2,2″-dimethoxy-1,1′:3′,1″-terphenyl as a novel protective group for low-coordinated phosphorus compounds: The case of diphosphenes

Article abstract of DOI:10.1002/hc.10162

A synthetic approach, to meta-terphenyls iodides bearing methoxy groups in the 2 and 2? positions has been described. 2,2″-Dimethoxy-1,1′:3′,1″terphenyl groups have been shown to stabilize diphosphenes in solution. The existence of conformers of the dipho

Full text of DOI:10.1002/hc.10162

Heteroatom Chemistry
Volume 14, Number 4, 2003
ꢀꢀ
ꢀ ꢀ ꢀꢀ
2,2 -Dimethoxy-1,1 :3 ,1 -terphenyl as a
Novel Protective Group for Low-Coordinated
Phosphorus Compounds: The Case of
Diphosphenes
Alex S. Ionkin and William J. Marshall
DuPont Central Research and Development, Experimental Station, Wilmington, Delaware
19880-0328
Received 22 February 2003
group of alpha-diimine Ni(II) complexes, make a
ABSTRACT: A synthetic approach to meta-terphenyls
considerable impact, for example, on the resulting
iodides bearing methoxy groups in the 2 and 2ꢀꢀꢀ posi-
polyethylene [4]. Methoxy-substituted bisphosphi-
tions has been described. 2,2ꢀꢀ -Dimethoxy-1,1ꢀ:3ꢀ,1ꢀꢀ-
nes like 1,3-bis(2,6-dimethoxyphenylphosphino)-
terphenyl groups have been shown to stabilize diphos-
propane happen to be among the most efficient lig-
phenes in solution. The existence of conformers of
ands for copolymerization of ethylene and carbon
ꢁ
C
the diphosphene 7 has also been recorded.
2003
monoxide [5]. In this report we describe a syn-
thetic approach to the meta-terphenyl substituted
diphosphenes bearing methoxy-groups, which could
be used as ligands for late transition-metal catalytic
applications.
Wiley Periodicals, Inc. Heteroatom Chem 14:360–364,
2003; Published online in Wiley InterScience (www.
interscience.wiley.com). DOI 10.1002/hc.10162
RESULTS AND DISCUSSION
INTRODUCTION
A one-pot synthesis of meta-terphenyls via a two-
aryne sequence was tested to prepare methoxy-
substititued meta-terphenyl iodides [6–8]. These
compounds are necessary synthetic intermedi-
ates for building meta-terphenyldihalophosphines,
which are the precursors to diphosphenes in the
synthetic route developed by Yoshifujii [9]. 2,2ꢀꢀ-
Dimethoxy-1,1ꢀ:3ꢀ,1ꢀꢀ-terphenyl-2ꢀ iodide (1) was syn-
thesized fairly easily through the tandem aryne
addition of the Grignard reagent prepared from
1-bromo-2-methoxy-benzene to the 1,3-dichloro-2-
iodo-benzene 2 (see Scheme 1).
Bulky carbo-substituted meta-terphenyl groups have
been used for the stabilization of the diphosphene
derivatives [1–3]. The carbo-substituted meta-
terphenyl substituted diphosphenes have been iso-
lated with yields varying from 20 to 86%, which
looks satisfactory from a preparation point of
view. The introduction of methoxy groups near
the metal center has proved to be of vital impor-
tance in late transition-metal catalysis. The small
deviations in the size and electronic properties
of the ortho-substituents, including the methoxy-
Compound 1 was isolated as a white stable crys-
talline material, and its structure was proved by
X-ray analysis (Fig. 1). As it can be seen from Fig. 1,
the two methoxy-phenyl rings are almost perpendic-
ular to the central phenyl ring. The methoxy groups
Correspondence to: Alex S. Ionkin; e-mail: alex.s.ionkin@usa.
dupont.com.
Contract grant sponsor: DuPont.
Contract grant number: 8389.
2003 Wiley Periodicals, Inc.
c
ꢁ
360

2,2ꢀꢀ-Dimethoxy-1,1ꢀ:3ꢀ,1ꢀꢀ-terphenyl as a Novel Protective Group for Low-Coordinated Phosphorus Compounds 361
SCHEME 2 Preparation of 2-iodo-1,3-dimethoxy-benzene
(3).
