An efficient, scalable synthesis of ferrocenylphosphine and dichloroferrocenylphosphine

Article abstract of DOI:10.1039/c5ra27594f

A new synthetic route to FcPH₂ and FcPCl₂ (Fc = ferrocenyl) is presented. This method avoids the challenging monolithiation of ferrocene, as well as any tedious purification steps. All reactions are high yielding and easily conducted on a relatively large scale, using economical and commercially available synthetic precursors.

Full text of DOI:10.1039/c5ra27594f

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An efficient, scalable synthesis of ferrocenylphosphine and
dichloroferrocenylphosphine
Brian A. Surgenor,a Laurence J. Taylor,a Andreas Nordheider,a Alexandra M. Z. Slawin,a Kasun S.
Athukorala Arachchige,a J. Derek Woollinsa and Petr Kilian*a
Received 00th January 20xx,
Accepted 00th January 20xx
DOI: 10.1039/x0xx00000x
www.rsc.org/
A new synthetic route to FcPH2 and FcPCl2 (Fc = Ferrocenyl) is distillation of the FcPCl2 to remove the various ferrocene
presented. This method avoids the challenging containing sideproducts. At 52%, the yield is acceptable but
monolithiation of ferrocene, as well as any tedious not ideal, and the use of tBuLi makes the reaction dangerous
purification steps. All reactions are high yielding and easily to conduct on large scale. This problem is further
conducted on a relatively large scale, using economical and exacerbated by the need for careful control of the lithiation
a
commercially available synthetic precursors.
reaction conditions.
Since its discovery in the 1950s,1,2 which kickstarted
Another literature method utilises the Friedel-Crafts
research into the field of organometallic chemistry,3 ferrocene reaction of ferrocene with Me2NPCl2 (Scheme 1, bottom).12,13
has cemented itself as one of the most important The yields are low (11%) and repeated attempts to improve on
organometallic compounds due to its high stability and the this reaction demonstrated the yields to be highly variable and
relative ease with which it can be functionalised. The often much lower.14,15 Nonetheless, this method was still being
Cambridge structural database currently contains over 2500 used relatively recently.15,16
entries for phosphorus functionalised ferrocene derivatives.
These include strained ferrocenophanes serving as precursors
P(NEt2)2
i. BuLi
PCl2
for ring opening polymerisation,4,5 or chiral phosphine ligands
with a ferrocene backbone.6 Ferrocene is an interesting group
to introduce due to its redox activity and strong electron
donating properties, which allow it to stabilise electron
deficient species. In fact, the first “all-carbon” phosphenium
cation to be isolated was stabilised by two Fc substituents.7
Despite all of this, the archetypal ferrocenyl phosphorus
synthons, FcPH2 and FcPCl2, remain significantly underutilised.
This is due largely to a lack of convenient synthetic routes to
these molecules. So far, the main hurdle appeared to be the
monolithiation of ferrocene, which is notoriously challenging
and requires the use of highly pyrophoric tBuLi.8–10
t
PCl3 (xs)
Fe
Fe
Fe
ii. (Et2N)2PCl
- Et2NPCl2
52% yield;
requires laborious
purification
PCl2
Me2NPCl2
AlCl3
Fe
Fe
11% yield;
yields variable
Scheme 1: Previous syntheses of FcPCl2.11–13
The most recent synthesis of ferrocenylphosphine, FcPH2,
was reported by Wright and co-workers in 2009. In this
procedure diethyl ferrocenylphosphonate is reduced by
LiAlH4/Me3SiCl.17 The diethyl ferrocenylphosphonate was itself
prepared by monolitiation of ferrocene, followed by reaction
with chlorodiethylphosphate (Scheme 2).18 FcPH2 was
obtained in relatively good overall yields (50–60%), but the
procedure requires the use of tBuLi and column
chromatography, which hinders scale-up of the reaction.
