Chemoselective reaction of formalin with 2-(5-substituted-2- hydroxybenzylamino)phenols: Synthesis of 6-substituted 3-(2-hydroxyphenyl)-3,4- dihydro-2H-benzo[e][1,3]oxazines

Article abstract of DOI:10.1002/jhet.5570450444

(Chemical Equation Presented) Reaction of 2-(5-substituted-2- hydroxybenzylamino)phenols (2) with formalin in ethanol under reflux has chemoselectively led to 2-(6-substituted-2H-benzo[e][1,3]oxazin-3(4H)-yl)phenols (3) in good yield involving the ring cl

Full text of DOI:10.1002/jhet.5570450444

Jul-Aug 2008
1207
Chemoselective Reaction of Formalin with 2-(5-Substituted-2-
hydroxybenzylamino)phenols: Synthesis of 6-Substituted 3-(2-
hydroxyphenyl)-3,4-dihydro-2H-benzo[e][1,3]oxazines
Ramaiyan Manikannan and Shanmugam Muthusubramanian*
Department of Organic Chemistry, School of Chemistry, Madurai Kamaraj University,
Madurai - 625 021, India.
muthumanian2001@yahoo.com
Received June 26, 2007
R
R
N
N
H
OH
OH
O
OH
Reaction of 2-(5-substituted-2-hydroxybenzylamino)phenols (2) with formalin in ethanol under reflux
has chemoselectively led to 2-(6-substituted-2H–benzo[e][1,3]oxazin-3(4H)-yl)phenols (3) in good yield
involving the ring closure of the hydroxyl group of the C-aryl ring and not that of the N-aryl ring.
J. Heterocyclic Chem., 45, 1207 (2008).
INTRODUCTION
far to analyse the course of the reaction of formalin with
N-benzylaniline with hydroxyl groups in the ortho
position of both the aromatic rings. The cyclisation by
formalin can occur at the C-aryl ring to give 3,4-dihydro-
benzo[e][1,3]oxazine derivative, but there is a possibility
for the cyclisation involving the ortho hydroxyl group of
the N-aryl ring forming a five membered heterocyclic
compound 4. In the present work, it has been planned to
investigate the course of the above reaction.
The substituted N-benzylanilines, the precursors for the
investigation, 2-(5-substituted-2-hydroxybenzylamino)-
phenols (2), have been prepared by the sodium
borohydride reduction of the respective imines (1) [15] by
an eco-friendly path using silica gel without solvent
following a reported procedure [16]. All the synthesized
compounds 2 are new and are fully characterized by nmr.
Amines 2 on treatment with formalin under reflux in
ethanol has led to the formation of a single product 3
identified as 6-substituted 3-(2-hydroxyphenyl)-3,4-di-
hydrobenzoxazine in very good yield (Scheme 1). All
compounds were characterized by nmr spectral data. The
1H nmr spectrum of 3a exhibits two sharp singlets at 4.34
and 5.00 ppm each accounting for two hydrogens for the
methylene protons of the oxazine ring indicating that the
oxazine ring is not rigid [17]. In the 13C nmr spectrum, the
respective carbons appear at 51.6 and 81.0 ppm. It can be
noted that polymerization, which is common for N-aryl
benzoxazines, did not take place under the reaction
conditions. The reaction has taken place chemoselectively
with the hydroxyl group in the aryl ring of the benzyl
group and not that of the N-phenyl group.
Substituted 1,3-benzoxazines have been found to
possess a wide range of biological activities like
antimicrobial [1-3], antitumour [4-5], antituberculosis
[6-7], anthelmintic [8] etc. They are also capable of acting
as tranquilizing and sedating agents [9]. In view of this, it
has been planned to synthesize a new set of heterocyclic
compounds with benzoxazine unit. Accordingly, the ring
closure of N-phenyl-N-benzyl amines with ortho hydroxyl
groups in both the aromatic rings has been effected by the
reaction with formalin leading to a set of hitherto
unknown N-(2-hydroxphenyl)-3,4-dihydro-benzo[e][1,3]-
oxazines.
