Novel routes to aminophosphonic acids: Interaction of dimethyl H-phosphonate with hydroxyalkyl carbamates

Article abstract of DOI:10.1002/hc.20404

It was found that the reaction of dimethyl H-phosphonate (1) with 2-hydroxyalkyl-N-2′-hydroxyalkyl carbamates at 135°C includes several chemical reaction steps: (i) chemical transforma-tions of 1-methyl-2- hydroxyethyl-N-2′-hydroxyethyl carbamate (2) and 2-methyl-2-hydroxyethyl- N-2′-hydroxyethyl carbamate (3); (ii) transesterification of dimethyl H-phosphonate with 2 and 3, and with secondary hydroxyl-containing compounds that are formed during the course of the chemical transformation of 2-hydroxyalkyl-N-2′-hydroxyalkyl carbamates; (iii) hydrolysis of 1 and dialkyl H-phosphonates, formed via transesterification of 1 with secondary hydroxyl-containing compounds. The interaction was studied by means of ¹H, ¹³C, ³¹P NMR, and FAB mass spectroscopy.

Full text of DOI:10.1002/hc.20404

Heteroatom Chemistry
Volume 19, Number 2, 2008
N
ovel Routes to Aminophosphonic Acids:
Interaction of Dimethyl H-Phosphonate with
Hydroxyalkyl Carbamates
1
1
2
K. Troev, N. Koseva, and G. H a¨ gele
1
Institute of Polymers, Bulgarian Academy of Sciences, Sofia 1113, Bulgaria
2
Institute of Inorganic Chemistry and Structural Chemistry, Heinrich-Heine University,
40255 D u¨ sseldorf, Germany
Received 28 April 2006; revised 15 December 2006
ꢀ
carbamate
2 and 2-methyl-2-hydroxyethyl-N-2 -
ABSTRACT: It was found that the reaction of
dimethyl H-phosphonate (1) with 2-hydroxyalkyl-N-
hydroxyethyl carbamate 3 at elevated temperatures
>160 C) resulted in 3-ethyl-2-hydroxy-2-oxo-1,4,2-
oxazaphosphorinane (8), a hitherto nondescribed
cyclic α-aminophosphonic acid (Scheme 1) [1–3].
Obviously, 8 cannot be obtained directly from
diesters of H-phosphonic acids 1 and the mixture of
◦
(
ꢀ
◦
2
-hydroxyalkyl carbamates at 135 C includes several
chemical reaction steps: (i) chemical transforma-
ꢀ
tions of 1-methyl-2-hydroxyethyl-N-2 -hydroxyethyl
ꢀ
carbamate (2) and 2-methyl-2-hydroxyethyl-N-2 -
hydroxyethyl carbamate (3); (ii) transesterification
of dimethyl H-phosphonate with 2 and 3, and with
secondary hydroxyl-containing compounds that are
formed during the course of the chemical transforma-
2
and 3. It is produced via the reaction of diesters
of H-phosphonic acids with secondary compounds
that in turn are formed as a result of the chemical
transformations of 2 and 3. It results from the addi-
tion of the P H group of H-phosphonic acids to the
C N double bond (from Schiff bases).
It was shown [4] that 2 and 3 undergo several
chemical transformations, resulting in the formation
of several secondary compounds (Scheme 2).
ꢀ
tion of 2-hydroxyalkyl-N-2 -hydroxyalkyl carbamates;
(iii) hydrolysis of 1 and dialkyl H-phosphonates,
formed via transesterification of 1 with secondary
ꢀ
ꢀ
hydroxyl-containing compounds. The interaction
1
13
31
was studied by means of H, C, P NMR, and
FAB mass spectroscopy. ꢁC 2008 Wiley Periodicals, Inc.
We describe the continuation of our efforts to
prove the mechanism of the formation of 8. In this
communication, we report results from studying the
Heteroatom Chem 19:119–124, 2008; Published online in
Wiley InterScience (www.interscience.wiley.com). DOI
1
0.1002/hc.20404
interaction of dimethyl H-phosphonate (1, R = CH
3
)
with a mixture of 2 and 3.
INTRODUCTION
RESULTS AND DISCUSSION
Recently, it has been reported that the reaction of
phosphonic acid diesters 1 [(RO)
, C , i-C , C , and C
ture of 1-methyl-2-hydroxyethyl-N-2 -hydroxyethyl
2
P(O)H, R = CH
3
,
Studies by FAB spectroscopy of the reaction mix-
ture obtained after heating 1 with 2 and 3 at 135 C
revealed that during the heating several new com-
pounds were formed (Fig. 1).
◦
C
2
H
5
3
H
7
3
H
7
4
H
9
6
H
5
] with a mix-
ꢀ
Correspondence to: K. Troev; e-mail: ktroev@polymer.bas.bg.
Contract grant sponsor: Bulgarian Academy of Sciences.
Contract grant sponsor: Deutsche Forschungsgemeinschaft.
ꢀ
c 2008 Wiley Periodicals, Inc.
Besides the peaks of the starting compounds m/z
111.0 for 1 and 164.1 for 2 and 3, additional new
peaks were detected (Table 1).
119

