The preparation of dialkyl 1-hydroxyalkylphosphonates in the reaction of trialkyl phosphites with oxonium salts derived from aldehydes or ketones

Article abstract of DOI:10.1055/s-2006-950200

The reaction of trialkyl phosphites with aldehydes or ketones in the presence of hydrogen chloride gives dialkyl 1-hydroxyalkylphosphonates via Arbusov-like reaction of oxonium salts derived from aldehydes or ketones. This reaction is a very convenient instant method for the preparation of dialkyl 1-hydroxyalkylphosphonates with a good yield as an alternative to the well-known Abramov reaction. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-2006-950200

PAPER
3019
The Preparation of Dialkyl 1-Hydroxyalkylphosphonates in the Reaction of
Trialkyl Phosphites with Oxonium Salts Derived from Aldehydes or Ketones
Preparation of
Dialkyl
1
a
-Hydroxya
l
l
kylpho
d
sphonates emar Goldeman, Mirosław Soroka*
Politechnika Wrocławska, Department of Chemistry, Wybrzeże Wyspiańskiego 27, 50370 Wrocław, Poland
Fax +48(71)3284064; E-mail: miroslaw.soroka@pwr.wroc.pl
Received 16 March 2006; revised 19 June 2006
The activation of dialkyl phosphonates by bases causes
Abstract: The reaction of trialkyl phosphites with aldehydes or ke-
tones in the presence of hydrogen chloride gives dialkyl 1-hydroxy-
alkylphosphonates via Arbusov-like reaction of oxonium salts
derived from aldehydes or ketones. This reaction is a very conve-
two main problems. The first problem is the reversibility
of the reaction of dialkyl phosphonates with aldehydes or
ketones,13 especially when a high temperature is neces-
nient instant method for the preparation of dialkyl 1-hydroxyalkyl- sary to distill the products. In this case instead of dialkyl
phosphonates with a good yield as an alternative to the well-known
Abramov reaction.
1-hydroxyalkylphosphonate, the substrates, namely a
mixture of dialkyl phosphonate and the carbonyl com-
Key words: Abramov reaction, nucleophilic addition, addition re-
actions, 1-hydroxyphosphonates
pound, can be distilled from the reaction mixture when a
base is present. The second problem is a well-known
phosphonate–phosphate rearrangement, which gives the
alkyl phosphates instead of the desired 1-hydroxyalkyl-
The synthesis of 1-hydroxyalkylphosphonates has been phosphonates.7,14 This problem exists especially when a
extensively studied and described in the literature. Search- strong base is applied as the catalyst in the Abramov reac-
ing common databases gives more than 5001 papers de- tion. Additionally, the anions of dialkyl phosphonates, ob-
voted to the preparation of a broad spectrum of 1- vious ambident nucleophiles, can react by their electron
hydroxyalkylphosphonates. However, most of them are pair located on the phosphorus atom, as well as by those
just obvious modifications of the old method described for located on the oxygen, for example, when silver dialkyl
the first time in 19502 by Abramov3 and independently by phosphonates react with some halides, the alkylation on
Pudovik4 and Fields.5 This method is based on the reac- oxygen is observed predominantly.15 Finally, the basic
tion of aldehydes or ketones with dialkyl phosphonates, in catalyst could also cause the well-known aldol reaction,
the presence of a catalytic amount of base (sodium alkox- and the products of the aldol reaction could react with di-
ides were applied by Abramov and Pudovik, and triethyl- alkyl phosphonates to give a complex reaction mixture.
amine by Fields). Except for some activated carbonyl
Studying the literature we found some precedents where
compounds like hexafluoroacetone6 or trichloroacetalde-
acid catalysts like boron trifluoride etherate, aluminum
hyde,7 the addition of base is essential for the Abramov re-
trichloride or hydrogen chloride,16 lithium perchlorate and
action, since the reaction between dialkyl phosphonates
diethyl ether17 and TFA or TfOH,18 were used for the ac-
and aldehydes or ketones does not start spontaneously be-
tivation of dialkyl phosphonates and aldehydes in the
cause: (i) the phosphonate is too weakly acidic to activate
Abramov reaction, however, with moderate results.
the aldehyde or ketone, and (ii) the aldehyde (or ketone)
Surprisingly, we found very few reports describing the re-
is too weakly basic to activate the dialkyl phosphonates.
actions of trialkyl phosphites with aldehydes or ketones,
Therefore, most methods devoted to the synthesis of 1-hy-
despite the fact that trialkyl phosphites are obviously
droxyalkylphosphonates concentrate on finding a better
much better nucleophiles than dialkyl phosphonates, and
catalyst than reported previously.
they are certainly P-nucleophiles because of their free
Some of these catalysts were described in context of their
electron pairs located only on the phosphorus atom.
usefulness for preparative applications. For example,
Abramov19 reported that the reaction of trialkyl phosphi-
Texier-Boullet et al.8 described the convenient synthesis
tes and aldehydes gives the corresponding dialkyl 1-
of 1-hydroxyalkylphosphonates from aldehydes and di-
alkoxyalkylphosphonates, though with rather low yields,
alkyl phosphonates in the presence of potassium or ceasi-
and under very harsh reaction conditions (high tempera-
um fluorides, then on alumina,9 and finally on potassium
ture and pressure). Most aldehydes are unreactive towards
fluoride on alumina.10 Baraldi et al.11 described the prep-
trialkyl phosphites under neutral conditions at room tem-
aration of several diethyl 1-hydroxyalkylphosphonates
perature,19 but if forced, by employing a high temperature
using triethylamine as catalyst. Gawron et al.12 described
and pressure, give complex reaction mixtures.20 Also, 4-
an activation of diethyl phosphonate by ethylmagnesium
methyl-4-dichloromethylcyclohexadien-1-one,21 acetone,
bromide.
and cyclohexanone were resistant to trialkyl phosphites,
even when they were refluxed for a long time.20b The mix-
SYNTHESIS 2006, No. 18, pp 3019–3024
x
x.
x
x
.
