Synthesis, spectral characterization and antimicrobial activity of novel 5-[(substituted) methyl]-5-oxo-1, 3, 2λ4, 5λ 5-dioxaselena phosphinan-2-ones

Article abstract of DOI:10.3987/COM-10-11910

A series of novel 5-[(substituted) methyl]-5-oxo-1,3,2λ⁴, 5λ⁵-dioxa selenaphosphinan-2-ones (4-17) were successfully synthesized from tris(bromomethyl)phosphine oxide (1) and sodium selenite (2) to form the intermediate(3) which on further treatment with various alcohols/thiols/phenols/aminoacid esters afforded the title compounds (4-17) and their structures were established by multinuclear NMR (¹H-, ¹³C-and³¹P-) and mass spectral data. Their antimicrobial activity was evaluated and they exhibited promising antibacterial activity. The Japan Institute of Heterocyclic Chemistry.

Full text of DOI:10.3987/COM-10-11910

HETEROCYCLES, Vol. 81, No. 5, 2010
1183
HETEROCYCLES, Vol. 81, No. 5, 2010, pp. 1183 - 1192. © The Japan Institute of Heterocyclic Chemistry
Received, 16th January, 2010, Accepted, 25th February, 2010, Published online, 1st March, 2010
DOI: 10.3987/COM-10-11910
SYNTHESIS,
SPECTRAL
CHARACTERIZATION
AND
ANTIMICROBIAL ACTIVITY OF NOVEL 5-[(SUBSTITUTED)
METHYL]-5-OXO-1, 3, 2λ4, 5λ5–DIOXASELENA PHOSPHINAN-2-ONES
S. Subba Reddy, B. Satheesh Krishna, V. Koteswara Rao, and C. Naga Raju*
Department of Chemistry, Sri Venkateswara University, Tirupati-517 502, India.
E-mail:naga_raju04@yahoo.co.in
Abstract – A series of novel 5-[(substituted) methyl]-5-oxo-1,3,2λ4,5λ5-dioxa
selenaphosphinan-2-ones (4-17) were successfully synthesized from
tris(bromomethyl)phosphine oxide (1) and sodium selenite (2) to form the
intermediate(3) which on further treatment with various alcohols/ thiols/ phenols/
aminoacid esters afforded the title compounds (4-17) and their structures were
13
31
established by multinuclear NMR (1H-, C- and P-) and mass spectral data.
Their antimicrobial activity was evaluated and they exhibited promising
antibacterial activity.
INTRODUCTION
Six-membered phosphorus heterocycles containing O, N as hetero atoms and P as P=O (S) have been the
subject of research ever since cyclophosphamide [2-bis-2-(2-chloroethyl)amino]-2H-[1,3,2]-
oxazaphosphorinane-2-oxide was discovered as an anti-cancer drug.1, 2 Success of cyclophosphamide as
an anti-cancer drug led to the synthesis of several [1,3,2]-oxazaphosphorinane derivatives. Schmidt et al3
synthesized two new compounds 2-[bis(2-chloroethyl)amino]-2,3-dioxo-7-thia-1-aza-2-phosphobicyclic[4.4.0]-
decane and [4.3.0] nonane in their search for less toxic potential antitumor agents. 4-Carbonyl and 4-aryl
cyclophosphamides were synthesized by Takamizawa4 and Shin5 respectively. 3-Cyclohexyl-6-(1,1-dimethyl)-
3,4-dihydro-2-substituted-2H-[1,3,2]benzoxazaphosphorin-2-oxides were found to possess high antitumor
activity.6 Their 4-bromophenyl and naphthyl substituted analogues also exhibited significant
bioactivity.7 Even though several compounds related to six membered phosphorus heterocycles have been
synthesized, none of them was found to possess satisfactory pharmacological properties. Hence the search
continued for the development of potential bioactive molecule from six membered phosphorus

