The document discusses direct fluorination reactions in microreactors. It proposes acetylating alcohols prior to fluorination to protect the alcohol group. The fluorination would take place in a microreactor using a gas-liquid system with elemental fluorine and nitrogen. Previous attempts at direct fluorination of alcohols and polyhedral boranes in batch reactors are described. The document outlines characterization techniques that could be used to analyze products from the proposed microreactor fluorination experiments.

1. Jelliarko Palgunadi
a Research Proposal
presented in Dept. of Chemistry,
Freiburg University, Germany

2. Introduction1
• 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.
1. Green chemistry, 5(2003)240

3. Direct fluorination reaction in
microreactors (gas-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

4. Direct fluorination of alcohols, facts
& 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

5. Attempts on the direct fluorination
of alcohols
• Acetylation provides a protecting group for many
tertiary alcohols during AF (aerosol fluorination).9
• Batch direct fluorination of adamantanol.10a,b
F2/N2 NaOH/EtOH
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

6. Proposed acetylation
• Non-solvent acetylation of alcohols catalyzed by
perchloric acid immobilized on silica gel11, (SiO2-HClO4).*
HO R1 AcO R1
SiO2-HClO4 Ac2O or AcCl
Yield 90%
R.T., 0.5 - 2h
* 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
11. Chem. Commun., (2003)1896

7. Direct fluorination of alcohols in a
microreactor
Recycled
OH OH HO R1 R2 OH Protected
R6 wodniw noitavresbO No
R1
R2 R5 Perfluorinated
R3 R4 alcohols ?
OH
HO R1
gimröfsag ,deeF
yes
R3
*
Microreactor (micro bubble)
R1
R2
collected
OH OH F2/N2
R1 R8 Investigation:
R2 R7 •Flow rates
R3 R
4 R5 R6 Non-protected •Solvent effect
•Gradient of fluorine concentration
R1-8 = H, CH3, alkyl... •Gradient of reaction temperature, &
•Recycle process

8. Synthesis of
dodecahydrododecaborate
Scheme 1.12
• Na[B3H8] in diglyme, reflux under nitrogen until colorless, then
diglyme
NaBH4 + I2 Na[B3H8] + NaI + H2
Reflux 100 oC
under N2
Scheme 2.13
• Na[B3H8] treated with concentrated (CH3)3NHCl in water and
cooled to R.T. The solid is separated, dried, and recrystallized
from water-ethyl alcohol to give (Me3NH)2B12H12.
diglyme
NaB3H8 + [HNMe3]Cl [HNMe3]2B12H12 + NaCl
100 oC, under N2
12. Yingyong Huaxue, Chem. Abstr., 15(1998)111.; 13. J. Am. Chem. Soc., 85(1963)3885

9. Attempts on the fluorination of
dodecahydrododecaborate
• Scheme 1.14
Supercritical HF
Cs2B12H12 Cs2B12F12 (38% yield)
550 oC, 5h
Batch reactor, high press. & high temp. reaction.
• Scheme 2.15
in L-AHF*
K2B12H12 K2B12H8F4
70 oC, 14h
20% F2/N2
K2B12H8F4 K2B12F12 (72% yield)
20 oC, 72h
Batch reactor, two steps reaction.
* L-AHF = liquid anhydrous HF
14. Koord. Khim., 18(1992)340.; 15. J. Am. Chem. Soc., 125(2003)4694

10. Direct fluorination of polyhedral
borane
Direct fluorination of
polyhedral borane
Batch Continuous
millireactor microreactor
High/low temp. Non-corrosive Low temp. Non-corrosive
L-AHF medium reaction media L-AHF medium reaction media

11. 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

12. Product isolation, characterization
& quantification
Crude
quantification Identification product
GC or GC/MS collection
Isolation & Fractional
purification distillation
NMR
1H,13C,11B HF removal
Product Adsorption on
Heating at HF b.p.
Boiling point dried NaF
high low
Isolation &
purification
Water(-organic) Column chrom. Fractional Recrystall.
multi steps extraction separation distillation
Target product stored
drying
Isolation
• Depending the nature of target products (i.e. boiling points) and size of product quantity.
• Essentially, HF removal from product mix