Syntheses, spectral property, and antimicrobial activities of 6-α-amino dibenzo [d,f][1,3,2]dioxaphosphepin 6-oxides

Article abstract of DOI:10.1002/hc.20226

Diethyl α-aminophosphonates (4) were prepared in excellent yield from three-component reaction of aldehydes (1), amines (2), and triethylphosphite (3) under solvent-free conditions in the presence of ceric ammonium nitrate (CAN) and were reacted with 2,2'-dihydroxybiphenyl (5) using p-toluene sulfonic acid monohydrate (PTSA) as a catalyst to obtain 6-α-aminodibenzo[d, f][1,3,2]dioxaphosphepin 6-oxides (6) in good yield. It is a first report on the cyclizations of 4 with 5. An antimicrobial activity of numbers of 6 is evaluated.

Full text of DOI:10.1002/hc.20226

Heteroatom Chemistry
Volume 18, Number 1, 2007
Syntheses, Spectral Property, and
Antimicrobial Activities of 6-ꢀ-Amino Dibenzo
[d,f ][1,3,2]Dioxaphosphepin 6-Oxides
M. Kasthuraiah, K. Ananda Kumar, C. Suresh Reddy,
and C. Devendranath Reddy
Department of Chemistry, Sri Venkateswara University Tirupati 517 502, India
Received 15 November 2004; revised 21 April 2005
a one-pot procedure. The key intermediates of
ABSTRACT: Diethyl ꢀ-aminophosphonates (4)
ꢀ-aminophosphonates (4) are known as pep-
were prepared in excellent yield from three-component
tidomimetics [4], antibiotics, and pharmacological
reaction of aldehydes (1), amines (2), and triethylphos-
agents [5,6]. Lewis acid catalyzed addition of diethyl
phite (3) under solvent-free conditions in the presence
phosphite to aldimine provided a useful method
of ceric ammonium nitrate (CAN) and were reacted
for the preparation of ꢀ-aminophosphonates [7].
with 2,2ꢀ-dihydroxybiphenyl (5) using p-toluene
Recently, three-component synthesis starting from
sulfonic acid monohydrate (PTSA) as a catalyst to ob-
aldehyde, amine, and diethyl/triethyl phosphite has
tain 6-ꢀ-aminodibenzo[d,f ][1,3,2]dioxaphosphepin
been reported using Lewis acids such as LiClO4[8]
6-oxides (6) in good yield. It is a first report on the
and InCl3[9], and lanthanide trifolates [10] of late
cyclizations of 4 with 5. An antimicrobial activity of
microwave reactions in the presence of TaCl5-
ꢁ
C
numbers of 6 is evaluated.
2007 Wiley Periodicals,
SiO2[11],Al2O3, and montmorillonite clay [12,13]
have been developed for their synthesis [14]. Due to
the growing concern of the toxic influence of the or-
ganic solvent on the environment and its life forms,
solvent-free organic syntheses have determined for
the attention of organic chemists [15].
Inc. Heteroatom Chem 18:2–8, 2007; Published online in
Wiley InterScience (www.interscience.wiley.com). DOI
10.1002/hc.20226
INTRODUCTION
Dibenzodioxaphosphocins, dioxathiaphosphocins,
and dioxaphosphepins have been used as antioxi-
dants [1,2] and superior ligands [3]. Our con-
tinuous effort to look for bioactive heterocyclic
compounds led to the accomplishment of a new and
efficient synthesis of 6-ꢀ-amino dibenzo[d,f ]-
[1,3,2]dioxaphosphepin 6-oxides (6). The procedure
involves treatment of 2,2ꢀ-dihydroxybiphenyl (5)
with various ꢀ-aminoalkyl phosphonates (4) in
RESULTS AND DISCUSSION
A versatile, straightforward, and relatively inexpen-
sive solvent-free one-pot synthesis of ꢀ-aminophos-
phonates (4) was carried out using ceric ammo-
nium nitrate (CAN) as a catalyst. The viability of this
procedure and efficiency of CAN as a catalyst was
tested with several structurally varied aldehydes and
amines. The reaction was successfully completed
with all of them in 20–40 min affording varied yields
(89–98%) depending on the nature of the reactants
(Table 1). A typical experimental procedure for 4 is
that a mixture of aldehyde, amine, triethylphosphite,
Correspondence to: C. Suresh Reddy; e-mail: csureshsvu@
yahoo.com.
