Novel aminophosphonothiophene derivatives from β-keto-δ- carbethoxyphosphonates and phosphineoxides

Article abstract of DOI:10.1080/17415993.2011.570763

The reaction of β-keto-δ-carbethoxyphosphonates and phosphineoxides with active methylene nitriles leads to the corresponding phosphonoalkylidenes. Treatment of these compounds with sulfur, under the classical Gewald reaction conditions, gives a ca. 1:1 mixture of novel aminophosphonothiophene derivatives 3 and 3′. In order to improve the regioselectivity of the reaction, novel conditions have been developed for the Gewald condensation, in which we used an inorganic base NaH in THF as the solvent. These conditions afforded exclusively the 3-regioisomer in good yield.

Full text of DOI:10.1080/17415993.2011.570763

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Novel aminophosphonothiophene
derivatives from β-keto-δ-
carbethoxyphosphonates and
phosphineoxides
Emna Chebil a , Moufida Chamakhi a & Soufiane Touil a
a Laboratoire de Chimie Organique des Hétéroéléments,
Département de Chimie, Faculté des Sciences de Bizerte,
Université de Carthage, 7021, Jarzouna, Tunisia
Published online: 04 Apr 2011.
To cite this article: Emna Chebil , Moufida Chamakhi & Soufiane Touil (2011): Novel
aminophosphonothiophene derivatives from β-keto-δ-carbethoxyphosphonates and
phosphineoxides, Journal of Sulfur Chemistry, 32:3, 249-256
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Journal of Sulfur Chemistry
Vol. 32, No. 3, June 2011, 249–256
Novel aminophosphonothiophene derivatives from
β-keto-δ-carbethoxyphosphonates and phosphineoxides
Emna Chebil, Moufida Chamakhi and Soufiane Touil*
Laboratoire de Chimie Organique des Hétéroéléments, Département de Chimie, Faculté des Sciences de
Bizerte, Université de Carthage, 7021 Jarzouna, Tunisia
(Received 3 February 2011; final version received 5 March 2011)
The reaction of β-keto-δ-carbethoxyphosphonates and phosphineoxides with active methylene nitriles leads
to the corresponding phosphonoalkylidenes. Treatment of these compounds with sulfur, under the classical
Gewald reaction conditions, gives a ca. 1:1 mixture of novel aminophosphonothiophene derivatives 3 and
3ꢀ. In order to improve the regioselectivity of the reaction, novel conditions have been developed for the
Gewald condensation, in which we used an inorganic base NaH in THF as the solvent. These conditions
afforded exclusively the 3-regioisomer in good yield.
O
X
X
EtO2C
R2P
1/8 S8, Et2NH
EtOH, 50°C
+
O
R2P
NH2
EtO2C
NH2
S
R2P
CO2Et
S
O
O
1
O
+
MeCO2NH4, MeCO2H
Benzene, reflux, 24 h
3'
3
(~ 1:1 ratio)
R2P
CO2Et
O
X
CN
X
CN
1/8 S8, NaH
THF, 0°C
X
2
R2P
EtO2C
NH2
S
3
Keywords: thiophenes;aminophosphonothiophenes;ketophosphonates;Gewaldreaction;regioselectivity
1. Introduction
Thiophene derivatives prepared via the Gewald reaction (1–4) recently have seen increasing
interest due to the utility of these heterocycles as starting points for the synthesis of a variety
of agrochemicals (4, 5), dyes (6) and pharmacologically active compounds. For instance, it has
recently been reported that these thiophene scaffolds are valuable intermediates in the synthesis
of inhibitors of the phosphatase PTP1B (7), kainate receptor subtype GluR6 (8), human leuko-
cyte elastase (9), adenosine receptor A3 (10) and multitargeted kinase (11). In this area, we
*Corresponding author. Email: soufiane.touil@fsb.rnu.tn
ISSN 1741-5993 print/ISSN 1741-6000 online
© 2011 Taylor & Francis
DOI: 10.1080/17415993.2011.570763
http://www.informaworld.com

