A study on the acidic hydrolysis of cyclic phosphinates: 1-Alkoxy-3-phospholene 1-oxides, 1-ethoxy-3-methylphospholane 1-oxide, and 1-ethoxy-3-methyl-1,2,3,4,5,6-hexahydrophosphinine 1-oxide

Article abstract of DOI:10.1002/hc.21394

The hydrochloric acid-catalyzed hydrolysis of phosphinates was studied on 1-alkoxy-3-phospholene 1-oxides, 1-ethoxy-3-methylphospholane 1-oxide, and 1-ethoxy-3-methyl-1,2,3,4,5,6-hexahydrophosphinine 1-oxide as the model compounds. Under the conditions applied, the isomerization of the 3-phospholene moiety to the 2-phospholene ring also occurred leading to mixtures of the corresponding 1-hydroxy-3-phospholene oxide and 1-hydroxy-2-phospholene oxide. According to our optimized method, using 3 equivalents (0.5?mL) of concentrated hydrochloric acid in 1?mL of water per ca. 2 mmol of the substrate at reflux, the completion required 3-10?hour. The hydrolyses were characterized by pseudo-first-order rate constants and the isomerizations by rate constants. The application of p-toluenesulfonic acid under microwave irradiation at 140°C in the hydrolysis of 1-alkoxy-3-methyl-3-phospholene oxides associated with reaction times of 1-3?hour. The reactivity order of the 5- and 6-ring phosphinates in hydrolysis was set up.

Full text of DOI:10.1002/hc.21394

Received: 12 July 2017
DOI: 10.1002/hc.21394
Revised: 18 August 2017
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R E S E A R C H A R T I C L E
A study on the acidic hydrolysis of cyclic phosphinates: 1-Alkoxy-
3-phospholene 1-oxides, 1-ethoxy-3-methylphospholane 1-oxide,
and 1-ethoxy-3-methyl-1,2,3,4,5,6-hexahydrophosphinine 1-oxide
György Keglevich1
Nóra Zsuzsa Kiss1
Zita Rádai1
Nikoletta Harsági1
Áron Szigetvári2
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1Department of Organic Chemistry and
Technology, Budapest University of
Technology and Economics, Budapest,
Hungary
Abstract
The hydrochloric acid-catalyzed hydrolysis of phosphinates was studied on
1-alkoxy-3-phospholene 1-oxides, 1-ethoxy-3-methylphospholane 1-oxide, and
1-ethoxy-3-methyl-1,2,3,4,5,6-hexahydrophosphinine 1-oxide as the model com-
pounds. Under the conditions applied, the isomerization of the 3-phospholene moiety
to the 2-phospholene ring also occurred leading to mixtures of the corresponding
1-hydroxy-3-phospholene oxide and 1-hydroxy-2-phospholene oxide. According to
our optimized method, using 3 equivalents (0.5 mL) of concentrated hydrochloric
acid in 1 mL of water per ca. 2 mmol of the substrate at reflux, the completion
required 3-10 hour. The hydrolyses were characterized by pseudo-first-order rate
constants and the isomerizations by rate constants. The application of p-
toluenesulfonic acid under microwave irradiation at 140°C in the hydrolysis of
1-alkoxy-3-methyl-3-phospholene oxides associated with reaction times of 1-3 hour.
The reactivity order of the 5- and 6-ring phosphinates in hydrolysis was set up.
2Gedeon Richter Plc., Budapest, Hungary
Correspondence
György Keglevich, Department of Organic
Chemistry and Technology, Budapest
University of Technology and Economics,
Budapest, Hungary.
Email: gkeglevich@mail.bme.hu
Funding information
National Research Development and
Innovation Fund, Grant/Award Number:
HK119202
K E Y W O R D S
Cyclic phosphinates, 1-alkoxy-3-phospholene and phospholane oxide, 1-ethoxy-1,2,3,4,5,6-
hexahydrophosphinine 1-oxide, acidic hydrolysis, phosphinic acids, rate constants.
