Emerging Technologies - Sustainable Development
Keith Smith
Centre for Clean Chemistry
University of Wales Swansea
Need for Chemicals
•Pharmaceuticals and health products
•Plastics and other materials for
construction and manufacturing
•Agriculture - pesticides,
weed - killers, fertilisers
•Fuels and lubricants
•Other - paints, dyes, liquid
crystals, specialities, etc.
The World’s Population
1950
2.5 billion
1989
5.2 billion
2050
11 billion?
Concerns and Solutions
•Global population growth, leading
to increased consumption
•Pollution of the environment, becoming
increasingly controlled
•The chemicals/pharmaceuticals industry will come
under increasing pressure to adjust its processes to
ones that are more sustainable
•Chemists need to devise new sustainable reactions
Sustainable Development
• Renewable energy.
• Recycle all products.
• Recover all waste.
• Use atom efficient reactions.
Search for Clean Chemistry
Principles of Clean Chemistry
•High yield of a single product.
•Replace bulk reactants by catalysts.
•Avoid/minimise use of solvent or replace
by water.
•Use near - ambient conditions to minimise
fuel use.
•Recycle any by-products or waste products.
Electrophilic aromatic substitution
• Many commercially important reactions
• Acid activators often required
• Waste acid streams need treatment
• Excess reagents used, often involving heavy
metals or other undesirable materials
• Reactions often not regioselective
Need for clean chemistry
Nitration of Toluene — a Dirty Process
CH3
CH3
CH3
CH3
NO2
H2SO4
+
+
HNO3
NO2
toluene
ortho-nitrotoluene
NO2
meta-nitrotoluene
para-nitrotoluene
Disadvantages:
•Yield of para product only about 35%.
•Large excess of H2SO4 and excess HNO3 used.
•Washes needed, giving large volume of acidic waste - water that has to be treated.
•Fuel costs associated with distillation and sulfuric acid recovery.
The Swansea Nitration Method
CH3
CH3
CH3
CH3
NO2
HNO3
+
Ac2O
Hß
+
NO2
toluene
ortho-nitrotoluene
NO2
meta-nitrotoluene
para-nitrotoluene
Advantages:
•Yield of para product is about 80%.
•The only by-product (acetic acid) is easily recovered.
•The H- catalyst can be re-used several times.
•No water washing required.
•Distillation costs (fuel) reduced.
Comparison of the Old and New Nitration Methods
To produce 100 tons para -nitrotoluene
tons
200
Old
Old
150
100
Old
New
New
New
50
Toluene required
Nitric acid required
By-product produced
How the H- Catalyst Works
Zeolite 
•H- is a solid material known as a zeolite (the word
“zeolite” means “boiling stone”).
•Zeolites are Si and Al mixed oxides with associated
cations, such as H+.
•The H+ ions mean that zeolites can be strong acids,
making them useful as catalysts.
•Zeolites have crystalline porous structures like
a mineral sponge.
•The holes in the “sponge” have regular sizes,
with different sizes for different zeolites.
•The reaction takes place within the confines of the pores.
Shape - Selectivity in a Zeolite Pore
mainly
para-product
produced
Interaction at a
catalytic site
favoured for
attack at the
para-position.
CH3
REAGENT
Potential catalytic sites
Further Nitration of Toluene
CH3
CH3
CH3
CH3
NO2
+
+
NO2
NO2
18
3
CH3
O2N
79
CH3
NO2
NO2
NO2
CH3
O2N
NO2
NO2
Nitration of o-nitrotoluene
CH3
CH3
CH3
NO2
NO2
O2N
NO2
+
NO2
Nitration is slow using acetic anhydride but quick using TFAA
HNO3/TFAA
high yield
2
:
1
HNO3/TFAA/H
high yield
3
:
1
Zeolite has little effect on rate, but enhances selectivity a little
Perhaps slowing down the reaction by adding diluent will help
Effect of adding acetic anhydride
CH3
CH3
NO2
CH3
NO2
O2N
NO2
+
NO2
HNO3/ TFAA/Ac2O
16%
2
:
1
HNO3/TFAA/Ac2O/H
99%
17
:
1
Reaction much slower without zeolite
Zeolite enhances rate and selectivity substantially
o-Nitrotoluene (17.5 mmol), HNO3 (17.5 mmol of 90%),
TFAA (3.5 ml, 24 mmol), Ac2O (3.5 ml), H (1 g), -10 oC, 2 h
One step dinitration of toluene
CH3
CH3
CH3
NO2
O2N
NO2
+
NO2
Literature results:
2HNO3/H2SO4
24HNO3/Ac2O/Claycop/CCl4
HNO3/H/reflux
4
:
1
85%
9
:
1
?%
14
:
1
S.G.Carvalheiro, B.Manuela, P.Laszlo and A.Cornelis, PCT Int Appl, WO 94, 19, 310, 1/9/1994.