RESULTS AND DISCUSSION
3,4-Dihydro-1,3-benzoxazine can be easily obtained by
the reaction of C-(2-hydroxybenzyl)-N-arylamine with
formalin. The N-aryl-3,4-dihydro-1,3-benzoxazines are
well known to undergo polymerization upon heating [10].
With unsubstituted phenol, formaldehyde and primary
aromatic amines as the starting materials, a series of
monofunctional benzoxazine resins with low viscosities
have been developed at room temperature [11]. However,
monomeric N-aryl-1,3-benzoxazines have also been
prepared. Condensation of 2-hydroxybenzyl alcohol with
primary aromatic amines gave N-aryl benzoxazines,
among other products [12]. Benzoxazines derived from
aniline and 4-hydroxybenzoic acid and from phenol and
4-aminobenzoic acid were prepared with two different
synthetic approaches [13]. Different N-(4-substituted
phenyl) benzoxazines were prepared by the reaction of
formaldehyde with the reduction product of 2-(imino-
methyl)phenols [14].
The analytical and nmr data are not sufficient to
conclude that the compound formed in Scheme 1 is not
3-benzyl-2,3-dihydrobenzo[d]oxazole 4. Even different
two dimensional nmr spectra reveal same type of
connectivity for both the structures 3 and 4. However, the
Though there are several reports on the formation of
monomeric benzoxazines, no attempt has been made so

1208
R. Manikannan and S. Muthusubramanian
Vol 45
ines
3 have been studied against Gram positive
Scheme 1
(Staphylococcus aureus and Bacillus subtilis) and Gram
negative (Escherichia coli, Klebsiella pneumoniae and
Pseudomonas aeruginosa) bacteria by dilution method.
Unfortunately, all the compounds (3) do not show any
significant activity in vitro against the tested organisms.
R
R
N
N
H
Silica gel/NaBH4
OH
OH
OH
OH
2
1
Formalin/ethanol
Reflux (4-6 h)
EXPERIMENTAL
All chemicals were of reagent grade quality and used without
further purification. All melting points were recorded in open
OH
R
N
1
capillaries and are uncorrected. The H and 13C NMR spectra
N
O
OH
were recorded on a Bruker 300 MHz spectrometer at 300 MHz
and 75 MHz respectively in CDCl3/DMSO-d6 using TMS as
internal standard. The signals due to NH and OH are so broad
that in many cases they are not all visible at all, but exchange
with D2O. Microanalyses were carried out on a Perkin-Elmer
instrument. GC-MS spectra were record on Thermo Finnigan
spectrophotometer. All chromatographic separations were
performed on 60-120 mesh silica gel using petroleum ether-
ethyl acetate as eluent.
O
R
3
4
Compound 1, 2 and 3
R
a
b
c
d
e
f
g
h
i
C(CH3)3
CH(CH3)2
C6H5
Cl
OCH3
C(C2H5)(CH3)2
C(C6H5)(CH3)2
Br
General procedure for preparation of the 2-(5-substituted-
2-hydroxylbelzylamino)phenols (2) [16]. To a ground mixture
of 2-(2-hydroxy-5-substituted benzylideneamino)phenol (3
mmoles), sodium borohydride (12 mmoles) and 2 g of silica gel
(60 - 120 mesh) a few drops of chloroform followed by a few
drops of water were added. After vigorous stirring for ten
minutes, the reduction product (2) was extracted with hot
chloroform and recrystallised from ethyl acetate.
C2H5
fact that the hydroxyl group of the C-aryl ring is involved
in ring closure and not that of the N-aryl ring is proved by
carrying out the reaction under identical condition on
simple 2-(benzylamino)phenol without success in the
expected ring closure. The mass spectra of 3b and 3h
have been recorded under EI mode. Both the compounds
do not exhibit molecular ion peak. However, both
compounds show peaks due to the fragments X-C8H7O
(m/e = 162.10, X = CH(CH3)2; m/e = 197.97, X = Br)
which can result only from structure 3 and not 4,
supporting the assignment.