by the hydrolysis of diethyl arylphosphonates performed
in 6 equivalents of concentrated (cc.) hydrochloric acid at
1
INTRODUCTION
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The hydrolysis of P-esters, such as phosphinic-, phosphonic-,
and phosphoric-acid esters is an important synthetic pro-
tocol; however, its realization is more difficult than that of
carboxylic acid esters.[1,2] In most cases, the acid-catalyzed
hydrolysis is preferred, carried out by boiling the mixture
of the P-ester in aqueous hydrochloric acid. Most of the hy-
drolyses have not been optimized, and hence, the quantity
of the hydrochloric acid and the conditions including the
reaction time are excessive.[3,4] This is well demonstrated
the boiling point for 12 hour. After simple filtration, the
arylphosphonic acids were obtained in 71%-93% yields.[5]
1-Alkoxyphospholane oxides were hydrolyzed in 3 mol L−1
hydrochloric acid at reflux for 5-8 hour to give the cor-
responding phosphonic acids in yields of 60%-68%.[6]
Occasionally, dioxane was also used as a cosolvent or
as the sole solvent.[7] Instead of HCl, HBr may also be
used.[7-9] Trifluoroacetic acid-catalyzed hydrolysis of
phosphinates was also reported.[10] It is also possible to
carry out hydrolyses under basic conditions using aque-
ous NaOH or KOH.[11-17] Amine-catalyzed hydroly-
ses were also described.[18-21] A special protocol for the
Contract grant sponsor: National Research Development and Innovation Fund.
Contract grant number: K119202.
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Heteroatom Chemistry. 2017;28:e21394.
https://doi.org/10.1002/hc.21394
wileyonlinelibrary.com/journal/hc
© 2017 Wiley Periodicals, Inc.
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R1
O
Me
OH
R1
O
Me
2
RESULTS AND DISCUSSION
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2.1
Hydrolysis of the ring phosphinates in
|
P
P
the presence of hydrochloric acid catalyst on
conventional heating
OR2
1
2
∆
1-Ethoxy-3-methyl-3-phospholene 1-oxide (1a), 1-ethoxy-3,4-
dimethyl-3-phospholene 1-oxide (1b), and 1-methoxy-3-
methyl-3-phospholene 1-oxide (1c) were chosen as the starting
phosphinates. In the first approach, cc. hydrochloric acid and
water were measured in different quantities and ratios. After the
different periods of boiling the mixtures, they were extracted
with dichloromethane, and the residues obtained after evapo-
rating the solvent were analyzed by 31P NMR spectroscopy.
The results on the hydrolysis of 1-ethoxy-3-methyl-
3-phospholene oxide 1a are shown in Scheme 1 and in Table 1.
It can be seen that in the absence of hydrochloric acid, there was
no hydrolysis (Table 1, entry 1). It is also obvious that under
the conditions applied, the starting 1-ethoxy-3-phospholene
oxide 1a may have undergone partial isomerization to the
2-phospholene derivative 3a, and hydrolysis of the two phosph-
inates (1a and 3a) furnished the corresponding phosphinic acids
(2a and 4a, respectively). Boiling 1.9 mmol phosphinate 1a with
0.5 mL of cc. hydrochloric acid in 2 mL of water, the conversion
was 61% after a reaction time of 6 hour. All possible components
were present in the reaction mixture (Table 1, entry 2). Working
in a more concentrated solution, the conversion was 47% after
3 hour, and the completion required 6 hour. The ratio of the
1-hydroxy-3-phospholene oxide (2a) and its 2-phospholene
isomer (4a) was 1:9 (Table 1, entries 3 and 4). Decreasing the
quantity of water and hydrochloric acid to the half amount, the
conversion remained incomplete (92%) (Table 1, entry 5).
Adding 0.1 mL of [emim][HSO4] ionic liquid to the reac-
tion mixtures, somewhat lower conversions were obtained.
This was surprising, as in other kind of reactions, the use of
ionic liquid additives was highly beneficial.[28-32]
cc.
