Workshop for Secondary School Teachers

Dr. W M TSUI

Department of Chemistry, HKUST

Workshop for Secondary School Teachers

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Experiments of Microscale Organic Chemistry

Department of Chemistry

Outline2

Introduction of Microscale Organic Chemistry Introduction of designing experimental

procedures Microscale Organic Glassware Techniques in Microscale Organic Experiments:

Solvent /Reagent Dispensing, Reaction Setup Liquid-Liquid Extraction, Filtration Purification methods

Characterization Method of Organic Compounds Experiment highlights

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Organic synthesis & natural products synthesis

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Complex and fascinating molecular structures can be assembled from simple starting materials.

Designed molecular frameworks containing carbon atoms in combination with H, O, N, S, and halogens, can be synthesized on demand and tested for various applications.

Department of Chemistry

Organic synthesis & natural products synthesis

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These useful compounds range from biological tools and medicines to high-value materials for cosmetics, computers and useful devices

OH

CO OH

O

CO OH

CO

CH3

OH

CO2

NaOH (CH3CO)2O

aspirin

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Introduction of Microscale Organic Chemistry

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Had been gradually recognized and adopted at secondary school level

Handle with small quantities of chemical substances

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Macroscale vs. Microscale6

Macroscale Microscale

Quantities of chemicals

5-100 g 0.005-0.5 g

Glasswares 25 - 500 mL Microscale kit (<5mL)

Cost per experiment

$100-1000 $10-100

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Advantages7

1. Require smaller storage area2. Save laboratory space3. Reduce amount of chemical waste4. Improve laboratory safety (smaller amount of

…)5. Shorter reaction time (efficient heat

transfer…)6. Save time for preparation and work up7. More time for evaluation and communication8. ………….

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Microscale Organic Glassware8

Various designs

http://www.sigmaaldrich.com/labware/glassware-catalog/glassware-kits-microscale.html

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Microscale Organic Glassware

All-purpose kit:

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Designing experimental procedures

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Stage 1: Setup reaction Experimental setup, Temperature, Time,

Catalyst, Solvent

Stage 2: Isolation of crude product Solvent extraction, Filtration, Precipitation

Stage 3: Purification of crude product Distillation, Recrystallization, Sublimation

Stage 4: Characterization Melting point, Boiling point, IR, MS

Department of Chemistry Technique: Transfer of reagent/dispensing of solvent11

1.0 mL Syringe

Macroscale: Measuring cylinder Beaker Conical flask Dropping funnel

Microscale: Syringe Needle Septum

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Technique: Setup for Organic Synthesis

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Organic Synthesis: Formation and breaking of C-C bond, C-O bond, C-H bond, C-X bond, etc.

Reflux: for long reaction time

Macroscale reflux setup

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Technique: Microscale Experiment Setup

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Microscale Round-Bottom Flasks, Threaded

Microscale Condenser, Threaded

Water in

Water out

Microscale reflux setup

Microscale Organic Synthesis: Water condenser

Sand bath

Reagents (+ catalyst)

Anti-bumping granules

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Technique: Microscale Experiment Setup

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Microscale Organic Synthesis: Air condenser

Reagents (+ catalyst)

Anti-bumping granules

Mic

roscale

R

ou

nd

-Bott

om

Fla

sks,

Th

read

ed

Microscale reflux setup

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Isolation Technique: Filtration15

Vacuum filtration: Probably the most

common type of filtration used by chemists. The funnel used for this method is called Hirsch funnel. This funnel has a flat disc inside which is made from porous ceramic materials

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Isolation Technique: Filtration

Pipette filtration: For small quantity

of crystals

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Isolation Technique: Liquid-liquid Extraction

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Partition coefficient Solubility in solvents

Screw capTest tube

Separatory funnel

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Purification Technique: Distillation

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For liquids with various volatilities

Macroscale distillation setup

Microscale distillation setup

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Purification Technique: Sublimation

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For solids

Macroscale sublimation setup

Microscale sublimation setup

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Purification Technique: Recrystallization

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For solids Various Solubility

Macroscale 250mLConical flask

Microscale 5mLConical flask

Temperature controlled by depth in sand

Microscale 5mLReaction tube

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Purification Technique: Recrystallization

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Steps in Recrystallization:1. Dissolution (various choice of Solvent)2. Hot Filtration3. Decolorization4. Crystallization5. Collection

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Purification Technique: Recrystallization

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The general idea is to follow the “like dissolves like” principle, e.g. compounds containing hydroxyl groups are best recrystallized from hydroxy-containing solventsClass of compound Suggested solvents

Hydrocarbons Light petroleum, pentane, cyclohexane and toluene

Ethers Diethyl ether and dichloromethane

Halides Dichloromethane

Carbonyl compounds Ethyl acetate and acetone

Alcohols, acids EthanolSalts Water

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Methods for crystallization

2Ice Ice bathbath

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Purification Technique: Recrystallization

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Crystallization Slow cooling: the easiest method and works for

most cases Scratching: induced crystallization by scratching

the inside of the beaker or flask with a glass stirring rod. This will produce microscopic fragments of glass that may act as surfaces on which crystal growth can begin

Seeding: taking a small crystal from the original solid or the other groups and dropping them into the solution

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Characterization of organic compound

Melting point / melting point apparatus

Simplest and most common characterization method for solid organic compounds

Purity check Affordable

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Department of Chemistry

Characterization of organic compound

Boiling point / distillation apparatus Simplest and most

common characterization method for liquid organic compounds

Purity check Affordable

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Characterization of organic compound Infrared spectrum

Infrared spectrophotometer

Absorption of infrared electromagnetic radiation

Information of functional groups

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Characterization of organic compound• To allow passage of IR, most sample

cuvettes have mineral salt windows [Caution! Avoid high humidity.]