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HETEROCYCLES, Vol. 81, No. 5, 2010
heterocycles. In the present investigation, we have made an attempt and synthesized first time
successfully novel six-membered heterocyclic compounds containing Se and P. A series of novel
5-[(substituted)methyl]-5-oxo-1,3,2λ4,5λ5-dioxa selena phosphinan-2-ones were successfully synthesized
and their structures were established by elemental analyses, multinuclear NMR (1H, 13C and 31P) and
mass spectral data and their antimicrobial activity was evaluated.
RESULTS AND DISCUSSION
CHEMISTRY
To a cooled (10 °C) and stirred solution of sodium selenite 2 in 20 mL of dry THF, a solution of
tris(bromomethyl)phosphine oxide 1 in 10 mL of dry THF was added over a period of twenty minutes.
After completion of addition, the temperature of the reaction mixture was raised to room temperature and
stirred for one hour to form the intermediate 3 and sodium bromide salt was removed. The filtrate was
further treated with various alcohols/ thiols/ phenols/ amino acid esters in the presence of triethylamine to
obtain the title compounds 4-17 as shown in Scheme 1 and Table 1.
O
O
Se 2
Se
1
O
Br
Br
Br
O
O
HR
O
O 3
4
THF
O
P
O
P
+
O
+ Et3N.HBr
Se
0-40°C
-2NaBr
TEA
6
P
ONa
NaO
5
Br
7
R
2
1
3
4-17
Scheme 1
The title compounds exhibited P=O, Se=O and P-C stretching frequencies in the region(s) 1234-1254,
1
1201-1220 and 742-756 cm-1 respectively.8-11 In H NMR spectra of 4-17 the chemical shifts of the
aromatic protons showed complex multiplets9 in the region(s) 6.94-8.02 ppm. The methylene protons
appeared as multiplets in the region(s) δ 2.54-5.02. The amino acid esters were observed in the expected
region(s).8, 11 The 13C NMR chemical shifts for aromatic skeleton were observed in the range of 115.1-164.4
ppm. The methylene carbons which are directly linked to phosphorus experienced coupling with it and
resonated as doublets in the region(s) 54.10-54.30 (d, J = 126-132 Hz).12 The 31P NMR chemical shifts of
title compounds were appeared in the region(s) 19.23-24.39 ppm as singlets.13,14

HETEROCYCLES, Vol. 81, No. 5, 2010
1185
Table 1. Synthesis of title compounds 4-17
Entry
4
R
Entry
11
R
11
10
8
12
9
O
NO2
OH
O
13
11
14
10
11
12
10
H
COOCH2CH3
8
9
12
9
12
N
O
Cl
8
6'
1'
13
5'
14
2'
5
6
4'
3'
10
11
9
10
H
COOCH3
CH2 CH2 Cl
9
8
N
N
13
14
8
6'
1'
CH2 CH2 Cl
5'
11
12
2'
4'
3'
12
11
N
8
9
10
10
16
11
8
14
9
17
7
8
N
N
CH3
COOCH125
18
13
14
12
13
19
20
17
H
N15
16
18
19
14
15
21
12
H
13
20
NH2
H
9
11
N
10
N
9
8
8
COOCH3
10
11
H
16 N
18
17
19
20
15
9
16
17
22
13
14
21
H
NH2
9
11
N
9
S
10
8
COOCH2CH3
8
10
11
12
1C3 H3
H
N
H
10
OH
9
C
CH CH3
11
S
8
9
12
10
14
8
COOCH3
10
11
BIOLOGICAL ACTIVITY
Antibacterial Activity
All the compounds 4-17 were screened for their antibacterial activity against the growth of
Staphylococcus aureus and Escherichia coli at three concentrations15,16 of 100 g / disc, 50 g / disc and
25 g / disc. All the compounds 4-17 showed moderate to high antibacterial activity against both the
bacteria when compared with that of the standard. These results are presented in Table 2. The title
compounds exhibited very significant antibacterial activity when compared to similar six-membered
phosphorus heterocycles.17

