New (α-hydroxyalkyl)phosphorus amphiphiles: Synthesis and dissociation constants

Article abstract of DOI:10.1021/jo9805551

Direct synthesis of free (α-hydroxyalkyl)phosphinic acid amphiphiles 1 can be readily realized by sonication of the heterogeneous mixture of 50% aqueous hypophosphorous acid and long-chain aldehydes in the presence of catalytic amounts of hydrochloric aci

Full text of DOI:10.1021/jo9805551

J . Org. Chem. 1998, 63, 7223-7230
7223
New (r-Hyd r oxya lk yl)p h osp h or u s Am p h ip h iles: Syn th esis a n d
Dissocia tion Con sta n ts
Dominique Albouy,† Alice Brun,† Aurelio Munoz,‡ and Guita Etemad-Moghadam*,†
Laboratoire des IMRCP (UMR 5623) and Fe´de´ration de Recherche FR 14, Universite´ Paul Sabatier, 118
route de Narbonne, Baˆt. 2R1, 31062 Toulouse Cedex 04, France
Received March 25, 1998
Direct synthesis of free (R-hydroxyalkyl)phosphinic acid amphiphiles 1 can be readily realized by
sonication of the heterogeneous mixture of 50% aqueous hypophosphorous acid and long-chain
aldehydes in the presence of catalytic amounts of hydrochloric acid. Oxidation of these phosphinic
acids by DMSO in the presence of catalytic amounts of iodine quantitatively leads to the
corresponding phosphonic acids 3. IR spectra of the phosphinic acids 1 in the condensed phase
and in solution reveal the presence of intra- and intermolecular associations. Dissociation constants
of the phosphorus acids 1 and 3 determined by potentiometric and 31P NMR titrations show a good
correlation between the two methods. The phosphinic acid amphiphiles 1 are slightly stronger
than the corresponding phosphonic acids 3. (R-Hydroxyalkyl)phosphonium chlorides are prepared
in good yields from the phosphine PH3 and long-chain aldehydes in acidic media.
In tr od u ction
compounds under base-catalyzed8-13 or under anhydrous
strong acidic conditions are reported.14,15 More recently,
the synthesis of R-hydroxy phosphonates by the combi-
natorial method on the Wang resin has been described.16
Our previous works are focused on the study of the
reactivity of amorphous red phosphorus.17,18 Recently,
we have demonstrated that red phosphorus can react
with aromatic and R,â-ethylenic aldehydes in basic media
via the phosphine, PH3, and in acidic media via hypo-
phosphorous acid, H3PO2, leading to (R-hydroxyalkyl)-
phosphinic acids (Scheme 1).19
In recent years, the preparation of R-hydroxyphos-
phoryl derivatives (phosphonic and phosphinic acids,
esters and salts) has attracted significant attention, due
to their potential biological activities with broad applica-
tions as enzyme inhibitors (renin,1 EPSP synthase,2 HIV
protease,3 and PTPase4) or as dinucleotide analogues
having antiviral properties.5 In addition, they are useful
intermediates in the synthesis of other R- and γ-substi-
tuted phosphorus compounds.6 Their usefulness is also
well-known as extractants in the recovery and separation
of some metal ions.7 Furthermore, the (R-hydroxyalkyl)-
phosphorus substrates (phosphines, phosphine oxides,
and phosphonium salts) can be considered as starting
materials for the synthesis of organophosphorus polymers
possessing flame-resistant and ion-exchange properties
and resins for the production of corrosion-resistant films
on metal surfaces.7
Pursuing our investigation into the reactivity of the
P-H labile phosphorus derivatives,20 and in view to the
preparation of (R-hydroxyalkyl)phosphorus acid am-
phiphiles, we wish to report here the reactivity of
(8) (a) Pudovik, A. N.; Konovalova, I. V. Synthesis 1979, 81. (b)
Wynberg, H.; Smaardijk, Ab A. Tetrahedron Lett. 1983, 24, 5899. (c)
Wolfsberger, von W. Chem. Z. 1985, 109, 317. (d) Majewski, P.
Synthesis 1987, 555.
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Asymmetry 1994, 5, 499. (b) Rath, N. P.; Spilling, C. D. Tetrahedron
Lett. 1994, 35, 227. (c) Blazis, V. J .; Koeller, K. J .; Spilling, C. D. J .
Org. Chem. 1995, 60, 931.
Known preparations of (R-hydroxyalkyl)phosphorus
acids included the Pudovik addition reactions of dialkyl-
H-phosphonates, phosphites, or phosphines to carbonyl
(10) (a) Yokomatsu, T.; Yamagishi, T.; Shibuya, S. Tetrahedron:
Asymmetry 1993, 4, 1779 and 1783. (b) Yokomatsu, T.; Yoshida, Y.;
Shibuya, S. J . Org. Chem. 1994, 59, 7930.
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(b) Sum, V.; Kee, T. P. J . Chem. Soc., Perkin Trans. 1 1993, 1369. (c)
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L. Phosphorus, Sulfur, Silicon Relat. Elem. 1990, 49/ 50, 259. (b) Yuan,
C.; Li, S.; Li, C.; Chen, S.; Huang, W.; Wang, G.; Pan, C.; Zhang, Y.
Heteroatom Chem. 1997, 8, 103.
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(b) Texier-Boullet, F.; Lequitte, M. Tetrahedron Lett. 1986, 27, 3515.
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1978, 100, 3467.
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Silicon Relat. Elem. 1996, 117, 37.
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Tetrahedron Lett. 1994, 35, 3297.
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Albouy, D.; Etemad-Moghadam, G.; Vinatoru, M.; Koenig, M. J .
Organomet. Chem. 1997, 529, 295.
(19) Albouy, D.; Etemad-Moghadam, G.; Koenig, M. To be published.
(20) Semenzin, D.; Etemad-Moghadam, G.; Albouy, D.; Diallo, O.;
Koenig, M. J . Org. Chem. 1997, 62, 2414.
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S0022-3263(98)00555-6 CCC: $15.00 © 1998 American Chemical Society
Published on Web 09/22/1998

7224 J . Org. Chem., Vol. 63, No. 21, 1998
Albouy et al.
