Phosphorus containing mixed anhydrides-their preparation, labile behaviour and potential routes to their stabilisation

Article abstract of DOI:10.1039/c2ob07164a

Simple mixed anhydrides are known to pose synthetic difficulties relating to their thermal lability and ways to stabilise such mixed anhydride systems by relying on either electronic or steric effects were therefore explored. Thus, a series of acyloxyphosphines and acylphosphites derived from either propanoic acid or phenylacetic acid were prepared and their in solution stability assessed. These compounds were, where stability allowed, fully characterised using standard analytical techniques. NMR studies, in particular, unearthed interesting coupling behaviour for a number of the acyloxyphosphines and acylphosphites as well as their rearrangement products which could be linked to their chiral nature. Furthermore, the crystal structures for three of the prepared mixed anhydrides were determined using X-ray crystallography and are reported herein.

Full text of DOI:10.1039/c2ob07164a

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PAPER
Phosphorus containing mixed anhydrides—their preparation, labile
behaviour and potential routes to their stabilisation†
Jacorien Coetzee,a Graham R. Eastham,b Alexandra M. Z. Slawina and David J. Cole-Hamilton*a
Received 22nd December 2011, Accepted 2nd March 2012
DOI: 10.1039/c2ob07164a
Simple mixed anhydrides are known to pose synthetic difficulties relating to their thermal lability and
ways to stabilise such mixed anhydride systems by relying on either electronic or steric effects were
therefore explored. Thus, a series of acyloxyphosphines and acylphosphites derived from either propanoic
acid or phenylacetic acid were prepared and their in solution stability assessed. These compounds were,
where stability allowed, fully characterised using standard analytical techniques. NMR studies, in
particular, unearthed interesting coupling behaviour for a number of the acyloxyphosphines and
acylphosphites as well as their rearrangement products which could be linked to their chiral nature.
Furthermore, the crystal structures for three of the prepared mixed anhydrides were determined using
X-ray crystallography and are reported herein.
Introduction
We have previously reported that mixed anhydrides or (acyloxy)
diorganylphosphines of the general form Ph2POC(O)R1, where
R1 contains 2,3-unsaturation can be used for the hydrogenation
of the parent acrylic acid when reacted with hydrogen in the
presence of rhodium complexes such as Wilkinson’s catalyst.1
The mechanism by which these reactions occur involves impor-
tant steps at the metal centre and at P (Scheme 1).1 Based on the
principle of microscopic reversibility the reverse reactions, dehy-
drogenations of saturated mixed anhydrides, should in theory
also be possible and should occur through C–H activation
promoted by binding of the P atom, providing a potential new
route to their functionalisation.
Saturated mixed anhydrides are accessible via a number
of synthetic routes. They can be prepared readily either by the
treatment of chlorophosphines with sodium carboxylates or
carboxylic anhydrides or by reaction with carboxylic acids in
the presence of an amine base.2 However, their propensity
to undergo spontaneous and irreversible condensation and
rearrangement reactions, even at low temperatures, is known to
Scheme 1 Mechanism for the hydrogenation of 3-methylbut-2-enoic
aEaStCHEM, School of Chemistry, Purdie Building, University of
St. Andrews, St. Andrews, Fife, Scotland, KY16 9ST, UK. E-mail:
djc@st-andrews.ac.uk; Fax: +44 (0)1334 463808; Tel: +44 (0)1334
463805
acid using Rh complexes of mixed anhydrides of diphenylphosphinous
acid and acrylic acids.1 P = PPh3.
bLucite International Technology Centre, P.O. Box 90, Wilton,
Middlesborough, Cleveland, England, TS6 8JE, UK. E-mail: graham.
eastham@lucite; Fax: +44 (0)1642 447119; Tel: +44 (0)1642 447109
†Electronic supplementary information (ESI) available: Full crystallo-
graphic data. CCDC reference numbers 860547 (10), 860548 (11),
860549 (13). For ESI and crystallographic data in CIF or other electronic
format see DOI: 10.1039/c2ob07164a
complicate both the synthesis and in particular the purification of
these compounds.2–4
Surprisingly, unsaturated mixed anhydrides derived from
acrylic acids such as but-2-enoic acid {CH3CHvCHCO2H}, 3-
methylbut-2-enoic acid {(CH3)2CvCHCO2H}, pent-3-enoic
acid {(CH3)2CvCHCH2CO2H)}, and 2-methyl-3-phenylacrylic
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acid {PhCHvC(Me)CO2H} prove to be remarkably stable in
solution at room temperature and indefinitely stable in the
solid state under an inert atmosphere.5 At the other extreme,
unsaturated mixed anhydrides derived from the less substituted
acrylic acid {CH2vCHCO2H} and but-3-enoic acid {CH2v
CHCH2CO2H}, rearrange rapidly in solution to yield tetraphe-
nyldiphosphine monoxide {Ph2PP(O)Ph2} together with
carboxylic anhydrides as the major products.6,7 Although no
mechanistic studies for this dimerisation have been performed,
the formation of Ph2PP(O)Ph2 is postulated to occur via an
intermolecular disproportionation reaction.6
In a number of more recent reports, changing from chloropho-
sphines to chlorophosphites as precursors to mixed anhydrides
was shown to afford (acyl)phosphites with enhanced thermodyn-
amic stability.8–11 However, despite this general improved stab-
ility of these compounds, the formation of byproducts during
the synthesis of more simple (acyl)phosphites was still noted.10
Stable (acyl)phosphites have shown promise as ligands in cata-
lysts for both isomerisation8 and asymmetric hydroformylation11
as well as asymmetric hydrogenation reactions10 and have also
been employed as precursors in the preparation of complex
diaryl phosphonates of medicinal importance.9
Considering the discussed challenges surrounding the prep-
aration and isolation of stable mixed anhydrides, an investigation
into possible ways to stabilise such compounds was launched
and the outcome of this study is reported herein. A series of new
(except one) mixed anhydrides derived from chlorophosphines
or chlorophosphites and propanoic acid were prepared and fully
characterised where their stability allowed. In later work, we
shall report the coordination chemistry and catalytic potential of
these interesting ligands.
compound could also be prepared, using an adaptation of a pro-
cedure proposed by Cupertino and Cole-Hamilton,5 by treatment
of a propanoic acid solution in thf at −10 °C with chlorodiphe-
nylphosphine and triethylamine for 10 min [Scheme 2(b)].
However, although 1 could be prepared in high purity using
either one of the described methods, reactions were on occasions
complicated by the facile rearrangement of 1 in solution to tetra-
phenyldiphosphine monoxide, Ph2P(O)PPh2. Moreover, follow-
ing successful preparation of this compound, rearrangement
would generally take place during storage, even at temperatures
as low as −22 °C, to afford large amounts of Ph2P(O)PPh2 as
a white solid. This rearrangement has also been observed by
Bollmacher and Sartori12 during attempts to purify the ligand by
fractional distillation. Similarly, rearrangements of this type have
also been described by Irvine and co-workers6 for simple unsatu-
rated mixed anhydrides derived from chlorodiphenylphosphine
and acrylic or vinylacetic acid.
In view of the difficulties associated with the thermal stability
of 1, an investigation into potential ways to stabilise mixed
anhydrides of this kind was launched. Encouraged by literature
reports on more stabile (acyl)phosphites,8–11 we envisaged two
possible approaches to achieving more stable ligands and pre-
venting unwanted side reactions—approach A: by decreasing the
nucleophilicity of the phosphorus atom through the incorporation
of electron withdrawing heteroatoms directly bonded to phos-
phorus, or approach B: by increasing the steric requirements of
the groups attached to phosphorus so as to inhibit neighbouring
molecules from participating in intermolecular disproportiona-
tion reactions.