120 Troev, Koseva, and H a¨ gele
The main peak with m/z = 146 can be assigned
to 5-methyl-3-(2-hydroxyethyl)-2-oxazolidinone 4,
which is formed by dehydration of 2 (Scheme 2)
[4]. The decarboxylation of 4 furnished the Schiff
base 5 (m/z 102.1). The experimental results show
◦
that decarboxylation proceeds at 135 C. The lower
temperature of decarboxylation [5,6] could be ex-
plained with the acidity of the reaction mixture.
Under these conditions, the reaction mixture con-
tained the monomethyl ester of phosphonic acid
CH
acid 12 (H
decarboxylation of 5-methyl-3-(2-hydroxyethyl)-2-
3
OP(O)(H)OH (11) (m/z 97.0) and phosphonic
3
PO ) (m/z 83.0), which initiate the
3
31
oxazolidinone (4). P{H} NMR spectra (Fig. 2) of
the reaction mixture showed signals in the range
from 11.83 to 6.38 ppm. From 11.61 to 10.68 ppm,
SCHEME 1
Synthesis of 3-ethyl-2-hydroxy-2-oxo-1,4,2-
oxazaphosphorinane 8.
SCHEME 2 Chemical transformation of 2 and 3.
Heteroatom Chemistry DOI 10.1002/hc

Novel Routes to Aminophosphonic Acids: Interaction of Dimethyl H-Phosphonate with Hydroxyalkyl Carbamates 121
FIGURE 1 FAB spectrum of the reaction mixture obtained after heating of 1 with 2 and 3.
there were four signals that can be assigned to the
phosphorus atoms of the products 6, 9, 10, and 13,
respectively.
Product 6 is formed by transesterification of 1
with 4 (Eq. (1)).
(2)
TABLE 1 FAB-MS Spectral Data of the Reaction Products
Obtained by the Interaction of 1 with the Mixture of 2 and 3
Product
[M + H]+
Product
[M + H]+
1
111.0 (2.4)
164.1 (9.6)
146.1 (100)
102.1 (20.5)
224.0 (68.8)
210.1 (23.1)
166.0 (16.1)
242.0 (23.4)
320.0 (25.9)
11
12
13
14
15
97.0 (62.4)
83.0 (13.7)
155.1 (10.0)
123.1 (7.9)
88.1 (48.2)
59.0 (17.3)
137.1 (20.7)
128.1 (21.9)
2
4
5
6
7
8
9
, 3
(
1)
= 11.05 ppm,
doublet of sextets with
The corresponding signal at δ
which represents
P
a
16
a
a
17
1
3
JPH = 705.3 Hz and
J
PH = 11.5 Hz, can be as-
a
18
signed to the phosphorus atom of 6. The hydrolysis
of 6 (Eq. (2)) furnished product 7 with m/z = 210
10
Peak intensities are given in parenthesis.
and the signal at δ
P
1
= 7.24 ppm, which is a dou-
a
+
The marked (M + H) is formed under FAB conditions after dehy-
3
blet of triplets with JPH = 665.6 and JPH = 7.7 Hz.
dratation.
Heteroatom Chemistry DOI 10.1002/hc

122 Troev, Koseva, and H a¨ gele
(4)
The intramolecular transesterification [7] of 2
or 3 yielded 2-oxazolidinone 15 (m/z = 88) and
∗
1
,2-propanediol 16 (m/z = 59.0) (Scheme 2) [4]. 1,2-
Propanediol participates in a transesterification
reaction with 1 to yield methyl-2-hydroxypropyl
H-phosphonate (13). The peak with m/z = 155.1
can be assigned to 13. The subsequent in-
tramolecular transesterification of 13 (Eq. (5)) re-
sulted in 4-methyl-1,3,2-dioxaphospholane (14) with
m/z = 123.1.
3
1
FIGURE 2
P{H} NMR spectrum of the reaction mixture
obtained after heating of 1 with 2 and 3.
A FAB spectrum shows a peak at m/z 166
(16.1%), which can be assigned to 8a or 8. We as-
sume that the thermal decarboxylation of 7 results
in the formation of the Schiff base 8a. Addition of the
P H group to the C N double bond then furnishes
8.
The transesterification of 1 with 2 or 3 (Eq. (3))
leads to the formation of product 9 with m/z = 242.
(5)
The resulting 13 undergoes an intramolecular
transesterification yielding 14. The intramolecular
transesterification is favored because 13 represents
an α-hydroxy-ethyl ester of phosphonic acid [8–11].
1
13
31
The structure of 14 was verified by H, C, and
P
NMR and FAB spectroscopy. Since 4-methyl-1,3,2-
dioxaphospholane 13 contains a chiral center in the
molecule, it is expected to exist as a mixture of di-
astereomers (having the methyl functions either cis
or trans with respect to the P O function). NMR
(
3)
The signal at δ
P
= 10.92 ppm can be assigned to the
31
phosphorus atom of product 9. The transesterifica-
tion of 9 with 1 (Eq. (4)) resulted in the formation of
product 10 with m/z = 320.
data confirm this assumption. P{H} NMR (Fig. 3a)
shows two signals at δ
at an intensity ratio of 1:1. H-coupled P NMR
P
= 23.92 and δ
P
= 23.10 ppm
1
31
Heteroatom Chemistry DOI 10.1002/hc

