Synthesis of new organophosphorus-substituted derivatives of functionalized propionates and their analogues

Article abstract of DOI:10.1002/hc.20446

Nucleophilic or radical addition of trimethylsilyl esters of trivalent organophosphorus acids to various functionalized acrylates and their cyclic analogues is proposed as convenient methods for the synthesis of new 2-trimethylsiloxycarbonylsubstituted al

Full text of DOI:10.1002/hc.20446

Heteroatom Chemistry
Volume 19, Number 4, 2008
Synthesis of New Organophosphorus-
Substituted Derivatives of Functionalized
Propionates and Their Analogues
Andrey A. Prishchenko, Mikhail V. Livantsov, Olga P. Novikova,
Ludmila I. Livantsova, and Valery S. Petrosyan
Department of Chemistry, M. V. Lomonosov Moscow State University, Moscow, 119991 Russia
Received 14 November 2007; revised 14 February 2008
and organoelement fragments were obtained in
ABSTRACT: Nucleophilic or radical addition of
high yields via addition of trimethylsilyl esters
trimethylsilyl esters of trivalent organophosphorus
of trivalent organophosphorus acids to various
acids to various functionalized acrylates and their
organic compounds containing multiple bonds
cyclic analogues is proposed as convenient methods
[5–7]. In the present work, we report the re-
for the synthesis of new 2-trimethylsiloxycarbonyl-
sults of the nucleophilic or radical addition of
substituted alkylphosphonites and their derivatives
bis(trimethylsiloxy)phosphine, trimethylsilyl phos-
under mild conditions. Also the new functionalized
phites, and phosphonites to trimethylsilyl acrylate
derivatives of these phosphonites, including amino,
and its various functionalized or cyclic analogues
amido, and amino acids fragments as well as cer-
such as γ-crotonolactone, trimethylsilyl esters of
tain properties of these compounds, are presented
2-(acetylamino)acrylic, itaconic, maleic, acetylene-
as important precursors of new organophosphorus-
dicarboxylic,
and 1H-indene-2-carboxylic acids. The obtained
phosphonites were easily transformed to
cinnamic,
3-(2-furyl)propionic,
substituted derivatives of functionalized propionates
ꢀ
C
and their analogues.
2008 Wiley Periodicals, Inc.
Heteroatom Chem 19:418–428, 2008; Published online
in Wiley InterScience (www.interscience.wiley.com). DOI
10.1002/hc.20446
aminomethyl phosphinates using various methods
of aminomethylation thoroughly investigated by us
(cf. [8]). These reactions provide a convenient syn-
thetic route to new organophosphorus-substituted
derivatives of functionalized propionates and
their analogues including fragments of indan,
γ-butyrolactone, furan, pyridine, proline, and
sarcosine.
INTRODUCTION
Organophosphorus analogues of amino acids
containing carboxyl and amino groups as well as
heterocyclic and organoelement fragments are of
great interest as promising ligands and biologi-
cally active compounds [1–4]. Recently, we have
found that various derivatives of functionalized
organophosphorus acids with aryl, heterocyclic,
RESULTS AND DISCUSSION
In the present work, we showed that the reaction of
bis(trimethylsiloxy)phosphine A with trimethylsilyl
acrylate and its various functionalized or cyclic
analogues is a convenient route to functionalized
2-(trimethylsiloxycarbonyl)alkylphosphonites 1–8.
So phosphine A in methylene chloride readily
reacts with trimethylsilyl or methyl esters of acrylic,
Correspondence to: Andrey A. Prishchenko; e-mail:
aprishchenko@yandex.ru.
Contract grant sponsor: Russian Foundation of Basic Sciences.
Contract grant number: 08-03-00282.
2008 Wiley Periodicals, Inc.
c
ꢀ
418

Synthesis of New Organophosphorus-Substituted Derivatives of Functionalized Propionates and Their Analogues 419
2-(acetylamino)acrylic, and 2-(carboxymethyl)-
Phosphonite 1 smoothly reacts with trimethylsi-
lyl acrylate in methylene chloride via 1,4-addition
involving the POSi fragment to form correspond-
ing ketene bis(trimethylsilyl) acetal 12 in high yield
(cf. [11]), and treatment of acetal 12 with diethyl
phosphite yields phosphinate 13 with two propi-
onate fragments (Eq. (5)).
acrylic (itaconic) acids exclusively by way of
3,4-addition involving the PH fragment to form
phosphonites 1–4 in high yield. The phosphonite
2 is a new organophosphorus analogue of aspartic
acid (Eq. (1); cf. [9]).
Under the similar conditions, excess of phos-
phine A readily adds to maleic and acetylenedicar-
boxylic acid diesters to give phosphonites 5,6, and
bisphosphonite 7, incorporating a succinic acid frag-
ment (Eq. (2)).
By a similar way, the functionalized phospho-
nites with element or heterocyclic fragments [5,6]
were transformed by us after the treatment of the in-
termediate acetals B with diethyl phosphite to phos-
phinates 14–19, containing sometimes two different
fragments with the carboxyl groups (Eq. (6)).
The functionalized and cyclic analogues of
trimethylsilyl acrylate possess the lower ac-
tivity toward phosphine A. So bis(trimethy-
lsiloxy)phosphine A slowly adds to γ-crotonolactone
at 20◦C to form phosphonite 8, and heating at 100◦C
is required for the reaction to be completed (Eq. (3)).
The addition of phosphine A to trimethylsi-
lyl esters of cinnamic, 3-(2-furyl)propionic, and
1H-indene-2-carboxylic acids proceeds only in the
presence of azobis(isobutyronitrile) at 100–130◦C to
give phosphonites 9–11 in high yields (Eq. (4); cf.
[10]). Note that the influence of phenyl or furyl frag-
ments on the orientation of the addition in these
reactions is more preferable (cf. [6]).
Diethyl trimethylsilyl phosphite adds to
trimethylsilyl acrylate only by heating at 120–
130◦C to give ketene acetal 20 in high yield,
which was transformed to phosphonate 21 after
the treatment with diethyl phosphite (Eq. (7); cf.
[12–14]).
Also the heating of a mixture of γ-crotonolactone
with diethyl phosphite and diethyl trimethylsilyl
phosphite at 120◦C in the presence of zinc chloride
leads to formation of phosphonate 22 in high yield.
