Synthesis and characterization of new O, O-Diethyl phosphorothioates derived from substituted tetrazolo [1, 5-a] Quinolin- 4-Ylmethanol derivatives

Article abstract of DOI:10.1002/hc.20570

A simple and convenient method is developed for the synthesis of new O, O-diethyl 0-(substituted tetrazolo[1, 5-a] quinolin-4-yl) methyl phosphorothioates, which has been synthesized for the first time from tetrazolo [1,5-a] quinolines via tetrazolo [1,5-a] quinolin-4-ylmethanol derivatives. The structures of the all newly synthesized compounds were elucidated by analytical and spectral methods.

Full text of DOI:10.1002/hc.20570

Heteroatom Chemistry
Volume 20, Number 7, 2009
S
ynthesis and Characterization of New
O,O-Diethyl Phosphorothioates Derived from
Substituted Tetrazolo[1,5-a]Quinolin-
4
-Ylmethanol Derivatives
Amol H. Kategaonkar, Rajkumar U. Pokalwar, Sandip A. Sadaphal,
Pravin V. Shinde, Bapurao B. Shingate, and Murlidhar S. Shingare
Department of Chemistry, Dr. Babasaheb Ambedkar Marathwada University, Aurangabad 431 004,
Maharashtra, India
Received 14 August 2009
pesticides [3]. Phosphorodithioates have been the
ABSTRACT: A simple and convenient method
subject matter of several investigations involving
various applications including antiviral compounds
is developed for the synthesis of new O,O-diethyl
O-(substituted tetrazolo[1,5-a]quinolin-4-yl)methyl
[4], plant growth regulators [5], inhibitors of num-
phosphorothioates, which has been synthesized
for the first time from tetrazolo[1,5-a] quinolines
via tetrazolo[1,5-a]quinolin-4-ylmethanol derivatives.
The structures of the all newly synthesized compounds
were elucidated by analytical and spectral methods.
ber different enzymes [6], and as lubricants [7]. In
recent years, a number of phosphorodithioates have
been introduced as thionating agents [8,9]. Despite
their wide range of pharmacological activity, in-
dustrial and synthetic applications, the synthesis of
phosphorodithioates has received little attention.
Schrader-Clark [10] proposed that organophospho-
rus compounds containing the general structure
ꢀ
2
C
2010 Wiley Periodicals, Inc. Heteroatom Chem
0:436–441, 2009; Published online in Wiley InterScience
(
www.interscience.wiley.com). DOI 10.1002/hc.20570
(
A) might have significant biological activity. All
organophosphorus compounds are inherently good
phosphorylating agents of enzymes by virtue of the
group P-XYZ in the general structure (A).
INTRODUCTION
Organophosphorus compounds have found a wide
range of applications in the areas of industrial,
agricultural, and medicinal chemistry owing to their
biological and physical properties as well as their
utility as synthetic intermediates [1]. The synthesis
of phosphate esters is an important objective in
organic synthesis, since they have found use in the
preparation of biologically active molecules and are
also versatile intermediates in synthesis of amides
and esters [2]. Among the phosphate esters, phos-
phorodithioate derivatives are of interest as effective
Slight variation in structure can have very dramatic
effects on the efficiency of organophosphorus com-
pounds in bioactivity. These chemically and biolog-
ically variable parameters that are hard to estimate
and are involved in deciding “structure–activity” re-
lationship of these compounds.
Correspondence to: M. S. Shingare; e-mail: prof msshingare@
Phosphorothioates are commonly synthesized
by reaction of dialkyl phosphites with sulfenyl
rediffmail.com
ꢀ
c 2010 Wiley Periodicals, Inc.
436

Synthesis and Characterization of New O,O-Diethyl Phosphorothioates 437
SCHEME 1 Synthesis of new O,O-diethyl phosphorothioates (4a–i).
chlorides [11], sulfenyl cyanides [12], thiosulfonates
13], disulfides [14] and sulfur [15], as well as by con-
densation of phosphorochloridates with thiols [16].
All these methods suffer from some disadvantages,
including drastic reaction conditions and severe side
reactions.