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HETEROCYCLES, Vol. 81, No. 5, 2010
Table 2. Antibacterial Activitya of compounds 4-17 in terms of zone inhibition (mm)
Zone of inhibition (mm)
Entry
Escherichia coli (μg / disc)
Staphylococus aureus (μg / disc)
100a
23
23
23
22
22
21
20
19
21
20
19
20
19
19
50a
11
10
12
10
11
13
11
10
10
12
10
10
10
12
12
25a
100a
24
25
24
24
22
19
20
18
20
19
18
18
18
16
20
50a
11
11
10
10
9
25a
4
6
7
5
4
6
6
5
6
7
6
5
8
5
6
9
4
11
11
10
9
5
10
11
12
13
14
15
16
17
5
5
5
5
6
6
6
8
8
5
10
9
7
7
6
6
10
10
10
7
5
7
Penicillin 20
6
8
a Concentrations expressed in ppm
Antifungal Activity
All the compounds 4-17 were tested for their anti fungal activity against the growth of Aspergillus niger
and Helminthosporium oryzae at three concentrations 100 µg / disc 50, 25 µg/disc.18 When compared
with the reference compound Griseofulvin, the title compounds exhibited moderate to high activity
against the growth of both the fungi at three different concentrations. The results are furnished in Table 3.
Compounds 4-17 showed very promising antifungal activities when compared to similar six-membered
phosphorus heterocycles.17,19

HETEROCYCLES, Vol. 81, No. 5, 2010
1187
Table 3. Antifungal Activitya of compounds 4-17 in terms of zone inhibition (mm)
Zone of inhibition (mm)
Entry
Aspergillus niger (μg / disc)
Helminthosporium oryzae (μg /
disc)
100a
50a
25a
100a
50a
25a
4
5
15
10
7
14
9
5
19
19
20
18
21
20
19
20
18
19
18
18
18
20
9
6
5
4
6
6
5
4
7
6
6
5
5
6
5
15
14
14
13
19
20
18
13
19
14
15
14
16
20
7
6
3
6
5
4
7
6
5
4
8
7
7
5
7
5
6
10
12
11
11
10
9
7
9
8
7
9
10
11
10
8
10
11
12
11
12
10
11
10
10
10
13
12
10
9
14
15
16
17
10
11
10
Griseofulvin
aConcentrations expressed in ppm
EXPERIMENTAL
Chemicals were obtained from Sigma-Aldrich, used as such without further purification. All solvents (AR
or extra pure grade) used for spectroscopic and other physical studies were further purified by literature
methods. All operations were performed under nitrogen atmosphere using standard glasswares. Melting
points were determined using a calibrated thermometer by Guna Digital Melting Point apparatus.
Elemental analyses were performed by Thermo Finnigan Flash EA 1112 at University of Hyderabad,
1
Hyderabad. IR Spectra were recorded with Nicolet 380 FT-IR spectrophotometer. H and 13C NMR