Arguably, the best synthesis of FcPCl2 was published by
Pietschnig and Niecke in 1997.11 In their protocol (Scheme 1,
top) ferrocene is monolithiated with tBuLi, followed by the
addition of (Et2N)2PCl. The resulting FcP(NEt2)2 is converted to
FcPCl2 by reaction with excess PCl3. The work up for the
reaction is rather laborious, involving removal of excess PCl3
and the Et2NPCl2 byproduct by distillation, then vacuum
O
i. tBuOK, tBuLi
P(OEt)2
PH2
LiAlH4
Fe
Fe
Fe
ii. ClP(O)(OEt2)2
Me3SiCl
50-60% yield
Scheme 2: Recent synthesis of FcPH2.17,18
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In all of the lithiation based syntheses, the biggest issue has purification. This represents a marked improvement over the
been the selective addition of a single phosphorus moiety to Pietschnig synthesis which, in addition to requiring purification
the ferrocene ring, avoiding the disubstituted species formed by vacuum distillation, gave FcPCl2 in a lower yield (52% vs.
through overlithiation to 1,1’-dilithioferrocene. An elegant 65%
overall
yield).
Although
the
toxicity
of
bypass of the lithiation strategy was identified in the phosgene/triphosgene is a concern in this procedure, we feel
regiospecific reaction of ferrocene with P4S10, which yields the these compounds are easier to handle on a large scale than
perthiophosphonic anhydride Fc2P2S4 (Scheme 3). The reaction the pyrophoric tBuLi, and have repeatedly carried out this
is accomplished by refluxing the two components in xylenes, transformation on a relatively large scale (ca. 60 g FcPH2).
with the air stable product being collected by filtration in >80%
yield.19 The reaction is relatively facile, and has been scaled to
ca. 250 g ferrocene with little difficulty.
Somewhat surprisingly, the crystal structures of FcPH2 and
FcPCl2 have not been reported previously.24 Using the pure
material obtained via our procedure, crystals suitable for X-ray
diffraction were obtained with relative ease. The structures
are shown in Figure 1,25,26 both compounds are as expected,
with P–C bond lengths of 1.818(9) Å for FcPH2 and 1.778(4)
[1.784(4)] Å for FcPCl2.27
Perthiophosphonic anhydrides (general formula R2P2S4) are
well known in the literature, with the most famous example
being Lawesson’s reagent20 (R = 4-MeOC6H4). Although the
reactivity of selected perthiophosphonic anhydrides has been
studied in some detail,21 their use as thionation reagents has
been most prominent.22,23 Nevertheless, no reports on
reductions of such species with hydridic reagents have
appeared in the literature to date. We have found that
reduction of Fc2P2S4 using LiAlH4 gave the primary phosphine
FcPH2 as a low melting solid in 79% yield (66% overall yield,
Scheme 3). This reaction was conducted on a 100 g scale
without issue, something which would be very difficult and
potentially dangerous to do using tBuLi as in the Wright
synthesis.17,18 Crucially, the reaction proceeds cleanly when 4
eq. LiAlH4 are used per Fc2P2S4. The FcPH2 obtained was found
to be exceptionally pure by microanalysis, as well as 1H, 31P
and 13C NMR spectroscopy, with no need for further
purification.
1/4 P4S10
S
S
S
Fe
P
P
1/2
Fe
Fe
S
∆T
Fc2P2S4
(>80%)
2 LiAlH4
COCl2/
CO(OCCl3)2
PCl2
PH2
Fe
Fe
Figure 1: Solid state structures of FcPH2 (top) and FcPCl2 (bottom).
Thermal ellipsoids are drawn with 50% probability. Carbon bound H
atoms and second molecule in asymmetric unit (FcPCl2) are omitted
for clarity. Selected bond lengths (Å) and angles (°): FcPH2: C1–P1
1.818(9); FcPCl2: C1–P1 1.778(4) [1.784(4)], Cl1–P1–Cl2 97.95(8)
[98.34(7)].27
FcPCl2
FcPH2
(79%)
(quantitative)
Scheme 3: Two-step synthesis of FcPH2 from ferrocene via the
perthiophosphonic anhydride Fc2P2S4. Also shown is subsequent
quantitative transformation into FcPCl2.