250 E. Chebil et al.
have previously shown that α, β and γ-ketophosphonates undergo Gewald condensation to give
aminophosphonothiophene derivatives (12–15). We report in the present investigation the exten-
sion of this reaction to the β-keto-δ-carbethoxyphosphonates and phosphineoxides 1 (16). Our
ultimate aim here was to compare the reactivity of carbons in the α, αꢀ positions with the keto func-
tion in order to obtain more precise information about the regioselectivity of the Gewald reaction
and to access new aminophosphonothiophene derivatives bearing the ethoxycarbonyl group.
2. Results and discussion
The condensation of compounds 1 with active methylene nitriles performed in refluxing benzene
for 24 h, in the presence of catalytic amounts of ammonium acetate and acetic acid, leads to the
phosphonoalkylidenes 2 in 60–90% yield. Treatment of alkylidenes 2 with an equimolar quantity
of sulfur, under the classical Gewald reaction conditions (Method A), that is, using a catalytic
amount of diethylamine in ethanol as solvent and heating the solution at 50◦C for 24–48 h, gives
a mixture of two aminophosphonothiophenes 3 and 3ꢀ (Scheme 1) in an approximate 1:1 ratio
and a combined yield of 55–87% (Table 1).
O
O
MeCO2NH4, MeCO2H
Benzene, reflux, 24 h
R2P
CO2Et
R2P
CO2Et
X
CN
+
O
X
CN
1
2
O
X
X
EtO2C
R2P
1/8 S8, Et2NH
EtOH, 50°C
R2P
2
+
NH2
EtO2C
NH2
S
S
O
3'
3
3, 3¢
a
b
c
d
e
f
g
O
O
O
P
P
R
Ph
EtO
CN
MeO
Ph
EtO
R2P
X
O
X
CN
CN
CO2Et
CO2Et
CN
CN
Scheme 1. Synthesis of aminophosphonothiophenes 3 and 3ꢀ (Method A).
Mechanistically (12–15), it is clear that deprotonation of 2 with diethylamine produces an
equilibrium mixture of α- and γ-anions which react with sulfur leading to thiophenes 3 and 3ꢀ
(Scheme 2).
2.1. Regioselective synthesis of aminophosphonothiophenes 3 (Method B)
With the aim to improve the regioselectivity of the reaction, we first carried out a theoretical AM1
calculation with Gaussian 03 program, in order to compare the acidity of hydrogens at the α, αꢀ
positions to the C=C double bond in alkylidenes 2. The results suggest that the hydrogens at the
α position to the ethoxycarbonyl group are the most acidic (Scheme 3).

Journal of Sulfur Chemistry 251
Table 1. Synthesis of aminophosphonothiophenes 3 and 3ꢀ.
Entry
Method
Products
% 3/3ꢀ
Reaction time (h)a
Yield (%)b
1
2
3
4
5
6
7
8
9
10
11
12
13
14
A
A
A
A
A
A
A
B
B
B
B
B
B
B
3a + 3ꢀa
3b + 3ꢀb
3c + 3ꢀc
3d + 3ꢀd
3e + 3ꢀe
3f + 3ꢀf
3g + 3ꢀg
3a
44/56
52/48
55/45
59/41
56/44
53/47
52/48
–
–
–
–
–
–
–
24
24
24
24
24
48
48
3
3
3
3
3
87
68
72
79
55
68
57
81
70
76
72
63
75
78
3b
3c
3d
3e
3f
3g
3
3
Notes: aThe progress of the reactions was monitored by TLC; bYield of isolated products.