2
0
0
6
ture of benzophenone and trimethylphosphite does not re-
Advanced online publication: 15.08.2006
DOI: 10.1055/s-2006-950200; Art ID: T04106SS
act at 160 °C even after several days.20e
© Georg Thieme Verlag Stuttgart · New York

3020
W. Goldeman, M. Soroka
PAPER
Under such circumstances, we decided to apply the tri- that diethyl phosphonate does not react with benzalde-
alkyl phosphites with simultaneous in situ activation of hyde in the presence of equimolar amounts of hydrogen
the carbonyl group of aldehydes or ketones by an acid. We chloride.
assumed that the strong acid, for example hydrogen chlo-
To test the scope and limitation of this reaction we exam-
ride, would activate the carbonyl group by protonation of
ined some representative carbonyl compounds under sim-
oxygen, to generate the corresponding oxonium salt.
ilar conditions. The reaction of acetone with triethyl
Then, the oxonium salt, a very strong electrophile, should
phosphite gave diethyl 1-hydroxy-1-methylethylphospho-
react with nucleophilic trialkyl phosphite giving the inter-
nate in about 50% yield (by means of 31P NMR spectros-
mediate phosphonium salt, which could be transformed to
copy), and diethyl phosphonate as a side-product derived
the final dialkyl 1-hydroxyalkylphosphonate analogously
from dealkylation of triethyl phosphite. However, when
to the last step of the Arbuzov reaction (Scheme 1).
we used a 50% excess of triethyl phosphite, the yield in-
creased to about 85%. Also in the case of aliphatic alde-
hydes, an excess of phosphites was useful. Benzophenone
H
+
R1
O
H-Cl
R1
O
(Alk-O)3P
did not give 1-hydroxyphosphonate at all, which indicates
that the dealkylation reaction of trialkyl phosphite is a few
orders of magnitude faster than the reaction of triethyl
phosphite with a sterically hindered oxonium salt. There-
fore, the only product detected in the reaction mixture was
diethyl phosphonate. Dialkyl 1-oxoalkylphosphonates re-
act easily with an equimolar amount of trialkyl phosphites
to give tetraalkyl 1-hydroxyalkylidenebisphosphonates in
excellent yields (Scheme 3).
Cl–
R2
OH
R2
Cl–
O-Alk
OH
R1
R1
O-Alk
+
P
P
O-Alk
O-Alk
– Alk-Cl
O-Alk
R2
R2
O
Scheme 1
Indeed, when we examined the reaction of triethyl phos-
phite with benzaldehyde in the presence of a stoichiomet-
ric amount of hydrogen chloride in anhydrous diethyl
ether at temperatures below –10 °C, we found by means
of 31P NMR spectroscopy that the crude reaction mixture
contains as much as 88% of diethyl 1-hydroxy-1-phenyl-
methylphosphonate and a minor amount of diethyl phos-
phonate. To exclude the possibility that the triethyl
phosphite was dealkylated by the hydrogen chloride to di-
ethyl phosphonate (which could also give the final diethyl
1-hydroxy-1-phenylmethylphosphonate in the reaction
with benzaldehyde), we accomplished the cross-experi-
ment. Thus, when we mixed stoichiometric amounts of
benzaldehyde, triisopropyl phosphite, diethyl phospho-
nate, and hydrogen chloride in diethyl ether –10 °C, we
observed only diisopropyl 1-hydroxy-1-phenylmethyl-
phosphonate in 94% yield (but not diethyl 1-hydroxy-1-
phenylmethylphosphonate). We also recovered unreacted
diethyl phosphonate with traces of diisopropyl phospho-
nate in about 6% yield (Scheme 2).
R1
O
O
R1
(Alk-O)3P, HCl
– Alk-Cl
Alk-O
Alk-O
O-Alk
O-Alk
P
P
P
O-Alk
OH
O
O
O-Alk
Scheme 3
For example, we prepared the tetraethyl 1-hydroxyeth-
ylidenebisphosphonate in over 95% yield, by the reaction
of diethyl 1-oxoethylphosphonate with triethyl phosphite
in the presence of hydrogen chloride. This seems to be a
good method for the preparation of 1-hydroxybisphos-
phonates, which is competitive with those described in the
literature.22
In summary, we have found that the reaction of trialkyl
phosphites with aldehydes or ketones in the presence of
hydrogen chloride23 at a low temperature is a very good
method for the preparation of dialkyl 1-hydroxyalkyl-
phosphonates. This procedure is very simple, instant, and
gives the final products in very good yields. Moreover,
usually the final products are pure enough to be used di-
rectly for further steps, without the necessity of additional
operations like chromatographic separation, for example.