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HETEROCYCLES, Vol. 81, No. 5, 2010
spectra were recorded as solutions in DMSO-d6 on a Bruker AMX 400 MHz spectrometer operating at
400 MHz for 1H, 100 MHz for 13C, 161.9 MHz for 31P and 76.2 MHz for 77Se. The 1H and 13C chemical
31
77
shifts were referenced to tetramethylsilane, P chemical shifts to 85% H3PO4 and Se Chemical shifts
were referenced to dimethylselenium in CFCl3. LC mass spectra were recorded on a Jeol SX 102 DA /
600 Mass Spectrometer.
Tris(bromomethyl)phosphine oxide (1):
Tris(bromomethyl)phosphine oxide (1) was prepared by following the literature procedure.20
5-[(1-Bromo)methyl]-5-oxo-1, 3, 2λ4, 5λ5-dioxaselenaphosphinan-2-one (3).
To a cooled (10 °C) and stirred solution of sodium selenite (2, 0.86 g, 0.005 mole) in 50 mL of dry THF,
a solution of tris(bromomethyl) phosphineoxide (1, 1.43 g, 0.005 mole) in 15 mL of dry THF was added
dropwise over a period of 20 min. After completion of the addition, the temperature of the reaction
mixture was raised to room temperature and stirred for 1 h to form 5-[(1-bromo)methyl]-5-oxo-
1,3,2λ4,5λ5-dioxaselenaphosphinan-2-one 3. After completion of the reaction, sodium bromide was
separated by filtration and the solvent was removed from the filtrate in a rota-evaporator. Then the
resulted crude product was recrystallized from 2-propanol to obtain the compound-3. The progress of the
1
reaction was judged by the TLC analysis. Yield: 69% (1.01 g), H NMR (DMSO-d6) : 3.68 (m, 4H,
P-CH2-O-), 3.34 (m, 2H, P-CH2-Br). LCMS (%): 295 [M+] (100), 297 [M+2] (97).
5-[(4-Nitrophenoxy)methyl]-5-oxo-1,3,2λ4,5λ5-dioxaselenaphosphinan-2-one (4).
To the intermediate 3 (1.01 g, 0.003 mole), p-nitrophenol (0.42 g, 0.003 mole) in dry THF (10 mL) was
added in the presence of triethylamine at 10-15 °C over a period of 30 min. After the addition,
temperature of the reaction mixture was slowly raised to 30-35 °C and continued stirring. The progress of
the reaction was monitored by the TLC analysis (EtOAc: hexane 1:2). After completion of the reaction,
Et3N:HBr was separated by filtration and the solvent was removed from the filtrate in a rota-evaporator.
The resulting crude product was recrystallized from 2-propanol to obtain pure compound of 4. Yield 1.18
g, 67%: mp 161-163 °C. The same procedure was adopted for the preparation of other compounds 5-17.
Physical, Analytical and Spectral data for the compounds 4-17.
5-[(4-Nitrophenoxy)methyl]-5-oxo-1,3,2λ4,5λ5-dioxaselenaphosphinan-2-one (4).
Yield 67%, mp 161-163 °C, IR (KBr): νmax 1243 (P=O), 1201 (Se=O), 742 cm-1(P-Calip). 77Se NMR
(CDCl3) δ: 1289. 31P NMR (85%, H3PO4) δ: 21.62. 1H NMR (DMSO-d6) : 7.01-7.85 (m, 4H, Ar–H), 5.01
(m, 2H, P-CH2-O-Ar), 3.69 (m, 4H, P-CH2-O). 13C NMR : 54.3 (d, J = 127 Hz) C4 and C6, 55.7 (d, J =
127 Hz) C7, 164.4 C9, 115.1 C10 and C14, 126.7 C11 and C13, 142.2 C12. Anal. Calcd for C9H10NO7PSe: C

