1 - Acid/Base Extraction & Crystallization

Extraction
Goal
Separate solid compounds (acids/base/neutral)
Basis
Differing solubility based on pH of the solution
Charging the target will take it out of the organic layer and into the aqueous layer; then returning target
back to neutral form will cause it to precipitate if it is in an aqueous solvent
Safety
Flammable Diethyl Ether
Corrosive HCl and NaOH
Procedures
Diethyl Ether as solvent
Carried out in the separatory funnel

Use acid to extract amine; use base to neutralize

Use base to extract acid; use acid to neutralize
Target compound will be in aqueous extracts
Neutralize to form precipitates; vacuum filter product

Add sodium chloride solution (more polar) to remove water from ether solution
Further dry the ether over anhydrous sodium sulfate
Decant and evaporate ether to leave behind basic compound
Notes
Use 1M for extractions b/c want more aqueous water for separation from organic
Use 6M for neutralization b/c want less water to precipitate the target

Crystallization
Goal
Remove impurities from the product
Basis
By dissolving the product in hot solvent and then cooling, the product crystals out and impurities remain in the
solvent
Safety
Flammable hexane
Procedures
Hexane as solvent

Heat hexane up to just below boiling

Dissolve hexane in minimum amount of hexane
Cool at room temperature and in ice bath to obtain crystals
Vacuum filter product
Setup
Hot plate with water bath for hexane and compound
Buchner funnel
Notes
Hot hexane b/c heat encourages solubility of the organic product
Minimum amount of hexane b/c otherwise too much of the product will remain in the solvent even after cooling
2 – Distillation

Goal
Separate liquid solvents
Basis
Liquids have differing boiling points and vapor pressures
Lower boiling point (high vapor pressure) liquid will evaporate and condense out first
Safety
Flammable and toxic solvents
Procedures
Solvents are heated in a thermowell
Vapors pass through the distillation column and the water condenser and out as a liquid distillate
Setup

Notes
Fractional is better at separation and will give an S-shaped distillation graph
Simple is not as good at separation and will give a exponential shaped distillation graph
3- Friedel Craft's Acylation & Column Chromatography

Friedel Craft's Acylation

Goal
Make mono and diacetyl ferrocene from ferrocene using Friedel Craft's Acylation
Basis

Safety
Acetyl chloride and Aluminum chloride are corrosive and release HCl when in contact with water
Procedures
Reaction is taken place in conical vial with methylene chloride as the solvent
Reaction mixture is placed in a centrifuge tube with cold water
Neutralize AlCl3 acid using 6M NaOH
Spin in centrifuge and extract ferrocene derivatives (organic layer at bottom)
Dry over sodium sulfate
Setup

Notes
Methylene Chloride is a good solvent for extractions b/c it dissolves many organic compounds and is immiscible
with water
Cold water b/c low temperature gives low solubility encourages clean separation
More acetyl chloride used yielded more of the di and mono products
Acetyl groups attached to different rings b/c the presence of 1 acetyl group deactivates the ring
Column Chromatography
Goal
Separate products using column chromatography (larger scale)
Basis
Compounds will elute from the column in order of increasing polarity
Nonpolar compounds will not interact with the polar silica so they will elute from the column first
Polar compounds will be eluted with more polar solvents as those intermolecular forces pulls the compound
out of the column
Safety
Silica stays in lungs if breathed in
Procedures
Burette column filled with bands of cotton (bottom), sand, silica, solvent, sand (top)
Add sample
Elute first colored band using 90 hexane/10 acetone (most nonpolar)
Increase acetone proportion to elute more polar compounds
Notes
Solvent has to be above the silica b/c otherwise silica dries out and does not interact with the compound
4 - Reactivities of Aromatic Compounds

Goal
Find out which substituent group (between aniline, anisole, and acetanilide) was the strongest activator
Basis
Strong activators are resonance activating and will cause the ring to become more substituted in a time limit
Safety
HBr causes chemical burns
Br2 is volatile and toxic
Br needs to be quenched with sodium bisulfite (makes lachrymator when in contact with acetone)
Procedures
Glacial acetic acid as the solvent
Reaction carried out in conical vial
Cotton moistened with sodium bisulfite to prevent Br vapor from escaping
Quench reaction mixture with bisulfite
Cool to form crystals; filter solids with Buchner funnel
Setup

Notes
Glacial acetic acid contains little or no water
Glacial acetic acid as a solvent b/c water would make OH-
Order of activation : aniline > anisole > acetanilide
Water condenser b/c reaction is carried out over a long time and solvent needs to reflux
Br2 is transported by snap cap vial and used only in the hood to remove dangerous vapors
Quench w/ bisulfite b/c aqueous solvent (acidic environment)
5 - Stereochemistry of Bromine Addition

Goal
Find out how by what mechanism bromine adds to an alkene
Basis
Different brominated products (arose from different mechanisms) will have different melting points
Safety
Br is corrosive
Br2 is volatile and toxic
Br needs to be quenched with sodium bisulfite (makes lachrymator when in contact with acetone)
Cyclohexane releases a poisonous odor
Procedures
Methylene chloride as solvent
Reaction carried out in setup same as Lab 4
Quench reaction mixture with cyclohexane
Cool and collect product by vacuum filtration
Notes
Quench w/ cyclohexane b/c organic solvent of methylene chloride
Br adds to the double bond by bromonium ion mechanism (anti addition)
6 - Grignard Reaction