With the proposed strategies in mind, a collection of com-
pounds was prepared and their stability in solution as well as
under solvent free conditions assessed mainly by 31P NMR spec-
troscopy. This collection of compounds can be divided into three
series (Fig. 1), where series I comprises of mixed anhydrides
1–3 which contain neither electron withdrawing groups bonded
directly to phosphorus (with the exception of the acyloxy
moiety) nor bulky substituents on the phenyl rings, while series
II includes mixed anhydrides 8–9 which do possess electron
withdrawing atoms directly bonded to the phosphorus atom, but
no bulky substituents on the rings. Finally, series III comprises
of mixed anhydrides 10–13 that bear both electron withdrawing
groups attached to phosphorus and bulky ring substituents.
It is worth mentioning, however, that together with a gain in
stability, approach A would also bring about a loss in the overall
electron richness of the ligand, which might prove detrimental
to their later application in C–H activation. A fine balance will,
therefore, need to be reached between their stability and donor
abilities. For this reason, diols containing electron donating alkyl
groups as ring substituents were chosen for the preparation of the
chlorophosphite precursors to compounds 10–13 of series III in
an attempt to counterbalance the electron withdrawing effects of
the oxygen atoms to some extent with inductive effects. The
function of the alkyl substituents in the 3 and 3′-positions of the
rings is dual in this series, acting both as donors of electron
density and sterically demanding groups.
Results and discussion
The incentive for this study came from difficulties experienced
during the preparation of the simple mixed anhydride, (propa-
noyloxy)diphenylphosphine, 1. The synthesis of this compound
has been reported before by Bollmacher and Sartori12 in a study
directed towards the synthesis of Cu(I) and Ag(I) complexes of
this ligand. During their studies, the desired mixed anhydride
could be prepared in yields of 86–90% by the treatment of
chlorodiphenylphosphine with sodium propanoate. Following a
similar approach, 1 could be prepared by treatment of a suspen-
sion of sodium propanoate in tetrahydrofuran with an equimolar
amount of chlorodiphenylphosphine at 0 °C for 1 h and then a
further 2 h at room temperature [Scheme 2(a)]. Alternatively, this
Within series I, the preparation and unstable nature of
(propanoyloxy)diphenylphosphine, 1, has already been des-
cribed. To make this series more comprehensive, the related
(phenylacetyloxy)diphenylphosphine (2) was prepared from
Scheme 2 Reaction scheme for the preparation of (propanoyloxy)-
diphenylphosphine (1) via (a) a route reported by Bollmacher and
Sartori12 and (b) an adaptation of the procedure reported by Cupertino
and Cole-Hamilton.5
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Scheme 3 Reaction scheme for the preparation of compounds 8 and 9
from chlorophosphites 4 and 5, respectively. (i) Sodium propanoate, thf,
45 °C, 2 h.
the general formula (RO)2P(O)P(OR)2 were observed for these
compounds.
31P NMR spectra, however, did reveal the presence of minor
amounts of by-products 14 and 15 (for 8 and 9, respectively;
Scheme 4). These by-products most likely originated from the
base catalysed reaction of dialkylphosphonates (DP) with dialkyl
acylphosphonates (DAP) (Scheme 4), and similar reaction path-
ways have been reported in the literature for the preparation of
tetraethyl 1-hydroxyalkylidenediphosphonates and their isomeric
phosphates.15 These reactions initially generate 1-hydroxyalkyli-
denediphosphonate esters as intermediates which then undergo
spontaneous rearrangement to the more stable phosphates, 14
and 15. The dialkylphosphonate (DP) precursors are generated
by hydrolysis of the mixed anhydrides in the presence of trace
amounts of water, while the dialkyl acylphosphonates (DAP) are
formed by the Arbuzov rearrangement of the ligands 8 and
9. Rearrangements of this type are not uncommon for mixed
anhydride ligands and similar rearrangements have been noted
before by Lindner and Wuhrmann for (perfluoracyloxy)-
diorganylphosphines.2
Compounds 8–9 are air and moisture sensitive white solids
which are soluble in most aprotic organic solvents such as
chloroform, dichloromethane, thf, diethyl ether, toluene, hexane
and pentane (sparingly). Furthermore, compounds 8–9 are
indefinitely stable both in solution and the solid state at room
temperature, provided that a dry, base-free and inert atmosphere
is maintained. These findings are in good agreement with litera-
ture reports on the general stability of (acyl)phosphites and there-
fore indicate that a moderate increase in stability can be achieved
by the use of electron withdrawing groups on phosphorus.9,10
Finally, to complete the collection, mixed anhydrides 10–13
(constituting series III) were prepared from their corresponding
chlorophosphites 6–714 (Scheme 5) using the same method-
ologies as described for the preparation of compounds 8 and 9.
Following approach B, sterically demanding tert-butyl groups
were included as substituents in the 3-positions of both phenyl
rings, shielding the phosphorus centre from neighbouring mol-
ecules. This stabilisation approach proved very successful with
measured NMR spectra providing no evidence for the presence
of any disproportionation products. Moreover, the analytically
Fig. 1 Series I—mixed anhydrides 1–3 containing neither electron
withdrawing groups bonded to the phosphorus (with the exception of
the acyloxy moiety) nor bulky substituents on the phenyl rings; Series II
—mixed anhydrides 8–9 with electron withdrawing atoms directly
bonded to the phosphorus atom, but no bulky ring substituents and
Series III—mixed anhydrides 10–13 bearing both electron withdrawing
groups directly attached to phosphorus and bulky ring substituents.
phenylacetic acid using a similar procedure to that used for 1.
Not surprisingly, the behaviour of this compound in solution
as well as in the solid state was similar to that of 1. In
addition, an attempt to prepare the related mixed anhydride
5-(propanoyloxy)dibenzophosphole, 3, where the phosphorus
atom forms part of a phosphole ring, was made. We expected
this compound to be even more prone to rearrangement reac-
tions, since the greater C–P–O angles (brought about by ring
constraints) make the phosphorus atom even more accessible to
neighbouring molecules. A suspension of sodium propanoate in
thf was therefore treated with 5-chlorodibenzophosphole at room
temperature for 2 h, after which the formed NaCl was removed
by filtration and all volatiles evaporated under reduced pressure
to furnish the crude product as a white solid. However, as antici-
pated, this solid solely consisted of rearrangement products of
which the Ph2P(O)PPh2 analogue [5,5′-bibenzo[b]phosphindole]
5-oxide, constituted the major component. Although it is prob-
able that the lifetime of 3 can be prolonged by lowering the reac-
tion temperature, no further efforts to synthesise and isolate this
compound were made.
Next, the effects of electron withdrawing atoms (approach A)
were explored by constructing series II. Following a literature
based procedure,13,14 chlorophosphites 4 and 5 were reacted with
a suspension of sodium propanoate in thf at 45 °C for 2 h to
afford (propanoyl)phosphites 8 and 9, respectively, upon work-
up (Scheme 3). Overall, 8 and 9 displayed much greater stability
than the (acyloxy)phosphines and no rearrangement products of
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Scheme 4 Formation of by-products 14 and 15 from ligands 8 and 9 in the presence of water and base.
Spectroscopic analysis
Nuclear magnetic resonance
1H, 13C{1H}, and 31P{1H} NMR spectroscopic data were col-
lected for dichloromethane-d2 or chloroform-d1 solutions of
1–13 and are listed in detail under the Experimental section.