H
HCl/ 2O
R1
O
Me
OH
R1
O
Me
P
P
OR2
Me
3
4
R1
R2
H
H
R1
H
A
Me
B
Et Et Me
c
a
b
SCHEME 1 Acid-catalyzed hydrolysis of 3-methyl- and
3,4-dimethyl-1-alkoxy-3-phospholene 1-oxides (1)
>P(O) OR → >P(O)OH transformation involves a fission
by the effect of trimethylsilyl bromide.[22-24] Enzymatic hy-
drolysis is also a good option.[25] According to an indirect
approach, the phosphinate is converted to the corresponding
phosphinic chloride by reaction with phosphorus pentachlo-
ride, and the P-chloride so formed is hydrolyzed.[26] It is
worth noting that a microwave (MW)-assisted protocol was
elaborated for the hydrochloric acid-catalyzed hydrolysis of
phosphinate diesters.[27]
In this article, we investigate the hydrolysis of a se-
ries of cyclic phosphinates under acidic conditions. We
wished to explore the optimum conditions for the acidic
hydrolysis of a few 1-alkoxy-3-phospholene 1-oxides,
1-ethoxy-3-methylphospholane1-oxide,and1-ethoxy-3-methyl-
1,2,3,4,5,6-hexahydrophosphinine 1-oxide using hydrochlo-
ric acid on conventional heating, or in a few cases, para-
toluenesulfonic acid under MW conditions.
TABLE 1 Hydrolysis of 1-ethoxy-3-methyl-3-phospholene 1-oxide (1a)a in the presence of hydrochloric acid
cc. HCl
Compositionb (%)
Me
Me
Me
OH
Me
OH
P
P
P
P
O
OEt
O
OEt
O
O
1a
3a
2A
4A
Entry
H2O (mL)
(mL)
(equiv.)
t (h) Conversion (%)
1
2
3
4
5
1
0
-
6
6
3
6
6
0
100
18
2
0.5
0.5
0.5
0.25
3
61
47
100
92
21
28
27
16
10
19
34
31
90
73
1
3
25
1
3
0.5
1.5
2
6
Values in Italics stand for the optimum conditions of the hydrolysis.
aThe quantity of phosphinate 1a was 1.9 mmol.
bOn the basis of relative 31P NMR integrals.

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TABLE 2 Time dependence of the hydrolysis of 1-ethoxy-3-methyl-3-phospholene oxide (1a) under the optimum conditions
Compositiona (%)
Me
Me
Me
OH
Me
OH
P
P
P
P
O
OEt
O
OEt
1a + 3a
(%)
O
O
1a
3a
2A
4A
t (h)
Conversion (%)
0.25
0.5
1
2
4
81
74
51
25
11
0
3
6
16
19
16
0
16
18
24
24
11
10
8
0
2
9
32
62
90
92
16
20
33
56
73
100
84
80
67
44
27
0
6
7b
0
0
aOn the basis of relative 31P NMR intensities.
bFurther heating after complete hydrolysis.
The hydrolysis of cyclic phosphinate 1a performed under
optimal conditions (1.9 mmol of 1a, 1 mL of H2O, 0.5 mL of
cc. HCl/6 hour, Δ) was monitored by 31P NMR spectroscopy.
The data can be seen in Table 2 and Figure 1. The curves on the
data points were fitted using the nonlinear generalized reduced
gradient method of Microsoft Excel Solver (see Section 3). The
pseudo-first-order rate constants for the hydrolysis of phosphi-
nates 1a and 3a obtained by the program package were 0.42 and
0.45 hour−1, respectively. The rate constants for the 1a → 3a
and 2A → 4A isomerizations were found 0.25 and 0.52 hour−1,
respectively. The rate constants determined should be regarded
approximate values that are good indicators of the reactivity.
It was proved by a separate experiment that 1-hydroxy-3-
methyl-3-phospholene 1-oxide (2A) may be isomerized to
the 2-phospholene 1-oxide (4A) under the conditions of the
FIGURE 1 Concentration profile for the components during
the hydrolysis of 1-ethoxy-3-methyl-3-phospholene oxide (1a) under
optimum conditions. The R2 measure of goodness of fit is .983
TABLE 3 Time dependence of the
Compositiona (%)
hydrolysis of 1-ethoxy-3,4-dimethyl-3-
phospholene 1-oxide (1b) under the
optimum conditions
Me
Me
Me
O
Me
Me
O
Me
P
P
P
O
OEt
H
H
O
O
Conversion
(%)
1b
2B
4B
t (h)
1
2
3
4
6
68
39
23
16
6
31
54
67
69
73
1
7
11
15
21
32
61
78
84
94
aOn the basis of relative 31P NMR intensities.

