Hydrofluorocarbon 245fa: A versatile new synthon in alkyne chemistry

Article abstract of DOI:10.1039/b207979h

The CFC replacement 1,1,1,3,3-pentafluoropropane (HFC 245fa) has been established as a convenient source of trifluoropropynyllithium under mild conditions; a range of novel and known trifluoropropynyl-containing systems has been prepared in a one-pot procedure.

Full text of DOI:10.1039/b207979h

Hydrofluorocarbon 245fa: a versatile new synthon in alkyne chemistry
Alan K. Brisdon* and Ian R. Crossley
Department of Chemistry, UMIST, P.O. Box 88, Manchester M60 1QD, UK.
E-mail: alan.brisdon@umist.ac.uk; Fax: +44 161 200 4559; Tel: +44 161 200 4459
Received (in Cambridge, UK) 15th August 2002, Accepted 6th September 2002
First published as an Advance Article on the web 20th September 2002
The CFC replacement 1,1,1,3,3-pentafluoropropane (HFC
245fa) has been established as a convenient source of
trifluoropropynyllithium under mild conditions; a range of
novel and known trifluoropropynyl-containing systems has
been prepared in a one-pot procedure.
Reagent 4, generated in this fashion, is stable for several
hours when held below 0 °C, but decomposes rapidly above this
temperature to afford an intractable material. Stability is
significantly reduced when THF is used in place of ether, 4
having a lifetime of a few minutes at 278 °C. Treatment of 4,
generated as described, with ethereal solutions of a range of
electrophiles, allows for preparation of the respective tri-
fluoropropynyl compounds, typically in good to excellent
yields. In this way a range of organic and organometallic
derivatives has been prepared (Fig. 1). In a typical reaction,9 an
ethereal solution of triphenyltin chloride was added to a stirred
solution of 4, at 210 °C, then the mixture allowed to warm
slowly to ambient temperature overnight. The reaction is
conveniently monitored by 19F-NMR spectroscopy; extracts
withdrawn from the mixture revealing gradual loss of the
complex multiplet resonances associated with HFC-245fa at
264.3 and 2116.8 ppm, and concomitant development of a
singlet at 250.8 ppm, with attendant tin satellites (JSnF 12 Hz).
The product was isolated as a pale yellow solid by addition of an
excess of hexane, to precipitate the inorganic salts, and
subsequent concentration of the filtered solution in vacuo. The
presence of an acetylenic unit was confirmed by the infrared
spectrum, which exhibits a strong absorption at 2183 cm21
(C·C str.) and by multinuclear NMR studies. The CF3 unit
inferred by the 19F-NMR spectrum, is also apparent in the 13C-
NMR spectrum as a quartet resonance (1JCF 260 Hz) at 111.5
ppm. Additionally, two further quaternary resonances are
observed at dC 94.5 and 91.8, which also exhibit quartet
multiplicities. Coupling constants of 50 and 6 Hz allow for
assignment of the resonances to the b and a acetylenic carbon
atoms respectively.
Over recent years there has been a surge of interest in the
chemistry of fluorinated compounds, with particular focus on
the development of systems with pharmaceutical, agrochemical
and materials applications.1,2 We have been actively involved
in the investigation of systems bearing the trifluorovinyl
(CFNCF2) group,3 which is readily introduced by means of
trifluorovinyllithium, obtained via the low-temperature reaction
of hydrofluorocarbon 134a (1,1,1,2-tetrafluoroethane,
CF3CH2F) with two equivalents of n-butyllithium.4 This has led
us to screen a range of commercially available HFCs for similar
reactivity and potential as synthetic precursors. Here we report
that HFC-245fa (1,1,1,3,3-pentafluoropropane, CF3CH2CF2H)
is a convenient source of the trifluoropropynyl anion, through
its reaction with 3 equivalents of n-butyllithium.
Introduction of the trifluoropropynyl group to organic and
organometallic systems has classically been achieved through
the use of the respective organolithium,5 Grignard6 or organo-
zinc7 reagents. In each case, reliance upon trifluoropropyne as a
precursor incurs experimental difficulties, associated with the
handling of a gaseous reagent (b.p. 248 °C), and has significant
cost implications. Recently, two independent reports have
suggested that 3,3,3-trifluoro-2-bromopropene serves as an
experimentally and economically more viable precursor for
trifluoropropynyl lithium,8 which is generated by reaction of the
propene with two equivalents of LDA at 278 °C, in THF.