O
O
R2P
O
_
C
N
X
X
O
+
X
R2P
Et2NH2
1/8
S8
S_
γ
R2P
CO2Et
H
H
EtO2C
R2P
- Et2NH
C
EtO2C
NH2
NH
S
X
CN
S
CO2Et
3
+
-Et2NH2
Et2NH
O
R2P
CO2Et
X
CN
2
+
-Et2NH2
Et2NH
O
_
X
C
N
_
X
X
+
Et2NH2
EtO2C
EtO2C
R2P
CO2Et 1/8
S8
α
H
S
CO2Et
- Et2NH
R2P
NH
R2P
O
NH2
X
CN
S
S
PR2
O
O
3'
Scheme 2. Reaction mechanism (Method A).
0.0712 - 0.0834
0.0907 - 0.1028
O
R2P-CH2-C-CH2-CO2Et
X
CN
2
Scheme 3. Calculated Mulliken charges of hydrogen at α, αꢀ positions to the C=C double bond
in alkylidenes 2.
On the basis of these results, we surmised that kinetic control of the reaction using a strong
base such as NaH, at lower temperature, could allow us to abstract selectively the more acidic
hydrogen at the α position to the ethoxycarbonyl group, leading regioselectively to compounds 3.

252 E. Chebil et al.
Experimentally, thereactionofalkylidenes2 withsulfurat0◦C, usinganequimolaramountofNaH
in THF as solvent, and stirring the solution at the same temperature for 3 h leads regioselectively
to aminophosphonothiophenes 3 in good yield (Scheme 4).
O
O
C
N
X
O
R2P
CO2Et
S_
R2P
CO2Et 1/8
S8
NaH / THF
0°C
H
R2P
C
X
CN
X
CN
2
CO2Et
O
O
O
X
N
X
R2P
+
X
R2P
R2P
H
/ H2O
H
H
EtO2C
EtO2C
NH2
EtO2C
NH
S
S
S
3
3a
3b
3c
3d
3e
3f
3g
O
O
P
P
R
X
Ph
EtO
MeO
CN
Ph
EtO
R2P
O
O
CN
CN
CO2Et
CO2Et
X
CN
CN
Scheme 4. Regioselective synthesis of aminophosphonothiophenes 3 (Method B).
The formation of compounds 3 and 3ꢀ was confirmed by IR, NMR (1H, 31P, 13C) and mass spec-
tral data. We observed, in particular, the appearance of broad singlets at 5–6 ppm, corresponding
to the protons of NH2 groups. For compounds 3, we observed a doublet at 3.5–4.5 ppm, ascribable
to the CH2–P=O protons. Such a doublet is characteristic of the coupling with phosphorus with
a 2JPH coupling constant of about 10–15 Hz. As for compounds 3ꢀ, we notice the absence of the
signal assignable to the CH2–P=O protons and the presence of a singlet (in some cases a doublet
4
with a small JPH coupling constant) towards 3.8 ppm corresponding to the methylene at the α
position to the ethoxycarbonyl group.
Other evidence of structure for aminophosphonothiophenes 3 and 3ꢀ is provided by 13C
NMR. Indeed, we find the signals of all carbons and particularly those corresponding to the
thiophene ring.
3. Experimental section
1H, 31P and 13C NMR spectra were recorded with CDCl3 as the solvent, on a Bruker-300 spec-
trometer. The chemical shifts are reported in ppm relative to TMS (internal reference) for 1H and
13C NMR and relative to 85% H3PO4 (external reference) for 31P NMR. The coupling constants
are reported in hertz. For the 1H NMR, the multiplicities of signals are indicated by the following
abbreviations: s, singlet; d, doublet; t, triplet; q, quartet; qp, quintet; m, multiplet.
Mass spectra were determined on a Micromass Quatro-ultima Pt (triple quadrupole) spec-
trometer, under electrospray ionization (ESI) conditions. IR spectra were recorded on a
Perkin Elmer Paragon 1000 PC spectrometer. The progress of the reactions was monitored
by TLC. Purification of products was performed by column chromatography using silica gel
60 (Fluka).