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As the third model, the 1-methoxy-3-methyl-3-phospholene
oxide (1c) was also subjected to hydrolysis under the conditions
applied in the previous cases. Both intermediates (3c and 2A)
appeared, and the series of transformations was already com-
plete after 3 hour (Table 4; Scheme 1; Figure 3). Similarly the
case of the hydrolysis of 1-ethoxy-3-phospholene oxide 1a, the
phosphinic acid formed by isomerization (4A) dominated in the
final mixture.
The pseudo-first-order rate constants for hydrolyses
1c → 2A and 3c → 4A were 1.77 and 2.95 hour−1, respec-
tively, while the rate constants for isomerizations 1c → 3c
and 2A → 4A were 0.71 and 0.49 hour−1, respectively. One
can see that the hydrolysis of the methyl ester 1c is signifi-
cantly faster (k1c→2A = 1.77 hour−1) than that of the ethyl
ester 1a (k1a→2A = 0.42 hour−1).
FIGURE 2 Concentration profile for the components during the
hydrolysis of 1-ethoxy-3,4-dimethyl-3-phospholene oxide (1b) under
optimum conditions. The R2 measure of goodness of fit is .981
We then wished to investigate the hydrolysis of a
saturated five-ring species. The model compound was
1-ethoxy-3-methylphospholane 1-oxide (5), and the hydro-
lysis was performed under the optimum conditions explored
above (Scheme 2).
hydrolysis (3 mL H2O, 1.5 mL cc. HCl/6 hour, Δ). Under
these conditions, 90% of 2A was isomerized to 4A.
The hydrolysis of 1-ethoxy-3,4-dimethyl-3-phospholene
1-oxide (1b) under the optimum conditions (1.9 mmol of
1b/0.50 mL of cc. HCl/1 mL of H2O/Δ, 6 hour) mentioned
above led to similar results (tcompletion ~ 6 hour), but phosphinate
3b (the isomer of starting 1b) was not an intermediate, sug-
gesting a simple 1b → 2B → 4B protocol (Table 3; Scheme 1;
Figure 2). The pseudo-first-order rate constant for the hy-
drolysis 1b → 2B and the rate constant for the isomerization
2B → 4B obtained on the basis of the fitted curves with the help
of the program mentioned above were 0.45 and 0.07 hour−1,
respectively.
The hydrolysis under discussion was monitored by 31P
NMR spectroscopy, and it was found that the hydrolysis of
1-ethoxyphospholane oxide 5 was slower, as compared to
the unsaturated cases. It is noted that although 1-ethoxy- and
1-hydroxy-3-methylphospholane oxides 5 and 6 comprise
two diastereomers in a comparable quantity, only broader sig-
nals could be seen in their 31P NMR spectra. The hydrolysis
was complete after a reflux of 8 hour (Table 5; Figure 4). The
pseudo-first-order rate constant for the hydrolysis obtained on
the basis of the fitted curves with the help of a suitable program
was 0.39 hour−1.
The inclination of 3-phospholene oxide 2B for isomeriza-
tion to 2-phospholene derivative 4B is significantly lower than
the ability of monomethylphospholene oxide 2A to undergo the
double-bond rearrangement. This is demonstrated well by the rate
constants for 2B → 4B and 2A → 4A isomerizations that were
found to be 0.07 and 0.52 hour−1, respectively, and is the conse-
quence of the different number of the Me groups in the skeleton.
Finally, 1-ethoxy-3-methyl-1,2,3,4,5,6-hexahydrophosphinine
1-oxide (7) was also subjected to hydrolysis under the optimized
conditions (Scheme 3).
The conversion-time data (Table 6; Figure 5) revealed that
the rate of the hydrolysis of phosphinate 7 is somewhat slower
TABLE 4 Time dependence of the hydrolysis of 1-methoxy-3-methyl-3-phospholene oxide (1c) under the optimum conditions
Compositiona (%)
Me
Me
Me
OH
Me
OH
P
P
P
P
e
M
O
O
OMe
O
1c + 3c
(%)
O
O
c
3
1c
2A
4A
t (h)
Conversion (%)
0.25
0.5
1
2
3
45
32
17
7
8
11
0
6
0
38
41
43
28
21
9
47
57
83
87
100
53
43
17
13
0
16
40
59
79
0
aOn the basis of relative 31P NMR intensities.

