A Direct Catalytic Synthesis of Sodium Diarylphosphinates and Their Corresponding Acids from Sodium Phosphinate

Article abstract of DOI:10.1002/ejoc.201601222

In this contribution we present the direct conversion of sodium phosphinate (NaH₂PO₂·H₂O) to symmetrical sodium diarylphosphinates and their corresponding acids by using palladium catalysis. This route eliminates the need for chlorinated precursors, such as PCl₃and intermediate alkyl- or ammoniumphosphinates.

Full text of DOI:10.1002/ejoc.201601222

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Accepted Article
Title: A direct catalytic synthesis of sodium diarylphosphinates and their correspon-
ding acids from sodium phosphinate
Authors: Laurian Botez; G. Bas De Jong; J. Chris Slootweg; Berth-Jan Deelman
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To be cited as: Eur. J. Org. Chem. 10.1002/ejoc.201601222
Link to VoR: http://dx.doi.org/10.1002/ejoc.201601222
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COMMUNICATION
A direct catalytic synthesis of sodium diarylphosphinates and
their corresponding acids from sodium phosphinate
Laurian Botez,[a,b] G. Bas de Jong,[b] J. Chris Slootweg,[b] and Berth-Jan Deelman*[a]
Abstract: In this contribution we present the direct conversion of
sodium phosphinate (NaH2PO2·H2O) to symmetrical sodium
diarylphosphinates and their corresponding acids using palladium
catalysis. This route eliminates the need for chlorinated precursors,
such as PCl3, or intermediate alkyl- or ammoniumphosphinates.
electroless plating.[2] They are registered under REACH as non-
hazardous compounds.[6] In synthesis, sodium phosphinate has
7
]
been applied as
a
reducing agent,[
and for the
hydrophosphination of alkenes and terminal alkynes.[8]
Organophosphinic acids R2P(O)OH (R
= hydrocarbyl
group) and their esters and salts are relevant compounds in
many fields: from flame retardants to solar cells and from ligands
for catalysis to pharmaceutical applications and metal
extraction.[1, 2] They can also be interesting intermediates in the
synthesis of other P-derivatives such as phosphines via
reduction and/or functionalization.[3]
Current processes for the industrial production of
organophosphinic acids and derivatives involve the use of
phosphorus trichloride (PCl3) as starting material. Its availability
is often taken for granted, but it should be realized that its
production requires the use of chlorine gas which carries
inherent risks and is energy intensive. Furthermore, arylation or
alkylation is accomplished by using Grignard-, Michaelis-
Arbuzov- or Michaelis-Becker- type coupling reactions starting
from N,N-dialkylphosphoramide dichlorides (R2NPCl2) or N,N-
dialkylphosphoramic dichlorides (R2NP(O)Cl2) or alternatively by
reacting aryldiazonium fluoroborates with PCl3 in the presence
of a catalyst (CuBr).[ 4 ] These methods generally give sub-
optimal yields, often lead to mixtures, and also generate
significant amounts of waste salts.
Scheme 1. Synthesis of diarylphosphinic acids through arylation of
H,H-phosphinate esters or ammonium salts (1’)[9,10] and directly from
NaH2PO2·H2O (1; this work)
Inspired by previous work on diarylphosphinate
synthesis,[9,10] we investigated the direct diarylation of sodium
phosphinate 1 to sodium diarylphosphinates 2 (Scheme 1,
bottom route). Diarylphosphinates 2’ have been prepared from 1
before, but only indirectly through the corresponding esters or
ammonium salts 1’, which require at least two extra steps to
generate the diarylphosphinic acids 3 (Scheme 1, top route).
Direct diarylation of 1 has only been mentioned so far as a side
reaction in the monoarylation of H,H-phosphinates.[11]
To explore the feasibility of converting 1 (δ(31P) 2.2 ppm in
toluene:methanol = 1:1) directly into 3, we chose Pd(OAc)2 or
Pd2(dba)3 combined with the large bite angle bidentate
phosphine ligands dppf, dppp and xantphos as catalysts to
promote rapid reductive elimination during the P–C coupling
reaction.[12] Initially, with iodobenzene as substrate (Pd loading
4.0 mol%), we only observed low yields of sodium
diphenylphosphinate 2a (2–7% by in-situ NMR spectroscopy;
δ(31P) 20.6 ppm in toluene:methanol = 1:1).[13] Monohydrate 1
performed better than water-free sodium phosphinate (equation
1).[ 14 ] Analysis of the crude reaction mixture by 31P NMR
spectroscopy indicated that significant amounts of unreacted 1
were present along with small amounts of sodium
monophenylphosphinate (δ(31P) 15.0 ppm in toluene:methanol =
1:1).[15]
In an attempt to develop
a
more efficient and
environmentally friendly[5] synthetic pathway for diarylphosphinic
acids, we considered the direct arylation of sodium phosphinate
(also known as sodium hypophosphite, NaH2PO2·H2O, 1). By
starting from this raw material, the use of chlorine gas can be
eliminated, potentially improving overall atom efficiency and
reducing the risks associated with the process. Sodium
phosphinate and its monohydrate are odorless, air- and water-
stable solids produced industrially at multi-ton scale via basic
hydrolysis of white phosphorus (P4) and mainly used in
[a]
[b]
L. Botez, Prof. dr. B.-J. Deelman
Research & Development
ARKEMA B.V.
