Carbonate based ionic liquids Carbonate based ionic liquids and beyond and beyond

(1)

Carbonate based ionic liquids

and beyond

Alvise Perosa

Today

Today’s

’s

outline

1. 1. Synthesis

Synthesis of

of carbonate

carbonate ionic

ionic liquids

liquids

2. 2. Organocatalysis

Organocatalysis

2.1

2.1 Carbon

Carbon--Carbon

Carbon bond

bond

2.2

2.2 Transesterification

Transesterification

3. 3. Multiphase

Multiphase systems

systems

4. 4. Luminiescent

Luminiescent ionic

ionic liquids

liquids

5.

(2)

1. 1. Syntheses

Syntheses of

of ionic

ionic liquids

liquids

1. 1. QUATERNARISATION REACTION:

QUATERNARISATION REACTION:

Amines

Amines/Phosphines

/Phosphines

Amonium

Amonium/Phosphonium

/Phosphonium

1. 1. DIMETHYLCARBONATE

DIMETHYLCARBONATE as

as methylating

methylating reagent

reagent::

DMC

Ionic liquids synthesis, our toolbox

(3)

Why

Why use

use dimethylcarbonate?

dimethylcarbonate?

O

S

O

CH

3

H

3

C

DMC Dimethylsulfate (DMS) Methyl iodide

H

3

C

I

δ+

O

CH

3

H

3

C

δ+

Dimethylcarbonate,

Dimethylcarbonate, its

its syntheses

syntheses

MeO H

cat 1

(4)

Dimethylcarbonate,

methylation reactivity

CH

₃

O

CH

3

O

NuCH

3

+ CH

3

OH + CO

2

NuH

Dimethylcarbonate

Dimethylsulfate

2NuCH

3

+ H

2

SO

4

2NuH

O

Si

O

CH

₃

H

3

C

catalyst

For

For more on

more on dimethylcarbonate

dimethylcarbonate

… or poster no. 57!

You might have

You might have visisted

visisted

poster no. 56!

Jess Stanley

(5)

“

“Parent

Parent”

” Ionic

Ionic liquids

liquids:

:

Amines

Amines//phosphines

phosphines +

+ dimethylcarbonate

dimethylcarbonate

R N

+

R

CH

3-

_O

_OCH

3

O

R P

+

R

CH

3-

_O

_OCH

3

O

100%

Conditions: 140 °C, 20 h, some methanol

Workup: remove volatiles

Perosa et al. Chem. Eur. J. 2009, 15, 12273;

“

“Offspring

Offspring”

” ionic

ionic liquids

liquids::

by

by anion

anion exchange

exchange

R P

+

R

CH

₃

-O

OCH

3

O

R P

+

R

CH

₃

-O

OCH

3

O

H

2

O

H-X

R

P

+

R

CH

₃

-O

OH

O

+ CH

3

OH

R P

+

R

CH

3

X

+ CO

2

+ CH

3

OH

100%

Conditions: RT, 5 - 60 minutes, no solvent

Workup: remove methanol

(6)

With

With MW

MW irradiation

irradiation as

as well…

well…

Rogers et al. Green Chem. 2010, 12, 407;

Imidazolium

Imidazolium methylcarbonate

methylcarbonate

N

O

+

N

O

N

O

+

(7)

Some

Some recent

recent examples

examples::

[N

8,8,8,1

]

SO

₃

-NH

₂

O

-O

[P

_8,8,8,1

]

[P

_8,8,8,1

]

[P

_8,8,8,1

]

[P

8,8,8,1

]

O

[P

8,8,8,1

]

Manuela

Manuela Facchin

Facchin

P

i4,i4,i4,1

P

4,4,4,1

P

6,6,6,1

P

8,8,8,1

N

6,6,6,1

N

8,8,8,1

N

8,1,1,1

OCOOCH

3

*

HOCOO

NO

3

Halides

TosO

PhO

CF

3

COO

CH

3

COO

NTf

2

Anthranilate

HPO

3

Dicyanomethanide

4-nitrobenzoate

In

In summary

summary::

(8)

Cation

Anion

[P

8,8,8,1

]

[N

8,8,8,1

]

(-)Menthylcarbonate*

1-Phenyl ethyl carbonate*

(-)-Menthyloxyacetate

(+)Camphor-10-sulfonate

L-Phenylalaninate

L-Valinate

*not isolated

Chiral

Chiral ionic

ionic liquids

liquids::

Truly green synthesis…

“SIMPLE, EFFICIENT, & SAFE”

