JelliarkoJelliarko PalgunadiPalgunadi

a Research Proposala Research Proposal

presented in Dept. of Chemistry, presented in Dept. of Chemistry,

FreiburgFreiburg University, GermanyUniversity, Germany

IntroductionIntroduction11

1. Green chemistry, 5(2003)240

• Direct fluorination reaction of organic compound is difficult associated with the safety of elemental fluorine and the reaction is extremely exothermic.

• Microreactor in principle is a reactor which is designed and fabricated to perform a micro-scale reaction mimicking a large-scale conventional reaction.

• Microreactor is found to have more benefits than conventional large reactor, i.e. large surface-to-volume ratio, comfortable to handle dangerous reactions (i.e. exothermic), scale-up by multiple apparatus, easy to control the reaction parameters etc.

Direct fluorination reaction in Direct fluorination reaction in

microreactorsmicroreactors (gas(gas--liquid contact)liquid contact)

• Microreactor for elemental fluorine.2

• Gas–liquid thin film microreactors for selective direct fluorination3

• Direct fluorination of toluene using elemental fluorine in gas/liquid microreactors.4

• Selective direct fluorination of 1,3-ketoesters and 1,3-diketones using gas/liquid microreactor technology.5

2. Chem. Commun.,(1999)883; 3. Lab on a Chip,1(2001)132;4. J. Of fluorine Chemistry,105(2000)117; 5. Lab on a Chip,5(2005)1132

Direct fluorination of alcohols, facts Direct fluorination of alcohols, facts

& figures& figures

• Direct fluorination using a four-zone cryogenic reactor, from - 120 oC to room temp.6

• There is a potential reaction between alcohol site and HF to produce unstable hypofluorite.7

• The –OH site is essentially protected by inert protective agent. (acetylation, i.e. perfluoroacyl fluoride in the PERFECT reaction developed by Asahi Glass).8

6. J. Chem. Soc. Perkin Trans.,1(1991)871; 7. J.Am.Chem.Soc.,87(1965)230;8. Adv.Synth.Catal.,343(2001)215

• Acetylation provides a protecting group for many tertiary alcohols during AF (aerosol fluorination).9

• Batch direct fluorination of adamantanol.10a,b

9. J.Org.Chem.,61(1996)5073; 10a. J.Org.Chem.,60(1995)1999;10b. Abstracts of 14th European Symposium on fluorine Chemistry, 2004, Poland

NaOH/EtOHF2/N2

Attempts on the direct fluorination Attempts on the direct fluorination

of alcoholsof alcohols

Proposed acetylationProposed acetylation

• Non-solvent acetylation of alcohols catalyzed by perchloric acid immobilized on silica gel11, (SiO2-HClO4).*

11. Chem. Commun., (2003)1896

R1HO

Ac2O or AcCl

R.T., 0.5 - 2h

R1AcO

SiO2-HClO4

* SiO2-HCLO4 is prepared by treated SiO2 with 70% solution of HCLO4 and concentrated to get the residue, followed by heating to 100 oC under vacuum

Yield 90%

Protected

Non-protected

OH OH

R7

R8R1

R2

R4R3 R5

R6

HO OHR1 R2

OH

*

R1R2

R3

OH OH

R5

R6

R2

R1

R3 R4

R1HO

R1-8 = H, CH3, alkyl...

Feed, gasförmig

Observation window

Feed, gasförmig Feed, gasförmig

Observation window

F2/N2

Microreactor (micro bubble)

Direct fluorination of alcohols in a Direct fluorination of alcohols in a

microreactormicroreactor

Investigation:•Flow rates•Solvent effect•Gradient of fluorine concentration•Gradient of reaction temperature, &•Recycle process

Recycled

collected

Perfluorinatedalcohols ?

yes

No

Synthesis of Synthesis of

dodecahydrododecaboratedodecahydrododecaborate

Scheme 1.12

• Na[B3H8] in diglyme, reflux under nitrogen until colorless, then

Scheme 2.13

• Na[B3H8] treated with concentrated (CH3)3NHCl in water and cooled to R.T. The solid is separated, dried, and recrystallizedfrom water-ethyl alcohol to give (Me3NH)2B12H12.

12. Yingyong Huaxue, Chem. Abstr., 15(1998)111.; 13. J. Am. Chem. Soc., 85(1963)3885

Reflux 100 oCunder N2

NaBH4 + I2 Na[B3H8] + NaI + H2

diglyme

NaB3H8 + [HNMe3]Cl [HNMe3]2B12H12 + NaCldiglyme

100 oC, under N2

Attempts on the fluorination of Attempts on the fluorination of

dodecahydrododecaboratedodecahydrododecaborate

• Scheme 1.14

Batch reactor, high press. & high temp. reaction.

• Scheme 2.15

Batch reactor, two steps reaction.

14. Koord. Khim., 18(1992)340.; 15. J. Am. Chem. Soc., 125(2003)4694

Cs2B12H12 Cs2B12F12 (38% yield)

Supercritical HF

550 oC, 5h

K2B12H12 K2B12H8F4

in L-AHF*

70 oC, 14h

K2B12H8F4K2B12F12 (72% yield)

20% F2/N2

20 oC, 72h

* L-AHF = liquid anhydrous HF

Direct fluorination of polyhedral Direct fluorination of polyhedral

boraneborane

Direct fluorination of polyhedral borane

Non-corrosive reaction media

Batch millireactor

Continuous microreactor

Low temp.L-AHF medium

Non-corrosive reaction media

High/low temp.L-AHF medium

Benchmark study (batch reactor)Benchmark study (batch reactor)

Conventional batch fluorination system (constructed from stainless steel)16

1. F2/N2 mixture 2. N2 flushing gas 3. Flow checker 4. Liquid sampler

5. Parr Reactor (100 mL) 6. Stirrer 7. Dry F2 scrubber (Al2O3 or soda lime)

8. Wet F2 scrubber (5% KOH sol’n) 9. Gas sampler

16. Reaction Media Research Center, KIST, 2005

Product isolation, characterization Product isolation, characterization

& quantification& quantification

Isolation• Depending the nature of target products (i.e. boiling points) and size of product quantity.• Essentially, HF removal from product mix

Heating at HF b.p.

Crude product

Adsorption ondried NaF

Product Boiling point

low

HF removal

Fractional distillation

Water(-organic)multi steps extraction

collection

Target productdrying

Column chrom. separation

Fractional distillation

Recrystall.

GC or GC/MS

NMR1H,13C,11B

Isolation & purification

Identificationquantification

Isolation & purification

stored

high