P.O. Box 70, 4380 AB Vlissingen, The Netherlands
E-mail: berth-jan.deelman@arkema.com
L. Botez, G. B. de Jong, Assoc. Prof. dr. J. C. Slootweg
Department of Chemistry and Pharmaceutical Sciences
Vrije Universiteit Amsterdam, De Boelelaan 1083
1081 HV Amsterdam, The Netherlands
Equation 1. Direct diarylation of NaH2PO2·H2O (1) with PhI.
We then continued our studies using bromobenzene as
substrate, iPr2EtN as the base, and Pd(OAc)2/dppf or
Pd(OAc)2/dppp as catalysts, which gave much better
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/chem.2016xxxxx.
1
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European Journal of Organic Chemistry
10.1002/ejoc.201601222
COMMUNICATION
Table 2. Direct diarylation of NaH2PO2·H2O (1), scope extension.[a]
conversions (Table 1, entries 1–3). The choice of solvent
(toluene:DME or DMF) is crucial as there was little or no
conversion in protic solvents (methanol, acetic acid, water; not
shown). More interestingly, the catalyst derived from the low
valent Pd precursor Pd2(dba)3/xantphos gave even higher
conversions (Table 1, entries 5–7).
Isolated
yield %[b]
δ(31P)
ppm[f]
Table 1. Direct diarylation of NaH2PO2·H2O (1) with PhBr.[a]
Compound
Ar2P(O)OH
3a
86
78
23.4
24.1
Entry
Catalyst
Ligand
Solvent
31P NMR yield %[b]
3b
3c
1
2
3
4
5
6
7
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd2(dba)3
Pd2(dba)3
Pd2(dba)3
dppf
tol:DME (9:1)
tol:DME (9:1)
DMF
40
25
35
63
50
82
dppp
dppp
81
83
24.1
xantphos
xantphos
xantphos
xantphos
DME
DMF
DME
2d[c]
20.1[g]
toluene
90 (100[c]
)
[a] Reaction conditions: NaH2PO2·H2O (1.0 mmol) in solvent (5 mL); entries
1-4: PhBr (2 equiv.), Pd(OAc)2 (4.0 mol%), ligand (4.4 mol%), iPr2EtN (2.3
equiv.); entries 5-7: PhBr (2.5 equiv.), Pd2(dba)3 (2.0 mol%), xantphos (4.4
mol%); iPr2EtN (3.5 equiv.); tol = toluene. [b] determined in-situ by 31P NMR
spectroscopy. [c] Separate experiment using 10 mmol of NaH2PO2·H2O.
3e[d]
66
61
81
27.0[h]
Following these in-situ studies, we used the set of
conditions of entry 7 (Table 1) with a reduced Pd concentration
(2.0 mol%) for preparative work. To isolate diphenylphosphinic
3f
22.8
acid 3a in pure form and to extend the scope of the reaction,[16]
a
simple purification protocol was devised. This involved
evaporation of the volatiles after the reaction, dissolving the
residue in diethyl ether, extracting the ether solution with
aqueous sodium hydroxide followed by acidification and back
extraction into dichloromethane. Evaporation of solvent afforded
the disubstituted phosphinic acids 3a-j (see Table 2 and the
Supporting Information for more details).
3g
21.6
3h
65
21.2
This method afforded 3a[17] (δ(31P) in [D6]DMSO: 23.4 ppm)
in 86% isolated yield. Good yields (75–83%) were also obtained
when using the substrates 4-bromotoluene (3b[18]), 5-bromo-1,3-
19
xylene (3c[ ]), 4-bromobiphenyl (2d, new compound), 4-
3i[e]
bromofluorobenzene (3g[ 20 ]), and even 4-bromonitrobenzene
(3j[ 21 ]). A reduction in yield (41–66%) was observed for the
deactivated 3- and 4-bromoanisoles (3e[22] and 3f[23]), and for
bromoarenes containing groups sensitive to reduction (ethyl 4-
bromobenzoate (3i[ 24 ]) and/or aldol condensation (3h, new
compound). In all cases the mass balance was completed by
unconsumed starting material. The reaction can be run in air
with only a 15% drop in yield (3a).