Clean

100% yields, 100% purity, 100% atom economy

one step

halide-free

some methanol as solvent

use of green reagents

no workup

no by-products

Modular

not limited to one target product

make whole classes of compounds

tune properties

Clear and robust materials

(Relatively) large volumes

(9)

1

_H-NMR

Neat 60

°

C

17 Dibenzoylmethanate

Dibenzoylmethanate

1

_H-NMR

Neat, 60

°

_C

2 2--Thenoyltrifluoroacetonate

Thenoyltrifluoroacetonate

(10)

Nitroethanoate

Nitroethanoate IL

IL

Nitromethane disappears

WHAT WE OBSERVED

WHAT WE OBSERVED::

•• the

the methylcarbonate

methylcarbonate anion slowly disappeared;

anion slowly disappeared;

•• nitroethane

nitroethane was converted 100%;

was converted 100%;

(11)

We

We hypothesised

hypothesised an

an

α

--elimation

elimation--rearrangement

rearrangement of

of

nitroethane

nitroethane to

to yield

yield the nitrite

the nitrite anion

anion and

and ethylene

ethylene::

NO

2 O

O

NO

2 CO

2 CH

3 OH

Zimmerman, H. E.; Munch, J. H.,. Journal of the American Chemical Society 1968, 90 (1), 187-196.

Further observations:

•• Griess

Griess test was certainly positive for

test was certainly positive for

nitrite: NO

₂

•• conflicting evidence for the presence of

conflicting evidence for the presence of

ethylene (GC

(12)

…

… so

so we

we read

read the

the literature

literature::

NO

₂

H

₃

C

OH

N

H

₃

C

OH

N

O

H

3

C

N

O

H

3

C

OH

N

O

H

3

C

O

H

+

…

… still

still wondering

wondering what

what happens

happens..

Can. J. Chem. 1969, 47, 3107; J. Am. Chem. Soc. 1940, 62, 2604; J. Chem. Soc. 1900, 77, 1262; J. Chem. Soc. 1891, 59, 410

…but, it appears we have a route to nitrite ILs

(13)

2. 2. Organocatalysis

Organocatalysis

2.1 2.1 Carbon

Carbon--Carbon

Carbon Bond

Bond

IL

IL organo

organo--catalyst

catalyst

P

(14)

The first

The first hint

hint

Conditions: room temperature, no solvent, 0.4%

P

_8,8,8,1

MC

Michael reaction

A

A second

second hint

hint: Henry

: Henry Reaction

Reaction

0 20 40 60 80 100 120 140 160 180 200 0 20 40 60 80 100 pKa=24,34 pKa=20,84 pKa=18,82 % n it ro a ld o l Time (min) DBU (C8H17)3P + CH3 -OCOOH (C8H17)3P + CH3 -OCOOCH3 PhTMG NEt3 DMAP pKa=17,95

NO

₂

+

0,5 M in CDCl

₃

, Nitroethane 5 equiv., 25°C

Catalyst:aldehyde ratio = 5%

O

OH

NO

2

catalyst

(15)

A

A second

second hint

hint: Henry

: Henry Reaction

Reaction

M. Fabris, M. Noè, A. Perosa, M. Selva, R. Ballini J. Org. Chem. 2012, 77, 1805

Aldehyde

R

time (h)

Nitroaldol product

(%, by NMR)

Y (%)

b

CH

2

CH

2

Ph

2

96

88 CH(CH

3

)Ph

2

96

93 C

2

H

5

2

93

90 C

10

H

21

2

99

97 4-NO

2

C

6

H

4

2

95

91 4-ClC

6

H

4

3

82

71 C

6

H

5

2

35

35 T = 25

°

C

R

_O

+

NO

2

_R

OH

NO

2

[P

8,8,8,1

][CH

3

COO]

The

The third

third hint

hint

Baylis

(16)

Accepted

Accepted Baylis

Baylis--Hillman

Hillman

reaction

reaction mechanism

mechanism

So,

So, why

why does

does P

P

_8,8,8,1

MC

MC behave

behave as

as a

a

strong base/nucleophile?

Probably

Probably not

not just due

just due to

to the

the pKa

pKa

N (Anion) pKa E (Cation) rate h-1 MeOCO2− 5.51 P8,8,8,1 12.60 Br− -4.9 P8,8,8,1 0.00 P1-tBu 26.98 - 9.37 DBU 24.34 - 1.48

Initial rates of conversion of cyclohexenone to the dimer in the presence of different nucleophilic N and electrophilic catalyst E.

