Lab A&B General

Labs A & B

1. Two-Step Synthesis of Aspirin.

2. Lab A (Week 1): Synthesis of Salicylic acid.

3. Lab B (Week 2): Synthesis of Aspirin.

4. Techniques:

   1. Vacuum Filtration,

   2. Recrystallization,

   3. Melting Point Determination.

Lab A (Week 1)

1. Synthesis of Salicylic Acid.

2. Reaction: Saponification of Methyl Salicylate with Sodium Hydroxide (NaOH).

3. Procedure:

   1. 2.0 mL Methyl Salicylate + 30 mL of 4M NaOH

   2. heated to boil for 15 minutes.

   3. After cooling,

   4. acidified with 6M HCl to pH <3 to precipitate salicylic acid.

   5. Product is isolated via vacuum filtration and

   6. purified by recrystallization from hot water (60 mL).

Lab B (Week 2)

1. Synthesis of Aspirin.

2. Reaction: Esterification of Salicylic Acid with Acetic Anhydride.

3. Procedure:

   1. x

      1. 90% of dry Salicylic Acid (or 1.00 g if yield <1.20g)

      2. + calculated volume of Acetic Anhydride (3.0 equivalents)

      3. + 5 drops of 85% Phosphoric Acid catalyst.

   2. Heated in warm water bath for 10 minutes,

   3. then cooled in ice bath.

   4. Aspirin isolated by vacuum filtration and

   5. purified by recrystallization from chosen solvent (water or ethanol based on solubility tests).

Methyl Salicylate

1. Starting material for Lab A.

2. Aka oil of wintergreen.

3. Natural product

4. minty smell.

5. Liquid compound.

6. Molecular Weight: 152.14 g/mol.

7. Density: 1.18 g/mL.

8. Hazards: Can be toxic in high doses.

9. Volume used: 2.0 mL.

Salicylic Acid

1. Product of Lab A

2. reactant for Lab B.

3. White crystalline solid.

4. Found naturally in willow bark extracts.

5. pKa values:

   1. Carboxylic acid proton ~3,

   2. Phenol proton ~13.6.

6. Solubility:

   1. 1 g requires

      1. 460 mL cold water

      2. or 15 mL boiling water,

   2. making it ideal for water recrystallization.

7. Hazards: Irritates stomach lining.

Aspirin

1. (Acetylsalicylic Acid, ASA)

2. Final product of Lab B.

3. Trade name aspirin from Spiraea Ulmaria.

4. Developed by Felix Hofmann at Bayer to reduce gastrointestinal side effects of salicylic acid.

5. Widely used painkiller with

   1. anti-inflammatory

   2. and anti-clotting properties.

6. Metabolized in vivo to salicylate.

Saponification

1. Reaction in Lab A.

2. Base-mediated hydrolysis of an ester to a carboxylic acid.

3. Example: Methyl Salicylate + 2 NaOH → Sodium Salicylate + CH₃OH + H₂O.

4. Term comes from "soap making" process.

Acetic Anhydride

1. Reactant in Lab B.

2. Used in excess (3.0 equivalents) to drive the equilibrium toward aspirin formation.

3. Serves as both reactant and solvent.

4. Reaction with salicylic acid requires acid catalyst (H₃PO₄).

Phosphoric Acid

1. H₃PO₄

2. Catalyst used in Lab B.

3. 85% solution.

4. 5 drops added by TA.

5. Acid catalyst promotes the esterification reaction between salicylic acid and acetic anhydride.

Iron Trichloride Test

1. FeCl₃

2. Purity test performed in Lab B. Qualitative test for phenols.

3. 0.02 M aqueous solution.

4. Positive test: purple color indicates presence of salicylic acid (phenol group).

5. Used to detect unreacted salicylic acid in crude and recrystallized aspirin.

Recrystallization

1. Purification technique used for both salicylic acid (Lab A) and aspirin (Lab B).

2. Process:

   1. Dissolve impure solid in minimal hot solvent,

   2. cool slowly to form pure crystals.

   3. For salicylic acid: solvent is water (60 mL).

   4. For aspirin: solvent is chosen based on solubility tests (water or ethanol).

Vacuum Filtration

1. Technique used to isolate solid products.

2. Uses Buchner funnel, filter paper, and vacuum flask.

3. Steps:

   1. Wet filter paper,

   2. apply vacuum,

   3. pour mixture,

   4. rinse with cold solvent (3 mL tap water for salicylic acid;

   5. 2x2 mL ice-cold water for aspirin),

   6. pull air for 2 minutes to dry.