SCHEME
1
The route to 2,2ꢀꢀ-dimethoxy-1,1ꢀ:3ꢀ,1ꢀꢀ-
terphenyl-2ꢀ iodide (1).
ation of 1,3-dimethoxy-benzene (4) and subsequent
reaction with iodine [13,14] (Scheme 2).
are on opposite sides of the molecule and point away
from the central ring. Only one conformer of 1, with a
very sharp melting point, was found in the solid state.
The situation in the solution was different. The chlo-
roform solution of 1 gave two sets of signals in 1H and
13C NMR spectra. This can be explained by the pres-
ence of two stable conformers of 1 in solution. The
ratio between the conformers of 1 was about 2:3; and
it did not change upon varying the solvent, for exam-
ple toluene-D-8 instead of CDCl3, or upon increasing
the temperature of the toluene-D-8 solution of 1 up to
100◦C. An unambiguous assignment of the structures
to each conformer was not possible, as no single im-
portant feature stands out from NMR data. There is
some literature on the existence of the conformers in
alkoxy-substituted terphenyl compounds. Two con-
formers have been described in the case of an oxacy-
clophane with terphenyl core [7]. The so-called “up–
up” and “up–down” conformers differ by the position
of alkoxy groups relative to each other and relative to
the aromatic side rings. There are a few calculations
describing conformers of terphenyls, resulting from
the rotation of aromatic side rings around the central
ring [10–12]. The methoxy groups that mainly cause
the increase in the energy barrier toward coplanar
conformation [10].
3.3 equivalents of the Grignard reagent made
from 3 were allowed to react with 1 equivalent
of 2 according to the standard synthetic protocol
for tandem aryne addition of the aryl Grignard
reagent, which was followed by quenching with io-
dine [6–8]. An intended iodine derivative could not
be isolated. Instead 2,2ꢀꢀ,6,6ꢀꢀ-tetramethoxy-1,1ꢀ:3ꢀ,1ꢀꢀ-
terphenyl (5) was obtained (see Scheme 3) [7]. The
structure of compound 5 was proved by 1H, 13C NMR
data, elemental, and X-ray analyses (Fig. 2).
The same phenomenon was observed in attempts
to synthesize terphenyl iodide with bulky 2,4,6-tri-
tert-butylphenyl groups [15], (instead of the 2,6-di-
methoxyphenyl group that we used). The authors
cited possible steric reasons for the failure to pro-
duce the desired iodine derivative and this can be
the explanation in our case too. The self-capture
mode of an aryne formed from 1,3-dimethoxy mag-
nesium iodide might be a second possibility for the
formation of 5. An analogous path for the prepa-
ration of the 2,2ꢀꢀ,6,6ꢀꢀ-tetrachloro-1,1ꢀ:3ꢀ,1ꢀꢀ-terphenyl
has already been published [8,16]. The report that
the Grignard reagent formed from 2-bromo-1,3-
dimethoxy-benzene was stable in the condition of
the same tandem aryne addition [7] implies that we
are leaning toward the sterical reason for explaining
the failure to produce the desired iodide in the above
reaction.
To increase the sterical bulk for more efficient
protection of diphosphenes, a tetra-methoxy analog
of 1 was sought. The starting compound 2-iodo-1,3-
dimethoxy-benzene (3) was prepared by direct lithi-
Since only the moderately bulky terphenyl io-
dide 1 was isolated, we proceeded with this deriva-
tive. The lithiation of 1 was carried out by the
butyllithium in hexanes. The 2ꢀ-dichlorophosphino-
2,2ꢀꢀ-dimethoxy-1,1ꢀ:3ꢀ,1ꢀꢀ-terphenyl 6 was prepared
by the reaction of above terphenyllithium reagent
with phosphorus(III) chloride (Scheme 4). The 31P
SCHEME 3 Formation of 2,2ꢀꢀ,6,6ꢀꢀ-tetramethoxy-1,1ꢀ:3ꢀ,1ꢀꢀ-
terphenyl (5).
FIGURE 1 ORTEP drawing of 1.

362 Ionkin and Marshall
SCHEME 5 The dechlorination of 6.
analysis was grown from benzene. We did not ob-
serve any hydrogen bonding between the oxygen of
methoxy groups and hydrogen of phosphinic acid
(P O H), but we did record a hydrogen bond be-
tween oxygen of phosphoryl group and acidic hy-
drogen (P O H) in the solid state. This hydrogen
bonding dimer, although common with carboxylic
acid groups, is rarer for phosphinic acids. A search
of the Cambridge Crystal Database yielded only three
other structures with a similar arrangement [18–20].