Journal of Sulfur Chemistry 253
3.1. Synthesis of phosphonoalkylidene intermediates 2
A mixture of β-keto-δ-carbethoxyphosphonate or phosphineoxide 1 (0.01 mol), active methylene
nitrile (0.01 mol), ammonium acetate (0.15 g) and acetic acid (0.2 ml) in dry benzene (25 ml) was
heated at reflux, with Dean-Stark separation of water, for 24 h. The mixture was then cooled,
diluted with water (30 ml) and extracted with CHCl3 (2 × 25 ml). The organic phase was dried
over Na2SO4 and concentrated in vacuo. The obtained residue was recrystallized from a mixture
of toluene, hexane and ether.
3.2. Synthesis of aminophosphonothiophenes 3 and 3ꢀ (Method A)
To a mixture of phosphonoalkylidene 2 (0.01 mol) and sulfur (0.011 mol) in ethanol (30 ml), a
solution of diethylamine (1 ml) in ethanol (5 ml) was added dropwise with stirring. The reaction
mixture was then stirred at 50◦C for 24–48 h (Table 1). The ethanol was removed under reduced
pressure and then CHCl3 (100 ml) was added. The organic phase was washed with 5% aqueous
HCl solution (2 × 50 ml), dried over Na2SO4 and concentrated in vacuo. The obtained residue was
chromatographed on a silica gel column using a mixture of ether and ethanol 98:2 as the eluent.
3.3. Regioselective synthesis of aminophosphonothiophenes 3 (Method B)
To a mixture of phosphonoalkylidene 2 (0.01 mol), sulfur (0.011 mol) and THF (30 ml), cooled
at 0◦C and maintained under a nitrogen atmosphere, a suspension of NaH (0.01 mol) in THF
(5 ml) was added dropwise with stirring. The reaction mixture was then stirred at 0◦C for 3 h. A
5% aqueous HCl solution (30 ml) was added and stirring was continued for 15 min. The mixture
was then extracted with CHCl3 (2 × 30 ml). The organic phase was dried over Na2SO4 and
concentrated in vacuo. The obtained residue was chromatographed on a silica gel column using
a mixture of ether and ethanol 98:2 as the eluent.
3a: m.p. = 185◦C; 31P NMR (121.5 MHz, CDCl3): δ = 29.1 ppm; 1H NMR (300 MHz,
CDCl3): δ = 1.20 (t; 3H; 3JHH = 7.2 Hz; CH3–CH2–O); 4.02 (q; 2H; 3JHH = 7.2 Hz; CH3–CH2–
O); 4.26 (d; 2H; 2JPH = 13.5 Hz; CH2–P); 6.12 (broad s; 2H; NH2); 7.26–7.80 (m; 10H; arom-H);
13C NMR (75.5 MHz, CDCl3): δ(JCP): 12.4 (CH3); 30.1 (62.4 Hz; CH2–P); 58.3 (CH3–CH2–O);
87.9 (12.0 Hz; C–CN); 113.0 (CN); 129.9 (EtO2C–C–S); 137.5 (9.3 Hz; C–CH2–P); 141.9 (C–
NH2); 166.4 (C = O); Phenyl carbons: 126.8, 126.9, 129.6, 129.7, 130.1, 131.3, 132.0; IR (neat):
νNH = 3305–3412 cm−1; νCN = 2220 cm−1; νC=O = 1728 cm−1; νP=O = 1264 cm−1; ESI-MS:
2
m/z = 411.414([M + H]+).
3b:Oil, 31PNMR(121.5 MHz, CDCl3):δ = 27.8 ppm;1HNMR(300 MHz, CDCl3):δ = 0.75–
1.36 (m; 9H; 3 CH3–CH2–O); 3.99–4.19 (m; 8H; 3 CH3–CH2–O and CH2–P); 5.76 (broad s; 2H;
NH2); 13C NMR (75.5 MHz, CDCl3): δ (JCP): 13.2 (CH3–CH2–O); 15.1 (3.8 Hz; CH3–CH2–O–
P); 32.0 (168.3 Hz; CH2–P); 60.4 (CH3–CH2–O); 61.7 (4.5 Hz; CH3–CH2–O–P); 90.7 (C–CN);
114.3 (CN); 124.5 (EtO2C–C–S); 129.5 (5.3 Hz; C–CH2–P); 156.9 (C–NH2); 164.0 (C = O);
IR (neat): νNH = 3200–3310 cm−1; νCN = 2225 cm−1; νC=O = 1720 cm−1; νP=O = 1260 cm−1
;
2
ESI-MS: m/z = 347.329([M + H]+).
