Synthesis and antibacterial, antifungal activities of some 2r,4c-diaryl-3-azabicyclo[3.3.1]nonan-9-one-4-aminobenzoyl hydrazones

Article abstract of DOI:10.1007/s00044-010-9528-6

A series of biologically active seven 2r, 4c-diaryl-3-azabicyclo[3.3.1] nonan-9-one-4-aminobenzoyl hydrazone derivatives have been synthesized in good yield. The structures of compounds have been established on the basis of IR, ¹H, ¹³C NMR, and elemental analysis. The structure-activity relationships (SAR) have been studied by screening of antimicrobial activity over a representative panel of bacterial and fungal strains using two-fold serial dilution method. All these synthesized compounds exhibited significant activities against all bacterial and fungal strains. Springer Science+Business Media, LLC 2010.

Full text of DOI:10.1007/s00044-010-9528-6

MEDICINAL
CHEMISTRY
RESEARCH
Med Chem Res (2012) 21:345–350
DOI 10.1007/s00044-010-9528-6
ORIGINAL RESEARCH
Synthesis and antibacterial, antifungal activities of some
2r,4c-diaryl-3-azabicyclo[3.3.1]nonan-9-one-4-aminobenzoyl
hydrazones
•
J. John Francis Xaiver K. Krishnasamy
•
C. Sankar
Received: 16 August 2010 / Accepted: 2 December 2010 / Published online: 7 January 2011
Ó Springer Science+Business Media, LLC 2010
Abstract A series of biologically active seven 2r,
4c-diaryl-3-azabicyclo[3.3.1]nonan-9-one-4-aminobenzoyl
hydrazone derivatives have been synthesized in good yield.
The structures of compounds have been established on the
antihistaminic, anti-inflammatory, anticancer, and central
nervous system (CNS) stimulant and depressant activities
(Mobio et al., 1989; Katritzky and Fan, 1968 and refer-
ences cited therein; Ganellin and Spickett, 1965). Lijinsky
and Taylor (1975) found that the blocking of a-positions to
that of nitrogen in 3-azabicyclanone using alkyl groups
provided advantages over unblocked ones in terms of
biological activity. The 3-azabicyclonone pharmacopore is
present in numerous naturally abundant diterpenoid/nordi-
terpinoid alkaloids and is responsible for a wide variety of
pharmacological actions.
1
basis of IR, H, 13C NMR, and elemental analysis. The
structure–activity relationships (SAR) have been studied by
screening of antimicrobial activity over a representative
panel of bacterial and fungal strains using two-fold serial
dilution method. All these synthesized compounds exhib-
ited significant activities against all bacterial and fungal
strains.
Meanwhile, hydrazide-hydrazones have been claimed to
exhibit appreciable antimicrobial (Eisa et al., 1991; Gursoy
et al., 1997; Rollas et al., 2002; Vicini et al., 2002), anti-
tubercular (Sankar and Pandiarajan, 2010), anticonvulsant
(Sinha et al., 2010), antiviral (El-Sabbagh and Rady, 2009),
and anti-inflammatory (Kalsi et al., 1990) activities. On the
basis of these observations, the authors had the impetus to
synthesize a number of hydrazones of the synthetically
accessible 3-azabicyclo[3.3.1]nonanes and subsequently
evaluate their in vitro antimicrobial activity.
Keywords 2r,4c-Diaryl-3-azabicyclo[3.3.1]nonan-
9-one ꢀ 4-Aminobenzoic acid hydrazide ꢀ Antibacterial
activity ꢀ Antifungal activity
Introduction
In the broad spectrum of biological activity, in recent years,
there has been a growing interest in the synthesis of bio-
active compounds in the field of heterocyclic chemistry.