41
75
21.5
18.3
3j
[a] Reaction conditions: NaH2PO2·H2O (5.0 mmol); ArBr (2.5 equiv.),
Pd2(dba)3 (1.0 mol%), xantphos (2.2 mol%); iPr2EtN (3.5 equiv); toluene (25
mL), reaction time: 20 h. [b] after acid work-up, and corrected for the HPLC
purity. [c] isolated as the [Ar2POO]Na salt. [d] 1 mmol scale. [e] from the
diethylester due to hydrolysis during work up. [f] in [D6]DMSO unless
otherwise specified. [g] in [D4]methanol. [h] in [D1]acetic acid.
Our new method outperforms the known procedures for
making these phosphinic acids, certainly when considering the
fact that the reaction times were not optimized to allow better
comparison between the different substrates.
With the exception of poorly soluble 2d, the reaction
products were isolated as the acids Ar2P(O)OH, which are all
2
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European Journal of Organic Chemistry
10.1002/ejoc.201601222
COMMUNICATION
stable towards air and moisture. They were obtained as white
(3a-c, 3e-i), yellow (3j) or greyish (2d) solids. They generally
dissolve well in methanol, ethanol, alkaline solutions and DMSO
(except for 2d that only dissolved with difficulty in alcoholic and
alkaline solutions).
The reaction intermediate, the monoarylated phosphinate
[Ar(H)P(O)O]Na, has a higher solubility in organic solvents
compared to 1. Thus, consumption of [Ar(H)P(O)O]Na to form
[Ar2P(O)O]Na is faster than the first aryl introduction on 1. In this
way, the disubstituted phosphinates are selectively formed over
the monosubstituted ones, which were only observed in small
amounts as intermediates.
In summary, the novel Pd-catalyzed direct formation of
symmetrical diarylphosphinic acids (Ar2P(O)OH) and their
sodium salts [Ar2P(O)O]Na from the inexpensive, hazard-free
sodium phosphinate NaH2PO2·H2O and bromoarenes is
achieved. The method is well-suited for the synthesis of
diarylphosphinic acids and derivatives with a wide variety of aryl
groups, and tolerates functional groups, such as keto and
carboxyl moieties, that are incompatible with the classical
approach that employs Grignard or organolithium reagents.
M. Hess, E. Killian, H. Maumela, D. S. McGuinness, D. H. Morgan, A.
Neveling, S. Otto, M. Overett, A. M. Z. Slawin, P. Wasserscheid , S.
Kuhlmann, J. Am. Chem. Soc. 2004, 126, 14712–14713.
[5]
[6]
O. Gantner, W. Schipper, J. J. Weigand in Sustainable Phosphorus
Management, (Eds.: R. W. Scholz, A. H. Roy, F. S. Brand, D. T.
Hellums, A. E. Ulrich), Springer Science+Business Media, Dordrecht,
the Netherlands 2014, pp. 240, doi: 10.1007/978-94-007-7250-2.
REACH (Registration, Evaluation, Authorisation and Restriction of
Chemicals) is a regulation of the European Union adopted in 2007 to
improve the protection of human health and the environment in the
European Union (see http://echa.europa.eu/web/guest/regulations/
reach/). Sodium phosphinate is registered under EC no. 231-669-9 and
not classified (status last checked on http://echa.europa.eu on June 12,
2016).
[7]
[8]
a) S. K. Boyer, J. Bach, J. McKenna, E. Jagdmann, J. Org. Chem. 1985,
50, 3408–3411; b) C. Guyon, E. Métay, N. Duguet, M. Lemaire, Eur. J.
Org. Chem. 2013, 5439–5444.
a) S. Deprèle, J.-L. Montchamp, J. Org. Chem. 2001, 66, 6745–6755;
b) to alkyl phosphonates RPO3H2: M. Hill, H. Bauer, W. Krause
(Clariant Finance (Bvi) Limited) US8293938 2012; c) S. Gouault-
Bironneau, S. Deprèle, A. Sutor, J.-L. Montchamp, Org. Lett. 2005, 7,
5909–5912.
Acknowledgements
[9]
Reviews on P–C couplings: a) F. M. J. Tappe, V. T. Trepohl, M.