Melting Point Range

1. Characterization method to identify purity.

2. Inaccurate if product is wet.

3. Salicylic acid MP determined in Week 2.

4. Aspirin MP determined the following week.

5. Important to have dry crystals for accurate measurement.

Equivalents

1. Calculation used for reactant amounts.

2. For aspirin synthesis: 3.0 equivalents of acetic anhydride to 1.0 equivalent of salicylic acid.

3. Used to calculate volume of acetic anhydride needed based on mass of salicylic acid.

Procedure: Lab A Step 1-2

1)

1. Obtain 2.0 mL methyl salicylate from Organic Dispensing Hood.

2. Transfer to 50 mL Erlenmeyer flask with stir bar.

2)

1. Add 30 mL of 4 M NaOH from Reagents Hood.

2. Immediate formation of white precipitate.

Procedure: Lab A Step 4-6

1. Heat on hot plate with stirring to boiling.

2. Solution turns from cloudy white to clear.

3. Once boiling, reduce heat to 250 and boil gently for 15 minutes with continuous stirring.

Procedure: Lab A Step 8-10

1. Cool flask in ice-water bath to 18°C.

2. Add 6M HCl incrementally (10 mL + 10 mL + 1-2 mL via Pasteur pipette) with stirring after each addition.

3. Check pH with paper (should turn pink).

4. Heavy white precipitate forms.

Procedure: Lab A Recrystallization

Transfer crude salicylic acid to 125 mL Erlenmeyer flask. Add exactly 60 mL tap water. Heat to boiling until clear. Cool slowly on bench top (5 minutes), then ice-water bath (2 minutes) after crystals form. Vacuum filter product.

Procedure: Lab B Step 2-4

Calculate 90% of dry salicylic acid mass. If yield <1.20g, use 1.00g provided by TA. Calculate required volume of acetic anhydride. Transfer to 50 mL Erlenmeyer flask. TA adds 5 drops of 85% H₃PO₄. Loosely stopper with inverted beaker.

Procedure: Lab B Step 6-7

Let stand undisturbed for 10 minutes in fume hood. Then place in warm water bath (150 mL beaker) for 10 minutes until homogeneous. Cool in ice-water bath. Scratch inside of flask with glass rod to induce crystallization. White/yellowish paste forms.

Procedure: Lab B Solvent Test

Test tiny amount of aspirin in two test tubes: one with water, one with ethanol. Shake and observe solubility at room temperature. Choose solvent where aspirin is insoluble at room temperature for recrystallization.

Procedure: Lab B Recrystallization

Transfer impure aspirin to clean 50 mL Erlenmeyer flask. Add minimum amount (~10 mL) of chosen solvent. Heat to boiling until clear. Cool slowly, then ice bath. Vacuum filter crystals.

Safety: NaOH and HCl

Both are corrosive. Handle with gloves in fume hood. Add HCl to cooled solution (18°C) with flask clamped on bench top, NOT on hot plate, to avoid violent reaction and splashing.

Safety: Waste Neutralization

All acidic filtrates must be neutralized with NaHCO₃ in Neutralizing Hood before disposal. Test pH with paper (light green = pH 7). Pour neutralized waste down sink with running water.

Safety: Glassware Handling

Clamp Erlenmeyer flasks, vacuum flasks, round bottom flasks. DO NOT clamp beakers. Cover glassware during transport. Use beakers as covers, not glass stoppers. Wrap hot plate cord safely.

Waste Disposal: Sharps

Used glass pipettes go into Red Sharps container. NOT in biohazards waste box.

Waste Disposal: Solvents

Ethanol solutions from FeCl₃ tests go into C,H,O Non-Halogenated Container. Water solutions can go down drain. Aq. FeCl₃ waste goes into specially labeled container.

Waste Disposal: Acetone Rinsings

Rinsates from 100 mL Round Bottom Flask and 125 mL Erlenmeyer Flasks (for Lab C) go into "Acetone rinsings" container.

Notebook Requirements

Title, reaction schemes, table of reagents with calculations (mass, mmoles, equivalents, hazards). Record observations: colors, masses, volumes, times, appearances. Include % yield calculations. Record dry masses and melting points.

Historical Context

Willow bark extracts used since Hippocrates. Felix Hofmann at Bayer developed aspirin in late 19th century. Aspirin reduces gastrointestinal side effects of salicylic acid. Over 30 million pounds consumed annually in US.

Medical Significance

Salicylic acid: pain reliever, anti-inflammatory. Aspirin: pain relief, anti-inflammatory, anti-clotting, reduces heart attack risk, prevents ischemic strokes. Humans may synthesize salicylic acid in vivo from benzoic acid.

Salicylate Poisoning

Can be fatal (teenage athlete death from Bengay overuse). Detected by FeCl₃ test (urine turns purple). Test sensitive to 300 mg aspirin dose. Not specific - any phenol gives positive result.

Laboratory Techniques

Week 1: Synthesis, Vacuum Filtration, Recrystallization. Week 2: Melting Point, Chemical Information lookup, Recrystallization, FeCl₃ purity test.

Zubrick Readings (11th Ed)

Recrystallization: Chap 13, p89-91; Vacuum Filtration: Chap 13, p93-95,97-98; Melting Point: p76-79.

Zubrick Readings (10th Ed)

Recrystallization: p92-95,102-105; Melting Point: p74-77,80-82; Vacuum Filtration: p97-100.