c
ꢁ
2007 Wiley Periodicals, Inc.
2

Syntheses, Spectral Property, and Antimicrobial Activities of 6-ꢀ-Amino Dibenzo [d,f][1,3,2]Dioxaphosphepin 6-Oxides
3
TABLE 1 Synthesis of ꢀ-Aminophosphonate (4a–p)
Time Yield
(min) (%)
Compd.
R
R1
IR (cm−1
)
4a
4b
4c
4d
4e
4f
4g
4h
4I
C H5
C6H5
C H5
C6H5
30
30
30
30
35
25
30
35
25
96 3331, 2982, 1604, 1512, 1240, 1025, 970, 758
93 3328, 2973, 1617, 1514, 1226, 1014, 965, 754
93 3362, 2890, 1670, 1540, 1385, 1090, 970, 730
96 3324, 2972, 1564, 1520, 1230, 1020, 970, 750
92 3360, 3180, 1630, 1570, 1530, 1200, 1070, 750
96 3382, 3002, 1682, 1530, 1268, 1070, 971, 770, 562
93 3360, 3008, 1700, 1550, 1270, 1050, 980, 770, 660
93 3362, 3010, 1670, 1552, 1278, 1040, 970, 776
96 3378, 3076, 2370, 1768, 1507, 1242, 1090, 790, 730
92 3376, 3102, 2908, 1630, 1560, 1290, 1080, 962, 790, 560
90 3302, 3214, 3070, 1670, 1570, 1242, 1086, 980, 880, 770
91 3397, 1510, 1250, 1020, 970, 780
92 3340, 2980, 2750, 1760, 1618, 1450, 1230, 970, 840,
790, 548
C6H5CH
2
4 6 CH O C H5
3,4 (H3CO)62 C6H3 2 6 H3C C6H4
3
4 HO C6H4
4 H3C C6H4
4 Cl C6H4
4 O2N C6H4
C H5
C H5
2 6 H3C C6H4
C H5
C6H5
6
CH3O C6H4
4j
4k
4l
C6H5
2 Br, 4 H3C C6H3 30
2 Cl C6H4 40
2 Br, 4 H3C C6H3 35
2 6 HO C6H4
4 H3C C6H4
C6H11
4m
C6H5
30
4n
4o
4p
C H5CH CH
C6H5CH CH
2 6 Naphthyl
C H5
30
30
30
90 3306, 2990, 2922, 1613, 1592, 1240, 1020, 968, 809, 702
90 3306, 2970, 2910, 1610, 1590, 1240, 1010, 970, 801, 708
93 3382, 2982, 1720, 1475, 1320, 1242, 1100, 872, 820, 762
4 6 H3C C6H4
C6H5
and catalytic amount of CAN is refluxed with vig-
orous stirring, and the progress of the reaction was
monitored by TLC. The crude ꢀ-aminophosphonates
(4) were purified by column chromatography (see
Scheme 1).
SCHEME 1
The merit of the above procedure is further
proved when poor yields of ꢀ-aminophosphonate
(4a) resulted when the same reaction is carried out
with other catalyst, Mn(OAc)3 with/without solvent
(Table 2).
The success of this reaction may be attributed
to the catalytic role played by CAN. The cerium by
virtue of its strong stabilizing ability of the imine (A)
and carbocation (B) facilitates initial nucleophilic
attack of phosphorus at the imine carbon leading
to the formation of ylide C. Further, the inherent
tendency of C to break down to form more sta-
ble ꢀ-aminophosphonates (4) drives the reaction to
completion.