Oestreich, Synthesis 2010, 3037–3062; b) A. Schwan, Chem. Soc. Rev.
2004, 33, 218–224; c) I. P. Beletskaya, M. A. Kazankova, Russian J.
Org. Chem. 2002, 38(10), 1391–1430; d) D. Prim, J.-M. Campagne, D.
Joseph, B. Andrioletti, Tetrahedron 2002, 58, 2041–2075.
We gratefully thank the European Union (Marie Curie ITN SusPhos,
Grant Agreement No. 317404) for financial support. We thank Ben
Bruyneel and Elwin Jansen (Vrije Universiteit Amsterdam) for measuring
high resolution mass-spectra and Prof. dr. K. Lammertsma for his
generous support.
[10] Diarylation of phosphinates: a) Y. Xu, Z. Li, J. Xia, H. Guo, Y. Huang,
Synthesis 1983, 5, 377–378; b) H. Lei, M. S. Stoakes, A. W.
Schwabacher, Synthesis 1992, 12, 1255–1260; c) C. Huang, X. Tang,
H. Fu, Y. Jiang, Y. Zhao, J. Org. Chem. 2006, 71, 5020–5022; d) M.
Kalek, J. Stawinski, Tetrahedron 2009, 65, 10406–10412; e) O. Berger,
C. Petit, E. L. Deal, J.-L. Montchamp, Adv. Synth. Catal. 2013, 355,
1361–1373.
Keywords: Phosphinate • Homogeneous catalysis • Cross-
coupling • Palladium • Sustainable Chemistry • Industrial
Chemistry
[11] Y. R. Dumond, J.-L. Montchamp, J. Am. Chem. Soc. 2001, 123, 510–
511.
[12] Abbreviations: dba = dibenzylideneacetone; dppf = 1,1’-bis (diphenyl
[1]
Uses of phosphinates: a) S. Levchik, Phosphorus-Based FRs, in Non-
Halogenated Flame Retardant Handbook, (Eds.: A. B. Morgan, C. A.
Wilkie), John Wiley & Sons, Inc., Hoboken, NJ, USA 2014, pp. 17–74,
doi: 10.1002/9781118939239.ch2; b) H. Shen, H. Lin, Y. Liu, J. Zhang,
N. Wang, J. Li, Electrochem. Acta 2001, 56, 2092–2097; c) W.
Ruettinger, M. Yagi, K. Wolf, S. Bernasek, G. C. Dismukes, J. Am.
Chem. Soc. 2000, 122, 10353–10357; d) M. Schuman, X. Lopez, M.
Karplus, V. Gouverneur, Tetrahedron 2001, 57, 10299–10307; e) A. W.
Schwabacher, A. D. Stefanescu, A. Rehman, J. Org. Chem. 1999, 64,
1784–1788; f) P. Schrögel, M. Hoping, W. Kowalsky, A. Hunze, G.
Wagenblast, C. Lennartz, P. Strohrieg, Chem. Mater. 2011, 23(22),
4947–4953.
phosphino)ferrocene, dppp
= 1,3-bis (diphenylphosphino)propane;
xantphos = 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene; DME =
1,2-dimethoxyethane; DMF = dimethylformamide.
[13] J. Chojwoski, M. Cyprik, J. Michalski, L. Wozniak, G. Lanneau,
Tetrahedron 1989, 45, 4403–4414
[14] Variations
in
Pd
catalyst,
ligand,
base
(trimethylamine,
ethyldiisopropylamine, propylene oxide), and solvent (toluene, DME,
toluene:DME = 9:1) gave only modest improvements. A quick test to
achieve a catalytic Ullmann coupling[10c] gave no conversion.
[2]
D. C. Fee, D. R. Gard, C.- H. Yang, Phosphorus compounds in Kirk-
Othmer Encyclopedia of Chemical Technology 4th ed., vol. 18 (Eds.: P.
M. Siegel, B. Richman, E. Zayatz, L. Altieri), John Wiley & Sons, Inc.,
[15] Lower yields of aryliodides vs arylbromides have been observed
previously in the context of P-C coupling. [10d, 10e]
New
York,
USA
1999,
pp.
317-377,
doi:
[16] The influence of different bases was briefly studied: potassium
carbonate did not afford any transformation (most likely because of
limited solubility) while pyridine, Et3N, iPr2EtN provided similar results,
iPr2EtN being the best.
10.1002/0471238961.16081519060505.a01.pub2.
[3]
[4]
Phosphines from phosphinates: a) O. Berger, J.-L. Montchamp, Angew.
