Orgo 2 Lab Final

Purpose of oxidizing methoxybenzyl alcohol (exp 1)

• Oxidize methoxybenzyl alcohol to methoxybenzaldehyde

• using sodium hypochlorite as oxidizing agent & tetrabutylammonium hydrogen sulfate as the phase-transfer catalyst

• IR

Oxidation (exp 1)

 adding oxygen or removing hydrogen from organic molecule

Types of Chromium, +6 Oxidation State [Cr(VI)] (exp 1)

• Chromate (CrO4^2-)

• Dichromate (Cr2O7^2-)

• Chromium Trioxide (CrO3) 

What do chromate (CrO4^2-) & dichromate (Cr2O7^2-) do (exp 1)

•  used under acidic, aqueous conditions 

• Primary alcohols  → carboxylic acids

• Secondary alcohols  → ketones  

Collin’s Reagent (exp 1)

• CrO3-pyridine₂ & CH2Cl2 (solvent)

• Toxic 

• Primary alcohol  → aldehyde (no water so dones’t oxidize further into carb acid) 

What happens to chromium in experiment 1

• Reduced to Cr(III) in this reaction

• Doesn’t react with tertiary alcohols (toxic) 

What does Potassium Permanganate (KMnO4) do (exp 1)

• Primary alcohols  → potassium carboxylate salt 

  • Add strong acid (ex: dil HCl): forms carboxylic acid

• Doesn’t oxidize DB/TB alcohols or secondary alcohols to form ketones because they react further with KMnO4 

What happens to potassium permanganate (KMnO4) in experiment 1

Oxidation state reduced from 7 to 4, aka manganese dioxide (MnO2- a muddy, brown precipitate)

Sodium Hypochlorite (NaOCl) (exp 1)

• substitute for Collin’s Reagant 

• aromatic/aliphatic secondary alcohol →  ketones 

• Primary aromatic alcohol →  aldehydes (what we did in experiment)

  • Primary aliphatic alcohol oxidizes slowly, so NaOCl only oxidizes secondary alcohols in the presence of primary alcohols 

• Formation of alkyl hypochlorite intermediate 

What is the issue in experiment 1

• Starting alcohol soluble in organic solvents (dichloromethane/ethyl acetate) but not water 

• NaOCl soluble in water but not organic solvents 

Phase Transfer Catalyst (TBAS) (exp 1)

• a substance that speeds up reactions between reactants in different phases (like water and oil) by shuttling ions or molecules from one phase to another (aqeous & organic layer); usually anions from aq phase to organic phase

• Quaternary ammonium salt (water soluble) containing 4 alkyl groups (ethyl acetate soluble)

• Exchanges HSO4- with CIO- so CIO- can enter ethyl acetate later and react with alcohol 

Why does the end product have so many possible structures ? (exp 1)

Alcohol is disubstituted so can be meta-, para-, or ortho-

Purpose of reducing benzil (exp 2)

• Reduce benzil using sodium borohydride (NaBH4)

• TLC, MP, IR

Reduction (exp 2)

• Reduction: hydrogen is added to, or oxygen is lost from an organic molecule 

  • Reducing Reagents: LiAlH4 & NaBH4

LiAlH4 (exp 2)

• Room temp, powerful reducing agent that reduces carboxylic acids, nitriles, amides, aldehydes, ketones, ester  

• Used in inert, anhydrous solvent, such as tetrahydrofuran or diethyl ether 

What can LiAlH4 create (exp 2)

• H is more EN than Al so has neg. charge

• LiAlH4 reacts violently w/ protic solvents (ex: H2O or alcohols) to form H2, aka flammable hydrogen gas 

NaBH4 (exp 2)

• Room temp, only reduces ketones & aldehydes 

• Reacts slowly with protic solvents so reductions can be conducted using alcohol as solvent 

• Decomposes when there are acidic functional groups (ex: carboxylic acid) so neutralize acid group with base (sodium hydroxide) before ketone/aldehyde gets reduced 

What can aq. acid (ex: H3O+) be used for in experiment 2

used to free reduced product from a complex mixture 

How many molecules can 1 molecule of LiAlH4 & NaBH4 reduce (exp 2)

• Reaction proceeds by adding a hydride ion, H-, to the organic substrate

• One molecule (4 H+ ions) of LiAlH4 or NaBH4 can reduce up to 4 molecules of a ketone that has 1 carbonyl group

Acetophenone to (R)-1-phenylethanol & (S)-1-phenylethanol (exp 2)

• Product contains a chiral center & are non-imposable mirror image stereoisomers (enantiomers) 

• H- can attack both sides of ketone, two enantiomers are formed, creating a racemic mixture 

How many products can form in experiment 2

Five

What are the first 2 possible products (exp 2)

• Reduction of only 1 out of 2 carbonyl groups of benzil 

• (+)-benzoin & (-)-benzoin 

• Identical physical properties 

What are the last 3 possible products (exp 2)

• Reduction of BOTH carbonyl groups of benzil to form vicinal diols 

• Creates a max of 4 stereoisomers, but only 3 exist since 1 is a meso-compound

• Meso-hydro-benzoin & (+/-)-hydrobenzoin 

How to distinguish (+/-)-hydrobenzoin from (+/-)-benzoin or meso-hydrobenzoin (exp 2)

• Melting Point

• (+/-)-hydrobenzoin: 122-123

• (+/-)-benzoin: 135-137

• Meso-hydrobenzoin: 137-139

Distinguish b/w +/-)-benzoin & meso-hydrobenzoin using IR (exp 2)

• (+/-)-benzoin has carbonyl & OH stretch 

• Meso-hydrobenzoin has no carbonyl 

Purpose of Synthesis of Phenacetin (Williamson Ether) - Exp 3

• Synthesize phenacetin by formation of an ether functional group 

• MP, H NMR, IR

Phenacetin (exp 3)

active constituent of APC tablets, used as an analgesic to relieve pain & an antipyretic to reduce fever but removed from market when discovered its carcinogenic when ingested for long periods 

How is aspirin, phenacetin, & caffeine synthesized (exp 3)

• Aspirin & phenactin synthesized chemically

• caffeine obtained as by-product from production of caffeine-free coffee

Final Product of Phenacetin Synthesis (exp 3)

Phenacetin or p-ethoxyacetanilide (ether/amide para on benzene) 

Williamson Ether Synthesis (exp 3)

formation of an ether by reacting alkyl halide w/ conjugate base of alcohol/phenol 

Step 1 of Williamson Ether Synthesis (exp 3)

p-acetamidophenol placed in basic solution & H removed from phenol group 

Why does the OH get attacked first in step 1  (exp 3)

• Occurs to completion because phenols have lower pKa, so are stronger acids than alcohols with a high pK, such as methanol produced 

• In acid-base equilibrium, bases prefer to deprotonate stronger acids (aka lower pKa), and since OH is more acidic than CH3 & amide, it will react with OH instead

Step 2 of Williamson Ether Synthesis (exp 3)

• p-acetamidophenoxide ion becomes like a nucelophile & reacts w/ bromoethane to yield phenacetin

  • SN2 reaction, use uncrowded primary alkyl halides 

mole ratio for methoxide ion & p-acetamidophenol  (exp 3)

Moles of methoxide ion = moles of p-acetamidophenol

What if there is not enough methoxide ion (exp 3)

 p-acetamidophenol can’t turn into conjugated base & won’t react to bromoethane 

What if there is excessive methoxide ion (exp 3)

methoxide ion competes as nucelophile w/ p-acetamidophenoxide ion, reducing yield of phenacetin