Heteroatom Chemistry DOI 10.1002/hc

420 Prishchenko et al.
Note that under other reaction conditions the start-
ing lactone and the intermediate ketene acetal C
readily polymerize (Eq. (8)).
We have developed the methods for synthesis
of new phosphinates with propionate, aminomethyl,
and pyridine fragments by 2-carboxyethylation of
available functionalized phosphonites containing
the P(O)H moieties [15]. Thus these phosphonites
add to trimethylsilyl acrylate on heating to 140◦C
in the presence of triethylamine or pyridine to give
phosphinates 25–33 in high yield (Eq. (10)).
Under similar conditions, the reactions of
trimethylsilyl esters of phosphorous acid with
trimethylsilyl 1H-indene-2-carboxylate yield the new
phosphonates 23,24 containing fragments of indan-
1-carboxylic acid. Apparently, these reactions in-
volve intermediate formation of unstable ketene
acetals D (Eq. (9)).
Functionalized phosphonites 1–11 are conve-
nient synthons for preparing various organophos-
phorus analogues of amino acids and their deriva-
tives with promising properties [3,4]. In the present
work, we propose a universal synthetic approach
to such compounds on the basis of amino- or
amido-methylation of the highly reactive phos-
phonites 1,3–5,9 with N-chloromethylamines, N-
chloromethylamides, and N,N-dimethylcarbamoyl
chloride. These reactions proceed under mild condi-
tions in methylene chloride and form phosphinates
25,28,34–47 in high yields (Eq. (11)).
Heteroatom Chemistry DOI 10.1002/hc

Synthesis of New Organophosphorus-Substituted Derivatives of Functionalized Propionates and Their Analogues 421
In contrast, the aminomethylation of the phos-
phonites 8,10,11 with aminals takes place at 120–
130◦C in the presence of zinc chloride to form
functionalized phosphinates including carboxyl and
aminomethyl moieties 48–54 (Eq. (12); cf. [8]).
Thus we proposed the convenient synthesis
of trimethylsilyl derivatives of new functionalized
organophosphorus analogues of amino acids in-
cluding various amino and carboxyl groups 1–54
(see Tables 1–3). Trimethylsilyl esters of several
functionalized organophosphorus acids were useful
for obtaining the series of water-soluble acids and
their sodium salts (cf. [5–7]). So O-trimethylsilyl-
substituted phosphonites 1–11 smoothly react with
diluted solutions of sodium methylate in methanol,
giving stable crystalline sodium salts of function-
alized 2-carboxyalkylphosphonous acids 55–65 (see
Table 4; Eq. (13)).
Also the treatment of phosphonates 23,24 and
phosphinates 14–18 with diluted solution of sodium
methylate in methanol results in formation of water-
soluble sodium phosphonates 66,67 and sodium
phosphinates 68–76 as white hygroscopic crystals
(Eq. (14)).
Also phosphonate 21 and phosphinates 13,
25–33 were easily transformed to corresponding
organophosphorus acids 77–88 via treatment with
methanol in high yields (Eq. (15)).
Heteroatom Chemistry DOI 10.1002/hc

422 Prishchenko et al.
ing catalytic complexes as well as biologically active
compounds (cf. [3, 4]). The elemental analysis data
of some synthesized compounds are summarized in
Table 6.
EXPERIMENTAL
The 1H, 13C, and 31P NMR spectra were registered on
the Varian VXR-400 and Bruker Avance-400 spec-
trometers (400, 100, and 162 MHz, respectively) in
CDCl3 (1–54) or D2O and (CD3)2SO (55–88) against
TMS (1H, 13C) and 85% H3PO4 in D2O (31P). All reac-
tions were carried out under dry argon in anhydrous
solvents.
O,O-Bis(trimethylsilyl)-2-(trimethylsiloxycarbonyl)-
ethylphosphonite (1). A solution of
6
g
of
trimethylsilyl acrylate in 20 mL of methylene
chloride was added dropwise with stirring and
cooling to 10◦C to a solution of 9 g of phosphine A in
60 mL of methylene chloride. The reaction mixture
was kept for 24 h at 20◦C, the solvent was then
removed, and the residue was distilled in a vacuum
to obtain 10.1 g of phosphonite 1.
Synthesized acids and salts 66–88 are white hy-
groscopic crystals (acid 77 is thick oil; see Table 5)
and may be used as water-soluble ligands in promis-
Phosphonites 2–7 were prepared similarly.
TABLE 1 Yields, Product Constants, and NMR Spectral Data for the PC1HmC2HnC3 Fragmentsa (δ, ppm; J, Hz) of Phospho-
nites 1–11a
Compound
Yield (%)
Bp (◦C) (p, mmHg)
δ(C1) (d )
1JPC
δ(C2) (d )
2JPC
δ(C3)(d)
3JPC
δ(P) (s )
1
68
83
83
81
89
83
74
86 (1)
146 (1)
126 (1)
133 (1)
115 (1)
127 (1)
148 (1)
36.41
44.16
42.28
42.46
52.02
53.89
54.15c
52.75e
41.59
53.31
46.24
52.72
25.8
32.3
30.2
30.3
38.9
38.2
16.1
49.1
24.6
28.8
28.9
29.5
27.74
49.53
35.00
36.82
27.99
30.39
54.15
52.75
26.90
34.83
32.27
32.16
13.0
11.6
11.3
11.6
12.1
14.1
16.1
13.0
14.5
18.1
15.0
23.9
173.63
173.25
36.21
9.0
5.7
6.5
7.2
7.4
9.1
6.6
<1
4.6
7.8
8.9
<1
159.49
156.87
155.58
156.35
145.55
146.63
144.62
146.83
146.29
151.52
144.55
159.38
2b
3
4
38.19
5
172.73
172.72
169.76d
168.93
176.63
138.12
152.44
172.61
6
7
8f
9
74
89
89
87
122 (1)
121 (1)
126 (1)
152 (1)
10
11g
aAll signals of alkyl, aryl, furyl, and trimethylsilyl groups are in the standard area. The 1H NMR signals of the protons of the groups C1HmC2HnC3
are multiplets. According to the NMR spectra, compound 7 is a mixture of two stereoisomers. Their ratio was determined from the 1H NMR
and 31P NMR spectra as 60:40. The spectral parameters of the major isomer are given first. Fragments COOR in 13C NMR spectra, d, 3JPC, 3:
174.65, 4.8, and 171.50 s; 4: 175.07, 5.9, and 171.90 s; d, 2JPC, 5: 170.57, 6.4; 6: 170.29, 6.6; 9: 172.44, 11.1; 10: 172.62, 9.1.
bFragment NHC(O)Me. In 1H NMR spectra: 1.82 s (Me), 7.22 d (NH, 3JHH 7.6). In 13C NMR spectra, s: 22.73 (Me), 169.43 [C(O)N]].
