Keith SmithKeith Smith

Centre for Clean ChemistryCentre for Clean ChemistryUniversity of Wales SwanseaUniversity of Wales Swansea

Emerging Technologies - Sustainable DevelopmentEmerging Technologies - Sustainable Development

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.

19502.5 billion

205011 billion?

19895.2 billion

The World’s Population

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.Renewable energy.

• Recycle all products.Recycle all products.

• Recover all waste.Recover all waste.

• Use atom efficient reactions.Use atom efficient reactions.

Search for Clean Chemistry

Principles of Clean Chemistry

•High yield of a single product.High yield of a single product.

•Replace bulk reactants by catalysts.Replace bulk reactants by catalysts.

•Avoid/minimise use of solvent or replace Avoid/minimise use of solvent or replace by water.by water.

•Use near - ambient conditions to minimise Use near - ambient conditions to minimise fuel use.fuel use.

•Recycle any by-products or waste products.Recycle any by-products or waste products.

Electrophilic aromatic substitution

• Many commercially important reactionsMany commercially important reactions

• Acid activators often requiredAcid activators often required

• Waste acid streams need treatmentWaste acid streams need treatment

• Excess reagents used, often involving heavyExcess reagents used, often involving heavy metals or other undesirable materials metals or other undesirable materials

• Reactions often not regioselectiveReactions often not regioselective

Need for clean chemistry

Nitration of Toluene — a Dirty Process

Disadvantages:

H2SO4

HNO3

CH3

toluene

CH3

NO2

para-nitrotoluene

+

CH3

NO2

meta-nitrotoluene

+

CH3

NO2

ortho-nitrotoluene

•Yield of para product only about 35%.

•Large excess of H2SO4 and excess HNO3 used.

•Fuel costs associated with distillation and sulfuric acid recovery.

•Washes needed, giving large volume of acidic waste - water that has to be treated.

The Swansea Nitration Method

Advantages:

HNO3

Ac2OHß

CH3

toluene

CH3

NO2

para-nitrotoluene

+

CH3

NO2

meta-nitrotoluene

+

CH3

NO2

ortho-nitrotoluene

•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

Toluene required Nitric acid required By-product produced

50

100

150

200

tons

Old Old

Old

New

New New

Zeolite

How the H- Catalyst Works

•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.

Potential catalytic sites

Interaction at a catalytic site favoured for attack at the para-position.

mainlymainly parapara-product-product producedproduced

Shape - Selectivity in a Zeolite Pore

CH3 REAGENT

Further Nitration of Toluene

CH3

NO2

CH3

NO2

NO2

O2N

CH3

NO2

NO2

O2N

CH3 CH3

NO2

CH3

NO2

CH3

NO2

+ +

18 3 79

Nitration of o-nitrotolueneCH3 CH3

NO2

NO2NO2

CH3

NO2

+

O2N

HNO3/TFAA/H high yield 3 : 1

HNO3/TFAA high yield 2 : 1

Zeolite has little effect on rate, but enhances selectivity a little

Perhaps slowing down the reaction by adding diluent will help

Nitration is slow using acetic anhydride but quick using TFAA

Effect of adding acetic anhydrideCH3 CH3

NO2

NO2NO2

CH3

NO2

+

O2N

HNO3/TFAA/Ac2O/H 99% 17 : 1

HNO3/ TFAA/Ac2O 16% 2 : 1

Zeolite enhances rate and selectivity substantially

Reaction much slower without zeolite

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 tolueneCH3 CH3

NO2

NO2

CH3

NO2

+

O2N

2HNO3/H2SO4 4 : 1

24HNO3/Ac2O/Claycop/CCl4 85% 9 : 1

Literature results:

S.G.Carvalheiro, B.Manuela, P.Laszlo and A.Cornelis, PCT Int Appl, WO 94, 19, 310, 1/9/1994.

HNO3/H/reflux ?% 14 : 1

R. Prins et al., poster at Europacat IV, Rimini, September 1999

One step dinitration of toluene

CH3 CH3

NO2

NO2

CH3

NO2

+

O2N2 HNO3

Ac2O

TFAA

H

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

NO2

NO2

CH3

NO2

+

O2N

CH3

HNO3

Ac2O

H

HNO3

Ac2O

H

TFAA

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

H Suzuki, S Yonezawa, N Nonoyama and T Mori, J. Chem. Soc., Perkin Trans. 1, 1996, 2385

Cl Cl

NO2

Cl

NO2

Cl

NO2

+ +

32 <1 68

N2O4, O2

Fe(acac)3

0 oC, 48 h

Modified approach to selective nitration

X X

NO2

X

NO2

X

NO2

+ +N2O4, O2

0 oC, 48 h

H

Substrate Yield (%) Proportionsortho meta para

toluene 85 53 2 45benzene 50 -- -- --fluorobenzene 95 7 0 93chlorobenzene 95 14 <1 85bromobenzene 94 22 <1 77

iodobenzene 95 37 1 62

K Smith, S Almeer and S J Black, Chem. Commun., 2000, 1571

Bromination of Toluene - Traditional Method 1

Problem: the two products have almost identical boiling temperature, so very difficult to separate — expensive in fuel and time.

Advantages: reactants cheap; only one step.

ca. 50%

ca. 50%

Br2

Fe(cat.)