In the 31P{1H} NMR spectrum of 1, disproportionation to
Ph2P(O)PPh2 is easily recognised, by the appearance of two
1
doublets (at δ 36.9 and δ −22.1, JP–P = 229.4 Hz) at the
expense of 1 (δ 98.9s, Fig. 2) and are in good agreement with
the literature values reported for this compound.16 Similarly, the
by-products 14 and 15 show very distinctive spectral profiles in
the 31P NMR spectra of ligands 8 and 9, respectively, and could
be identified using standard 1D and 2D NMR spectroscopic
1
techniques (13C-DEPT, COSY, HMQC, HSQC). In the H NMR
spectrum of 8, the central –CH– group of the by-product 14
gives rise to a very distinctive multiplet at δ 5.41 (Fig. 3) as a
result of coupling to phosphorus in addition to the diastereotopic
methylene protons. Likewise, the methylene protons give rise to
a complex multiplet at δ 2.34, while the methyl group gives rise
to a doublet of doublets observed as a broad triplet at δ 1.39.
In the 31P NMR spectrum, the two distinct P-atoms of 14
are observed as doublets at δ 1.9 and δ 26.4 (4JP–P = 24.1 Hz).
Furthermore, in the 2D HMQC spectrum these resonances
Scheme 5 Reaction scheme for the preparation of compounds 10–13
from chlorophosphites 6 and 7. (i) Sodium propanoate, thf, 45 °C, 2 h;
(ii) phenylacetic acid, −10 °C; (iii) NEt3, −10 °C, 20 min; (iv) 20 min,
room temperature.
1
display H–31P correlations of different intensities and are there-
fore consistent with a structure where one of the phosphorus
atoms is incorporated in a phosphate group. In contrast, the
by-product 15 gives rise to two sets of doublets in the 31P{1H}
NMR spectrum with distinct 31P–31P coupling constants (Fig. 4)
owing to the planar chirality of the binol and the chirality at the
central carbon atom.
pure compounds 10–13 are fairly air stable white solids that
proved remarkably stable towards rearrangement in solution even
at temperatures as high as 60 °C. In addition, these compounds
are indefinitely stable in the solid state under an inert atmos-
phere, emphasizing the substantial increase in stability brought
about by the incorporation of steric bulk. Although 10–13 are
incompatible with protic solvents, they are soluble in most other
organic solvents such as chloroform, dichloromethane, tetra-
hydrofuran, diethyl ether, toluene and even very non-polar sol-
vents such as hexane and pentane. Owing to the superior
stability of these compounds, single crystals suitable for crystal
structure determination could be obtained for 10, 11 and 13, and
are discussed in more detail in the crystallographic section.
Since the starting diol used during the preparation of 9 was
fixed as the (R)-isomer, only two possible diastereomers can
be formed for this specific by-product; they are (R, S, R) and
(R, R, R). The two distinct diastereomers observed in the 31P
NMR spectrum of 15, display slightly different 31P–31P coupling
constants of 23.3 Hz and 28.9 Hz, respectively.
In the 13C NMR spectra of 10 and 11 all carbon atoms are
chemically inequivalent owing to the rotated disposition of the
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Fig. 2 Examples of typical 31P{1H} NMR spectra measured for compound 1 (a) following successful preparation thereof and (b) after rearrangement
largely to Ph2P(O)PPh2 has taken place.
Experimental section. In all cases, mixed anhydrides show
strong absorption bands in the region 1740–1729 cm−1 attribu-
table to the characteristic CvO stretching vibrations. These
values are in good agreement with those reported for the litera-
ture examples (R)-acetyl-(1,1′-binaphthyl-2,2′-diyl)phosphite
(1736 cm−1
1740 cm−1).10,12
)
and (propanoyloxy)diphenylphosphine (1;
Mass spectrometry
EI-MS spectrometric data were collected for compounds 8–13
and the relevant peaks are listed in the Experimental section.
Very little fragmentation was, however, observed for these com-
pounds with this mild ionization technique and as a result, the
only diagnostic peaks can be assigned to the molecular ions
[M]+ and peaks originating from the loss of either a propanoy-
loxy group (for 8–10 and 12) or of a phenylacetyloxy group (for
11 and 13).
Fig. 3 Multiplicity and coupling constants observed for the complex
1H NMR resonance of the central –CH– group in the by-product 14.
rings (to minimize steric interactions) as well as the chirality of
these compounds. Despite this, however, like carbons in com-
pounds 12 and 13 display accidental equivalence giving rise to
single resonances in the relevant regions. Furthermore, it is
worth mentioning that for 10 and 11 the constants measured for
13C–31P coupling between C4 to P (0 Hz) and C14 to P (4.7–5.0
Hz, see Fig. 5 for numbering scheme) differ significantly. The
values of germinal coupling constants are influenced by the
angle between the coupled atoms, and variations in the P–O–
C angles θ and β (Fig. 5) may therefore be the cause of the
observed inconsistencies.
Crystallography
The crystal and molecular structures of compounds 10, 11 and
13 were determined by single crystal X-ray diffraction.† Com-
pound 10 crystallises from a concentrated hexane solution as col-
ourless prisms in the orthorhombic space group Pna21 with
4 molecules in the unit cell. Fig. 6 depicts the molecular struc-
ture and numbering scheme of 10 and selected bond lengths and
angles are summarised in the figure caption. Within the molecu-
lar structure of 10, the two aromatic ring systems are rotated
about the central carbon bond at torsion angles of 61.4(9)° and
60.0(9)° in order to minimise steric interactions between the
different ring substituents. Although no crystal structures for free
mixed anhydrides ligands of the general formula (RO)2POC(O)
R′ have been reported to date, the measured P(1)–O(1) bond
length of 1.654(5) Å is in close agreement with that reported
for the phosphorus ester bond in 2-(methylamino)benzoate-
1,4-dihydro-1-methyl-4-oxo-2H-3,1,2-benzoxazaphosphorin-2-yl
Surprisingly, for compound 12 or 13, C4 and C14 are only
observed as a single resonance signal split into a doublet by
equal coupling to phosphorus [4.7 Hz (12) and 5.0 Hz (13)].
Infrared spectroscopy
Routine FT-IR data were collected for compounds 2 and 8, 9 and
10–13, with all relevant absorption bands listed under the
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Fig. 4 31P{1H} NMR spectrum measured for compound 9 showing the presence of minor amounts of the two diastereomers of by-product 15.
Fig. 5 Numbering scheme for NMR assignments and discussions relat-
ing to compounds 10–13, where θ and β represents the C4–O–P and
C14–O–P angles, respectively.
ester [1.6462(13) Å].17 A very slight variation is observed
between the distances for the two analogous P(1)–O(3) and
P(1)–O(4) bonds [1.614(5) Å and 1.645(5) Å], and observed
bond lengths are comparable to those of the related literature
example, 1,1′-biphenyl-2,2′-diyl-bis[(5,5′,6,6′-tetramethyl-3,3′-
di-tert-butyl-1,1′-biphenyl-2,2′-diyl)phosphite] [1.617(2) Å and
1.639(2)].18 Interestingly, the P(1)–O(3)–C(4) and P(1)–O(4)–
C(10) angles of 123.0(4)° and 114.5(4)°, respectively, differ sig-
nificantly. This is therefore in good agreement with earlier 13C
NMR spectroscopic observations concerning 13C–31P coupling
constants, where large differences observed in the coupling be-
haviour of C(4) to P(1) and C(10) to P(1) were tentatively
ascribed to variations in the relevant P–O–C angles. However, it
is noted that the structures in solution and in the solid may be
different because of crystal packing effects and correlation of
such connectivity data with other analytical results should there-
fore be interpreted with caution.