The reaction of O, O-diethyl ꢀ-aminophospho-
nates (4) with 2,2-dihydroxybiphenyl (5) in the pres-
ence of p-toluene sulfonic acid (PTSA) as a catalyst in
toluene with stirring at reflux temperature afforded
6-ꢀ-aminodibenzo[d,f ][1,3,2]dioxaphosphepin 6-
oxides in high yield (Table 3). Ethanol formed
during the course of the reaction was distilled out
along with toluene till its volume was reduced to
half to prevent a reverse reaction. It is a first report
on similar cyclizations using PTSA.
All the members of 6 exhibited characteristic IR
absorption [16,17] for P O and P OC(aromatic) groups.
In their 1H NMR spectra, phenylaminobenzyl
dibenzodioxaphosphepin moieties showed complex
multiplets in the range of 6.60–7.7 for the 18 protons.
Heteroatom Chemistry DOI 10.1002/hc

4
Kasthuraiah et al.
TABLE 2 Effect of the Solvent and Reagents
pounds 6c–h exhibited very high activity against
Klebsiella pneumoniae when compared to the ac-
tivity of the standard penicillin. The compound 6d
showed the highest activity. In view of their very
strong antibacterial activity, further detailed study
on the evaluation of their antimicrobial activity is in
progress to explore their commercial applications.
Compd.
Solvent
Reagent
Yield (%)
4a
4a
4a
4a
CH3CN
No solvent
CH3CN
Mn(OAc)3
Mn(OAc)3
CAN
78
80
82
96
No solvent
CAN
P-CH methylene proton in all the compounds ap-
EXPERIMENTAL
peared as a doublets in the range of 4.42–5.0 (2 JCH
P
All reactions were carried out under anhydrous con-
ditions in nitrogen atmosphere. Melting points were
determined in Mel-Temp apparatus using open cap-
= 22.5–24.36 Hz). The aliphatic methyl and methoxy
protons of 6-substituted moieties exhibited signals
at δ 2.10 and 3.95, respectively. Then 13C NMR
chemical shifts (see Tables 4 and 5) were inter-
preted based on comparison with carbon chemical
shifts of 5 and related systems [17,18]. The 31P
NMR signals are observed in the range of 29.2–
43.9 ppm [19] for 6-substituted-ꢀ-aminodibenzo
[d,f ][1,3,2]dioxaphosphepin 6-oxides (6 a–h) (see
Table 3).
illary tubes and are uncorrected. IR spectra (νmax
,
cm–1) were measured with Shimadzu-435/Perkin
Elmer 1000 FTIR. NMR spectra were taken on a
Bruker AC 300 spectrometer operating at 300 MHz
1
for H, 75.45 MHz for 13C, and 121.7 MHz for 31P
NMR. Chemical shifts of 1H and 13C were expressed
in δ (ppm) downfield from an internal standard
tetramethylsilane (TMS). 31P chemical shifts are ex-
pressed in δ (ppm) with respect to 85% phospho-
ric acid used as external standard. Microanalyses
were performed at the Central Drug Research Insti-
tute (CDRI) Lucknow, India. TLC monitoring was
carried out using precoated Kieselgel 60F254 plates
(E-Merck).
ANTIMICROBIAL ACTIVITY
Antibacterial activity [20] of 6a–h was screened
against the growth of Staphylococcous aureus (gram
positive) and Klebsiella pneumoniae (gram negative)
at concentrations 200 and 400 ppm. All these com-
pounds exhibited high activity against both the or-
ganisms. Similarly, their antifungal activity was also
studied against the growth of Pellicularia solmani-
color (pink disease) and Macrophomina phoseolina
(dry root rot of sunflower and citrus) at two differ-
ent concentrations (200 and 400 ppm) [21]. All these
results are presented in Table 6. Most of the com-
pounds showed good antifungal activity against the
growth of both the fungi. Penicillin and griseofulvin
was used as a reference standard for bacteria and
fungi, respectively.