2
ct, 1JPC = JPC
ed. d.
.
.
3
dt, 2JPC = JPC
f Fragment CH2O: δC 66.68 d, 2JPC 16.8.
gFragment
, in 13C NMR spectra: 32.16 d (C4, 2JPC 23.9), 144.84 d (C5, 3JPC 9.4), 141.73 d (C5, 3JPC4.2).
Heteroatom Chemistry DOI 10.1002/hc

Synthesis of New Organophosphorus-Substituted Derivatives of Functionalized Propionates and Their Analogues 423
TABLE 2 Yields, Product Constants, and NMR Spectral Data for the PC1H2C2H2C3(O) Fragmentsa (δ, ppm; J, Hz) of
Phosphinates 12–19, 32, 33 and Phosphonates 20–24
Compound
Yield (%)
64
Bp (◦C) (p, mmHg)
155 (2)
nD20
δ(C1)d
1JPC
δ(C2)d
2JPC
δ(C3)d
3JPC
δ(P)s
12
1.4455
25.77
24.64b
25.68
23.12
23.25
23.27
22.52
23.80
23.46
24.51
22.13
25.72
29.73d
23.97b
21.16
30.98
36.52
38.35
25.27
30.78d
24.32
30.86d
94.4
93.6
94.1
95.8
95.8
96.4
95.8
93.6
94.1
91.5
93.0
92.5
92.9
141.9
143.2
151.6
147.2
152.9
92.6
92.0
93.7
92.0
28.73
72.68
28.68
27.90
27.43
27.50
27.28
27.81
27.88
28.83
27.63
28.81
30.67
72.75
29.35
27.93
52.35
52.94
28.73
27.56
27.56
24.14
<1
9.2
3.0
3.9
<1
<1
<1
<1
<1
<1
1.2
2.5
3.0
10.3
4.0
4.2
<1
5.8
<1
<1
<1
<1
172.54
152.63
172.54
171.22
171.20
171.64
14.4
11.7
14.9
14.4
11.1
17.0
18.3
–
43.86
13
14
88
81
135 (1)
186 (1)
1.4480
1.4610
43.46
39.67
39.84
38.53
39.30
44.21
44.17
44.04
45.43
42.45
15
16
76
83
178 (1)
197 (1)
1.4640
1.4969
171.63
c
c
–
17
18
19
80
82
86
163 (2)
178 (1)
187 (1)
1.4522
1.4932
1.4817
172.76
171.90
172.62
160.78
152.70
172.27
174.16
171.29
171.63
172.66
150.09
171.53
132.31
13.8
15.3
15.2
14.3
13.8
17.9
12.3
5.8
20
21
22
23
24
32
74
78
64
83
86
81
95 (1)
104 (2)
155 (1)
173 (1)
165 (1)
192 (2)
1.4375
1.4310
1.4565
1.4888
1.4771
1.4869
27.09
27.82
23.37
28.75
11.09
41.32
9.3
14.6
21.6
15.0
15.0
33
88
185 (1)
1.4811
41.78
aAll signals of alkyl, trimethylsilyl, aryl, and heterocyclic groups are in the standard area. The 1H NMR signals of the protons of the groups
C1H2C2H2C3(O) are multiplets. According to the NMR spectra, compounds 14–16 are mixtures of two stereoisomers. Their ratio was determined
from the 1H NMR and 31P NMR spectra as 60:40 for 14,16 and as 55:45 for 15. The spectral parameters of the major isomer are given first. In 13
C
NMR spectra, fragments:
for 15, first isomer, 37.09 d (C1, 1JPC93.2), 32.82 s (C2), 148.92 d (C3, 3JPC7.6), 170.30 d (C4, 2JPC16.5), second isomer, 38.07 d (C1, 1JPC93.1),
for 14, δC, 33.87 d (C1, 1JPC97.6), 27.03 s (C2), 171.21 d (C3, 3JPC11.5), 65.75 s (C5);
33.26 s (C2), 148.92 d (C3, 3JPC5.4), 170.22 d (C4, 2JPC16.7);
for 16, first isomer, 39.42 d (C1, 1JPC93.2), 52.17 s (C2), 32.13
1 2
3
3
s (C4), 141.26 d (C5, JPC6.8) and 138.80 d (C5, JPC7.1), second isomer, 39.70 d (C1, JPC96.6), 51.68 d (C2, JPC6.4), 31.69 s (C4), 141.96
d (C5, 3JPC 6.4) and 138.99 d (C5, 3JPC6.4), 171.68–172.05 m (C3) for two isomers; for 23, 36.52 d (C1, 1JPC147.2), 52.35 s (C2), 32.16 s (C4),
140.97 d (C5, 3JPC10.8), and 138.75 d (C5, 3JPC9.9), 171.29 d (C3, 3JPC5.8); for 24, 38.35 d (C1, 1JPC152.9); 52.94 d (C2, 2JPC5.8), 32.84 s (C4),
3
3
3
1
2
141.44 d (C5, JPC7.7) and 139.13 d (C5, JPC7.4), 171.63 d (C3, JPC9.3); C1H2C2H2Si for 17, 24.47 d (C1, JPC91.6); 2.60 d (C2, JPC7.4);
for 18, 37.33 d (C1, 1JPC98.6); 32.80 s and 32.82 s (C2), 140.90 s (C3); CH2O for 22, 66.28 s.
bFragment PC1H2C2H C3.
c171.68–172.05 m, two C O groups from two stereoisomers.
dFragment PC1H2C2H2CP3y
.
