Purification by Crystallization

Real-Life Hook: From Lab to Pharma

Ever wondered how pharmaceutical companies ensure your medicines are 99.9% pure? Or how sugar crystals in your kitchen are separated from impurities? Crystallization is the answer! From ancient salt crystallization in seawater evaporation ponds to modern drug purification in billion-dollar pharma labs, this technique has been humanity’s trusted purification method for millennia.

In forensic labs, crystallization helps purify extracted compounds for analysis. In semiconductor manufacturing, ultra-pure silicon crystals are grown for computer chips. Understanding crystallization isn’t just about passing JEE - it’s about mastering a fundamental technique that powers multiple industries!

What is Crystallization?

Crystallization is a purification technique based on the difference in solubility of a compound in a hot and cold solvent. The impure solid is dissolved in a minimum amount of hot solvent, and on cooling, pure crystals separate out while impurities remain in solution (mother liquor).

The Science Behind It

The process exploits three key principles:

1. Temperature-dependent solubility: Most solids are more soluble in hot solvents than cold ones
2. Selective crystallization: The desired compound crystallizes preferentially over impurities
3. Supersaturation: Cooling creates a supersaturated solution that forces crystallization

Principle of Crystallization

Solubility Curves

For crystallization to work effectively:

• The compound should have high solubility in hot solvent
• The compound should have low solubility in cold solvent
• Impurities should remain highly soluble even in cold solvent (or be insoluble throughout)

Solubility vs Temperature Graph:

Solubility
    ↑
    |     Desired Compound
    |    /
    |   /
    |  /_____ Impurities (stays in solution)
    | /
    |/
    |________________→ Temperature
   Cold          Hot

Types of Impurities Removed

1. Soluble impurities: Remain dissolved in mother liquor (most common)
2. Insoluble impurities: Removed by hot filtration before crystallization
3. Colored impurities: Removed using activated charcoal (decolorization)

Step-by-Step Crystallization Procedure

Materials Required

• Impure organic compound
• Suitable solvent (ethanol, water, ethyl acetate, etc.)
• Beaker (250 mL)
• Conical flask
• Funnel and filter paper
• Watch glass
• Glass rod
• Water bath
• Ice bath
• Activated charcoal (if needed for decolorization)

Detailed Procedure

Step 1: Choice of Solvent

Select a solvent where:

• Compound is highly soluble when hot
• Compound is sparingly soluble when cold
• Compound does NOT react with the solvent
• Solvent has low boiling point (for easy evaporation)

Common solvents: Water, ethanol, methanol, ethyl acetate, acetone, benzene, chloroform, petroleum ether

Memory Trick - “WAEMAC” Water, Acetone, Ethanol, Methanol, Acetate (ethyl), Chloroform

Step 2: Dissolution

1. Take impure solid in a beaker
2. Add minimum amount of solvent (just enough to dissolve)
3. Heat on water bath (never direct flame for organic solvents!)
4. Stir continuously with glass rod
5. Add more solvent dropwise if needed

⚠️ Critical Point: Use MINIMUM solvent - excess reduces yield!

Step 3: Hot Filtration (if needed)

If insoluble impurities are present:

1. Heat the funnel by pouring hot solvent through it
2. Quickly filter the hot solution
3. Use fluted filter paper for faster filtration
4. Keep the receiving flask warm to prevent premature crystallization

Step 4: Decolorization (if needed)

If solution is colored:

1. Add a pinch of activated charcoal to hot solution
2. Boil for 2-3 minutes
3. Filter hot to remove charcoal (which has adsorbed colored impurities)

Step 5: Cooling and Crystallization

1. Allow filtrate to cool slowly at room temperature first
2. Then place in ice bath for complete crystallization
3. DO NOT disturb during crystallization
4. Crystals form as solubility decreases with temperature

Nucleation Techniques (if crystals don’t form):

• Scratch the inner walls of the beaker with glass rod
• Add a tiny seed crystal of pure compound
• Cool in refrigerator
• Concentrate the solution by gentle evaporation

Step 6: Filtration of Crystals

1. Filter using Buchner funnel under vacuum (suction filtration)
2. Wash crystals with cold solvent (removes adhering mother liquor)
3. Press gently with glass stopper to remove excess solvent

Step 7: Drying

1. Spread crystals on watch glass
2. Dry in air or in desiccator
3. For hygroscopic compounds, use vacuum desiccator
4. Determine melting point to check purity

Why Each Step Matters

Interactive Demo: Visualize Crystallization Process

See how crystals form as temperature decreases and solubility changes.