FIGURE 2 ORTEP drawing of 5.
NMR spectrum of 6 showed two close singlets at
δ = 160.7 and 160.6, with a ratio of about 2:3. As
discussed with parent iodide 1, the existence of two
conformers of compound 6 is obvious. Dechlorina-
tion of 6 was performed by potassium in hexanes
(see Scheme 5). The use of magnesium has been
reported to cause complete ortho-phosphorylation
in carbo-substituted meta-terphenyl dichlorophos-
phines [1].
The orange color attributed to the diphosphene
species built up gradually in the above reaction. It
took 2 days for complete conversion of the starting
dichloride 6 to the mixture of 7 and 8. The con-
formers of the diphosphene 7 have chemical shifts
in 31P NMR spectrum at δ = 510.4 and 505.7 with a
ratio of about 1:2. Such downfield shifts are char-
acteristic for trans orientation of the substituents in
the diphosphene moiety [17]. The conformers of the
fused cyclic phosphorus compound 8 have chemical
shifts in 31P NMR spectrum at δ = 129.4 and 127.6
with a ratio of about 3:1. The ortho-phosphorylation
was the predominant process in above reaction and
the ratio between 8 and 7 was 5:2.
Various unsymmetrical diphosphenes (R P
P
Rꢀ) bearing different protective groups at the
phosphorus atoms have been described [21]. To our
knowledge this is the first case of the observation of
conformers in diphosphenes. The rotational isomers
in low-coordinated phosphorus chemistry have been
noted in the family of 1,4-diphospha-1,3-butadienes
[22]. The application of 1 for the stabilization of
other low-coordinated phosphorus compounds is in
progress.
The CCDC contains the supplementary crys-
tallographic data for this paper. These data can
be obtained free of charge from www.ccdc.cam.
ac.uk/conts/retrieving.html (or from the Cambridge
Crystallographic Data Centre, 12, Union Road, Cam-
bridge CB2 1EZ, UK; fax: +44 1223 336033; or
deposit@ccdc.cam.ac.uk). The deposition numbers
are CCDC 202908, 202907, and 202909 for 1, 5, and
9 respectively.
The diphosphene 7 was stable in solution for
a month. However, the attempts to isolate it in
solid form (including the chromatography on silica
gel under inert atmosphere) caused its decomposi-
tion. Compound 8 was isolated as the correspond-
ing phosphinic acid 9 (Scheme 6). Its structure was
proved by NMR data, elemental, and X-ray analyses,
(Fig. 3). A crystal of substance 9 suitable for X-ray
EXPERIMENTAL
2,2ꢀꢀ-Dimethoxy-1,1ꢀ:3ꢀ,1ꢀꢀ-terphenyl-2ꢀ Iodide (1)
To Grignard reagent prepared freshly from 68.54 g
(0.3665 mol) 1-bromo-2-methoxy-benzene and
10.55 g (0.4341 mol) of magnesium turnings in
SCHEME 4 The path to 2ꢀ-dichlorophosphino-2,2ꢀꢀ-dimeth-
oxy-1,1ꢀ:3ꢀ,1ꢀꢀ-terphenyl (6).
SCHEME 6 1-Methoxy-6-(2-methoxy-phenyl)-5-oxo-5H-
5λ5-dibenzophosphol-5-ol (9).

2,2ꢀꢀ-Dimethoxy-1,1ꢀ:3ꢀ,1ꢀꢀ-terphenyl as a Novel Protective Group for Low-Coordinated Phosphorus Compounds 363
FIGURE 3 ORTEP drawing of (9)2·(C6H6)2.
128.69, 129.16, 130.70, 134.71, 144.84, 156.36. 13C
NMR (CDCl3) (minor conformer) δ = 55.64, 107.16,
111.22, 120.32, 127.50, 128.76, 129.18, 130.95,
134.83, 144.84, 156.50. Anal. Calcd. for C20H17IO2:
C, 57.71; H, 4.12. Found: C, 57.36; H, 3.83.
300 ml of THF was added the solution of 25.0 g
(0.0916 mol) of 1,3-dichloro-2-iodo-benzene (2) in
100 ml of THF at room temperature. The reaction
mixture was refluxed for 10 h and allowed to cool
down to ambient temperature. The solution of
34.4 g (0.1354 mol) of I2 in 150 ml of THF was
added dropwise to the reaction mixture with
cooling by water/ice bath. After the mixture was
stirred for 12 h at room temperature, a solution of
50.00 g Na2SO3 in 250 ml of water was added to de-
stroy the excess iodine and to dissolve the inorganic
salts. The organic layer was dried over MgSO4, the
solvents removed in vacuum, and the residue was
recrystalized from ethyl alcohol. The yield of 1 as
a white solid was 28.42 g (75%) with m.p. 128.2◦C.