HETEROCYCLES, Vol. 81, No. 5, 2010
1189
30.53, H 2.85, N 3.96. Found: C 30.49, H 2.82, N 3.95%. LCMS(%): 354 [M+, 50], 341 (100), 327 (67),
314 (17), 226 (39), 134 (7).
5-[(4-Chlorophenoxy)methyl]-5-oxo-1,3,2λ4,5λ5-dioxaselenaphosphinan-2-one (5).
77
Yield 69%, mp 168-169 °C, IR (KBr): ν
1240 (P=O), 1213 (Se=O), 745 cm-1(P-Calip). Se NMR
max
(CDCl3) δ: 1295. 31P NMR (85%, H3PO4) δ: 19.27. 1H NMR(DMSO-d6) : 7.02-7.46 (m, 4H, Ar–H), 5.02
13
(m, 2H, P-CH2-O-Ar), 3.82 (m, 4H, P-CH2-O). C NMR : 54.1 (d, J = 126 Hz) C4 and C6, 55.2 (d, J =
129 Hz) C7, 159 C9, 116 C10 and C14, 131 C11 & C13, 128 C12. Anal. Calcd: for C9H10ClO5PSe. C 31.46, H
2.93. Found: C 31.42, H 2.89 %. LCMS(%): 343 [M+, 28], 297 (45), 260 (31), 223 (100), 187 (23), 150 (45),
125 (66), 98 (39).
5-[(Bis(2-chloroethyl)amino)methyl]-5-oxo-1,3,2λ4,5λ5-dioxaselenaphosphinan-2-one (6).
Yield 68%, mp 168-170 °C. IR (KBr): νmax 1234 (P=O), 1209 (Se=O), 747 cm-1(P-Calip). 77Se NMR
(CDCl3) δ: 1288. 31P NMR (85%, H3PO4) δ: 22.19. 1H NMR (DMSO-d6) : 4.05 (m, 4H, P-CH2-O-), 3.65
(m, 2H, P-CH2-N), 2.84 (t, J= 8.2 Hz, 4H, NCH2-CH2), 2.54 (t, J = 7.8 Hz, 4H, NCH2-CH2-Cl). 13C NMR
: 54.1 (d, J = 126 Hz) C4 and C6, 55.3 (d, J = 129 Hz) C7, 59.2 C9 and C11, 43.5 C10 and C12 . Anal. Calcd:
for C7H14NO4Cl2PSe; C 23.55, H 3.95, N 3.92. Found: C 23.50, H 3.88%, N 3.90. LCMS (%): 360 [M+4],
358[M+2], 356[M+, 37], 301 (51), 282 (22), 251 (65), 164 (100), 151 (33), 136 (41), 86 (19).
5-[(N-Methylpiperazino)methyl]-5-oxo-1,3,2λ4,5λ5-dioxaselenaphosphinan-2-one (7). Yield 71%, mp
160-161 °C. IR (KBr): ν
1245 (P=O), 1219 (Se=O), 744 cm-1(P-Calip). 77Se NMR (CDCl3) δ: 1299. 31P
max
NMR (85%, H3PO4): δ 23.19. 1H NMR (DMSO-d6):  4.05 (m, 4H, P-CH2-O-), 3.65 (m, 2H, P-CH2-N),
2.62 (t, J= 7.5 Hz, 4H, NCH2-CH2), 2.54 (t, J= 8.2 Hz, 4H, NCH2-CH2), 2.32 (s, 3H, N-CH3). 13C NMR:
 54.1 (d, J = 127 Hz) C4 and C6, 55.2 (d, J = 128 Hz) C7, 52 C9 and C13, 57 C10 and C12, 44 C14. Anal.
Calcd: for C8H17N2O4PSe: C 30.49, H 5.44, N 8.89. Found: C 30.45, H 5.41, N 8.86%. LCMS (%): 315
[M+, 31], 287 (100), 263 (52), 224 (25), 152 (74), 138 (33), 114 (41), 75 (16).
5-[(2-Aminoethylamino)methyl]-5-oxo-1,3,2λ4,5λ5-dioxaselenaphosphinan-2-one (8).
Yield 68%, mp 151-153 °C. IR (KBr): νmax 3409 (N-H), 1239 (P=O), 1211 (Se=O), 746 cm-1(P-Calip). 77Se
NMR (CDCl3) δ: 1305. 31P NMR (85% H3PO4): δ 24.33. 1H NMR (DMSO-d6):  5.4 (m, 1H, NH), 4.81 (t,
2H, J = 7.8 Hz, NH2), 4.05 (m, 4H, P-CH2-O-), 3.65 (m, 2H, P-CH2-N), 2.83 (m, 2H, -NHCH2-CH2), 2.79
(m, 2H, -CH2NH2).13C NMR:  54.2 (d, J = 128 Hz) C4 and C6, 55.1 (d, J = 126 Hz) C7, 52 C9 , 41 C10.
Anal. Calcd: for C5H13N2O4PSe: C 21.83, H 4.76, N 10.18. Found: C 21.78, H 4.72, N 10.17%. LCMS
(%): 275 [M+, 28], 234 (64), 207 (32), 169 (100), 137 (47), 103 (58), 74 (81).
5-[(2-Aminoethylsulfanyl)methyl]-5-oxo-1,3,2λ4,5λ5-dioxaselenaphosphinan-2-one (9).
Yield 73%, mp 163-165 °C. IR (KBr): νmax 3417 (N-H), 1235 (P=O), 1215 (Se=O), 749 cm-1(P-Calip). 77Se

