Studies on organophosphorus compounds: Synthesis and reactions of some new 5′-cyano-2′(4-methoxyphenyl)spiro[cycloalkane-1,6′-[1,3,2] thiazaphosphixane]-2′,4′-disulfide derivatives

Article abstract of DOI:10.1080/10426500307871

2,4-Bis(4-methoxyphenyl)-1,3,2,4-dithiadiphosphetane-2,4-disulfide (Lawesson's Reagent, LR, 1) reacts with cycloalkylidenecyanothioacetamides (2 and 3) to give 5′-cyano-2′-(4-methoxyphenyl)spiro[cyclopentane(cyclohexane)-1, 6′-perhydro-[1,3,2]thiazaphosphixane]-2′,4′-disulfide (4 and 5). The reaction of compounds 4 and 5 with α-halo compounds led to the formation of the substituted thio-compounds 6a-e and 7a-e, respectively, these compounds, upon treatment with sodium ethoxide, produce the corresponding thienothiazaphosphixine derivatives 8a-e and 9a-e respectively. Compounds 8a-e and 9a-e react with LR under different reaction conditions to give polyfused heterocyclic compounds 10a-d and 11a-d respectively. Treatment of compounds 8b and 9b with CS₂ and (CH₃)₂SO₄ gave the corresponding dithiocarbamate methyl ester derivatives 12 and 13, respectively, which on treating with hydrazine hydrate yielded compounds 14 and 15 respectively. Compounds 14 and 15 reacted with LR to yield compounds 16a,b and 17a,b respectively.

Full text of DOI:10.1080/10426500307871

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Studies on Organophosphorus Compounds:
Synthesis and Reactions of Some New 5′-Cyano-2′-
(4-methoxyphenyl)spiro[cycloalkane-1,6′-
[1,3,2]thiazaphosphixane]-2′,4′-disulfide Derivatives
H. M. Moustafa a
a Chemistry Department, Faculty of Science , South Valley University , Sohag, Egypt
Published online: 27 Oct 2010.
To cite this article: H. M. Moustafa (2003) Studies on Organophosphorus Compounds: Synthesis and Reactions of Some New 5′-
Cyano-2′-(4-methoxyphenyl)spiro[cycloalkane-1,6′-[1,3,2]thiazaphosphixane]-2′,4′-disulfide Derivatives, Phosphorus, Sulfur,
and Silicon and the Related Elements, 178:7, 1397-1412, DOI: 10.1080/10426500307871
To link to this article: http://dx.doi.org/10.1080/10426500307871
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Phosphorus, Sulfur, and Silicon, 178:1397–1412, 2003
C
Copyright Taylor & Francis Inc.
ISSN: 1042-6507 print
DOI: 10.1080/10426500390212500
STUDIES ON ORGANOPHOSPHORUS COMPOUNDS:
SYNTHESIS AND REACTIONS OF SOME NEW
50-CYANO-20-(4-METHOXYPHENYL)-
SPIRO[CYCLOALKANE-1,60-[1,3,2]THIAZA-
PHOSPHIXANE]-20,40-DISULFIDE DERIVATIVES
H. M. Moustafa
Chemistry Department, Faculty of Science, South Valley
University, Sohag, Egypt
(Received October 29, 2002; accepted December 13, 2002)
2,4-Bis(4-methoxyphenyl)-1,3,2,4-dithiadiphosphetane-2,4-disulfide
(Lawesson’s Reagent, LR, 1) reacts with cycloalkylidenecyanoth-
ioacetamides (2 and 3) to give 50-cyano-20-(4-methoxyphenyl)spiro
[cyclopentane(cyclohexane)-1,60-perhydro-[1,3,2]thiazaphosphixane]-
20,40-disulfide (4 and 5). The reaction of compounds 4 and 5 with -halo
compounds led to the formation of the substituted thio-compounds
6a–e and 7a–e, respectively, these compounds, upon treatment with
sodium ethoxide, produce the corresponding thienothiazaphosphixine
derivatives 8a–e and 9a–e respectively. Compounds 8a–e and 9a–e
react with LR under different reaction conditions to give polyfused
heterocyclic compounds 10a–d and 11a–d respectively. Treatment of
compounds 8b and 9b with CS2 and (CH3)2SO4 gave the correspond-
ing dithiocarbamate methyl ester derivatives 12 and 13, respectively,
which on treating with hydrazine hydrate yielded compounds 14
and 15 respectively. Compounds 14 and 15 reacted with LR to yield
compounds 16a,b and 17a,b respectively.
Keywords:
2,4-Bis(4-methoxyphenyl)-1,3,2,4-dithiadiphosphetane-
2,4-disulfide; cycloalkylidenecyanothioacetamides; P-heterocycles
Heterocycles containing phosphorus continue to attract consid-
erable attention which mainly arises from the large variety of
interesting pharmacological and biological activities observed with
heterocycles containing phosphorus, which including, herbicidal,1
4
insecticidal,2
antibacterial,5,6 antifungal,5 and anticancer7,8 prop-
erties.
2,4-Bis(4-methoxyphenyl)-1,3,2,4-dithiadiphosphetane-2,4-
disulphide (Lawesson’s reagent, LR, 1), beside its effectiveness as
Address correspondence to H. M. Moustafa, Chemistry Department, Faculty of
Science, Sohag, Egypt. E-mail: hassa20002000@yahoo.com
1397