CH3

toluene

CH3

Br

CH3

Br

CH3

NO2

CH3

NH2

CH3

N2+ Cl-

CH3

Br

H2SO4

HNO3

Fe/HClNaNO2

HCl CuBr

CH3

NO2

+

CH3

NO2

+

Bromination of Toluene Traditional Route 2

Easily separated by distillation

Advantage: easy separation at nitro stage; single isomer after.

Problems: Low overall yield; several stages, each having its own waste.

CH3

toluene

Bromination of Toluene — a Clean Approach

CH3CH3

Br

toluene

Br2

Na-Y 99% yield

NaBr+

H-Y

heat

The protonated catalyst can be re-activated by heating.

Old method possibility 1

Old method possibility 2

New method

To produce 100 tons para -bromotoluene

Bromine used

Toluene used

Waste products

Other materials used

150

450

tons

600

300

Comparison of the Old and New Bromination Methods

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: (Melt-processible thermotropic liquid crystalline polyesters)

Coatings, Inks and Adhesives: (Improvements in flex, surface hardness, etc.)

An interesting problem - selective 2,6-dialkylation of naphthalene

CO2Me

MeO2C

R

R

(an important PEN intermediate) (a potential precursor)

R

R

alkylating agent (eg ROH)

catalyst (eg H-form zeolite)

The nature of the problem

Requirements

•A high yield of the desired 2,6-dialkylnaphthalene

•Very little of any other dialkylnaphthalene, especially 2,7-

•A high conversion of naphthalene to alkylated products

alkylating agent (eg ROH)

catalyst (eg H-form zeolite)

alkylating agent (eg ROH)

catalyst (eg H-form zeolite)

alkylating agent (eg ROH)

catalyst (eg H-form zeolite)

alkylating agent (eg ROH)

catalyst (eg H-form zeolite)

Recently published results for 2,6-dialkylnaphthalene (DAN)

selectivity

Catalyst

Naphthaleneconversion (%)

DAN (%)

2,6-DAN (%)

2,6/2,7

Reference

HM

74.4

36.3

25.7

3.0

Kim et al.Applied Catal.A:Gen.,

131, 1995, 15.

HY

94.0

43.2

18.6

1.2

Moreau et al.J. Org. Chem., 57, 1992, 5040.

HY

52.4

27.8

23.3

Moreau et al.Applied Catal.A:Gen.,

159, 1997, 305.

5.9

Preliminary investigation: Varying the catalyst

Catalyst (Si/Al)

Naphthalene conversion (%)

DTBN (%)

2,6-DTBN (%)

2,6/2,7

HY (15)

89

45

33

2.7

HZSM-5 (25)

0

0

0

-

HBeta (12)

49

4

2

1.1

HM (10)

22

2

2

-

HMMS (10)

43

9

6

1.9

2 h autoclave reactions at 160 oC

(Catalyst (0.5 g), Nap (10 mmol), ButOH (20 mmol), cyclohexane (100 ml))

ButOH

•Increasing the temperature

•Increasing the amount of tert-butanol

•Increasing the reaction time

•Increasing the amount of catalyst

•Decreasing the amount of solvent

•Increasing the Si/Al ratio

•Multistage reactions in 10 ml solvent

Optimisation of the reaction

Multistage reactions in 10 ml solvent

Stage

Naphthalene conversion (%)

DTBN (%)

2,6-DTBN (%)

2,6/2,7

4

97

64

61

19.1

1

72

44

43

37.1

3

96

65

62

25.1

2

92

65

63

34.8

1 h autoclave reactions at 180 oC

(HM (Si/Al (10) (4.0 g), Nap (10 mmol), ButOH (80 mmol), cyclohexane (10 ml))

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

Naphthalene conversion (%)

DTBN (%)

2,6-DTBN (%)

2,6/2,7

Reference P. Moreau et al.Applied Catal.A:Gen.,

159, 1997, 305.

HY

52.4

27.8

23.3

5.9

K. Smith and S.D. RobertsCatalysis Today, 2000, 60, 227-233.

HM

96

61

60

50.6

Conclusions

•New nitration reaction using N2O4 and O2 over H.

•Direct nitration of toluene to 2,4-dinitrotoluene (near quantitative yield, 2,4:2,6 ratio around 70).

•Selective di-tert-butylation of naphthalene to the 2,6-isomer in 60% yield with a 2,6-:2,7- ratio of over 50.

•Bromination of aromatics with superb regioselectivity.

•Nitration of aromatics with very high regioselectivity.

ThanksThanksThe Funding Bodies:Zeneca, EPSRC, DERA, Zeneca, EPSRC, DERA, Governments of Qatar and Kuwait, Governments of Qatar and Kuwait, Zeolyst International (for samples)Zeolyst International (for samples)

The Funding Bodies:Zeneca, EPSRC, DERA, Zeneca, EPSRC, DERA, Governments of Qatar and Kuwait, Governments of Qatar and Kuwait, Zeolyst International (for samples)Zeolyst International (for samples)

Simon D RobertsSimon D Roberts

Tracy Gibbins (Ross Millar, Rob Claridge)Tracy Gibbins (Ross Millar, Rob Claridge)

Saeed Almeer (Steve Black)Saeed Almeer (Steve Black)

My Research GroupMy Research Group

ResearchersAdam Musson (Gareth DeBoos)Adam Musson (Gareth DeBoos)

Dawoud BahzadDawoud Bahzad

1999