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HETEROCYCLES, Vol. 81, No. 5, 2010
NMR (CDCl3) δ: 1302. 31P NMR (85%, H3PO4) δ: 21.45, 1H NMR (DMSO-d6) : 4.82 (t, 2H, J = 7.6 Hz,
NH2), 4.06 (m, 4H, P-CH2-O-), 3.64 (m, 2H, P-CH2-S), 2.83 (t, J = 7.6 Hz, 2H, -SCH2-CH2), 2.76 (m, 2H,
-CH2NH2). 13C NMR : 54.1 (J = 126 Hz) C4 & C6, 55.2 (J = 128 Hz) C7, 53 C9 , 42 C10. Anal. Calcd: for
C5H12NO4PSSe; C 20.56, H 4.14, N 4.79. Found: C 20.52, H 4.13, N 4.78%. LCMS (%): 292 [M+].
5-[(2-Hydroxyethylsulfanyl)methyl]-5-oxo-1,3,2λ4,5λ5-dioxaselenaphosphinan-2-one (10).
Yield 71%, mp 173-175 °C. IR (KBr): νmax 3417 (O-H), 1254 (P=O), 1208 (Se=O), 747 cm-1(P-Calip). 77Se
NMR (CDCl3) δ: 1288. 31P NMR (85%, H3PO4) δ: 23.43. 1H NMR (DMSO-d6) : 4.82 (t, 1H, J = 7.8 Hz,
OH), 4.06 (m, 4H, P-CH2-O-), 3.64 (m, 2H, P-CH2-S), 2.83 (t, J = 7.4 Hz, 2H, -S-CH2-CH2), 2.76 (t, J =
7.4 Hz, 2H, -S-CH2-CH2). 13C NMR : 54.2 (J = 127 Hz) C4 and C6, 55.2 (J = 128 Hz) C7, 52 C9 , 41 C10,
Anal. Calcd: for C5H11O5PSSe: C 20.49, H 3.78. Found: C 20.44, H 3.76%. LCMS (%): 293 [M+].
5-[(2-Hydroxyethoxy)methyl]-5-oxo-1,3,2λ4,5λ5-dioxaselenaphosphinan-2-one (11).
Yield 67%, mp 167-168 °C. IR (KBr): νmax 3432 (O-H), 1244 (P=O), 1212 (Se=O), 745 cm-1(P-Calip). 77Se
NMR (CDCl3) δ: 1298. 31P NMR (85% H3PO4) δ: 22.22.1H NMR (DMSO-d6) : 4.80 (t, 1H, J = 7.8 Hz,
OH), 4.07 (m, 4H, P-CH2-O-), 3.62 (m, 2H, P-CH2-O), 3.84 (t, J = 8.4 Hz, 2H, -CH2-OH), 3.56 (t, J = 8.2
Hz, 2H, O-CH2-CH2) 2.76 (t, J = 7.4 Hz, 2H, -O-CH2-CH2). 13C NMR : 54.2 (d, J = 128 Hz) C4 and C6,
55.1 (d, J = 126 Hz) C7, 52.4 C9, 41.7 C10. Anal. Calcd: for C5H11O6PSe: C 21.68, H 4.00. Found: C 21.62,
H 3.98%. LCMS (%): 277 [M+].
5-[(Phenyl glycine ethyl ester)methyl]-5-oxo-1,3,2λ4,5λ5-dioxaselenaphosphinan-2-one (12).
25
Yield 71%, mp 179-181 °C.