Quinolines and their derivatives are important
constituents of pharmacologically active synthetic
compounds. The quinoline nucleus can also be
frequently recognized in the structure of numerous
naturally occurring alkaloids. They have been asso-
ciated with broad spectrum of biological activities
by the reaction of substituted 2-chloroquinoline-3-
carbaldehyde derivatives (1a–i) with sodium azide
in DMSO/AcOH mixture [26] as shown in Scheme 1.
Furthermore, we have done the carbonyl reduction
of compounds (2a–i) in the presence of sodium boro-
hydride in methanol at room temperature, affording
the corresponding alcohols (3a–i) in excellent yields
(75%–95%). When the synthesized tetrazolo[1,5-
a]quinolin-4-ylmethanol derivatives (3a–i) were
further treated with O,O-diethyl phosphorochlori-
dothioate in acetone in the presence of sodium hy-
droxide at room temperature afforded the corre-
sponding phosphorothioates (4a–i) in moderate to
good yields (62%–88%).
[
[17,18]. The fusion of quinoline to the tetrazole ring
is known to increase the biological activity. The
tetrazole group, which is considered as analogues
to the carboxylic group as a pharmacore, possesses
a wide range of biological activities. Several sub-
stituted tetrazoles have been shown to possess
anticonvulsant [19], anti-inflammatory [20], central
nervous system dispersant [21], antimicrobial [22],
anti-AIDS [23], and antifertility agents [24].
By considering all above-mentioned aspects, for
the first time we have synthesized the phosphoroth-
ioates in regard to develop our on going research
work [25].
Structures of the synthesized compounds (3a–i)
and (4a–i) were elucidated on the basis of the FT-IR,
1
13
H NMR, C NMR, and mass spectroscopic analy-
sis. Assignments of selected characteristic IR band
positions provide significant indication for the for-
mation of compounds (3a–i) and (4a–i). Compounds
(3a–i) showed intense bands in the region of 3311–
−
1
3367 cm corresponding to ν (O H) stretch, and
this region is absent in compounds (4a–i). Also the
compounds (4a–i) have showed intense bands in the
−
1
region of 1227–1250 cm corresponding to ν (P S)
−
1
stretch and 1017–1024 cm for ν (P O C) stretch,
which confirms the formation of desired compounds
RESULTS AND DISCUSSION
(4a–i). The aromatic protons of the compounds (3a–
In the present article, we report straightforward
and convenient synthesis of new O,O-diethyl phos-
phorousthioates containing highly bioactive tetra-
zole moiety. The key intermediate tetrazolo [1,5-a]
quinoline-4 carbaldehydes (2a–i) were prepared
i) and (4a–i) are in the region of 7.07–8.68 ppm
and 7.10–8.70 ppm, respectively. In H NMR, two
1
protons from Ar-CH position in compounds (3a–i)
2
have been observed at 4.92–5.21 ppm and in com-
pounds (4a–i) at 5.28–5.64 ppm. This confirms that
Heteroatom Chemistry DOI 10.1002/hc

438 Kategaonkar et al.
the conversion of CH
2
OH to CH
2
OP. The aro-
Tetrazolo[1,5-a]quinolin-4-ylmethanol
(3a).
◦
−1
matic carbons of compounds (3a–i) and (4a–i) are in
the region of 115.9–145.8 ppm and 105.5–158.9 ppm,
respectively.
In conclusion, we have developed a simple
and efficient procedure for the synthesis of new
O,O-diethyl phosphorothioates from tetrazolo[1,5-
a]quinolin-4-ylmethanol derivatives using O,O-
diethyl phosphorochloridothioate in the presence of
sodium hydroxide under mild conditions in short
time and with quantitative yields.
Yield 95%; mp 188–190 C; IR (KBr, ν /cm ): 3367
max
1
(O H); H NMR (200 MHz, CDCl , δ ppm): 5.15 (d,
3
2H, J = 2 Hz, Ar-CH ), 7.70 (t, 1H, J = 8, 14 Hz,
2
Ar-H), 7.84 (t, 1H, J = 8 Hz, Ar-H), 8.02 (d, 1H, J =
10 Hz, Ar-H), 8.06 (s, 1H, Ar-H), 8.86 (d, 1H, J =
13
8 Hz, Ar-H); C NMR (75 MHz, CDCl , δ ppm): 58.5
3
(OCH ), 115.9, 123.8, 127.0, 127.6, 127.9, 128.5,
2
129.1, 129.9, 145.8 (Ar-C); MS: m/z 201.2 (m + 1);
elemental analysis: C H N O Calcd.: C: 59.99; H:
10
8
4
4.03; N: 27.99; Found: C: 59.70, H: 4.12, N: 27.68.