A multi-component approach by irradiating a mixture
of 4-substituted phenol, 2-aminophenol and formaldehyde
has led to the formation of the target compound 3 with
poor yield, the rest of the reaction mixture being
polymeric in nature. Thus, it is clear that an approach
involving the initial formation of the secondary amine
followed by the formalin treatment seems more beneficial
than the single pot approach wherein the polymerization
dominates over the formation of the monomeric
benzoxazine. Blocking the ortho positions of the aryl
rings would have probably prevented the polymerization
in the former approach. It is also observed that the
reaction of 2 with formalin proceeds smoothly under
microwave irradiation without any solvent giving 3 in
comparable yield with reduced reaction time. Reaction
gets completed in less than five minutes under microwave
radiation suggesting this method to be more advantageous
than the conventional one.
2-(5-tert-Butyl-2-hydroxybenzylamino)pheno1 (2a). This
compound was obtained as brown crystals (Ethyl acetate), yield
1
95%, mp 119-120 °C; H nmr (300 MHz, CDCl3): ꢀ 1.31 (s,
9H), 4.40 (s, 2H), 6.77-6.91, (m, 5H), 7.16 (d, J = 2.4 Hz, 1H),
7.23 (dd, J = 8.4, 2.4 Hz, 1H); 13C nmr (75 MHz, CDCl3): ꢀ
31.5, 34.0, 49.0, 114.7, 115.2, 116.0, 120.6, 121.5, 122.3, 125.6,
125.9, 135.9, 142.8, 144.9, 154.2. Anal. calcd. for C17H21NO2: C,
75.25; H, 7.80; N, 5.16%. Found: C, 75.21; H, 7.83; N, 5.13%.
2-(5-iso-Propyl-2-hydroxybenzylamino)pheno1 (2b). This
compound was obtained as brown crystals (Ethyl acetate), yield
85%, mp 110-112 °C; 1H nmr (300 MHz, CDCl3): ꢀ 1.23 (d, J =
6.9 Hz, 6H), 2.84 (m, J = 6.9 Hz, 1H), 4.38 (s, 2H), 6.76-7.20
(m, 7H); 13C nmr (75 MHz, CDCl3): ꢀ 24.3, 33.3, 48.9, 114.7,
115.2, 116.4, 120.6, 121.6, 122.8, 126.6, 126.9, 136.0, 140.5,
144.8, 154.6. Anal. calcd. for C16H19NO2: C, 74.68; H, 7.44; N,
5.44%. Found: C, 74.64; H, 7.40; N, 5.39%.
2-(5-Phenyl-2-hydroxybenzylamino)pheno1 (2c). This
compound was obtained as brown crystals (Ethyl acetate), yield
1
90%, mp 105-107 °C; H nmr (300 MHz, CDCl3): ꢀ 4.41 (s,
2H), 6.71-7.56 (m, 12H); 13C nmr (75 MHz, CDCl3): ꢀ 49.0,
114.9, 115.5, 117.0, 120.9, 121.5, 123.5, 126.6, 127.3, 127.6*,
128.7, 133.3, 135.8, 140.7, 145.1, 156.2. [*one aromatic carbon
was merged with other]. Anal. calcd. for C19H17NO2: C, 78.33;
H, 5.88; N, 4.81%. Found: C, 78.29; H, 5.85; N, 4.78%.
2-(5-Chloro-2-hydroxybenzylamino)pheno1 (2d). This
compound was obtained as brown crystals (Ethyl acetate), yield
1
88%, mp 113-115 °C; H nmr (300 MHz, CDCl3): ꢀ 4.39 (s,
2H), 6.72-7.45 (m, 7H); 13C nmr (75 MHz, CDCl3): ꢀ 48.6,
114.8, 115.5, 117.9, 121.1, 121.6, 124.6, 128.1, 128.7, 129.3,
135.4, 144.9, 155.3. Anal. calcd. for C13H12ClNO2: C, 62.53; H,
4.84; N, 5.61%. Found: C, 62.50; H, 4.80; N, 5.57%.