Sch em e 1
Sch em e 2
hypophosphorous acid and phosphine, PH3, toward long-
chain aldehydes in acidic media. To the best of our
knowledge, no (R-hydroxyalkyl)phosphinic acid am-
phiphiles have been already described. Furthermore, the
presence of hydrophobic substituents must widen their
application fields by enhancing their coordinating and
biological properties since the hydrophilic and the hy-
drophobic groups coexist in the molecule.21,22
Ta ble 1. Yield s a n d NMR P a r a m eter s of
(r-Hyd r oxya lk yl)p h osp h in ic Acid s 1 a n d 2
compd
no.
a,b
c,d
d
R
%
δ(31P)(1J PH
)
δ(13C) (1J CP
)
δ(1H)d
60a
51b
7a
34.6 (548)c
31.5 (516)d
49.7; 48.5c
35.0 (546)c
32.8 (516)d
49.1; 47.6c
35.0 (543)c
32.9 (517)d
48.5; 47.0c
34.2 (532)c
32.9 (517)d
48.7; 47.2c
68.2 (111)
69.0 (112)
67.7 (113)
68.2 (112)
3.48
1a
2a
1b
2b
1c
2c
1d
CH3(CH2)6
{
{
{
{
80a
76b
5a
3.02
3.48
3.45
CH3(CH2)8
CH3(CH2)10
CH3(CH2)12
85a
75b
5a
Resu lts a n d Discu ssion
Syn t h esis of (r-H yd r oxya lk yl)p h osp h in ic Acid
Am p h ip h iles. The addition reaction of hypophospho-
rous acid to carbonyl compounds has already been
described.23 It often requires crystalline hypophospho-
rous acid, and it occurs upon prolonged heating under
acid catalysis, affording the mono- and bis(R-hydroxy-
alkyl)phosphinic acids.23
70a
62b
3a
2d
Initial yields of 1 and 2 determined by 31P NMR analysis of
a
b
the crude reaction mixture. Isolated yields of 1. c 31P NMR
d
1
spectra of the crude mixture; J in Hz. 31P, 13C, and H NMR data
for the methyne groups of isolated products in DMSO-d6.
We have optimized the reaction conditions of hypo-
phosphorous acid with a series of aliphatic aldehydes
bearing C8-C14 fatty chains by use of commercially
available 50 wt % aqueous hypophosphorous acid and
catalytic amounts of hydrochloric acid under ultrasonic
irradiation. Actually, the efficiency of ultrasound is well-
known in the case of heterogeneous reactions,20,24 and this
technique allows one to reduce the reaction time to 1 h
with respect to classical heating (2-4 h at 80 °C) (Scheme
2).
Indeed, the reaction of 50 wt % aqueous hypophospho-
rous acid with 1.2 equiv of aldehyde in the presence of
0.2-0.5 equiv of hydrochloric acid in dioxane under
sonication for 1 h affords the mono(R-hydroxyalkyl)-
phosphinic acids 1 as the main product (60-85%),
accompanied by the corresponding bis-adducts 2 (3-7%)
as side products. The use of an excess of hypophospho-
rous acid (3 equiv) allows one to avoid the formation of
the bis-adduct 2. The (R-hydroxyalkyl)phosphinic acids
1 are easily purified and obtained in good yields (Table
1).
For the mono(R-hydroxyalkyl)phosphinic acids 1, two
diastereomers are expected due to the presence of two
asymmetric centers: (1) the carbon bonded to the phos-
phorus atom and (2) the phosphorus atom bearing four
different substituents. However, the later loses its
asymmetric character due to the rapid prototropic trans-
fer of the acidic proton between the phosphoryl (PdO)
and the acidic (P-OH) sites.25 The 31P NMR spectra of
1 are characterized by chemical shifts about 32 ppm
(single signal for 31P{1H} NMR spectra) and a coupling
1
constant J PH about 516 Hz. The chemical shift of the
carbon atom in the R position of phosphorus (δ(13C) ∼
68) and its coupling constant with the phosphorus atom
(1J CP ∼ 112 Hz) are consistent with the presence of an
(R-hydroxyalkyl)phosphinic moiety. The methyne proton
resonates in most cases as a multiplet about 3.5 ppm.
The bis(R-hydroxyalkyl)phosphinic acids 2 obtained as
byproducts are only characterized by 31P NMR spectros-
copy of the reaction mixture. They exist in three dia-
stereomeric forms (two meso and one racemic form),
depending on the chirality of the two carbon atoms
bonded to the phosphorus atom, which is itself a pseudo-
asymmetric center.8d,25 However, as in the case of
monosubstituted acids 1, the 31P NMR spectra of 2 exhibit
degeneracies due to the rapid prototropic transfer of the
acidic proton, and only two signals are observed with a
diastereomeric ratio 2:1, as revealed by means of 31P
NMR spectroscopy.8d,25
(21) (a) Herranz, C. Tenside Detergents 1981, 18, 190. (b) Herranz,
C.; Martinez, M. J . J . Dispersion Sci. Technol. 1988, 9, 209. (c)
Martinez, M.; Herranz, C.; Miralles, N.; Sastre, A. Ibid. 1995, 16, 221.
(d) Martinez, M.; Miralles, N.; Sastre, A.; Herranz, C. Hydrometallurgy
1993, 33, 95.
(22) (a) Byrd, H.; Whipps, S.; Pike, J . K.; Ma, J .; Nagler, S. E.;
Talham, D. R. J . Am. Chem. Soc. 1994, 116, 295. (b) Seip, C. T.;
Granroth, G. E.; Meisel, M. W.; Talham, D. R. J . Am. Chem. Soc. 1997,
119, 7084. (c) Talham, D. R.; Seip, C. T.; Whipps, S.; Fanucci, G. E.;
Petruska, M. A. Comments Inorg. Chem. 1997, 19, 133.
(23) (a) Ville, M. J . Ann. Phys. Chim. 1891, 23, 289. (b) Marie, M.
C. C. R. Acad. Sci. 1903, 136, 234. (c) Marie, M. C. Ann. Phys. Chim.
1904, 3, 335. (d) Marie, M. C. Ann. Chim. 1904, 8, 411. (e) Kosolapoff,
G. M.; Maier, L., Organic Phosphorus Compounds; Wiley-Inter-
science: New York, 1972; Vol. 6, pp 24-25.
(24) (a) Suslick, K. S.; Hammerton, D. A.; Cline, R. E. J . Am. Chem.
Soc. 1986, 108, 5641. (b) Einhorn, C.; Einhorn, J .; Luche, J . L. Synthesis
1989, 787. (c) Etemad-Moghadam, G.; Rifqui, M.; Layrolle, P.; Berlan,
J .; Koenig, M. Tetrahedron Lett. 1991, 32, 5965. (d) Hubert, C.;
Oussaid, B.; Etemad-Moghadam, G.; Koenig, M.; Garrigues, B. Syn-
thesis 1994, 51.
Hyd r ogen Bon d in g in (r-Hyd r oxya lk yl)p h osp h in -
ic Acid s. The (R-hydroxyalkyl)phosphinic acids are
eminently suited to intra- and intermolecular hydrogen
bonding leading to cyclic dimers.26,27 We have studied
(25) Eliel, E. L.; Wilen, S. H.; Mander, L. N. Stereochemistry of
Organic Compounds; Wiley-Interscience: New York, 1994, pp 67, 123,
and 230.