O,O-Bis(trimethylsilyl)-2-oxotetrahydrofur-4-ylph-
osphonite (8). A solution of 12.4 of γ-
of phosphine A, 14.2 g of trimethylsilyl cinnamate,
and 0.2 g of azobis(isobutyronitrile) was heated at
100–130◦C for 1.5 h and then distilled in a vacuum
to obtain 24.6 g of phosphonite 9.
g
crotonolactone in 20 mL of methylene chloride
was added dropwise with stirring to a solution of
37 g of phosphine A in 50 mL of methylene chloride.
The resulting mixture was stirred for 1 h, the solvent
was removed by distillation, and the residue was
heated for 1 h at 100◦C and then distilled to obtain
32 g phosphonite 8.
Phosphonites 10,11 were prepared similarly.
O-Trimethylsilyl-2-(trimethylsiloxycarbonyl)ethyl-
3,3-bis(trimethylsiloxy)propen-2-ylphosphinate (12).
A solution of 5.1 g of trimethylsilyl acrylate in 15 mL
of methylene chloride was added dropwise with
stirring and cooling to 10◦C to a solution of 8.9 g
of phosphonite 1 in 50 mL of methylene chloride.
O,O-Bis(trimethylsilyl)-1-trimethylsiloxycarbonyl-
2-phenylethylphosphonite(9). A mixture of 13.5 g
Heteroatom Chemistry DOI 10.1002/hc

424 Prishchenko et al.
TABLE 3 Yields, Product Constants, and NMR Spectral Data for the PC1HmC2HnC3 and PC4H2NFragmentsa (δ, ppm; J, Hz)
of Aminomethyl Phosphinates 25–31, 34–54
Compound Yield (%) Bp (◦C) (p, mmHg) nD20 (Mp, ◦C) δ(C1) d 1JPC
δ(C1)s δ(C3)d JPC
δ(C4)d
1JPC
δ(P)s
3
25
26
27
28
29
30
81
86
86
83
86
79
126 (2)
151 (4)
175 (4)
167 (3)
152 (1)
180 (2)
1.4485
1.4510
1.4610
(52)
1.4650
1.4655
24.43
24.33
25.65
24.29
24.35
27.95
28.01
24.32
25.12
23.52
24.78
93.4
89.7
88.0
95.3
93.5
99.3
97.6
86.3
91.6
93.1
91.5
28.99
28.89
28.61
172.84 15.0
172.74 15.3
172.47 15.5
53.58
54.77
58.82
58.43
58.10
54.29
54.21
45.93
47.03
42.01
47.71
116.3 39.49
115.3 39.52
114.5 40.05
113.7 39.50
115.2 39.41
124.3 41.09
122.4 39.06
105.2 38.55
103.8 37.51
105.2 37.35
104.5 37.74
156.5 23.46
115.3 37.89
115.1 37.97
114.8 38.72
115.0 38.57
121.4 31.90
118.3 32.11
122.1 31.25
119.2 31.08
114.9 28.55
112.8 29.02
114.8 36.51
113.8 37.48
113.2 35.99
112.6 36.80
101.3 34.92
102.5 33.87
102.5 34.10
104.0 33.02
103.7 35.16
104.6 33.93
118.1 36.01
117.7 36.81
121.8 34.91
115.5 35.67
117.2 34.16
116.5 34.49
116.8 34.66
116.7 34.84
116.1 34.00
111.0 34.02
116.1 34.44
115.5 34.86
113.1 41.14
113.6 39.85
28.78b 172.71 15.3
28.96
28.96
28.90
172.83 15.2
172.19 15.7
172.05 15.8
31
34
35
36
37
38
87
74
78
81
87
89
140 (1)
151 (2)
181 (1)
192(1)
152 (1)
141 (1)
1.4558
1.4595
1.4710
1.4708
1.4581
1.4590
28.95b 172.61 13.6
28.69
27.42
28.72
29.14
34.73b
34.98
36.40b
36.58
29.02
30.58
28.88
30.65
28.76
30.06
36.09
36.19
35.94
36.08
36.15
35.90
36.01
35.89
36.12
35.70
28.08
28.15
28.07
27.96
32.22
33.13
32.64
33.70
32.59
33.74
32.81
33.57
53.23
51.83
172.72 16.4
171.68 16.9
172.71 16.2
25.31 103.6
172.48 15.7 169.13c
29.04
28.66
28.72
29.07
41.07
43.72
40.97
43.89
41.81
42.98
42.80
44.24
42.79
44.12
43.20
43.86
42.95
43.88
42.17
43.20
33.85
33.97
93.4
93.2
93.4
93.6
79.7
79.7
80.4
80.6
79.9
80.7
88.5
88.0
89.0
88.7
86.7
87.0
86.8
87.7
88.0
87.3
98.9
99.5
35.22
35.27
37.14
37.60
5.1
5.4
3.9
4.0
58.27
58.70
59.09
58.66
56.74
56.35
56.21
55.84
47.92
47.15
57.47
56.65
56.78
56.14
46.21
45.55
42.01
41.75
46.35
45.71
57.34
57.48
56.27
56.39
56.09
55.80
56.07
55.77
55.97
55.41
53.35
53.09
57.64
57.54
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
81
74
78
80
83
85
80
85
78
68
69
74
72
78
78
81
157 (1)
160 (1)
165 (1)
205 (2)
175 (1)
181 (1)
206 (3)
193 (1)
204 (1)
162 (1)
195 (1)
143 (2)
175 (1)
183 (2)
186 (1)
186 (1)
1.4510
1.4652
1.4535
1.4680
1.4965
(45)
171.47 15.5
171.09 16.2
171.47 15.7
171.30 17.0
170.90 15.2
170.64 16.7
137.63
137.35
137.38
137.01
136.56
136.12
136.42
136.13
136.25
136.10
6.2
3.6
6.2
4.0
6.0
3.4
7.3
4.2
7.2
4.6
1.4972
1.4981
1.4850
1.4635
(65)
174.62 10.4
174.82 12.3
33.88 100.0
174.40
174.69
149.49
149.27
149.85
149.73
149.77
149.53
149.88
149.61
9.3
9.3
8.8
6.7
8.0
6.2
7.8
6.9
7.8
6.9
33.61
34.88
37.34
35.34
37.75
35.36
37.81
35.20
37.61
38.89
38.54
97.2
92.0
91.2
91.8
91.4
92.7
92.2
91.1
90.9
96.0
96.5
1.4665
1.4755