(
7-Methyltetrazolo[1,5-a]quinolin-4-yl)methanol
EXPERIMENTAL
◦
(
3b). Yield 92%; mp 194–196 C; IR (KBr, νmax
/
−
1
1
All chemicals and solvents were purchased
from Merck (Darmstadt, Germany), Spectrochem
cm ): 3378 (O H); H NMR (200 MHz, CDCl3,
δ ppm): 2.6 (s, 3H, Ar-CH ), 2.86 (t, 1H, J = 6 Hz,
3
(Mumbai, India), Lancaster (Ward Hill, MA, USA),
OH), 5.21 (dd, 2H, J = 6 Hz, Ar-CH ), 7.66 (dd, 1H,
2
and S. D. Fine-chem (Mumbai, India). Melting
points were determined in open capillaries on
Kumar’s melting point apparatus (India), and are
uncorrected. IR spectra were recorded on JASCO
J = 8 Hz, Ar-H), 7.75 (s, 1H, Ar-H), 7.89 (s, 1H, Ar-
H), 8.59 (d, 1H, J = 8 Hz, Ar-H); MS: m/z 215.2 (m +
1); elemental analysis: C H N O Calcd.: C: 61.67;
11
10
4
H: 4.71; N: 26.15; Found: C: 61.58, H: 4.78, N: 26.28.
1
FT-IR 4100, Japan, using KBr disks. H NMR and
1
3
C NMR spectra were recorded on Bruker DRK-
00 and NMR spectrometer AC200. Mass spectra
(8-Methyltetrazolo[1,5-a]quinolin-4-yl)methanol
◦
3
(3c). Yield 81%; mp 200–202 C; IR (KBr, νmax/
−
1
1
were recorded on single-quadrupole mass detector
100, Waters. Elemental analyses were performed
cm ): 3345 (O H); H NMR (200 MHz, CDCl3,
3
δ ppm): 2.53 (s, 3H, Ar-CH ), 2.91 (t, 1H, J = 6 Hz,
3
on CHNS analyzer Flash 1112, Thermo Finnigan.
The progress of the reactions was monitored by
TLC on Merck silica plates. Results are presented
as, chemical shift δ in ppm, multiplicity, Jvalues in
Hertz (Hz), number of protons, proton’s position.
Multiplicities are shown as the abbreviations: s (sin-
glet), d (doublet), dd (doublet of doublet), dt (doublet
of triplet), t (triplet), q (quartet), and m (multiplet).
Solvents were commercially available reagent grade
materials.
OH), 5.33 (dd, 2H, J = 6 Hz, Ar-CH ), 7.58 (dd, 1H,
2
J = 8 Hz, Ar-H), 7.80 (s, 1H, Ar-H), 7.97 (s, 1H, Ar-
H), 8.67 (d, 1H, J = 8 Hz, Ar-H); MS: m/z 215.2 (m +
1); elemental analysis: C H N O Calcd.: C: 61.67;
11
10
4
H: 4.71; N: 26.15; Found: C: 61.72, H: 4.59, N: 26.24.
(9-Methyltetrazolo[1,5-a]quinolin-4-yl)methanol
◦
(3d). Yield 90%; mp 198–200 C; IR (KBr, νmax/
−
1
1
cm ): 3364 (O H); H NMR (200 MHz, CDCl3,
δ ppm): 2.48 (s, 3H, Ar-CH ), 2.84 (t, 1H, J = 6 Hz,
3
OH), 5.27 (dd, 2H, J = 6 Hz, Ar-CH
2
), 7.62 (dd, 1H,
J = 8 Hz, Ar-H), 7.78 (s, 1H, Ar-H), 7.86 (s, 1H, Ar-
General Procedure for the Synthesis of
Substituted Tetrazolo[1,5-a]quinolin-
H), 8.62 (d, 1H, J = 8 Hz, Ar-H); MS: m/z 215.2 (m +
1
); elemental analysis: C11
H
10
4
N O Calcd.: C: 61.67;
4
-ylmethanols (3)
To the stirred solution of tetrazolo[1,5-a]quinoline-
-carbaldehyde 2 (1.5 g, 7.2 mmol) in methanol
10 mL), sodium tetrahydridoborate (0.2 g,
.2 mmol) was slowly added at room temperature.
