Microscale chemistry Current use and future
opportunities
An organic view from Strathclyde
Dr. Colin Gibson
Navigating the presentation: What is microscale all about and a brief history?
Reasons for introducing microscale @ Strathclyde.
The advantages/disadvantages:- Strathclyde/elsewhere.
The available resources.
What we do (time, what experiments, apparatus, work-up,
purification & analysis).
+/- of the teaching/learning experience.
The future?
What is microscale?
“…an environmentally safe pollution prevention method of
performing chemical processes using small quantities of
chemicals without compromising the quality and standard
of chemical applications in education and industry.”
(www.microscale.org)
“Thus, where students formerly worked with 10-50 g of
starting material and 50-500 g of solvent, they may now
work with 10-150 mg of reactant and 1-10 g of
solvent”
(Butcher et al. JCE, 1985, 62(2), 147.)
Microscale timeline
1983
Introduced at Bowdoin College, Merrimack College
and Brown University, USA to improve laboratory air
quality which lacked high efficiency ventilation.
1986
Microscale inorganic chemistry developed @
Merrimack.
1987
First all microscale inorganic laboratory @ Merrimack.
1993
National microscale chemistry center (NMCC)
established @ Merrimack.
2003
Funding for NMCC ceases.
Why microscale @ Strathclyde?
1992
Asked to look at modernizing 3rd year organic labs.
Prescriptive set of semi-microscale (1-5 g) preparations
and qualitative organic analysis.
No change from 2nd year labs.
Modernize chemistry, remove unknowns (use nmr, ir)
and introduce choice of experiments.
It’ll cost too much for chemicals.
We’ll use microscale to trim costs and as better
preparation for placement year. Introduced in 1993.
Advantages cited by others & in retrospect
Reduction of hazardous waste disposal
“…most of the product generated in the (semi-micro)
laboratory is never employed for any useful chemical
purpose.”
(Szafran et al. JCE, 1989, 66(11), A263.)
“…if you need 100 mg, make 100 mg, don’t make 5 g and
throw away 4.9 g”
(Breuer, CEJ, 2004, 79(2), 17.)
Advantages cited by others & in retrospect
Reduction of hazardous waste disposal
“In 1992, a large (US) university taught both macroscale &
microscale laboratory courses, simultaneously to over 1000
students. … The cost of waste disposal per student in this
course was 25 times less than the corresponding macroscale
course.”
(Williamson, Macroscale & Microscale Organic Experiments, 1993, D. C.
Heath & Co.)
In 1986 Arizona State university observed an 80% reduction
of waste for microscale compared to conventional labs.
(Chloupek-McGough, JCE, 1989, 66(1), 92.)
Advantages cited by others & in retrospect
Pedagogic (A)- Reduced experiment times, increases
number of manipulations per session:40% time reduction to complete Grignard experiment.
(Pickering et al., JCE 1986, 63(6), 535.)
Pedagogic (B)- Students develop better manipulative skills
and teaches them to work carefully:limited tolerances for accidental losses with 100 mg of
product.
Advantages cited by others & in retrospect
Reduced cost of chemicals:Allows introduction of choice of experiments.
Reduced cost of chemicals:Opportunity to use more sophisticated/expensive reagents.
Reduced apparatus footprint:More economical on fumecupboard use (≤ 5 experiments
per hotplate-stirrer).
Advantages cited by others
Improvement of laboratory air quality
Reduced contact with toxic chemicals
Reduction of fire/explosion hazard
Use of non-commercial reagents
Glassware is more durable
Reduces storage space
Reasons cited against using microscale
Our students are not skillful enough.
Strathclyde students are no better/worse than others but
do quite well with microscale.
Students don’t meet standard equipment.
True, if only microscale is introduced, why not a mixture of
micro (100 mg)/semi-microscale (1-5 g)?
It’s inappropriate training for research and industry.
Organic research does use microscale as does some areas
of pharmaceutical research. Few places can teach pilot
scale chemistry!
Expensive equipment.
True, but using a mixture of micro/semi-microscale (1-5 g)
then a kit is not needed for each student.
