Facile synthesis of novel 6-methyl-5-phenyl-2-sulfido-1,2,3,5-tetrahydro-4H[1,2] oxazolo[4′,5′:5,6]pyrano[2,3-d][1,3,2]diazaphosphinines

Article abstract of DOI:10.1080/17415993.2018.1455837

A number of 6-methyl-5-phenyl-2-sulfido-1,2,3,5-tetrahydro-4H[1,2]oxazolo[4′,5′: 5,6]pyrano[2,3-d][1,3,2]diazaphosphinines 4–11 were synthesized via an interaction of tetraphosphorus decasulfide and Lawesson’s reagent under different conditions with 6-amino-3-methyl-4-phenyl-4H-pyrano[3,2-d][1,2]oxazole-5-carbonitrile (3). The reaction mechanisms for these products were discussed. Structures of the newly synthesized products were established on the basis of elemental analysis and spectral data.

Full text of DOI:10.1080/17415993.2018.1455837

Journal of Sulfur Chemistry
ISSN: 1741-5993 (Print) 1741-6000 (Online) Journal homepage: http://www.tandfonline.com/loi/gsrp20
Facile synthesis of novel 6-methyl-5-
phenyl-2-sulfido-1,2,3,5-tetrahydro-4H[1,2]
oxazolo[4′,5′:5,6]pyrano[2,3-d]
[1,3,2]diazaphosphinines
Tarik E. Ali, Mohamed A. Assiri, Somaia M. Abdel-Kariem & Ibrahim S. Yahia
To cite this article: Tarik E. Ali, Mohamed A. Assiri, Somaia M. Abdel-Kariem & Ibrahim S.
Yahia (2018): Facile synthesis of novel 6-methyl-5-phenyl-2-sulfido-1,2,3,5-tetrahydro-4H[1,2]
oxazolo[4′,5′:5,6]pyrano[2,3-d][1,3,2]diazaphosphinines, Journal of Sulfur Chemistry, DOI:
10.1080/17415993.2018.1455837
To link to this article: https://doi.org/10.1080/17415993.2018.1455837
Published online: 27 Mar 2018.
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JOURNAL OF SULFUR CHEMISTRY, 2018
https://doi.org/10.1080/17415993.2018.1455837
Facile synthesis of novel 6-methyl-5-phenyl-2-sulfido-1,2,3,5-
tetrahydro-4H[1,2] oxazolo[4ꢀ,5ꢀ:5,6]pyrano[2,3-d][1,3,2]
diazaphosphinines
Tarik E. Alia, Mohamed A. Assirib, Somaia M. Abdel-Kariema and Ibrahim S. Yahiac,d
aDepartment of Chemistry, Faculty of Education, Ain Shams University, Roxy, Cairo, Egypt; bAdvanced
Materials and Green Chemistry, Chemistry Department, Faculty of Science, King Khalid University, Abha,
Saudi Arabia; cAdvanced Functional Materials & Optoelectronic Laboratory, Department of Physics, Faculty of
Science, King Khalid University, Abha, Saudi Arabia; dNano-Science & Semiconductor Labs, Department of
Physics, Faculty of Education, Ain Shams University, Roxy, Cairo, Egypt
ABSTRACT
ARTICLE HISTORY
Received 15 February 2018
Accepted 17 March 2018
A number of 6-methyl-5-phenyl-2-sulfido-1,2,3,5-tetrahydro-4H[1,2]
oxazolo[4ꢀ,5ꢀ: 5,6]pyrano[2,3-d][1,3,2]diazaphosphinines 4–11 were
synthesized via an interaction of tetraphosphorus decasulfide and
Lawesson’s reagent under different conditions with 6-amino-3-
KEYWORDS
1,3,2-Diazaphosphinine;
pyrano[3,2-d][1,2]oxazole;
tetraphosphorus decasulfide;
Lawesson’s reagent
methyl-4-phenyl-4H-pyrano[3,2-d][1,2]oxazole-5-carbonitrile
(3).