3c: Oil, 31P NMR (121.5 MHz, CDCl3): δ = 31.3 ppm; 1H NMR (300 MHz, CDCl3): δ = 1.06
(t; 3H; 3JHH = 9.0 Hz; CH3–CH2–O); 3.85 (d; 6H; 2JPH = 3 Hz ; 2 CH3–O); 4.05 (d; 2H; 2JPH
=
9.0 Hz; CH2–P); 4.24 (q; 2H; 3JHH = 9.0 Hz; CH3–CH2–O); 6.15 (broad s; 2H; NH2); 13C NMR
(75.5 MHz, CDCl3): δ (JCP): 12.7 (CH3–CH2–O); 29.8 (166.0 Hz; CH2–P); 58.8 (9.8 Hz; CH3–
O); 67.8 (CH3–CH2–O); 90.7 (C–CN); 111.1 (CN); 129.6 (EtO2C–C–S); 136.7 (C–CH2–P);
151.9 (C–NH2); 164.5 (C = O); IR (neat): νNH = 3285–3400 cm−1; νCN = 2215 cm−1; νC=O
=
2
1710 cm−1; νP=O = 1270 cm−1; ESI-MS: m/z = 319.277([M + H]+).

254 E. Chebil et al.
3d: Oil, 31P NMR (121.5 MHz, CDCl3): δ = 27.1 ppm; 1H NMR (300 MHz, CDCl3): δ = 0.79–
1.29 (m; 6H; 2 CH3–CH2–O); 3.14–4.31 (m; 4H; 2 CH3–CH2–O); 3.59 (d; 2H; 2JPH = 12.0 Hz;
CH2–P); 6.45 (broad s; 2H; NH2); 7.21–7.83 (m; 10H; arom-H); 13C NMR (75.5 MHz, CDCl3): δ
(JCP): 11.9 (CH3CH2O2C); 13.2 (CH3CH2O2C–C–S); 40.9 (83.0 Hz; CH2–P); 58.6 (CH3–CH2–
O2C); 58.9 (CH3CH2O2C–C–S); 127.2 (C–CO2Et); 130.5 (11.3 Hz; C–CH2–P); 131.9 (S–C–
CO2Et); 161.0 (C–NH2); 165.1 (CO2Et); 165.9 (S–C–CO2Et); Phenyl carbons: 127.4, 127.8,
127.90, 127.94, 130.1, 130.3, 130.4; IR (neat): νNH = 3320–3410 cm−1; νCN = 2215 cm−1
;
2
νC=O = 1728 cm−1; νP=O = 1265 cm−1; ESI-MS: m/z = 458.462([M + H]+).
1
3e: Oil, 31P NMR (121.5 MHz, CDCl3): δ = 28.1 ppm; H NMR (300 MHz, CDCl3): δ =
0.75–1,28 (m; 12H; 4 CH3–CH2–O); 4.15–4.56 (m; 10H; 4 CH3–CH2–O and CH2–P); 6.85
(broad s; 2H; NH2); 13C NMR (75.5 MHz, CDCl3): δ (JCP ): 14.7 (CH3CH2O2C–CH2); 14.2
(CH3–CH2–O–C); 15.1 (6.8 Hz; CH3–CH2–O–P); 30.2 (126.0 Hz; CH2–P); 60.7 (CH3CH2O2C);
62.1 (CH3CH2O2C–C–S); 62.6 (6.0 Hz; CH3–CH2–O–P); 119.2 (C–CO2Et); 121.3 (EtO2C–C–
S); 129.6 (C–CH2–P); 139.6 (7.5 Hz; C–NH2); 163.0 (CO2Et); 167.8 (S–C–CO2Et); IR (neat):
νNH = 3350–3463 cm−1; νCN = 2214 cm−1; νC=O = 1730 cm−1; νP=O = 1267 cm−1; ESI-MS:
2
m/z = 394.379([M + H]+).