Recrystallization

Recrystallization is repeating the crystallization process to further purify the compound. Each cycle increases purity but decreases yield.

When to Recrystallize?

1. Melting point is not sharp (indicates impurities)
2. Mixed melting point test shows depression
3. Color is still present
4. Required purity not achieved (for pharmaceuticals, semiconductors)

Single vs Multiple Recrystallization

• Single crystallization: 70-80% purity, 80-90% yield
• Double recrystallization: 90-95% purity, 60-70% yield
• Triple recrystallization: 98-99% purity, 40-50% yield

Solvent Selection Guide

Common Solvent Systems

Mixed Solvent System

Sometimes a single solvent doesn’t work. Use a solvent pair:

• Dissolve in one solvent (where highly soluble)
• Add second solvent (where poorly soluble) until cloudiness appears
• Heat to get clear solution
• Cool to crystallize

Example: Ethanol-Water system

• Dissolve compound in hot ethanol (good solvent)
• Add water dropwise (poor solvent) until slight turbidity
• Heat again to dissolve
• Cool to crystallize

Solvent Selection Tests

Perform small-scale tests:

1. Take small amount of compound in test tube
2. Add 1 mL solvent at room temperature
3. Note solubility (should be low)
4. Heat and observe (should dissolve completely)
5. Cool in ice (crystals should form)

Memory Tricks and Mnemonics

“CHILLED CRYSTALS” - Crystallization Checklist

• Choose appropriate solvent
• Heat to minimum volume
• Insoluble impurities - hot filter
• Lighten color with charcoal
• Let cool slowly
• Ensure complete crystallization (ice bath)
• Drain mother liquor (suction filter)
• Cold solvent wash
• Recrystallize if needed
• Yield calculation
• Store properly
• Test purity (m.p.)
• Analyze results
• Label and document
• Safely dispose waste

“Hot to Dissolve, Cold to Evolve”

Remember: Heat increases solubility, cooling decreases it - that’s when pure crystals evolve (form)!

Solubility Rule

“Like dissolves like” - Polar solvents for polar compounds, non-polar for non-polar

Common Procedural Mistakes

Mistake 1: Using Excess Solvent

Problem: Low yield because compound remains dissolved even when cold

Solution: Add solvent dropwise until just dissolved. Better to have slight undissolved solid than excess solvent.

Recovery: Concentrate solution by gentle evaporation, then cool again

Mistake 2: Rapid Cooling

Problem: Small, impure crystals form; impurities get trapped in crystal lattice

Solution: Cool slowly at room temperature first, then ice bath. Patience yields purity!

Why: Slow cooling allows selective crystallization and orderly crystal growth

Mistake 3: Hot Filtration When Not Needed

Problem: Product loss, time waste, potential for accidents

Solution: Use hot filtration ONLY when insoluble impurities are visible

Mistake 4: Washing Crystals with Hot Solvent

Problem: Dissolves your hard-earned crystals!

Solution: ALWAYS use cold solvent for washing (ice-cold is better)

Amount: Use minimum - just enough to remove mother liquor

Mistake 5: Direct Heating of Organic Solvents

Problem: Fire hazard! Many organic solvents are flammable

Solution: ALWAYS use water bath for heating volatile/flammable solvents

Temperature: Water bath provides gentle, controlled heating (<100°C)

Mistake 6: Disturbing During Crystallization

Problem: Disturbs nucleation and crystal growth

Solution: Place beaker in ice bath and leave undisturbed for 15-30 minutes

Mistake 7: Incomplete Drying

Problem: Incorrect mass measurement, difficulty in storage

Solution: Dry completely in air or desiccator; check for constant mass

Test: Weigh, dry for 10 more minutes, weigh again - should be same

Mistake 8: Not Using Seed Crystals

Problem: Supersaturated solution doesn’t crystallize

Solution: Add tiny pure crystal as nucleation site OR scratch walls with glass rod

Practical Applications

Industrial Applications

1. Pharmaceutical Industry

   • Purifying drug molecules (aspirin, paracetamol)
   • Ensuring drug purity >99.5% for safety
   • Removing toxic impurities

2. Food Industry

   • Sugar refining (white sugar from raw brown sugar)
   • Salt purification
   • Citric acid production

3. Chemical Industry

   • Purifying organic intermediates
   • Producing fine chemicals
   • Manufacturing dyes and pigments

4. Semiconductor Industry

   • Growing ultra-pure silicon crystals
   • Zone refining (repeated crystallization)
   • Purity required: 99.9999999% (9N purity!)