1.4750
1.4702
(67)
171.86 <1
171.92 <1
aAll signals of alkyl, trimethylsilyl, aryl, and heterocyclic fragments are in the standard area: the signals of these fragments are multiplets
and partially or completely overlap. The signals of the diastereotopic protons of the methylene groups C4H2 of 25–31, 34–36, 38–54 are
characteristic ABX multiplets in the range 2–3 ppm. In the spectra of the stereoisomers of phosphinates 30, 38–54, the signals of these protons
partially overlap. According to the NMR spectra, compounds 30, 38–54 are mixtures of two stereoisomers. Their ratio was determined from
the 1H NMR and 31P NMR spectra as 55:45 for 39,53; 60:40 for 30,38,40,42,48,50,52,54; 65:35 for 41,49,51; 70:30 for 43–47. The spectral
parameters of the major isomer are given first. In 13C NMR spectra, fragments COOR, δC, 30: 173.39 s, and 173.25 s; 38: 170.83 s, 172.99
d, 3JPC5.8, and 173.10 d, 3JPC5.9, 170.90 s; 39: 171.49 s, 173.61 d, 3JPC4.2 and 171.43 s, 173.46 d, 3JPC5.1; 40: 168.94 s, and 169.11 s; 41:
2
2
2
168.87 s, and 169.19 s; 42: 168.15 s, and 168.13 s; 43: 171.58 d, JPC17.5, and 171.65 d, JPC16.3; 44: 171.50 d, JPC17.3 (the signals of
2
2
2
2
the stereoisomers coincide); 45: 171.31 d, JPC18.7, and 171.13 d, JPC18.7; 46: 171.28 d, JPC17.7, and 171.05 d, JPC17.9; 47: 171.19 d,
2JPC18.4, and 170.95 d, JPC18.6, 169.81 s (COOMe for two stereoisomers); 50: 170.18 d, JPC16.5, and 170.27 d, JPC16.9; 51: 170.68 d,
2
2
2
2JPC16.5, and 170.79 d, JPC16.5; 52: 170.72 d, JPC16.5, and 170.76 d, JPC16.7; 53: 170.74 d, JPC13.8, and 170.90 d, JPC15.9, 169.88 s,
2
2
2
2
2
3
and 169.83 s (COOEt); fragment NC(O), δC, 34: 169.58 s; 35: 174.17 s; 36: 174.52 s; 45: 169.88 s and 170.0 s; 46: 174.0 d, JPC2.7, and
173.93 d, 3JPC3.1; 47: 156.14 s, and 156.2 s; fragment CH2OC(O), δC, 48: 66.73 s; 49: 66.80 s; fragment of
54, δC: first isomer,
32.10 s (C4), 141.25 d (C5, 3JPC7.1) and 139.39 d (C5, 3JPC6.1), second isomer, 31.85 s (C4), 141.56 d (C5, 3JPC6.9) and 139.14 d (C5, 3JPC7.1).
bd, 2JPC, 28: 3.1; 31: 3.0; 38: 3.8; 39: 4.2.
cFragment PC(O)NMe2, two nonequivalent Me groups: δH 3.08 s and 2.50 s; δC 36.16 s and 34.57 s.
Heteroatom Chemistry DOI 10.1002/hc

Synthesis of New Organophosphorus-Substituted Derivatives of Functionalized Propionates and Their Analogues 425
TABLE 4 Yields, Product Constants, and NMR Spectral Data for the HPC1HmC2HnC3 Fragmentsa (δ, ppm; J, Hz) of Sodium
Phosphonites 55–65a
Compound
Yield (%)
δ(H) PH, d
1JPH
3JHH
δ(C1)d
1JPC
δ(C2)s
δ(C3)d
3JPC
δ(P) sb
55
56
57
58
59
60
61
62
63
64
65
97
96
94
96
97
95
96
97
95
97
97
6.95
6.96
7.02c
6.94c
7.07
6.98
6.90d
6.82
6.84
7.12d
7.17
510.2
517.6
515.2
509.2
514.1
506.7
521.2
518.8
515.6
527.2
522.4
<1
<1
1.8
1.6
<1
<1
1.6
<1
<1
4.0
<1
30.78
32.33
33.58
34.95
44.57
43.29
36.13
45.17
40.24
43.95
47.26
86.7
88.2
88.1
89.3
92.5
91.6
92.7
84.3
86.4
98.9
88.7
91.97
47.41
36.51
41.04
26.75
27.14
28.63
33.77
34.29
181.74
176.90
36.99
11.5
12.1
8.3
11.4
10.7
11.2
10.6
6.2
27.57
21.98
21.81
25.58
22.86
26.48
24.13
36.40
24.89
31.74
29.02
42.57
177.83
177.57
181.11
136.62
151.48
180.44
175.13
7.3
4.6
12.0
55.05
e
aThe salts 55–65 are very hygroscopic crystals; therefore, their melting points were not measured. In 1H NMR spectra, all signals of the alkyl,
aryl, and furyl fragments are in the standard area; the signals of these fragments are multiplets and partially or completely overlap. In 13C NMR
spectrum, fragment NC(O) of 56; δC 171.78 s; fragments COOR, δC, d, 57: 177.32, 3JPC9.1, and 174.86 s; 58: 183.57, 3JPC7.8, and 181.32 s;
59: 175.49, 2JPC4.5; 60: 175.74, 2JPC5.2; 62: 177.05, 2JPC17.5; 63: 180.04, 2JPC17.5; fragment CH2O of 61, δC 68.99 s; fragment
of 64, δC: 55.05 d (C2, 2JPC 9.5); 32.84 s (C4); 143.48 d (C5, 3JPC13.5), and 144.78 d (C5, 3JPC11.8).
1
bData of 31P{ H} spectra.
cd. t.
dd. d.
eC1 = C2.
The reaction mixture was kept for 24 h at 20◦C,
the solvent was then removed, and the residue was
distilled in a vacuum to obtain 8 g of phosphinate
12.
acrylate was heated at 100–120◦C for 2 h and then
distilled to give 5.8 g of phosphonate 20.