1H NMR (CDCl3) (major conformer) δ = 3.78 (s, 6H,
Me), 6.94–7.39 (m, 11H, Ar-H); 1H NMR (CDCl3)
(minor conformer) δ = 3.81 (s, 6H, Me), 6.92–7.41
(m, 11H, Ar-H). 13C NMR (CDCl3) (major con-
former) δ = 55.58, 106.84, 111.05, 120.26, 127.38,
2-Iodo-1,3-dimethoxy-benzene (3)
One hundred eighty-seven milliliters of 1.7 M so-
lution of butyllithium in hexanes was added drop-
wise to the solution of 40.0 g (0.2895 mol) of 1,3-
dimethoxybenzene (4) in 150 ml of ethyl ether
containing 0.1 g of tetramethylenediamine at 0◦C.
The reaction mixture was stirred overnight and 74.0
g (0.2913 mol) of iodine in 150 ml of THF was added
again at 0◦C. After stirring the mixture overnight, it
was poured into saturated aqueous Na2SO3 and ex-
tracted by 200 ml of ethyl acetate. The organic phase
was dried over magnesium sulfate and recrystallized
from acetone. The yield of 3 was 66.00 g (86%) with

364 Ionkin and Marshall
m.p. 103.8◦C. 1H NMR (CDCl3) δ = 3.89 (s, 6H, Me),
6.49 (d, 2H, J = 8.0 Hz, Ar-H), 7.25 (d, 1H, J = 8.0
Hz, Ar-H).
The yield of 9 was 2.71 g (64%) as slightly yellow
hygroscopic solid with m.p. 93.7◦C with decompo-
sition. 1H NMR (DMSO-d6) δ = 3.71 (s, 3H, Me),
4.01 (s, 3H, Me), 6.94–8.34 (m, 10H, Ar-H). 31P NMR
(DMSO-d6) δ = 36.3. Anal. Calcd for C20H17O4P: P,
8.79. Found: P, 8.49.
2,2ꢀꢀ,6,6ꢀꢀ-Tetramethoxy-1,1ꢀ:3ꢀ,1ꢀꢀ-terphenyl (5)
To Grignard reagent prepared freshly from 30.00 g
(0.1136 mol) 3 and 5.45 g (0.2242 mol) of magnesium
turnings in 200 ml of THF was added the solution of
9.40 g (0.0344 mol) of 2 in 100 ml of THF at room
temperature. The reaction mixture was refluxed for
10 h and allowed to cool down to ambient tempera-
ture. The solution of 31.74 g (0.1250 mol) of I2 in 150
ml of THF was added dropwise to the reaction mix-
ture with cooling by water/ice bath. After the mixture
was stirred for 12 h at room temperature, a solution
of 50.00 g Na2SO3 in 250 ml of water was added to de-
stroy the excess iodine and to dissolve the inorganic
salts. The organic layer was dried over MgSO4, the
solvents removed in vacuum, and the residue was
purified by chromatography on silica gel with the
mixture of petroleum ether/ethyl ether 8:2 as an elu-
ent. The yield of 5 as a white solid was 2.78 g (23%)
with m.p. 177.5◦C. 1H NMR (CDCl3) δ = 3.67 (s, 12H,
Me), 6.54 (d, J = 8.3 Hz ,4H, Ar-H-3,3ꢀꢀ,5,5ꢀꢀ), 7.29 (t,
J = 8.3 Hz, 2H, Ar-H-4,4ꢀꢀ) 7.30–7.50 (m, 4H, central
Ar-H). 13C NMR (CDCl3) δ = 55.75, 104.26, 119.92,
126.51, 128.13, 129.20, 132.78, 133.55, 157.68. Anal.
Calcd for C22H22O4: C, 75.41; H, 6.33. Found: C, 75.15;
H, 6.32.
ACKNOWLEDGMENT
The authors thank Vicki North for assistance with
DSC measurements.
REFERENCES
[1] Twamley, B.; Sofield, C. D.; Olmstead, M. M.; Power,
P. P. J Am Chem Soc 1999, 121, 3357–3367.
[2] Urnezius, E.; Protasiewicz, J. D. Main Group Chem
1996, 1, 369–372.