Laboratory Applications

1. Organic Synthesis: Purifying reaction products
2. Natural Product Isolation: Purifying compounds from plants
3. Analytical Chemistry: Preparing pure standards
4. Research: Obtaining pure compounds for characterization

Practice Problems

Level 1 - JEE Main (Basics)

Problem 1: Why is activated charcoal added during crystallization?

Solution: Activated charcoal adsorbs colored impurities due to its large surface area and porous structure. It acts as a decolorizing agent, removing colored impurities from the solution. After adsorption, it is removed by hot filtration.

Problem 2: In crystallization, should we use minimum or maximum amount of solvent? Why?

Solution: We should use the minimum amount of solvent.

Reason:

• If excess solvent is used, even on cooling, a large amount of compound remains dissolved in the mother liquor
• This reduces the yield of crystals
• Minimum solvent ensures maximum compound comes out as crystals on cooling

Problem 3: Why is water bath used instead of direct heating for crystallization of organic compounds?

Solution: Water bath is used because:

1. Many organic solvents are volatile and flammable (ethanol, acetone, ether)
2. Direct heating can cause:
   • Fire hazard
   • Bumping (sudden violent boiling)
   • Decomposition of heat-sensitive compounds
3. Water bath provides gentle, uniform heating up to 100°C
4. Prevents localized overheating

Level 2 - JEE Main (Application)

Problem 4: A compound has solubility 5 g/100 mL at 20°C and 40 g/100 mL at 80°C. If 50 g of impure compound (90% pure) is crystallized from 100 mL water, what is the maximum theoretical yield?

Solution:

Given:

• Solubility at 80°C = 40 g/100 mL
• Solubility at 20°C = 5 g/100 mL
• Amount of impure compound = 50 g (90% pure)
• Volume of water = 100 mL

Step 1: Pure compound present = 50 × 0.90 = 45 g

Step 2: At 80°C, all 45 g will dissolve (since 100 mL can dissolve 40 g, we can dissolve 45 g by adding little more water or using supersaturation)

Step 3: On cooling to 20°C, solubility = 5 g/100 mL Amount that remains dissolved = 5 g

Step 4: Amount crystallized = 45 - 5 = 40 g

Answer: Maximum theoretical yield = 40 g

Percentage recovery = (40/45) × 100 = 88.9%

Problem 5: Why do we cool the crystallization solution slowly first at room temperature and then in ice bath?

Solution:

Slow cooling at room temperature (first):

• Allows formation of large, well-formed crystals
• Gives time for proper crystal lattice formation
• Impurities remain in solution
• Results in high purity

Rapid cooling in ice bath (later):

• Forms small, impure crystals
• Impurities get trapped in crystal lattice
• Reduces purity

Two-stage cooling:

1. Room temperature: Most crystallization occurs slowly → pure, large crystals
2. Ice bath: Completes crystallization → maximizes yield

Best of both worlds: High purity (slow cooling) + High yield (complete crystallization)

Problem 6: During crystallization of benzoic acid from water, a student added excess water and obtained very low yield. How can the student recover more product without starting fresh?

