A new synthesis of pentafluorosulfanylbenzene

Article abstract of DOI:10.1021/ol0491991

(Equation Presented) A new and convenient three-step synthesis of pentafluorosulfanylbenzene from 1,4-cyclohexadiene with an overall yield of >70% is reported along with a number of derivatization reactions.

Full text of DOI:10.1021/ol0491991

ORGANIC
LETTERS
2004
Vol. 6, No. 14
2417-2419
A New Synthesis of
Pentafluorosulfanylbenzene
Tatiana A. Sergeeva and William R. Dolbier, Jr.*
Department of Chemistry, UniVersity of Florida, GainesVille, Florida 32611
wrd@chem.ufl.edu
Received April 30, 2004
ABSTRACT
A new and convenient three-step synthesis of pentafluorosulfanylbenzene from 1,4-cyclohexadiene with an overall yield of >70% is reported
along with a number of derivatization reactions.
Interest in the chemistry of aromatic pentafluorosulfanyl
compounds was briefly ignited in 1960 when Sheppard
reported the first low yield synthesis of pentafluorosulfanyl-
benzene (1) via the reaction of aryl disulfides or aryl sulfur
trifluorides with silver difluoride at 120 °C.1 Sheppard’s
process was better suited for preparation of 3- and 4-nitro-
pentafluorosulfanylbenzenes, which were prepared in 30%
yield. In this initial report, the first examples of reactions of
the 1990s, when Sheppard’s AgF2 method was elaborated
and improved upon by Thrasher to prepare ortho-substituted
pentafluorosulfanylbenzenes7 and a new direct fluorination
method was developed by Bowden and Greenhall of F2
Chemicals for conversion of 3- and 4-nitrophenyl disulfides
to the respective SF5 nitrobenzenes.8-10 However, since
Sheppard’s original report, there have been only two other
methods reported for the preparation of the parent compound
1. Hoover and Coffman were able to take advantage of the
addition of pentafluorosulfanylacetylene (itself a challenging
compound to make) to butadiene to make 1,11 whereas Ou
and Janzen found that XeF2 was a sufficiently strong
fluorinating agent to convert phenyl disulfide to penta-
fluorosulfanylbenzene, although again in but a modest, 25%
yield.12
1 were provided, including electrophilic aromatic substitution
reactions, Sandmeyer chemistry, and Grignard chemistry.
After a brief flurry of activity, mostly involving the reporting
of physical and spectroscopic properties of 1 and some of
its derivatives,2-6 there ensued a period of little activity
related to pentafluorosulfanylbenzene and its derivatives until
(1) Sheppard, W. A. J. Am. Chem. Soc. 1962, 84, 3064-3072.
(2) Sheppard, W. A. J. Am. Chem. Soc. 1962, 84, 3072-3076.
(3) Brownlee, R. T. C.; Hutchinson, R. E. J.; Katritzky, A. R.; Tidwell,
T. T.; Topsom, R. D. J. Am. Chem. Soc. 1968, 90, 1757-1767.
(4) Brownlee, R. T. C.; English, P. J. Q.; Katritzky, A. R.; Topsom, R.
D. J. Phys. Chem. 1969, 73, 557-564.
Thus, until the present work, there existed no satisfactory
general procedure for synthesis of pentafluorosulfanyl-
(5) Chawla, B.; Pollack, S. K.; Lebrilla, C. B.; Kamlet, M. J.; Taft, R.
W. J. Am. Chem. Soc. 1981, 103, 6924-6930.
(6) Eaton, D. R.; Sheppard, W. A. J. Am. Chem. Soc. 1963, 85, 1310-
1313.
(7) Sipyagin, A. M.; Bateman, C. P.; Tan, Y.-T.; Thrasher, J. S. J.
Fluorine Chem. 2001, 112, 287-295.
10.1021/ol0491991 CCC: $27.50 © 2004 American Chemical Society
Published on Web 06/08/2004