In many cases the products just crystallize directly out of
the reaction mixture. The side products (volatile alkyl ha-
lides and dialkyl phosphonates) could be easily removed
by simple evaporation. Also noteworthy is that the dialkyl
1-hydroxyalkylphosphonates obtained by our method nei-
ther decompose nor rearrange during their eventual distil-
lation.
O
P
O-i-Pr
O-i-Pr
OEt
OEt
HCl
+
+
P
H
Ph
O
CH2Cl2
O-i-Pr
OH
O
O
OEt
O-i-Pr
O-i-Pr
+
Ph
H
P
+
H
P
P
OEt
O-i-Pr
O-i-Pr
O
Scheme 2
After the reaction, the crystalline diisopropyl 1-hydroxy-
1-phenylmethylphosphonate was isolated in 83% yield
NMR spectra were recorded on a Bruker Avance 300 MHz spec-
and its structure was confirmed. This double cross-exper- trometer in CDCl3. FTIR spectra were measured on Perkin Elmer
2000 spectrometer as KBr pellets (1/200) for crystalline or as a film
iment additionally shows that hydrogen chloride neither
for liquid products. Melting points were determined on a Boetius
dealkylates the trialkyl phosphite nor activates dialkyl
microscope with electrical hot plate and were corrected. The carbo-
phosphite. Moreover, in a separate experiment we found
Synthesis 2006, No. 18, 3019–3024 © Thieme Stuttgart · New York

PAPER
Preparation of Dialkyl 1-Hydroxyalkylphosphonates
3021
Table 1 Dialkyl 1-Hydroxyalkylphosphonates
OH
R1
O-Alk
P
O-Alk
R2
O
R1
Ph
Ph
R2
H
Alk
i-Pr
Et
(AlkO)3P/R1R2C=O
Yield (%)
83
Mp ( °C) or bp (°C/mmHg)
1:1
1:1
1:1
1:1
1:1
3:2
3:2
3:2
3:2
3:2
3:2
3:2
1:1
3:2
1:1
89–923b
H
74
78–802i,3b
4-MeO-C6H4
H
Et
80
121–12224
Ph-CH=CH-
H
Et
79
104–10724,13b,4b
93–943d,24
3-O2N-C6H4
H
Et
80
Me
H
Et
72
148–156/15a 3b,13b,5
147–154/15a, 3b,j,5
147–153/15a, 13b
73–7510,14f
Et
H
Et
84
i-Pr
H
Et
83
Ph
Me
Me
Me
Et
41
Me
Et
73
131–150/15a 3b,13b,5
140–160/15a
71–723b,10
Pr
Et
66
-(CH2)5-
4-MeO-C6H4-
-(CH2)5-
Me
Et
80
H
i-Pr
i-Pr
Et
88
150–151
79
97–983b
P(O)(OEt)2
98
Oil14b
a Bulb-to-bulb vacuum distillation, therefore the boiling ranges were very broad.
nyl compounds were acquired from a local supplier and were dis-
tilled before use. All reagents and solvents were of commercial
quality and purchased from a local supplier. The procedures and
isolations of products described in this paper were not optimized.
31P NMR: d = 21.5
Dialkyl 1-Hydroxyalkylphosphonates; General Procedure
To a cold (ca. –10 °C, ice–salt bath) solution of the carbonyl com-
pound (0.020 mol) and trialkyl phosphite (0.020 mol for aromatic
aldehydes, or 0.030 mol for aliphatic aldehydes or ketones), in
CH2Cl2 (25 mL), a cold (ca. –10 °C) solution of HCl (0.020 or 0.030
mol, respectively) in Et2O was added dropwise. The reaction mix-
ture was stirred for about 1 h at the same temperature, and then kept
in the refrigerator (below –10 °C) overnight. The solvent and vola-
tile by-products were evaporated in vacuo in a warm water bath (be-
low 40 °C) to give an oily residue, which was crystallized from Et2O
(20 mL) or from Et2O–hexane (1:1, 20 mL). The crystallizing mix-
ture was kept in the refrigerator at ca. –10 °C for about 1 h, and then
the product was filtered, washed with cold Et2O (3 × 5 mL) (or
Et2O–hexane), and dried. The liquid 1-hydroxyalkylphosphonates
were distilled in vacuo. When the product is crystalline, the reaction
could be performed in Et2O–hexane, so the product crystallizes di-
rectly from the reaction mixture.
Cross-Experiment
To a cold (ca. –10 °C, ice–salt bath) solution of benzaldehyde (2.1
g, 0.020 mol), P(i-PrO)3 (4.2 g, 0.020 mol) and O=PH(OEt)2 (2.8 g,
0.020 mol), in CH2Cl2 (25 mL), a cold (ca. –10 °C) solution of HCl
(5 M; 4 mL, 0.020 mol) in Et2O was added dropwise. The reaction
mixture was stirred for about 1 h at the same temperature, and then
kept in the refrigerator (below –10 °C) overnight. Then, a sample
(0.25 mL) was taken from the reaction mixture, evaporated to dry-
ness in vacuo in a cold water bath, and the residue was dissolved in
1
CDCl3 (0.50 mL). 31P and H NMR spectroscopy gave only three
peaks at 21.6 ppm (diisopropyl 1-hydroxy-1-phenylmethylphos-
phonate), 9.0 ppm (diethyl phosphonate), and traces of diisopropyl
phosphonate at 6.1 ppm. The rest of the reaction mixture was con-
centrated in vacuo in a warm water bath (below 40 °C) to give an
oily residue, which was crystallized, to give 4.5 g (83%) of diiso-
propyl 1-hydroxy-1-phenylmethylphosphonate.
