What is Microscale Chemistry?
Why Microscale Chemistry?
Synthesis of Aspirin.
Synthesis of E –Benzal
Synthesis of Azodyes
Synthesis of 1-Bromo-3-chloro-5-iodobenzene
Separation Of Component Mixture
Microscale chemistry is an environmentally safe
pollution prevention method of performing chemical
processes using small quantities of chemicals with out
compromising the quality and standard of chemical
applications in education and industry.
The best way to succeed in this effort is by
eliminating chemical waste at the source.
Reduction of chemical use to the minimum level at
which experiments can be effectively performed
Microscale Chemistry is performed by using:
1-Drastically reduced amounts of chemicals
2-Safe and easy manipulative techniques
3-Miniature labware and high quality skills
Microscale Chemistry amounts to a Total Quality Management
(TQM) approach to the use of chemicals.
Microscale Chemistry is recognized as Small scale Chemistry by
the International Union of Pure and Applied Chemistry
Microscale Chemistry offers many benefits:
It reduces chemical use promoting waste reduction at
It offers vastly improved laboratory safety by
Better Laboratory Air Quality.
Least Exposure to Toxic Chemicals.
No Fire and Explosion Hazards.
No Spills and Accidents.
It sharply reduces laboratory cost.
It requires shorter experiment time.
It implements excellent lab manipulative techniques.
It lowers glass breakage cost.
It saves storage space.It improves laboratory skills.
It provides clean and productive environment.
It promotes the principle of 3Rs: Reduce, Recover
It creates the sense of 'Green Chemistry'.
It is user friendly to people with physical disabilities.
1- CONICAL VIALS:
•These take the place of large,
round-bottom flasks used in the
• It is used as a reaction vessel, for
extractions, and as a storage
•Air Condensers: These are glass tubes with
an inner joint at the bottom and an outer joint
at the top. They are usually attached to a
reaction vial (conical vial) and used to prevent
vapors from escaping from a hot or boiling
•Water-cooled or Jacketed Condensers: These
serve the same purpose as the air condensers,
except that cooling is made more efficient by
circulating cold tap water through an outer
glass jacket. Water goes into the bottom
connector and out the top to prevent trapping
air in the water jacket. For lower-boiling
liquids, this additional cooling is necessary to
prevent the escape of vapors.
Craig Tube: The Craig tube is used for
small-scale recrystallization, which is a
method for the purification of small
quantities of solid compounds.
It has two parts: an outer body, which
functions like a vial or test tube; and an
inner plunger, which fits partly into the
body and rests on a ground-glass surface.
The ground-glass joint is not greased, so
that liquids can leak through it but solids
Claisen Head or Claisen Adaptor: allows
introducing chemical reagents (usually
liquids) into a reaction mixture without
taking apart the whole apparatus.
Hickman Distilling Head: The purpose of a still
is to heat a liquid until is passes into the gas
(vapor) phase, and then allow the vapor to cool
and condense back into the liquid phase, with
the condensed liquid trapped in a second
The Hickman still functions like the air condenser
in condensing vapors with the cool glass
surface, but the liquid drips down the inside to
be trapped in a small circular depression, or
collar, in the lower part of the tube.
The tube is used to protect the reaction from
moisture in the atmosphere while still allowing the
passage of air to equalize pressure. To accomplish
this the tube is packed with a glass wool plug, a
quantity of moisture-absorbing solid (the "drying
agent"), and another glass wool plug.
The flat, long blade can be used to weigh out
solids, stir mixtures, remove "O" rings, scratch
glass surfaces to induce crystallization
•Disposable Pasteur pipettes: are used
for dispensing small quantities of
liquids, as filtration devices, and as
columns for small-scale column
•A Filtering Pipette: is used to remove
solid impurities from a liquid with a
volume less than 10-mL. To prepare it, a
small piece of cotton is inserted into
the top of a Pasteur pipette and pushed
down to the beginning of the lower
constriction in the pipette.
•A Filter-tip Pipette: is useful for
transferring volatile solvents during
extractions and in filtering very small
amounts of solid impurities from
•Aspirin is the trade name for the molecule acetylsalicylic acid
The earliest known use of this molecule has been traced back
to the fifth century B.C.