O,O-Diethyl 6-ꢀ-aminophosphonates 4a–p
General Procedure: A mixture of the aldehyde (1,
5 mmol), amine (2, 5 mmol), and triethylphosphite
(3, 5 mmol) and catalytic amount of ceric ammo-
nium nitrate (CAN) was stirred under reflux for
30 min. After completion of the reaction as indi-
cated by TLC, the residue was purified by column
chromatography (60–120 mesh silicagel) using ethyl
acetate-hexane (1:2) as an eluent to afford pure ꢀ-
aminophosphonates as solids. Synthetic and spectral
data for 4a–p are given in Tables 1, 3, and 4.
It is interesting to note that the compounds
6c–h exhibited very high antimicrobial activity. Com-
TABLE 3 Synthesis of 6-ꢀ-Aminodibenzo[d,f ][1,3,2]dioxaphosphepin 6-oxides (6a-h)
Elemental Analysis (%)
Calcd.
Found
mp
Yield
(%)
M. Formula
(Molec. weight)
31 P NMR
(ppm)
Compd.
( ◦C)
C
H
C
H
IR (cm−1
)
6a
6b
6c
6d
6e
6f
148–150
172–173
140–141
168–169
152–153
139–140
165–166
178–180
82
75
80
76
72
70
74
72
C25H20NO3P (413.275) 72.63 4.86 72.50
4.70
5.00
4.92
5.33
4.92
4.08
5.00
4.31
37.8
3340, 1302, 1195, 965
C
C
26H22NO3P (427.30) 73.06 5.11 72.87
26H22NO4P (443.32) 70.42 5.06 70.28
43.4, 43.9 3310, 1308, 1221, 985
31.8 3320, 1299, 1235, 969
38.2, 38.8 3325, 1299, 1189, 968
41.2, 41.9 3335, 1298, 1206, 957
29.2, 30.1 3308, 1295, 1223, 961
C27 24
26H22NO4P (443.32) 70.42 5.06 70.26
BrNO3P (506.28) 61.67 4.18 61.51
H
NO3P (441.30) 73.46 5.47 73.30
C
C
H
26 21
6g
6h
C
27H22NO3P (439.30) 73.79 5.04 73.60
39.8
3327, 1308, 1202, 952
C
27H23BrNO3P (520.32) 62.32 4.45 62.16
31.2, 31.7 3315, 1290, 1208, 945
Heteroatom Chemistry DOI 10.1002/hc

Syntheses, Spectral Property, and Antimicrobial Activities of 6-ꢀ-Amino Dibenzo [d,f][1,3,2]Dioxaphosphepin 6-Oxides
5
TABLE 4 1H and 13C NMR Data of 4a–p
Compd.
1H NMR ꢁ
13C NMR
4a
1.1 (t, 3H, J = 7.1 Hz),1.28 (t, 3H, J = 7.1 Hz),
3.68–4.15 (m 4H), 4.75 (d, 1H, J = 24.1 Hz),
6.72 (t, 1H, J = 7.3 Hz) 7.12 (t, 2H, J = 7.3 Hz),
7.23 (m, 1H), 7.34 (t, 2H, J = 7.2Hz), 7.5 (m,
2H).