(R-Hydroxyalkyl)phosphorus Amphiphiles
J . Org. Chem., Vol. 63, No. 21, 1998 7225
Ta ble 2. IR Sp ectr oscop ic Da ta for (r-Hyd r oxya lk yl)p h osp h in ic Acid s 1c,e
νOH (cm-1
)
νPdO (cm-1
monomer
)
νP-H (cm-1
monomer
)
compd no.
conditions
KBr
monomer
intra
inter
inter
inter
2365
1c
3395
3303
3334
3303
3310
3237
3357
3302
3311
1089
1180
1174
1170
1192
1176
1178
1178
2450
2382
2348
2348
2442
2385
2353
2353
CDCl3
DMF (0.1 M)
DMF (0.01 M)
KBr
CDCl3
DMF (0.1 M)
DMF (0.01 M)
3548
3550
3466
3484
3420
3415
3480
3490
1218
1218
2339
2339
2252
1e
1197
1237
1237
3549
3549
2340
2340
Sch em e 3
the IR spectra of (R-hydroxydodecyl)- and (R-hydroxy-
benzyl)phosphinic acids, 1c,e, respectively, in the con-
densed phase (KBr) and in solution (CDCl3 and DMF),
to determine the nature of these intra- and intermolecu-
lar associations and to observe a possible influence of the
long-chain upon their self-association. The H-bond vi-
bration frequencies observed concern the hydroxyl (νOH),
the phosphoryl (νPdO), and the P-H (νPH) regions (Table
2).
The hydroxyl absorption of the condensed phase for the
two acids 1 (νOH assoc) is represented by two broad
intense bands in the range 3237-3303 and 3395-3420
cm-1. As the substances are diluted with CDCl3 or DMF
(due to the insolubility of 1c in CDCl3), the intensity of
the band at 3303 cm-1 decreases as a function of
concentration in favor of band at 3550 cm-1. This permits
an assignment of the absorption νOH inter to the former
band and the νOH monomer to the later. At a concentra-
tion of 0.01 M, νOH inter remains in the form of a weak
band (3310 cm-1), with νOH monomer as a strong band
(3550 cm-1) with concomitant appearance of a band at
3484 cm-1 whose intensity remains unchanged as a
function of concentration. We can attribute this band to
the absorption νOH intra. However, in this case H-
bonding with the solvent cannot be excluded. The
phosphoryl absorption bond at ∼1190 cm-1 (νPdO inter)
in the condensed phase undergoes at dilute solution a
splitting into two bands at ∼1170 cm-1 (νPdO inter) and
∼1218 cm-1 (νPdO monomer) for 1c, confirming the
participation of the PdO bond in the association pro-
cesses. We observe the same variations that above for
the P-H absorption bands. However, the nature of these
associations is complex owing to the presence of the
phosphoryl (PdO), acidic hydroxyl (P-OH), R-hydroxyl
(C-OH), and P-H groups (Scheme 3).
Sch em e 4
In conclusion, associated molecules of (R-hydroxyalkyl)-
phosphinic acids in the condensed phase and in solution
exist in the form of cyclic dimers with intermolecular
hydrogen bonds. They exist in various forms of free
monomer molecules in dilute solutions and are stabilized
by intramolecular H-bonds. The behavior of the (R-
hydroxydodecyl)- and the (R-hydroxybenzyl)phosphinic
acids 1c,e, as studied by IR spectroscopy, present no
noticeable differences.
imines has been already described. This reaction affords
the corresponding (R-aminoalkyl)phosphonic acids under
strongly acidic conditions and prolonged heating.28 To
find conditions that would allow the direct synthesis of
free (R-hydroxyalkyl)phosphonic acids, we attempted the
addition reaction of phosphorous acid to aldehydes under
heating or sonication (Scheme 4). Whatever the reaction
conditions, all attempts were unsuccessful. The phos-
phorous acid is much less reactive toward aldehydes than
hypophosphorous acid, as already observed for alkenes.29
Since the (R-hydroxyalkyl)phosphinic acids 1 can be
easily prepared in good yields from hypophosphorous acid
Syn t h esis of (r-H yd r oxya lk yl)p h osp h on ic Acid
Am p h ip h iles. The reaction of phosphorous acid with
(26) (a) Emsley, J .; Hall, D., The Chemistry of Phosphorus; Harper
and Row: London, 1976; p 91. (b) Bondarenko, N. A.; Matrosov, E. I.;
Tsvetkov, E. N.; Kabachnik, M. I. Bull. Acad. Sci. USSR 1980, 92. (c)
Shagidullin, R. R.; Trutneva, E. P. Ibid. 1975, 1637. (d) Islamov, R.
G.; Pominov, I. S.; Zimin, M. G.; Sobanov, A. A.; Pudovik, A. N. J . Gen.
Chem. USSR 1974, 44, 488. (e) Shagidullin, R. R.; Trutneva, E. P.;
Rizpolozhenskii, N. I.; Mukhametov, F. S. Bull. Acad. Sci. USSR 1974,
1226.
(28) Redmore, D. J . Org. Chem. 1978, 43, 992.
(29) Pudovik, A. N., Moshkina, T. M.; Konovalova, I. V. J . Gen.
Chem. USSR 1959, 29, 3301.
(27) Meyer, T. G.; Fisher, A.; Schmutzler, R. Z. Naturforsch. B,
Chem. Sci. 1993, 48, 659.

7226 J . Org. Chem., Vol. 63, No. 21, 1998
Albouy et al.
Sch em e 5
Sch em e 7
Sch em e 6
the nucleophilic addition of a phosphine to the carbonyl
compounds in the presence of electrophilic trapping
agents.7,33-35 The reactions of phosphine PH3 with alde-
hydes yield various products depending on their struc-
ture, the catalysts, and the solvent. Thus, with formal-
dehyde the corresponding phosphonium salt is obtained,
whereas with other aldehydes various compounds are
formed.7a,35 The pecularity of these reactions is mostly
due to transformations of unstable intermediate products
of the condensation of one or two aldehyde molecules with
the phosphine.19,36,37
The addition of phosphine PH3, generated by basic
hydrolysis of red phosphorus or acidic hydrolysis of zinc
phosphide,17-19 to long-chain aldehydes in acidic media
at 30 °C involves the appearance of an insoluble product
almost immediately upon the passage of phosphine. The
precipitate is collected by filtration and isolated in yields
of 54% (4b) and 70% (4c) (Scheme 7).
and various long-chain aldehydes, we have undertaken
the oxidation of their P-H bond by several methods. The
oxidation of phosphinic acid in water in the presence of
mercuric oxide has already been described.23c,d Our
attempts for oxidation of the P-H bond of the acids 1
with 30% aqueous hydrogen peroxide failed. Since the
oxidizing power of the sulfoxide group is well-known in
the oxidation of trivalent phosphorus compounds30 or
cyclic P-H phosphoranes,31 we attempted the oxidation
of the phosphinic acids 1 in the presence of a stoichio-
metric amount of DMSO and a catalytic amount of iodine
at 60 °C. The reaction time required is 4-5 h (Scheme
5).
The (R-hydroxyalkyl)phosphonic acids 3 are obtained
in good yields. The oxidation might proceed by formation
of a phosphonium iodide intermediate resulting from the
electrophilic attack of iodine to trivalent phosphorous
acids 1 (phosphonate-phosphite tautomeric equilibri-
um),32 which undergoes the addition of the oxygen atom
of DMSO to afford a phosphorane intermediate. The
nucleophilic attack of the iodide anion to the later and
the departure of methyl sulfide lead to the (R-hydroxy-
alkyl)phosphonic acids 3 (Scheme 6).