Fig. 6 Molecular structure of 10 showing the numbering scheme.
Thermal ellipsoids are set at 50% probability level and hydrogen atoms
are omitted for clarity. Selected bond lengths (Å) and angles (°): P(1)–
O(1) 1.654(5), P(1)–O(3) 1.614(5), P(1)–O(4) 1.645(5), O(1)–C(1)
1.285(10), O(3)–C(4) 1.415(8), O(4)–C(10) 1.418(8), O(2)–C(1) 1.342
(14), C(1)–C(2) 1.452(12), O(3)–P(1)–O(1) 99.5(3), O(4)–P(1)–O(1)
92.3(3), O(3)–P(1)–O(4) 103.6(2), C(1)–O(1)–P(1) 120.5(6), C(4)–
O(3)–P(1) 123.0(4), C(10)–O(4)–P(1) 114.5(4), O(1)–C(1)–O(2) 111.5
(10), O(4)–C(10)–C(15) 114.6(6), O(4)–C(10)–C(11) 121.4(6), C(4)–
C(9)–C(15) 120.5(6), C(10)–C(15)–C(9) 120.0(6).
lengths and angles listed in the figure captions. The dihedral
angles of 61.2(7)° and 56.7(8)° measured between the aryl rings
of 11 are analogous to those observed for 10 and the literature
example 1,1′-biphenyl-2,2′-diyl-bis[(5,5′,6,6′-tetramethyl-3,3′-di-
tert-butyl-1,1′-biphenyl-2,2′-diyl)phosphite].18
In contrast, the corresponding torsion angles in 13 are signifi-
cantly smaller [49.5(4)° and 42.7(4)°], suggesting that steric
repulsions between the methyl ring substituents contribute to the
widening of this angle in 10 and 11. From a comparison of the
bond lengths and angles of 10, 11 and 13 it is evident that
Compound 11 crystallises at room temperature from a hexane
layered toluene solution as colourless prisms in the monoclinic
space group P21/n, while 13 crystallises from chloroform also as
ˉ
colourless prisms in the triclinic space group P1. Fig. 7 and 8
depict ellipsoid representations of the molecular structures of 11
and 13, showing the numbering schemes with selected bond
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Fig. 7 Molecular structure of 11 showing the numbering scheme.
Thermal ellipsoids are set at 50% probability level and hydrogen atoms
are omitted for clarity. Selected bond lengths (Å) and angles (°): P(1)–
O(1) 1.682(4), P(1)–O(3) 1.629(4), P(1)–O(4) 1.607(5), O(1)–C(1)
1.345(9), O(3)–C(9) 1.441(7), O(4)–C(15) 1.406(8), O(2)–C(1) 1.203
(9), C(1)–C(2) 1.515(8), O(3)–P(1)–O(1) 92.92(19), O(4)–P(1)–O(1)
89.7(2), O(3)–P(1)–O(4) 102.4(2), C(1)–O(1)–P(1) 116.8(4), C(9)–
O(3)–P(1) 113.3(3), C(15)–O(4)–P(1) 123.8(3), O(1)–C(1)–O(2) 121.8
(6), O(4)–C(15)–C(20) 117.0(6), O(4)–C(15)–C(16) 120.0(5), C(9)–
C(14)–C(20) 119.5(5), C(14)–C(20)–C(15) 119.9(6).
Fig. 8 Molecular structure of 13 showing the numbering scheme.
Thermal ellipsoids are set at 50% probability level and hydrogen atoms
are omitted for clarity. Selected bond lengths (Å) and angles (°): P(1)–
O(1) 1.671(2), P(1)–O(3) 1.635(2), P(1)–O(4) 1.615(2), O(1)–C(1)
1.370(4), O(3)–C(9) 1.404(3), O(4)–C(15) 1.421(4), O(2)–C(1) 1.203
(4), C(1)–C(2) 1.499(5), O(3)–P(1)–O(1) 93.28(11), O(4)–P(1)–O(1)
100.39(12), O(3)–P(1)–O(4) 102.74(11), C(1)–O(1)–P(1) 117.4(2),
C(9)–O(3)–P(1) 117.60(18), C(15)–O(4)–P(1) 127.87(19), O(1)–C(1)–
O(2) 121.5(3), O(4)–C(15)–C(20) 117.7(3), O(4)–C(15)–C(16) 118.6
(3), C(9)–C(14)–C(20) 123.5(2), C(14)–C(20)–C(15) 124.6(3).
variations amongst like bonds are small, nevertheless, a few
observations are in order. On average, the P–O bond lengths in
10 are somewhat longer than those in 11 and 13, while the P(1)–
O(4) bond in 11 is slightly shorter than the equivalent bond in
13. The latter may too be the result of steric repulsions among
methyl substituents on the phenyl backbone. In line with these
observations, the P(1)–O(3)–C(9) and P(1)–O(4)–C(15) angles
in 13 are significantly greater than the related angles in 10 and
11. In all cases P(1)–O(3)–C(9) and P(1)–O(4)–C(15) are signifi-
cantly different so they do not provide an explanation for the
apparent equivalence of C(9) and C(15) in the 13C NMR spectra
of 12 and 13.
from Alfa Aesar. N,N′-Tetramethyl-1,2-diaminoethane (TMEDA)
and anhydrous copper(II) chloride (CuCl2), purchased from
Aldrich, were used as received unless otherwise stated. Pro-
panoic acid, purchased from BDH laboratories, was dried over
KOH pellets and distilled under N2 prior to use. 3,3′,5,5′-Tetra-
tert-butyl-1,1′-biphenyl-2,2′-diol was prepared using a standard
literature procedure.19 5-Chlorodibenzophosphole was prepared
from 2,2′-dibromobiphenyl following
a reported literature
procedure.13
Toluene, tetrahydrofuran (thf), diethyl ether and hexane were
dried using a Braun Solvent Purification System and degassed
by additional freeze–pump–thaw cycles when deemed necessary.
Methanol was distilled under nitrogen from calcium hydride
(CaH2). Deuterated dichloromethane and chloroform were
purchased from Aldrich and dried over phosphorus pentoxide
(P2O5), degassed via three freeze–pump–thaw cycles and trap-to-
trap distilled prior to use.
Experimental
General procedures and instruments
NMR spectra were recorded on a Bruker Avance 300 FT or
Bruker Avance II 400 MHz spectrometer (1H NMR at 300/
400 MHz, 13C NMR at 75/100 MHz and 31P NMR at 121/
162 MHz) with chemical shifts reported relative to TMS (1H,
13C) or 85% H3PO4 (31P) as external reference. 1H and 13C
NMR spectra were measured internally relative to deuterated
solvent resonances which were referenced relative to TMS.
Solid state IR spectra were recorded using pressed KBr pellets
on a Perkin Elmer Spectrum GX IR spectrometer. Elemental
analysis was performed by the University of St. Andrews micro-
analytic service using a Carlo Erba CHNS/O microanalyser.
Melting points were determined on a Gallenkamp apparatus and
are uncorrected. Mass spectra were recorded by the Mass Spec-
trometry Service Centre at the University of St. Andrews on
Reactions were carried out under dinitrogen gas (N2, passed
through a column of Cr(II) adsorbed on silica) using standard
Schlenk, vacuum-line and cannula techniques. All glassware was
flame-dried under vacuum. Triethylamine (NEt3), chlorodiphe-
nylphosphine (Ph2Cl) and phosphorus trichloride (PCl3) were
purchased from Aldrich and distilled under N2 prior to use.