Diethyl 1-Hydroxy-1-phenylmethylphosphonate
IR: 3264 (OH), 2990, 2931, 2908, 2829, 1601, 1492, 1479, 1450,
1391, 1367, 1328, 1228 (P=O), 1205, 1187, 1083, 1051 (POC),
1026 (POC), 978, 961, 852, 788, 762, 727, 701, 659, 629, 560, 531,
478, 412 cm–1.
1H NMR: d = 1.37 (t, J = 7.0 Hz, 6 H, CH3), 1.63 (br s, 1 H, OH),
2.5 (d, J = 13.8 Hz, 1 H, CHP), 4.20 (dq, J = 7.0, 7.0 Hz, 4 H,
OCH2), 7.20 (t, J = 7.1 Hz, 1 H, p-Ph), 7.30 (t, J = 7.0 Hz, 2 H, m-
Ph), 7.47 (d, J = 7.5 Hz, 2 H, o-Ph).
Diisopropyl 1-Hydroxy-1-phenylmethylphosphonate
IR: 3264 (OH), 3028, 2985, 2933, 2882, 1601, 1494, 1468, 1452,
1417, 1378, 1372, 1226 (P=O), 1207, 1186, 1143, 1107, 1080,
1046, 1024 (POC), 993 (POC), 937, 901, 892, 849, 789, 767, 746,
730, 701, 655, 630, 564, 545, 497, 458, 423 cm–1.
1H NMR: d = 1.13 (d, J = 6.2 Hz, 3 H, CH3), 1.25 (d, J = 6.1 Hz, 3
H, CH3), 1.27 (d, J = 5.5 Hz, 6 H, CH3), 3.44 (br s, 1 H, OH), 4.62
(m, 2 H, CH), 4.95 (d, J = 10.9 Hz, 1 H, CHP), 7.28–7.37 (m, 3 H,
m-,p-Ph), 7.47–7.50 (m, 2 H, o-Ph).
31P NMR: d = 28.4.
Synthesis 2006, No. 18, 3019–3024 © Thieme Stuttgart · New York

3022
W. Goldeman, M. Soroka
PAPER
Diethyl 1-Hydroxy-1-(4-methoxyphenyl)methylphosphonate
IR: 3258 (OH), 2992, 2962, 2933, 2909, 2834, 1614, 1586, 1512,
1477, 1462, 1438, 1389, 1368, 1329, 1251, 1228 (P=O), 1196,
1171, 1109, 1065 (POC), 1029 (POC), 976, 964, 862, 838, 797, 757,
710, 669, 639, 596, 557, 534, 495, 422 cm–1.
1H NMR: d = 1.14 (t, J = 7.1 Hz, 3 H, CH3), 1.20 (t, J = 7.1 Hz, 3
H, CH3), 3.5 (br s, 1 H, OH), 3.73 (s, 3 H, OCH3), 3.92–4.03 (m, 4
H, OCH2), 4.87 (d, J = 9.9 Hz, 1 H, CHP), 6.82 (d, J = 8.7 Hz, 2 H,
o-Ph), 7.33 (d, J = 8.7 Hz, 2 H, m-Ph).
3.0 (br s, 1 H, OH), 3.62 (dd, J = 6.05, 6.05 Hz, 1 H, CHP), 4.14 (dq,
J = 7.1, 7.1 Hz, 2 H, CH2O), 4.15 (dq, J = 6.9, 6.9 Hz, 2 H, CH2O).
31P NMR: d = 32.0.
Diethyl 1-Hydroxy-1-phenylethylphosphonate
IR: 3289 (OH), 2978, 2934, 2907, 1603, 1496, 1452, 1390, 1371,
1289, 1220 (P=O), 1200, 1186, 1162, 1139, 1126, 1098, 1051
(POC), 1026 (POC), 963, 946, 912, 833, 790, 762, 746, 698, 685,
658, 584, 562, 508, 471 cm–1.
31P NMR: d = 23.4.
1H NMR: d = 1.18 (t, J = 7.1 Hz, 3 H, CH3), 1.24 (t, J = 7.1 Hz, 3
H, CH3), 1.80 (d, J = 15.4 Hz, 3 H, CH3CP), 3.42 (br s, 1 H, OH),
3.95 (m, 2 H, OCH2), 4.07 (m, 2 H, OCH2), 7.27 (dd, J = 7.2, 1.6
Hz, 1 H, p-Ph), 7.33 (d, J = 7.9 Hz, 1 H, o-Ph), 7.36 (d, J = 7.4 Hz,
1 H, o-Ph), 7.59 (m, 2 H, m-Ph).
Diethyl 1-Hydroxy-3-phenyl-2-propenylphosphonate
IR: 3255 (OH), 2982, 2929, 2910, 2866, 1599, 1519, 1495, 1478,
1447, 1392, 1369, 1292, 1226 (P=O), 1190, 1113, 1052 (POC),
1021 (POC), 970, 855, 793, 759, 730, 698, 660, 562, 527, 485, 418
cm–1.