Their physical (melting points and elemental analyses)
1
and spectroscopic (31P, H, 13C NMR, mass, and infrared
spectra) data are consistent with the tetrakis(R-hydroxy-
alkyl)phosphonium chlorides. The phosphonium salt 4c
has already been described and characterized by its
melting point and elemental analysis,38 but no spectro-
scopic data have been reported.
The tetrakis(R-hydroxyalkyl)phosphonium chlorides
4b-c contain four asymmetric carbon atoms, so they
must be exist in 16 stereoisomeric forms. The tetrahedral
geometry of the molecule, together with the presence of
four identical substituents bonded to the phosphorus
atom, renders some structures equivalent,25 affording
three groups of isomers: group I (RRRR/SSSS); group II
(RRSS/ SSRR; RSRS/ SRSR; RSSR/ SRRS); group III
(RRRS/ SSSR; RRSR/ SSRS; RSRR/ SRSS; SRRR/
RSSS). The theoretical percentages of stereoisomers in
the groups I/II/III are in a ratio of 12.5/37.5/50.0, respec-
tively. The 31P NMR spectra analysis of 4b-c in CDCl3
exhibited three signals in a relative ratio nearly identical
with the calculated values (Table 3).
The 31P NMR spectra of 3 are characterized by chemi-
cal shifts about 24 ppm. The oxidation of phosphinic
acids to phosphonic homologues involves a shielding of
the P nucleus (∆δ(31P) ∼ 10). The chemical shift of the
R-carbon (δ(13C) ∼ 67) does not undergo a significant
variation, but its coupling constant with the phosphorus
atom (1J CP ∼ 160 Hz) increases about 50 Hz with respect
to phosphinic acids 1.
Syn th esis of Tetr a k is(r-h yd r oxya lk yl)p h osp h o-
n iu m Sa lts fr om P h osp h in e, P H3. The phosphonium
salts are widely studied and have significant interest due
to their numerous applications.7,33 Examples of forma-
tion of (R-hydroxyalkyl)phosphonium salts are consider-
ably rarer. Such compounds have been synthesized from
Dissocia tion Con sta n ts of (r-Hyd r oxya lk yl)p h os-
p h in ic a n d -p h osp h on ic Acid Am p h ip h iles. Owing
(33) (a) Kosolapoff, G. M.; Maier, L. Organic Phosphorus Com-
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1996, 12, 5881. (c) Kanazawa, A.; Tsutsumi, O.; Ikeda, T.; Nagase, Y.
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Dal Canto, R. A.; Roskamp, E. J . J . Org. Chem. 1992, 57, 406. (c)
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Reibenspies, J . H. Inorg. Chem. 1994, 33, 175.
(35) (a) Messinger, J .; Engels, C. Ber. 1888, 21, 326, 2919. (b) Bruker,
A. B.; Baranaev, M. K.; Grinshtein, E. I.; Novoselova, R. I.; Prokhorova,
V. V.; Soborovskii, L. Z. J . Gen. Chem. USSR 1963, 33, 1866. (c)
Grinshtein, E. I.; Bruker, A. B.; Soborovskii, L. Z. J . Gen. Chem. USSR
1966, 36, 311.
(36) Ettel, V.; Horak, J . Collect. Czech. Chem. Commun. 1960, 25,
2191.
(30) (a) Amonoo-Neizer, E. H.; Ray, S. K.; Shaw, R. A.; Smith, B. C.
J . Chem. Soc. 1965, 4296. (b) Dreux, M.; Leroux, Y.; Savignac, Ph.
Synthesis 1974, 506.
(31) (a) Munoz, A.; Gallagher, M.; Klaebe, A.; Wolf, R. Tetrahedron
Lett. 1976, 673. (b) Savignac, Ph.; Bre`que, A.; Bartet, B.; Wolf, R. C.
R. Acad. Sci. 1978, 287 (Ser. C), 13.
(37) (a) Buckler, S. A. J . Am. Chem. Soc. 1960, 82, 4215. (b) Buckler,
S. A.; Epstein, M. J . Am. Chem. Soc. 1960, 82, 2076.
(38) (a) Buckler, S. A.; Wystrach, V. P. J . Am. Chem. Soc. 1961, 83,
168. (b) Buckler, S. A. U.S. Patent, 3,013,085, 1961.
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Luz, Z.; Silver, B. J . Am. Chem. Soc. 1961, 83, 4518.

(R-Hydroxyalkyl)phosphorus Amphiphiles
J . Org. Chem., Vol. 63, No. 21, 1998 7227
Ta ble 3. Isola ted Yield s a n d 31P NMR P a r a m eter s of
Tetr a k is(r-h yd r oxya lk yl)p h osp h on iu m Ch lor id es 4
Ta ble 4. Eva lu a tion of th e p K Va lu es of th e P h osp h or u s
Acid s in DMF by P oten tiom etr ic a n d 31P NMR Titr a tion s
rel intensities
pK of phosphorus acids
compd
no.
yield
(%)
δ(31P)
(CDCl3)
calcd (%)
found (%)
method
H3PO2 1c
8.80 9.70 9.45
(1.4)b,53
9.60
1b
1e
3c
3b
3e
potentiometrica 9.40
11.00 10.75 10.80
4b
54
23.4
22.9
21.9
23.5
22.9
22.0
50
50
20
30
50
16
34
(1.1)b,53
12.5
37.5
50
12.5
37.5
31P NMRc
8.70
11.10 10.80 11.00
4c
70
In DMF at 20 °C. In water at 20 °C. c In DMF at 30 °C.
a
b
dissociation constants in DMF to the pK values in DMF
of the (R-hydroxybenzyl)phosphinic and -phosphonic ac-
ids, 1e and 3e, and the hypophosphorous acid for which
the pK values have been already determined in water.54
DMSO could not be used as solvent since hypophospho-
rous acid is oxidized by it.49
to their high complexing ability, organophosphorus acid
compounds can be used as extractants for liquid-liquid
extraction of metallic cations.7,39 Among these, alkyl-
phosphinic acids have been reported to possess higher
separation factors for lanthanides,40 actinides,41 heavy
rare earth elements,42 cobalt and nickel,43 and other
transition metal ions.44 For such an application, the
compounds must not be too soluble in water, and for this
reason, the presence of a long alkyl chain inducing a
hydrophobic character in these molecules is suitable.
Actually, various organophosphorus derivatives are known
as phase-transfer catalysts for two-phase reactions.45
The knowledge of the acidity constants is essential in
order to estimate their extractant properties. Dissocia-
tion constants of various phosphinic and phosphonic acids
have already been determined in water,46 in 75% and 95%
ethanol,47 in tert-butyl alcohol and pyridine,48 and in
DMSO, DME, and ethylene glycol.49,50 To determine the
influence of the polar head (phosphinic and phosphonic
acid) and the alkyl structure upon the acidity constants,
we have measured the pK values of the acids 1b-c and
3b-c. The water insolubility of the long-chain (R-
hydroxyalkyl)phosphorus acids 1 and 3 prevents the
determination of pK values in water. DMF, an aprotic
polar solvent with high dielectric constant (ꢀ ) 36.7) and
high dipolar moment (µ ) 3.86 D),51 is a good solvent for
all of the acids. It does not solvate the anions (absence
of hydrogen bonding)52 but strongly solvates the cations
due to the negative charge located at oxygen atom.53 To
have estimated pK values in water, we compared their
P oten tiom etr ic Titr a tion . For the potentiometric
titration in DMF at 20 °C, the calibration into pH units
of the glass electrode was carried out with 2,4-dini-
trobenzoic and 2,6-dihydroxybenzoic acids as buffers
neutralized by DBU (1,8-diazabicyclo[5.4.0]undec-7-ene).
