Synthesis of new benzoxazaphosphinine/benzoxazaphosphole/ diazaphosphaphenalene-2-sulfides using Lawesson's reagent

Article abstract of DOI:10.1080/00397910701649148

Synthesis of new benzoxazaphosphinine/benzoxazaphosphole/ diazaphosphaphenalene 2-sulfides were accomplished by the reaction of Lawesson's reagent (LR) with 4-bromo-2-[(phenylamino) methyl]phenol (1a), 4-bromo-2-[(4-chloro/bromo/methoxy/methylphenyl-amino)methyl]phenol (1b-e), 4-bromo-2-[(benzylamino)methyl]phenol (1f), 2-amino-4-chlorophenol (2a)/2-amino-4-methylphenol (2b), 1,8-diaminonaphthalene (3) respectively in anhydrous toluene. Products 4a-f, 5a-b and 6 were characterized by IR, 1H, 13C, 31P NMR and Mass spectra. Copyright Taylor & Francis Group, LLC.

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Synthesis of New Benzoxazaphosphinine/
Benzoxazaphosphole/
Diazaphosphaphenalene‐2‐sulfides using
Lawesson's Reagent
G. Syam Prasad a , B. Hari Babu a , C. Devendranath Reddy a , C. Naga Raju a
& C. Suresh Reddy a
a Department of Chemistry , Sri Venkateswara University , Tirupati, India
Published online: 25 Jan 2008.
To cite this article: G. Syam Prasad , B. Hari Babu , C. Devendranath Reddy , C. Naga Raju & C. Suresh Reddy
(2007) Synthesis of New Benzoxazaphosphinine/Benzoxazaphosphole/Diazaphosphaphenalene‐2‐sulfides
using Lawesson's Reagent, Synthetic Communications: An International Journal for Rapid Communication of
Synthetic Organic Chemistry, 38:1, 85-91, DOI: 10.1080/00397910701649148
To link to this article: http://dx.doi.org/10.1080/00397910701649148
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Synthetic Communicationsw, 38: 85–91, 2008
Copyright # Taylor & Francis Group, LLC
ISSN 0039-7911 print/1532-2432 online
DOI: 10.1080/00397910701649148
Synthesis of New Benzoxazaphosphinine/
Benzoxazaphosphole/
Diazaphosphaphenalene-2-sulfides using
Lawesson’s Reagent
G. Syam Prasad, B. Hari Babu, C. Devendranath Reddy,
C. Naga Raju, and C. Suresh Reddy
Department of Chemistry, Sri Venkateswara University, Tirupati, India
Abstract: Synthesis of new benzoxazaphosphinine/benzoxazaphosphole/diazapho-
sphaphenalene 2-sulfides were accomplished by the reaction of Lawesson’s reagent
(LR) with 4-bromo-2-[(phenylamino) methyl]phenol (1a), 4-bromo-2-[(4-chloro/
bromo/methoxy/methylphenyl-amino)methyl]phenol (1b–e), 4-bromo-2-[(benzyla-
mino)methyl]phenol (1f), 2-amino-4-chlorophenol (2a)/2-amino-4-methylphenol
(2b), 1,8-diaminonaphthalene (3) respectively in anhydrous toluene. Products 4a–f,
1
5a–b and 6 were characterized by IR, H, 13C, 31P NMR and Mass spectra.
Keywords: benzoxazaphosphinine/benzoxazaphosphole/diazaphosphaphenalene 2-
sulfides, Lawesson’s reagent
INTRODUCTION
Interest has increased in the past 20 years in the chemistry of phosphorus het-
erocyclics because of their unique physicochemical properties[1] and potential
biological activities.[2–5] Many classes of phosphorus hreterocyclic systems
bearing P-O and P-N moieties such as cyclophosphamide and its derivatives
are antitumor agents.[6] Cyclic phosphorus-containing hexapyranose analog
modified at the anomeric carbon are regulators in the carbohydrate-linked
life process.[7] 1,4-Dihydropyridine-5-cyclic phosphonate derivatives have
Received in India May 15, 2007
Address correspondence to C. Suresh Reddy, Department of Chemistry, Sri Venka-
teswara University, Tirupati, India. E-mail: csureshsvu@yahoo.com
85