• The Greek physician Hippocrates described an extract of
willow tree bark, a bitter powder that could be used to reduce
• In 1829, Salicin was isolated from willow bark and used as a
pain reliever. Unfortunately Salicin was not very popular since
it was found to be very acidic and a stomach irritant.
• In 1897 a German chemist named Felix Hoffman was
working for the Bayer chemical company. Hoffman was
looking for a less acidic pain reliever that his father could
take for his arthritis.
•His research led to the synthesis of acetylsalicylic acid (ASA)
•Today 80 billion aspirin tablets are consumed every year
across the globe to reduce fevers,relieve pain, and even help
prevent heart attacks.
In commercial aspirin products, a small amount of ASA
(300 to 400 mg) is bound together with a starch binder
and sometimes caffeine and buffers to make an aspirin
tablet. The basic conditions in the small intestine break
down the ASA to yield salicylic acid, which is absorbed
into the bloodstream. The addition of a buffer reduces
the irritation caused by the carboxylic acid group of the
Aspirin can be produced in a one step chemical process
by reacting salicylic acid with acetyl chloride, according
to the reaction:
Aspirin is a white solid that is almost
completely insoluble in water. We will use
this physical property of our product to
separate it from the final solution.
If time allows, we will synthesize methyl
salicylate, which is another ester of salicylic
acid. It occurs in a wide range of plants and
is known as ‘oil of wintergreen’.
It is still used in candies and in ointments for
joint and muscle pains. Salicylic acid
methanol Methyl salicylate (wintergreen).
Thin layer chromatography (TLC) is used to separate and identify aspirin.
• Safety Notes:
• 1. The acetyl chloride and pyridine
should only be dispensed in a hood.
• 2. Always wear appropriate eye
protection and gloves while handling
1. The acetyl chloride and pyridine should only be
dispensed in a hood.
2. Always wear appropriate eye protection and gloves
while handling the chemicals.
1. Place 150 mg (0.001 mol) of salicylic acid in a 10 mL test tube and add 0.1 mL
of pyridine (just sufficient to dissolve it) while the tube rests in a ice-cold
water bath. Keep the test tube in a hood while you are doing this.
2. For the next step, be sure that the open end of the tube is not pointing
toward you or anybody else. Occasionally the reaction goes quickly and
shoots material out of the tube! Add one-tenth milliliter of acetyl chloride
(slight excess over 0.001 mol )in one portion to the test tube. Again, keep
the mixture in a hood!
3. The mixture becomes viscous at this stage. Let the mixture sit in a beaker of
cold water bath for 15 min. – it does not need to be in the hood. While
waiting, set up a vacuum filter flask with a Buchner funnel and a piece of
filter paper which just fits the bottom of the funnel
4. Now add 5 mL of cold water to the test tube and cap it with a rubber stopper.
Shake the mixture. Do this cautiously at first until you are sure that no
violent reaction is occurring. The mixture should turn cloudy. Shaking is
continued until a white product appears (it may takes several minutes, be
5. Turn on the water faucet all the way and check to be sure you have good
suction. Break the suction by disconnecting the tube from the flask (leave the
water running). Pour the mixture into the funnel,trying to get as much of the solid
transferred as possible.Connect the hose and apply full suction for at least 30
Wash the crystals with cold water.Break the suction.Do not just turn off the water;
Dry them on the filter paper for about 5 min.
Part B- Recrystallization
6. Carefully scrape off most of your crystals into a 50 mL beaker. SAVE THE
FILTER PAPER! Add about 3 mL of cold water and place the mixture on a hot plate
in a hood.
Heat until all of the crystals dissolve (check with the instructor if complete
solution does not seem to be happening.) When the crystals are completely
dissolved in the hot solution, remove the beaker and allow it to cool. You should
see nice crystals of aspirin beginning to form! When the recrystallization is
complete, filter again, and dry.
SAVE THE FILTER PAPER for the next step!
