Reactions of Alcohols, Ethers, Epoxides, and SulfurContaining Compounds: Chapter 10

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Reactions of Alcohols, Ethers, Epoxides, and
Sulfur-Containing CompoundsChapter 10

• Organometallic Compounds

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Contents of Chapter 10

• Substitution and Dehydration of Alcohols
• Epoxides
• Sulfonate Leaving Groups
• Organometallic Compounds

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Conversion of Alcohols to Alkyl Halides

• Hydrogen halide reactions can be SN1 or SN2
• SN1 reactions give C rearrangements if they can!!

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Conversion of Alcohols into Sulfonate Esters

• Sulfonic acids are strong acids (pKa ? 1)
  hence the conjugate base is weak and an excellent
  leaving group

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Use of Sulfonate Esters

• Sulfonate esters commonly are prepared by
  reaction of the alcohol with a sulfonyl chloride
  via an SN2 reaction
• Sulfonate esters prepared to turn alcohols into
  good leaving groups
• Sulfonate ester is an electrophile like alkyl
  halide usually designed for SN2 reaction

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Use of Sulfonate Esters
para-toluenesulfonyl chloride, TsCl, is often used
The esters formed are called alkyl tosylates,
formula often abbreviated ROTs (ie. CH3CH2OTs)
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Dehydration of Alcohols

• Zaitsevs Rule is followed whenever possible
• Reaction can be E1 or E2 but will give C
  rearrangements if possible even if E2!!

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Dehydration of Alcohols

• Dehydration of a primary alcohol proceeds via an
  E2 mechanism, but the product may look as if it
  came from a carbocation rearrangement as if the
  reaction were E1
• Watch out for C rearrangements!!!!

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Dehydration of Alcohols
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Dehydration of Alcohols

• No C rearrangements with POCl3 dehydration if E2

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Cr6 Oxidation of Alcohols

• Acidic hexavalent chromium removes all ? Hs
  makes C-O bonds
• PCC removes only one ? H and makes an aldehyde
  from a 10 alcohol

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Substitution Reactions of Ethers

• Ethers can be cleaved only with HI and HBr, not
  HCl
• SN1 and SN2 reactions give opposite
  regioselectivity H goes on bulky C in SN2, and
  less-hindered in SN1
• Beware of C rearrangements with E1 reactions

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Epoxides

• Ethers in which the oxygen atom is incorporated
  into a three-membered ring are called epoxides
• Common names are based on the assumption that the
  oxygen atom is placed on top of the p bond of an
  alkene
• Name the alkene and follow with the word, oxide

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Epoxides

• Two ways to name epoxides in the IUPAC system
• substituted oxirane
• name the alkane with the prefix epoxy along
  with the numbers of the carbons bonded to the
  oxygen
• oxirane numbering system is a bit tricky works
  as if epoxide were an alkene

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Epoxides
Epoxides made by reacting alkenes with
peroxyacids, sometimes called peracids
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Epoxides
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Organometallic Compounds

• Most metals are less electronegative than carbon
• In general a carbon bonded to a metal is
  nucleophilic and carbanion-like (C)
• Three major classes of organometallic compounds
  are
• Organolithium compounds
• Grignard reagents
• Cuprates

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Organometallic Compounds

• Grignard and lithium Organometallic reagents made
  by reacting a halide with elemental metal
• Mg essentially slides into C-halogen bond
• Li simply replaces halogen

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Organometallic Compounds

• Although the carbonmetal bonds are not
  completely ionic, organolithium compounds and
  Grignard reagents react as if the carbon portion
  were a carbanion
• Consider the reaction of a Grignard reagent with
  an ethylene oxide
• Ethylene oxide is a good way to extend a carbon
  chain by two carbons via use of halide to make
  organometallic

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Organometallic Compounds

• Gilman reagents, also called organocuprates, are
  prepared from the reaction of an organolithium
  reagent with copper(I) iodide in diethyl ether or
  THF

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Organometallic Compounds

• When a Gilman reagent reacts with an alkyl halide
  (except F-) one of the alkyl groups replaces the
  halide
• Alkyl groups can substitute halogens attached to
  alkene or aromatic C with Gilman reagent
  impossible with SN1 or SN2 reaction
• Mechanism unknown, probably radical

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Organometallic Compounds

• Tetrakis(triphenylphosphine)palladium, Pd(Ph3P)4,
  is a magical reagent which substitutes ordinary
  unfunctionalized alkenes for halogen or triflate
  (OTf) leaving group attached to benzene or alkene
• Reagent can even be made to substitute alkyl
  groups if a tetraalkyltin reagent is used with it
• Can substitute halogen on alkyl grp for alkene or
  alkyl attached to catecholborane

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Retrosynthetic Analysis Using Ethylene Oxide (EO)

• Product has 2 extra Cs plus CN
• 2 extra Cs mean use EO
• Always work back to an ROH for EO analysis
• Retro EO addn removes 2 Cs and an OH
• Here CN has subd for an ROH-derived LG (leav
  grp)
• Make OTs the LG derive the ROTs from ROH
• Cyclohexyl C- attacks EO to make this ROH