Before distilling, the NEt3 was dried over potassium hydroxide
(KOH) pellets while PCl3 was refluxed for 3 h to remove any
free hydrochloric acid (HCl). 5,5′,6,6′-Tetramethyl-3,3′-di-tert-
butyl-1,1′-biphenyl-2,2′-diol, sodium propanoate and phenylace-
tic acid, were purchased from Aldrich and dried azeotropically
with toluene. 2,2′-Biphenyldiol (purified by sublimation), (R)-
(+)-1,1′-bi(2-naphthol) (dried azeotropically with toluene), 2,2′-
dibromobiphenyl and 2,4-di-tert-butylphenol were purchased
This journal is © The Royal Society of Chemistry 2012
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either a Micromass GCT EI/CI or a Micromass LCT ES
instrument.
which time the white sodium propanoate suspension cleared and
sodium chloride (NaCl) precipitated from solution. After the 2 h
stirring period, the formed NaCl was removed by filtration
(cannula fitted with a membrane filter) and the colourless filtrate
reduced to dryness in vacuo to yield the product as a colourless
viscous oil which analysed to consist solely of disproportiona-
tion products.
Synthesis
(Propanoyloxy)diphenylphosphine (1).
General procedure for the preparation of bisphenoxy-
phosphoruschlorides (4–7). These compounds were prepared
according to a modified literature procedure.14 A solution of the
appropriate diol (9.22 mmol) in thf (20 ml) was added to a
solution of PCl3 (1.27 g, 9.22 mmol, 0.81 ml) in thf (10 ml) at
−40 °C. NEt3 (1.87g, 18.45 mmol, 2.57 ml) was then added
dropwise via a syringe to the colourless solution. This led to the
immediate precipitation of the formed [HNEt3][Cl] as a white
solid. The resulting mixture was stirred at −40 °C for 1 h and
then for a further hour at room temperature. After this stirring
period, the mixture was filtered and reduced to dryness in vacuo
to obtain the pure products.
Compound 1 was prepared following either the known pro-
cedure12 or the adapted literature procedure5 as described here:
Ph2PCl (1.32 g, 6.0 mmol, 1.08 ml) was added dropwise to a
solution of propanoic acid (0.44 g, 6.0 mmol, 0.48 ml) in thf
(30 ml) at −10 °C. NEt3 (0.61 g, 6.0 mmol, 0.836 ml) was
added to the stirring mixture, leading to the immediate formation
of [HNEt3][Cl] in the form of a white precipitate. After having
been stirred at −10 °C for 10 min, the mixture was filtered over a
plug of anhydrous MgSO4 and all volatiles removed under
reduced pressure to furnish compound 1 as a colourless oil
(a) (1,1′-Biphenyl-2,2′-dioxy)chlorophosphine (4). Prepared
according to the general procedure described.
1
(yield: 1.43 g, 93%). H NMR (300 MHz, CD2Cl2): δH = 1.18
(t, 3H, 3J = 7.5 Hz; H3), 2.53 (m, 2H, 3J = 7.5 Hz; H2),
7.40–7.59 (m, 10H, Ph). 31P{1H} NMR (121 MHz, CD2Cl2): δP
= 98.9 (s). The spectra are consistent with those reported in the
literature.12
(Phenylacetyloxy)diphenylphosphine (2).
Starting diol: 2,2′-Biphenyldiol (1.72 g, 9.22 mmol). Title
product obtained as a viscous colourless oil (yield: 1.92 g, 83%).
3
1H NMR (300 MHz, CD2Cl2): δH = 7.29 (dm, 2H, J = 7.5 Hz;
3
H3/H9), 7.47 (td, 2H, J = 7.5 Hz,4J = 2.0 Hz; H4/H10), 7.40
3
3
4
(tm, 2H, J = 7.5 Hz; H5/H11), 7.56 (dd, 2H, J = 7.5 Hz, J =
2.0 Hz; H6/H12). 13C{1H} NMR (75 MHz, CD2Cl2): δC = 122.6
(d, JC–P = 1.9 Hz; C3/C9), 126.9 (s; C5/C11), 130.0 (s, C4/C10),
3
A solution of phenylacetic acid (1.36 g, 10.00 mmol) in thf
(30 ml) at −10 °C was treated with Ph2PCl (2.21 g,
10.00 mmol). NEt3 (1.01 g, 1.39 ml, 10.00 mmol) was then
added dropwise via a syringe leading to the immediate precipi-
tation of [HNEt3][Cl]. The resulting mixture was allowed to
stir for 10 min at −10 °C and subsequently filtered through a
plug of MgSO4 in a filter column. The filtrate was then reduced
to dryness to furnish the product as a white microcrystalline
130.3 (d, JC–P = 3.3 Hz; C1/C7), 130.7 (s; C6/C12), 149.7
3
(d, JC–P = 5.6 Hz; C2/C8).31P{1H} NMR (121 MHz, CD2Cl2):
2
δP = 179.7 (s).
(b) (R)-(1,1′-Binaphthalen-2,2′-dioxy)chlorophosphine (5). Pre-
pared according to the general procedure described.
1
solid (yield: 1.37 g, 72%). Mp 22–24 °C. H NMR (300 MHz,
CD2Cl2): δH = 3.91 (d, 2H, 4J = 1.0 Hz; H2), 7.42–7.65
(m, 15H, Ph). 13C{1H} NMR (75 MHz, CD2Cl2): δC = 42.6
3
4
(d, JC–P = 2.1 Hz; C2), 127.6 (s; Ph–Cpara), 128.9 (d, JC–P
=
Starting diol: (R)-(+)-1,1′-Bi(2-naphthol) (2.64 g, 9.22 mmol).
Title product obtained as a white solid (yield: 2.23 g, 69%). H
7.03 Hz; PPh–Cmeta), 129.0 (s; PPh–Cpara), 129.8 (s; Ph–Cmeta),
1
130.5 (s; Ph–Cortho), 131.2 (d, JC–P = 23.8 Hz, PPh–Cortho),
2
NMR (300 MHz, CD2Cl2): δH = 7.26–7.33 (m, 2H), 7.38 (dd,
134.2 (s; P–Cipso), 139.4 (d, JC–P = 19.4 Hz; PPh–Cipso).
1
2H, 3J = 8.1 Hz, J = 3.4 Hz), 7.49–7.52 (m, 3H), 7.55 (dd, 1H,
4
31P{1H} NMR (121 MHz, CD2Cl2): δP = 100.2 (s). IR (KBr):
ν˜ = 3058 [w, sp2 ν(C–H)], 3027–2860 [w, sp3 ν(C–H)], 1720 [st,
ν(CvO)], 1497–1439 [st, Ar ν(CvC)], 738 [st, ν(P–O)].
3J = 8.8 Hz, 4J = 0.9 Hz), 8.0 (dd, 2H, 3J = 8.2 Hz, 4J = 2.8 Hz),
8.05 (dd, 2H, 3J = 8.8 Hz, 4J = 2.8 Hz). 13C{1H} NMR
3
(75 MHz, CD2Cl2): δC = 121.5 (s), 121.9 (s), 123.5 (d, JC–P
=
3
5-(Propanoyloxy)dibenzophosphole (3). A solution of 5-
chloro-dibenzophosphole (0.97 g, 4.45 mmol) in thf (10 ml) was
2.8 Hz), 124.7 (d, JC–P = 5.8 Hz), 125.9 (s), 126.1 (s), 126.9
(s), 127.0 (s), 127.1 (s), 127.2 (s), 128.9 (s), 130.5 (s), 131.5 (s),
131.8 (s), 132.0 (s), 132.5 (s), 132.8 (s), 133.1 (s), 147.2
added to
a suspension of sodium propanoate (0.43 g,
2
2
4.45 mmol) in thf (10 ml) at room temperature. The resulting
mixture was allowed to stir at this temperature for 2 h, during
(d, JC–P = 3.0 Hz), 148.6 (d, JC–P = 4.86 Hz). 31P{1H} NMR
(121 MHz, CD2Cl2): 178.3 (s).