The reaction mechanisms for these products were discussed. Struc-
tures of the newly synthesized products were established on the
basis of elemental analysis and spectral data.
1. Introduction
The synthesis of phosphorus heterocycles, predominantly, phosphorus linked to an oxy-
gen and nitrogen atoms gained considerable attention due to their broad spectrum of
potent biological activities and pharmacological interest. Some of these heterocycles dis-
played anticancer [1], antimicrobial [2], insecticidal [3], herbicidal [4], and antibodies’
properties [5]. Further, phosphorus heterocycles possessing multi-rings are found to be
as stabilizers in polymers, as lubricant oil additives, and in organic synthesis as biocatalysts
[6]. However, six-membered phosphorus heterocyclic rings have gained much attention
since they are involved as intermediates in a number of synthetic, biological processes, and
CONTACT Tarik E. Ali
tarik_elsayed1975@yahoo.com
© 2018 Informa UK Limited, trading as Taylor & Francis Group

2
T. E. ALI ET AL.
pharmaceutical fields [7]. Recently, researchers are showing interest towards the synthe-
sis of 1,3,2-diazaphosphinine heterocycles due to their valuable biological importance and
various applications in synthetic chemistry [8–10]. On the other hand, oxygen-containing
heterocycles such as oxazole and pyran form very numerous and accessible groups of com-
pounds with a broad spectrum of useful properties, which include anti-inflammatory,
antibacterial, and anticancer [11–15]. Considering the above facts and our continuing
research on the development of new biologically active heterocyclic organophosphorus
compounds [16–18], we herein report an efficient method for the synthesis of novel
6-amino-3-methyl-4-phenyl-4H-pyrano[3,2-d][1,2]oxazole-5-carbonitrile (3) and chem-
ical transformations into 1,3,2-diazaphosphinines possessing a pyrano[3,2-d][1,2] oxazole
system via its reaction with some phosphorus sulfide reagents.
2. Results and discussion
The novel starting material 6-amino-3-methyl-4-phenyl-4H-pyrano[3,2-d][1,2] oxazole-
5-carbonitrile (3) was synthesized in 87% yield by the reaction of 3-methyl-1,2-oxazol-
5(4H)-one (1) with benzylidene-propanedinitrile (2) in distilled water containing a few
amount of sodium carbonate as a catalyst (Scheme 1). The IR spectrum of compound 3
showed the NH2 and C ≡N functions at 3463, 3323, and 2197 cm−1. Its 1H-NMR spec-
trum revealed the characteristic H–4 and NH2 protons as singlets at δ 4.96 and 6.69 ppm,
respectively. Moreover, its 13C-NMR spectrum displayed the carbon atoms of CH3, C–4,
and C ≡N at δ 14.7, 26.6, and 109.2 ppm, respectively. Furthermore, the molecular ion
peak of compound 3 was recorded at m/z 253, which confirmed the proposed structure.
The versatility of α-aminocarbonitrile substrate 3 is in great part due to its promptness
to both electrophilic and nucleophilic attack. For this reason, we used it in the synthesis
of 1,3,2-diazaphosphinine heterocycles via its reacting with tetraphosphorus decasulfide
and Lawesson’s reagent (LR) under different conditions especially they are known as pow-
erful, mild, and versatile reagents for building phosphorus and sulfur heterocycles [19].
Thus, when compound 3 was treated with molar equivalents of tetraphosphorus deca-
sulfide in dry toluene, the 6-methyl-5-phenyl-2-sulfanyl-2-sulfido-1,2,3,5-tetrahydro-4H-
[1,2]oxazolo[4ꢀ,5ꢀ:5,6]pyrano[2,3-d][1,3,2]diazaphosphinine-4-thione (4) was obtained in
56% yield (Scheme 2). The structure 4 was confirmed by elemental analysis, IR, 1H-, 13C-
,
31P-NMR, and mass spectra. Its IR spectrum revealed the absence of a strong band at
2197 cm−1, and appearance of new C =S group at 1129 cm−1. The 1H-NMR spectrum of
4 gave signals at δ 3.70 ppm for the sulfanyl proton and two D2O-exchangeable NH protons
at δ 10.04 and 11.79 ppm. Its 13C-NMR spectrum added a good support for the proposed
Scheme 1. Synthesis of 6-amino-3-methyl-4-phenyl-4H-pyrano[3,2-d][1,2]oxazole-5-carbonitrile (3).