Reasons cited against using microscale
Unsatisfactory lab experience through ‘lack’ of product.
Usually not the case with solid products.
Can be an issue with colourless oils but they learn that
there is enough product for tlc and an ir.
Difficulty students have learning small scale techniques
without having mastered large scale manipulations.
Maybe. Why not semi-microscale (1-5 g) then a mixture of
micro/semi-microscale?
Lack of experience with macroscale exothermic
experiments.
Macroscale = 500 g, few places can teach pilot scale
chemistry!!! Why not a mixture of micro/semi-microscale?
What resources are available?
There are 139 articles published between 1983 - March
2010 (mainly in Journal of Chemical Education (JCE)) of
experiments, equipment and the philosophy of microscale.
Ca 14 textbooks
techniques.
of
microscale
experiments
and
National
microscale
chemistry
center
(NMCC).
www.microscale.com
Plus 11 international microscale chemistry centres
throughout the World, but not the UK.
What we did/do
1993 set up microscale (ca 100 mg) and semi-microscale
(1-5 g) for our 3rd year students (= 2nd year in rest of UK).
Microscale were based on experiments from Mayo et al.,
“Microscale Organic Laboratory”, 2nd Edn., Wiley, 1989.
Subsequent experiments from Williamson, “Macroscale
and Microscale Organic Experiments”, 2nd Edn., D. C.
Heath & Co., 1994.
What we did/do
In 1993/94:- 6 weeks of 4 afternoons @ 4 h = 96 h.
In 2009/10:- 4 weeks of 4 afternoons @ 3 h = 48 h.
2009/10:- introduced microscale PCC oxidation into 2nd
year.
Uses 135 mg of alcohol and a silica column,
analysis by ir.
2009/10:- 2nd year carry out prescribed course of 1 semimacroscale (25 g), 3 semi-microscale experiments (1-5 g)
and microscale PCC oxidation.
What we do in 3rd year
Compulsory multistep Wittig reaction @ semi-macro and
semi-microscale. 3 Steps and worth 20 marks
2 Semi-microscale (ca 1-2 g) experiments from a choice of
five, worth 15 or 20 marks (crossed aldol, Diels-Alder
(anthracene), acylation of ferrocene, fenbufen preparation
and enantioselective yeast reduction).
2 Microscale experiments from a choice of four, worth 15
marks (Diels-Alder (sulfolene), Beckmann, enol acetate
preparation and PCC oxidation).
The microscale kits
The apparatus
On work-up, purification & analysis
Biphasic extractions are carried out in 3 or 5 ml reaction
vials using a Pasteur pipette to separate phases.
Recrystallizations are carried out in the reaction vials,
followed by filtration with a 10 mm ∅ Hirsch funnel.
We do not use Craig tubes!
Oils can be purified by silica column using pipette.
On work-up, purification & analysis
Analysis by solution cell ir using CH2Cl2 (20 mg) and mp,
tlc.
Remainder is handed in for marking
On the pluses
We have introduced choice.
Waste reduction.
Improved manipulative skills:- project students
happily carry out microscale transformations.
now
Students learn to take more care with experimental
conditions. Curbs the free-spirited experimentalists!
Students learn that chemistry is not just about making
grammes of white solid.
On the pluses
Students learn that ca 50 mg of a colourless oil is just
visible to the human eye and is enough for ir and tlc.
Reduced apparatus footprint is a huge advantage. Over
the last 4 years we have struggled to cope with student
numbers in the laboratory.
No mass failure of students. Just as many pass as did in
1992!
Strathclyde students are just as popular as ever as one
year industrial placement students.
On the minuses
Cost of the kits.
On the minuses:- cost of kits
£££
3 ml Reaction vial
14.60
5 ml Reaction vial
14.60
Drying tube
16.10
Claisen adapter
33.50
Air condenser
19.60
Water jacketed condenser
41.80
250 µl Syringe
42.08
2 ml Syringe + needle
6.73
Spin vane/stirrer
5.50
Caps, O-ring, septa
1.79
196.30
On the minuses
Cost of the kits.