Part C- Oil of Wintergreen
1. Place 1.00 gram of salicylic acid in a test tube. (record the actual mass used)
2. Add 5 ml of methyl alcohol and 3 drops of concentrated sulfuric acid.
3. Heat this mixture in a boiling water bath for 15 min.
4. Note the odor of the liquid in your tube.
Procedure (cont’d):Procedure (cont’d):
Benzaldehyde is irritant,Hydroxyle amine hydrochloride is
corrosive,Sodium hydroxyle pellets is corrosive &
hygroscopic,Ethanoyic acid is corrosive,Diethyl ether is
flammable & irritant.
VIAL e’ 0.12 ml
extracting with diethyl
1-Dissolve NaoH in water(0.12ml ) in 1ml reaction vial containing a spin
value allow the solution to cool and add ca. 0.02ml of the benzaldehyde
followed by ca. 20mg hydroxylamine hydrochloride .
2-Stopper the flack and stir vigorously, briefly stopping the stirring at
5min interval to add further position of benzaldehyde &hydroxylamine
until both reagents have been added completely.The reaction mixture will
become warm giving a homogenous solution with almond odor indicating
the total consumption of the benzaldehyde.
3-Neutralize the mixture by the addition of ethanoic acid &allow the
mixture to cool before extracting with diethyl ether.
4-Separate the organic extracts, dry by passing through a column of
MgSo4 into a preweighed reaction vial and remove the solvent then record
the yield of the product.
The reactions are:
H c l / N a N o 2
< 5 ° C
1-Put eight drops of aminobenzene in a 10 cm3 beaker and add 30 drops of
deionised water followed by 15 drops of concentrated hydrochloric acid. Swirl
the beaker and then put it in an ice bath.
2-Weigh 0.15 g of sodium nitrite into another beaker and add 1 cm3 of
water. Cool the beaker in the ice bath. Add one spatula of urea (this prevents
side reactions occurring).
3-Mix the contents of the two beakers together and keep in the ice bath.
4-Weigh 0.45 g of 2-naphthol into another beaker and add 3 cm3 of sodium
hydroxide solution. Swirl to dissolve.
5-Take a piece of cotton cloth 2 x 2 cm2 and, using tweezers, dip it into the
2-naphthol solution. Allow the solution to completely soak the cotton.
6-Dip the cloth completely into the diazonium salt solution. A red dye forms in
the fibers, dyeing the cloth.
An Improved Deamination of 4-Bromo-2-chloro-6-iodoaniline
i s o a m y l n i t r a t e
D M F
Reductive deamination step---the final step
N a c l o 4
1 ) H c l , C H 3 C H 2 O H
I C I
C H 3 C O 2 H
1 ) I s o a m y l n i t r i t e
D M F , 6 5 ° C
2 ) H C L , H 2 O
1-Under a fume hood, 1.65 mL of a 0.75 M isoamyl
nitrite_DMF solution is added to a 10-mL round-bottomed
flask containing a magnetic spin vane.
2-A reflux condenser is placed on the flask and the flask is clamped in a sand bath
heated to 65◦C.
3-With the isoamyl nitrite solution stirring rapidly, a solution of 4-bromo-2-chloro-
6-iodoaniline (0.25g, 0.75 mmol) dissolved in a minimal amount of DMF (2mL) is
added dropwise to the reaction solution over a period of 5 min.The evolution of
nitrogen gas is immediate and continues until all of the aniline solution is added.
4-After the gas evolution is complete (15 min), the reaction mixture
is allowed to cool to room temperature and then carefully
transferred to a 25-mL Erlenmeyer flask.
5-15mL of 20% aqueous hydrochloric acid solution is added to the
reaction mixture and the product is extracted from the reaction
mixture into two, 10-mL portions of ether.The combined
organic extract is washed with 15 mL of 10% aqueous
hydrochloric acid solution, dried over anhydrous magnesium
sulfate, filtered, and concentrated to yield the product as a
Liquid-liquid extraction is one of the most used methods for isolating an
organic compound from a mixture.This technique is commonly used to isolate
and purify products from chemical reactions and is also used to isolate natural
products.The process can be categorized into two types of liquid-liquid
-The first type takes advantage of the polarity of compounds and uses
water to extract or “wash” an organic mixture by removing highly polar
materials, such as inorganic salts, strong acids or bases, etc.