JOURNAL OF SULFUR CHEMISTRY
3
Scheme 2. Reaction of compound 3 with P4S10 in dry toluene and pyridine.
structure and revealed the carbon atom of C =S at δ 186.3 ppm. The 31P-NMR spectrum
of compound 4 recorded a singlet at δ 35.1 ppm. Moreover, its mass spectrum recorded its
expected molecular ion peak at m/z 381 (M+, 22%). A possible explanation for the course
of the formation of compound 4 is shown in Scheme 2. The reaction presumably proceeded
in two steps. Firstly, the addition of P4S10 on the nitrile group and conversion it into the
thioamide group in the nonisolable intermediate C [20,21]. Secondly, heterocyclization of
the neighboring amino groups through the reaction with PS2 cation to give the novel oxa-
zolopyranodiazaphosphinine system 4 (Scheme 2). Furthermore, when compound 3 was
allowed to react with the P4S10–Pyridine complex in dry pyridine at 80°C, the pyridinium
sulfide salt 5 was separated with 67% yield (Scheme 2) [22]. The isolated product 5 was also
obtained via warming of compound 4 in a little amount of pyridine at 60°C (Scheme 2).

4
T. E. ALI ET AL.
Elemental and mass spectral analysis of 5 led to an empirical formula C19H17N4O2PS3.
The 1H- and 13C-NMR spectra displayed the presence of the pyridine ring.
Next, the reaction of compound 3 with O,O-diethyldithiophosphoric acid (formed in
situ from reaction tetraphosphorus decasulfide with absolute ethanol) furnished the cor-
responding product 7 and not the expected 6 (Scheme 3). The structure of compound 7
was confirmed with mass spectrum which revealed the molecular ion peak at m/z 393
(M+, 100%) and the 1H- and 13C-NMR spectra data displayed the presence of the char-
acteristic ethoxy group. Mechanistically, the formation of the diazaphosphinine ring can
be explained on the basis of an initial nucleophilic addition of thiol group at the nitrile
group giving the nonisolable intermediate E, followed by an attack of the amino functional
group at phosphorus atom. This intramolecular cyclization gave the nonisolable interme-
diate F, which in turn rearranged to the desired fused triheterocyclic system via a Dimroth
rearrangement (Scheme 3).
Treatment of compound 3 with LR in dry toluene under reflux led to the formation 2-(4-
methoxyphenyl)-6-methyl-5-phenyl-2-sulfido-1,2,3,5-tetrahydro-4H[1,2]oxazolo[4ꢀ,5ꢀ:5,
6]pyrano[2,3-d][1,3,2]diazaphosphinine-4-thione (8) (Scheme 4). To explain the forma-
tion of compound 8, a plausible reaction mechanism is proposed in Scheme 4. Initially, due
Scheme 3. Reaction of compound 3 with P4S10 in absolute ethanol.

JOURNAL OF SULFUR CHEMISTRY
5
Scheme 4. Reaction of compound 3 with Lawesson’s reagent in dry toluene.
to the stronger nucleophilicity of the sulfur anion in LR fragment, the nucleophilic addi-
tion of sulfur anion to the nitrile group resulted in the formation of intermediate G, which
underwent the intramolecular cyclization of the amino group with phosphorus atom, fol-
lowed by Dimorth rearrangement affording the final product (Scheme 4). The IR spectrum
of compound 8 revealed the absence of the NH2 and C ≡N groups of starting material 3
and the presence of the NH at 3424 cm−1 as a broad band. The 1H-NMR spectrum showed
the presence of two NH protons at δ 9.21 and 11.26 ppm, and the OCH3 protons as a singlet
at δ 3.85 ppm. Also, its 13C-NMR spectrum supported the presence of the methoxy group
at δ 55.6 ppm. Furthermore, its 31P-NMR spectrum revealed a singlet at δ 52.3 ppm.