1398
H. M. Moustafa
12
thiation reagent for different carbonyl compounds,9
undergoes
ring closure reactions with substrates containing two functional
19
groups13
forming phosphorus heterocycles. To extend the use of
LR for the synthesis of new fused P-heterocycles its reaction with cy-
cloalkylidenecyanothioacetamides and different substrates containing
two functional groups has been investigated in this work.
RESULTS AND DISCUSSION
The parent compounds cycloalkylidenecyanothioacetamide 2 and 3
were prepared in a good yield via the reaction of the corresponding
cycloalkanone with cyanothioacetamide in the presence of piperi-
dine.20 Compounds 2 and 3 were allowed to react with LR in
boiling acetonitrile to give 50-cyano-20-(4-methoxyphenyl)spiro[cyclo-
pentane(cyclohexane)-1,60-perhydro[1,3,2]thiazaphosphixane]- 20,40-di-
sulfide (4 and 5). The reaction pathway was assumed to proceed via
a nucleophilic attack of the amino group on LR followed by a P-SH
addition to the ethylenic bond21 (Scheme 1).
The structure of compounds 4 and 5 were confirmed on the basis
of their elemental and spectral analyses (cf. Table I). The IR spectra
of compounds 4 and 5 showed the absence of the absorption bands
SCHEME 1

1399

1400

1401

1402

1403

1404

Studies on Organophosphorus Compounds
1405
SCHEME 2
corresponding to the amino groups while exhibiting characteristic
1
bands corresponding to P S at 657 and 644 cm respectively. The 1H-
NMR (DMSO) spectra of compounds 4 and 5 showed the absence of a
signal corresponding to NH2 groups while exhibiting new signals cor-
responding to four aromatic protons at 7.7–7.1, four aliphatic protons
at 3.9 (OCH3, s) and 3.5 (CH, s).
Reaction of compounds 4 and 5 with different -halo com-
pounds, namely chloroacetic acid, ethyl chloroacetate, chloroacetamide,
chloroacetanilide, and chloroacetonitrile in the presence of anhydrous
sodium acetate led to the formation of the corresponding thioethers
6a–e and 7a–e respectively. On refluxing compounds 6a–e and 7a–e
with sodium ethoxide in absolute ethanol gave the thienothiazaphos-
phixine derivatives 8a–e and 9a–e respectively (Scheme 2).
IR spectra of compounds 6a–e and 7a–e exhibited the absorption
bands corresponding to CN (2209–2229 cm 1) while the IR spectra of
compounds 8a–d and 9a–d showed the absence of the absorption bands
corresponding to CN groups and appearance of new bands correspond-
ing to NH2 groups (3197–3441 cm 1). The 1H-NMR spectra of com-
pounds 6a–e–9a–e are in agreement with the proposed structures (cf.
Table I).
Compounds 8a and 9a react with LR in anhydrous benzene at
80 C to give 3,1,2-oxazaphosphixin-4-one derivatives 10a and 11a
respectively. The formation of 10a and 11a is believed to occur via a

1406
H. M. Moustafa
SCHEME 3
nucleophilic attack of the carboxylate of the betaine on LR to give a
new betaine followed by ring closure through elimination of an H2S
molecule13 (Scheme 3).
The structures of products 10a and 11a were determined by elemen-
tal analysis, IR and 1H-NMR spectra (cf. Table I).
On the other hand, the reaction of compounds 8b and 9b with LR
at elevated temperature (140 C) produced 3,1,2-thiazaphosphixine-4-
thione derivatives 10b and 11b in moderate yield. As to the mechanism
for the formation of the P-heterocycles (10b and 11b), it is suggested
that a nucleophilic attack on LR gives A, followed by ring closure and
elimination of ethanol molecule to give B, subsequent thiation produce
10b and 11b (Scheme 4).
1,3,2-Diazaphosphixine-4-thione-2-sulfide derivatives 10c,d and
11c,d were formed by reacting compounds 8c,d and 9c,d with LR in re-
fluxing toluene. The mechanism for the formation of compounds 10c,d
and 11c,d is suggested as follows (Scheme 5).
The reaction of compounds 8e and 9e with LR in toluene at 110 C
yielded compounds which are identical in all respects with authen-
tic samples of compounds 10c and 11c respectively. It was suggested
that nucleophilic attack of the amino group on the phosphorus of
LR, followed by P-SH addition to the nitrile group and subsequent
rearrangement,22 yielded compounds 10c and 11c (Scheme 6, Table I).
Treatment of compounds 8b or 9b with NaOH, CS2 and (CH3)2SO4
afforded the corresponding dithiocarbamate methyl ester derivatives