D -120.8o; IR (KBr): νmax 3392 (NH), 1678 (C=O), 1238 (P=O), 1217
(Se=O), 747 cm-1(P-Calip). 77Se NMR (CDCl3) δ: 1310. 31P NMR (85%, H3PO4) δ: 19.23.1H NMR
(DMSO-d6) : 7.09-7.49 (m, 5H, Ar-H), 4.69 (q, 1H, NH), 4.07 (m, 4H, P-CH2-O-), 3.62 (m, 2H,
P-CH2-NH), 3.68 (q, 2H, O-CH2-CH3), 1.14 (t, (J = 10.2 Hz, 3H, O-CH2-CH3). 13C NMR : 54.2 (d, J = 128
Hz) C4 and C6, 55.2 (d, J = 132 Hz) C7, 67.7 C9, 172.1 C10, 62.2 C11, 17.6 C12, 135.8 C11, 129.8 C21 and C61,
1
1
129.1 C3 and C51, 127.6 C4 . Anal. Calcd: for C13H18NO6PSe; C 39.61, H 4.60, N 3.55. Found: C 39.57, H
4.59, N 3.52%. LCMS (%): 394 [M+].
5-[(Phenyl glycine methyl ester)methyl]-5-oxo-1,3,2λ4,5λ5-dioxaselenaphosphinan-2-one (13).
25
Yield 70%, mp 174-176 °C.


D -122.5o; IR (KBr): νmax 3404 (NH), 1687 (C=O), 1252 (P=O), 1210
(Se=O), 749 cm-1(P-Calip). Se NMR (CDCl3) δ: 1307. 31P NMR (85%, H3PO4) δ: 19.48. H NMR
77
1
(DMSO-d6) : 7.09-7.49 (m, 5H, Ar-H), 4.69 (q, 1H, NH), 4.07 (m, 4H, P-CH2-O-), 3.62 (m, 2H,
13
P-CH2-NH), 3.68 (s, 3H, O-CH3), 2.29 (d, J = 10.2 Hz, 1H, CH-CO). C NMR:  54.2 (d, J = 126 Hz) C4
and C6, 55.1 (d, J = 130 Hz) C7, 67.6 C9, 172.5 C10, 62.1C11, 135.7 C11, 129.9 C21 and C61, 129.0 C31 and C51,

HETEROCYCLES, Vol. 81, No. 5, 2010
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1
127.8 C4 Anal. Calcd: for C12H16NO6PSe: C 37.91, H 4.24, N 3.68. Found: C 37.85, H 4.23, N 3.64%.
LCMS (%): 380 [M+].
5-[(Proline ethyl ester)methyl]-5-oxo-1,3,2λ4,5λ5-dioxaselenaphosphinan-2-one (14).
25
Yield 68%, mp 168-170 °C.


D -119.3o; IR (KBr): νmax 1687 (C=O), 1237 (P=O), 1214 (Se=O), 756
77
31
1
cm-1(P-Calip). Se NMR (CDCl3) δ: 1312. P NMR (85%, H3PO4) δ: 24.39. H NMR (DMSO-d6) :
7.07-7.48 (m, 5H, Ar-H), 4.07 (m, 4H, P-CH2-O-), 3.62 (m, 2H, P-CH2-NH), 3.69 (s, 2H, O-CH2-Ar), 2.29
(d, J = 10.2 Hz, 1H, CH-CO), 1.91-2.02 (m, 2H, CH2), 1.64-1.79 (m, 2H, CH2), 2.02-2.21 (t, 2H, CH2).13C
NMR : 54.2 (d, J = 128 Hz) C4 and C6, 55.2 (d, J = 132 Hz) C7, 66.8 C9, 29.8 C10 22.7 C11, 57.6 C12, 171.6
1
1
1
C13, 63.1 C14, 135.8 C11 , 129.8 C2 and C61, 129.1 C3 and C51, 127.6 C4 . Anal. Calcd: for C15H20NO6PSe:
C 42.87, H 4.80, N 3.33 Found: C 42.82, H 4.77, N 3.30 %. LCMS (%): 420 [M+].
5-[(Tryptophan methyl ester)methyl]-5-oxo-1,3,2λ4,5λ5-dioxaselenaphosphinan-2-one (15). Yield
25
69%, mp 178-180 °C.