However, availability of the fluorocarbon and the necessity for
low reaction temperatures remain prohibitive factors, partic-
ularly for large-scale applications.
Verification of the trifluoropropynyl group was obtained by
an analogous reaction with 0.5 equivalents of HgCl2, affording
a moderate yield of Hg(CCCF3)2. The 13C-NMR spectrum
again consists of three characteristic quartet resonances in the
region 120–90 ppm, each exhibiting satellite coupling to
mercury, the magnitude of which diminishes with increasing
In contrast, we have found that HFC-245fa (1, b.p. 15 °C),
which has recently gone into mass production, affords good
yields of trifluoropropynyllithium under comparatively mild
conditions. Thus, the treatment of a diethyl ether solution of 1
with three equivalents of n-BuLi at 210 °C leads to good yields
of trifluoropropynyllithium 4, presumably by means of the
process illustrated in Scheme 1. Efforts to isolate intermediates
2 and 3 have been unsuccessful, as have attempts to trap the
anions from deprotonation of 1 or 2, though preliminary
deuterolysis experiments indicate a predominance of 4, suggest-
ing a largely concerted mechanism
Fig. 1 Reactions of trifluoropropynyllithium, derived from HFC-245fa,
Scheme 1 Conditions. Diethyl ether, 210 °C.
with a range of electrophiles (yields in parentheses, based on substrate).
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10
3 See for example: K. K. Banger, R. P. Banham, A. K. Brisdon, W. I.
Cross, G. Damant, S. Parsons, R. G. Pritchard and A. Sousa-Pedrares, J.
Chem. Soc., Dalton Trans., 1999, 427; N. A. Barnes, A. K. Brisdon, M.
J. Ellis and R. G. Pritchard, J. Fluorine Chem., 2001, 112, 35.
4 (a) J. Burdon, P. L. Coe, I. B. Haslock and R. L. Powell, Chem.
Commun., 1996, 49; (b) K. K. Banger, A. K. Brisdon and A. Gupta,
Chem. Commun., 1997, 139.
5 F. G. Drakesmith, O. J. Stewart and P. Tarrant, J. Org. Chem., 1968, 33,
280.
6 (a) See for example: A. L. Henne and M. Nager, J. Am. Chem. Soc.,
1952, 74, 650; (b) M. I. Bruce, D. A. Harbourne, F. Waugh and F. G. A.
Stone, J. Chem. Soc. (A), 1968, 356.
7 (a) J. E. Bunch and C. L. Bumgardner, J. Fluorine Chem., 1987, 36, 313;
(b) N. Yoneda, S. Matsuoka, N. Miyaura, T. Fukuhara and A. Suzuki,
Bull. Chem. Soc. Jpn., 1990, 63, 3124.
8 (a) T. Yamazaki, K. Mizutani and T. Kitazume, J. Org. Chem., 1995, 60,
6046; (b) A. R. Katritzky, M. Qi and A. P. Wells, J. Fluorine Chem.,
1996, 80, 145.
JCF
.
Analogous data has been obtained for a range of novel
and known organometallic and phosphorus based systems,
which have been prepared in good yield.
HFC-245fa is an equally versatile synthon for organic
chemistry; reagent 4 readily reacting with a range of organic
substrates to afford the anticipated products in good yield. Thus,
when ethereal PhCHO and 4 are allowed to react for 4 h,
quenching with methanol, followed by an aqueous work-up
allows for isolation of 4,4,4-trifluoro-1-phenyl-2-butyn-1-ol in
60% yield. Similarly, the reaction of 4 with benzoyl chloride
afforded the anticipated (1-phenyl)trifluoropropyn-1-one upon
aqueous work-up. Both materials were purified by distillation
and characterised as previously described, spectroscopic data
being consistent with literature reports.8,11 All materials
afforded satisfactory microanalysis.
In conclusion, the potentially useful trifluoropropynyl group
can be introduced to a wide range of systems via a convenient,
one-pot reaction, employing readily available starting materials.
The commercial availability of HFC-245fa and the relatively
mild conditions employed render trifluoropropynyllithium
more widely available than ever before, its availability being
comparable to that of any other organolithium. Significantly, for
the first time, trifluoropropynyllithium is now an economically
viable proposition for industrial-scale applications.