When the previous reaction was carried out in absolute ethanol instead of toluene, we
found that the isolated product was compound 8. The proposed mechanism for the for-
mation of compound 8 by this method suggested that LR reagent may react with absolute
ethanol to give the nonisolable 4-MeOC6H4P(S)(SH)(OEt) which reacted with starting
material 3 according to the mechanism shown in Scheme 5.
The final point in this work was the treatment of compound 3 with P-(4-
methoxyphenyl)-N,Nꢀ-diphenylphosphonothioic diamide (10) which was prepared from
the reaction of LR with fourth folds of distilled aniline according to the reported method
[23]. The reaction of the latter compound 10 with α-aminocarbonitrile 3 in dry toluene
required 16 h to give the isolated product 11 (46% yield) in a pure form. The formation of

6
T. E. ALI ET AL.
Scheme 5. Reaction of compound 3 with Lawesson’s reagent in absolute ethanol.
the latter compound can be interpreted in terms of nucleophilic attack by the amino group
on the phosphorus atom of reagent 10 to give with concomitant elimination of an ani-
line moiety formed the nonisolable intermediate K, followed by ring closure through the
addition of NH on the nitrile group. The participation of both amino and nitrile groups
was evident if we consider the disappearance of the corresponding signals from 1H- and
13C-NMR spectra, respectively. Further, the 1H-NMR spectrum of product 11 exhibited
characteristic signals at δ 9.61 and 11.07 ppm attributable to NH protons, multiplets at δ
6.81–7.67 ppm easily attributable to the aromatic protons introduced by the aniline used
and LR and a singlet at δ 3.88 ppm relative to the methoxy group. Unambiguous proof for
the obtained product 11 was aroused from its 13C-NMR data. Particularly, a new methoxy
group introduced by the LR at δ 54.3 ppm and a singlet at δ 157.2 ppm attributable to the
C=NH. The 31P-NMR spectra of this compound reinforce the above by showing the phos-
phorus atom signal at δ 48.3 ppm. The mass spectrum was in agreement with the molecular
formula (Scheme 6).

JOURNAL OF SULFUR CHEMISTRY
7
Scheme 6. Reaction of compound 3 with phosphonothioic diamide 10 in dry toluene.
3. Conclusion
Facile routes were achieved to synthesize novel 6-methyl-5-phenyl-2-sulfido-1,2,3,5-
tetrahydro-4H[1,2]oxazolo[4ꢀ,5ꢀ:5,6]pyrano[2,3-d][1,3,2]diazaphosphinines in one step
starting from 6-amino-3-methyl-4-phenyl-4H-pyrano[3,2-d][1,2]oxazole-5-carbonitrile
(3) with some phosphorus sulfides in different solvents. We hope that this approach may be
valuable to others seeking novel synthetic fragments with unique properties for medicinal
chemistry.
4. Experimental
4.1. General remarks
The melting point was determined in an open capillary tube on a digital Stuart SMP-3
apparatus. Infrared spectra were measured on an FT-IR (Nicolet IS10) spectrophotometer
using KBr disks and a Perkin-Elmer 293 spectrophotometer using KBr disks. The 1H- and
13C-NMR spectra were measured on a Gemini-300BB spectrometer (400 and 100 MHz),
using DMSO-d6 as a solvent and TMS (δ) as an internal standard. 31P-NMR spectra were
measured on a Bruker (162 MHz) spectrophotometer using DMSO-d6 as a solvent, TMS as
an internal standard, and 85% H3PO4 as an external reference. Mass spectra were recorded
on a Gas Chromatographic GCMSqp 1000 ex Shimadzu instrument at 70 eV. Elemental
microanalysis was performed on Perkin-Elmer 2400II at the Chemical War department,
Ministry of Defense. The purity of the synthesized compounds was checked by thin layer
chromatography (TLC) and elemental microanalysis.