Among the family of heterocyclic compounds, the nitro-
gen-containing heterocycles especially 3-azabicyclonones
have gained considerable importance presumably because
of their varied biological properties, such as antiviral,
antitumor (El-Subbagh et al., 2000), analgesic (Jerom and
Spencer, 1988), local anesthetic (Perumal et al., 2001;
Hagenbach and Gysin, 1952) antibactericidal, antifungi-
cidal (Parthiban et al., 2010), herbicidal, insecticidal,
Materials and methods
Measurements and instruments
Ethyl-4-amino benzoate was purchased from Sigma-
Aldrich. All the other chemicals were used as analytic
grade. Reactions were monitored by TLC. All the reported
melting points were measured in open capillaries and are
uncorrected. FT-IR spectra were recorded as potassium
bromide pellets on AVATAR 330 FT-IR Thermo Nicolet
Spectrometer. 1H and 13C NMR spectra were recorded
at ambient temperature on a Bruker AMX 500 NMR
J. John Francis Xaiver ꢀ K. Krishnasamy (&) ꢀ C. Sankar
Department of Chemistry, Annamalai University,
Annamalainagar 608 002, Tamilnadu, India
e-mail: krishbala56@yahoo.co.in
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Med Chem Res (2012) 21:345–350
spectrometer operating at 400.13 MHz for 1H and
100.62 MHz for 13C NMR spectra. Solutions for the
measurement of spectra were prepared by dissolving 10 mg
of the sample in 0.5 ml DMSO-d6 and chemical shifts (d)
are expressed in parts per million (ppm). Elemental anal-
yses were carried out in Heraeus Carlo Erba 1108
CHN analyzer. Splitting patterns are designated as fol-
lows: s—singlet; d—doublet; t—triplet; q—quartet; and
m—multiplet.
by visual observations after 24 h (for bacteria) and 72–96 h
(for fungi except C. albicans) of incubation. Streptomycin
and Amphotericin B were used as standards for bacterial
and fungal studies, respectively.
Results and discussion
Chemistry
Microbiology
The authors have synthesized of seven 2r,4c-diaryl-3-
azabicyclo[3.3.1]nonan-9-one-4-aminobenzoyl hydrazone
derivatives as illustrated in Scheme 1. A three-step syn-
thetic strategy yielded the compounds (9–15). According to
the literature precedent (Baliah and Jeyaraman, 1971),
2,4-diaryl-3-azabicyclo[3.3.1]nonan-9-ones 1–7 were pre-
pared by the condensation of cyclohexanone, substituted
benzaldehyde, and ammonium acetate in 1:2:1.5 ratio
in ethanol. These reaction mixtures were very gently
warmed and stirred until the completion of the reaction.
The crude products formed were filtered and washed with
an ethanol–ether (1:5) mixture to yield the compounds 1–7
and recrystallized from ethanol–chloroform–acetone to
obtain the pure compounds 1–7. 4-Aminobenzoic acid
hydrazide (8) was prepared from ethyl-4-aminobenzoate
and hydrazine hydrate in ethanol medium. 2r,4c-Diaryl-3-
azabicyclo[3.3.1]nonan-9-one-4-aminobenzoyl hydrazones
(9–14) were synthesized from condensation reaction of
3-azabicyclo[3.3.1]nonan-9-ones and 4-aminobenzoic acid
hydrazide.
All the bacterial strains, namely, Salmonella typhimurium
(MTCC 98), Escherichia coli (MTCC 443), Vibrio chol-
erae (recultured), Salmonella typhi (MTCC 531), Pseudo-
monas aeruginosa (MTCC 741), Klebsiella pneumoniae
(MTCC 2272), Bacillus subtilis (MTCC 121), and Staph-
ylococcus aureus (MTCC 96), and the fungal strains,
namely, Candida albicans, Fusarium oxysporum, Asper-
gillus flavus, Aspergillus niger, and Cryptococcus neofor-
mans were obtained from the Faculty of Medicine,
Annamalai University, Annamalainagar, Tamilnadu, India.
In vitro antibacterial and antifungal activity
In vitro antimicrobial activities of the compounds were
tested in Sabouraud’s dextrose broth (SDB, Hi-media,
Mumbai) for fungi and in nutrient broth (NB, Hi-media,
Mumbai) for bacteria by the two-fold serial dilution
method (Dhar et al., 1968). The test compounds were
dissolved in dimethylsulfoxide (DMSO) to obtain 1 mg/ml
stock solutions. Seeded broth (broth containing microbial
spores) was prepared in nutrient broth from 24-h-old bac-
terial cultures on nutrient agar (Hi-media, Mumbai) at
37 1°C, while fungal spores from 24 h to 7 days old
Sabouraud’s agar slant cultures were suspended in SDB.