31P NMR: d = 30.9.
1H NMR: d = 1.31 (t, J = 7.1 Hz, 3 H, CH3), 1.32 (t, J = 7.1 Hz, 3
H, CH3), 3.9 (br s, 1 H, OH), 4.18 (dq, J = 7.1, 7.1 Hz, 4 H, OCH2),
4.66 (ddd, J = 12.9, 6.1, 1.4 Hz, 1 H, CHP), 6.31 (ddd, J = 15.9, 6.1,
6.0 Hz, 1 H, CHCP), 6.77 (ddd, J = 15.9, 4.8, 1.4 Hz, 1 H, PhCH),
7.23 (t, J = 7.4 Hz, 1 H, p-Ph), 7.30 (t, J = 7.4 Hz, 2 H, m-Ph), 7.30
(d, J = 7.4, 2 H, o-Ph).
Diethyl 1-Hydroxy-1-methylethylphosphonate
Crystallizes in the refrigerator and melts at r.t.
IR: 3315 (OH), 2982, 2934, 2911, 1699, 1445, 1393, 1375, 1237
(P=O), 1193, 1136, 1162, 1139, 1126, 1098, 1050 (POC), 1028
(POC), 971, 857, 792, 762, 666, 529, 436 cm–1.
1H NMR: d = 1.27 (t, J = 7.2 Hz, 6 H, CH3), 1.38 (d, J = 15.3 Hz, 6
H, CH3CP), 4.1 (dq, br s, J = 7.2, 7.2 Hz, 5 H, 2 × CH2O, OH).
31P NMR: d = 28.6.
31P NMR: d = 34.5.
Diethyl 1-Hydroxy-1-(3-nitrophenyl)methylphosphonate
IR: 3245 (OH), 2983, 2932, 2914, 2869, 1537 (NO2), 1479, 1445,
1395, 1351 (NO2), 1320, 1296, 1260, 1236, 1209 (P=O), 1189,
1166, 1091, 1044 (POC), 1020 (POC), 972, 906, 842, 810, 781, 738,
719, 687, 667, 568, 537 cm–1.
1H NMR: d = 1.24 (t, J = 7.05 Hz, 3 H, CH3), 1.28 (t, J = 7.05 Hz,
3 H, CH3), 4.11 (m, 4 H, OCH2), 5.15 (d, J = 11.5 Hz, 1 H, PCH),
5.7 (br s, 1 H, OH), 7.5 (t, J = 7.8 Hz, 1 H, m-Ph), 7.79 (d, J = 7.8
Hz, 1 H, o-Ph), 8.12 (d, J = 7.8 Hz, 1 H, p-Ph), 8.39 (s, 1 H, o-Ph).
Diethyl 1-Hydroxy-1-methylbutylphosphonate
IR: 3316 (OH), 2981, 2963, 2935, 2911, 2875, 1699, 1645, 1468,
1457, 1445, 1393, 1369, 1292, 1227 (P=O), 1167, 1135, 1098, 1031
(POC), 967 (POC), 912, 848, 794, 766, 711, 670, 570, 520 cm–1.
1H NMR: d = 0.9 (t, J = 7.2 Hz, 3 H, CH3CH2), 1.3 (t, J = 7.2 Hz, 6
H, CH3CH2O), 1.35 (d, J = 15.9 Hz, 3 H, CH3CHP), 1.45 (m, 2 H,
CH3CH2CH), 1.65 (m, 2 H, CH2CHP), 3.1 (br s, 1 H, OH), 4.13 (dq,
J = 7.2, 7.2 Hz, 2 H, OCH2), 4.14 (dq, J = 7.2, 7.2 Hz, 2 H, OCH2).
31P NMR: d = 21.6.
31P NMR: d = 34.4.
Diethyl 1-Hydroxyethylphosphonate
Diethyl 1-Hydroxycyclohexylphosphonate
IR: 3317 (OH), 2983, 2935, 2911, 2873, 1651, 1479, 1445, 1393,
1369, 1220 (P=O), 1164, 1114, 1100, 1053 (POC), 1028 (POC),
968, 902, 867, 795, 692, 553, 474 cm–1.
1H NMR: d = 1.30 (t, J = 7.1 Hz, 3 H, CH3), 1.31 (t, J = 7.2 Hz, 3
H, CH3), 1.4 (dd, J = 17.5, 7.2 Hz, 3 H, CH3CP), 3.9 (br s, 1 H, OH),
4.00 (dq, J = 14.2, 7.2 Hz, 1 H, CHP), 4.13 (dq, J = 7.2, 7.2 Hz, 2
H, OCH2), 4.14 (dq, J = 7.1, 7.1 Hz, 1 H, OCHH), 4.15 (dq, J = 7.0,
7.0 Hz, 1 H, OCHH).
IR: 3259 (OH), 2984, 2936, 2865, 2849, 1484, 1444, 1397, 1367,
1320, 1262, 1220 (P=O), 1163, 1139, 1071, 1047, 1024, (POC), 970
(POC), 957, 932, 911, 902, 847, 802, 760, 699, 582, 520, 502, 491,
452 cm–1.