H: 4.71; N: 26.15; Found: C: 61.56, H: 4.83, N: 26.31.
4
(
5
(7-Methoxytetrazolo[1,5-a]quinolin-4-yl)metha-
nol (3e). Yield 88%; mp 218–220 C; IR (KBr,
max/cm ): 3343 (O H); H NMR (200 MHz, CDCl
δ ppm): 3.98 (s, 3H, OCH
), 5.17 (dd, 2H, J = 4 Hz,
Ar-CH
◦
−
1
1
ν
3
,
The progress of the reaction was monitored on TLC.
After completion of reaction (5 min), the reaction
mixture was poured on crushed ice. The solid ob-
tained was extracted with chloroform (2 × 50 mL)
and washed with water (2 × 10 mL) and brine
3
2
), 7.40 (d, 1H, J = 8 Hz, Ar-H), 7.45 (dd, 1H,
J = 8 Hz, Ar-H), 8.00 (s, 1H, Ar-H), 8.59 (d, 1H, J =
10 Hz, Ar-H); MS: m/z 231.2 (m + 1); elemental anal-
ysis: C11
H
10
N
4
2
O Calcd.: C: 57.39; H: 4.38; N: 24.34;
(
2 × 20 mL). Thus a separated organic layer was
Found: C: 57.45, H: 4.52, N: 24.06.
dried over anhydrous Na
2
SO . The solvent was re-
4
moved under reduced pressure. The obtained crude
product was purified by column chromatography on
a silica gel by hexane: ethyl acetate as an eluent.
(8-Methoxytetrazolo[1,5-a]quinolin-4-yl)metha-
◦
nol (3f). Yield 81%; mp 230–232 C; IR (KBr, νmax
/
,
−
1
1
cm ): 3353 (O H); H NMR (200 MHz, CDCl
3
Heteroatom Chemistry DOI 10.1002/hc

Synthesis and Characterization of New O,O-Diethyl Phosphorothioates 439
δ ppm): 2.64 (t, 1H, J = 6 Hz, OH), 4.02 (s, 3H,
OCH ), 7.43 (d, 1H,
), 5.23 (dd, 2H, J = 4 Hz, Ar-CH
J = 8 Hz, Ar-H), 7.35 (dd, 1H, J = 8 Hz, Ar-H), 8.07
s, 1H, Ar-H), 8.74 (d, 1H, J = 10 Hz, Ar-H); MS:
2 × CH
2
), 5.60 (dd, 2H, J = 10 Hz, CH
2
), 7.73 (dd,
3
2
1H, J = 6 Hz, Ar-H), 7.9 (dd, 1H, J = 2 Hz, Ar-H),
8.00 (dd, 1H, J = 8 Hz, Ar-H), 8.05 (s, 1H, Ar-H),
13
(
8.7 (d, 1H, J = 8 Hz, Ar-H); C NMR (75 MHz,
3 3 2
m/z 231.2 (m + 1); elemental analysis: C11
H
10
N
4
O
2
CDCl
64.5 (OCH
129.9, 130.8, 145.5 (Ar-C); MS: m/z 353.2 (m + 1);
elemental analysis: C14 PS Calcd.: C: 47.72;
, δ ppm): 15.5 (2 × CH
), 53.3 (OCH ), 63.5,
Calcd.: C: 57.39; H: 4.38; N: 24.34; Found: C: 57.28,
H: 4.53, N: 24.47.
2
), 115.9, 121.3, 123.1, 127.8, 128.7, 129.5,
H
17
N
4
O
3
(
7-Ethoxytetrazolo[1,5-a]quinolin-4-yl)methanol
H: 4.86; N: 15.90, S: 9.10; Found: C: 47.65, H: 4.65,
N: 15.68, S: 9.18.