8
T. E. ALI ET AL.
4.2. Synthesis of 6-amino-3-methyl-4-phenyl-4H-pyrano[3,2-d][1,2]oxazole-5-
carbonitrile (3)
A mixture of 3-methyl-1,2-oxazol-5(4H)-one (1) (0.5 g, 5 mmol) and benzylidene-
propanedinitrile (2) (0.77 g, 5 mmol) in distilled water (25 ml) containing 0.1 g of sodium
carbonate was stirred at 60°C for 3 h. The formed solid was filtered off, washed with
water several times and crystallized from ethanol to give yellow crystals in 87% yield; mp
194–196°C. IR (KBr), (νmax, cm−1): 3463, 3323 (NH2), 2930 (C–Haliph), 2197 (C≡N),
1
1663 (NHdef ), 1593 (C=N), 1522 (C=C). H-NMR (400 MHz, DMSO-d6): 2.35 (s,
3H, CH3), 4.96 (s, 1H, H–4), 6.69 (s, 2H, NH2), 7.61–7.76 (m, 5H, Ph–H). 13C-NMR
(100 MHz, DMSO-d6): 14.7 (CH3), 26.6 (C–4), 72.9 (C–5), 109.2 (C≡N), 118.1 (C–3a),
125.5 (C–3ꢀ,5ꢀ), 128.9 (C–4ꢀ), 131.1 (C–2ꢀ,6ꢀ), 134.6 (C–1ꢀ), 143.9 (C–3), 152.1 (C–7a),
162.2 (C–6). MS (m/z, I %): 253 (M+, 8%). Anal. Calcd for C14H11N3O2 (253.26): C,
66.40%; H, 4.38%; N, 16.59%. Found: C, 66.09%; H, 4.12%; N, 16.23%.
4.3. Synthesis of 6-methyl-5-phenyl-2-sulfanyl-2-sulfido-1,2,3,5-tetrahydro-
4H-[1,2]oxazolo[4ꢀ,5ꢀ:5,6]pyrano[2,3-d][1,3,2]diazaphosphinine-4-thione (4)
A mixture of tetraphosphorus decasulfide (1.11 g, 2.5 mmol) and compound 3 (0.63 g,
2.5 mmol) in dry toluene (40 ml) was heated under reflux for 5 h. The formed solid on heat-
ing was filtered off and recrystallized from diluted ethanol to give orange crystalline solid in
56% yield; mp 160−162°C. IR (KBr), (νmax, cm−1): 3400, 3300 (br, 2 NH), 3050 (C–Harom),
2925 (C–Haliph), 2605 (br, SH), 1599 (C=N), 1573 (C=C), 1129 (C=S), 1049 (O–C), 691
(P=S). 1H-NMR (400 MHz, DMSO-d6): 2.37 (s, 3H, CH3), 3.70 (br, 1H, SH), 4.89 (s, 1H,
H–5), 7.28–7.32 (m, 2H, Ph–H), 7.40–7.48 (m, 3H, Ph–H), 10.04 (brs, 1H, NH), 11.79 (brs,
1H, NH). 13C-NMR (100 MHz, DMSO-d6): 15.2 (CH3), 25.9 (C–5), 79.5 (C–4a), 119.6
(C–5a), 124.3 (C–3ꢀ,5ꢀ), 127.4 (C–4ꢀ), 130.7 (C–2ꢀ,6ꢀ), 134.8 (C–1ꢀ), 142.2 (C–6), 153.0
(C–8a), 161.4 (C–9a), 186.3 (C–4). 31P-NMR (162 MHz, DMSO-d6): 35.1 ppm. MS (m/z,
I %): 381 (M+, 22%). Anal. Calcd for C14H12N3O2PS3 (381.44): C, 44.08%; H, 3.17%; N,
11.02%; S, 25.22%. Found: C, 43.82%; H, 2.84%; N, 10.74%; S, 24.88%.