1H NMR: d = 1.29 (t, J = 7.1 Hz, 6 H, CH3), 1.5 (m, 2 H, 4-CH2),
1.6 (m, 6 H, 2-,3-,5-,6-CH2), 1.8 (m, 2 H, 2-,6-CH2), 3.08 (br s, 1 H,
OH), 4.13 (dq, J = 7.1, 7.1 Hz, 4 H, OCH2).
31P NMR: d = 33.6.
31P NMR: d = 32.8.
Diisopropyl 1-Hydroxy-1-(4-methoxyphenyl)methylphospho-
nate
IR: 3268 (OH), 2978, 2937, 2898, 2873, 2837, 1613, 1584, 1511,
1460, 1438, 1389, 1377, 1357, 1344, 1300, 1249, 1226 (P=O),
1202, 1190, 1170, 1143, 1107, 1063, 1028 (POC), 995, 900, 891,
856, 786, 757, 737, 712, 673, 638, 596, 559, 546, 511, 471, 433, 418
cm–1.
1H NMR: d = 1.13 (d, J = 6.2 Hz, 3 H, CH3), 1.27 (d, J = 6.2 Hz, 6
H, CH3), 1.28 (d, J = 6.2 Hz, 3 H, CH3), 3.56 (br d, J = 3.6 Hz, 1 H,
OH), 3.80 (s, 3 H, OCH3), 4.61 (m, 2 H, CH), 4.87 (d, J = 10.0 Hz,
1 H, CHP), 6.88 (d, J = 8.7 Hz, 2 H, o-Ph), 7.41 (d, J = 8.7 Hz, 1 H,
m-Ph), 7.42 (d, J = 8.7 Hz, 1 H, m¢-Ph).
Diethyl 1-Hydroxypropylphosphonate
IR: 3312 (OH), 2981, 2935, 2878, 1470, 1444, 1393, 1369, 1215
(P=O), 1165, 1119, 1091, 1053 (POC), 1028 (POC), 968, 792, 619,
566, 506 cm–1.
1H NMR: d = 1.04 (t, J = 7.4 Hz, 3 H, CH3CH2CH), 1.30 (t, J = 7.1
Hz, 6 H, CH3CH2O), 1.70 (m, 1 H, OCHHCH3), 1.77 (m, 1 H,
OCHHCH3), 3.7 (ddd, br s, J = 13.7, 4.1 Hz, 2 H, CHP, OH), 4.13
(dq, J = 7.1, 7.1 Hz, 2 H, OCH2), 4.132 (dq, J = 7.1, 7.1 Hz, 1 H,
OCHH), 4.137 (dq, J = 7.1, 7.1 Hz, 1 H, OCHH).
31P NMR: d = 32.2.
Diethyl 1-Hydroxy-2-methylpropylphosphonate
31P NMR: d = 21.7.
IR: 3313 (OH), 2982, 2934, 2910, 2875, 1645, 1470, 1445, 1392,
1368, 1216 (P=O), 1165, 1130, 1097, 1050 (POC), 1030 (POC),
968, 851, 799, 708, 624, 564, 515, 455 cm–1.
1H NMR: d = 1.037 (d, J = 6.8 Hz, 3 H, CH3CH), 1.042 (d, J = 7.1
Hz, 3 H, CH3CH), 1.31 (t, J = 7.1 Hz, 6 H, CH3), 2.06 (m, 1 H, CH),
Diisopropyl 1-Hydroxycyclohexylphosphonate
IR: 3275 (OH), 2991, 2978, 2946, 2858, 1759, 1471, 1448, 1407,
1384, 1358, 1259, 1227 (P=O), 1176, 1159, 1141, 1105, 1070,
Synthesis 2006, No. 18, 3019–3024 © Thieme Stuttgart · New York

PAPER
Preparation of Dialkyl 1-Hydroxyalkylphosphonates
3023
1037, 996 (POC), 982 (POC), 933, 915, 896, 881, 763, 756, 699,
681, 581, 538, 494, 426 cm–1.
1H NMR: d = 1.33 (d, J = 6.2 Hz, 12 H, CH3), 1.53 (m, 2 H, 4-CH2),
1.58–1.77 (m, 6 H, 2-, 3-5-,6-CH2), 1.83 (m, 2 H, 2-,6-CH2), 2.27
(br s, 1 H, OH), 4.75 (dsept, J = 6.2, 12.4 Hz, 2 H, CHO).
Obshch. Khim. 1953, 23, 1013; Chem. Abstr. 1954, 48,
8169d. (o) Khairullin, V. K.; Ledeneva, A. I.; Abramov, V.
S. Zh. Obshch. Khim. 1959, 29, 2551; Chem. Abstr. 1960,
54, 10835g.
(4) (a) Pudovik, A. N. Dokl. Akad. Nauk SSSR 1950, 73, 499;
Chem. Abstr. 1951, 45, 2856d. (b) Pudovik, A. N.; Kitaev,
Yu. O. Zh. Obshch. Khim. 1952, 22, 467; Chem. Abstr. 1953,
47, 2687a.
31P NMR: d = 26.8.