◦
(
3h). Yield 75%; mp 124–126 C; IR (KBr, νmax
/
,
−
1
1
cm ): 3336 (O H); H NMR (200 MHz, CDCl
δ ppm): 1.50 (t, 3H, J = 8, 14 Hz, CH
3
3
), 2.6 (s, 1H,
), 4.92 (dd, 2H, J =
O,O-Diethyl O-(7-methyltetrazolo[1,5-a]quinolin-
4-yl)methyl phosphorothioate (4b). Yield 79%; mp
OH), 4.16 (q, 2H, J = 14 Hz, CH
2
◦
−1
4
1
8
Hz, CH
2
), 7.07 (d, 1H, J = 2 Hz, Ar-H), 7.35 (dd,
78–80 C; IR (KBr, νmax/cm ): 2982 (C H), 1236
1
H, J = 6 Hz, Ar-H), 7.80 (d, 1H, J = 12 Hz, Ar-H),
.16 (s, 1H, Ar-H); MS: m/z 245.2 (m + 1); elemen-
(P S), 1017 (P O C); H NMR (200 MHz, CDCl
δ ppm): 1.36 (dt, 6H, J = 6 Hz, 2 × CH ), 2.60 (s,
3H, CH ), 5.58 (dd, 2H,
), 4.14–4.29 (m, 4H, 2 × CH
J = 10 Hz, CH ), 7.68 (dd, 1H, J = 8 Hz, Ar-H),
.77 (s, 1H, Ar-H), 7.97 (s, 1H, Ar-H), 8.58 (d, 1H,
J = 8 Hz, Ar-H); C NMR (75 MHz, CDCl
15.7 (2 × CH ), 21.1 (Ar-CH ), 53.5 (OCH
64.6 (OCH ), 115.9, 121.3, 123.3, 127.8, 128.3, 129.9,
132.3, 138.2, 145.5 (Ar-C); MS: m/z 367.2 (m + 1);
elemental analysis: C15 PS Calcd.: C: 47.17;
3
,
3
tal analysis: C12
H
12
N
4
O
2
Calcd.: C: 59.01; H: 4.95; N:
3
2
2
2.94; Found: C: 59.25, H: 4.68, N: 22.72.
2
7
13
(
9-Ethyltetrazolo[1,5-a]quinolin-4-yl)methanol
3
, δ ppm):
◦
−1
(
3i). Yield 77%; mp 110–112 C; IR (KBr, νmax/cm ):
3
3
2
), 63.7,
1
3
1
3
311 (O H); H NMR (200 MHz, CDCl
.33–1.41 (m, 3H, CH
), 2.23 (t, 1H, J = 6 Hz, OH),
.27 (q, 2H, J = 14 Hz, CH ), 4.94 (d, 2H, J = 4 Hz,
), 7.53 (d, 1H, J = 6 Hz, Ar-H), 7.60 (m, 1H, Ar-
H), 7.68 (m, 1H, Ar-H), 8.24 (s, 1H, Ar-H); MS: m/z
O Calcd.:
3
, δ ppm):
2
3
H
19
N
4
O
3
2
CH
2
H: 5.23; N: 15.29, S: 8.75; Found: C: 47.25, H: 5.38,
N: 15.54, S: 8.85.
2
29.2 (m + 1); elemental analysis: C12
H
12
N
4
C: 63.15; H: 5.30; N: 24.55; Found: C: 63.54, H: 5.40,
N: 24.45.
O,O-Diethyl O-(8-methyltetrazolo[1,5-a]quinolin-
4-yl)methyl phosphorothioate (4c). Yield 69%; mp
◦
−1
5
(
4–56 C; IR (KBr, νmax/cm ): 2973 (C H), 1242
1
P S), 1024 (P O C); H NMR (200 MHz, CDCl ,
3
General Procedure for the Synthesis of
O,O-Diethyl O-(substituted
tetrazolo[1,5-a]quinolin-4-yl)methyl
Phosphorothioates (4)
δ ppm): 1.28 (dt, 6H, J = 6 Hz, 2 × CH
3
), 2.57 (s, 3H,
), 5.53 (dd, 2H,
Ar-CH
3
), 4.20–4.38 (m, 4H, 2 × CH
2
J = 10 Hz, Ar-CH
.69 (s, 1H, Ar-H), 8.03 (s, 1H, Ar-H), 8.64 (d, 1H,
J = 8 Hz, Ar-H); MS: m/z 367.2 (m + 1); elemental
analysis: C15 PS Calcd.: C: 47.17; H: 5.23; N:
2
), 7.52 (dd, 1H, J = 8 Hz, Ar-H),
7
O,O-diethylphosphorochloridothioate
.9 mmol), was added under stirring to a solution
of tetrazolo[1,5-a]quinolin-4-ylmethanol (3) (1.0 g,
.8 mmol) and sodium hydroxide (5 g, 12.5 mmol)
(1.5 g,
7
H
19
N
4
O
3
15.29, S: 8.75; Found: C: 47.28, H: 5.17, N: 15.38, S:
8.54.