R. Prins et al., poster at Europacat IV, Rimini, September 1999
One step dinitration of toluene
CH3
CH3
2 HNO3
CH3
NO2
O2N
NO2
TFAA
+
Ac2O
H
NO2
0.5 g H (17.5 mmol scale) 98%
14
:
1
1.0 g H (17.5 mmol scale) 98%
25
:
1
One pot two step dinitration of toluene
CH3
CH3
CH3
NO2 O2N
HNO3
HNO3
TFAA
Ac2O
Ac2O
H
NO2
CH3
NO2
+
H
NO2
99% overall yield
70
:
1
ca. 3% of other isomers
isolated yield 90% with 99% purity
K Smith, T Gibbins, R W Millar and R Claridge, J. Chem. Soc., Perkin Trans. 1, 2000, 2753
Another approach to “clean” nitration
Cl
Cl
Cl
Cl
NO2
N2O4, O2
+
+
Fe(acac)3
NO2
o
0 C, 48 h
NO2
32
<1
H Suzuki, S Yonezawa, N Nonoyama and T Mori,
J. Chem. Soc., Perkin Trans. 1, 1996, 2385
68
Modified approach to selective nitration
X
X
X
X
NO2
N2O4, O2
+
+
H
0 oC, 48 h
Substrate
toluene
benzene
fluorobenzene
chlorobenzene
bromobenzene
iodobenzene
NO2
Yield (%)
85
50
95
95
94
95
NO2
Proportions
ortho
meta
para
53
-7
14
22
37
2
-0
<1
<1
1
45
-93
85
77
62
K Smith, S Almeer and S J Black, Chem. Commun., 2000, 1571
Bromination of Toluene - Traditional Method 1
CH3
Advantages:
reactants cheap; only one
step.
ca. 50%
CH3
Problem:
the two products have
almost identical boiling
temperature, so very
difficult to separate —
expensive in fuel and time.
Br2
Br
Fe(cat.)
CH3 ca. 50%
toluene
Br
Bromination of Toluene
Traditional Route 2
CH3
CH3
H2SO4
HNO3
Advantage: easy separation at nitro stage;
single isomer after.
toluene
Problems: Low overall yield; several
stages, each having its own waste.
NO2
+
CH3
CH3
CH3
NO2
CH3
+
CH3
Fe/HCl
NaNO
2
CuBr
HCl
NO2
Easily separated
by distillation
NH2
N2+
Cl-
Br
Bromination of Toluene — a Clean Approach
CH3
CH3
toluene
Br2
Na-Y
99% yield
Br
heat
NaBr
+
H-Y
The protonated catalyst can be re-activated by heating.
Comparison of the Old and New Bromination Methods
To produce 100 tons para -bromotoluene
tons
600
Old method possibility 1
450
Old method possibility 2
New method
300
150
Bromine
used
Toluene
used
Other
materials used
Waste
products
PEN - an important speciality polymer
(PEN is the homopolymer of ethylene glycol
with 2,6-naphthalenedicarboxylic acid)
Applications of PEN:
Films:
(Magnetic recording tapes, flexible printed circuit
boards)
Industrial Fibres:
(Rubber reinforcement for tyres, hoses and belts)
Packaging:
(High acidity foods, carbonated beverages)
Liquid Crystalline Polymers:
Coatings, Inks and Adhesives:
(Melt-processible thermotropic liquid crystalline
polyesters)
(Improvements in flex, surface hardness, etc.)