4.4. Synthesis of pyridinium 6-methyl-5-phenyl-2-sulfido-4-thioxo-1,2,3,5-tetrah-
ydro-4H-[1,2]oxazolo[4ꢀ,5ꢀ:5,6]pyrano[2,3-d][1,3,2]diazaphosphinine-2-sulfide (5)
Method A: A solution of compound 4 (0.15 g) in dry pyridine (5 ml) was warmed at 60°C
for 15 min. After cooling, the mixture was poured into cold water and neutralized with
diluted 5% hydrochloric acid. The formed solid was filtered off, washed with water and
crystallized from diluted dioxane to give yellow solid in 67% yield; mp 156−157°C.
Method B: A solution of tetraphosphorus decasulfide (1.11 g, 2.5 mmol) in pyridine
(20 ml) was heated under reflux for 2 h to form the pyridine complex. A solution of com-
pound 3 (0.63 g, 2.5 mmol) in dry pyridine (10 ml) was added to the above solution and
further under reflux for 6 h. After cooling, the mixture was poured into cold water and
neutralized with diluted 5% hydrochloric acid. The formed solid was filtered off, washed
with water, and crystallized from diluted dioxane to give yellow solid in 34% yield; mp
155−156°C. IR (KBr), (νmax, cm−1): 3421 (br, 2 NH), 3030 (C–Harom), 2934 (C–Haliph),
1594 (C=N), 1540 (C=C), 1126 (C=S), 1025 (O–C), 692 (P=S). 1H-NMR (400 MHz,

JOURNAL OF SULFUR CHEMISTRY
9
DMSO-d6): 2.43 (s, 3H, CH3), 5.03 (s, 1H, H–5), 7.33–7.49 (m, 5H, Ar–H), 7.57–7.62 (m,
2H, Ar–H), 7.69–7.72 (m, 2H, Ar–H), 7.95 (d, 1H, Ar–H), 8.56 (s, 1H, NH), 9.79 (brs, 1H,
NH), 11.06 (brs, 1H, NH). 13C-NMR (100 MHz, DMSO-d6): 15.4 (CH3), 27.3 (C–5), 78.5
(C–4a), 118.9 (C–5a), 123.6 (C–β,βꢀpyridine), 125.4 (C–3ꢀ,5ꢀ), 128.3 (C–4ꢀ), 132.4 (C–2ꢀ,6ꢀ),
133.5 (C–γ pyridine), 135.2 (C–1ꢀ), 140.3 (C–αpyridine), 144.8 (C–6), 151.3 (C–8a), 161.1
(C–9a), 182.5 (C–4). MS (m/z, I %): 460 (M+, 6%). Anal. Calcd for C19H17N4O2PS3
(460.43): C, 49.56%; H, 3.69%; N, 12.17%; S, 20.86%. Found: C, 49.22%; H, 3.31%; N,
11.89%; S, 20.51%.
4.5. Synthesis of 2-ethoxy-6-methyl-5-phenyl-2-sulfido-1,2,3,5-tetrahydro-4H-
[1,2] oxazolo[4ꢀ,5ꢀ:5,6]pyrano[2,3-d][1,3,2]diazaphosphinine-4-thione (7)
A solution of tetraphosphorus decasulfide (1.11 g, 2.5 mmol) in absolute ethanol (30 ml)
was heated under reflux for 1 h to give O,O-diethyldithiophosphoric acid in situ. Com-
pound 3 (0.63 g, 2.5 mmol) was added to the previous ethanolic solution. The mixture was
heated under reflux for 14 h. The reaction mixture was concentrated into its half volume
and left to cool. The formed solid was filtered off and recrystallized from diluted ethanol to
give orange solid in 43% yield; mp 173−175°C. IR (KBr), (νmax, cm−1): 3421 (br, 2 NH),
3050 (C–Harom), 2934 (C–Haliph), 1593 (C=N), 1552 (C=C), 1131 (C=S), 1025, 1006
(O–C), 758 (P=S). 1H-NMR (400 MHz, DMSO-d6): 1.14 (t, 3H, J = 7.2 Hz, CH3), 2.32
(s, 3H, CH3), 3.40 (q, 2H, J = 7.2 Hz, OCH2), 4.98 (s, 1H, H–5), 7.20–7.30 (m, 2H, Ph–H),
7.47 (d, 1H, J = 8.4 Hz, Ph–H), 7.64–7.73 (m, 2H, Ph–H), 9.07 (s, 1H, NH), 11.71 (brs, 1H,
NH). 13C-NMR (100 MHz, DMSO-d6): 15.2 (CH3), 17.7 (CH3), 28.3 (C–5), 56.8 (OCH2),
80.2 (C–4a), 116.9 (C–5a), 123.5 (C–3ꢀ,5ꢀ), 128.7 (C–4ꢀ), 132.2 (C–2ꢀ,6ꢀ), 135.1 (C–1ꢀ),
144.4 (C–6), 152.1 (C–8a), 161.7 (C–9a), 183.6 (C–4). MS (m/z, I %): 393 (M+, 100%).