Diethyl 2-oxotetrahydrofur-4-ylphosphonate (22).
A mixture of 6.5 g of γ-crotonolactone, 20 g of diethyl
trimethylsilyl phosphite, 10 g of diethyl phosphite,
and 0.1 g of zinc chloride was heated at 100–120◦C
for 2 h and then distilled to give 10.9 g of phospho-
nate 22.
O-Trimethylsilyl-bis[2-(trimethylsiloxycarbonyl)-
ethyl]phosphinate (13). A mixture of 5 g of phos-
phinate 12 and 2.8 g of diethyl phosphite was heated
at 100◦C for 1 h and then distilled in a vacuum to
obtain 3.8 g of phosphinate 13.
Phosphonates 23,24 were prepared similarly.
Phosphinate 21 was prepared similarly.
O-Trimethylsilyl-2-(trimethylsiloxycarbonyl)ethyl-
[2-(2-furyl)-1-(trimethylsiloxycarbonyl)ethyl]phosph-
inate (15). A solution of 2.5 g of trimethylsilyl
acrylate in 5 mL of methylene chloride was added
with stirring to a solution of 7.3 g of phosphonite
10 in 10 mL of methylene chloride. The reaction
mixture was refluxed for 30 min, and then a solution
of 2.4 g of diethyl phosphite in 5 mL of methylene
chloride was added. The solvent was removed, and
the residue was heated to 120◦C, and then distilled
to obtain 6.5 g phosphinate 15.
O-Trimethylsilyl-diethylaminomethyl-(trimethyl-
siloxycarbonyl)ethylphosphinate (25). (a) A mixture
of 6.7 g of O-trimethylsilyl diethylaminomethylphos-
phonite [15], 6.2 g trimethylsilyl acrylate, and 3 mL
of pyridine was heated at 110◦C for 2 h and then
distilled to obtain 8.9 g of phosphinate 25.
Phosphinates 26–33 were prepared similarly.
(b) A solution of 3 g of N-chloromethyldiethyl-
amine in 15 mL of methylene chloride was added
dropwise with stirring to a solution of 9 g of phos-
phonite 1 in 20 mL of methylene chloride. The mix-
ture was heated to the boil, the solvent was distilled,
and residue was distilled in a vacuum to give 7.7 g
of phosphinate 25 (yield 85%).
Phosphinates 14,16–19 was prepared similarly.
O,O-Diethyl
3,3-bis(trimethylsiloxy)propen-2-
ylphosphonate (20). A mixture of 5.9 g of diethyl
trimethylsilyl phosphite and 3.1 g of trimethylsilyl
Phosphinates 28 (yield 86%) and 34–47 were ob-
tained analogously.
Heteroatom Chemistry DOI 10.1002/hc

426 Prishchenko et al.
TABLE 5 Yields, Product Constants, and NMR Spectral Data for the PC1HmC2HnC3 and PC4H2NFragmentsa (δ, ppm; J, Hz)
of Sodium Phosphonates 66,67, Sodium Phosphinates 68–76, Phosphonic and Phosphinic Acids 77–88a
Compound
Yield (%)
Mp (◦C)
δ(C1)d
1JPC
δ(C2)d
2JPC
δ(C3)
3JPC
δ(C4)d
1JPC
δ(P)s
66
67
68
97
96
94
–
–
–
36.80
41.83
33.12
24.05b
38.54
26.78b
42.89
26.54 b
24.59
23.62b
33.65
26.34 b
38.70
39.77
39.27
42.04
20.39
23.32
28.72
28.82
26.36
27.05
27.38
26.97
24.42
28.32
24.95b
29.31
25.80b
30.06
24.96b
142.0
133.8
95.2
90.8
92.4
88.7
95.4
88.7
92.6
90.5
98.1
89.8
86.3
86.0
87.1
94.8
144.2
92.2
98.8
99.2
99.0
99.3
99.1
99.8
97.1
88.5
92.6
93.0
92.0
89.7
91.4
54.04
56.72
28.01
26.93
35.26
29.72
55.41
31.04
2.45
29.03
34.05
30.89
34.96
35.37
35.26
55.41
26.75
26.40
29.68
29.71
27.24
27.91
28.36
29.04
27.01
27.60
26.67
27.72
28.92
25.03
27.64
6.1
6.3
<1
3.1
<1
4.0
11.9
6.4
7.2
<1
<1
6.1
<1
<1
<1
12.5
<1
<1
7.5
8.6
3.9
3.4
3.1
3.6
3.1
<1
<1
<1
<1
<1
<1
174.96
183.47
174.64
179.07
152.45
182.12
183.06
180.05
–
178.64
143.94
180.94
152.60
152.70
152.59
181.87
173.74
176.36
180.00
179.93
177.49
178.18
178.48
176.82
177.31
156.65
177.51
164.36
174.74
139.51
177.89
5.9
5.4
7.8
14.9
6.3
15.2
5.7
15.4
–
14.3
9.8
15.7
6.9
6.1
–
–
–
–
–
–
32.08
21.46
35.37
69
70
71
72
96
97
95
98
–
–
–
–
–
–
–
–
–
–
–
–
31.44
42.03
39.98
39.05
73
74
75
76
77
78c
79
80
81
82
83
84
85
86
96
95
97
97
96
96
97
96
98
96
98
95
95
95
–
–
–
–
Oil
159
185
145
220
167
198
152
168
Oil
56.78
56.59
56.23
57.39
–
104.7
101.1
103.7
100.3
–
32.86
32.57
32.50
37.64
28.61
57.15
26.85
26.76
31.37
30.88
26.79
25.42
29.45
38.16
6.2
4.9
18.2
15.0
14.6
15.2
14.1
14.4
14.9
15.0
13.8
13.7
15.1
14.7
15.1
15.2
15.2
–
–
53.22
54.14
55.21
56.18
56.75
52.98
37.57
–
84.5
83.7
83.6
82.5
81.76
89.4
90.9
–
87
88
96
97
89
–
–
–
–
39.04
39.27
168
aThe salts 66–76 are very hygroscopic crystals; therefore, their melting points were not measured. All signals of alkyl, aryl, and heterocyclic
fragments are in the standard area. In 1H NMR, the signals of presented fragments are multiplets. Fragment
, 66, δC, 32.78 s
(C4), 141.64 d, 3JPC9.1 and 143.49 d, 3JPC9.7 (C5); 67, δH, 4.11 d. d (C2H, 3JPH16.0, 3JHH7.2), δC 35.03 s (C4), 143.93 d, 3JPC7.6 and 144.31 d,
3
3
3
3
3JPC7.6 (C5); 70, δH, 4.09 d. d (C2H, JPH16.2, JHH7.6), δC 32.17 s (C4), 140.02 d, JPC6.7 and 142.91 d, JPC6.8 (C5); 76, δH, 4.06 d. d (C2H,
3JPH15.6, 3JHH7.2), δC 32.58 s (C4), 142.90 d, 3JPC6.6 and 142.97 d, 3JPC7.2 (C5). Fragment CH2OC(O) of 68, δC66.28 s. Fragment COONa, δC,
69: 179.95 d, 2JPC14.8; 73: 180.43 d, 2JPC15.2; 74: 180.51 d, 2JPC15.3; 75: 180.47 d, 2JPC15.8. Fragment PCH2N, δH, d (2JPH), 76: 2.56 (8.4),
3
79: 3.07 (8.4), 80: 3.11 (8.0), 81: 3.20 (8.2), 82: 3.21 (8.4), 85: 3.55 (7.8). Fragment
of 84, δH, 3.67 d. d (C1H, JHHA8.6,
3JHHB6.4), δC 66.64 d (C1, 3JPC 8.9), 171.65 s (C2), 54.92 d (C3, 3JPC2.8), 23.59 s (C4), 27.54 s (C5).