The antibacterial activity of the synthesized
6-substituted 3-(2-hydroxyphenyl)-3,4-dihydrobenzoxaz-

Jul-Aug 2008
Synthesis of Novel 3,4-Dihydro-1,3-benzoxazines
1209
2-(2-Hydroxy-5-methoxybenzylamino)pheno1 (2e). This
compound was obtained as brown crystals (Ethyl acetate), yield
91%, mp 166-167 °C; 1H nmr (300 MHz, DMSO-d6): ꢀ 3.67 (s,
3H), 4.08 (s, 2H), 6.58-6.90 (m, 5H), 7.14 (d, J = 7.8 Hz, 1H),
7.69 (d, J = 2.5 Hz, 1H); 13C nmr (75 MHz, DMSO-d6): ꢀ 53.2,
54.5, 112.5, 114.9, 115.0, 115.1, 118.4, 120.7, 122.9, 124.3,
135.0, 148.7, 151.1, 151.4. Anal. calcd. for C14H15NO3: C, 68.56;
H, 6.16; N, 5.71%. Found: C, 68.52; H, 6.13; N, 5.67%.
2-(5-tert-Pentyl-2-hydroxybenzylamino)pheno1 (2f). This
compound was obtained as yellow crystals (Ethyl acetate), yield
93%, mp 105-106 °C; 1H nmr (300 MHz, CDCl3): ꢀ 0.69 (t, J =
7.5 Hz, 3H), 1.26 (s, 6H), 1.61 (q, J = 7.5 Hz, 2H), 4.39 (s, 2H),
6.71-6.99 (m, 5H), 7.08 (d, J = 2.4 Hz, 1H), 7.17 (dd, J = 8.4,
2.4 Hz, 1H); 13C nmr (75 MHz, CDCl3): ꢀ 9.2, 28.6, 37.0, 37.2,
49.1, 114.7, 115.2, 116.0, 120.5, 121.5, 122.3, 126.3, 126.6,
136.0, 141.1, 144.9, 154.1. Anal. calcd. for C18H23NO2: C, 75.76;
H, 8.12; N, 4.91%. Found: C, 75.73; H, 8.09; N, 4.87%.
2-(2-Hydroxy-5-(2-phenylpropan-2-yl)benzylamino)phen-
o1 (2g). This compound was obtained as brown crystals (Ethyl
acetate), yield 82%, mp 101-102 °C; 1H nmr (300 MHz, CDCl3):
ꢀ 1.76 (s, 6H), 4.38 (s, 2H), 6.71-7.45 (m, 12H); 13C nmr (75
MHz, CDCl3): ꢀ 30.8, 42.1, 48.7, 114.6, 115.0, 115.8, 120.5,
120.8, 122.6, 125.4, 126.6, 127.2, 127.9*, 135.8, 142.2, 145.3,
150.8, 154.1. [*one aromatic carbon was merged with other].
Anal. calcd. for C22H23NO2: C, 79.25; H, 6.95; N, 4.20%. Found:
C, 79.21; H, 6.90; N, 4.17%.
151.3, 151.5. Anal. calcd. for C18H21NO2: C, 76.29; H, 7.47; N,
4.94%. Found: C, 76.24; H, 7.43; N, 4.90%.
2-(6-iso-Propyl-2H–benzo[e][1,3]oxazin-3(4H)-yl)phenol (3b).
This compound was obtained as brown crystals (Ethanol), yield
89%, mp 103-105 °C; 1H nmr (300 MHz, CDCl3): ꢀ 1.22 (d, J =
6.9 Hz, 6H), 2.83 (m, J = 6.9 Hz, 1H), 4.32 (s, 2H), 4.98 (s, 2H),
6.65-7.22 (m, 7H); 13C nmr (75 MHz, CDCl3): ꢀ 24.1, 33.3,
51.4, 81.0, 114.6, 116.8, 120.2, 120.4, 124.3, 124.4, 126.0,
127.2, 136.0, 141.6, 151.3, 151.8. Anal. calcd. for C17H19NO2: C,
75.81; H, 7.11; N, 5.20%. Found: C, 75.77; H, 7.07; N, 5.17%.