Goal
Convert compounds into products that are easier to analyze and identify (derivatization)
Basis
Convert bromobenzene into carboxylic acid by a Grignard reaction and analyze melting point to identify starting
compound
Safety
Flammable Diethyl Ether
Flame drying glassware with a bunsen burner can become dangerous
Dry ice can cause frostbites or displace oxygen in the air
Procedures
Anhydrous diethyl ether as solvent
Mg + unknown brominated compound + diethyl ether to make Grignard
Slow addition of ether as it refluxes
Add prepared Grignard to dry ice (solid CO2)
Purify the product (extraction and recrystallization)
Setup

Notes
Grignards are strong bases so they become denatured in the presence of any acidic hydrogens
Extraction is to separate carboxylic acid from alkylphenyl byproduct (neutral)
OH does not show up in NMR b/c it exchanges with the solvent
OH shows up broad on the NMR b/c it can hydrogen bond, giving a wider range of hydrogen environments
Quench remaining Grignard using HCl
7 - Elimination of Alkyl Halides

Goal
React 2-bromoheptane with NaOCH3 and KtBuO to determine SN2/SN1/E2/E1 mechanisms
Basis
By analyzing composition of the product, mechanism of the nucleophiles can be determined
Safety
N/A
Procedures
Carry out reaction in conical vial & spin vane with heat
Use water condenser and drying tube to reflux reaction for 30 mins
Cool reaction and add to centrifuge tube with hexane and water
Product is in organic layer once isolated
Dry solution over sodium sulfate and decant
Analyze with GCMS
Notes
NaOCH3 and KtBuO are both water sensitive and can become deactivated if exposed to air for too long
Heptene products are volatile and will evaporate quickly
8 - Oxidation of Borneol & Reduction of Camphor

Goal
Investigate which stereoisomer camphor reduction favors
Basis
Analysis by melting point, NMR, GCMS will tell whether borneol or isoborneol is favored by camphor reduction
Safety
Dangerous chemicals - methylene chloride, sodium hypochlorite, concentrated acetic acid, and acetone
Flammable acetone and acetic acid

NaBH4 reacts violently with water to produce dangerous H2 gas

Procedures
Oxidation of Borneol
Water bath temperature retained around 50 C
Acetone as solvent and slowly add NaOCl (oxidizing agent) over the course of the hour
Use TLC to monitor reaction (ideally all isoborneol turns into camphor)

Isolate camphor into centrifuge tube with methylene chloride for extraction
Lower methylene chloride extracts contain the camphor
Add sodium bicarbonate (NaHCO3) to neutralize left over acetic acid
Add sodium bisulfite (NaHSO3) to reduce left over NaOCl and HOCl
Dry over sodium sulfate (Na2SO4), decant, and evaporate solvent

Reduction of Camphor
Dissolve camphor in methanol
Add NaBH4 and heat while reaction takes place
Cool to room temperature then add ice water to form crystals; vacuum filtrate
Redissolve solid in methylene chloride (to remove all traces of water)
Dry over sodium sulfate; decant; vacuum filtrate
Setup

Notes
Ideally TLC would show no color change if added to KMnO4 (oxidizing agent)
Color change identifies compound that can oxidize and camphor is already fully oxidized
Acetic acid and NaOCl makes HOCl which carries out the actual oxidation
Methanol is instead of water in NaBH4 reduction b/c water deactivates the NaBH4
Favored product is isoborneol b/c underside attack of camphor has less steric hindrance
Analytical Techniques

Melting Point
Basis
Different compounds have different melting points b/c of polarity (polarity is proportional to melting point)
Advantage
For identification
Fast and easy to do
No analysis or calculation needed
Disadvantage
Not the most accurate (compounds need to have very different melting points)
Impure compounds complicate results (broadens and lowers melting point range)

Gas Chromatography
Basis
Lower boiling point components will move faster through the GC column (order of peaks)
More ions from combustion gasses if in greater amounts (area of peak)
Advantage
For identification and percent composition
Fast and easy to do
Simple analysis
Disadvantage
Limited to only liquid components
Need standards for comparison and correction factors
Gives rough estimates of area for percent composition and retention times

NMR
Basis
Differing hydrogen environments give different signals when placed in an applied magnetic field
Advantage
For identification and percent composition
Widely applicable
Accurate
Disadvantage
Takes a lot of analysis
Expensive machinery and tubes
Need enough of product to even run NMR analysis

Thin-Layer Chromatography (TLC)

Basis
Compounds with different polarities will have different retention factors (Rf values)
Nonpolar compounds have higher Rf values than polar compounds
Polar solvents increase Rf values of polar compounds
Advantage
For comparing purposes (identification, polarity, presence of compound)
Fast and easy to do
Simple Analysis
Disadvantage
Only gives information about polarity and whether a compound is present or not
Sometimes require extra equipment to see dots (UV lamps, KMnO4)
GCMS
Basis
GC distinguishes based on boiling point
MS distinguished based on mass to charge ratio (m/z)
Advantage
Accurate
Computerized analysis
Can distinguish between diastereomers
Gives identification and percent composition
Disadvantage
Computerized library can identify incorrectly
More complicated analysis

Equations

Percent Recovery
Experiment/Expected x 100%