Microreactors for elemental fluorine

Article abstract of DOI:10.1039/a901473j

A microreactor has been designed for use with elemental fluorine, both for selective fluorination and for perfluorination of organic compounds.

Full text of DOI:10.1039/a901473j

Microreactors for elemental fluorine
Richard D. Chambers and Robert C. H. Spink
University of Durham, Department of Chemistry, South Road, Durham, UK DH1 3LE.
E-mail: r.d.chambers@durham.ac.uk.
Received (in Liverpool, UK) 18th January 1999, Accepted 29th March 1999
A microreactor has been designed for use with elemental
fluorine, both for selective fluorination and for perfluorina-
tion of organic compounds.
term is intended to indicate that the liquid forms an outer
cylinder, coating the reactor surface, with the gas flowing
through the centre) as opposed to slug flow (alternate slugs of
liquid and gas), which might have been anticipated. Indeed, the
former provides enormous advantages in that it provides very
large surface to volume ratios for the liquid phase, which is
highly beneficial for efficient reaction over a short distance in
the reactor. There is also excellent mixing and very effective
opportunities for heat control, through the cooling channels
indicated. Furthermore, a surprisingly large through-put for
such a small channel is possible, e.g. 0.5–5 ml h21 have been
used routinely.
Products were trapped out in a half inch diameter FEP tube,
cooled by either a salt–ice bath or an acetone–carbon dioxide
slush bath. Residual gases were scrubbed in a soda-lime tower
and any dissolved hydrogen fluoride was removed by either
adding sodium fluoride to the product mixture or washing with
water.
Interest in the use of elemental fluorine directly, for the
synthesis of fluorine-containing organic compounds, has in-
creased dramatically in the last few years,1–3 but scale-up will
always present problems of safe handling and temperature
control, for some of the most exothermic reactions in organic
chemistry.
There is currently much interest in the development of
microreactors for chemical processing,4 because the benefits
would include arithmetic scale-up from the performance of a
single reactor to a theoretically unlimited number. Also, in
principle, this scale-up could be achieved by the techniques of
the electronics industry.
Microreactors have considerable attraction for application to
direct fluorination processes because there is (i) a small
inventory of fluorine in the reaction zone, (ii) opportunity for
good mixing and temperature control, and (iii) simple scale-up.
However, prior to this work, there was little knowledge
available on the practicability of this approach.
Using this system, we have successfully carried out various
selective fluorinations, as shown in Schemes 1 and 2. Sulfur
pentafluoride derivatives are of considerable interest5 and
After much development, we have now designed a simple
micro-reactor, fabricated from a block of nickel (or copper),
from which we have cut a groove as the micro-reactor; the
design is indicated in Fig. 1, where the seal is provided by a
block of polychlorotrifluoroethene, which also enables direct
viewing of the reaction zone. Reactants and solvent were
injected via a syringe and syringe-pump, while fluorine in
nitrogen was introduced directly from a small cylinder via a
mass-flow controller. Using this technique, all of the liquid–gas
mixing that we carried out proceeded via cylindrical flow (the
S
S
SF5
i
NO2
NO2
NO2
1
2 75%
SF3
SF5
i
NO2
NO2
3
4 44%
Scheme 1 Reagents and conditions: i, MeCN (5 ml h21), 10% F2 in N2 (10
ml min21), room temp.
O
O
O
O
i
OEt
OEt
99% Conversion
F
6 73%
5
O
O
O
O
ii
OEt
OEt
F
90% Conversion
Cl
Cl
7
8 62%
Scheme 2 Reagents and conditions: i, 10% F2 in N2 (10 ml min21), 5 °C,
HCO2H (0.5 ml h21); ii, 10% F2 in N2 (10 ml min21), 5 °C, HCO2H
(0.25 ml h21).
Fig. 1 Microreactor top and side view.
Chem. Commun., 1999, 883–884
883

O
F
O
However, while bulk fluorination of ethyl 2-chloroacetoacetate
7 gives only low conversion to 8,6 the flow system is clearly
efficient and the fluorinated metal surface obviously promotes
the formation of enol.
RF
RF
RHF
RFH
i, ii
52% Recovery
9
10 91%
We have also demonstrated that the technique can be used for
perfluorination. In this case, however, we need an additional
heated stage to complete the reaction and this is connected
simply to the outlet of the reactor. Results are shown in Scheme
3 and there is no reason why these otherwise hazardous
procedures could not be scaled up with safety. Traditionally,
cobalt trifluoride (obtained using elemental fluorine) is used in
industry to perfluorinate hydrocarbons, but for some of the
examples shown here, the temperature required for perfluorina-
tion with elemental fluorine is significantly lower than that
required for perfluorination using cobalt trifluoride.7
These experiments illustrate the significant potential for this
approach to the use of elemental fluorine, both in the laboratory
and at the industrial scale.
RFH
RF
iii–v
F
82% Recovery
RFH
RF
12 70%
11
RFH = CF2CFHCF3
RF = CF2CF2CF3
Scheme 3 Reagents and conditions: i, 0.5 ml h21, 50% F2 in N2 (15
ml min21), room temp.; ii, 0.5 ml h21, 50% F2 in N2 (15 ml min21), room
temp. then 280 °C; iii, 0.5 ml h21, 20% F2 in N2 (20 ml min21), room temp.;
iv, 0.5 ml h21, 50% F2 in N2 (10 ml min21), room temp. then 50 °C; v, 0.5
ml h21, 50% F2 in N2 (15 ml min21) room temp. then 280 °C.
We acknowledge financial support from BNFL.
Notes and references
fluorination can be achieved directly from the di(m-nitrophenyl)
disluphide 1. However, for the p-nitro system 3, due to its very
low solubility in MeCN, preliminary fluorination (in bulk) to
produce soluble trifluorides was performed and then the more
difficult fluorination to pentafluorides was carried out in the
microreactor.
Fluorination of b-dicarbonyl compounds proceeded with
high efficiency and, moreover, these reactions demonstrated
clearly a catalytic effect by the fluorinated metal surface.
Fluorination is usually limited by either the concentration of
enol, at equilibrium, or the rate constant for forming the enol.
1 J. Hutchinson and G. Sandford, Top. Curr. Chem., 1997, 193, 1.
2 S. Rozen, Acc. Chem. Res., 1996, 21, 307.
3 S. T. Purrington, B. S. Kagen and T. B. Patrick, Chem. Rev., 1986, 86,
997.
4 A. Green, Chem. Ind. (London), 1998, 168.
5 WO 9705,106 (Chem. Abstr., 1997, 126, 199340)
6 R. D. Chambers, M. P. Greenhall and J. Hutchinson, Tetrahedron, 1996,
52, 1.
7 R. D. Chambers, B. Grievson, F. G. Drakesmith and R. L. Powell,
J. Fluorine Chem., 1985, 29, 323.
Communication 9/01473J
884
Chem. Commun., 1999, 883–884