4
in 10 mL of acetone, and the mixture was stirred
until the reaction was complete (15 min). The
reaction mixture was poured on crushed ice; solid
obtained was extracted with dichloromethane
O,O-Diethyl O-(9-methyltetrazolo[1,5-a]quinolin-
4-yl)methyl phosphorothioate (4d). Yield 73%; mp
◦
−1
96–98 C; IR (KBr, νmax/cm ): 2964 (C H), 1251
1
(
2 × 50 mL) and washed with water (2 × 10 mL),
brine (2 × 20 mL) thus separated organic layer,
dried over anhydrous Na SO . The solvent was re-
(P S), 1022 (P O C); H NMR (200 MHz, CDCl
δ ppm): 1.32 (dt, 6H, J = 6 Hz, 2 × CH ), 2.53 (s, 3H,
Ar-CH ), 5.67 (dd, 2H,
), 4.11–4.23 (m, 4H, 2 × CH
3
,
3
2
4
3
2
moved under reduced pressure. The obtained crude
product was purified by column chromatography on
silica gel by hexane: ethyl acetate (8:2) as an eluent.
J = 10 Hz, Ar-CH ), 7.61 (dd, 1H, J = 8 Hz, Ar-H),
2
7.75 (s, 1H, Ar-H), 8.11 (s, 1H, Ar-H), 8.48 (d, 1H, J =
8 Hz, Ar-H); MS: m/z 367.2 (m + 1); elemental analy-
sis: C15
H
19
N
4
O PS Calcd.: C: 47.17; H: 5.23; N: 15.29,
3
O,O-Diethyl O-tetrazolo[1,5-a]quinolin-4-ylme-
S: 8.75; Found: C: 47.06, H: 5.12, N: 15.41, S: 8.81.
◦
thyl phosphorothioate (4a). Yield 88%; mp 64–66 C;
−1
IR (KBr, νmax/cm ): 2984 (C H), 1227 (P S), 1019
O,O-Diethyl O-(7-methoxytetrazolo[1,5-a]quino-
1
(
(
P O C); H NMR (200 MHz, CDCl
3
, δ ppm): 1.36
lin-4-yl)methyl phosphorothioate (4e). Yield 82%;
◦
−1
dt, 6H, J = 6, 8 Hz, 2 × CH ), 4.14–4.26 (m, 4H,
3
mp 128–130 C; IR (KBr, νmax/cm ): 2979 (C H),
Heteroatom Chemistry DOI 10.1002/hc

