The role of flow chemistry in

sustainable chemical manufacturing

John Tsanaktsidis| Chief Research Consultant

22 November 2014

MANUFACTURING FLAGSHIP

WASTECH International Summit & Expo , 21-22 November 2014 Mahatma Mandir, Gandhinagar, Gujarat, India

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Agenda

• CSIRO

• The global chemical economy

• Conventional Batch Manufacture

• Continuous flow processing – Flow Chemistry

• Case studies

• Summary & conclusion

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CSIRO – Delivers solutions through Flagships

Commonwealth Scientific and Industrial Research Organisation

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CSIRO – Impact through Innovation

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CSIRO – Our partners are local and global

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Chemical manufacturing is a global business

• The chemical industry is global, and

• underpins the modern world economy

• Uses existing (oil, natural gas, water, metals, & minerals) and renewable

(crops) raw materials to produce >140,000 products

• Represents a $4.12 trillion (2010) global enterprise*

– growing by ~3% pa

* UNEP report, Global Chemical Outlook 2012

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Conventional batch manufacture of chemicals

• Batch processing

– mainstay of fine chemical & pharmaceutical industries

• Capital & labour intensive

– high capital, operation & maintenance costs

• Waste intensive

– 5-100+ kg of chemical wastes per kilogram of fine chemicals & pharmaceuticals produced

• Safety issues

– high risk of exposure, runaway reactions, catastrophic events....

Discovery Development Pilot scale Batch manufacturing scale

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However, ....

“The chemical sector has long been viewed by wider society as being ‘dirty’; ....”

Green Chem., 2012, 14, 38

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175 times, and then....

T2 Laboratories, Florida

• Production of fuel additive - methylcyclopentadienyl manganese tricarbonyl

• Catastrophic thermal runaway lead to Plant destruction!

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So how do we do it better?

• Better chemical processes

• Higher yields

• Fewer by-products

• Less waste

• Shorter processing times

• Smaller plant footprint

• Lower plant & operating costs

• Safer processes & processing

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Process intensification

• Deep understanding of the underlying chemistry

• Use of intensive reactor technologies

• Transition from batch to continuous processing

• Modular plug & play approach

• mix of process technologies (batch & continuous)

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Flow chemistry

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5 - 40mL reactor volume; up to 250 oC; up to hundreds of grams per day

Flow reactors – Laboratory scale

Vapourtec R2/R4 Uniqsis FlowSyn

CRD Polar Bear

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Flow reactors – Pilot and industrial scale

CRD Shell and Tube reactor

100mL- 2L, up to 250 oC & 30bar, up to hundreds of kilograms per day

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Chemtrix MR260 plate reactor

100mL+, up to 250 oC & 20bar, multi-kilograms per day

Chanel dimensions 2.0 x 2.0mm

Flow reactors – Pilot and industrial scale

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Flow chemistry – Critical process parameters

Reaction Temperature

Residence Time (in flow reactor)

Concentration (stoichiometry)

Pressure

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Flow chemistry – Key attributes & benefits

• Better process control

• higher product yields & purities,

• shorter processing times,

• less waste generation

• Easily (infinitely) scalable

• Temporal relationship, not spacial

– Scale = Total Flow Rate x Time

• Smaller physical footprint

• Reduced capital, operating & maintenance costs - reduced energy usage

• Inherently safer

• Lower risk of catastrophic events & exposure

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Case study 1: Production of a pharmaceutical

Pilot-scale API manufacture

Reaction time: 2 min in flow vs 2days in batch Yield: ~100% increase over batch process Purity: cleaner crude product � simpler purification Throughput: Flexible; infinitely scalable Plant costs: About 1/10th the cost of a batch plant

John Tsanaktsidis, unpublished data

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Case study 2: Synthesis of a photochromic dye

• 9 step synthesis ; 8 steps done in in flow (1kg scale)

Mark York, unpublished data

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Case Study 3: Fine chemicals from refined sugars

Carbohydrate

g/10 mL (conc.)

Solvent T (ºC) Flow Rate (mL/min)

RT (min)

Yield (%)

Sucrose (10g) 1.0 (0.29 m) DCE 130 5 + 5 1 61

D-glucose 0.2 (0.11 m) DCE 120 1 + 1 5 58

D-fructose (10g) 1.0 (0.56 m) CH2Cl2 100 5 + 5 1 79

M. Brasholz, K. von Kaenel, C. H. Hornung, S. Saubern, J. Tsanaktsidis, Green Chemistry, 2011, 13, 1114

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Case Study 4: Polymer synthesis

before thermolysis after thermolysis

Christian Hornung , unpublished data

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Summary & conclusions

• Sustainable chemical manufacturing is essential!

• Competitive advantage

• Reduced environmental footprint

• Flow chemistry provides new paradigm for fine chemical manufacture

• Key benefits

– Better process control (less waste)

– Infinite scalability

– Small physical footprint

– Better safety

• Take home

• Fine chemicals can be manufactured at scale, with better quality outcomes (yield, purity), at lower cost, & with better safety.

CSIRO MANUFACTURING FLAGSHIP

Thank you

Dr John Tsanaktsidis

Chief Research Consultant

john.tsanaktsidis@csiro.au