synthesis reactions - midterm 2

alkoxide + methyl/primary alkyl halides

ethers

• sn2 rxn

  • the william ether synthesis rxn

alcohol + NaH

epoxide

• hydroxide cannot be used because it won’t make enough product which would give a mix of both hydroxide ions and alkoxide

dehydration

the elimination rxn of alcohols

• solvent: H₂SO₄ or TsOH

• alkene will be made

• good for secondary + tertiary alcohols = E1

• carbocation rearrangements can occur

• highly substituted alkene is favored

alcohol → alkyl halides using H-X

• best for methyl, primary, and tertiary substrates

• tertiary = Sn1

• methyl + primary = Sn2

• stereochemistry: 100% inversion

alcohol → alkyl halides other methods

• solvents: PBr₃ + pyrimidine

• solvents: SOCl₂ + pyrimidine

• next round of solvents: NaX

• first solvent (PBr₃ or SOCl₂) will attach to oxygen on alcohol → pyrimidine will deprotonate and leaving group from first will do backside attack + take off oxygen

• pyrimidine prevents buildup of HBr or HCl so that racemization and carbocation rearrangements do not occur

• only for methyl, primary, or secondary alcohols bc mechanism is only Sn2 + 100% inversion occurs

alcohols → sulfonate esters

• addition → elimination

• alcohol is added to sulfonyl chlorides (ex: TsCl) → pyrimidine deprotonates oxygen to create tosylate

• retention of configuration

• nucleophiles can then attack tosylates + do an Sn2 reaction bc sulfate anion is a good LG → inversion will occur bc

alcohols → sulfonate esters → alkyl halides

• solvents: TsCl, pyrimidine → NaX

• first step creates tosylate

• second step creates alkyl halide as Sn2 occurs → inversion

substitution of ethers

• solvents: hot HI or HBr

• Sn1 = LG gives a secondary or tertiary carbocation

• Sn2 = carbocation won’t form if LG makes it unstable

acid-catalyzed ring opening of epoxides

• solvents: acid catalyst + H₂O/alcohols

• nucleophile will attack most substituted side and give one regiosiomer

• backside attack will occur once hydroxyl group is made

nucleophilic ring opening of epoxides

• solvents: alkoxides/strong bases

• strong nucleophile will attack least substituted side

alternative to dehydration of primary alcohols

• use: PBr₃, pyrimidine; SOCl₂, pyrimidine; TosCl, pyrimidine; HBr → make alkyl halide and make hydroxyl group into a good LG

• then use a very hindered base to promote E2

addition of hydrogen halides to alkenes

• use HCl, HBr, or HI

• hydrogen attaches to one carbon (RDS), and halide attaches to the other and breaks pi bond

• major product: hydrogen is attached to least substituted and halide attached to most substituted and has most stable carbocation → that way a primary carbocation does not form

  • markovnikov’s product is major

• need to watch for carbocation rearrangements

• stereochemistry: if reactant was achiral and product becomes chiral, racemic mixture will occur

  • syn and anti addition occur

hydration = water + alkene

• solvents: strong acid + water

• alcohol will form

• reverse reaction of dehydration

• regioselectivity: markovikov’s product is major → one with the most stable carbocation

• alkenes that make tertiary carbocation are favored

• hydrogen goes to the least substituted side and hydroxyl goes to most substituted side

vicinal dihalides - halogenation

• alkene + Br₂/Cl₂

• only anti addition

• racemix mixture

• halides will be on opposite sides

bromohydrin

• bromonium ion (from halogenation) + water

• all reactants in the rxn: Br₂ + H₂O

• one bromine on one side and a hydroxyl group on the other

• water attacks most substituted side

hydroboration of alkenes

• solvents: BH₃, THF

  • then: H₂O₂, ^-OH (either NaOH or H₂O)

• regioselectivity: BH₃ is bulky, so will be on least substituted side + hydrogen will go on most substituted side

  • syn addition will occur (anti mark. product)

  • can be favorable since rearrangements won’t occur

• OH group will replace B which will be the oxidation step

acetylide ion

• a terminal alkyne that has been deprotonated by a strong base

• solvents: NaNH₂, NH₃ (l)

• a good nucleophile that can react with primary or methyl halides

  • can get internal alkynes

  • another option to get from epoxide → alcohol (breaks open the epoxide ring)

• DO NOT USE FOR SECONDARY BC E2 WILL OCCUR AND WE WANT SN2 REACTION

preparation of alkynes

• double elimination

  • vicinal/geminal dihalides + ^-NH₂ (ex: NaNH₂)

  • will go from alkane → alkene → alkyne

• if making a terminal alkyne, need to have three steps (alkene → terminal alkyne)

  • Br₂, 3 eq. ^-NH₂, + H₃O⁺/H₂O

addition of H-X to alkynes

• solvents: H-X, CCl₄ (carbon tetrachloride is just a solvent)

• 1 eq. of H-X = alkene

• 2 eq. of H-X = alkane

  • will create a geminal dihalide

• a resonance structure can be made

hydration of alkynes

• solvents: H₂O, H₂SO₄, HgSO₄ (only add this if its a terminal alkyne bc it needs an extra catalyst)

• an enol will be produced in middle of rxn (alkene and an alcohol)

• tautomerization will occur once an enol is formed

  • alkyne → enol

  • enol + resonance structures → ketone

  • ketone + enols are tautomers

  • ketones will automatically form with acid + base present

• markonikov’s rule applies → terminal and alkynes will produce ketones

• regioselectivity: hydrogen is added to least substituted side

• unsymmetrical alkynes will give a mixture of products (C=O can be on either side)

bromine/chlorine + alkyne

• solvents: Br₂/Cl₂, CCl₄

• _{1 eq. = trans alkene}

• _{2 eq. = tetra alkane}

hydroboration of alkynes

• solvents: BH₃, THF

  • use 9-BBN or (sia)₂B-H if unsymmetrical or terminal alkynes

• base catalyzed tautomerization will occur → need to use ^-OH and H₂O₂

  • terminal alkynes = aldehydes → anti-markonikov

  • internal alkynes = ketones

catalytic hydrogenation

• solvents: H₂ + catalyst (Pd will be used on exams)

• stereoselective: syn addition

• only works for carbonyls (ketones and aldehydes)

hydrogenation of other double bonds

• solvents: LiAlH₄

full hydrogenation of alkynes (reduction)

• solvents: H₂, Pd

  • 2 equiv. needed for full with catalyst

partial hydrogenation of alkynes

• for syn addition: use H₂ + Lindlar’s catalyst

• for anti addition: use Na + NH₃(l)

use of LiAlH₄

• SN2 reactions will occur

  • reagent will attack at least substituted side for epoxides

• solvents: LiAl₄ + H₂O

• good for unhindered primary and methyl substrates

  • good for epoxides → another method to use to get an alcohol from epxoides

  • can work for alkyl halides