An interesting problem - selective
2,6-dialkylation of naphthalene
R
CO2Me
MeO2C
(an important PEN intermediate)
R
(a potential precursor)
The nature of the problem
R
alkylating agent (eg ROH)
catalyst (eg H-form zeolite)
R
Requirements
•A high conversion of naphthalene to alkylated products
•A high yield of the desired 2,6-dialkylnaphthalene
•Very little of any other dialkylnaphthalene, especially 2,7-
Recently published results for
2,6-dialkylnaphthalene (DAN)
selectivity
Catalyst
HM
HY
HY
Naphthalene
conversion (%)
74.4
94.0
52.4
DAN (%)
36.3
43.2
27.8
2,6-DAN (%)
25.7
18.6
23.3
2,6/2,7
3.0
1.2
5.9
Reference
Kim et al.
Applied Catal.A:Gen.,
131, 1995, 15.
Moreau et al.
J. Org. Chem.,
57, 1992, 5040.
Moreau et al.
Applied Catal.A:Gen.,
159, 1997, 305.
Varying the catalyst
Preliminary investigation:
ButOH
2 h autoclave reactions at 160 oC
(Catalyst (0.5 g), Nap (10 mmol), ButOH (20 mmol), cyclohexane (100 ml))
Catalyst (Si/Al)
HZSM-5 (25)
HM (10)
HBeta (12)
HY (15)
HMMS (10)
Naphthalene conversion (%)
0
22
49
89
43
DTBN (%)
0
2
4
45
9
2,6-DTBN (%)
0
2
2
33
6
2,6/2,7
-
-
1.1
2.7
1.9
Optimisation of the reaction
•Increasing the temperature
•Increasing the reaction time
•Increasing the amount of catalyst
•Increasing the amount of tert-butanol
•Decreasing the amount of solvent
•Increasing the Si/Al ratio
•Multistage reactions in 10 ml solvent
Multistage reactions in 10 ml solvent
1 h autoclave reactions at 180 oC
(HM (Si/Al (10) (4.0 g), Nap (10 mmol), ButOH (80 mmol), cyclohexane (10 ml))
Stage
1
2
3
4
Naphthalene conversion (%)
72
92
96
97
DTBN (%)
44
65
65
64
2,6-DTBN (%)
43
63
62
61
37.1
34.8
25.1
19.1
2,6/2,7
Observations:
Increases the conversion
Maximum yield of DTBN and 2,6-DTBN by 2nd stage
Decreases the 2,6/2,7 ratio somewhat
Comparison of results for 2,6-di-tert-butylnaphthalene
(DTBN) selectivity after optimisation
Catalyst
HY
HM
Naphthalene conversion (%)
52.4
96
DTBN (%)
27.8
61
2,6-DTBN (%)
23.3
60
2,6/2,7
5.9
50.6
P. Moreau et al.
Applied Catal.A:Gen.,
159, 1997, 305.
K. Smith and S.D. Roberts
Catalysis Today, 2000, 60, 227-233.
Reference
Conclusions
•Nitration of aromatics with very high regioselectivity.
•Direct nitration of toluene to 2,4-dinitrotoluene
(near quantitative yield, 2,4:2,6 ratio around 70).
•New nitration reaction using N2O4 and O2 over H.
•Bromination of aromatics with superb regioselectivity.
•Selective di-tert-butylation of naphthalene to the 2,6isomer in 60% yield with a 2,6-:2,7- ratio of over 50.
Thanks
The Funding Bodies:
Zeneca, EPSRC, DERA,
Governments of Qatar and Kuwait,
Zeolyst International (for samples)
Researchers
Adam Musson (Gareth DeBoos)
Tracy Gibbins (Ross Millar, Rob Claridge)
Saeed Almeer (Steve Black)
Dawoud Bahzad
Simon D Roberts
My Research Group