1
3f: Oil; 31P NMR (121.5 MHz, CDCl3): δ = −7.5 ppm; H NMR (300 MHz, CDCl3): δ =
3
1.30 (t; 3H; JHH = 6.0 Hz; CH3–CH2–O); 3.46–4.71 (m; 8H; CH3–CH2–O, –O–CH2–CH2–
O– and CH2–P); 5.32 (broad s; 2H; NH2); 13C NMR (75.5 MHz, CDCl3): δ (JCP): 13.0 (CH3);
32.1 (174,3 Hz; CH2–P); 63.8 (6.8 Hz; –O–CH2–CH2–O); 64.4 (CH3–CH2–O); 97.5 (C–CN);
105.7 (CN); 124.5 (C–CO2Et); 134.8 (C–CH2–P); 161.8 (C–NH2); 178.5 (C = O); IR (neat):
νNH = 3300–3410 cm−1; νCN = 2220 cm−1; νC=O = 1725 cm−1; νP=O = 1270 cm−1; ESI-MS:
2
m/z = 317.241([M + H]+).
3g: m.p. = 88◦C; 31P NMR (121.5 MHz, CDCl3): δ = −8.8 ppm; 1H NMR (300 MHz, CDCl3):
δ = 1.18 (t; 3H; 3JHH = 3.0 Hz; CH3–CH2–O); 2.16 (s; 6H; 2 CH3); 3.95(d; 4H; 3JPH = 12.0 Hz;
2 CH2–O–P); 4.05–4.12 (m; 4H; CH3–CH2–O and CH2–P); 5.27 (broad s; 2H;NH2); 13C
NMR (75.5 MHz, CDCl3): δ (JCP): 17.4 (CH3CH2O2C); 21.8 (2 CH3): 28.6 (Me2C); 41.2
(129.8 Hz; CH2–P); 56.9 (CH3–CH2–O); 59.1 (6.0 Hz; 2 CH2–O–P); 92.8 (C–CN); 109.0 (CN);
114.8 (C–CO2Et); 132.0 (C–CH2–P); 141.1 (C–NH2); 161.7 (C = O); IR (neat): νNH = 3245–
2
3360 cm−1;νCN = 2226 cm−1;νC=O = 1730 cm−1;νP=O = 1260 cm−1;ESI-MS:m/z = 359.328
([M + H]+).
3ꢀa: m.p. = 176◦C; 31P NMR (121.5 MHz, CDCl3): δ = 20.1 ppm; 1H NMR (300 MHz, CDCl3):
δ = 1.18 (t; 3H; 3JHH = 7.2 Hz; CH3–CH2–O); 3.83 (d; 2H; 4JPH = 0.7 Hz; CH2–CO2Et); 3.98
(q; 2H; 3JHH = 7.2 Hz; CH3–CH2–O); 5.51 (broad s; 2H; NH2); 6.95–7.72 (m; 10H; arom-H); 13
C
NMR (75.5 MHz, CDCl3): δ (JCP): 12.2 (CH3); 32.1 (23.1 Hz; CH2–CO2Et); 58.8 (CH3–CH2–
O); 88.3 (2.6 Hz; C–CN); 106.9 (117.9 Hz; P–C–S); 112.9 (CN); 142.0 (7.8 Hz; C–CH2–CO2Et);
159.3 (2.5 Hz; C–NH2); 166.6 (7.1 Hz; C = O); Phenyl carbons: 126.5, 126.6, 129.2, 129.3,
129.5, 130.0, 130.5; IR (neat): νNH = 3280–3396 cm−1; νCN = 2216 cm−1; νC=O = 1737 cm−1
;
2
νP=O = 1250 cm−1; ESI-MS: m/z = 411.421([M + H]+).