Solution:

Method 1: Concentration by Evaporation

1. Gently heat the mother liquor (filtrate after first crystallization)
2. Evaporate water to reduce volume to about half
3. Cool again slowly
4. More crystals will form

Method 2: Salting Out

1. Add common salt (NaCl) to mother liquor
2. Decreases solubility of benzoic acid (common ion effect is not applicable here, but salt decreases solubility of organic compounds in water)
3. More benzoic acid crystallizes out

Method 3: Change Solvent

1. Evaporate water completely
2. Redissolve in minimum amount of fresh water
3. Crystallize properly

Best approach: Method 1 (simple evaporation and re-cooling)

Level 3 - JEE Advanced (Conceptual & Numerical)

Problem 7: A mixture contains compound A (m.p. 110°C) and compound B (m.p. 150°C). In solvent S, at 60°C: A has solubility 30 g/100 mL, B has solubility 2 g/100 mL. At 10°C: A has solubility 3 g/100 mL, B has solubility 0.2 g/100 mL. If 50 g mixture (equal parts A and B) is crystallized from 100 mL of solvent S, which compound crystallizes preferentially and what is its purity in first crop of crystals?

Solution:

Given:

• Mixture: 25 g of A + 25 g of B
• Solvent: 100 mL of S

At 60°C:

• A: solubility = 30 g/100 mL (all 25 g will dissolve)
• B: solubility = 2 g/100 mL (only 2 g dissolves, 23 g remains undissolved)

Problem: B won’t dissolve completely at 60°C!

Need more solvent OR higher temperature OR B is removed by hot filtration

Assuming hot filtration removes undissolved B:

Solution now contains:

• 25 g of A
• 2 g of B (dissolved)

On cooling to 10°C:

A that crystallizes = 25 - 3 = 22 g B that crystallizes = 2 - 0.2 = 1.8 g

Total crystals = 22 + 1.8 = 23.8 g

Purity of A in crystals = (22/23.8) × 100 = 92.4%

Answer: Compound A crystallizes preferentially with 92.4% purity

Alternative interpretation (if we heat to dissolve both):

At higher temperature (say 90°C), if both dissolve:

• On cooling, both will crystallize
• But A shows larger Δsolubility (30-3=27) vs B (2-0.2=1.8)
• A crystallizes more preferentially

Problem 8: Explain why adding a seed crystal helps in crystallization of a supersaturated solution. What is the molecular mechanism?

Solution:

Supersaturated Solution:

• Contains more dissolved solute than equilibrium solubility
• Thermodynamically unstable but kinetically stable
• Needs activation energy to start crystallization

Role of Seed Crystal:

1. Nucleation Site: Provides surface for crystal growth
2. Crystal Lattice Template: Dissolved molecules align with existing lattice
3. Lowers Activation Energy: Heterogeneous nucleation (on surface) requires less energy than homogeneous nucleation (in solution)

Molecular Mechanism:

Supersaturated solution → High molecular disorder (high entropy)
                         ↓
Seed crystal provides ordered surface
                         ↓
Dissolved molecules align with crystal lattice
                         ↓
Hydrogen bonding / Van der Waals forces stabilize
                         ↓
Crystal grows layer by layer (epitaxial growth)
                         ↓
Entropy decreases, but enthalpy decrease is larger
                         ↓
ΔG = ΔH - TΔS becomes negative → Spontaneous

Why scratching glass walls works:

• Creates micro-nucleation sites
• Glass surface provides heterogeneous nucleation points
• Similar effect to seed crystal

Thermodynamic View:

• Barrier to nucleation = Formation of critical nucleus size
• Seed crystal bypasses this barrier
• Growth proceeds spontaneously once started

Problem 9: In fractional crystallization of a binary mixture (A and B), derive the condition for complete separation in one step. If A has solubility curve SA(T) and B has SB(T), what should be the relationship?

Solution:

For complete separation in one crystallization:

Condition 1: At high temperature TH, both A and B should dissolve completely Condition 2: At low temperature TL, only one component should crystallize

Mathematical Condition:

Let mixture contain:

• mA mass of A
• mB mass of B
• Volume of solvent = V

At TH:

• SA(TH) × V ≥ mA (A dissolves)
• SB(TH) × V ≥ mB (B dissolves)

At TL:

• SA(TL) × V < mA (A crystallizes)
• SB(TL) × V ≥ mB (B stays in solution)

For complete separation:

Amount of B that crystallizes should be negligible:

• All crystallized solid is A
• All B remains in solution

Ideal case:

This means: A should have much steeper solubility-temperature curve than B

Practical Reality:

• Complete separation in one step is rare
• Usually need fractional crystallization (multiple cycles)
• Each cycle enriches one component

Example: Separating KNO₃ and NaCl

• KNO₃: Solubility increases dramatically with temperature
• NaCl: Solubility almost constant with temperature
• Heat mixture in water → both dissolve
• Cool → KNO₃ crystallizes, NaCl stays in solution

Problem 10: A student obtained crystals with melting point range 95-102°C instead of sharp m.p. at 100°C. Diagnose the problem and suggest solutions.