Conclusions
With an efficient synthesis of FcPH2 in hand, it was
subsequently found that FcPH2 can be chlorinated by
triphosgene (considered a safer substitute for phosgene gas)
or phosgene (commercially supplied as a solution in toluene)
to give FcPCl2 in quantitative yield (Scheme 3). This reaction is
simple to conduct, although an efficient fumehood is
necessary. The reaction is completed in a few hours with
either chlorinating reagent. Removal of volatiles in vacuo
affords FcPCl2 as a red-brown oil, which solidifies on standing
at room temperature. The purity of the compound, as
determined by microanalysis and multinuclear NMR
spectroscopy, was exceptionally high with no need for further
The electrophilic substitution reaction of ferrocene with
P4S10 has been used to introduce a single phosphorus moiety
onto ferrocene with complete regiospecificity and in high yield.
Subsequently, the two archetypal phosphorus synthons FcPH2
and FcPCl2 were obtained in high yields and purity through the
reduction of Fc2P2S4 with LiAlH4, followed by chlorination with
triphosgene/phosgene. By avoiding the difficult monolithiation
of ferrocene and associated use of pyrophoric tBuLi, it was
possible to scale this new synthetic route to multi-gram
quantities (ca 60 g).
2 | Dalton Trans., 2016, 00, 1-3
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Manners, J. Organomet. Chem., 2015, 784, 24–30.
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22. T. Ozturk, E. Ertas, and O. Mert, Chem. Rev., 2007, 107, 5210–
5278.
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1958.
Experimental
Fc2P2S4: A slight modification of the literature procedure
was employed.19 Ferrocene (37.7 g, 202 mmol) and P4S10 (20.0
g, 45.0 mmol) were heated under reflux in xylenes (300 mL) for
3 hours before being allowed to cool. Fc2P2S4 was collected by
filtration as an air stable, dark orange solid, which was washed
with toluene (2 × 100 mL) and diethyl ether (2 × 50 mL) and
dried in vacuo. Yield 41.8 g (75.0 mmol, 83%).
FcPH2: To a vigorously stirred suspension of Fc2P2S4 (6.00 g,
10.7 mmol) in diethyl ether (70 mL), cooled to 0 °C, a
suspension of LiAlH4 (1.62 g, 42.7 mmol) in diethyl ether (30
mL) was added dropwise via cannula and the mixture allowed
to warm to RT. Insoluble by-products were removed by
filtration and washed with diethyl ether (2 × 20 mL). The
orange filtrate and washings were cooled to 0 °C, degassed
water (10 mL) was added cautiously and the resulting
suspension was warmed to RT. The solid formed was removed
by filtration and washed with DCM (2 × 20 mL). The filtrate and
washings were collected and volatiles removed in vacuo to
yield FcPH2 as a dark orange, low melting solid (3.67 g, 16.8
mmol, 79%). Crystals suitable for single crystal X-ray diffraction
were obtained by melting and recrystallisation of the solid
between 25–40 °C.25 Mp 36–37 °C. Found: C 55.16; H 5.25.
Calc. for C10H11FeP: C 55.09; H 5.09. IR (thin layer) νmax/cm−1
1
3094s (νCH), 2262s (νPH), 1206s, 1024s, 817vs, 495s. H NMR
δH (270 MHz; CDCl3) 4.31–4.29 (4H, m, 4 × CpH), 4.20 (5H, s, 5
× CpH), 3.86 (2H, d, JHP = 203 Hz, PH2). 13C{1H} NMR (75 MHz;
1
CDCl3) 75.7 (d, 2JCP = 14.0 Hz, CH, subst. Cp ring), 70.7 (d, 3JCP
3.6 Hz, CH, subst. Cp ring), 69.3 (s, CH, unsubst. Cp ring), 64.1
=
1
(d, JCP = 4.7 Hz, qC). 31P NMR δP (121 MHz; CDCl3) −143.6 (t,
1JPH = 203 Hz). 31P{1H} NMR δP (109 MHz; CDCl3) −143.8 (s).