Anal. Calcd for C16H16N3O3PS2 (393.43): C, 48.85%; H, 4.10%; N, 10.68%; S, 16.30%.
Found: C, 48.53%; H, 3.85%; N, 10.27%; S, 16.01%.
4.6. Synthesis of 2-(4-methoxyphenyl)-6-methyl-5-phenyl-2-sulfido-1,2,3,5-tetrah-
ydro-4H-[1,2]oxazolo[4ꢀ,5ꢀ:5,6]pyrano[2,3-d][1,3,2]diazaphosphinine-4-thione (8)
Method A: LR (1.0 g, 2.5 mmol) was added to a solution of compound 3 (0.63 g, 2.5 mmol)
in dry toluene (30 ml). The mixture was heated under reflux for 7 h. The solution was con-
centrated to its half volume and left to cool. The oily product was treated with petroleum
ether to give the precipitate which was filtered off and recrystallized from diluted ethanol
to give orange solid in 71% yield; mp 103−104.
Method B: A solution of LR (1.0 g, 2.5 mmol) in absolute ethanol (30 ml) was heated under
reflux for 2 h. Compound 3 (0.63 g, 2.5 mmol) was added to the previous ethanolic solution.
The mixture was heated under reflux for 11 h. The reaction mixture was concentrated into
its half volume and left to cool. The formed solid was filtered off and recrystallized from
diluted ethanol to give orange solid in 68% yield; mp 105−106°C. IR (KBr), (νmax, cm−1):
3424 (br, 2 NH), 3020 (C–Harom), 2934, 2838 (C–Haliph), 1601 (C=N), 1573 (C=C), 1127
(C=S), 1027 (O–C), 692 (P=S). 1H-NMR (400 MHz, DMSO-d6): 2.42 (s, 3H, CH3), 3.85
(s, 3H, OCH3), 4.97 (s, 1H, H–5), 6.86 (t, 2H, J = 7.2 Hz, H-3ꢀꢀ,5ꢀꢀ), 7.60–7.63 (m, 2H,
Ph–H), 7.69–7.74 (m, 3H, Ph–H), 7.90 (d, 2H, J = 7.2 Hz, H-2ꢀꢀ,6ꢀꢀ), 9.21 (s, 1H, NH),
11.26 (s, 1H, NH). 13C-NMR (100 MHz, DMSO-d6): 14.3 (CH3), 28.1 (C–5), 55.6 (OCH3),

10
T. E. ALI ET AL.
79.9 (C–4a), 113.8 (C-3ꢀꢀ,5ꢀꢀ), 116.4 (C–5a), 123.0 (C–3ꢀ,5ꢀ), 127.7 (C–4ꢀ), 130.4 (C–2ꢀ,6ꢀ),
130.9 (d, J = 160 Hz, C–1ꢀꢀ), 132.4 (C–2ꢀꢀ,6ꢀꢀ), 133.6 (C–1ꢀ), 141.4 (C–6), 150.5 (C–4ꢀꢀ),
151.3 (C–8a), 164.4 (C–9a), 183.1 (C–4). 31P-NMR (162 MHz, DMSO-d6): 52.3 ppm. MS
(m/z, I %): 455 (M+, 5%). Anal. Calcd for C21H18N3O3PS2 (455.50): C, 55.38%; H, 3.98%;
N, 9.23%; S, 14.08%. Found: C, 55.02%; H, 3.71%; N, 8.98%; S, 13.87%.
