Multicatalytic processes based on Supported Ionic Liquid-Like … · some of them show evidence of...

Multicatalytic processes based on SILLPs S.V. Luis

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Multicatalytic processes based on Supported Ionic Liquid-Like Phases (SILLPs)

S.V. Luis B. Altava, M.I. Burguete, E. García-

Verdugo, E. Peris, R. Porcar Sustainable and Supramolecular

Chemistry Group University Jaume I

Castellón, Spain www.quimicasostenible.uji.es


XXI CENTURY: THE SEARCH FOR SUSTAINABILITY

27/05/2014 S. Luis 2


XXI CENTURY: THE SEARCH FOR SUSTAINABILITY

27/05/2014 S. Luis 3

Methods

Substrates

Added-value

Products


4

Green Chemistry

Toolbox

Tools

Catalysis Heterogeneous catalysis

Alternative Solvents

Microwave heating

Flow Process


5

It is possible to design ionic liquids of suitable properties

by combining appropriate anions, cations, and varying

their structure

Why ILs?

N.V. Plechkova, K.R. Seddon Chem Soc Rev, 37 (1) (2008), pp. 123–150


6

….Nobody is perfect!!


7

Biphasic liquid-liquid systems:

require relatively large amounts of IL.

relatively expensive

some of them show evidence of low

biodegradability and high (eco)toxicological

properties.

require an extraction solvent

The immobilisation of ILs onto a support or structured

material (e.g. by simple impregnation, covalent linking

of the cation, sol-gel method, etc):

SILLP: Supported Ionic Liquid-Like Phases IL

Ionic liquids as “Green Solvents”


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Ionic liquids as “Green Solvents”: SILLPs

SILLPs: Immobilisation of ILs onto a support or structured materials

(by covalent linking of the cation) to transfer the properties of the IL to an

inert support

minimize the amount of ILs used: lower cost

easy separation and recyclability

potential for the development of continuous processes

solventless reactions or in SCFs

N

N

R

N

N

R

N

NR

N

N

R

N

NR

Cl

Cl Cl Cl

Cl

Cat

Cat

Cat

Substrates Products

Flow Flow

SCF SCF

E-1

S P


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Monomers or monomeric-ILs

or

Films

Beads

Rods

Membrane

Polymerization/modification

Soluble materials

Polymerization/modification

+

+

Crosslinking insoluble materials

100 m

Polymeric Ionic Liquids (PILs)

FilmsElectrospinning

NPs-PILs solutions

PILS SILLPS

Ionic liquids as “Green Solvents”: SILLPs


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Transfer the properties of the IL to an inert support

What properties?

modular

thermal stability

polarity

Mw heating

ability to stabilise different catalysts

ILs vs. SILLPs:

How much do they look alike?


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Cl

The length of the chain in the IL allows to modulate

the polarity

* Hydrophylicity: -Me > -Bu > -De

macro-PS-DVB 1.2 mmol Cl/g

N

NCH3

Cl N

NC4H9

Cl

N

NC10H21

Cl

Properties of SILLPs:

Polarity/Behaviour in water


12

Synthesis of Supported Ionic Liquid-Like Phases:

SILLPs

TGA

-80

-60

-40

-20

0

20

40

60

80

TfO - NTf

2

-

BF 4

-

SbF 6

-

Cl -

D T

Anion 1.2 meq. / g. 2.2 meq. / g. 4.3 meq. / g.

Chem. Eur. J., 2011


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Pyrene as solvatochromic fluorescent probe

The pyrene solvent polarity scale is defined as

the II/IIII emission intensity ratio

II/IIII increases with increasing solvent polarity

Hexane

0.61

Toluene

1.11

MeOH

1.33

CH3CN

1.75

DMF

1.82

- +

II/IIII

Properties of SILLPs: Polarity

Chem. Eur. J., 2011

1.15 1.29 1.40 1.64 0.93

N

N

Cl

N

N

NTf2

N

N

BF4

N

N

SbF6

Cl


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Rose Bengal

O

OII

O2C

Cl

ClCl

ClI

ONa

I

N

N

R

X

N NR

x2

x1

Photocatalysts

Organometalic and

metalic catalysts

Organocatalysts

MeNPs

Biocatalysts

Supported Ionic Liquid-Like Phases (SILLPs)


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Benchmark Reaction: Heck reaction

Monolithic microreactor:

IL-DVB 40:60

2,1 meq IL/g

0,21 meq Pd(0)/g

0

20

40

60

80

100

120

20 40 60 81 101 121 141 Cycles (bed vol.)

