  • Preparation of Alcohols, Ethers, and Epoxides 

    • All are products of SN2 (rules for SN2 still apply ⇒ backside attack 

      • Ether Synthesis : 

      • Alcohol Synthesis

  • Alcohols

    • Naming Alcohols 

      • Identified by suffix -ol 

      • Find the longest chain containing the OH group

        • **OH group takes priority (gets the lowest number) 

        • Alcohol is not included in substituents

    • Synthesis via SN2 

    • Reaction 

      • Dehydration (removing H2O) using a strong acid (H2SO4, pTsOH) 

        • Regioselective → follows Zaitsev’s rule (more substituted) 

        • SECONDARY and TERTIARY alcohols react with E1 mechanism 

          • With E1 (and SN1) can always find the cis/trans

        • PRIMARY alcohols react with E2 mechanism 


  • Ethers 

    • Naming Ethers

      • Common Names: name both alkyl groups and arrange them alphabetically add the work ETHER 

        • Use oxygen as the center 

      • IUPAC Names: name the simpler alkyl group + O as a substituent as to the rest of the molecule 

    • Synthesis via SN2 

  • Epoxides 

    • Naming Epoxides 

      • Can name as EPOXYALKANE or OXIRANE (parent chain) 

        • **no alcohol ⇒ ane 

        • ** with alcohol ⇒ an 

    • Synthesis via SN2 – Intramolecular (reaction with itself) 

      • When usinga strong base (NAH) first step is always Acid-Base 

      •  

        • Does NOT work if both groups are on a ring and in same direction → backside attack cannot happen (can’t rotate the ring) ⇒ can happen on a chai (with rotation) 

Dehydration 

  • POCl3 and pyridine ⇒ ALWAYS E2

Alcohols → Alkyl Halides 


  • via H-X 

    • METHYL and PRIMARY alcohols react via SN2 mechanism 

    • SECONDARY and TERTIARY alcohols react via SN1 mechanism 

  • Reactivity of H-X increases with Acididity 

    • H-Cl → → → H-Br 

  • via SOCl2 and PBr3 ⇒ react via SN2 mechanism 

    • SOCl2 and PBr3 are NOT strong acids but tirn alcohols into GOOD LEAVING GROUPS

      •  

Alcohol Group  → Tosylate 

  • RETAINS STEREOCHEMISTRY 

  • Is NOT SN2 (its it own category) 

    • Reaction: 

Epoxides 


Formation of Epoxides → have to be able to backside attack (if both are on same side on RINg ⇒ no reaction; if both are on same side on CHAIN ⇒ rotate for reaction) 

Overview 

  • Addition of ONE OXYGEN to an ALKENE ⇒ forms EPOXIDE 


Peroxyacids 

 

  • Don’t need to know mechanism 

Stereoochemistry 

  • TRANS in CHAIN ⇒ TRANS in EPOXIDE

  • CIS in CHAIN ⇒CIS in EPOXIDE 

    • Both groups can either be wedged or dashed → 50/50 chance 


Reaction of Epoxides 

  • Opening an epoxide ring with a strong NUCLEOPHILE (full negative charge)

    • When EQUALLY substituted ⇒ nucleophole will attack BOTH SIDES EQUALLY (SN2)

    • When NOT EQUALLY substitued ⇒ nucleophile will attack the LESS SUBSTITUED carbon (less sterically hindered) 

  • Opening an epoxide ring with a strong ACID (always protendate first)

    • When EQUALLY substituted, the nucleophile will attack BOTH SIDES EQUALLY 

    • When NOT EQUALLY substituted, the nucleophile will attack the MORE substituted carbon UNDER ACIDIC CONDITIONS

    • Example: 

      • Have to do Step 1 and complete and them do Step 2  

Alkenes 


Naming 

  • IUPAC 

    • Alkenes → suffix -ene 

    • Takes priority over alkyl substiuents but NOT alcohol groups 

    • For multiple alkenes → di, tri… 

    • a is added for pronunciation 

Stereoisomers 

  • Trans vs Cis ⇒ E vs. Z 

    • Does NOT have to be the same R groups (like cis and trans) 

      • On eahc carbon (in alkene) assign priority as either 1 or 2

        • 1 = stronger (more stuff) 

    • E Isomer: two highest priority groups on OPPOSITE sides 

    • Z Isomer: two highest priority groups on SAME side 

      • E is more stable than Z isomer  


Preparation of Alkenes 

    • 3 “Formulas”

      • R-X + good base = alkene 

      • R-OTS + good base = alkene 

      • R-OH + H2SO4/PTSOH or POCL3, pyr = alkene 

    • Good bases (and Nu) 



  • KOTBu

  • LDA

  • DBU

  • DBN

  • -OH 

  • -OR

  • -NH2

  • -H 


Addition Reactions

  • SYN addition: A and B are added to SAME side 

  • ANTI addition: A and B are added to OPPOSITE

Hydrohalengation 

  • π bond is REACTIVE 

    •  

  • Markovikov’s Rule 

    • Hydrogen is added to the MORE substituted carbon (carbon with more Hs) 

    • Note: Carbocations form on more substituted carbon so carbocation rearragnements can occur 

      •  

  • Stereochemistry 

    • Hydrohalengation occurs via SYN and ANTI addition of H-X 

  • Example: 

    • **benzene is not an alkene 

Alkene Reactions


Hydration to alkene 

  • replacement of alkene with weak nucleophile 

    • Follows Markovnikov’s Rule (most substituted) → carbocation rearaggements can occur 

      • Addition occurs both SYN and ANTI 

  • Example: **2 CH3s → not chiral so no stereochemistry 

Equilibrium → molecules could either form an ALKENE or an ALCOHOL 

    • Temperature 

      • HIGH temperatures forms an ALKENE 

      • LOW temperatures form an ALCOHOL 

    • LeChatlier’s Principle 

      • Add H2O favors ALCOHOL 

      • Remove H2O favors ALKENE 

Halogenation 

  • X2 = Cl or Br (Cl-Cl , Br-Br) 

    • No carbocation rearrangements 

    • ONLY ANTI addition because of backside attack (comes in opposite of original) 

Halohydrin Formation 

  • X2 = Cl or Br (Cl-Cl , Br-Br) AND any WEAK Nucleophile 

    • No carbocation rearrangements 

    • ONLY ANTI ADDITION because of backside attack 

      • Weak nucleophile can attack on either side of an equally substituted carbon of the halonium ion 

  • Unequally Substituted 

    • Weak nucleophile attacks MORE substituted carbon of the halonium ion 

    •  


Hydroboration-Oxidation 

    • Mechanism 

      • ANTI-MARKOVNIKOV: goes to the LESS substituted alkene 

      • NO carbocation rearrangements 

        • Addition via SYN addition 

        • Other reagents: 

          • Replace BH3 ⇒ 9-BBN or B2H6