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FIGURE 4 Concentration profile for the 1-ethoxy-3-
FIGURE 3 Concentration profile for the components during
the hydrolysis of 1-methoxy-3-methyl-3-phospholene oxide (1c) under
optimum conditions. The R2 measure of goodness of fit is .921
methylphospholane oxide (5) and the corresponding phosphinic
acid (6) during the acidic hydrolysis investigated. The R2 measure of
goodness of fit is .994
∆
Me
Me
OH
H
cc. HCl
2O,
P
P
O
OEt
O
TABLE 6 Time dependence of the hydrolysis of 1-ethoxy-3-
methyl-1,2,3,4,5,6-hexahydrophosphinine oxide (7) under the optimum
conditions
5
6
SCHEME 2 Acid-catalyzed hydrolysis of 1-ethoxy-3-
methylphospholane 1-oxide (5)
Compositiona (%)
Conversiona
t (h)
7a
7b
8
(%)
TABLE 5 Time dependence of the hydrolysis of 1-ethoxy-3-
methylphospholane oxide (5) under the optimum conditions
1
2
4
6
8
10
32
19
6
1
1
40
25
21
20
8
28
56
73
79
91
100
28
56
73
79
91
100
t (h)
Conversiona (%)
1
2
4
6
8
29
56
84
88
96
0
0
aOn the basis of relative 31P NMR intensities.
aOn the basis of relative 31P NMR intensities.
∆
cc.
Me
Me
H
HCl
2O,
P
P
O
OEt
O
OH
7
8
SCHEME 3 Acid-catalyzed hydrolysis of 1-ethoxy-3-methyl-
1,2,3,4,5,6-hexahydrophosphinine 1-oxide (7)
than that of the 5-ring analogue (5). Completion of the hydro-
lysis of phosphinate 7 required ca. 10 hour. In this instance,
the fate of the two diastereomers of the starting phosphinate
(7) could be monitored separately. The pseudo-first-order
rate constant for the hydrolysis obtained on the basis of the
fitted curves with the help of the program was 0.35 hour−1.
This rate constant is based on the average reactivity of the
diastereomers.
FIGURE 5 Concentration profile for the diastereomers
of 1-ethoxy-hexahydrophosphinine oxide (7a and 7b) and the
corresponding phosphinic acid (8) during the acidic hydrolysis
investigated. The R2 measure of goodness of fit is .981

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It can be seen that the reactivity of the P-alkoxy ring
phosphinates (1a-c, 5 and 7) in hydrolysis is the following:
Me
Me
Me
Me
Me
~
<
<
<
P
P
P
P
P
O
OEt
O
OEt
O
OMe
O
OEt
O
OEt
7
5
1b
1a
1c
presence of 3 equivalents of the catalyst. After a 1-hour ir-
radiation, the conversion was complete, and the ratio of the
1-hydroxy-3-phospholene and 1-hydroxy-2-phospholene
derivatives (2A and 4A) was 12-88 (Table 7, entry 7).
It means that the phosphinates with saturated ring 5 and
7 are less reactive than the 3-phospholene derivatives (1a-c).
An additional skeletal Me group decreases the reactivity (re-
gard 1a vs 1b), and the methyl ester (1c) is more reactive than
the ethyl derivative (1a).
The
results
of
the
experiments
with
the
1-ethoxy-3-methyl-3-phospholene oxide (1a) revealed the lower
reactivity of this phosphinate in hydrolysis. At 120°C or at 140°C
in the presence of 3 equivalents of PTSA, the completion of the
hydrolysis required 5.5 and 3 hour, respectively (Table 7, entries
8 and 9). Under similar conditions, complete hydrolysis of the
1-methoxy analogue 1c required irradiation times of ca. 2.75 and
1 hour, respectively (Table 7, entries 3 and 7). The isomerized
hydroxyphospholene oxide (4A) predominated in both cases.
In conclusion, the MW-assisted hydrolyses at 120°C in
the presence of PTSA require similar reaction times as the
thermal versions in the presence of hydrochloric acid (6 and
3 hour) for the two models 1a → 4A and 1c → 4A studied. At
the same time, the MW variations at 140°C may be compet-
itive, as the hydrolyses are significantly faster. (The reaction
times are 3 and 1 hour for the two models investigated).