Tetraethyl 1-Hydroxyethylidenediphosphonate
IR: 3250 (OH), 2985, 2934, 2911, 2871, 1479, 1445, 1393, 1368,
1251, (P=O), 1165, 1098, 1027 (POC), 973 (POC), 842, 797, 734,
639, 542 cm–1.
1H NMR: d = 1.21 (t, J = 7.1 Hz, 12 H, CH3CO), 1.53 (t, J = 16.2
Hz, 3 H, CH3CP), 3.94–4,15 (m, br s, 9 H, 4 × CH2, OH).
(5) Fields, E. K. Pat. US 2,579,810, 1951; Chem. Abstr. 1952,
46, 6140h.
(6) Janzen, A. F.; Pollitt, R. Can. J. Chem. 1970, 48, 1987.
(7) (a) Barthel, W. F.; Alexander, B. H.; Giang, P. A.; Hall, S.
A. J. Am. Chem. Soc. 1954, 76, 4186. (b) Lorenz, W.;
Henglein, A.; Schrader, G. J. Am. Chem. Soc. 1955, 77,
2554.
(8) (a) Texier-Boullet, F.; Foucaud, A. Synthesis 1982, 165.
(b) Texier-Boullet, F.; Foucaud, A. Tetrahedron Lett. 1980,
21, 2161.
31P NMR: d = 27.2.
Acknowledgment
(9) Texier-Boullet, F.; Foucaud, A. Synthesis 1982, 916.
(10) Texier-Boullet, F.; Lequitte, M. Tetrahedron Lett. 1986, 27,
3515.
We thank Mrs. Elżbieta Mróź for recording the IR spectra.
(11) Baraldi, P. G.; Guarneri, M.; Moroder, F.; Pollini, G. P.;
Simoni, D. Synthesis 1982, 653.
References
(12) Gawron, O.; Grelecki, C.; Reilly, W.; Sands, J. J. Am. Chem.
Soc. 1953, 75, 3591.
(1) Since citation of more than 500 papers in this short article is
not appropriate we will send a copy of a text file with the
citations to interested readers.
(13) (a) Abramov, V. S.; Semenowa, L. P.; Semenowa, L. G.
Dokl. Akad. Nauk SSSR 1952, 84, 281; Chem. Abstr. 1953,
47, 3227i. (b) Kharasch, M. S.; Mosher, R. A.; Bengelsdorf,
I. S. J. Org. Chem. 1960, 25, 1000. (c) Gancarz, R.
Tetrahedron 1995, 51, 10627. (d) Gancarz, R.; Gancarz, I.;
Walkowiak, U. Phosphorus, Sulfur Silicon Relat. Elem.
1995, 104, 45.
(14) (a) Pudovik, A. N.; Guryanova, I. V.; Banderova, L. V.;
Romanov, G. V. Zh. Obshch. Khim. 1968, 38, 143; Chem.
Abstr. 1968, 69, 96839d. (b) Fitch, S. J.; Moedritzer, K. J.
Am. Chem. Soc. 1962, 84, 1876. (c) Kukhtin, V. A.;
Abramov, V. S.; Orekhova, K. M. Dokl. Akad. Nauk SSSR
1959, 128, 1198; Chem. Abstr. 1960, 54, 7536b. (d)Hall, R.
A. L.; Stephens, C. W. J. Am. Chem. Soc. 1956, 78, 2565.
(e) Hall, R. A. L.; Stephens, C. W.; Drysdale, J. J. J. Am.
Chem. Soc. 1957, 79, 1768. (f) Timmler, H.; Kurz, J. Chem.
Ber. 1971, 104, 3740. (g) Gancarz, R.; Gancarz, I.; Deron,
A. Phosphorus, Sulfur Silicon Relat. Elem. 2000, 161, 61.
(15) Arbuzov, B. A.; Krasil’nikova, E. A. Izv. Akad. Nauk SSSR,
Ser. Khim. 1959, 30; Chem. Abstr. 1959, 53, 14982c.
(16) Pudovik A. N., Zimin M. G., Sobanov A. A., Musina A. A.;
Zh. Obshch. Khim.; 1976, 46: 1455; Chem. Abstr. 1976, 85,
143203j.
(2) The chemistry of 1-hydroxyalkylphosphonic acids is of
course much older. 1-Hydroxyalkylphosphonic acids were
prepared in the 19th and 20th centuries by Marie and Fossek:
(a) Marie, C. C. R. Hebd. Seances Acad. Sci. 1902, 135, 107.
(b) Marie, C. C. R. Hebd. Seances Acad. Sci. 1903, 136, 48.
(c) Marie, C. Ann. Chim. (Paris) 1904, 8, 335. (d) Fossek,
W. Monatsh. Chem. 1884, 5, 121. (e) Fossek, W. Monatsh.
Chem. 1886, 5, 627. (f) Fossek, W. Monatsh. Chem. 1886,
7, 20. Later, Conant described the preparation of some 1-
hydroxyalkylphosphonic acids in the reaction of
phosphorous (phosphonic) acid or phosphorus trichloride
with aldehydes or ketones: (g) Conant, J. B. J. Am. Chem.
Soc. 1917, 39, 2679. (h) Conant, J. B.; Cook, A. A. J. Am.
Chem. Soc. 1920, 42, 830. (i) Conant, J. B. J. Am. Chem.
Soc. 1921, 43, 1705.