Studies on Organophosphorus Compounds
1407
SCHEME 4
SCHEME 5

1408
H. M. Moustafa
SCHEME 6
12 and 13, respectively, which on treating with hydrazine hydrate
yielded compounds 14 and 15 respectively (Scheme 7). Compounds 14
and 15 were allowed to react with Lawesson’s reagent (LR) in refluxing
toluene to afford compounds 16a,b and 17a,b respectively. As to the con-
certed mechanism23 for the formation of compounds 16a,b and 17a,b,
it is suggested that a nucleophilic attack by NH2 group on LR gives the
transient intermediate which underwent intramolecular cyclization via
elimination of H2S molecule to give 16a and 17a. Subsequent thiation
of compounds 16a and 17a produced compounds 16b and 17b, respec-
tively (Scheme 7).
The structures of compounds 12–17 were determined by elemental
analysis, IR and 1H-NMR spectra (cf. Table I).
EXPERIMENTAL
Synthesis of Compounds 4 and 5
General Procedure
A mixture of 2,4-bis(4-methoxyphenyl)-1,3,2,4-dithiadiphosphetane-
2,4-disulfide LR (0.005 mmol) and compound 2 or 3 (0.01 mmol) in dry
acetonitrile (70 ml) was refluxed until no more of the reactants could

Studies on Organophosphorus Compounds
1409
SCHEME 7
be detected (TLC) ( 7 h). The reaction mixture was concentrated and
cooled. The resultant precipitate was collected by filtration and recrys-
tallized from the suitable solvent to give compounds 4 and 5 respectively
(cf. Table I).
Synthesis of Compounds 6a–e and 7a–e
General Procedure
A mixture of compound 4 and/or 5 (0.01 mmol), anhydrous sodium ac-
etate (0.01 mmol), and a proper chloro compound (0.01 mmol) in ethanol

1410
H. M. Moustafa
(70 ml) was refluxed for 2 h. The reaction mixture was filtered while
hot, concentrated, and cooled. The resultant precipitate was collected
by filtration and the filter cake was washed with water. The crude prod-
uct was purified by recrystallization from an appropriate solvent to give
compounds 6a–e and 7a–e respectively (cf. Table I).
Synthesis of Compounds 8a–e and 9a–e
General Procedure
The sulfide (6a–e and/or 7a–e) (0.01 mmol) was refluxed in absolute
ethanol (60 ml) in the presence of sodium ethoxide (0.23 g of Na in
5 ml ethanol) for 5 h. The mixture was concentrated and cooled. The
resultant precipitate was collected by filtration and the filter cake was
washed with water. The crude product was purified by recrystallization
from an appropriate solvent to give compounds 8a–e and 8a–e respec-
tively (cf. Table I).
Synthesis of Compounds 10a and 11a
General Procedure
A mixture of compound 8a or 9a (0.005 mmol) and LR (0.005 mmol)
in dry benzene (70 ml) was refluxed for 10 h. The reaction mix-
ture was concentrated and cooled. The resultant precipitate was col-
lected by filtration. The crude product was purified by recrystallization
from the suitable solvent to give compounds 10a and 11a respectively
(cf. Table I).
Synthesis of Compounds 10b and 11b
General Procedure
A mixture of compound 8b or 9b (0.005 mmol) and LR (0.005 mmol) in
dry xylene (40 ml) was refluxed for 24 h. The solvent was evaporated to
dryness under reduced pressure, and the residue was triturated with
methanol. The separated solid was collected by filtration. The crude
product was purified by recrystallization from an appropriate solvent
to give 10b and 11b respectively (cf. Table I).
Synthesis of Compounds 10c,d and 11c,d
General Procedure
A mixture of compound 8c–e or 9c–e (0.005 mmol) and LR
(0.005 mmol) in dry toluene (60 ml) was refluxed for 12 h. The solvent
was evaporated to dryness under reduced pressure, and the residue
was triturated with methanol. The separated solid was collected by fil-
tration. The crude product was purified by recrystallization from the