1
3ꢀb: Oil; 31P NMR (121.5 MHz, CDCl3): δ = 19.6 ppm; H NMR (300 MHz, CDCl3): δ =
0.75–1.36 (m; 9H; 3 CH3–CH2–O); 3.82 (s; 2H; CH2–CO2Et); 3.99–4.19 (m; 6H; 3 CH3–CH2–
O); 5.76 (broad s; 2H; NH2); 13C NMR (75.5 MHz, CDCl3): δ (JCP): 14.2 (CH3–CH2–O–C);
15.2 (3.8 Hz; CH3–CH2–O–P); 26.4 (23.4 Hz; CH2–CO2Et); 60.1 (CH3–CH2–O); 62.8 (6.0 Hz;
CH3–CH2–O–P); 90.9 (C–CN); 104.0 (158.5 Hz; P–C–S); 114.3 (CN); 139.7 (7.5 Hz; C–CH2–
CO2Et); 157.0 (C–NH2); 167.8 (C = O); IR (neat): νNH = 3196–3310 cm−1; νCN = 2221 cm−1
;
2
νC=O = 1740 cm−1; νP=O = 1240 cm−1; ESI-MS: m/z = 347.335([M + H]+).
3ꢀc: Oil; 31P NMR (121.5 MHz, CDCl3): δ = 28.5 ppm; 1H NMR (300 MHz, CDCl3): δ = 1.19
3
3
(t; 3H; JHH = 9.0 Hz; CH3–CH2–O); 3.71 (s; 2H; CH2–CO2Et); 3.82 (d, 6H; JPH = 3 Hz;
2 CH3–O); 4.17 (q; 2H; JHH = 9.0 Hz; CH3–CH2–O); 5.90 (broad s; 2H; NH2); 13C NMR
3
(75.5 MHz, CDCl3): δ (JCP):12.6 (CH3–CH2–O); 34.9 (30.0 Hz; CH2–CO2Et); 58.9 (9.8 Hz;

Journal of Sulfur Chemistry 255
CH3–O); 67.0 (CH3–CH2–O); 87.6 (C–CN); 110.8 (CN); 112.1 (164.5 Hz; P–C–S); 145.3
(C–CH2–CO2Et); 148.9 (C–NH2); 163.2 (C = O); IR (neat): νNH = 3290–3380 cm−1; νCN
=
2
2210 cm−1; νC=O = 1733 cm−1; νP=O = 1250 cm−1; ESI-MS: m/z = 319.262([M + H]+).
1
3ꢀd: Oil; 31P NMR (121.5 MHz, CDCl3): δ = 21.5 ppm; H NMR (300 MHz, CDCl3): δ =
0.79–1.29 (m; 6H; 2 CH3–CH2–O); 3.14–4.31 (m; 4H; 2 CH3–CH2–O); 3.39 (s; 2H; CH2–
CO2Et); 6.45 (broad s; 2H; NH2); 7.21–7.83 (m; 10H; arom-H); 13C NMR (75.5 MHz, CDCl3):
δ (JCP): 12.7 (CH3CH2O2C–CH2); 12,9 (CH3CH2O2C); 29.1 (30.9 Hz; CH2–CO2Et); 59.9
(CH3CH2O2C–CH2); 60.3 (CH3CH2O2C); 127.5 (C–CO2Et); 112.9 (98.1 Hz; P–C–S); 129.9
(C–CH2–CO2Et); 161.6 (C–NH2;) 162.0 (CH2–CO2Et); 165.9 (CO2Et); Phenyl carbons: 127.58,
127.61, 128.1, 129.8, 129.9, 130.0, 131.5; IR (neat): νNH = 3300–3390 cm−1; νCN = 2210 cm−1
;
2
νC=O = 1740 cm−1; νP=O = 1260 cm−1; ESI-MS: m/z = 458.449([M + H]+).