%

0

50

100

150

200

250

300

TO

N

Yield

TON

• 100% trans

• high stability 420min (7h)

• TON/cycle: 2.28

• Residence time: 2.98min

scEtOH

(Tc=241oC, Pc=61 bar)

J. Catal., 2010

Application of SILLPs: Catalytic supported PdNPs

I

Cat

+CO2MeCO2Me

• T>150oC

• T>250oC transesterification.


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Entry Cycle Yield (%)

TOF50 (h-1)

1 2 99 2727

2 8 99 2970

HPLC chromatograms

Salt containing Salt free

Under continuous flow with scCO2:

Salt free, solvent free

Adv. Synth. Catal., 2010

Application of SILLPs: Catalytic supported PdNPs

Polymeric cocktail


Biocatalytic continuous biodiesel

synthesis in scCO2

The presence of t-butanol as

cosolvent avoids poisoning of

the biocatalyst by the side

product glycerol

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Application of SILLPs: Supported biocatalysts

ChemSusChem 2012


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Why?

Reaction induced by light.

Clean and selective processes.

How?

adsorbing Rose of Bengal.

N

N

CH3

Cl-

MeOH/ Tambiente /48h

RB-COONaRB-COO-

N

N

CH3

NaCl

N

N

CH3Cl-

450 500 550 600

0,0

0,2

0,4

0,6

0,8

1,0

Abs

Longitude de onda (nm)

0 min

60 min

120 min

180 min

240 min

RB =

Application of SILLPs: Supported photocatalysts


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0.1 mL/min

0.1 mL/min

0.05 mL/min Fluidized bed reactor

10 mL

250 mg RB-SILLP

Application of SILLPs: Supported photocatalysts


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Cyanosilylation of Carbonyl Compounds

BF4 SbF6 NTf2 TfO Cl

0

20

40

60

80

100

120

Re

lative

Re

action r

ate

0 50 100 150 200 250 300 350 400 450 500

0

10

20

30

40

50

60

70

80

90

100

Time (minutes)

Yie

ld (

%)

BF4 SbF6 NTf2 TfO Cl

NN R

R'X

Functionalisation Degree

Type of substitution

Polymer Type

Counterion

More basic SILLP more active catalyst > 99% yield for different

ketones and aldehydes

Green Chem., 2014, 16, 1639.


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Cyanosilylation of Carbonyl Compounds

Green Chem., 2014

Fix –bed

reactor

ATR-FTIR

pump

0 10 20 30 40 50 60 70 80 90 100 110 120

0,00

0,02

0,04

0,06

0,08

0,10

0,12

0,14

0,16

Ab

s. p

rod

uc

t (c

m-1)

time (min)

0,00

0,05

0,10

0,15

0,20

0,25

0,30

Ab

s. re

ac

tan

t (c

m-1)

0.1 mL/min 0.2 mL/min

0.3

mL/min

0.4

mL/min

0.5 mL/min

GC(Yield):36% GC(Yield):87% GC(Yield):95%

GC(Yield):

95%

GC(Yield):

93%

95% yield,

solvent-free,

excellent catalytic activity,

continuous monitoring

FLOW PROCESS


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Natural biosynthetic systems

many catalytic reactions occurring in the

same vessel

products from one step do not inhibit the next

one.

Reagents compatibility: oxidants/reductants

or nucleophile/electrophile together.

linear combination of irreversible steps

Cells produce complex compounds


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Non-natural biosynthetic systems

A + B C D E F

Isolation of incompatible catalysts

Reagent(s)/product(s) compatibility.

linear combination of irreversible steps


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Synthesis of cyanohydrin

Step 2: two reactions: hydrolysis of

TMSOR and acetylation

Step 3: Enzymatic trans-esterification,

enantiopure cyanohydrins

Overall: 4 reactions in 3 consecutive steps

Step 1 Step 2

Step 3


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1 Step 2 Step

Batch process:

3 Step

1 eq acetophenone

1,2 eq TMSCN; rt,

24h.