Studies on Organophosphorus Compounds
1411
suitable solvent to give 10c,d and 11c,d respectively. Compounds 8e
and 9e yielded compounds which are identical in all respects with au-
thentic samples of compounds 10c and 11c respectively (cf. Table I).
Synthesis of Compounds 12 and 13
General Procedure
To a vigorously stirred solution of compound 8b or 9b (0.01 mmol) in
DMSO (10 ml) at room temperature was added CS2 (0.013 mmol) and
aq. solution of NaOH (0.013 mmol). After stirring for 30 min at room
temperature, the reaction mixture was cooled in ice-bath (5–10 C) and
dimethyl sulfate (0.013 mmol) was added with stirring. The stirring
was continued for additional 3 h; then the reaction mixture was poured
into ice-water mixture (500 ml). The separated solid was collected by
filtration and dried. The crude product was purified by recrystallization
from an appropriate solvent to give compounds 12 and 13 respectively
(cf. Table I).
Synthesis of Compounds 14 and 15
General Procedure
To a stirred solution of compound 12 or 13 (0.005 mmol) in ethanol
(30 ml) hydrazine hydrate (0.0052 mmol) was added dropwise. After the
addition, the reaction mixture was refluxed for 3 h. On cooling, the solid
that separated out was collected by filtration and the filter cake was
washed with water. The crude product was purified by recrystallization
from an appropriate solvent to give compounds 14 and 15 respectively
(cf. Table I).
Synthesis of Compounds 16a,b and 17a,b
General Procedure
A mixture of compound 14 or 15 (0.005 mmol), LR (0.005 mmol),
and dry toluene (60 ml) was refluxed for 12 h. The reaction mixture
was filtered while hot. The resultant precipitate was collected by filtra-
tion and crystallized from ethanol, where compounds 16a and 17a were
obtained. The filtrate was concentrated and the separated solid was col-
lected by filtration. The crude product was purified by recrystallization
from dioxan to give compounds 16b and 17b respectively.
REFERENCES
[1] He Liang-Nian, Zhu Ren-Xi, Chen Ru-Yu, Li Kai, and Zham You-Jie, Heteroatom
Chem., 10(2), 105 (1999).

1412
H. M. Moustafa
[2] M. S. Chande, R. S. Jagtap, and R. N. Sharma, Indian J. Chem., 36B, 199 (1997).
[3] M. S. Chande, R. S. Jagtap, and R. N. Sharma, Indian J. Chem., 34B, 911 (1995).
[4] C. D. Reddy, K. D. Berlin, R. S. Reddy, C. N. Raju, M. Elmasri, and S. Subramanian,
Phosphorus, Sulfur and Silicon, 81, 61 (1993).
[5] K. V. Raghu and C. Devendrahath Reddy, Indian J. Chem., 35B, 1228 (1996).
[6] L. N. Rao, V. K. Reddy, and C. D. Reddy, Heteroat. Chem., 11(5), 323 (2000).
[7] H. Zimmer and A. Sill, Prog. Drug Res., 5, 150 (1964).
[8] E. O. J. Bull and M. S. R. Naidu, Phosphorus, Sulfur, and Silicon, 162, 231 (2000).
[9] B. S. Pedersen, S. Scheibye, N. H. Nilsson, and S.-O. Lawesson, Bull. Soc. Chim.
Belg., 87, 223(1978).
[10] B. S. Pedersen, S. Scheibye, K. Clausen, and S.-O. Lawesson, Bull. Soc. Chim. Belg.,
87, 293 (1978).
[11] S. Scheibye, B. S. Pedersen, and S.-O. Lawesson, Bull. Soc. Chim. Belg., 87, 299
(1978).
[12] A. A. El-Barbary, K. Clausen, and S.-O. Lawesson, Tetrahedron, 36, 3309 (1980).
[13] A. A. El-Barbary and S.-O. Lawesson, Tetrahedron, 37, 2641 (1981).
[14] R. Shabana, F. H. Osman, and S. S. Atrees, Tetrahedron, 50, 6975 (1994).
[15] A.-B. A. G. Ghattas, E.-E. A. M. El-Khrisy, and S.-O. Lawesson, Sulfur Lett., 69
(1982).
[16] T. P. Andersen, A.-B. A. G. Ghattas, and S.-O. Lawesson, Tetrahedron, 39, 3419
(1983).
[17] H. M. Moustafa, Phosphorus, Sulfur, and Silicon, 148, 131 (1999).
[18] H. M. Moustafa, Phosphorus, Sulfur, and Silicon, 164, 11 (2000).
[19] A.-B. A. G. Ghattas, O. A. Abd Allah, and H. M. Moustafa, Phosphorus, Sulfur, and
Silicon, 157, 1 (2000).
[20] G. E. H. El-Gemeie, J. Chem. Soc. Perkin Trans. 1, 1267 (1990).
[21] S. Scheibye, S.-O. Lawesson, and C. Romming, Acta Chem. Scand, B35, 139 (1981).
[22] B. S. Pedersen and S.-O. Lawesson, Tetrahedron, 35, 2433 (1979).
[23] S. Scheibye, J. Kristensen, and S.-O. Lawesson, Tetrahedron, 35, 1339 (1979).