Chem. Int. Ed. 2013, 52(43), 11377–11380; b) E. R. Kyba, C. N. Clubb,
Inorg. Chem. 1984, 23, 4766–4768; c) E. Soulier, J.-C. Clément, J.-J.
Yaouanc, H. des Abbayes, Tetrahedron Lett. 1988, 39, 4291–4294.
[17] For comparison, the reported total yield for compound 3a, starting from
PCl3 appears to be at best 49 - 52 % (76% in B. Quanxing,
Jiagang, F. Riqing (Huangshi Lifuda Medicine Chemical Co. Ltd.),
CN105001258A, 2015) in steps: diphenylphosphinic acid from
chlorodiphenylphosphine in 90 - 96 % yield,[4b] chlorodiphenylphosphine
from N,N-diisopropylphosphoramide dichloride and phenyl-Grignard in
80% yield, N,N-diisopropylphosphoramide dichloride from PCl3 in 68%
yield and the yield of phenyl-Grignard from bromobenzene assumed to
be quantitative.[4c] The reported yield of 3a via P-C coupling is 85%. [10d]
C.
a) R.S. Edmundson, The synthesis of phosphonic and phosphinic acids
and their derivatives: Non-functionalized acids in The chemistry of
organophosphorus compounds, vol. 4, Ter- and quinque-valent
phosphorus acids and their derivatives (Eds.: Frank R. Hartley), John
3
Wiley
& Sons, Ltd, Chichester, England 1996, pp. 99–112, doi:
10.1002/9780470682531.pat0062; b) L. R. Ocone, C. W. Schaumann,
B. P. Block, E. N. Walsh, Diphenylphosphinic acid in Inorganic
Syntheses, vol. 8, (Eds.: H. F. Holtzclaw, Jr.), John Wiley & Sons, Inc.,
Hoboken,
NJ,
USA
1966,
pp.
71–74,
doi:
10.1002/9780470132395.ch19; c) A. Bollmann, K. Blann, J. T. Dixon, F.
3
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European Journal of Organic Chemistry
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COMMUNICATION
[18] Chlorotoluene also afforded 3b in 10% yield; For comparison, the best
reported yield for compound 3b is 75% via Grignard reaction (G. M.
Kosolapoff, J. Am. Chem. Soc. 1949, 71, 369–370).
[19] For comparison, the best reported yield for compound 3c is 76% via
Grignard reaction (K. Mashima, K.-h. Kusano, N. Sato, Y.-i. Matsumura,
K. Nozaki, H. Kumobayashi, N. Sayo, Y. Hori, T. Ishizaki, S.
Akutagawa,H. Takaya, J. Org. Chem. 1994, 59, 3064–3076).
[20] For comparison, the best reported yield for compound 3g is 7% (by-
product of monoarylation) via the reaction of diazonium fluoroborate
with PCl3 and catalyst (CuBr). (R. W. Bost, L. D. Quin, A. Roe, J. Org.
Chem. 1953, 18(4), 362–366).
[21] For comparison, the best reported yield for compound 3g is 14% via the
reaction of diazonium fluoroborate with PCl3 and catalyst (CuBr) (G.O.
Doak, L.D. Freedman, J. Am. Chem. Soc. 1951, 73(12), 5656–5657).
[22] For comparison, the reported yield for compound 3e via P-C coupling is
89%.[10d]
[23] For comparison, the best reported yield for compound 3f is 59% via
Grignard reaction (J. Cornforth, Sir, A. F. Sierakowski, T. W. Wallace, J.
Chem. Soc., Perkin Trans. 1982, 1, 2299–2315).
[24] For comparison, the best reported yield for compound 3i is 16% via the
reaction of diazonium fluoroborate with PCl3 and catalyst (CuBr),
followed by oxidation (L. D. Freedman, G. O. Doak, J. Org.
Chem. 1959, 24(5), 638–641).
4
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COMMUNICATION
Entry for the Table of Contents
COMMUNICATION
Laurian Botez, G. Bas de Jong, J. Chris
Slootweg, and Berth-Jan Deelman*
Page No. – Page No.
A direct catalytic synthesis of sodium
diarylphosphinates and their
corresponding acids from sodium
phosphinate
Widely available, hazard-free sodium phosphinate directly furnishes sodium
diarylphosphinates and acids in yields up to 86 % using Pd-catalysis. This versatile
method tolerates moieties such as keto and carboxyl, incompatible with the
classical Grignard or organolithium reagents. This route also eliminates the need for
PCl3, or alkyl- and ammoniumphosphinates.
5
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