[3] Shah, S.; Burdette, S. C.; Swavey, S.; Urbach, F. L.;
Protasiewicz, J. D. Organometallics 1997, 16, 3395–
3400.
[4] Schmid, M.; Eberhardt, R.; Klinga, M.; Leskelae, M.;
Rieger, B. Organometallics 2001, 20, 2321–2330.
[5] Preparation of phosphide intermediates for poly-
merization catalysts. Neth Appl (1989), 28 pp. NL
8800770.
[6] Du, C. J. F.; Hart, H.; Ng, K. K. D. J Org Chem 1986,
51, 3162–3165.
[7] Grewal, R. S.; Hart, H.; Vinod, T. K. J Org Chem 1992,
57, 2721–2726.
[8] Saednya, A.; Hart, H. Synthesis 1996, 12, 1455–1458.
[9] Yoshifuji, M.; Shibayama, K.; Inamoto, N.;
Matsushita, T.; Nishimoto, K. J Am Chem Soc
1983, 105, 2495–2497.
[10] Pan, J.-F.; Chua, S.-J.; Huang, W. Thin Solid Films
2000, 363, 1–5.
[11] Anariba, F.; McCreery, R. L. J Phys Chem B 2002, 106,
10355–10362.
1-Methoxy-6-(2-methoxy-phenyl)-5-oxo-5H-5ꢀ5-
dibenzophosphol-5-ol (9)
Five grams (0.0120 mol) of 1, 100 ml of hexanes, and
8.5 ml of 1.7 M solution of butyllithium in hexanes
were stirred at room temperature for 48 h. Phos-
phorus(III) chloride (2.75 g, 0.020 mol) was added
to the reaction mixture. The reaction mixture was
kept at room temperature for an additional 24 h. The
solvents were removed under vacuum (0.1 mm) at
room temperature and the residue was redissolved
in 200 ml of hexanes. The precipitate was filtered
off. The 31P NMR spectrum of the filtrate contained
only two singlets at δ = 160.7 and 160.6 with ratio
about 2:3. It was used as “it is” in the dechlorination
step. Small pieces of potassium metal (0.93 g, 0.0238
mol) were placed in the above-prepared solution of
the dichlorophosphine 6 at the room temperature
with magnetic stirrer in the nitrogen glovebox. Af-
ter 2 days the mixture was filtered. The solvent was
removed in vacuum and the residue was purified by
chromatography on silica gel, using benzene as an
eluent. Any residual solvent was removed from the
product by drying in vacuum at 0.1 mm over night.
[12] Chavatte, P.; Yous, S.; Marot, C.; Baurin, N.; Lesieur,
D. J Med Chem 2001, 44, 3223–3230.
[13] Bennetau, B.; Rajarison, F.; Dunogues, J.; Babin, P.
Tetrahedron 1993, 49, 10843–10854.
[14] Anderson, J. C.; Pearson, D. J. J Chem Soc, Perkin
Trans 1 1998, 2023–2029.
[15] Schiemenz, B.; Power, P. P. Organometallics 1996, 15,
958–964.
[16] Kress, T. H.; Leanna, M. R. Synthesis 1988, 803–805.
[17] Quin, L. D. A Guide to Organophosphorus Chemistry;
Wiley: New York, 2000; pp. 333–334.
[18] Reis, A. H.; Peterson, S. W.; Druyan, M. E.; Gebert,
E.; Mason, G. W.; Peppard, D. F. Inorg Chem 1976,
15, 2748–2752.
[19] Tkachev, V. V.; Zh Strukt Khim 1991, 32, 125–133.
[20] Kazakov, P. V.; Odinets, I. L.; Antipin, M. Yu.;
Petrovskii, P. V.; Kovalenko, L. V.; Struchkov, Yu. T.;
Mastryukova, T. A. Izv Akad Nauk SSSR Ser Khim
1990, 2120–2127.
[21] Yoshifuji, M. In Multiple Bonds and Low Coordina-
tion in Phosphorus Chemistry; Regitz, M.; Scherer,
O. J. (Eds.); Georg Thieme Verlag: Stuttgart, 1990;
pp. 321–337.
[22] Yoshifuji, M.; Ichikawa, Y.; Toyota, K.; Kasashima, E.;
Okamoto, Y. Chem Lett 1997, 1, 87–88.