16.2, 16.5, 59.5, 62.8, 63.0, 127.2, 128.0, 128.4,
128.6, 128.75, 1289.9, 135.5, 139.6
4b
1.18 (t, 3H, J = 7.2 Hz), 1.30 (t, 3H, J = 7.1 Hz),
2.2 (s, 3H), 3.72–3.82 (m, 1H), 3.95–4.2 (m,
3H), 4.71 (dd, 1H, J = 23.8, 7.0 Hz), 5.3 (dd,
1H, J = 7.0, 2.0 Hz), 6.30 (d, 1H, J = 7.8 Hz),
6.78 (d, 1H, J = 7.8 Hz), 7.26–7.52 (m, 6H)
1.17 (t, 3H, J = 7.1 Hz), 1.23 (t, 3H, J = 7.1 Hz),
3.67 (s, 3H), 3.94–4.17 (m, 4H), 4.82 (d, 1H,
J = 23.6 Hz), 6.61–6.72 (m, 5H), 6.80–6.96 (m,
2H), 7.10–7.22 (m, 2H)
1.14 (t, 3H, J = 6.6 Hz), 1.20 (t, 3H, J = 6.7 Hz),
2.31 (s, 3H), 3.64–3.70 (m, 4H), 3.82 (s, 6H),
3.92–4.18 (m, 3H), 4.72 (d, 1H, J = 23.8 Hz),
6.42 (d, 1H, J = 7.8 Hz), 6.64 (d, 1H, J = 7.6
Hz), 6.80 (d, 1H, J = 7.4 Hz), 6.94–7.10 (m, 9H)
1.18 (t, 3H, J = 6.8 Hz), 1.26 (t, 3H, J = 6.7 Hz),
3.9–4.18 (m, 4H), 4.95 (d, 1H, J = 23.8 Hz),
6.62–6.8 (m, 3H), 6.80–6.96 (m, 2H), 7.12–7.30
(m, 4H), 8.86 (br, s, 1H, OH)
16.4, 16.6, 56.3, 63.5, 113.0, 118.5, 128.0,
128.7, 129.2, 130.0, 136.0, 146.3
4c
4d
16.4, 16.5, 55.3, 55.6, 63.4, 114.1, 118.2, 120.4,
125.2, 127.8, 129.0, 132.7, 146.5, 150.4
16.2, 16.4, 20.2, 54.6, 55.6, 57.4, 62.8, 62.9,
110.8, 110.9, 111.0, 113.8, 119.8, 120.0,
127.2, 128.2, 129.4, 144.0, 144.8, 148.4,
148.6, 148.9
4e
4f
16.4, 16.6, 47.8, 50.6, 62.2, 63.6, 114.0, 115.8,
118.5, 120.0, 129.2, 130.0, 131.8, 132.2,
151.7, 158.4, 159.6
1.18 (t, 3H, J = 7.0 Hz), 1.26 (t, 3H, J = 7.0 Hz),
2.25 (s, 3H), 2.31 (s, 3H), 3.60–3.82 (m, 1H),
4.05–4.16 (m, 2H), 4.62 (br, s, 1H, NH),4.72 (d,
1H, J = 23.6 Hz), 6.36 (d, 1H, J = 8.0 Hz), 6.62
(t, 1H, J = 8.0 Hz), 7.0 (t, 1H, J = 8.1 Hz), 7.10
(d, 2H, J = 8.2 Hz) 7.36 (d, 2H, J = 8.2 Hz)
1.16 (t, 3H, J = 6.8 Hz), 1.28 (t, 3H, J = 6.8 Hz),
3.62–3.82 (m, 2H), 4.07–4.2 (m, 2H), 4.63 (br, s,
1H); 6.6 (t, 1H, J = 7.4 Hz), 6.62–6.89 (m, 5H),
16.1, 16.2, 16.3, 17.3, 20.6, 54.2, 57.2, 62.8,
63.0, 111.2, 117.8, 122.6, 126.7, 127.4, 127.6,