1
3ꢀe: Oil; 31P NMR (121.5 MHz, CDCl3): δ = 17.7 ppm; H NMR (300 MHz, CDCl3): δ =
0.75–1.28 (m; 12H; 4 CH3–CH2–O); 4.15–4.56 (m; 10H; 4 CH3–CH2–O and CH2–CO2Et);
5.03 (broad s; 2H; NH2); 13C NMR (75.5 MHz, CDCl3): δ (JCP): 12.9 (CH3–CH2O2C–CH2–
); 13.1 (4.5 Hz; CH3–CH2–O–P); 17.2 (CH3–CH2–O2C); 28.5 (24.6 Hz; CH2–CO2Et); 60.7
(CH3–CH2O2C–CH2); 64.0 (6.0 Hz; CH3–CH2–O–P); 67.0 (CH3–CH2–O2C); 109.5 (113.0 Hz;
P–C–S); 114.4 (C–CO2Et); 129.5 (C–CH2–CO2Et); 156.0 (C–NH2); 157.0 (CH2–CO2Et), 167.8
(CO2Et); IR (neat): νNH = 3338–3444 cm−1; νCN = 2222 cm−1; νC=O = 1740 cm−1; νP=O
=
2
1270 cm−1; ESI-MS: m/z = 394.363([M + H]+).
3ꢀf: Oil; 31P NMR (121.5 MHz, CDCl3): δ = −8.7 ppm; 1H NMR (300 MHz, CDCl3): δ = 1.20
3
(t; 3H; JHH = 6.0 Hz; CH3–CH2–O); 3.46–4.71 (m; 8H; CH3–CH2–O, CH2–CO2Et and –O–
CH2–CH2–O–); 5.79 (broad s; 2H; NH2) 13C NMR (75.5 MHz, CDCl3): δ (JCP): 13.2 (CH3); 28.2
(23.4 Hz; CH2–CO2Et); 59.2 (CH3–CH2–O); 66.4 (6.0 Hz; –O–CH2–CH2–O); 97.6 (C–CN); 96.0
(150.0 Hz; P–C–S); 105.6 (CN); 151.1 (9.1 Hz; C–CH2–CO2Et); 161.9 (C–NH2); 165.1 (C = O);
IR (neat): νNH = 3320–3430 cm−1; νCN = 2210 cm−1; νC=O = 1740 cm−1; νP=O = 1240 cm−1
;
2
ESI-MS: m/z = 317.252([M + H]+).
1
3ꢀg: m.p. = 88◦C; 31P NMR (121.5 MHz, CDCl3): δ = −14.6 ppm; H NMR (300 MHz,
3
CDCl3): δ = 1.22 (t; 3H; JHH = 6.0 Hz; CH3–CH2–O); 2.37 (s; 6H; 2CH3); 3.87 (d; 4H;
3JPH = 9.0 Hz; 2 CH2–O–P); 4.07 (s; 2H; CH2–CO2E); 4.05–4.12 (m; 2H; CH3–CH2–O); 5.78
(broad s; 2H; NH2); 13C NMR (75.5 MHz, CDCl3): δ (JCP): 13.2 (CH3–CH2O2C); 20.6 (2
CH3): 28.3 (Me2C); 31.2 (6.0 Hz; CH2–CO2Et); 57.4 (CH3–CH2–O); 66.9 (6.0 Hz; 2 CH2–O–P);
89.0 (C–CN); 104.9 (135.0 Hz; P–C–S); 111.2 (CN); 131.9 (C–CH2–CO2Et); 146.7 (C–NH2);
165.1 (C = O); IR (neat): νNH = 3215–3336 cm−1; νCN = 2222 cm−1; νC=O = 1732 cm−1
;
2
νP=O = 1230 cm−1; ESI-MS: m/z = 359.342([M + H]+).
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