(3) This reaction is commonly called the Abramov reaction. For
the most representative Abramov papers, see: (a) Abramov,
V. S. Dokl. Akad. Nauk SSSR 1950, 73, 487; Chem. Abstr.
1951, 45, 2855h. (b) Abramov, V. S. Zh. Obshch. Khim
1952, 22, 647; Chem. Abstr. 1953, 47: 5351e. (c) Abramov,
V. S.; Semenowa, L. P. Sb. Statei Obshch. Khim. 1953, 1,
393; Chem. Abstr. 1955, 49, 838g. (d) Abramov, V. S. Zh.
Obshch. Khim. 1957, 27, 169; Chem. Abstr. 1957, 51,
12878e. (e) Abramov, V. S.; Pall, S. Zh. Obshch. Khim.
1957, 27, 172; Chem. Abstr. 1957, 51, 12878g.
(17) Azizi N., Saidi M. R.; Phosphorus, Sulfur Silicon Relat.
Elem.; 2003, 178: 1255.
(18) Nifant’ev, E. E.; Kukhareva, T. S.; Popkova, T. N.;
Davydochkina, O. V. Zh. Obshch. Khim. 1986, 56, 304;
Chem. Abstr. 1986, 105, 209046a.
(f) Abramov, V. S.; Kapustina, A. S. Zh. Obshch. Khim.
1957, 27, 173; Chem. Abstr. 1957, 51, 12878h.
(19) Abramov, V. S. Dokl. Akad. Nauk SSSR 1954, 95, 991;
(g) Abramov, V. S.; Dimitrieva, R. V.; Kapustina, A. S. Zh.
Obshch. Khim. 1953, 23, 257; Chem. Abstr. 1954, 48,
2572c. (h) Abramov, V. S.; Khairullin, V. K. Zh. Obshch.
Khim. 1956, 26, 811; Chem. Abstr. 1956, 50: 14606b.
(i) Abramov, V. S.; Khairullin, V. K. Zh. Obshch. Khim.
1959, 29, 1222; Chem. Abstr. 1960, 54, 1347b.
(j) Abramov, V. S.; Il’ina, N. A. Zh. Obshch. Khim. 1954,
24, 124; Chem. Abstr. 1955, 49; 2997g. (k) Abramov, V. S.;
Kapustina, A. S. Zh. Obshch. Khim. 1954, 24, 311; Chem.
Abstr. 1955, 49; 4507a. (l) Abramov, V. S.; Nazmutdinova,
A. S. Zh. Obshch. Khim. 1955, 25, 1141; Chem. Abstr. 1956,
50, 3214b. (m) Abramov, V. S.; Kuznetsov, N. S. Sb. Statei
Obshch. Khim. 1953, 1, 398; Chem. Abstr. 1955, 49, 839a.
(n) Abramov, V. S.; Bochkova, Yu. A.; Polyakova, A. D. Zh.
Chem. Abstr. 1955, 49, 6084d.
(20) (a) Arbuzov, B. A.; Zoroastrova, V. M. Izv. Akad. Nauk
SSSR, Ser. Khim. 1960, 1030; Chem. Abstr. 1960, 54,
24627g. (b) Ginsburg, V. A.; Jakubovich, A. Ya. Zh.
Obshch. Khim. 1960, 30, 3979; Chem. Abstr. 1961, 55,
22099c. (c) Kukhtin, V. A.; Orekhova, K. M. Zh. Obshch.
Khim. 1960, 30, 1208; Chem. Abstr. 1961, 55, 358h.
(d) Kukhtin, V. A.; Kirillova, K. M. Zh. Obshch. Khim.
1961, 31, 2226; Chem. Abstr. 1962, 56, 3507e. (e)Poshkus,
A. C.; Herweh, J. E. J. Org. Chem. 1964, 29, 2567.
(f) Ramirez, F.; Patwardhan, A. V.; Heller, S. R. J. Am.
Chem. Soc. 1964, 86, 514. (g) Ramirez, F.; Bhatia, S. B.;
Smith, C. P. Tetrahedron 1967, 23, 2067.
Synthesis 2006, No. 18, 3019–3024 © Thieme Stuttgart · New York

3024
W. Goldeman, M. Soroka
PAPER
finished, we accidentally found this paper which is
(21) Miller, B. J. Org. Chem. 1963, 28, 345.
(22) (a) Schmidt, P. Patent CH 316,731, 1956; Chem. Abstr.
1958, 52, P2066h. (b) Schmidt, P. Patent CH 321,397, 1957;
Chem. Abstr. 1958, 52, 2067. (c) McConnell, R. L.; Coover,
H. W. J. Am. Chem. Soc. 1956, 78, 4450. (d) Cade, J. A. J.
Chem. Soc. 1959, 2272.
(23) Consiglio, G.; Failla, S.; Finocchiaro, P. Phosphorus, Sulfur
Silicon Relat. Elem. 1996, 117, 37. When this work was
complementary to ours. We could not find this citation
searching the Beilstein database which is in common use in
our lab, since this paper for unknown reason was not
abstracted.
(24) Sardarian, A. R.; Kaboudin, B. Synth. Commun. 1997, 27,
543.
Synthesis 2006, No. 18, 3019–3024 © Thieme Stuttgart · New York