Cat: 25 mg/mmol

benzaldehyde

Yield: >99%

Step 1 Step 2

Step 3

1 eq substrate, 2 eq Ac2O, 40ºC,

24h.

50 mg cat / mmol substrate.

Yield: >99%

9,8 ml methyl-THF, 0,15ml n-propanol and

100 mg CAL-B (Novozyme 435) /mmol

substrate; 60ºC, 24h.

50% conv.,

ROH: 98% e.e., AcOR: 99% e.e.


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Batch process:

1 Step 2 Step

3 Step

One-pot multistep batch process


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Synthesis of cyanohydrin- Flow process

Step 1

Step 2

T = 25 oC, 500 mg cat

T = 50 oC

500 mg cat

1 eq. + 1.1 eq 95 % Yield

2 eq

0.01 mL/min

99 % Yield

0.019 mL/min

Up to 85 overall yield

for the two steps

Single pot reactor mixing catalyst

and reagents does not work

Stable for up to 12h continuous use

9 µL/min

0

20

40

60

80

100

3,5 5,7 6,2 8,9 11,7

Yie

ld (

%)


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0

20

40

60

80

100

4 5 6 6 7 8 21 22 24 27 28 30 45 47 47 49 51 53 54 55 56 57 70

Yie

ld (%

)

Time (hours)

62 % Yield

92 % Yield


1.5 equiv 2 equiv


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Step 3 T = 65 oC

100 mg cat

0.35 mL/min Me-THF:IPA,

0.1 M AcOR

0

20

40

60

80

100

20 35 50 65 70

Time (min)

Yie

ld (

%)

Up to 48 % conversion

99% e.e. ROH

95% e.e. AcOR


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R-I

R-II pump-1

pump-2 pump-3

R-III (CALB)

2 equiv.

1 + 1.2 equiv.



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Four consecutive reactions

Three synthetic steps “one-pot”

Metal free synthesis

Five days ToS highly stable.

Final product in high yield

> 98%ee for the (R) acetylated product

R-I

R-II pump-1

pump-2 pump-3

R-III (CALB)

2 equiv.

1 + 1.2 equiv.


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Synthesis of amino alcohols

RCO2OH

H2O2

H2O

RCO2HR'OH +

RCO2R'

Cat-1

Cat-1

R-1

R-2

R-3(1)

O

(2)

Step-1

R''NH2

Cat-2O

(2)

Step-2

R-4

OH

NHR''(3)

Four consecutive reactions

Two synthetic steps “one-pot”

two (Bio)catalytic steps (enz. and chemo)

Potential transfer to flow conditions.

Epoxidation

Ring-opening of epoxide


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Synthesis of amino alcohols- Epoxidation

RCO2OH

H2O2

H2O

RCO2HR'OH +

RCO2R'

Cat-1

Cat-1

R-1

R-2

R-3(1)

O

(2)

Step-1

Step 1: lipase‐mediated epoxidation of cyclohexene

DMC as solvent and source of peroxy acids (residues CO2 and MeOH)


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Synthesis of amino alcohols-

Flow Epoxidation

RCO2OH

H2O2

H2O

RCO2HR'OH +

RCO2R'

Cat-1

Cat-1

R-1

R-2

R-3(1)

O

(2)

Step-1

Stable catalyst for

hydroperoxydation


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Flow Epoxidation

RCO2OH

H2O2

H2O

RCO2HR'OH +

RCO2R'

Cat-1

Cat-1

R-1

R-2

R-3(1)

O

(2)

Step-1

cyclohexene (1equiv.), H2O2 (50%) (2.5

equiv.), dimethyl carbonate (0.1 mmol/mL),

1/8 TFA fix-bed reactor (180 mg),

45 ºC , 5µL/min, 97% of yield was obtained.

same conditions but 1 equiv. of H2O2 (50%),

72% of yield was obtained.