In summary, the hydrochloric acid-catalyzed hydrolysis of
cyclic phosphinates, such as 1-alkoxy-3-phospholene 1-oxides,
1-ethoxy-3-methylphospholane1-oxide,and1-ethoxy-3-methyl-
1,2,3,4,5,6-hexahydrophosphinine 1-oxide, was optimized
and characterized by rate constants. The best method involves
the use of three equivalents of cc. hydrochloric acid in 1 mL
of water for 2 mmol of the substrate and requires a 3-10 hour
reflux. The microwave-assisted hydrolysis at 140°C in the
presence of p-toluenesulfonic acid may be another option.
The reactivity of the cyclic phosphinates was mapped as fol-
lows: The 1-alkoxy-3-phospholene 1-oxides were found more
reactive than the saturated derivatives.
We saw that the inclination for the double-bond rearrange-
ment was at the lowest level in case of the dimethylphospho-
lene oxide derivatives (eg 2B).
2.2
Microwave-assisted hydrolysis in the
|
presence of p-toluenesulfonic acid catalyst
The MW-assisted variation of the hydrolysis of
1-ethoxy-3-methyl-3-phospholene 1-oxide (1a) in the pres-
ence of hydrochloric acid did not show any advantage, as there
was no acceleration. The hydrolysis was also attempted in the
presence of p-toluenesulfonic acid (PTSA) as the catalyst.
PTSA is more attractive than aqueous HCl, due to the problem
of corrosivity with HCl. The data obtained are listed in Table 7.
The first experiment was carried out using 1 equivalent
of PTSA at 120°C. After an irradiation of 4.5 hour, the
conversion was 89% in respect of the hydrolyzed products
2A (43%) and 4A (46%). The proportion of the unreacted
starting material (1c) and the isomerized variation (3c) was
6% and 5%, respectively (Table 7, entry 1). Applying 3
equivalents of the catalyst, and allowing a reaction time of
2 hour, again all the four possible components 1c, 3c, 2A,
and 4A were present, on this occasion, in quantities of 11%,
18%, 23%, and 48%, respectively (Table 7, entry 2). After
a somewhat longer reaction time (2.5 hour), the conversion
was 94%, with predominating presence of isomerized hy-
droxyphospholene oxide 4a (78%) (Table 7, entry 3). The
role of MW irradiation is significant, as can be seen from
the comparison of the outcome of the experiments marked
by entries 4 and 2. To achieve more complete conver-
sions, the next hydrolyses were performed at 140°C. 0.33
Equivalents of the PTSA were not enough, as after a 2-
hour irradiation, the conversion was incomplete (81%), and
all possible components (1c, 3c, 2A and 4A) were present
(Table 7, entry 5). Increasing the quantity of the catalyst
to 1 equivalent, the 1-hydroxy-2-phospholene oxide 4A
became the predominant product (69%), but some (12%)
unreacted phosphinate (3c) also remained in the mixture
(Table 7, entry 6). The best result could be obtained in the
3
EXPERIMENTAL
General
|
3.1
|
The 31P, 13C, 1H NMR spectra were taken on a Bruker DRX-500
spectrometer operating at 202.4, 125.7, and 500 MHz, respec-
tively. The couplings are given in Hz. LC-MS experiments were
performed with an Agilent 1200 liquid chromatography system
coupled with a 6130 quadrupole mass spectrometer equipped
with an ESI ion source (Agilent Technologies, Palo Alto, CA,
USA). High-resolution mass spectrometric measurements were

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TABLE 8 31P NMR characterization of the cyclic phosphinates and phosphinic acids involved in our study
δ 31P NMR
δ 31P NMR
Cyclic phosphinates
Found
Literature
74.7[35]
M + H
Phosphinic acids
Found
Literature
M + H
76.0
161.2
74.6 (bs)
133.2
Me
e
M
P
P
O
O
O
OEt
O
OH
1a
2A
77.6
77.2
76.8[36]
147.2
161.2
Me
P
OMe
1c
79.7 (bs)
133.2
Me
Me
OH
P
3aa
P
OEt
O
4Ab
78.2
67.6
76.4[37]
147.2
175.2
e
M
P
e
OM
O
3c
68.3[38]
69.7 (bs)
70.8 (bs)
79.4 (bs)d
52.4 (bs)d
147.2
147.2
135.2
149.2
Me
Me
Me
Me
P
P
O
OEt
O
OH
1b
2B
Me
Me
P
O
OH
4Bc
80.8 (bs)d
79.4[39]
163.2
177.2
80.2 (bs)[38]
51.8 (bs)[38]
Me
Me
P
P
O
OEt
O
OH
5
6
50.4 (45%)
51.5 (55%)
51.8[40]
Me
Me
P
P
O
OEt
O
OH
7
8
a[M + H]+found = 161.0742, C7H14O2P requires 161.0726.