129.0, 129.2, 129.8, 132.6, 132.7, 137.4,
137.6, 144.0, 144.5
4g
4h
4i
16.2, 16.4, 59.5, 62.8, 63.2, 127.2, 128.2, 128.6,
128.8, 128.9, 130.0, 135.8, 146.5
6.9–7.10 (m, 2H), 7.11–7.30 (m, 2H)
1.18 (t, 3H, J = 7.0 Hz), 1.30 (t, 3H, J = 7.0 Hz),
16.3, 16.5, 59.5, 62.8, 63.8, 127.2, 128.4, 128.6,
129.2, 129.6, 130.0, 135.8, 146.4, 150.8
3.7–3.87 (m, 2H), 4.17–4.3 (m, 2H), 4.70 (br, s,
1H), 6.58 ( t, 1H, J = 7.4 Hz), 6.7–7.1 (m 5H),
7.32–7.48 (m, 2H), 8.0–8.08 (m, 2H)
1.15 (t, 3H, J = 6.8 Hz), 1.26, (t, 3H, J = 6.8 Hz),
15.7, 15.8, 15.9, 16.2, 20.6, 54.2, 58.0, 62.4,
62.8, 70, 113.4 114.6, 114.8, 121.9, 127.1,
127.4, 127.8, 127.9, 120.0 128.1, 128.3,
129.4, 132.2, 135.6, 139.8, 140.2, 152.0
3.67 (s, 2H), 3.61–4.19 (m, 4H), 4.66 (d, 1H,
J = 24.0 Hz), 6.52 (d, 2H, J = 8.2 Hz) 6.68 (d,
2H, J = 8.2 Hz), 7.21–7.38 (m, 3H), 7.40–7.50
(m, 2H)
4j
1.15 (m, 3H, J = 7.2 Hz), 1.28 (m, 3H, J = 7.0
Hz), 2.25 (br, s, 1H, NH), 3.50 (d, 1H, J = 11.8
Hz), 3.72–4.16 (m, 6H), 7.22–7.46 (m, 6H),
7.22–7.50 (m, 1H)
16.2, 16.3, 16.5, 19.7, 56.0, 57.0, 63.2, 63.3,
110.4, 112.6, 127.6, 127.8, 127.9, 128.3,
128.5, 128.7, 132.6, 135.4, 135.6, 140.8,
141.0
(Continued)
Heteroatom Chemistry DOI 10.1002/hc

6
Kasthuraiah et al.
TABLE 4 Continued
Compd.
1H NMR ꢁ
13C NMR
4k
1.18 (t, 3H, J = 7.2 Hz), 1.24 (t, 3H, J = 7.2
Hz), 3.80–3.92 (m, 1H), 4.05–4.20 (m, 3H),
4.80 (br, s, 1H, NH), 5.05 (d, 1H, J = 23.9
Hz), 6.57 (d, 2H, J = 7.8 Hz), 6.82 (t, 1H,
J = 7.6 Hz), 6.84 (d, 1H, J = 7.6 Hz), 9.05
(br, s, 1H, 6H)
16.4, 16.5, 46.8, 50.3, 62.6, 63.4, 115.6, 118.4,
120.8, 129.4, 130.9, 132.0 132.4, 150.6, 158.9,
159.6
4l
1.18 (t, 3H, J = 7.0 Hz), 1.29 (t, 3H, J = 7.0
Hz), 2.18 (s, 3H), 2.38 (s, 3H), 3.8–3.86 (m,
1H), 3.9–4.20, (m, 3H), 4.70 (d, 1H, J = 7.8
Hz), 6.80 (d, 1H, J = 7.6 Hz), 7.10 (d, 2H,
J = 7.8 Hz), 7.20–7.40 (m, 3H)
16.4, 16.6, 20.3, 21.4, 59.4, 62.6, 62.8, 64.0,
114.8, 118.6, 129.6, 129.8, 130.0, 130.6, 135.2,