Baylis

(17)

There

There must

must be

be something

something else

else going

going on …

on …

Maybe

Maybe activation

activation by

by the cation?

the cation?

To

To look at

look at this

this we

we decided

decided to

to “separate” the

“separate” the effect

effect of

of the

the

anion

anion (N)

(N) from

from the

the effect

effect of

of the cation (E):

the cation (E):

we

we used

used DBU

DBU as

as the nucleophile (N)…

the nucleophile (N)…

… and

… and added

added increasing

increasing amounts

amounts of

of P

P

8,8,8,1

Br

--N (Anion) pKa E (Cation) rate h-1 MeOCO2− 5.51 P8,8,8,1 12.60 Br− -4.9 P8,8,8,1 0.00 P1-tBu 26.98 - 9.37 DBU 24.34 - 1.48

Initial rates of conversion of cyclohexenone to the dimer in the presence of different nucleophilic N and electrophilic catalyst E. 0 1 2 3 4 5 6 7 8 9 0,0 0,2 0,4 0,6 0,8 1,0 1,2 1,4 1,6 N E {E}/{N} rate h−1 {N} {E} Br− 0.015 P8,8,8,1 0.015 1.00 0.00

Added

Added amounts

amounts of

of P

P

_8,8,8,1

Br

--DBU by itself

ra

te

Increasing amounts of

P

8,8,8,1

Br

(18)

Ambiphilic

Ambiphilic activation

activation?

?

Electrophile

Nucleophile

V.Lucchini, M. Noe` , M. Selva, M. Fabris A. Perosa Chem. Commun., 2012, 48, 5178

Deconvolution

(19)

Precedents...

H. Schmidbaur, W. Buchner, F. H. Köhler, J. Am. Chem. Soc., 1974, 96, 6208-6210

J. McNulty, J. Dick, V. Larichev, A. Capretta, A. J. Robertson, Lett. Org. Chem., 2004, 1, 137-139

…

… hypotheses

hypotheses without

without experimental

experimental proof

proof..

Interesting application...

H N N4,4,4 O O O CH3 H3C + + N CH3

Continuous flow microwave N4,4,4,1 O O OCH3 H N O O O CH3 H3C +

(20)

2. 2. Organocatalysis

Organocatalysis

2.2 2.2 Transesterification

Transesterification

Alessio Caretto

Jess Stanley

Transesterification

Transesterification of organic

of organic

carbonates.

O

H

₃

C

O

+

R

-OH

CH

3

ILs cat

90-240 °C

O

H

3

C

_O

O

R

R-OH =

95-98%

+ CH

₃

OH

HO

No

(21)

Transesterification

Transesterification of organic

of organic

carbonates.

O

H

3

C

_O

O

CH

3

IL 1%

200 °C

O

H

3

C

_O

O

99%

+ CH

₃

OH

HO

+

Catalyst

Conversion (%)

Selectivity (%)

[P

8881

][CH

3 OCOO]

52 >99

[P

₈₈₈₁

][HOCOO]

68 [P

₈₈₈₁

][AcO]

93 [P

8881

][PhO]

78

M. Selva, M. Noè, A.Perosa, M. Gottardo Org. Biomol. Chem., 2012, 10, 6569

Transesterification

Transesterification of organic

of organic

carbonates.

OH OH HO Ph Ph OH Ph Ph OH Ph O O OCH3 H3C O O O O O O O O O (1 mol%) Ph Ph Ph Ph OMe Ph 90-220 °C 220 °C (10 mol%) 90 o_C 200 oC 220 o_C [P8881] [AcO] [P8881] [AcO]

(22)

Transesterification

Transesterification of organic

of organic

carbonates.

M. Selva, M. Noè, A.Perosa, M. Gottardo Org. Biomol. Chem., 2012, 10, 6569

O O OCH3 H3C O O CH3 [P8881] O O O CH3 CH3 O O OCH3 [P 8 8 8 1_] OH R HO O CH3 [P8881] + electrophilic activation nucleophilic activation O O OR H3C NAcS + [P8881] OCH3 CH3OH RO O C O

Transesterification

(23)

1,2 diols

1,3 diols

1,4 diols

1,6 diols

1,1

1h

1,2

-2,2

-2,3

- - -OH OH R R

Transesterification

Transesterification of

of diols

diols

0 50 100 150 200 250 300 350 400 0 20 40 60 80 100 % time (min) 1e 2e 3e 0 50 100 150 200 250 300 350 400 0 20 40 60 80 100 % time (min) 1e 2e 3e 0 50 100 150 200 250 300 350 400 0 20 40 60 80 100 % time (min) 1e 2e 3e