86
G. S. Prasad et al.
antihypertensive activity.[8] The reaction between Lawesson’s reagent (LR)
and aliphatic[9] and aromatic[9] diols run in boiling toluene led to exclusively
cyclic anisylphosphonothioates. This readiness of diol derivatives to undergo
intramolecular cyclization[10] led to the synthesis of five- and seven-membered
phosphorous heterocycles. LR, widely known as a powerful thionation reagent
in organic synthesis, offers another route to complexes containing P/S-based
anionic ligands.[11,12] The burgeoning field of heterocyclic phosphorus
compounds with LR has been fully reviewed.[10–13] As a continuation of
our work[14] on synthesis and bioactive phosphorus heterocycles, a few new
five- and six-membered phosphorus heterocycles have been synthesized by
reacting 1a–f, 2a–b, and 3 with 2,4-bis(4-methoxyphenyl)-1,3,2,4-dithiadi-
phosphetane-2,4-disulfide (LR).
RESULTS AND DISCUSSION
On reaction with 1a–f prepared by condensation of various aromatic amines,
4-bromophenol, and aqueous formaldehyde,[17,20] LR, 2a–b, and 3 in
anhydrous toluene in 1:1 molar ratio at reflux temperature under nitrogen
atmosphere for 6–8 h afforded the heterocycles 4a–f, 5a–b, and 6 in
moderate yields (Scheme 1). Their chemical structures are confirmed by
elemental analysis; IR (Table 1); 1H, 13C, and 31P NMR (Table 2); and
mass spectra. Characteristic absorption bands for P55S, P-O, and
O-C(aromatic) stretching vibrations were observed for them in the regions
732–763, 923–998 and 1205–1225 cm21 respectively.[15,16] Compounds
Scheme 1.

Table 1. Physical and IR spectral data of 4, 5, and 6
Elemental analysis (%) found (calcd.)
IR (cm21
)
Compd. Mp (8C) Yield (%)
Mol. formula (mol. wt)
C
H
N
P55S P-O O-C(aromatic) N-H
4a
4b
4c
4d
4e
4f
122–124
170–173
182–184
142–144
147–150
174–176
194–196
187–189
210–213
39.6
40.4
38.6
38.3
41.3
42.0
32.0
32.6
40.2
C20H17BrNO2PS (446.30)
C20H16BrClNO2PS (480.74)
C20H16Br2NO2PS (525.19)
C21H19BrNO3PS (476.32)
C21H19BrNO2PS (460.32)
C21H19BrNO2PS (460.32)
C13H11ClNO2PS (311.72)
C14H14NO2PS (291.31)
C17H15N2OPS (326.35)
53.89 (53.82) 3.82 (3.84) 3.17 (3.14) 752 978
49.96 (49.97) 3.29 (3.35) 2.88 (2.91) 756 990
45.82 (45.74) 3.01 (3.07) 2.61 (2.67) 753 969
52.90 (52.95) 3.96 (4.20) 2.91 (2.94) 750 998
54.72 (54.79) 4.06 (4.16) 3.02 (3.04) 752 989
54.73 (54.79) 4.11 (4.16) 3.07 (3.04) 749 979
50.12 (50.09) 3.48 (3.56) 4.43 (4.49) 738 924
57.69 (57.72) 4.81 (4.84) 4.83 (4.81) 742 923
1212
1205
1225
1225
1225
1216
1217
1221
—
—
—
—
—
—
—
5a
5b
6
3215
3219
3285
62.51 (62.56) 4.57 (4.63) 8.41 (8.58) 763
—

88
G. S. Prasad et al.
Table 2. (1H, 13C, and 31P) NMR spectral data (d, CHCl3) of 4, 5, and 6
Compd.
1H NMR
13C NMR
—
31P NMR
88.59
4a
6.27–8.01 (m, 12H, HAr),
3.99–4.14 (m, 2H, CH2), 3.87
(s, 3H, OCH3)
4b
4c
6.88–7.80 (m, 11H, HAr),
4.47–4.85 (m, 2H, CH2), 3.83
(s, 3H, OCH3)
51.61, 55.40, 113.99,
114.15, 121.05, 127.37,
129.24, 129.55, 132.22,
144.90, 149.27, 162.98
51.39, 55.37, 113.92,
114.08, 116.43, 120.95,
122.46, 126.49, 129.48,
131.00, 132.39, 142.38,
148.38, 163.31
77.86
77.80
6.88–8.0 (m, 11H, HAr),
4.44–4.90 (m, 2H, CH2), 3.83
(s, 3H, OCH3)
4d
4e
4f
6.73–7.84 (m, 11H, HAr),
4.36–4.84 (m, 2H, CH2),
3.70 (s, 3H, OCH3), 3.83
(s, 3H, OCH3)
52.13, 55.32, 113.73,
113.94, 114.29, 119.08,
120.94, 128.27, 128.76,
129.47, 131.87, 136.54,
149.35, 163.01
78.59
78.21
81.08
6.77–7.82 (m, 11H, HAr),
4.42–4.86 (m, 2H, CH2),
3.83 (s, 3H, OCH3), 2.26
(s, 3H, CH3)
20.85, 51.73, 55.35,
113.77, 113.93, 116.19,
118.60, 126.21, 126.81,
129.69, 130.08, 131.92,
140.55, 149.66, 163.22
46.76, 55.52, 114.08,
6.77–8.26 (m, 12H, HAr),
4.53–5.15 (m, 2H, CH2), 3.87 117.58, 118.63, 120.23,
(s, 2H, CH2), 3.81 (s, 3H,
OCH3)
121.12, 127.43, 128.13,
128.63, 130.11, 132.69,
134.18, 136.22, 138.01,
150.18, 161.58, 163.95
—
5a
5b
6
6.91–8.23 (m, 7H, HAr), 5.35
(d, J ¼ 10.7 Hz, 1H, NH), 3.85
(s, 3H, OCH3)
67.04
70.96
43.88
6.71–8.23 (m, 7H, HAr), 5.28
(s, 1H, NH), 3.87 (s, 3H,
OCH3), 2.28 (s, 3H, CH3)
20.77, 55.53, 114.10,
123.23, 126.46, 127.61,
133.76, 134.43
6.57–7.71 (m, 10H, HAr), 5.47 55.32, 110.10, 113.85,
(d, J ¼ 10.9 Hz, 1H, NH), 3.69
114.00, 120.83, 127.12,
132.35, 136.67
(s, 3H, CH3)
4a–f, 5a–b, and 6 exhibited a complex multiplet at 6.27–8.26 ppm for
aromatic protons. Methylene protons in 4a–f resonated as multiplets at d
3.99–5.15 indicating their nonequivalence and coupling with phosphorus.[17]
It is interesting to observe a doublet for the NH in 5a and 6, while 5b gave as a
singlet for it at d 5.28–5.47. The observed 13C NMR chemical shifts for them