bFragment PC1H2C2H2C3(O)
ccf. [16].
O-Trimethylsilyl diethylaminomethyl 2-oxotetra-
hydrofur-4-ylphosphinate (48). A mixture of 6 g of
phosphonite 8, 2.7 g of bis(dimethylamino)methane,
and 0.1 g of zinc chloride was heated at 110–120◦C
for 1.5 h and then distilled to obtain 3.9 g of phos-
phinate 48.
10 mL of ether was added with stirring at 10◦C to a
solution of 2.2 g of sodium methylate in 50 mL of
methanol. The resulting mixture was heated to the
boil, the solvent was removed, and the residue was
kept in a vacuum (1 mmHg) for 1 h to give 9.3 g of
salt 57 as colorless hygroscopic crystals.
Phosphinates 49–54 were prepared similarly.
The salts 55,56,58–76 were obtained similarly.
Sodium 2,3-bis(methoxycarbonyl)propylphospho-
Diethylaminomethyl 2-carboxyethylphosphinic
nite (57). A solution of 14.7 g of phosphonite 3 in
acid (79). A solution of 8 g of phosphinate 25 in
Heteroatom Chemistry DOI 10.1002/hc

Synthesis of New Organophosphorus-Substituted Derivatives of Functionalized Propionates and Their Analogues 427
TABLE 6 Elemental Analyses Data of Synthesized Compoundsa
Calcd. (%)
Found (%)
Compound
Empirical Formula
Formula Weight
C
H
C
H
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
61
62
63
64
65
66
67
68
C18H43O6PSi4
C15H35O6PSi3
498.85
426.74
366.50
492.73
514.78
424.73
398.58
387.55
354.60
282.34
222.18
370.44
458.72
367.70
395.63
379.51
381.66
393.61
423.60
455.83
387.55
401.58
367.52
379.53
407.58
353.49
353.43
469.75
379.48
381.45
403.49
455.41
457.50
443.91
455.71
531.94
279.35
321.39
405.58
445.64
447.62
477.64
427.63
182.02
239.08
246.13
262.05
232.11
248.01
172.05
258.12
248.09
270.13
318.08
320.25
308.11
266.10
43.34
42.22
42.60
46.32
51.33
48.08
54.24
49.59
44.04
42.54
43.25
55.12
49.75
45.74
48.58
47.46
44.07
48.82
45.37
42.16
49.59
50.85
42.48
44.30
47.15
40.77
44.19
43.47
47.48
44.08
35.72
55.35
52.49
51.44
52.72
49.69
43.00
44.86
47.38
51.21
48.30
47.78
53.37
19.79
25.12
34.16
22.92
31.05
19.37
27.92
41.88
33.89
44.46
22.66
52.51
38.98
31.60
8.89
8.27
7.43
7.57
7.64
9.73
7.84
7.80
8.81
8.21
6.81
7.35
7.69
9.32
9.68
9.03
8.45
9.22
8.09
9.29
7.80
8.03
8.23
7.97
8.41
7.98
7.98
8.58
7.97
7.40
6.50
8.41
7.93
7.72
7.52
7.20
7.94
7.53
7.95
8.14
7.66
7.60
8.01
2.77
3.37
4.91
2.31
4.34
1.62
3.52
3.51
2.85
3.36
3.17
5.66
2.62
3.41
43.05
41.94
42.28
46.03
51.15
47.92
53.99
49.28
43.69
42.38
42.92
54.89
49.57
45.59
48.40
47.21
43.86
48.68
45.22
41.97
49.26
50.70
42.26
44.12
46.95
40.63
43.97
43.28
47.26
43.92
35.59
55.12
52.31
51.28
52.58
49.52
42.83
44.59
47.05
51.03
47.98
47.69
53.12
19.60
24.93
33.97
22.68
30.87
19.20
27.59
41.72
33.68
44.28
22.52
52.33
38.83
31.49
8.52
8.09
7.26
7.49
7.58
9.64
7.75
7.67
8.70
8.29
6.74
7.26
7.62
9.12
9.57
8.87
8.28
9.14
8.03
9.07
7.62
7.91
8.09
7.83
8.29
7.86
7.89
8.49
7.86
7.26
6.40
8.26
7.82
7.64
7.41
7.03
7.89
7.38
7.81
8.06
7.52
7.53
8.06
2.80
3.50
4.98
2.26
4.28
1.65
3.65
3.47
3.03
3.43
3.23
5.59
2.67
3.34
C13H27O6PSi2
C19H37O7PSi3
C22H39O6PSi3
C17H41O4PSi3
C18H31O4PSi2
C16H30NO4PSi2
C13H31O5PSi2
C10H23O5PSi
C8H15O5P
C17H27O5PSi
C19H35O5PSi3
C14H34NO4PSi2
C16H38NO4PSi2
C15H34NO4PSi2
C14H32NO5PSi2
C16H36NO4PSi2
C16H34NO6PSi2
C
C
16H42NO4PSi4
16H30NO4PSi2
C17H32NO4PSi2
C
C
13H30NO5PSi2
14H30NO5PSi2
C16H34NO5PSi2
12H28NO5PSi2
C13H28NO6PSi
C
C
C
17H40NO6PSi
15H30NO6PSi
C14H28NO7PSi
12H26NO8PSSi
C
C
21H38NO4PSi2
C20H36NO5PSi2
C19H34NO5PSi2
C20H34NO5PSi2
C22H38NO8PSi2
C10H22NO4PSi
C12H24NO5PSi
C
16H32NO5PSi2
C19H36NO5PSi2
C18H34NO6PSi2
C19H36NO7PSi2
C19H34NO4PSi2
C3H5Na2O4P
C5H8NNa2O5P
C7H12NaO6P
C5H6Na3O6P
C6H10NaO6P
C4H4Na3O6P
C4H6NaO4P
C9H9Na2O4P
C7H7Na2O5P
C10H9Na2O4P
C6H10Na2O8P2
C14H18NaO5P
C10H8Na3O5P
C7H9Na2O6P
(Continued)
Heteroatom Chemistry DOI 10.1002/hc