4.7. Synthesis of 3,5-diphenyl-4-imino-2-(4-methoxyphenyl)-6-methyl-2-sulfido-
1,2,3,5-tetrahydro-4H-[1,2]oxazolo[4ꢀ,5ꢀ:5,6]pyrano[2,3-d][1,3,2]
diazaphosphinine (11)
A mixture of LR (0.5 g, 1.25 mmol) and distillated aniline (0.5 ml, 5 mmol) in dry toluene
was heated under reflux for 4 h. Compound 3 (0.63 g, 2.5 mmol) was added to the previ-
ous mixture. The mixture was further heated under reflux for 16 h. The reaction mixture
was concentrated into its half volume and left to cool. The formed solid was filtered
off, washed with petroleum ether, and recrystallized from diluted ethanol to give pale
brown solid in 46% yield; mp 140−142°C. IR (KBr), (νmax, cm−1): 3420 (br, 2 NH),
3035 (C–Harom), 2956, 2839 (C–Haliph), 1602 (C=N), 1573 (C=C), 1028 (O–C), 655
1
(P=S). H-NMR (400 MHz, DMSO-d6): 2.39 (s, 3H, CH3), 3.88 (s, 3H, OCH3), 4.98
(s, 1H, H–5), 6.81 (d, 2H, J = 7.2 Hz, H–3ꢀꢀꢀ,5ꢀꢀꢀ), 6.93–6.97 (m, 5H, Ph–H), 7.17 (t, 1H,
J = 6.4 Hz, Ph–H), 7.32–7.40 (m, 3H, Ph–H), 7.48–7.57 (m, 1H, Ph–H), 7.67 (d, 2H,
J = 8.0 Hz, H–2ꢀꢀꢀ,6ꢀꢀꢀ), 9.61 (brs, 1H, NH), 11.07 (brs, 1H, NH). 13C-NMR (100 MHz,
DMSO-d6): 15.4 (CH3), 27.9 (C–5), 54.3 (OCH3), 79.7 (C–4a), 112.8 (C–3ꢀꢀꢀ,5ꢀꢀꢀ), 115.0
(C–5a), 122.9 (C–3ꢀꢀ,5ꢀꢀ), 124.2 (C–3ꢀ,5ꢀ), 125.0 (C–4ꢀꢀ), 127.1 (C–4ꢀ), 130.6 (d, J = 140 Hz,
C–1ꢀꢀꢀ), 132.0 (C–3ꢀꢀ,5ꢀꢀ), 133.3 (C–2ꢀꢀꢀ,6ꢀꢀꢀ), 134.4 (C–2ꢀ,6ꢀ), 135.2 (C–1ꢀ), 139.9 (C–1ꢀꢀ),
142.9 (C–6), 149.3 (C–4ꢀꢀꢀ), 151.2 (C–8a), 157.2 (C–4), 160.9 (C–9a). 31P-NMR (162 MHz,
DMSO-d6): 48.3 ppm. MS (m/z, I %): 514 (M+, 11%). Anal. Calcd for C27H23N4O3PS
(514.55): C, 63.03%; H, 4.51%; N, 10.89%; S, 6.23%. Found: C, 62.78%; H, 4.24%; N, 10.51%;
S, 5.96%.
Disclosure statement
No potential conflict of interest was reported by the authors.
Funding
The authors extend their appreciation to the Deanship of Scientific Research at King Khalid Univer-
sity for funding this work through research groups program under grant number R.G.P.1/22/38.
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