9 Typical reaction. HFC-245fa (0.25 cm3, 2.46 mmol) as solution in ether
(80 cm3) is held at 210 °C, while n-BuLi (2.5 M in hexane, 2.7 cm3,
6.75 mmol) is added, maintaining the temperature. After 10 min.
Ph3SnCl (0.867 g, 2.25 mmol) as solution in ether is added, maintaining
210 °C, then the mixture allowed to warm slowly to r.t. and stir
overnight. An excess of hexane (150 cm3) is added then the settled
mixture filtered through Celite®. Concentration of the resulting solution
in vacuo affords a pale yellow solid, which is purified by column
chromatography on silica gel, eluting with 1+1 toluene/hexane.
10 Selected characterising data (CDCl3). Ph3SnCCCF3: dF –50.8 (s), dC
111.5 (C, q JCF 260 Hz), 94.5 (C, q JCF 50 Hz), 91.8 (C, q, JCF 6 Hz).
Anal. (Calcd.) C 57.1 (57.0), H 3.6 (3.4), F 12.6 (12.8). n(C·C) 2183
cm21. Hg(CCCF3)2: dF 251.6 (s, JHgF 39 Hz). dC 116 (C, q JCF 7, JHgC
2726 Hz), 111.2 (C, q JCF 258, JHgC 69 Hz), 89.9 (C, q JCF 51, JHgC 675
We thank the Engineering and Physical Sciences Research
Council (EPSRC) and UMIST for financial support, and
Honeywell Speciality Chemicals for donation of HFC-245fa.
We acknowledge the EPSRC for support of the UMIST NMR
(GR/L52246) and FTIR-Raman (GR/M30135) facilities.
Hz). Anal. (Calcd.) C 18.2 (18.6), F 30.5 (29.5 ). n(C·C) 2202 cm21
.
Ph2PCCCF3: dF 250.9 (d, JPF 6 Hz). dP 234.5 (q, JPF 6 Hz). dC 111.6
(C, qd JCF 259, JCP 1.4 Hz), 90.3 (qd. JCF 52, JCP 1.2 Hz), 85.7 (C, dq.
JCF 7, JCP 31 Hz). Anal. (Calcd.) C 64.9 (64.7), H 3.7 (3.6), F 20.2
(20.4). n(C·C) 2198 cm21. [(Bu3P)2Pt(CCCF3)2]: dF 246.7 ( t, JPF 3,
JPtF 13 Hz). dP 4.35 (septet.JPF 3, JPtP 2245 Hz). dC 113 (C, qt. JCF 254,
JCP 1.5 Hz), 107.9 (C, m), 93.8 (C, qt. JCF 47, JCP 2 Hz). Anal. (Calcd.)
Notes and references
1 See for example: R. Filler and Y. Kobayashi, Biomedical Aspects of
Fluorine Chemistry, Kodasha/Elsevier, New York, NY, 1982; R. E.
Banks, Organofluorine Chemicals and Their Industrial Applications,
Ellis Horwood Ltd., Chichester, 1979.
2 See for example: R. E. Banks, Organofluorine Chemistry: Principles
and Commercial Applications, Plenum Press, New York, 1994; R. E.
Banks, Fluorine Chemistry at the Millennium: Fascinated by Fluorine,
Elsevier Science Ltd, Amsterdam, 2000 and references therein.
C 47 (46), H 7.1 (7.0), P .
6.6 (7.5). n(C·C) 2130 cm21
PhCH(OH)CCCF3: dF 250.9 (d, JHF 2.6 Hz). dC 114 (C, q JCF 258 Hz),
86.9 (C, q JCF 6.5 Hz), 73.8 (C, q JCF 53 Hz), 64.4 (CH, s). Anal.
(Calcd.) C 60.15 (60.0), H 3.5 (3.5), F 28.8 (28.5). n(C·C) 2278 cm21
.
PhCOCCCF3: dF 251.6 (s). dC 163.7 (C, s), 114.1 (C, q, JCF 259 Hz),
81.3 (C, q, JCF 6 Hz), 75.4 (C, q, JCF 54 Hz). Anal. (Calcd.) C 60.9
(60.6), H 2.6 (2.5), F 28.5 (28.6). n(C·C) 2272 cm21
.
11 M. Yonovich-Weiss and Y. Sasson, Synthesis,1984, 35.
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