2-(6-Phenyl-2H–benzo[e][1,3]oxazin-3(4H)-yl)phenol (3c).
This compound was obtained as brown crystals (Ethanol), yield
1
90%, mp 87-88 °C; H nmr (300 MHz, CDCl3): ꢀ 4.42 (s, 2H),
5.07 (s, 2H), 6.79 (td, J = 7.5, 1.5 Hz, 1H), 6.97-7.00 (m, 2H),
7.12 (td, J = 7.5, 1.5 Hz, 1H), 7.19 (dd, J = 7.5, 1.5 Hz, 1H),
7.22 (d, J = 2.1 Hz, 1H), 7.27-7.55 (m, 6H); 13C nmr (75 MHz,
CDCl3): ꢀ 51.4, 81.2, 114.7, 117.4, 120.5, 120.8, 124.3, 125.4*,
126.7, 126.9, 127.4, 128.8, 134.4, 135.8, 140.5, 151.3, 153.5
[*one aromatic carbon was merged with other]. Anal. calcd. for
C20H17NO2: C, 79.19; H, 5.65; N, 4.62%. Found: C, 79.23; H,
5.61; N, 4.65%.
2-(6-Chloro-2H-benzo[e][1,3]oxazin-3(4H)-yl)phenol (3d).
This compound was obtained as brown crystals (Ethanol), yield
1
92%, mp 72-74 °C; H nmr (300 MHz, CDCl3): ꢀ 4.33 (s, 2H),
5.03 (s, 2H), 6.76 (td, J = 7.5, 1.5 Hz, 1H), 6.85 (d, J = 8.7 Hz,
1H), 6.95-7.17 (m, 5H); 13C nmr (75 MHz, CDCl3): ꢀ 51.0, 81.1,
114.9, 118.4, 120.5, 122.0, 124.1, 125.9, 126.5, 127.4, 128.1,
135.5, 151.1, 152.5. Anal. calcd. for C14H12ClNO2: C, 64.25; H,
4.62; N, 5.35%. Found: C, 64.21; H, 4.59; N, 5.38%.
2-(5-Bromo-2-hydroxybenzylamino)pheno1 (2h). This
compound was obtained as brown crystals (Ethyl acetate), yield
1
85%, mp 115-117 °C; H nmr (300 MHz, CDCl3): ꢀ 4.38 (s,
2H), 6.75-7.57 (m, 7H); 13C nmr (75 MHz, CDCl3): ꢀ 48.5,
110.9, 112.1, 116.2, 118.4, 119.4, 120.6, 121.1, 129.2, 134.5,
136.3, 149.9, 161.9. Anal. calcd. for C13H12BrNO2: C, 53.08; H,
4.11; N, 4.76%. Found: C, 53.05; H, 4.08; N, 4.73%.
2-(6-Methoxy-2H-benzo[e][1,3]oxazin-3(4H)-yl)phenol (3e).
This compound was obtained as brown crystals (Ethanol), yield
93%, mp 94-96 °C; H nmr (300 MHz, CDCl3): ꢀ 3.76 (s, 3H),
4.34 (s, 2H), 4.99 (s, 2H), 6.50-7.17 (m, 7H); 13C nmr (75 MHz,
CDCl3): ꢀ 51.3, 55.6, 80.8, 111.1, 114.1, 114.6, 117.7, 120.3,
121.1, 124.2, 127.1, 135.8, 147.7, 151.1, 153.8. Anal. calcd. for
C15H15NO3: C, 70.02; H, 5.88; N, 5.44%. Found: C, 70.05; H,
5.90; N, 5.48%.