benzene in decent yield from readily available starting
materials, in particular, without the use of highly energetic
reagents. In the meantime, considerable interest in penta-
fluorosulfanyl aromatics emerged during the 1990s within
the agrochemical and pharmaceutical industries,13,14 as
witnessed by a surge in related patent applications. The
Bowden/Greenhill work particularly served to bolster this
interest.8,10
After our recent discovery of a simple, benchtop procedure
for carrying out the addition of SF5Cl to alkenes and
alkynes,15 we sought to find a way to utilize this chemistry
in the synthesis of pentafluorosulfanylbenzene. In the end,
our successful strategy involved the three step conversion
of readily available 1,4-cyclohexadiene to pentafluoro-
sulfanylbenzene in an overall yield of >70%.16,17 Experi-
mental details for all three steps may be found in the
Supporting Information.
alkenes have been prepared by 1,2-elimination of hydrogen
chloride using K2CO3 in acetone, KOH in aqueous or H2O/
i-PrOH media, or a KOH-diethyl ether system. In our
particular case, treatment of the compound 3 with a large
(up to 12-15-fold) excess of potassium hydroxide in ether
did lead to 1, but in only a modest, 45-50% yield, even
after a prolonged reaction time (up to 3 days). The best
results were achieved using sodium ethoxide. Treatment of
3 with 1.5 M sodium ethoxide (7.5 equiv) led to formation
of 1 in a yield of 79%. Initially, the reaction was carried out
overnight, but it was found that only a few minutes at room
temperature were sufficient for the reaction to be complete.
The pentafluorsulfanylbenzene obtained in this manner is
sufficiently pure to be used directly in the following reactions
to prepare derivatives.
The pentafluorosulfanyl substituent is a powerful de-
activating and thus meta-directing group with respect to
electrophilic aromatic substitution, as was demonstrated by
Sheppard in 1960. Indeed, we found that our earlier method
for bromination of highly deactivated benzenes23 was also
effective for conversion of 1 to its 3-bromo derivative.
1,4-Cyclohexadiene was easily transformed into 4,5-
dichlorocyclohexene, 2,18 via its essentially quantitative
reaction with SO2Cl2 in CCl4 at room temperature. This was
followed by the key step in the synthesis, which was the
introduction of the SF5 group via the high yield, Et3B-
catalyzed addition of SF5Cl to 2 at -20 °C. To obtain the
reported high yield, it was essential that a longer reaction
time and larger (3.5-fold) excess of SF5Cl be used for this
addition, in comparison to the conditions that were necessary
for SF5Cl additions to simple alkenes. The product, 3, was
obtained as a mixture of stereoisomers that were not readily
separated, but which could be used directly in the subsequent
elimination reaction.
Nitration could also be readily carried out in very good
yield. 3-Nitropentafluorosulfanylbenzene, 5, had been ob-
tained earlier by direct fluorination of bis(3-nitrophenyl)-
disulfide in yields of 39-75%,9,10 whereas Sheppard had
reported the preparation of both 4 and 5 in his original 1962
paper.1
To facilitate the synthetic use of the parent 1, an improved
method for the conversion of 5 to 3-pentafluorosulfanyl-
aniline (6) is also reported in this paper, as is a procedure
for regioselective nitration of 424 and its subsequent reduction
to aniline derivative 9.
The elimination of HCl from SF5Cl adducts of simple
alkenes has been achieved previously using various elimina-
tive procedures.11,19-22 Thus, straight chain, SF5-substituted
(8) Bowden, R. D.; Greenhall, M. P. F2 Chemicals Ltd. PCT Int. Appl.,
2002.
(9) Chambers, R. D.; Spink, R. C. H. Chem. Commun. 1999, 883-884.
(10) Bowden, R. D.; Comina, P. J.; Greenhall, M. P.; Kariuki, B. M.;
Loveday, A.; Philp, D. Tetrahedron 2000, 56, 3399-3408.
(11) Hoover, F. W.; Coffman, D. D. J. Org. Chem. 1964, 29, 3567-
3570.
(12) Ou, X.; Janzen, A. F. J. Fluorine Chem. 2000, 101, 279-283.
(13) Carlini, F. M. Chim. Oggi 2003, 21, 14-16.
(14) Dolbier, W. R., Jr. Chim. Oggi 2003, 21, 66-69.
(15) Ait-Mohand, S.; Dolbier, W. R., Jr. Org. Lett. 2002, 4, 3013-3015.
(16) A paper reporting some additional, related approaches to the
synthesis of pentafluorosulfanylbenzene, using cyclohexene derivatives as
starting materials, appeared as this paper was going to press.17
(17) Winter, R. W.; Gard, G. L. J. Fluorine Chem. 2004, 125, 549-
552.
(18) Riemschneider, R.; Triebel, W. Chem. Ber. 1955, 88, 1442-1450.
(19) Klauck, A.; Seppelt, K. Angew. Chem., Int. Ed. Engl. 1994, 33,
93-95.
In conclusion, using SF5Cl as the source of the SF5 group,
we have reported a new and convenient three-step synthesis
(20) Case, J. R.; Ray, N. H.; Roberts, H. L. J. Chem. Soc. 1961, 2066-
2070.
(23) Duan, J.-X.; Zhang, L.-H.; Dolbier, W. R., Jr. Synlett 1999, 1245-
1246.
(24) NMR spectra of crude 8 indicated the presence of ∼10% of a minor
product, most likely the 6-nitro isomer. Because the spectra of 9 (in the
Supporting Informaiton) were of a sample prepared from crude 8, one can
see the respective 6-amino product as a ∼10% impurity in product 9.
(21) Fokin, A. V.; Studnev, Y. N.; Stolyarov, V. P.; Chilikin, V. G.;
Prigorelov, G. A. Russ. Chem. Bull. 1996, 45, 2804- -2806.
(22) Winter, R.; Gard, G. L. In Inorganic Fluorine ChemistrysToward
the 21st Century; Thrasher, J. S., Strauss, S. H., Eds.; American Chemical
Society: Washington, DC, 1994; Vol. 555, p 128-147.
2418
Org. Lett., Vol. 6, No. 14, 2004

of pentafluorosulfanylbenzene in an overall yield of >70%.
This synthesis provides a viable technological alternative to
the direct fluorination method for the preparation of SF5-
containing aromatic derivatives.
Supporting Information Available: Experimental pro-
cedures for all reactions and NMR spectra of compounds 4,
8, and 9. This material is available free of charge via the
Internet at http://pubs.acs.org.
Acknowledgment. Support of this research in part by the
National Science Foundation is gratefully acknowledged.
OL0491991
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