These mixtures were utilized in lieu of either dichloro-
acetic or picric acids neutralized by triethylamine that
had previously been used to determine pK values of some
organoboron and organophosphorus compounds.55 The
former acids are anhydrous cristalline materials that are
easier for handling than the latter ones, whereas DBU
is a stronger base than triethylamine.56 The pK value
of 2,4-dinitrobenzoic acid has already been reported in
DMSO (6.52) and in DMF (8.16).57 The pK value of 2,6-
dihydroxybenzoic acid was determined potentiometrically
in DMF and DMSO by DBU.58 Observed values 2.4
(DMF) and 0.4 (DMSO) do not agree with reported
parameters 3.56 (DMF)57 and 3.1 (DMSO).59 Neverthe-
less, the weak difference between the two last pK values
is abnormal since a difference of 1.5 to 2 pK units is
systematically observed between the two solvents. More-
over, neutralization curves of 2,6-dihydroxybenzoic acid
and picric acid are almost superimposable.58
Dissociation constants calculated from potentiometric
technique are presented in Table 4. All the pK values
obtained in DMF are in the range 8.8-11.0. We observe
that the (R-hydroxyalkyl)phosphinic and -phosphonic
acids are weakly dissociated in DMF and they can be
considered as weak acids in this solvent. However, their
pK values are very similar to the pK value in DMF of
the hypophosphorous acid, which is a strong acid in water
(pKwater ) 1.1).54a
The P-H phosphinic and phosphonic acids are in
tautomeric equilibrium with their trivalent isomers,
phosphorus and phosphonous acids, respectively, but
owing to the strength of the phosphoryl group, the
equilibrium shifts to the left (Scheme 8).32
(39) (a) Yuan, C.; Li, S.; Long, H. Phosphorus, Sulfur 1983, 18, 323.
(b) Doucet Ladeveze, G.; J abbari Azad, Y.; Rodehu¨ser, L.; Rubini, P.;
Selve, C.; Delpuech, J . J . Tetrahedron 1986, 42, 371. (c) Godbole, A.
G.; Mapara, P. M.; Swarup, R. J . Radioanal. Nucl. Chem. Lett. 1995,
200, 1.
(40) Cecconie, T.; Freiser, H. Solvent Extr. Ion Exch. 1989, 7, 15.
(41) Sabharwal, K. N.; Vasudeva Rao, P. R.; Srinivasan, M. Solvent
Extr. Ion Exch. 1994, 12, 1085.
(42) (a) Ohto, K.; Inoue, K.; Goto, M.; Nakashio, F.; Nagasaki, T.;
Shinkai, S.; Kago, T. Bull. Chem. Soc. J pn. 1993, 66, 2528. (b) Ohto,
K.; Yoshida, S.; Yoshizuka, K.; Inoue, K.; Ohtsuka, M.; Goto, M.;
Nakashio, F. Anal. Sci. 1995, 11, 637.
(43) Xun, F.; Golding, J . A. Anal. Sci. 1987, 5, 205.
(44) Miralles, N.; Sastre, A. M. Monatsh. Chem. 1993, 124, 987.
(45) Tomoi, M.; Takubo, T.; Ikeda, M.; Kakiuchi, H. Chem. Lett.
1976, 473. (b) Tomoi, M.; Hasegawa, T.; Ikeda, M.; Kakiuchi, H. Bull.
Chem. Soc. J pn. 1979, 52, 1653.
(46) (a) Quin, L. D.; Dysart, M. R. J . Org. Chem. 1962, 27, 1012. (b)
Schulz, P. C.; Fernandez-Band, B. S.; Vuano, B.; Palomeque, M.; Allan,
A. L. Colloid Polym. Sci. 1996, 274, 741.
(47) (a) Peppard, D. F.; Mason, G. W.; Andrejasich, C. M. J . Inorg.
Nucl. Chem. 1965, 27, 697. (b) Martinez, M.; Miralles, N.; Sastre, A.;
Bosch, E. Talanta 1993, 40, 1339.
(53) Zaugg, H. E.; Harron, B. W.; Borgwardt, S. J . Am. Chem. Soc.
1960, 82, 2895.
(54) (a) Emsley, J .; Hall, D. The Chemistry of Phosphorus; Harper
and Row: London, 1976; Chapter 8, p 307. (b) Lesfauries, P.; Rumpf,
P. C. R. Acad. Sci. 1949, 1018. (c) Viout-Lesfauries M. P. J . Recherches
CNRS 1954, 28, 15.
(48) Grayson, M.; Farley, C. E.; Streuli, C. A. Tetrahedron 1967,
23, 1065.
(49) Cook, A. G.; Mason, G. W. J . Inorg. Nucl. Chem. 1966, 28, 2579.
(50) (a) Guthrie, J . P. Can. J . Chem. 1979, 57, 236. (b) Matveeva,
A. G.; Terekhova, M. I.; Aladzheva, I. M.; Odinets, I. L.; Petrov, E. S.;
Mastryukova, T. A.; Kabachnik, M. I. Russ. J . Gen. Chem. 1993, 63,
428.
(51) Reichardt, C. Solvent Effects in Organic Chemistry; Flam-
marion: Paris, 1971.
(52) Parker, A. J . Q. Rev. 1962, 16, 163.
(55) Lamande´, L.; Boyer, D.; Munoz, A. J . Organomet. Chem. 1987,
329, 1.
(56) Hermecz, I. Adv. Heterocycl. Chem. 1987, 42, 83-201.
(57) Kolthoff, I. M.; Chantooni, M. K., J r. J . Am. Chem. Soc. 1971,
93, 3843.
(58) (a) Munoz, A.; Lamande´, L.; de Montauzon, D. VIIth Franco-
Spanish Symposium of Organic Chemistry, Pyla sur mer, France 1992.
(b) Ibid., to be published.
(59) Kolthoff, I. M.; Chantooni, M. K., J r.; Bhowmik, S. J . Am. Chem.
Soc. 1968, 90, 23.

7228 J . Org. Chem., Vol. 63, No. 21, 1998
Albouy et al.
from the plot of δ(31P) against pH in which the pK is equal
to the pH at half-neutralization (point of inflection). It
has recently been reported that the pK values of phos-
phonic acids are invariable with temperature.46b The
measures of pK were made at 30 °C for the NMR titration
and at 20 °C for the potentiometric method. Good
agreement is obtained between the two methods for the
phosphinic and phosphonic acids 1 and 3 (Table 4). The
parallelism of the two series is even closer if the fact that
pK measures only the acidity due to the ionization of the
most easily removed proton is taken into account.