1
2-(5-Ethyl-2-hydroxybenzylamino)pheno1 (2i). This
compound was obtained as brown crystals (Ethyl acetate), yield
95%, mp 106-108 °C; 1H nmr (300 MHz, CDCl3): ꢀ 1.21 (t, J = 7.5
Hz, 3H), 2.58 (q, J = 7.5 Hz, 2H), 4.37 (s, 2H), 6.74-7.16 (m, 2H),
6.81 (d, J = 8.1 Hz, 1H), 6.84-6.89 (m, 2H), 6.98 (d, J = 2.1 Hz,
1H), 7.04 (dd, J = 8.1, 2.1 Hz, 1H); 13C nmr (75 MHz, CDCl3): ꢀ
16.0, 28.1, 48.9, 114.8, 115.3, 116.5, 120.7, 121.5, 123.0, 128.1,
128.4, 135.9, 136.1, 145.0, 154.5. Anal. calcd. for C15H17NO2: C,
74.05; H, 7.04; N, 5.76%. Found: C, 74.01; H, 7.00; N, 5.72%.
General procedure for the synthesis of 2-(6-substituted-
2H-benzo[e][1,3]oxazin-3(4H)-yl)phenols (3). A mixture of 2-
(2-hydroxy-5-substituted belzylamino)phenol 2, (3 mmoles) and
formalin (35%, w/v, 6 mmoles) in ethanol (50 mL) was refluxed
for 5 h. The progress of the reaction was monitored on tlc. After
completion, ice-cold water (50 mL) was added to the reaction
mixture and extracted with chloroform, the combined organic
layers were dried over anhydrous sodium sulphate and the
solvent evaporated. The crude mixture was purified by column
chromatography using petroleum ether-ethyl acetate (99:1 v/v
mixture) as eluent to afford pure benzoxazines (3). The products
were recrystallised from ethanol.
2-(6-tert-Pentyl-2H–benzo[e][1,3]oxazin-3(4H)-yl)phenol (3f).
This compound was obtained as brown crystals (Ethanol), yield
82%, mp 68-70 °C; 1H nmr (300 MHz, CDCl3): ꢀ 0.70 (t, J = 7.5
Hz, 3H), 1.24 (s, 6H), 1.59 (q, J = 7.5 Hz, 2H), 4.38 (s, 2H), 5.02
(s, 2H), 6.78 (td, J = 7.5, 1.5 Hz, 1H), 6.85 (d, J = 8.7 Hz, 1H),
6.93-7.19 (m, 5H); 13C nmr (75 MHz, CDCl3): ꢀ 9.2, 28.5, 36.9,
37.3, 51.5, 81.0, 114.6, 116.4, 119.7, 120.3, 124.1, 124.3, 125.7,
127.2, 136.0, 142.3, 151.3, 151.4. Anal. calcd. for C19H23NO2: C,
76.73; H, 7.80; N, 4.71%. Found: C, 76.77; H, 7.83; N, 4.74%.
2-(6-(2-Phenylpropan-2yl)-2H–benzo[e][1,3]oxazin-3(4H)-
yl)phenol (3g). This compound was obtained as brown crystals
(Ethanol), yield 77 %, mp 112-114 °C; 1H nmr (300 MHz, CDCl3):
ꢀ 1.69 (s, 6H), 4.31 (s, 2H), 5.02 (s, 2H), 6.74-7.35 (m, 12H); 13
C
nmr (75 MHz, CDCl3): ꢀ 30.8, 42.4, 51.5, 81.0, 114.6, 116.5,
119.7, 120.3, 124.2, 124.8, 125.6, 126.6, 127.2, 127.9, 128.2,
135.9, 143.5, 150.6, 151.3, 151.6. Anal. calcd. for C23H23NO2: C,
79.97; H, 6.71; N, 4.05%. Found: C, 79.94; H, 6.67; N, 4.07%.
2-(6-Bromo-2H-benzo[e][1,3]oxazin-3(4H)-yl)phenol (3h).
This compound was obtained as a brown crystals (Ethanol),
2-(6-tert-Butyl-2H–benzo[e][1,3]oxazin-3(4H)-yl)phenol (3a).