428 Prishchenko et al.
TABLE 6 Continued
Calcd. (%)
Found (%)
Compound
Empirical Formula
Formula Weight
C
H
C
H
69
70
71
72
73
74
75
76
77
78
79
80
81
82
83
84
85
86
87
88
C10H10Na3O7P
C13H12Na3O6P
342.13
364.17
324.34
298.18
305.18
345.24
347.21
327.23
210.29
210.13
223.12
251.08
235.28
237.21
249.25
279.23
167.10
243.21
243.21
257.24
35.11
42.88
40.74
48.34
39.36
45.23
41.51
47.72
40.00
34.30
43.08
47.80
45.95
40.51
48.19
43.01
28.75
49.38
49.38
51.36
2.95
3.32
7.15
4.39
4.62
5.25
4.65
4.93
7.19
5.28
8.13
8.83
7.71
6.80
8.09
6.50
6.03
5.80
5.80
6.27
34.97
42.65
40.59
48.23
39.23
44.98
41.29
47.61
39.75
34.20
42.86
47.67
45.71
40.39
47.94
42.81
28.64
49.23
49.12
51.06
3.01
3.26
7.09
4.30
4.55
5.12
4.68
4.98
7.24
5.30
8.10
8.61
7.65
6.82
7.93
6.45
6.08
5.64
5.59
6.03
C
11H23Na2O4PSi
C12H13Na2O4P
C10H14NNa2O5P
C13H18NNa2O5P
C12H16NNa2O6P
C13H16NNa2O4P
C7H15O5P
C6H11O6P
C8H18NO4P
C10H22NO6P
C9H18NO4P
C8H16NO5P
C10H20NO4P
C10H18NO6P
C4H10NO4P
C10H14NO4P
C10H14NO4P
C11H16NO4P
aThe other compounds are unstable in the air atmosphere; therefore, these substances were analyzed as their sodium salts.
[6] Prishchenko, A. A.; Livantsov, M. V.; Novikova, O. P.;
Livantsova, L. I.; Petrosyan, V. S. Heteroatom Chem,
in press.
[7] Prishchenko, A. A.; Livantsov, M. V.; Novikova, O. P.;
Livantsova, L. I.; Petrosyan, V. S. Heteroatom Chem,
in press.
[8] Prishchenko, A. A.; Livantsov, M. V.; Petrosyan, V. S.
Zh Obsh Khim 1994, 64, 1316–1330 (in Russian).
[9] Livantsov, M. V.; Prishchenko, A. A.; Lutsenko, I. F.
Zh Obsh Khim 1985, 55, 2226–2233 (in Russian).
[10] Issleib, K.; Kitzrow, W.; Lutsenko, I. F. Phosphorus
1975, 5, 281–283.
[11] Thottathil, J. K.; Ryono, D. E.; Przybyla, C. A.;
Moniot, J. L.; Neubeck, R. Tetrahedron Lett 1984,
25, 4741–4744.
[12] Novikova, Z. S.; Lutsenko, I. F. Zh Obsh Khim 1970,
40, 2129 (in Russian).
[13] Novikova, Z. S.; Mashoshina, S. N.; Sapozhnikova,
T. A.; Lutsenko, I. F. Zh Obsh Khim 1971, 41, 2622–
2628 (in Russian).
[14] Okamoto, Y.; Sakurai, H. Synthesis 1982, 497–499.
[15] Prishchenko, A. A.; Livantsov, M. V.; Lorentz, K.-L.;
Grigoriev, E. V.; Luzikov, Yu. N. Zh Obsh Khim 1994,
64, 1577–1578 (in Russian).
[16] Gallagher, M. J.; Sussman, J. Phosphorus 1975, 5,
91–95.
20 mL of diethyl ether was added dropwise with
stirring at 10◦C to 30 mL of methanol. The resulting
mixture was heated to boil, the solvent was distilled
in a vacuum, and the residue was kept in a vacuum
(1 mmHg) for 1 h to give 4.7 g of acid 79 as colorless
hygroscopic crystals.
The acids 77,78,80–88 were obtained similarly.
REFERENCES
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phorus Sulfur Silicon 1999, 144–146, 313–316.
[2] Esswein, A.; Bauss, F.; Muehlbauer, R.; Guenther, H.;
Bosies, E. Phosphorus Sulfur Silicon 1999, 144–146,
13–16.
[3] Kukhar, V. P.; Hudson, H. R. Aminophosphonic and
Aminophosphinic Acids. Chemistry and Biological
Activity; Wiley: New York, 2000.
[4] Kolodiazhnyi, O. I. Usp Khim 2006, 75, 254–282 (in
Russian).
[5] Prishchenko, A. A.; Livantsov, M. V.; Novikova, O. P.;
Livantsova, L. I.; Petrosyan, V. S. Heteroatom Chem,
in press.
Heteroatom Chemistry DOI 10.1002/hc