Solution:

Diagnosis - Wide Melting Point Range:

A sharp melting point = pure compound (usually within 1-2°C range) Wide range (7°C here) = impurities present

Possible Causes:

1. Rapid Cooling: Trapped impurities in crystal lattice
2. Insufficient Washing: Mother liquor adhering to crystals
3. Incomplete Drying: Solvent still present
4. Wrong Solvent: Poor selectivity for compound vs impurities
5. Eutectic Mixture: Specific ratio of compounds with unique m.p.

Solutions:

Immediate Action:

1. Recrystallization: Dissolve crystals in minimum hot solvent, cool slowly
2. Better washing: Wash with ice-cold solvent to remove adhering impurities
3. Ensure complete drying: Dry in desiccator until constant mass

If problem persists: 4. Change solvent: Try different solvent or solvent pair 5. Decolorization: Add activated charcoal if colored impurities present 6. Multiple recrystallizations: 2-3 cycles usually achieve high purity

How to Confirm Success:

• Sharp m.p. range (±1°C)
• M.p. matches literature value
• Mixed melting point test shows no depression

Why 95-102°C specifically:

• Lower range (95°C): Eutectic of impurity + compound
• Upper range (102°C): Pure compound melts
• Gradual melting indicates continuous range of impurity concentrations

Cross-Links to Related Topics

Organic Chemistry Connections

1. Organic Principles - Purity Criteria: Understanding melting point, boiling point as purity indicators

2. Detection of Elements: After crystallization, testing for elemental composition

3. Distillation: Alternative purification method for liquids; compare with crystallization for solids

4. Chromatography: Modern technique for separating closely related compounds that can’t be separated by crystallization

5. Organic Tests: Testing functional groups in purified compounds

Inorganic Chemistry Connections

1. Solutions: Understanding solubility, concentration, temperature effects

2. Coordination Compounds: Crystallization of complex salts and coordination compounds

3. Qualitative Analysis: Salt analysis requires pure salts, often obtained by crystallization

Physical Chemistry Connections

1. Chemical Thermodynamics: Enthalpy and entropy changes during crystallization; Gibbs free energy

2. Equilibrium: Solubility equilibrium, supersaturation as metastable state

3. Solutions: Solubility product, common ion effect, temperature dependence

Key Takeaways

1. Crystallization purifies solids by exploiting temperature-dependent solubility differences

2. Minimum solvent is crucial for maximum yield

3. Slow cooling produces large, pure crystals; rapid cooling gives small, impure crystals

4. Hot filtration removes insoluble impurities; activated charcoal removes colored impurities

5. Recrystallization increases purity but decreases yield

6. Solvent selection is critical: compound should be highly soluble when hot, sparingly soluble when cold

7. Common mistakes: excess solvent, rapid cooling, washing with hot solvent, direct heating of organic solvents

8. Purity check: Sharp melting point indicates pure compound

9. Applications: From pharmaceutical purification to semiconductor manufacturing

10. Memory: “Hot to Dissolve, Cold to Evolve” + “CHILLED CRYSTALS” checklist

Quick Revision Points

✓ Principle: Temperature-dependent solubility difference ✓ Steps: Dissolve (hot, minimum solvent) → Filter (if needed) → Cool (slowly) → Filter crystals → Wash (cold) → Dry ✓ Decolorization: Activated charcoal ✓ Nucleation helpers: Seed crystal, scratching walls ✓ Yield maximization: Minimum solvent, ice bath ✓ Purity maximization: Slow cooling, recrystallization ✓ Safety: Water bath for organic solvents ✓ Purity test: Sharp melting point ✓ Recovery: Concentrate mother liquor and re-cool

Master crystallization, and you’ve mastered the art of purification! This technique is your foundation for all practical organic chemistry work in JEE and beyond.

Interactive Demo: Visualize Crystallization Process

Explore how temperature changes affect solubility and drive the crystallization process.