440 Kategaonkar et al.
1
1
250 (P S), 1024 (P O C); H NMR (200 MHz,
CDCl ), 3.68
, δ ppm): 1.29–1.42 (m, 6H, 2 × CH
), 4.06–4.23 (m, 4H,
), 5.64 (dd, 2H, J = 8 Hz, Ar-CH ), 7.58 (dd,
H, J = 10 Hz, Ar-H), 7.67 (s, 1H, Ar-H), 7.71 (s,
H, Ar-H), 8.25 (d, 1H, J = 8 Hz, Ar-H); C NMR
, δ ppm): 15.8 (2 × CH ), 53.4 (OCH ),
), 63.8, 64.8 (OCH ), 109.6, 117.9, 120.4,
22.1, 124.5, 124.9, 129.7, 145.2, 158.9 (Ar-C); MS:
PS
Calcd.: C: 47.12; H: 5.01; N: 14.65, S: 8.39; Found: C:
O,O-Diethyl O-(9-ethyltetrazolo[1,5-a]quinolin-4-
yl)methyl phosphorothioate (4i). Yield 74%; mp
3
3
◦
−1
(
dd, 3H, J = 6 Hz, Ar-OCH
3
116–118 C; IR (KBr, νmax/cm ): 2975 (C H), 1231
1
2
1
1
× CH
2
2
(P S), 1026 (P O C); H NMR (200 MHz, CDCl
δ ppm): 1.35 (dt, 6H, J = 8 Hz, 2 × CH ), 2.23 (t,
3H, J = 6 Hz, CH ), 3.27 (q, 2H, J = 8 Hz, CH ),
4.19–4.30 (m, 4H, 2 × CH ), 5.60 (dd, 2H, J = 4 Hz,
CH
), 7.35 (d, 1H, J = 2 Hz, Ar-H), 7.47 (dd, 1H,
J = 2 Hz, Ar-H), 7.99 (s, 1H, Ar-H), 8.59 (d, 1H, J =
8 Hz, Ar-H); C NMR (75 MHz, CDCl , δ ppm): 14.8
(CH ), 15.1, 15.9, 24.1 (CH ), 53.6 (OCH ), 63.8, 64.6
(OCH ), 110.4, 125.4, 127.14, 127.8, 128.9, 129.5,
35.4, 145.8, 147.5 (Ar-C); MS: m/z 381.2 (m + 1);
elemental analysis: C16 PS Calcd.: C: 50.52;
3
,
3
1
3
3
2
(75 MHz, CDCl
3
3
2
2
55.8 (OCH
3
2
2
1
13
m/z 383.2 (m + 1); elemental analysis: C15
H
19
N
4
O
4
3
3
3
2
4
7.01, H: 5.35, N: 14.41, S: 8.61.
2
1
H
21
N
4
O
3
O,O-Diethyl O-(8-methoxytetrazolo[1,5-a]quino-
H: 5.56; N: 14.73, S: 8.43; Found: C: 50.87, H: 5.07,
N: 14.94, S: 8.78.
lin-4-yl)methyl phosphorothioate (4f). Yield 78%;
◦
−1
mp 66–68 C; IR (KBr, νmax/cm ): 2971 (C H), 1248
1
(
P S), 1028 (P O C); H NMR (200 MHz, CDCl
δ ppm): 1.24–1.41 (m, 6H, 2 × CH ), 3.52 (dd, 3H,
), 4.11–4.28 (m, 4H, 2 × CH ),
3
,
3
J = 6 Hz, Ar-OCH
3
2
REFERENCES
5
1
8
.57 (dd, 2H, J = 8 Hz, Ar-CH ), 7.61 (dd, 1H, J =
2
[
[
1] Engel, R. Chem Rev 1977, 77, 349.
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0 Hz, Ar-H), 7.74 (s, 1H, Ar-H), 7.86 (s, 1H, Ar-H),
.51 (d, 1H, J = 8 Hz, Ar-H); MS: m/z 383.2 (m + 1);
(
b) Varma, R. S.; Meshram, H. M. Tetrahedron Lett
elemental analysis: C15
H
19
N
4
O
4
PS Calcd.: C: 47.12;
1997, 38, 7973; (c) Smyth, M. S.; Ford, H., Jr.; Burke,
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M. S.; Otaka, A.; Roller, P. P. Tetrahedron Lett 1993,
H: 5.01; N: 14.65, S: 8.39; Found: C: 47.26, H: 5.13,
N: 14.58, S: 8.57.
3
4, 4125; (f) Smyth, M. S.; Burke, T. R. Tetrahedron
O,O-Diethyl O-(9-methoxytetrazolo[1,5-a]quino-
lin-4-yl)methyl phosphorothioate (4g). Yield 69%;
Lett 1994, 35, 551; (g) Benayound, F.; Hammond, G.
B. Chem Commun 1996, 1447.
◦
−1
mp 110–112 C; IR (KBr, νmax/cm ): 2968 (C H),
[
[
3] Fest, C.; Schmidt, K. J. The Chemistry of
Organophosphorus Pesticides; Springer -Verlag:
Berlin, 1982.