3684 | Org. Biomol. Chem., 2012, 10, 3677–3688
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(c)
(5,5′,6,6′-Tetramethyl-3,3′-di-tert-butyl-1,1′-biphenyl-2,2′-
2 h, during which time the white sodium propanoate suspension
cleared and sodium chloride (NaCl) precipitated from solution.
After the 2 h stirring period, the formed NaCl was removed by
filtration (either over a MgSO4 plug or by using a cannula fitted
with a membrane filter) and the colourless filtrate reduced to
dryness in vacuo to yield the product as a colourless viscous oil
contaminated with ca. 8% (based on NMR integration) of the
by-product 14 (crude yield: 1.54 g, 93%). This impurity could
not be separated from the title compound, using standard purifi-
cation techniques. 1H NMR (300 MHz, CD2Cl2): δH = 1.18
dioxy)chlorophosphine (6). Prepared according to the general
procedure described.
3
3
(t, 3H, J = 7.4 Hz; H3), 2.46 (q, 2H, J = 7.4 Hz; H2), 7.27
3
4
3
(dd, 2H, J = 7.6 Hz, J = 1.2 Hz; H5/H11), 7.37 (td, 2H, J =
Starting diol: 5,5′,6,6′-Tetramethyl-3,3′-di-tert-butyl-1,1′-biphe-
nyl-2,2′-diol (3.27 g, 9.22 mmol). Title product obtained as a
7.6 Hz, 4J = 1.2 Hz; H7/H13), 7.45 (td, 2H, 3J = 7.6 Hz, 4J = 2.0
Hz; H6/H12), 7.54 (dd, 2H, J = 7.6 Hz, J = 2.0 Hz; H8/H14).
13C{1H} NMR (75 MHz, CD2Cl2): δC = 9.0 (s; C3), 28.9
(s; C2), 122.4 (s; C5/C11), 126.3 (s; C7/C13), 129.9 (s; C6/C12),
3
4
1
white solid (yield: 3.17 g, 82%). H NMR (300 MHz, CDCl3):
δH = 1.56 (s, 18H; H8/H18), 1.93 (s, 3H; H9), 1.99 (s, 3H; H19),
2.39 (s, 6H; H10/H20), 7.32 (s, 1H; H4), 7.33 (s, 1H; H14). 13C
{1H} NMR (75 MHz, CDCl3): δC = 16.6 (s; C10), 16.9 (s; C20),
20.1 (s, C9/C19), 31.2 (s; C8), 32.3 (d, 5JC–P = 5.0 Hz; C18), 34.7
(s; C7), 35.1 (s; C17),128.3 (s; C4), 129.0 (s; C14), 130.4 (d,
130.6 (s; C8/C14), 131.5 (d, JC–P = 3.4 Hz; C9/C15), 149.3
3
2
2
(d, JC–P = 4.9 Hz; C4/C10), 173.6 (d; JC–P = 5.1 Hz; C1). 31P
{1H} NMR (121 MHz, CD2Cl2): δP = 142.5 (s). IR (solution
in CH2Cl2): ν˜ = 3066 [w, sp2 ν(C–H)], 2970–2877 [w, sp3
ν(C–H)], 1740 [st, ν(CvO)], 1499–1436 [st, Ar ν(CvC)],
769 [st, ν(P–O)]. ES-MS: m/z (%) = 289 (8) [M]+, 215 (100)
[M − OC(O)CH2CH3]+. For by-product 14:
3JC–P = 2.8 Hz; C1), 131.9 (d, JC–P = 5.7 Hz; C11), 132.9 (s;
3
C5), 133.9 (s; C15), 137.6 (d, 3JC–P = 1.8 Hz; C3), 138.5 (d, 3JC–
= 3.5 Hz; C13), 143.9 (d, JC–P = 5.7 Hz; C2), 145.5 (s; C12).
2
P
31P{1H} NMR (121 MHz, CDCl3): δP = 164.3 (s).
(d) (3,3′,5,5′-Tetra-tert-butyl-1,1′-biphenyl-2,2′-dioxy)-chloropho-
sphine (7). Prepared according to the general procedure
described.
3
1H NMR (300 MHz, CDCl3): δH = 1.39 (dd, 3H, J = 7.5 Hz;
3
3
H3), 2.34 (m, 2H; H2), 5.41 (m, 1H, JH–H = 14.8 Hz, JH–H
=
8.1 Hz, 2JH–P = 6.6 Hz, 2JH–P = 4.9 Hz; H1), 7.20–7.54 (m, 16H;
Ph). 13C{1H} NMR (75 MHz, CDCl3): δC = 8.5 (s; C3), 25.7
(s; C2), 74.4 (d, JC–P = 7.5 Hz; C1). 31P{1H} NMR (121 MHz,
2
3
3
CDCl3): δP = 1.9 (d, JPA–PB = 24.1 Hz; PA), 26.4 (d, JPB–PA
=
24.1 Hz; PB).
Starting diol: 3,3′,5,5′-Tetra-tert-butyl-1,1′-biphenyl-2,2′-diol
(3.79 g, 9.22 mmol). Title product obtained as a white solid
1
(R)-Propanoyl-(1,1′-binaphthyl-2,2′-diyl)phosphite (9).
(yield: 3.24 g, 74%). H NMR (300 MHz, CDCl3): δH = 1.39
4
(s, 18H; H8/H18), 1.51 (s, 18H; H10/H20), 7.21 (d, 2H, J = 2.5
4
Hz; H4/H14), 7.50 (d, 2H, J = 2.5 Hz; H6/H16). 13C{1H} NMR
(75 MHz, CDCl3): δC = 31.5 (s; C8/C18), 31.5 (s; C10/C20), 34.8
(s; C9/C19), 35.6 (s; C7/C17), 124.9 (s, C4/C14), 126.8 (s; C6/
3
3
C16), 132.7 (d, JC–P = 4.2 Hz; C1/C11), 140.5 (d, JC–P = 2.2
Hz; C3/C13), 145.6 (d, JC–P = 6.2 Hz; C2/C12). 31P{1H} NMR
2
Compound 9 was prepared using the same method as was
described for 8, by treating a solution of 5 (1.28 g, 3.64 mmol)
in thf (15 ml) with a suspension of sodium propanoate (0.35 g,
3.64 mmol) in thf (20 ml) at 45 °C for 2 h. The title product was
obtained as a white solid contaminated by small amounts of
rearrangement products (8%, based on NMR integrals), which
could not be separated from 9 using standard purification
techniques without effecting further rearrangement. 1H NMR
(121 MHz, CDCl3): δP = 171.6 (s).
Propanoyl-(1,1′-biphenyl-2,2′-diyl)phosphite (8).
3
(300 MHz, CD2Cl2): δH = 1.15 (t, 3H, J = 7.5 Hz; H3), 2.40
3
4
(qd, 2H, J = 7.5 Hz, JH–P = 0.8 Hz; H2), 7.26–7.33 (m, 2H),
3
4
Adapted from a literature procedure for the preparation of (R)-
acetyl-(1,1′-binaphthyl-2,2′-diyl)phosphite.10 A solution of 4
(1.45 g, 5.80 mmol) in thf (20 ml) was added to a suspension of
sodium propanoate (0.557 g, 5.80 mmol) in thf (15 ml) at 45 °C.