Synthesis of New Benzoxazaphosphinine
89
are in the expected range.[17,18] 31P NMR signals[19] of 4a–f, 5a–b, and 6
appeared at 67.04–81.08 and 43.88 ppm, respectively. The mass spectra for
4e and 6 as representatives were recorded. 4e (FABMS): m/z (%) ¼ 461
[47, (Mþ þ 2)], 459 [43, (Mþ†)], 428 (36), 380 (17), 353 (24), 290 (40),
274 (49), 242 (25), 136 (65) and 6 (LCMS): m/z (%) ¼ 327 [100,
(Mþ þ 1)], 279 (21), 260 (10), 238 (8), 217 (3.5), 148.9 (8).
EXPERIMENTAL SECTION
Melting points were determined on a Mel-Temp apparatus and are uncorrected.
Elemental analyses were performed at the Central Drug Research Institute,
Lucknow, India. The IR spectra were recorded as KBr pellets on a Perkin-
1
Elmer 1430 unit. All H, 13C, and 31P NMR spectra were recorded on an
1
AMX 400-MHz spectrometer operating at 400 MHz for H, 100 MHz for
13C, and 161.9 MHz for 31P. Compounds were dissolved in CDCl3, and the
chemical shifts were referenced to TMS (1H and 13C) and 85% H3PO4 (31P).
4-Bromo-2-[(4-chlorophenylamino)methyl]phenol (1b)
To a stirred and cooled (10–208C) solution of aqueous formaldehyde (37%;
7.5 mL, 0.1 mol) in 1,4-dioxane (30 mL), 4-chloroaniline (11.10 g, 0.1 mol)
was added at 15–208C. To the stirred reaction mixture, a solution of 4-bromo-
phenol (17.3 g, 0.1 mol) in 1,4-dioxane (20 mL) was added dropwise through
a dropping funnel, and the resulting solution was kept at gentle reflux for 1 h.
Upon removal of 1,4-dioxane and water by a rotary evaporator, a sticky mass
remained, which was recrystallized with 95% ethanol to yield[20] 1b (26.5 g,
75%), mp 80–828C.
Similarly 1a, and 1c–f were prepared using corresponding aromatic
amines. LR was prepared according to published procedure.[21]
General Procedure for Synthesis of 4a–f, 5a and b, and 6
A three-necked flask equipped with a dropping funnel, stirrer, dry CaCl2 tube
and nitrogen gas inlet was charged with 10 mL of anhydrous toluene and
1 mmol of 1a–f, 2a–b, and 3. Lawesson’s reagent (1 mmol) was added to
the flask at room temperature, and the reaction mixture was refluxed with
stirring under dry nitrogen for 6–8 h until no starting materials could be
detected on thin-layer chromatography (TLC). Evaporation of solvent
followed by column chromatography on silica gel using petroleum ether–
ethyl acetate (8:2) as eluent afforded corresponding heterocycles 4a–f, 5a–b,
and 6. Their yields were determined after separation on a silica-gel column,
and structures were confirmed by elemental analysis and spectral data.

90
G. S. Prasad et al.
CONCLUSION
A simple methodology was developed for the synthesis of several six-
membered benzoxazaphosphinine 2-sulfides, benzoxazaphosphole 2-sulfides,
and diazaphosphaphenalene 2-sulfide, which are of value as potential
antibacterials.
ACKNOWLEDGMENT
The authors express thanks to Sophisticated Instruments Facility (SIF), Indian
Institute of Science (IISc), Bangalore, for providing the NMR spectral data.
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