136.4, 146.8, 147.9
4m
4n
1.12 (t, 3H, J = 7.2 Hz), 1.28 (t, 3H, J = 7.2
Hz), 1.30–1.86 (m, 1H), 2.63 (dd, 1H,
J = 19.0, 20.0 Hz), 3.95–4.15 (m, 4H),
6.65–7.15 (m, 5H)
16.4, 22.0, 27.2, 28.4, 29.8, 31.2, 39.9, 56.1, 62.6,
113.4, 117.8, 129.7, 129.9, 147.8
1.17 (t, 1H, J = 7.0 Hz), 1.23–1.38 (m 3H), 3.18 16.3, 20.2, 55.7, 62.7, 62.8, 63.4, 113.4, 123.6,
(br, s, 1H, NH), 4.15–4.22 (m, 4H), 4.45 (dd,
1H, J = 2.2, 2.1 Hz), 6.18–6.35 (m, 1H),
6.58–6.67 (m, 3H), 6.88–7.20 (m, 2H),
7.20–7.40 (m, 4H)
126.4, 127.6, 128.4, 129.6, 132.7, 133.0, 136. 2,
143.8
4o
4p
1.23–1.38, (m, 6H), 2.25 (s, 3H), 3.18 (br, s, 1H, 16.3, 20.1, 52.8, 55.9, 62.2, 62.7, 63.1, 113.6,
NH), 4.15–4.22 (m, 4H), 4.45 (dd, 1H,
J = 2.2, 2.1 Hz), 6.18–6.35 (m, 1H), 6.58–6.67
(m, 3H), 6.7–6.92 (m, 2H), 7.22–7.39 (m, 4H)
1.10 (t, 3H, J = 7.0 Hz), 1.30 (t, 3H, J = 7.0
Hz), 1.80 (br, s, 1H, NH), 3.60 (m, 1H), 3.9
(m, 1H), 4.15 (m, 2H), 4.76 (d, 1H, J = 23.8
Hz), 6.56–6.72 (m, 3H), 7.02–7.15 (m, 2H),
7.38–7.55 (m, 2H), 7.60 (d, 1H, J = 7.76 Hz),
7.75–7.82 (m, 4H)
123.6, 126.2, 127.4, 128.4, 129.2, 132.8, 132.9,
136.2, 144.0
15.6,15.8, 16.4, 16.5, 50.2, 53.2, 63.4, 113.6,
118.4, 122.9, 125.4, 125.8, 125.9, 126.2, 128.4,
128.6, 128.9, 129.2, 132.0 132.4, 133.4, 145.9,
146.2
TABLE 5 1H and 13C NMR Data of 6a–h
Compd.
1 H NMR
13 C NMR
6a
5.0 (d, 1H, J = 24.4 Hz), 6.47 (d, 1H) 6.94–7.5 (m,
53.7 (J = 110 Hz) 114.0, 117.2, 118.9, 121.0, 126.5,
128.1, 128.5 , 129.3, 130.0, 131.0, 134.0, 145.5,
153.2
18H)
6b
6c
6d
6e
4.1 (d, 1H, J = 24.4 Hz), 4.7 (m, 1H), 6.30 (br, s, 1H,
NH), 6.8–7.54 (m 18H)
56.3 (J = 121. Hz), 114.0, 118.5, 128.6, 128.9, 129.4,
130.0, 136.4, 146.8
3.64 (s, 3H), 4.80 (d, 1H, J = 23.8 Hz), 6.65 (brs, 1H,
55.4 (J = 128 Hz) , 55.6, 114.2, 118.2, 120.3, 125.2,
127.7, 129.0, 132.6, 146.8, 150.9,
16.4, 17.2, 20.8, 57.1 (J = 120 Hz), 63.0, 117.7, 122.6,
126.6, 127.3, 127.4, 132.6, 137.1, 137.3 145.0, 146.0.