The resulting mixture was allowed to stir at this temperature for
7.38 (m, 2H), 7.45–7.52 (m, 3H), 7.58 (dd, 1H, J = 8.8 Hz, J
= 0.9 Hz), 8.0 (d, 2H, 3J = 8.2 Hz), 8.05 (m, 2H). 13C{1H}
NMR (75 MHz, CD2Cl2): δC = 8.9 (s; C3), 28.9 (d, JC–P = 2.2
3
Hz; C2), 121.6 (s), 121.9 (s), 123.3 (d, JC–P = 2.5 Hz), 124.7
3
3
(d, JC–P = 5.6 Hz), 125.7 (s), 125.9 (s), 126.9 (s), 127.0 (s),
This journal is © The Royal Society of Chemistry 2012
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127.1 (s), 127.2 (s), 128.8 (s), 128.9 (s), 130.5 (s), 131.2 (s),
ν(C–H)], 1740 [st, ν(CvO)], 1480–1393 [m, Ar ν(CvC)],
738 [m, ν(P–O)]. ES-MS: m/z (%) = 456 (20) [M]+, 383 (100)
[M − OC(O)CH2CH3]+.
2
131.8 (s), 132.3 (s), 132.8 (s), 133.1 (s), 147.1 (d, JC–P = 2.2
2
2
Hz), 147.9 (d, JC–P = 4.1 Hz), 173.6 (d, JC–P = 5.0 Hz; C1).
31P{1H} NMR (121 MHz, CD2Cl2): δP = 141.8 (s). IR (KBr):
ν˜ = 3059 [w, sp2 ν(C–H)], 2980–2940 [w, sp3 ν(C–H)], 1739 [st,
ν(CvO)], 1508–1407 [m, Ar ν(CvC)], 746 [st, ν(P–O)]. For
by-product 15:
Phenylacetyl-(5,5′,6,6′-tetramethyl-3,3′-di-tert-butyl-1,1′-
biphenyl-2,2′-diyl)phosphite (11).
Diastereomer 1: 1H NMR (300 MHz, CDCl3): δH = 1.23
(dd, 3H, J = 7.5 Hz; H3), 2.18 (m, 2H; H2), 5.26 (m, 1H; H1),
3
Phenylacetic acid (0.53 g, 3.86 mmol) was dissolved in thf
(15 ml) and cooled to −10 °C. NEt3 (0.39 g, 0.54 ml,
3.86 mmol) was added dropwise via syringe to this solution and
the resulting mixture allowed to stir for 5 min. A solution of 6
(1.62 g, 3.86 mmol) in thf (20 ml) was then cannulated into the
mixture, while maintaining the external temperature at −10 °C.
The reaction solution was allowed to stir for 20 min at this temp-
erature and then for another 20 min at room temperature. The
formed [HNEt3][Cl] was subsequently removed by filtration
(cannula fitted with a membrane filter) and the colourless filtrate
stripped of all volatiles under reduced pressure to obtain the
crude product as a white foam. This foam was washed with
copious amounts of hexane (3 × 30 ml) and dried in vacuo to
yield the analytically pure product as a white solid (1.84 g,
92%). Colourless prisms suitable for single crystal X-ray analysis
could be obtained by slow diffusion of a hexane into a solution
of 11 in toluene at room temperature. Mp 164–166 °C. Anal.:
Found C 73.27, H 7.58; C32H39O4P requires C 74.11, H 7.58%.
1H NMR (300 MHz, CDCl3): δH = 1.44 (s, 9H; H11), 1.45
(s, 9H; H21), 1.82 (s, 3H; H12), 1.86 (s, 3H; H22), 2.28 (s, 3H;
H13), 2.30 (s, 3H; H23), 3.66 (s, 2H; H2), 7.23 (s, 1H; H6), 7.24
(s, 1H; H16), 7.18–7.34 (m, 5H, Ph). 13C{1H} NMR (75 MHz,
CDCl3): δC = 16.6 (s; C13), 16.9 (s; C23), 20.5 (s; C12/C22), 31.0
7.25–8.10 (m, 24H; Ph). 31P{1H} NMR (121 MHz, CDCl3): δP
3
3
= 3.57 (d, JPA–PB = 23.3 Hz; PA), 27.6 (d, JPB–PA = 23.3 Hz;
1
PB). Diastereomer 2: H NMR (300 MHz, CDCl3): δH = 1.43
(dd, 3H, J = 7.5 Hz; H3), 2.35 (m, 2H; H2), 5.27 (m, 1H; H1),
3
7.25–8.10 (m, 24H; Ph). 31P{1H} NMR (121 MHz, CDCl3): δP
= 2.67 (d, 3JPA–PB = 28.9 Hz; PA), 26.6 (d, 3JPB–PA = 28.9 Hz; PB).
Propanoyl-(5,5′,6,6′-tetramethyl-3,3′-di-tert-butyl-1,1′-biphe-
nyl-2,2′-diyl)phosphite (10).
Compound 10 was prepared using a similar methodology to that
which was described for the preparation of 8. A solution of 6
(1.17 g, 2.79 mmol) in thf was added to a suspension of sodium
propanoate (0.26 g, 2.79 mmol) in thf (10 ml) at 45 °C. After a
2 h stirring period, the formed NaCl was removed by filtration
(cannula fitted with a membrane filter) and the colourless filtrate
reduced to dryness in vacuo. The resulting white residue was
extracted with hexane (40 ml), filtered and subsequently stripped
of solvent under reduced pressure to furnish the analytically pure
product as a white solid (yield: 1.20 g, 94%). Crystals (colour-
less prisms) suitable for single crystal X-ray diffraction determi-
nation could be obtained by slowly cooling a saturated solution
of 10 in warm hexane (40 °C) to −22 °C. Mp 151–153 °C.
Anal.: Found C 71.07, H 8.59; C27H37O4P requires: C 71.03, H
8.17%. 1H NMR (300 MHz, CD2Cl2): δH = 1.09 (t, 3H, 3J = 7.5
Hz; H3), 1.45 (s, 9H; H11), 1.49 (s, 9H; H21), 1.83 (s, 3H; H12),
5
(d, JC–P = 4.5 Hz; C11), 31.5 (s; C21), 34.7 (s; C10), 34.9 (s;
C20), 41.8 (s; C2), 127.3 (s; Ph–Cpara), 128.1 (s; Ph–Cmeta),
128.3 (s; Ph–Cortho), 129.5 (s; C6), 130.2 (s; C16), 130.2 (s; C9),
132.0 (s; Ph–Cipso), 132.8 (s; C19), 132.4 (s; C7), 133.4 (s; C17),
134.4 (s; C8), 135.2 (s; C18), 137.2 (s; C5), 138.9 (s, C15), 143.9
(s; C4), 144.6 (d, 2JC–P = 4.7 Hz; C14), 170.5 (d, 2JC–P = 5.3 Hz;
C1). 31P{1H} NMR (121 MHz, CD2Cl2): δP = 129.3 (s). IR
(KBr): ν˜ = 3042 [w, sp2 ν(C–H)], 2952–2863 [st, sp3 ν(C–H)],
1729 [st, ν(CvO)], 1493–1359 [m, Ar ν(CvC)], 735 [st,
ν(P–O)]. ES-MS: m/z (%) = 518 (48) [M]+, 383 (100) [M − OC-
(O)CH2(C6H5)]+.