Consequently, the (R-hydroxyalkyl)phosphinic and
-phosphonic acid amphiphiles 1 and 3 having pH-de-
pendent 31P resonance signals lend themselves to 31P
NMR titration, and the dissociation constants obtained
by this method closely correlate with those determined
by the potentiometric technique. Whereas the (R-hy-
droxyalkyl)phosphinic and -phosphonic acid amphiphiles
1 and 3 are weakly dissociated in DMF, they can be
considered as relatively strong acids in water since their
pK values are very close to the dissociation constant in
DMF of hypophosphorous acid for which the pK value in
water is about 1.1. The complexing properties and the
molecular agregation of these functionalized phosphorus
acid amphiphiles are under investigation.
Sch em e 8
Ta ble 5. In flu en ce of p H u p on th e δ(31P ) a n d J P H (Hz)
1
of th e (r-Hyd r oxya lk yl)p h osp h in ic Acid s 1
phosphinic acid
pH
δ(31P)
1J PH (Hz)
1c
5.3
10.0
17.9
5.1
9.1
17.9
31.4
28.1
23.3
28.0
25.8
22.4
512
500
467
530
506
485
1e
Ta ble 6. In flu en ce of th e Con cen tr a tion u p on th e δ(31P )
1
a n d J P H (Hz) of (r-Hyd r oxyd od ecyl)p h osp h in ic Acid (1c)
in DMF
concentration (M)
0.1
0.01
0.005
δ(31P)
31.6
516
31.5
517
31.4
523
1J PH (Hz)
Therefore, acids 1 and 3 exist largely in the tetra-
coordinate form, and they are considered as mono- and
diacids, respectively. The P-H acidities of hydrophos-
phoryl compounds have been investigated in detail by the
potentiometric method in 95% ethanol and by the indica-
tor spectrophotometric method in DMSO and DME.50
They vary over a wide range (pKDMSO from 20.8 to 28.0),
depending on the nature of substituents on the phospho-
rus atom, and they show the very weak acidic character
of the P-H tetracoordinated phosphoryl compounds.
During the titration, we have never observed a second
acidity due to the P-H bond for the phosphinic acids 1
or due to the second P-OH group for the phosphonic
acids 3. In the later case, it is well-known that the second
acidity is about 5 pK units higher than the first acidity.54a
We observe that the phosphinic acids are slightly
stronger than the corresponding phosphonic acids (Table
4). A similar observation has been made for other
phosphinic and phosphonic acids.46a,54c,60 These are
monoacids, and no evidence for secondary ionization
(P-H acidity) is obtained. The nature of the substituents
(H, Ph, or long-chain alkyl) does not have a significant
influence on the dissociation constants of these acids.
Consequently, the increase of the acidity could arise from
the R-hydroxyl group.
Con clu sion s
The direct synthesis of free (R-hydroxyalkyl)phosphinic
acids from long-chain aldehydes and aqueous hypophos-
phorous acid, which is a cheap and safe raw material,
under sonication for 1 h constitutes a general and
convenient procedure for the preparation of new phos-
phorus acid amphiphiles. The ready oxidation of (R-
hydroxyalkyl)phosphinic acids to the corresponding phos-
phonic acids by DMSO in the presence of catalytic
amounts of iodine can be also considered of synthetic
interest. The presence of intra- and intermolecular
associations by hydrogen bonding is demonstrated by IR
spectroscopy in the condensed phase and in solution for
the (R-hydroxyalkyl)phosphinic acids. Owing to the
presence of the phosphoryl, acidic hydroxyl, R-hydroxyl,
and P-H groups, these acids exist in the form of cyclic
dimers (intermolecular H-bond) and free monomers
stabilized by intramolecular hydrogen-bonding. Dis-
sociation constants of (R-hydroxyalkyl)phosphinic and
-phosphonic acids determined in DMF by potentiometric
and 31P NMR titrations reveal a good correlation between
the two methods. The P-H (R-hydroxyalkyl)phosphinic
acids are slightly stronger than the corresponding phos-
phonic ones. Their pK values are very close to the
dissociation constant of hypophosphorous acid, and they
can be considered as relatively strong acids with potential
complexing properties due probably to the presence of a
P-H bond and the effect of the R-hydroxyl group.
Finally, the tetrakis(R-hydroxyalkyl)phosphonium chlo-
ride surfactants are easily prepared in acidic media from
the long-chain aldehydes and the phosphine, PH3, gener-
ated by basic hydrolysis of red phosphorus or acid
hydrolysis of zinc phosphide. Their applications as
intermediates in synthesis or as phase-transfer catalysts
are under investigation.
31P NMR Titr a tion . As in amino- and hydroxy-
substituted phosphonic acid compounds,61 the 31P-chemi-
cal shifts of the R-hydroxyalkyl acids 1 and 3 are strongly
dependent on the pH of the solution (Table 5).
An increase in the solution pH causes a shielding of
the phosphorus nucleus by approximately 6-8 ppm and
a decrease of the 1J PH values of about 40 Hz. In contrast,
the 31P NMR data in DMF appear insensitive to the
concentration (Table 6).
To make a direct comparison between the pK values
obtained by the potentiometric technique and by 31P
NMR titration,62 we have operated at 8 mM concentra-
tion. The dissociation constants were determined directly
(60) Baylis, E. K.; Campbell, C. D.; Dingwall, J . G. J . Chem. Soc.,
Perkin Trans. 1 1984, 2845.
(61) (a) Maier, L.; Diel, P. J . Phosphorus, Sulfur, Silicon Relat. Elem.
1994, 90, 259. (b) Glowacki, Z.; Hoffmann, M.; Topolski, M.; Rachon,
J . Ibid. 1991, 60, 67.
(62) (a) Appleton, T. G.; Hall, J . R.; Harris, A. D.; Kimlin, H. A.;
McMahon, I. J . Aust. J . Chem. 1984, 37, 1833. (b) Lachmann, H.;
Schnackerz, K. D. Org. Magn. Reson. 1984, 22, 101.

(R-Hydroxyalkyl)phosphorus Amphiphiles
J . Org. Chem., Vol. 63, No. 21, 1998 7229
dichloromethane, and then the insoluble material was filtered
off and recrystallized from THF to give a white powder.
(r-Hyd r oxyd ecyl)p h osp h on ic a cid (3b): yield 80%; mp
145-147 °C (from THF);63 31P NMR (81.01 MHz, DMSO-d6) δ
23.9 (dt, 2J PH ) 9.3 Hz, 3J PH ) 6.7 Hz); 1H NMR (250.13 MHz,
DMSO-d6) δ 8.00-5.50 (m), 3.43 (m, 1H), 1.56-1.25 (m, 16H),
Exp er im en ta l Section
Gen er a l Com m en ts. Red phosphorus (Prolabo), zinc
phosphide (Strem), 50% aqueous hypophosphorous acid and
aldehydes (Aldrich), 2,6-dihydroxybenzoic acid and 2,4-dini-
trobenzoic acid (Fluka), and (R-hydroxybenzyl)phosphinic acid
(1e) (J anssen) were used as received without prior purification.