Novel Routes to Aminophosphonic Acids: Interaction of Dimethyl H-Phosphonate with Hydroxyalkyl Carbamates 123
(6)
3
1
The P NMR signal at δ
P
= 8.79 ppm is a doublet
1
3
of quartets with JPH = 666.03 Hz and JPH = 12.1 Hz,
which can be assigned to the phosphorus atom of 11.
The signal at δ
phorus atom of the phosphonic acid 12.
P
= 6.39 ppm characterizes the phos-
Heating of the above-mentioned reaction mix-
◦
ture to 160 C yielded 8. This cyclic aminophosphonic
acid 8 appears as an insoluble white solid product
at the surface of the reaction mixture, which can be
isolated via treatment of the reaction mixture with
absolute methanol.
To sum up, the interaction of 1 with the mix-
◦
ture of 2 and 3 at 135 C includes several chemical
reactions: (i) chemical transformations of 2 and 3;
(ii) transesterification of dimethyl H-phosphonate
with 2 and 3, and with secondary hydroxyl-
containing compounds which are formed as a result
of the chemical transformation of 2-hydroxyalkyl-
ꢀ
N-2 -hydroxyalkyl carbamates; (iii) intramolecular
transesterification of methyl-2-hydroxypropyl H-
phosphonate; (vi) hydrolysis of 1 and dialkyl H-
phosphonates, formed via transesterification of 1
with secondary hydroxyl-containing compounds.
◦
At 135 C, 1,2-propanediol, 2-oxazolidinone, and
◦
8
were isolated by vacuum distillation. At 165 C, 3-
ethyl-2-hydroxy-2-oxo-1,4,2-oxazaphosphorinane 8
was obtained.
FIGURE 3 (a) H-decoupled 31P{H} NMR spectrum of 14.
1
1
b) H-coupled-31P NMR spectrum of 14.
EXPERIMENTAL
Materials
(
Dimethyl H-phosphonate
1
was purchased
from Aldrich, manufactured by Fluka AG,
(
Fig. 3b) unequivocally confirms the skeleton of 14.
CH-9470
fied by distillation prior to use.
of and
Buchs,
Switzerland
and
A
puri-
mixture
More detailed results from structural studies on 14
will be published separately.
2
3
was synthesized by reacting
Hydrolysis of 1 (Eq. (6)) furnished monomethyl
H-phosphonate 11 (m/z = 97) and H-phosphonic
acid 12 (m/z = 83).
propylene carbonate and ethanolamine as de-
scribed in [1]. NMR spectra were measured using
a Bruker 500 MHz spectrometer. Solutions were
Heteroatom Chemistry DOI 10.1002/hc