3
1.86 (s, 3H; H22), 2.29 (s, 6H; H13/H23), 2.36 (q, 2H, J = 7.5
Hz; H2), 7.23 (s, 1H; H6), 7.24 (s, 1H, H16). 13C{1H} NMR
Propanoyl-(3,3′,5,5′-tetra-tert-butyl-1,1′-biphenyl-2,2′-diyl)-
phosphite (12).
(75 MHz, CD2Cl2): δC = 8.6 (s; C3), 16.6 (s; C13), 16.8 (s; C23),
3
5
20.5 (s; C12/C22), 28.8 (d, JC–P = 2.5 Hz; C2), 31.1 (d, JC–P
=
4.6 Hz; C11), 31.7 (s; C21), 34.9 (s; C10), 35.1 (s; C20), 128.5
(s; C6), 128.8 (s; C16), 130.7 (d, JC–P = 2.9 Hz; C9), 132.2
3
(d, JC–P = 5.5 Hz; C19), 132.8 (s; C7), 133.9 (s; C17), 134.7 (s;
3
C8), 135.6 (s; C18), 137.7 (s; C5), 139.1 (d, 3JC–P = 3.2 Hz; C15),
144.2 (s; C4), 144.9 (d, JC–P = 5.0 Hz; C14), 173.5 (d, JC–P
=
2
2
5.6 Hz; C1). 31P{1H} NMR (121 MHz, CD2Cl2): δP = 129.6 (s).
IR (KBr): ν˜ = 3036 [w, sp2 ν(C–H)], 2952–2868 [st, sp3
3686 | Org. Biomol. Chem., 2012, 10, 3677–3688
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X-ray crystal structure determinations
Employing a similar procedure to that followed during the prep-
aration of compound 8, a solution of 7 (2.34 g, 4.93 mmol) in
thf (20 ml) was reacted with a suspension of sodium propanoate
(0.47 g, 4.93 mmol) in thf (15 ml) at 45 °C for 2 h. After work-
up (as described for 8), the product was extracted with hexane,
filtered and reduced to dryness in vacuo to yield the analytically
pure product as a white solid (yield: 2.34 g, 92%). Mp
139–143 °C. Anal.: Found C 72.77, H 9.31; C31H45O4P requires
A table containing a summary of the crystal data collection and
refinement parameters of compounds 9, 11 and 13 can be found
in the ESI.† Data sets were collected on a Rigaku Mo MM007
(dual port) high brilliance diffractometer with graphite mono-
chromated MoKα radiation (λ = 0.71075 Å). The diffractometer
is fitted with Saturn 70 and Mercury CCD detectors and two
XStream LT accessories. Data reduction was carried out with
standard methods using the software package Bruker SAINT,20
SMART,21 SHELXTL22 and Rigaku CrystalClear, CrystalStruc-
ture, HKL2000. All the structures were solved using direct
methods and conventional difference Fourier methods. All non-
hydrogen atoms were refined anisotropically by full-matrix
least squares calculations on F2 using SHELX-9723 within
an X-seed24,25 environment. The hydrogen atoms were fixed in
calculated positions. Figures were generated with X-seed and
POV Ray for Windows, with the displacement ellipsoids at 50%
probability level unless stated otherwise.
1
C 72.63, H 8.85%. H NMR (300 MHz, CD2Cl2): δH = 1.13
3
(t, 3H, J = 7.4 Hz; H3), 1.38 (s, 18H; H11/H21), 1.50 (s, 18H;
3
4
H13/H23), 2.44 (m, 2H, J = 7.4 Hz; H2), 7.23 (d, 2H, J = 2.5
Hz; H6/H16), 7.51 (d, 2H, J = 2.5 Hz; H8/H18). 13C{1H} NMR
4
(75 MHz, CD2Cl2): δC = 8.5 (s; C3), 28.5 (d, JC–P = 2.5 Hz;
3
C2), 31.1 (d, JC–P = 1.9 Hz; C11/C21), 31.6 (s; C13/C23), 35.5
5
(s; C12/C22), 34.7 (s; C10/C20), 124.6 (s; C6/C16), 126.6
(s; C8/C18), 132.7 (s; C9/C19), 140.5 (s; C5/C15), 145.0 (d, JC–P
2
= 4.7 Hz; C4/C14), 147.1 (s; C7/C17), 173.3 (d, JC–P = 5.1 Hz;
2
C1). 31P{1H} NMR (121 MHz, CD2Cl2): δP = 135.9 (s). IR
(KBr): ν˜ = 3054 [w, sp2 ν(C–H)], 2962–2871 [st, sp3 ν(C–H)],
1743 [st, ν(CvO)], 1459–1397 [m, Ar ν(CvC)], 748
[m, ν(P–O)]. ES-MS: m/z (%) = 512 (31) [M]+, 493 (100)
[M − OC(O)CH2CH3]+.
Conclusions
Slight stabilisation of mixed anhydride systems could be
achieved by the incorporation of electron withdrawing oxygen
atoms directly bonded to the phosphorus atom. Further stabilis-
ation could be realised by increasing the steric bulk surrounding
the phosphorus atoms, thus preventing neighbouring molecules
from reaching close proximity. The latter approach proved most
successful, with the resultant compounds being very stable both
in solution and in the solid state. Acylphosphites derived from
5,5′,6,6′-tetramethyl-3,3′-di-tert-butyl-1,1′-biphenyl-2,2′-diol and
3,3′,5,5′-tetra-tert-butyl-1,1′-biphenyl-2,2′-diol represent the
most stable of all the mixed anhydrides prepared during this
study. The solid state molecular structures could be determined
for three of these stable mixed anhydrides using single crystal
X-ray diffraction.
Phenylacetyl(3,3′,5,5′-tetra-tert-butyl-1,1′-biphenyl-2,2′-diyl)-
phosphite (13).
Compound 13 was prepared according to the procedure
described for 11, employing phenylacetic acid (0.82 g,
6.04 mmol), NEt3 (0.61 g, 0.84 ml, 6.04 mmol) and 7 (2.87 g,
6.04 mmol). The analytically pure product was obtained as a
white solid (yield: 3.12 g, 95%) and colourless prisms suitable
for analysis by single crystal X-ray diffraction could be obtained
by slow evaporation of a dichloromethane solution of 13 at room
temperature. Mp 165–167 °C. Anal.: Found C 75.11, H 8.50;
C36H47O4P requires C 75.23, H 8.24%. 1H NMR (300 MHz,
CD2Cl2): δH = 1.37 (s, 18H; H11/H21), 1.46 (s, 18H; H13/H23),
Acknowledgements
The authors would like to Lucite International for financial
support.
Notes and references
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3.71 (s, 2H; H2), 7.19 (d, 2H, J = 2.5 Hz; H6/H16), 7.20–7.35
4
(m, 5H, Ph), 7.46 (d, 2H, J = 2.5 Hz; H8/H18). 13C{1H} NMR
(75 MHz, CD2Cl2): δC = 31.0 (s; C13), 31.1 (s; C23), 31.6
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3
(d, JC–P = 3.7 Hz; C9/C19), 132.8 (s; Ph–Cipso), 140.5
(s; C5/C15), 145.0 (d, 2JC–P = 5.0 Hz; C4/C14), 147.2 (s; C7/C17),
2
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2955–2865 [st, sp3 ν(C–H)], 1730 [st, ν(CvO)], 1474–1394
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3688 | Org. Biomol. Chem., 2012, 10, 3677–3688
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