D -116.4o; IR (KBr): νmax 3396 (NH), 1677 (C=O), 1248 (P=O), 1217 (Se=O),
747 cm-1(P-Calip). 77Se NMR (CDCl3) δ: 1318. 31P NMR (85%, H3PO4) δ: 24.27. 1H NMR (DMSO-d6) :
10.21 (br s, 1H, Ar-NH), 6.94-7.67 (m, 5H, Ar-H), 4.72 (q, 1H, NH), 4.07 (m, 4H, P-CH2-O-), 3.69 (t, 2H,
CH2-Ar), 3.62 (m, 2H, P-CH2-NH), 3.68 (s, 3H, O-CH3), 2.29 (d, J = 10.2 Hz, 1H, CH-CO). M.F:
C15H19N2O6PSe: Anal. Calcd: C 41.58, H 4.42, N 6.47. Found: C 41.54, H 4.40, N 6.43%. LCMS (%):
433 [M+].
5-[(Tryptophan ethyl ester)methyl]-5-oxo-1,3,2λ4,5λ5-dioxaselenaphosphinan-2-one (16).
25
Yield 71%, mp 169-171 °C.


D -123.5o; IR (KBr): νmax 3392 (NH), 1678 (C=O), 1244 (P=O), 1220
(Se=O), 749 cm-1(P-Calip). 77Se NMR (CDCl3) δ: 1310. 31P NMR (85%, H3PO4) δ: 24.27. 1H NMR (DMSO-d6)
:10.11 (br s, 1H, Ar-NH), 6.94-7.67 (m, 5H, Ar-H), 4.72 (q, 1H, NH), 4.07 (m, 4H, P-CH2-O-), 3.69 (t, 2H,
CH2-Ar), 3.62 (m, 2H, P-CH2-NH), 2.29 (d, J = 10.2 Hz, 1H, CH-CO), 3.68 (q, 2H, O-CH2-CH3), 1.14 (t, J =
10.2 Hz, 3H, O-CH2-CH3). Anal. Calcd: for C16H21N2O6PSe: C 42.97, N 4.73, H 6.26. Found: C 42.94, N
4.70, H 6.25%. LCMS (%): 447 [M+].
5-[(Valine methyl ester)methyl]-5-oxo-1,3,2λ4,5λ5-dioxaselenaphosphinan-2-one (17).
25
Yield 70%, mp 177-178 °C.


D -124.9o; IR (KBr): νmax 3399 (NH), 1678 (C=O), 1251 (P=O), 1210
77
31
1
(Se=O), 745 cm-1(P-Calip). Se NMR (CDCl3) δ: 1315. P NMR (85%, H3PO4) δ: 24.29. H NMR
(DMSO-d6) : 4.07 (m, 4H, P-CH2-O-), 3.62 (m, 2H, P-CH2-NH), 4.72 (q, 1H, NH), 2.29 (d, J = 10.2 Hz,
1H, CH-CO), 3.68 (q, 2H, O-CH3), 2.10 (m, 1H, CH(CH3)2), 1.17 (t, J = 7.2 Hz, 6H, CH(CH3)2). Anal.
Calcd for C9H18NO6PSe: C 31.23, H 5.24, N 4.05. Found: C 31.18, N 5.21, H 4.04%. LCMS (%): 346
[M+].

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HETEROCYCLES, Vol. 81, No. 5, 2010
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