Reaction Scheme 1: Salicylic Acid

Methyl Salicylate + 2 NaOH → Sodium Salicylate + CH₃OH + H₂O. Followed by acidification: Sodium Salicylate + 2 HCl → Salicylic Acid + 2 NaCl.

Reaction Scheme 2: Aspirin

Salicylic Acid + Acetic Anhydride → Acetylsalicylic Acid (Aspirin) + Acetic Acid. Catalyzed by H₃PO₄. Equilibrium reaction driven by excess acetic anhydride.

Table of Reagents Example

Methyl Salicylate: ?/2.0 mL, ? mmol, MW 152.14, density 1.18, equiv 1.0. Sodium Hydroxide (4M): 30 mL, ? mmol, equiv ?, Hazard: Corrosive. 6M HCl: ? mL, Hazard: Corrosive.

Important Notes

Product must be DRY for accurate mass and melting point. Wet crystals give inaccurate results. Break up chunks on watch glass for even drying. Save all filtrates in labeled beakers until experiment complete.

Solubility Considerations

Salicylic acid: 1g/460mL cold water, 1g/15mL boiling water. Aspirin can hydrolyze back to salicylic acid in water, especially with heat and residual acid catalyst. Limit boiling time during recrystallization.

Calculation Example: Acetic Anhydride Volume

Based on 90% salicylic acid mass. Moles SA = mass/138.12. Moles AA needed = moles SA × 3.0. Volume AA = (moles AA × 102.09) / 1.08 g/mL.

Observation Examples

Color changes: cloudy white to clear during saponification. Heavy white precipitate during acidification. Crystal appearance: white needles for salicylic acid; white, small, shiny needles for aspirin.

FeCl₃ Test Results

Salicylic acid (control): purple color. Pure aspirin: no color change (negative test). Crude aspirin may show light purple if contaminated with salicylic acid.

Glassware Cleanup

Rinse with water only: Erlenmeyer flasks, graduated cylinders, vacuum flask, Buchner funnel, glass rods, stir bars. Rinse with acetone only: Round bottom flask, Erlenmeyer flasks for Lab C.

Neutralization Procedure

Carry waste beaker, glass rod, pH paper to Neutralizing Hood. Place beaker IN plastic bucket. Add NaHCO₃ scoopful, stir, test pH. When pH=7 (light green), pour down sink with running water.

Hot Plate Safety

On/off switch lower right. Orange indicator for heat, green for stirring. Cord wrapped under metal bar and around rod before plugging into top outlet on left side of hood. Flask must sit flat on hot plate surface.

Crystallization Tips

For recrystallization: cool slowly on bench top first to form nice crystals. Then use ice bath to complete crystallization. Scratching flask interior with glass rod induces crystallization.

Product Drying

After vacuum filtration, pull air over crystals for 2 minutes. Transfer to pre-weighed watch glass. Break up chunks. Dry until next lab period for accurate dry mass and melting point.

Yield Calculation

% Yield = (actual dry mass / theoretical mass) × 100%. Theoretical mass based on limiting reagent and reaction stoichiometry. Important for evaluating reaction success.

Material Reuse Decision

If dry salicylic acid mass ≥1.20g, use 90% for aspirin synthesis. If <1.20g, use 1.00g salicylic acid provided by TA. Ensures sufficient material for second reaction.

Solvent Choice for Aspirin Recrystallization

Based on room temperature solubility tests. Ideal solvent: aspirin insoluble at room temperature but soluble when hot. Prefer ethanol if water causes hydrolysis concerns.

Acid Addition Technique

Add 6M HCl in increments (10mL + 10mL + 1-2mL) with stirring after each addition. Use Pasteur pipette for final small additions. Check pH with paper to ensure pH<3.

Vacuum Valve Operation

Open ONLY the OUTER Grey Vacuum Valve by turning left. Close by turning right. Used for both filtration and pulling air over crystals to dry.

Filtrate Handling

Save acidic filtrates in labeled beakers. Neutralize with NaHCO₃ before disposal. Mother liquor from recrystallization can usually be disposed of in sink.

Timing Considerations

Week 1: Synthesize and recrystallize salicylic acid, obtain wet mass. Week 2: Obtain dry mass of salicylic acid, determine MP, synthesize aspirin. Following week: Determine dry mass and MP of aspirin.

References

Le Couter & Burreson: Napoleon's Buttons. Corey, Czako, Kurti: Molecules and Medicine. Mohrig et al.: Experimental Organic Chemistry. Journal references for medical studies.

Laboratory Objectives

Learn multi-step synthesis. Practice purification techniques (filtration, recrystallization). Characterize products (melting point, purity tests). Calculate yields. Understand reaction mechanisms and stoichiometry.

Common Pitfalls

Not drying products thoroughly. Adding HCl too quickly. Using wrong solvent for recrystallization. Boiling aspirin in water too long. Not recording observations in real time. Incorrect waste disposal.

Success Indicators

Good yield of white, crystalline products. Sharp melting point close to literature values. Negative FeCl₃ test for pure aspirin. Accurate calculations and complete notebook records.