FcPCl2: To a stirred solution of FcPH2 (3.00 g, 13.8 mmol) in
dichloromethane (70 mL), cooled to −10 °C, a solution of
triphosgene (2.7 g, 9.2 mmol) in dichloromethane (50 mL) was
added slowly via cannula. Alternatively, a solution of phosgene
(15.2 mL of a 1.9 M solution in toluene, 28.9 mmol) was added
dropwise over 30 min. The mixture was allowed to warm to RT
and stirred overnight. Volatiles were removed in vacuo to give
FcPCl2 as a red-brown oil which solidified on standing at room
temperature (3.93 g, 13.7 mmol, 99%). Crystals suitable for
single crystal X-ray diffraction were grown from toluene at −35
°C.26 Found: C 41.98; H 3.24. Calc. for C10H9Cl2FeP: C 41.86; H
3.16. IR (thin layer) νmax/cm−1 3099s (νCH), 1411s, 1163s,
1028s, 825s, 446vs. 1H NMR δH (400 MHz; CDCl3) 4.61–4.59
(4H, m, 4 × CpH), 4.30 (5H, s, 5 × CpH). 13C{1H} NMR (101 MHz;
24. The strutcure of the borane adduct (FcPH2·BH3) has been
reported recently, S. Pandey, P. Lönnecke, and E. Hey-Hawkins,
Eur. J. Inorg. Chem., 2014, 2456–2465.
25. Crystal data for FcPH2: C10H11FeP, Mr = 218.01, monoclinic,
P21/c, a = 12.658(10), b = 7.528(5), c = 10.432(8) Ǻ, β =
112.071(18)°, V = 921.2(12) Ǻ3, T = −180(1) °C, Z = 4, reflections
collected 5398, independent 1662 (Rint = 0.1024), R(obs) =
0.0944, wR(all data) = 0.2629. Deposition number CCDC 812314.
26. Crystal data for FcPCl2: C10H9Cl2FeP, Mr = 286.91, monoclinic,
P21/n, a = 12.9787(13), b = 13.2924(12), c = 13.6674(13) Ǻ, β =
110.613(8)°, V = 2206.9(4) Ǻ3, T = −100(1) °C, Z = 8, reflections
collected 14488, independent 4007 (Rint = 0.0499), R(obs) =
1
CDCl3) 79.5 (d, JCP = 52.3 Hz, qC), 73.3 (d, JCP = 4.5 Hz, CH,
subst. Cp ring), 71.1 (d, JCP = 22.5 Hz, CH, subst. Cp ring), 70.0
(s, CH, unsubst. Cp ring). 31P NMR δP (162 MHz; CDCl3) 164.6
(s). 31P{1H} NMR δP (162 MHz; CDCl3) 164.7 (s).
Acknowledgements
0.0472, wR(all data)
= 0.0779. Deposition number CCDC
This work was financially supported by the Engineering and
Physical Sciences Research Council (EPSRC) and by COST action
(grant CM1302, SIPs).
1437271.
27. Value in square brackets for second molecule of FcPCl2 in the
asymmetric unit.
Notes and references
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2. G. Wilkinson, M. Rosenblum, M. C. Whiting, and R. B.
Woodward, J. Am. Chem. Soc., 1952, 74, 2125–2126.
3. H. Werner, Angew. Chem. Int. Ed., 2012, 51, 6052–6058.
4. C. H. Honeyman, D. A. Foucher, F. Y. Dahmen, R. Rulkens, A. J.
Lough, and I. Manners, Organometallics, 1995, 14, 5503–5512.
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