• Transmission limit:– NaCl 650cm-1

– KBr 350cm-1

– CsI 56 μm (200cm-1)

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Characterization of organic compound

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BondBase Value

Strength / Shape

Comments

1 C=O 1715 s, "finger"Exact position depends on type of carbonyl

2 O-H 3600 s, broad Broad due to hydrogen bonding

3 N-H 3500 m Can tell primary from secondary

4 C-O 1100 s Also check for O–H and C=O

5 C=C 1650w alkene  m-s aromatic 

Alkene w due to low polarity  Aromatic usually in pairs

6 CΞC 2150 w, sharp Most obvious in terminal alkynes

7 C-H 3000 sAs hybridisation of C changes sp3-sp2-sp, the frequency increases

8 CΞN 2250 m, sharpCharacteristic since little else around this value

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Characterization of organic compound Functional groups can be identified

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Infrared spectrum of acetone

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Characterization of organic compound Mass spectrum / mass spectrometer mass-to-charge ratio of molecular ion

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Picture from http://www.mhhe.com/physsci/chemistry/carey/student/olc/ch13ms.html

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Characterization of organic compound Mass-to-charge

ratio: Molecular ion Fragmentation

pattern of molecular ion

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Molecular ionThe ion obtained by the loss of an electron from the molecule

M+ Symbol often given to the molecular ion

Radical cation

+ve charged species with an odd number of electrons

Fragment ions

Lighter cations formed by the decomposition of the molecular ion.  These often correspond to stable carbcations.

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Characterization of organic compound

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Decane (C10H22)

Molecular ion at m/z = 142

142-29 = 113 113-14 = 99 etc

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Characterization of organic compound Acetone (C3H6O) Molecular ion at m/z =

58

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–15

–28

58

43

15

CH3 CH3

C

O

Department of ChemistryExperiment 1: Microscale separation of components

in a mixture35

caffeine p-dimethoxybenzene acetaminophen

Separation based on their different physical and chemical properties

3 components

Department of ChemistryExperiment 1: Microscale separation of components in

a mixture36

Step 1: Solubility test Technique: Solid-liquid extraction

(Filtration)

Step 2: Acid-base chemistry Technique: Liquid-liquid extraction, Pipette

filtration, Evaporation

Step 3: Purity check Technique: TLC analysis

Department of ChemistryExperiment 1: Microscale separation of components in

a mixture37

Step 1: Solubility test water, dichloromethane, hexane

Powder

Insoluble

Slightly soluble

soluble

Department of ChemistryExperiment 1: Microscale separation of components in

a mixture38

Solid-liquid extraction (Filtration)

Department of ChemistryExperiment 1: Microscale separation of components

in a mixture39

Step 2: Acid-base chemistry

basic neutral

HCl

NaOHaq orgorg

Department of ChemistryExperiment 1: Microscale separation of components in

a mixture40

Liquid-liquid extraction Release pressure Which layer on the top? Test by adding water

Department of ChemistryExperiment 1: Microscale separation of components in

a mixture Some water will be

transferred into the organic phase because of the partial miscibility of the organic phase and water Organic solution contaminated with traces of water.

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Water

brine works to pull the water from the organic layer to the water layer

Department of ChemistryExperiment 1: Microscale separation of components

in a mixture42

Dry by anhydrous Na2SO4 (Preliminary purification)

Pipette filtration

Department of ChemistryExperiment 1: Microscale separation of components in

a mixture43

Evaporation

Needle

Compressed air

Department of ChemistryExperiment 1: Microscale separation of components in

a mixture44

Step 3: Purity check Thin layer chromatography (TLC)

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Thin layer chromatography (TLC)45

Chromatography: Separation of compounds by the distribution between two phases – Mobile phase & Stationary phase

Experiment 1: Microscale separation of components in

a mixture

Department of ChemistryExperiment 1: Microscale separation of components in

a mixture46

stationary phase(TLC plate: Silica gel)

Sample mixture

mobile phase (solvent)

Department of ChemistryExperiment 1: Microscale separation of components in

a mixture47

Department of ChemistryExperiment 2:Catalytic Hydrogenation of Methyl

Oleate48

Organic Synthesis by Hydrogenation Microscale Experiment Setup

Reagents: Methyl oleate, H2, Palladium on charcoal,

Methanol

methyl oleate methyl stearateH2(g)

Catalyst: Pd/C

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Catalytic Hydrogenation of Methyl Oleate

Setup: Generation of

hydrogen gas as reagent

Use of septum Use of needles Use of syringe

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HCl(aq)

Zn metal in 5mL flask

5mL flask

H2(g)

Syringe instead of dropping funnel

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Catalytic Hydrogenation of Methyl Oleate

Collect H2

into a

inverted measuring cylinder

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HCl(aq)

Zn metal in 5mL flask

5mL flask

H2(g)

Syringe instead of dropping funnel

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Catalytic Hydrogenation of Methyl Oleate

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Beginning of synthetic reaction

Use of syringe + needle

H2(g)

Meth

yl ole

ate

+ m

eth

an

ol

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Catalytic Hydrogenation of Methyl Oleate

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Use of parafilm to prevent leakage

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Catalytic Hydrogenation of Methyl Oleate

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Workup: Filter off Pd/C Evaporate excess CH3OH Purification of methyl stearate

Isolation of second crop of product (by adding H2O to filtrate)

Characterization Melting point determination