DMF, reagent grade product, was maintained over 4 Å
molecular sieves and stored in a dark bottle protected from
moisture. Elemental analyses were performed by the Mi-
croanalytical Service Laboratory of the “Laboratoire de Chimie
de Coordination” of Toulouse, France. An ultrasound genera-
tor, consisting of a 13-mm probe fitted to a Bioblock Vibracell
600 W (20 kHz) generator, was dipped into the solution.
Gen er a l P r oced u r e for th e Syn th esis of (r-Hyd r oxy-
a lk yl)p h osp h in ic Acid s (1). Hypophosphorous acid (50%
aqueous) (4.3 mmol) was added to a solution of aldehyde (5.16
mmol, 1.2 equiv) in dioxane (6 mL) and hydrochloric acid (37%
aqueous) (0.05 mL). The resulting heterogeneous mixture was
stirred under reflux for 2-4 h or sonicated for 1 h. Solvents
were removed under vacuum. After addition of distilled H2O
to the residue, products were extracted with Et2O. The organic
phase was evaporated to dryness. The white solid residue was
washed with n-hexane and then filtered off and dried under
vacuum.
3
0.86 (t, J HH ) 6.6 Hz, 3H); 13C NMR (62.90 MHz, DMSO-d6)
1
δ 66.9 (d, J CP ) 161.3 Hz), 33.7-22.0 (m), 13.8 (s); IR (KBr,
cm-1) 3202.5-2920.5 (OH), 2850.6 (P-OH), 1123 (PdO); MS
(DCI/NH3) m/z 238 (M)+•, 256 (M + NH4)+, 440 (2M - 2H2O)+•.
Anal. Calcd for C10H23O4P: C, 50.41; H, 9.73. Found: C, 50.62,
H, 9.68.
(r-Hyd r oxyd od ecyl)p h osp h on ic a cid (3c): yield 89%; mp
148-150 °C (from THF); 31P NMR (81.01 MHz, DMSO-d6) δ
23.8 (m); 1H NMR (250.13 MHz, DMSO-d6) δ 7.10 (m, 3H),
3
3.44 (m, 1H), 1.53-1.24 (m, 20H), 0.85 (t, J HH ) 6.1 Hz, 3H);
1
13C NMR (62.90 MHz, DMSO-d6) δ 66.8 (d, J CP ) 161.2 Hz),
31.2-22.0 (m), 13.8 (s); IR (KBr, cm-1) 3211.8 (OH), 2919.1
(P-OH), 1122.2 (PdO); MS (DCI/NH3) m/z 284 (M + NH4)+.
Anal. Calcd for C12H27O4P: C, 54.12; H, 10.22. Found: C,
54.27, H, 10.25.
(r-Hyd r oxytetr a d ecyl)p h osp h on ic a cid (3d ): yield 55%;
mp 152-154 °C (from THF); 31P NMR (81.01 MHz, DMSO-d6)
1
δ 24.0 (m); H NMR (250.13 MHz, DMSO-d6) δ 6.27 (m, 3H),
3
3.43 (m, 1H), 1.49-1.24 (m, 24H), 0.85 (t, J HH ) 5.3 Hz, 3H);
1
13C NMR (62.90 MHz, DMSO-d6) δ 66.9 (d, J CP ) 161.4 Hz),
(r-Hyd r oxyoctyl)p h osp h in ic a cid (1a ): yield 51%; mp
63-65 °C (from hexane); 31P NMR (32.44 MHz, DMSO-d6) δ
31.2-22.0 (m), 13.8 (s); IR (KBr, cm-1) 3215.2 (OH), 2918.3-
2850.1 (P-OH), 1008.3 (PdO); MS (DCI/NH3) m/z 295 (M +
1)+ , 312 (M + NH4)+. Anal. Calcd for C14H31O4P: C, 57.12;
H, 10.61. Found: C, 57.24, H, 10.44.
31.5 (d, J PH ) 516 Hz); 1H NMR (80.13 MHz, DMSO-d6) δ
1
6.70 (d,1J HP ) 517 Hz, 1H), 5.30 (m, 1H), 3.48 (m, 1H), 1.47-
1.26 (m, 12H), 0.85 (m, 3H); 13C NMR (62.90 MHz, DMSO-d6)
δ 68.22 (d, 1J CP ) 111 Hz), 31.14 (s), 29.25 (s), 28.71 (s), 28.52
(s), 24.91 (s), 21.98 (s), 13.84 (s); IR (KBr, cm-1) 3340.0 (OH),
2952.0-2847.7 (P-OH), 2398.4 (P-H), 1085.3 (PdO); MS
(DCI/NH3) m/z 195 (M + 1)+, 213 (M + 1 + NH4)+, 389 (2M +
1)+. Anal. Calcd for C8H19O3P: C, 49.48; H, 9.86. Found: C,
49.64; H, 9.87.
(r-Hyd r oxyben zyl)p h osp h on ic a cid (3e): yield 90%; mp
161-163 °C (from CH2Cl2);23d 31P NMR (81.01 MHz, DMSO-
2
1
d6) δ 19.5 (d, J PH ) 15.4 Hz); H NMR (200.13 MHz, DMSO-
2
d6) δ 9.00-8.00 (m, 2H), 7.45-7.22 (m, 6H), 4.69 (d, J HH
)
13.9 Hz); 13C NMR (62.90 MHz, DMSO-d6) δ 140.0 (s), 127.4-
126.7 (m), 70.3 (d, J CP ) 159.5 Hz); IR (KBr, cm-1) 3224.6
1
(r-Hyd r oxyd ecyl)p h osp h in ic a cid (1b): yield 76%; mp
(OH), 2839.9 (P-OH), 1006.0 (PdO); MS (DCI/NH3) m/z 188
(M)+•, 207 (M + 1 + NH4)+•, 224 (M + 1 + N2H7)+, 392 [2(M -
1) + NH4]+. Anal. Calcd for C7H9O4P: C, 44.69; H, 4.82.
Found: C, 44.61, H, 4.52.
74-75 °C (from hexane); 31P NMR (81.01 MHz, DMSO-d6) δ
1
1
32.8 (d, J PH ) 516 Hz); H NMR (250.13 MHz, DMSO-d6) δ
6.57 (m, 1H), 6.22 (d, 1J HP ) 518 Hz, 1H), 3.02 (m, 1H), 1.02-
0.77 (m, 16H), 0.37 (m, 3H); 13C NMR (62.90 MHz, DMSO-d6)
δ 69.03 (d, 1J CP ) 112 Hz), 32.13 (s), 30.12 (s), 29.81 (s), 29.69
(s), 29.56 (s), 25.91 (s), 25.72 (s), 22.92 (s), 14.69 (s); IR (KBr,
cm-1) 3395.4-3306.9 (OH), 2916.4-2850.1 (P-OH), 2364.8
(P-H), 1090.1 (PdO); MS (DCI/NH3) m/z 240 (M + NH4)+.