This compound was obtained as brown crystals (Ethanol), yield
1
1
95%, mp 133-135 °C; H nmr (300 MHz, CDCl3): ꢀ 1.29 (s,
yield 82%, mp 67-69 °C; H nmr (300 MHz, CDCl3): ꢀ 4.47 (s,
9H), 4.34 (s, 2H), 5.00 (s, 2H), 6.77 (td, J = 7.5, 1.5 Hz, 1H),
6.85 (d, J = 8.4 Hz, 1H), 6.94-6.99 (m, 2H), 7.10 (td, J = 7.5, 1.5
Hz, 1H), 7.17 (dd, J = 7.5, 1.5 Hz, 1H), 7.22 (dd, J = 8.4, 2.4 Hz,
1H); 13C nmr (75 MHz, CDCl3): ꢀ 31.5, 34.1, 51.6, 81.0, 114.6,
116.5, 119.8, 120.4, 123.4, 124.3, 125.1, 127.2, 136.0, 144.0,
2H), 5.18 (s, 2H), 6.88-7.43 (m, 5H), 7.75 (dd, J = 9, 2.1 Hz,
1H), 7.82 (d, J = 2.1 Hz, 1H); 13C nmr (75 MHz, CDCl3): ꢀ 50.8,
81.1, 114.9, 118.8, 120.5, 122.5, 124.1, 127.4, 129.4, 131.0,
135.6, 139.7, 151.1, 153.0. Anal. calcd. for C14H12BrNO2: C,
54.92; H, 3.95; N, 4.58%. Found: C, 54.94; H, 3.97; N, 4.61%.

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R. Manikannan and S. Muthusubramanian
Vol 45
52, 8210.
2-(6-Ethyl-2H-benzo[e][1,3]oxazin-3(4H)-yl)phenol (3i).
[2] Chylinska, J. B.; Janowiec, T.; Urbanski, T.; Venolet, J.
Polish Pat 48,464/1965; Chem. Abstr., 1966, 64, 15895.
[3] Gomezgomez, P.; Perez, M.; Carvajal, A.; Rincon, J. M. Rev.
Colomb Cienc Quim Farm 4, 1985, 15; Chem. Abstr. 1986, 104, 165195.
[4] Kuehne, M. E.; Konopka, E. A. J. Med. Chem. 1962, 5, 275.
[5] Chylinska, J. B.; Urbanski, T.; Mordarski, M. J. Med. Chem.
1963, 6, 484.
This compound was obtained as brown crystals (Ethanol), yield
85%, mp 65-67 °C; 1H nmr (300 MHz, CDCl3): ꢀ 1.36 (t, J = 7.5
Hz, 3H), 2.74 (q, J = 7.5 Hz, 2H), 4.48 (s, 2H), 5.15 (s, 2H), 6.91
(td, J = 7.5, 1.5 Hz, 1H), 6.96-7.41 (m, 6H); 13C nmr (75 MHz,
CDCl3): ꢀ 15.7, 28.1, 51.4, 81.0, 114.6, 116.8, 120.3, 120.4,
124.3, 125.9, 127.2, 127.5, 135.9, 137.0, 151.3, 151.8. Anal.
calcd. for C16H17NO2: C, 75.27; H, 6.71; N, 5.49%. Found: C,
75.31; H, 6.75; N, 5.51%.
[6] Chylinska, J. B.; Janowiec, M.; Urbanski, T. Br. J.
Pharmacol. 1971, 43, 649.
The in vitro activities of the compounds were tested in
Muller hintan agar for bacteria by the two fold serial dilution
method. The test compounds were dissolved in dimethyl
sulfoxide to obtain 5 mg mL-1 stock solutions. Seeded broth
(broth containing microbial spores) was prepared in Nutrient
broth from 24 old bacterial cultures on Nutrient agar at 37 °C.
The final inoculum’s size was 105 (colony forming units) cfu
mL-1 for antibacterial assay. Testing was performed at pH 7.4.
The minimum inhibitory concentrations were recorded by visual
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observations after 24 h (for bacteria). Penicillin G and
Streptomycin were used as a standards.
Acknowledgment. The authors thank DST, New Delhi for
assistance under the IRHPA program for the nmr facility. One of
the authors (R. M) thanks Madurai Kamaraj University for a
research fellowship
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