DMC : diol = 20 : 1

DMC : diol = 5 : 1

DMC : diol = 2 : 1

OH

O

OOH O O

Transesterification

(24)

Main

Product

Isolation

Purity %

Yield %

> 99%

90%

73%

68%

Distillation

Sublimation

Distillation

> 99%

70%

mixture

-

-Transesterification

Transesterification of

of diols

diols

C

h

a

in

le

n

g

h

t

e

ff

e

c

t

Steric hindrance effect

cyclic

carbonate

linear

carbonate

Transesterification

(25)

3. 3. Multiphase

Multiphase systems

systems

based

based on

on ionic

ionic liquids

liquids

Marina Gottardo

Multiphase

(26)

Multiphase

Multiphase systems

systems based

based on

on ILs

ILs

no IL

IL = [N

_8,8,8,1

][Cl]

org

H

2 O

H

2 O

IL + cat

Multiphase

Multiphase systems

systems based

based on

on ILs

ILs

applied

applied to

to the upgrade

the upgrade of

of bio

bio--based

based molecules

molecules

O

OH

O

OH

O

_H

2

O

H

2

γ

-Hydroxyvaleric acid

γ

-Valerolactone (GVL)

Levulinic Acid

heterogeneous catalyst

Catalyst:

(27)

Strategy

Strategy for

for multiphase

multiphase system design

system design

.

org

H

2

O

IL + cat

1. Choose organic solvent

2. Choose ionic liquid

Solvent

LA

solubility

GVL

solubility

Solubility in water @ 20°C

Iso-octane

no

immiscible

Cyclohexane

no

immiscible

Toluene

yes

0.52 g/L

Ethyl acetate

yes

0.83 g/L

Ethyl lactate

yes

miscible

Acetonitrile

yes

miscible

water

yes

miscible

Multiphase

Multiphase system design:

system design:

Organic

Organic solvent

solvent choice

choice

IL = [N

8,8,8,1

][Cl]

org

H

₂

O

IL + cat

O O

(28)

“Inverse”

“Inverse” multiphase

multiphase system

system

But… [N

_8,8,8,1

][Cl] is partially soluble in water….

IL = [N

8,8,8,1

][Cl]

i-octane

H

₂

O

IL

Levulinic acid and GVL

O OH O H2O O O γ-Valerolactone (GVL) Levulinic Acid

Multiphase

Multiphase system design:

system design:

Choice

Choice of

of IL

IL

i-octane

H

₂

O

IL

LA

Conversion

IL in H

2

O

(%, wt)

[N

8,8,8,1

][Cl]

32 2-3

[N

8,8,8,1

][NTf

2

]

100 not measurable

[P

8,8,8,1

][NTf

2

]

100 not measurable

[N

8,8,8,1

][TFA]

100

41 [P

8,8,8,1

][NO

3

]

100

17

O OH O H2O O O γ-Valerolactone (GVL) Levulinic Acid

(29)

Multiphase

Multiphase system

system

i-octane

H

₂

O

P

8,8,8,1

NTf

2 20 30 40 50 60 70 80 90 100 110 120 0 20 40 60 80 100

L

A

c

o

n

v

.

(%

1

H

-N

M

R

)

T (°C)

no IL [P 8,8,8,1][Ntf2]

Conversion of LA to GVL in the multiphase system with 5% Ru/C as a function of temperature after 30 min: (∆) without the IL third phase; ( ) with a third phase made by [P8,8,8,1][NTf2]. p[H2] = 35 bar, Ru 0.15 mol%, O OH O H2O O O γ-Valerolactone (GVL) Levulinic Acid

Multiphase

Multiphase system

system

i-octane

H

₂

O

P

8,8,8,1

NTf

2 0 1 2 3 4 5 6 7 8 0 20 40 60 80 100

L

A

c

o

n

v

.

(%

1

H

-N

M

R

)

Recycles

(30)

Same

Same thing

thing with

with homegenous

homegenous RuCl

RuCl

₃

O OH O H2O O O γ-Valerolactone (GVL) Levulinic Acid 0 1 2 3 4 5 6 0 20 40 60 80 100

L

A

c

o

n

v

.

(%

b

y

1

H

-N

M

R

)

Recycles

Conversion of LA to GVL: recycling of the RuCl3catalyst system {Conditions: 16 h, 150 °C, p[H2] = 35 bar, RuCl3(20 mg, 0.0765 mmol; Ru = 1.0 mol%)