Anal. Calcd for C10H23O3P: C, 54.04; H, 10.43. Found: C,
53.80; H, 10.54.
Gen er a l P r oced u r e for th e Syn th esis of (r-Hyd r oxy-
a lk yl)p h osp h on iu m Sa lts 4. The reaction was carried out
under an argon atmosphere. Phosphine (PH3) was generated
by basic hydrolysis of red phosphorus or acid hydrolysis of zinc
phosphide. To zinc phosphide (0.32 g, 1.24 mmol) in distilled
H2O or red phosphorus (0.31 g, 0.01 mol), stirred and heated
at 50 °C, was added dropwise an aqueous solution of sulfuric
acid or potassium hydroxide, respectively. The generated
phosphine was bubbled through the stirred solution of alde-
hyde (7.5 mmol) in dioxane (6 mL) and 37% aqueous hydro-
chloric acid (0.72 mL) at 30 °C for 1.5 h. The insoluble product
was formed immediately upon the passage of PH3. The
mixture was maintained under stirring at 30 °C for an
additional 1 h. The white solid was collected by filtration,
washed several times with n-hexane, and dried under vacuum.
Tetr a k is(r-h yd r oxyd ecyl)p h osp h on iu m ch lor id e (4b):
yield 54%; mp 112-115 °C (from hexane); 31P NMR (81.01
(r-Hyd r oxyd od ecyl)p h osp h in ic a cid (1c): yield 75%; mp
82-83 °C (from hexane); 31P NMR (81.01 MHz, DMSO-d6) δ
1
1
32.9 (d, J PH ) 517 Hz); H NMR (250.13 MHz, DMSO-d6) δ
1
2
6.7 (d, J HP ) 518 Hz, 1H), 6.42 (m, 1H), 3.48 (d, J HP ) 8.8
3
Hz, 1H), 1.53-1.24 (m, 20H), 0.85 (t, J HH ) 6 Hz, 3H); 13C
1
NMR (62.90 MHz, DMSO-d6) δ 67.74 (d, J CP ) 113 Hz),
31.25-22.0 (m), 13.80 (s); IR (KBr, cm-1) 3395.4-3302.6 (OH),
2915.5-2848.8 (P-OH), 2449.8-2365 (P-H), 1089.5 (PdO);
MS (DCI/NH3) m/z 268 (M + NH4)+, 251 (M + 1)+. Anal.
Calcd for C12H27O3P: C, 57.58; H, 10.87. Found: C, 57.58; H,
10.96.
1
MHz, CDCl3) δ 23.4 (50%), 22.9 (20%), 21.9 (30%); H NMR
(r-Hyd r oxytetr a d ecyl)p h osp h in ic a cid (1d ): yield 62%;
(80.13 MHz, C6D6) δ 5.12 (m, 4H), 4.81 (m, 4H), 1.84-1.33 (m,
64H), 0.97 (m, 12H); 13C NMR (62.90 MHz, C6D6) δ 60.00 (d,
1J CP ) 130 Hz), 43.84-22.26 (m), 14.43 (s); MS (positive FAB/
MNBA) m/z 659 (M)+; IR (KBr, cm-1) 3262.7 (OH). Anal.
Calcd for C40H84ClO4P: C, 69.08; H, 12.17; Cl, 5.10; P, 4.45.
Found: C, 68.80; H, 12.06; Cl, 4.97; P,4.46.
mp 90-92 °C (from EtOH); 31P NMR (81.01 MHz, DMSO-d6)
1
2
1
δ 32.9 (dd, J PH ) 517 Hz, J PH ) 9.7 Hz); H NMR (250.13
MHz, DMSO-d6) δ 6.7 (dd, 1J HP ) 517 Hz, 3J HH ) 1.2 Hz, 1H),
3
3.45 (m, 1H), 1.49-1.24 (m, 24H), 0.85 (t, J HH ) 6.6 Hz, 3H);
13C NMR (62.90 MHz, DMSO-d6) δ 68.20 (d, J CP ) 112 Hz),
1
31.21-22.0 (m), 13.82 (s); IR (KBr, cm-1) 3393.8-3306.1 (OH),
2914.8-2848 (P-OH), 2403.8 (P-H), 1090 (PdO); MS (DCI/
CH4) m/z 279 (M + 1)+, 307 (M + C2H5)+. Anal. Calcd for
Tetr akis(r-h ydr oxydodecyl)ph osph on iu m ch lor ide (4c):
yield 70%; mp 109-111 °C (from hexane);37 31P NMR (81.01
1
MHz, CDCl3) δ 23.5 (50%), 22.9 (16%), 22.0 (34%); H NMR
C
14H31O3P: C, 60.41; H, 11.22. Found: C, 60.73; H, 11.05.
Gen er a l P r oced u r e for th e Syn th esis of (r-Hyd r oxy-
(250.13 MHz, CDCl3) δ 5.30 (m, 4H), 4.78 (m, 4H), 1.26 (m,
80H), 0.88 (m, 12H); 13C NMR (62.90 MHz, C6D6) δ 62.84 (d,
1J CP ) 139.4 Hz), 43.92-22.09 (m), 14.10 (s); MS (positive FAB/
glycerol) m/z 771 (M)+; IR (KBr, cm-1) 3265.3 (OH). Anal.
Calcd for C48H100ClO4P: C, 71.37; H, 12.48. Found: C, 71.30;
H, 12.50.
a lk yl)p h osp h on ic Acid s 3. A solution of (R-hydroxyalkyl)-
phosphinic acid 1 (2.9 mmol), DMSO (0.22 g, 2.9 mmol, 1
equiv), and iodine (0.002 g, 0.01 equiv) in THF (5 mL) was
stirred under heating at 60 °C for 5 h. The completion of the
reaction was followed by 31P NMR. The mixture was evapo-
rated to dryness. The residue was washed several times with
(63) Fitch, S. J .; Moedritzer, K. J . Am. Chem. Soc. 1962, 84, 1876.

7230 J . Org. Chem., Vol. 63, No. 21, 1998
Albouy et al.
Deter m in a tion of th e Dissocia tion Con sta n ts of P h os-
p h or u s Acid s. For all emf measurements a Schott Gerate,
CG832, pH-meter equipped with a reference electrode, B220
(saturated solution of LiCl in methanol/KCl 2M), and a glass
electrode, Schott H 11280 DIN, 200 MΩ (Ag/AgCl) was used.
The calibration was carried out by titration of 2,6-dihydroxy-
benzoic acid (pKDMF ) 2.4) and 2,4-dinitrobenzoic acid (pKDMF
) 8.16) in DMF (8 × 10-3 M) with a solution of DBU in DMF
(0.1 M) at 20 °C. The acidity constants of different phosphorus
acids were determined under the same conditions. In general,
stable potentials were obtained within 10 min. A Bruker
AC200 was used for 31P NMR titration. The concentrations
were the same than above, but the measurements were carried
out at 30 °C. The accuracy of this method is within 0.1-0.2
pK unit.
Ack n ow led gm en t. We are grateful to Dr. D. de
Montauzon (Laboratoire de Chimie de Coordination-
CNRS) for helpful discussions.
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