Cost of losses and breakages.
2008/9:- 7 microsyringes, 5 drying tubes (microkit for
whole 4 week period).
Now students must sign in/out kits after each experiment
and kits are monitored by a technician.
2009/10:- 1 microsyringe, 9 stirring vanes.
On the minuses
Cost of the kits.
Cost of losses and breakages.
Need to use a ir solution cell with CH2Cl2.
Now have an ATR ir for small samples but KBr disks may
be a way forward.
On the minuses
Cost of the kits.
Cost of losses and breakages.
Need to use a ir solution cell with CH2Cl2.
Less tolerant to experimental errors. Hotplate too high, or
the ‘free-spirited’ student.
Students are less keen on microscale.
? I don’t have enough/any product.
Usually there is!
? Is this done in industry?
So, that’s it sorted?
“In the three years since 1985…., nearly 300 institutions
moved to convert to this type of program. The magnitude
and rapidity of adoptions really does mean that we are in
the midst of an educational revolution.”
(Mayo et al., “Microscale Organic Laboratory”, 2nd Edn., Wiley, 1989. )
“The revolution is over. The microscale era has arrived.
We are confident that future students will be assured the
opportunity to experience the thrill of coaxing one complex
molecular structure into another and to bring about these
transformations on quantities of material that are just
visible to the human eye!”
(Mayo et al., “Microscale Organic Laboratory”, 3rd Edn., Wiley, 1994. )
So, that’s it sorted- Sadly, no!
“At the time of writing about 66% of US universities and
colleges……use microscale experiments to some extent.”
(Breuer, CEJ, 2004, 79(2), 17.)
“At the time of writing about 66% of US universities and
colleges and about 33% of UK universities use
microscale experiments to some extent.”
(Breuer, CEJ, 2004, 79(2), 17.)
March 2010:- straw poll of OrgNet, still about 33% of UK
universities using microscale.
Future opportunities?
Encourage the 67% to adopt
some microscale element?
Future opportunities?
Really do need more modern and up-to-date
experiments.
Microscale Organic Papers
Experiments
Apparatus
Principles
12
10
8
6
4
2
2010
2005
2000
1995
1990
1985
0
Future opportunities?
Really do need more modern and up-to-date
experiments.
More kudos for demonstrating/developing undergraduate
laboratories.
Currently a poor relation to research and lecturing and
tutorials.
Future opportunities?
Really do need more modern and up-to-date
experiments.
Broaden to inorganic experiments.
Strathclyde will introduce 2 microscale inorganic
experiments over next 2 years. To reduce cobalt salt use.
Perhaps some using expensive catalysts or introduce
catalysis?
Perhaps some organometallic examples?
Future opportunities:- Microreactors
Network of micron sized channels etched into solid surface
(10-500 µm 1-8 cm)
Flow rates ~ 1-250 µl min-1 (10 ml min-1)
Reagent concentration ~ 0.01-2 M
Reaction times ~ 10-20 min (10 h)
Future opportunities:- Microreactors
Control reagent mixing.
Control thermal (high/low) or concentration gradients.
Better conversion & selectivity than batch reactors. So
better yields and purity.
More atom efficient.
Only small amounts of solvents and reagents needed.
Improved sustainability.
Watts et al., Chem Comm., 2007, 443
Wirth et al., OBC, 2007, 5, 733
Future opportunities:- Microreactors
Professor T. Wirth @ Cardiff University has University
funding to introduce microreactor experiments for
chemistry & pharmacy students.
T. Wirth, private communication, April 2010.
Who did/do all the hard work?
Lilias Rees
Dr. Debbie Willison
Dr. Marion Currie
Dr. Chris Dodds
Alasdair Shaw
Dr. John Haddow
Strathclyde 3rd year 1993-2010
Thank you
for listening
&
any questions?
What is microscale?
… “an environmentally safe pollution prevention method of
performing chemical processes using small quantities of
chemicals without compromising the quality and standard
of chemical applications in education and industry”
(www.microscale.org)
What is microscale?
The apparatus
(© Alasdair Shaw, Strathclyde University)