-Second, acid and base extraction, takes advantage of chemical properties
Acid extractions are intended to separate basic compounds from an
organic mixture. Organic bases, amines, are converted to their corresponding
cationic salts by reacting with acids. These salts are then soluble in water and
can be separated from the organic mixture.
Base extractions have a concept similar to acid extractions.
They are intended to separate acidic compounds from an
organic mixture. Organic acids, carboxylic acids, are converted
to their corresponding anionic salts by reacting with bases.
These anionic salts are usually soluble in water and can be
extracted from the organic mixture.
In this experiment you will be given a three-component
mixture, an acid (benzoic acid), a base (ethyl- 4-
aminobenzoate) and a neutral organic compound (9-
You will have to separate these three compounds
individually from the mixture
benzoic acid ethyl-4-aminobenzoate 9-
•-Weigh approximately 300 mg of the three-component mixture, which contains
100 mg of each: amine, carboxylic acid and neutral.
•-Place the solid into a 5 mL conical vial and add 2 mL of diethyl ether.
•-Top the vial with a teflon disk (slippery teflon side facing in) secured with a
screw cap and thoroughly shake its contents until the sample dissolves.
•-To this solution add 1 mL of 3M HCl.
1. Cap the vial and thoroughly shake its contents to complete the
reaction that selectively converts the amine to its water-soluble cationic
2. Allow the layers to settle in a beaker of ice. Carefully transfer just the
bottom (water) layer to a 3 mL conical vial using a Pasteur pipet. To the
smaller vial add 1 mL of pure ether, cap and shake the vial. Transfer just
the lower layer from this vial to a 10 ml beaker.
3. Add 6 M NaOH to this beaker until the solution is basic to pH paper.
The appearance of a white cloudiness indicates the reformation of the
4. Transfer the basic solution into a 5 mL conical vial. Add 1mL of diethyl
ether, cap and shake its content.Allow the layers to settle and separate
the two layers.Remove the bottom layer and place it in the same 10 mL
beaker.Remove the top layer and transfer it to a 10 mL Erlenmeyer
flask.Extract the aqueous bottom layer two more times with 1 mL diethyl
5-Combine the organic layer, dry the organic layer with Na2SO4[i] and
evaporate solvent on the steam bath.3
6-The yellow ether solutions remaining in the vials are recombined into the
5 mL vial. Add 1 mL of pure water, shake its content and then allow the
layers to settle. Remove and discard the bottom aqueous layer.
7-Add 1 mL of 3 M NaOH into the 5 mL conical vial that has the yellow ether
solution (benzoic acid and 9-fluorenone).
8-Cap and thoroughly shake the vial to allow completion of the reaction and
the dissolution of the compounds in their respective solvents. Allow the
layers to separate.
9-Carefully transfer the bottom layer to a 3 mL conical vial using a Pasteur
pipet.To the 3 mL vial add one ml of diethyl ether.Cap and shake its
contents.As before, transfer the lower layer, this time to a 10 mL
beaker.By now the contents of the beaker should be very pale or
10-Add dropwise 6 M HCl to the beaker until the mixture is acidic to pH paper.
11-Transfer the acidic solution into the 5 mL conical vial and extract the
aqueous solution three times with 1 mL of diethyl ether each. Combine the
diethyl ether layers and dry over Na2SO4.
12-Combine the previous left yellow ether layers into a 5 mL conical vial.
Add 1 mL of water, cap and shake its contents. Remove and discard the
water layer with a pipette. Dry the organic layer with Na2SO4 and evaporate
the ether on the steam bath.
Summary of the
In 5 ml vial
using a Hirsch funnel
The benefits of microscale are perhaps greatest
for biology & biochemistry majors as microscale
borrows techniques which are have been standard
in biochemistry for years also,converting to
microscale is one of the best ways to deal with the
problem of chemical wastes in academic labs.
The bottom line : Microscale is a cost effective,
productive and pollution prevention program.