4] (a) Seeberger, P. H.; Yau, E.; Caruthers, M. H. J. Am
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Cummins, L.; Graff, D.; Beaton, G.; Marshall, W. S.;
Caruthers, M. H. Biochemistry 1996, 35, 8734.
1
1
242 (P S), 1031 (P O C); H NMR (200 MHz,
CDCl ), 3.64 (dd,
, δ ppm): 1.20–1.37 (m, 6H, 2 × CH
H, J = 6 Hz, Ar-OCH ), 4.06–4.23 (m, 4H, 2 × CH ),
3
3
3
5
1
8
3
2
.51 (dd, 2H, J = 8 Hz, Ar-CH ), 7.65 (dd, 1H, J =
2
0 Hz, Ar-H), 7.77 (s, 1H, Ar-H), 7.94 (s, 1H, Ar-H),
.81 (d, 1H, J = 8 Hz, Ar-H); MS: m/z 383.2 (m + 1);
elemental analysis: C15
H
19
N
4
O
4
PS Calcd.: C: 47.12;
[5] Menzer, R. E.; Iqbal, Z. M.; Boyd, G. R. J Agric Food
Chem 1971, 19, 351.
H: 5.01; N: 14.65, S: 8.39; Found: C: 47.04, H: 5.24,
N: 14.73, S: 8.48.
[
6] Lu, H.; Berkman, C. E. Bioorg Med Chem 2001, 9,
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3
[
7] Menzer, M.; Phillips, J. R.; Slawin, A. M. Z.; Williams,
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O-(7-Ethoxytetrazolo[1,5-a]quinolin-4-yl)methyl
3
269.
O,O-diethyl phosphorothioate (4h). Yield 62%; mp
[
[
8] Doszczak, L.; Przychodzen, W.; Witt, P.; Rachon, J. J
Chem Soc, Perkin Trans 2 2002, 1747.
9] (a) Doszczak, L.; Rachon, J. J Chem Soc, Perkin Trans
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11] (a) Folkin, A. V.; Kolomiets, A. F.; Iznoskova, M.
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Schrader, G., US Patent 2 597 534, 1952.
[12] Michalski, J.; Modro, T.; Wieczorkowski, J. J Chem
Soc 1960, 1665.
◦
−1
5
(
6–58 C; IR (KBr, νmax/cm ): 2985 (C H), 1228
1
P S), 1019 (P O C); H NMR (200 MHz, CDCl ,
3
δ ppm): 1.34 (dt, 6H, J = 6 Hz, 2 × CH
3
), 1.5 (t, 3H,
), 5.28 (dd,
J = 6 Hz, CH
3
), 4.11–4.26 (m, 4H, 2 × CH
2
[
[
2
7
H, J = 10 Hz, CH
2
), 7.10 (dd, 1H, J = 4 Hz, Ar-H),
.38 (dd, 1H, J = 8 Hz, Ar-H), 7.90 (d, 1H, J = 12 Hz,
13
Ar-H), 8.17 (s, 1H, Ar-H); C NMR (75 MHz, CDCl
δ ppm): 14.4 (CH ), 53.8 (OCH
), 105.5, 121.7, 123.2, 127.7,
29.3, 135.8, 142.6, 145.6, 157.3 (Ar-C); MS: m/z
PS
3
,
3
), 15.6 (2 × CH
3
2
),
6
1
3
3.8, 64.4, 65.6 (OCH
2
[
13] (a) Michalski, J.; Wasiak, J. J Chem Soc, 1962,
056; (b) Michalski, J.; Wasiak, J.; Wieczorkowski,
5
97.2 (m + 1); elemental analysis: C16
H
21
N
4
O
4
J.; Pliszka, B. Roczn Chem 1959, 33, 247; (c) Harvey,
R. G.; Jacobson, H. I.; Jensen, E. V. J Am Chem Soc,
1963, 85, 1618.
Calcd.: C: 48.48; H: 5.34; N: 14.13, S: 8.09; Found:
C: 48.61, H: 5.67, N: 14.15, S: 8.34.
Heteroatom Chemistry DOI 10.1002/hc

Synthesis and Characterization of New O,O-Diethyl Phosphorothioates 441
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[
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2
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Heteroatom Chemistry DOI 10.1002/hc