124 Troev, Koseva, and H a¨ gele
◦
made in CDCl
3
, using TMS as internal and 85%
Heating at 165 C. Eleven grams of the reac-
H
3
PO as external standards. FAB spectra from
4
tion mixture obtained after separation of the above-
mentioned compounds was heated to and then kept
at 165 C for 6 h. Subsequently, the reaction mixture
compounds in glycerol were measured using a
Varian MAT 8200 spectrometer.
◦
was allowed to cool to room temperature and than
extracted with absolute methyl alcohol. The white
precipitate formed was filtered off and washed sev-
eral times with absolute methyl alcohol and dried
Reaction of Dimethyl H-Phosphonate with a Mix-
ture of 2 and 3. Heating at 135 C. Dimethyl H-
◦
phosphonate 1 (30.8 g, 0.28 mol) and the mixture of 2
and 3 (45.5 g, 0.28 mol) were put into a three-necked
flask equipped with a condenser, magnetic stirrer,
and thermometer. The reaction was performed at
◦
at 80 C to yield 1.4 g (12.7%) of 3-ethyl-2-hydroxy-
1
2-oxo-1,4,2-oxazaphosphorinane. H NMR (D
2
O), δ
); 1.64–1.80
), 1.83–1.97 (m, 1H, CH CH );
3.16–3.37 (m, 3H, CH and CH)), 4.18–4.36 (m, 2H,
). C{H} NMR (D O), δ (ppm): 10.11 (CH ),
21.4 (CH ), 44.7 (CH ), 55.92 (d,
PC = 136.7 Hz,
O), δ (ppm):
H
3
(ppm): 1.03 (t, 3H,
(m, 1H, CH CH
J
HH = 7.3 Hz, CH
3
◦
◦
1
3
(
20 C–128 C. Evolution of methanol began. After
5 min, the evolution of methanol ceased and 7.4 g
2
3
2
3
2
13
48%) of methanol was evolved. The reaction mix-
POCH
2
2
C
3
◦
1
ture was kept at 135 C for 30 min. Subsequently, the
reaction mixture was cooled to room temperature
and subjected to vacuum distillation to furnish the
following:
2
2
J
31
CH), 64.42 (CH
10.21.
2
). P{H} NMR (D
2
P
1
,2-Propanediol [2.3 g, 0.03 mol, 10,7%), bp
◦
−2
1
REFERENCES
3
1
4 C, 4 × 10 mmHg]; H NMR (CDCl
3
), δ (ppm):
H
3
.13 (d, JHH) = 6.6 Hz, 3H, CH
3
), 3.22–3.49 (m, 2H,
[
[
[
1] Troev, K. Phosphorus, Sulfur Silicon 1997, 127, 167–
13
1
CH
NMR (CDCl
8.63 (CH).
-methyl-1,3,2-dioxaphospholane 14 yield 11.6 g
2
), 3.70–3.80 (m, 1H, CH), 4.24 (br s, OH). C{ H}
170.
2] Troev, K.; Cremer, Sh.; H a¨ gele, G. Heteroat Chem
3
), δ (ppm): 19.11 (CH ), 68.19 (CH ),
C
3
2
1
999, 10, 627–631.
6
3] Troev, K.; H a¨ gele, G.; Kreidler, K.; Olschner, R.;
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4
◦
−2
1
(
33.9%); bp 56 C (2 × 10 mmHg); H NMR (CDCl
3
),
3
δ
H
(ppm): 1.37 (d, 3H, JHH = 6.3 Hz, CH
3
), 1.46 (d,
[4] Troev, K.; Koseva, N.; Mitova, V. J Org Chem
submitted).
3
(
3
(
H,
J
HH = 6.3 Hz, CH
3
), 3.81–3.86 and 4.23–4.32
), 3.98–4.02 and 4.45–4.53 (m, 2H,
[
5] Poindexter, G.; Owens, D.; Dolan, P.; Woo, E. J Org
Chem 1992, 57, 6257–6265.
m, 2H, POCH
POCH ), 4.64–4.69 (m, 1H, POCH), 4.77–4.81 (m,
2
2
[
6] Poindexter, G.; Strauss, K. M. Synth Commun 1993,
1
1
(
H, POCH), 7.25 (d, 1H, JPH = 717.54 Hz, PH), 7.28
),
(ppm):
2
3, 1329–1338.
1
31
d, 1H, JPH = 715.02 Hz, PH). P{H} NMR (CDCl
3
[7] (a) Homeyer, A. H. US Patent 2 399 118, 1946; (b)
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H. J Am Chem Soc 1957, 79, 672–675.
31
δ
P
(ppm): 23.92, 23.10; P NMR (CDCl
3.92, dd t, 23.10, eight lines from dddd; C{H}
NMR (CDCl ), δ (ppm): 76.1 (C4), 72.5 (C5), 19.8
): 75.4 (C4), 71.7 (C5), 19.4
).
3
), δ
P
13
2
3
C
3
(
(
d, JPOCC = 6.1 Hz, CH
3
[
8] Ogata, N.; Sanui, K.; Nakamura, H. Polym J 1978, 10,
3
d, JPOCC = 4.9 Hz, CH
3
499–504.
[
9] Nakamura, H.; Sakuma, H.; Ogata, N. Polym J 1979,
11, 279–284.
2-Oxazolidinone yield 7.9 g (0.09 mol, 32.4%), bp
◦
−2
1
8
3
9 C (4 × 10 mmHg); H NMR (CD
3
Cl) δ (ppm):
H
[
[
10] Puntambekar, H.; Naik, D.; Kapadi, A. Indian J Chem
B 1993, 32, 684–687.
11] Menger, F. M.; Smith, J. H. J Am Chem Soc 1969, 91,
5346–5349.
3
.64 (t,
J
HH = 8.2 Hz, 2H, N–CH
2
), 4.46 (m, 2H,
),
13
OCH
2
), 6.68 (br s, 1H, NH). C{H} NMR (CDCl
3
δ
C
(ppm): 41.0 (C4), 65,5 (C5), 161.5 (C2).
Heteroatom Chemistry DOI 10.1002/hc