b[M + H]+found = 133.0418, C5H10O2P requires 133.0413.
c[M + H]+found = 147.0578, C6H12O2P requires 147.0569.
dThe two isomers cannot be distinguished.
performed using a Q-TOF Premier mass spectrometer in posi-
tive electrospray mode. The MW-assisted hydrolyses were car-
ried out in a CEM Discover microwave reactor equipped with a
stirrer and a pressure controller using 30-50 W irradiation.
3.2
Evaluation of the 31P NMR spectra
|
The composition of the reaction mixture was determined by
the integration of the corresponding peaks in the 31P NMR

KEGLEVICH Et aL.
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spectra, or by peak deconvolution using ACD/Spectrus
Processor software package.[33]
3.5
General procedure for the hydrolysis of
|
1-alkoxy-3-phospholene 1-oxides (1a-c) under
MW conditions
3.3
Curve fitting on the time—relative
|
A mixture of 1.9 mmol of 1-alkoxy-3-phospholene 1-oxide
(1a: 0.30 g, 1c: 0.28 g) and 0.33 g (1.9 mmol) of para-
toluenesulfonic acid in 1.0 mL of water was irradiated in a
sealed tube placed in a CEM MW reactor (equipped with
a pressure controller) at 120-140°C (50 W) for 1.5-4 hour.
The reaction mixture was extracted with 3 × 10 mL of di-
chloromethane, and the organic phase was dried (Na2SO4).
Evaporation of organic solvent gave an oil that was analyzed
by LC-MS and 31P NMR spectroscopy.
quantity data pairs
The acidic hydrolysis and isomerization reactions were
modeled assuming pseudo-first-order kinetics. The concen-
tration of water and hydrochloric acid was constant during
the reaction. The calculated time—composition curves were
fitted to the experimental data using nonlinear least-squares
method. The pseudo-first-order rate constants were optimized
that the sum of squares of the residuals (ie the difference of
the experimental and the calculated composition) to be the
minimal. The approximate values of the rate constants were
found iteratively, using the nonlinear generalized reduced
gradient method[34] of Microsoft Excel Solver.
31P NMR and mass spectral data for cyclic phosphi-
nates 1a-c, 3a, 3c, 5, and 7 together with those of the phos-
phinic acids (2A, 4A, 2B, 4B, 6, and 8) are summarized
in Table 8.
3.4
General procedure for the
ACKNOWLEDGMENTS
|
hydrolysis of 1-alkoxy-3-phospholene 1-oxides
(1a-c), 1-ethoxy-3-methylphospholane 1-oxide
(5), and 1-ethoxy-3-methyl-1,2,3,4,5,6-
hexahydrophosphinine 1-oxide (7) under
conventional conditions
This project was supported by the National Research
Development and Innovation Fund (K119202). Zita Rádai
is grateful for the fellowship provided by Chinoin-Sanofi
Pharmaceuticals.
A mixture of 1.9 mmol of cyclic phosphinate (1a: 0.30 g, 1b:
0.33 g, 1c: 0.28 g, 5: 0.31 g, 7: 0.33 g), 0.50 mL (6.0 mmol)
of cc. hydrochloric acid, and 1.0 mL of water was stirred
at reflux for 3-10 hour. The reaction mixture was extracted
with 3 × 10 mL of dichloromethane, and the organic phase
was dried (Na2SO4). Concentration of the organic phase af-
forded an oil that was analyzed by LC-MS and 31P NMR
spectroscopy.
ORCID
György Keglevich
http://orcid.org/0000-0002-5366-472X
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How to cite this article: Keglevich G, Rádai Z,
Harsági N, Szigetvári Á, Kiss NZ. A study on the
acidic hydrolysis of cyclic phosphinates: 1-Alkoxy-3-
phospholene 1-oxides, 1-ethoxy-3-methylphospholane
1-oxide, and 1-ethoxy-3-methyl-1,2,3,4,5,6-
hexahydrophosphinine 1-oxide. Heteroatom Chem.
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