Epoxidation feasible with CALB as catalyst for hydroperoxydation


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Epoxide opening- Flow process

R''NH2

Cat-2O

(2)

Step-2

R-4

OH

NHR''(3)

cyclohexene epoxide (1equiv)

aniline (1equiv) in dimethyl

carbonate (0.25 mmol/mL)

(flow of 7µL/min),

TFA reactor packed with

SILLP-SO3-Sc (264 mg),

at 45 ºC.



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Epoxide opening- Flow process

R''NH2

Cat-2O

(2)

Step-2

R-4

OH

NHR''(3)

0

10

20

30

40

50

60

70

80

90

100

15 h 24 h 39 h 49 h 63 h 66 h 70 h 97 h

yield (%) cyclohexene epoxide (1equiv)

aniline (1equiv) in dimethyl

carbonate (0.25 mmol/mL)

(flow of 10µL/min),

SILLP-SO3-Sc (1g),

at 45 ºC.


Stable for 97 hours of

continuous use


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Coupled flow process

Step 1

Step 2

T = 45 oC

180 mg CALB-SILLP

T = 45 oC

265 mg cat

1 eq. + 1 eq 95 % Yield

0.1 mmol/mL

5µL/min

94 % Yield

0.25 mmol/mL

2µL/min

Up to 94 yield for step 2

Single-pot batch rector, mixing

catalyst and reagents does not

work (one pot two additions)


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RCO2OH

H2O2

H2O

RCO2HR'OH +

RCO2R'

Cat-1

Cat-1

R-1

R-2

R-3(1)

O

(2)

Step-1

R''NH2

Cat-2O

(2)

Step-2

R-4

OH

NHR''(3)

Five consecutive reactions


Three (Bio)catalytic steps (two enz. one chemo)

Possible to transfer to flow conditions.

Enantioselective production of amino alcohol


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Synthesis of amino alcohols-Resolution

Flow Process

Aminoalcohol (0.25 mmol/mL)

(flow of 7µL/min), Novozyme (264 mg),

at 50 ºC.


93 % ee

99 % ee 47% yield

99% ee carbonate

Step 1: aminoalcohol (1 eq),

CAL-B (50 mg), dimethyl

carbonate (1 mL) for 71 h at 50 ºC

and 250 rpm.


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Synthesis of amino alcohols-Resolution

Flow Process

47 % conversion

99 % e.e. ester

97 % e.e. alcohol

Stable 27 hours continuous

use

Enantioselective production of

amino alcohol

0

20

40

60

80

100

0

20

40

60

80

100

5 10 15 20 25

yield

(%)

conv.

e.e.

Time on Stream (hour)

(%)


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Flow Process Step 1

Step 2

T = 45 oC

180 mg CALB-SILLP

T = 45 oC

265 mg cat

1 eq. + 1 eq

95 % yield

0.1 mmol/mL

5µL/min

94 % yield

0.25 mmol/mL

2µL/min

T = 50 oC

500 mg Novozyme 435

3 Step 47% yield, 99% ee carbonate

Five consecutive reactions


Three (Bio)catalytic steps (two enz. one chemo)

Enantioselective production of amino alcohol


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It is possible the immobilisation of ILs onto a support by covalent linking,

transferring the IL properties to the solid phase leading to i.e. monolithic or gel-

type polymer supported ionic liquid phases (SILLPs) minimize the amount of ILs used

avoid toxicological concerns

easy separation and recyclability

mini-flow catalytic reactors for continuous processes in SCFs/green solvents

can be applied to both Chemical Catalysis and Biocatalysis

many potential applications beyond

Conclusion

Cat

A + B C D E F


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Acknowledgements

Dr. Eduardo García-Verdugo

Dr. M. Isabel Burguete

Dr. Belen Altava Dr. Maia Sokolova

Dr. Amrit Puzari

Dr. Naima Karbass

Dr. Victor Sans

Dr. Julian Restrepo

Dr.R. Porcar Dr. D. Izquierdo

S. Marti

S. Montoliu

M. Maciá,

E. Perís

D. Nuevo AND Hanno and Fabien and Milena, Ivan….

Funding:

- Spanish Education and Resarch

Department (Plan Nacional de I+D)

- Generalitat Valenciana

Dr. P. Lozano

University of Murcia

Multicatalytic processes based on Supported Ionic Liquid-Like … · some of them show evidence of...

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