55.4, 56.31 (J = 126 Hz), 114.3, 114.8, 121.4, 127.2,
127.4, 127.6, 127.5, 128.6, 132.5, 135.0, 139.8,
142.1, 152.2
NH) 6.8–7.42 (m, –18H)
2.28 (s, 3H), 2.35 (s, 3H), 4.6 (br, s, 1H, NH), 5.2 (d,
1H, J = 23.4 Hz), 6.60–7.46 (m,–16 H)
3.60 (s, 3H), 4.66 (d, J = 22.8 1H), 6.10 (br, s, 1H,
NH), 6.68–7.6 (m, 17H)
6f
2.37 (s, 3H,) 4.29 (m, 1H), 6.0 (br, s, 1H, NH) 6.8–7.4
(m, 18 H)
19.0, 56.2 (J = 130 Hz), 120.0, 125.0, 128.0, 128.4,
128.4, 130.0, 130.4, 131.2, 136.0, 136.2, 143.0,
154.0.
6g
6h
4.22 (m, 1H), 6.13–6.35 (m, 1H), 6.65–7.7 (m, 18H)
55.6 (J = 113.2 Hz), 113.0, 123.5 126.3, 127.5, 128.3,
129.5, 132.6, 136.8, 140.0, 142.8, 150.0, 154.8
20.3, 21.2, 57.2 (J = 115 Hz) , 114.8, 118.6, 120.8,
129.0, 131.6, 136.0, 142.0.
2.18 (s, 3H), 2.26 (s, 3H), 4.42 (m, 1H), 6.8–7.43 (m,
15H)
Heteroatom Chemistry DOI 10.1002/hc

Syntheses, Spectral Property, and Antimicrobial Activities of 6-ꢀ-Amino Dibenzo [d,f][1,3,2]Dioxaphosphepin 6-Oxides
7
TABLE 6 Antibacterial and Antifungal Activity of 6a–h
Zone of inhibition (%)
Fungi
Bacteria
P. solmanicolor
M. phaseolina
200a 400a
S. aureus
K. pneumonaie
Compd.
200a
400a
200a
400a
200a
400a
6a
9
30
38
51
50
49
56
59
62
10
18
18
26
22
26
20
23
21
–
24
31
31
40
42
50
48
50
8
33
48
48
60
49
66
54
50
18
30
30
42
20
27
28
28
–
32
53
53
61
38
50
54
60
6b
20
30
26
29
30
34
40
20
–
23
23
40
33
40
24
30
–
6c
6d
6e
6f
6g
6h
Griseofulvin
Penicillin
22
24
aConcentration in ppm.
ful discussions and to Dr. G. M. Sundaravalli, Depart-
ment of English, Sri Venkateswara University, Tiru-
pati, India for correcting in English the manuscript
and the Director, Central Drug Research Institute
(CDRI), Lucknow, Shasun Chemical and Drug Ltd.,
Chennai, India for analytical data, MK is grateful to
CSIR, New Delhi, India for the award of Senior Re-
search Fellowship.
6-ꢀ-aminodibenzo[d,f][1,3,2] dioxaphosphepin
6-oxides 6a–h
General Procedure: A mixture of ꢀ-aminophos-
phonate (4, 2 mmol) and 2,2-dihydroxy-biphenyl (5,
2 mmol) and catalytic amount of p-toluene sulfonic
acid in toluene (50 mL) was kept stirred under reflux.
50% of toluene was distilled off during the course
of reaction to remove ethanol formed in the reac-
tion. After completion of the reaction as indicated
by TLC analysis, the reaction mixture was cooled
to room temperature and quenched by addition of
saturated. NaHCO3 solution. The reaction mixture
was extracted with ethyl acetate, and the combined
extracts were washed with brine, dried over anhy-
drous Na2SO4, and concentrated to dryness to ob-
tain 6-ꢀ-aminodibenzo [d, f ][1,3,2]dioxaphosphepin
6-oxides (6a–g) as solids. Synthetic and spectral data
for 6a–h are given in Tables 1, 3, 4 and 5.
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We thank Dr. C. Nagaraju, Department of Chemistry,
Sri Venkateswara University, Tirupati, India for help-
Heteroatom Chemistry DOI 10.1002/hc

8
Kasthuraiah et al.
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Heteroatom Chemistry DOI 10.1002/hc