The colony-forming units (cfu) of the seeded broth were
determined by plate count technique and adjusted with the
help of McFarland standards in the range of 104–105 cfu/
ml. The final inoculums size was 105 cfu/ml for antibac-
terial assay, and 1.1–1.5 9 102 cfu/ml for antifungal assay.
Testing was performed at pH 6.5 0.2 for bacteria, and
pH 5.6 0.2 for fungal studies. Exactly 0.2 ml of the
solution of the test compound was added to 1.8 ml of the
seeded broth to form the first dilution. One milliliter of this
was diluted with a further 1 ml of the seeded broth to give
the second dilution and so on, till six such dilutions were
obtained. A set of assay tubes containing only the seeded
broth was kept as control and, likewise, the solvent controls
were also run simultaneously. The tubes were incubated in
Biochemical Oxygen demand (BOD) incubators at 37
1°C for bacteria, and 28 1°C for fungal studies. The
minimum inhibitory concentrations (MICs) were recorded
Structures of all the synthesized compounds were
1
established on the basis of IR, H NMR and 13C NMR
spectral data. The purities of the compounds were checked
by elemental analysis. The analytic data agreed well with
their proposed molecular formulas.
The atoms of the bicyclo[3.3.1]nonane part are num-
bered as shown in Fig. 1. The ipso carbons of the aryl
groups at C-2 and C-4 are designated as C-20 and C-40,
respectively. The other carbons of the aryl group at C-2 are
denoted as o, m, and p-carbons, and those of the aryl group
at C-4 are denoted as o0, m0, and p0-carbons. The carbons of
the 4-aminobenzoyl ring are designated using C-100, C-200,
and C-300. The protons are numbered accordingly. For
example, the benzylic proton at C-2 is denoted as H-2, that
at C-200 is denoted as H-200, and so on. The methylene
protons in the cyclohexane ring are denoted as axial and
equatorial protons assuming chair conformation for the
cyclohexane ring. Thus, the methylene protons at C-7 are
denoted as H-7a and H-7e.
In IR spectra, the presence of C=N stretching frequency
around 1640 and 1648 cm-1 confirms the hydrazone for-
mation. The piperidine NH stretching frequency was in the
range 3330–3370 cm-1, while the absorption bands in the
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Med Chem Res (2012) 21:345–350
347
O
Two protons signals that were observed at 1.64 and
1.45 ppm should, respectively, be due to methylene pro-
tons C-6 and C-8.
NH2
H
O
O
H
In 13C NMR spectra in compound 9, two signals were
observed around 163 and 161 ppm because of fluorine-
attached ipso carbons. The observed two signals were due
to C–F coupling between carbon and the attached fluorine
atom. Similarly, another pair of signals observed for all the
hydrazones in the region 135–145 ppm is assigned to C-20
and C-40 ipso carbons. C=O and C=N carbon signals
appeared at 165 and 167 ppm. However, there are two
signals around 65 and 62 ppm, which are conveniently
assigned to C-2 and C-4 carbons, respectively, whereas, the
bridgehead carbons C-1 and C-5 appeared at 46 and
40 ppm, respectively. In the 1H–1H-COSY spectrum of the
benzylic protons showed correlation with that of N(3)–H.
Also H-2 showed correlation with H-1, and H-4 showed
correlation with H-5. However, in all these cases H-1, H-2,
N(3)–H, H-4, and H-5 gave unresolved signals. The unre-
solved nature of the signals for H-1, H-2, H-4, and H-5
suggests that the vicinal couplings for these protons are
very small. However, H-7a showed three large couplings
(one geminal coupling with H-7e and two diaxial vicinal
coupling with H-6a and H-8a) and two small couplings
(one with H-6e and another with H-8e). All these obser-
vations are consistent with twin-chair (CC) (Fig. 2) con-
formation for these compounds (Table 1).
R1
R1
R1
+
COOCH2CH3
NH4OAc
R2
R2
NH2.NH2.H2O
Ethanol reflux 6 hrs
EtOH
warm
O
NH2
R1
R1
N
H
CONHNH2
R2
R2
(8)
(1-7)
MeOH:CHCl3/AcOH /
reflux
NH2
O
R1
R2
H
Br
F
Cl
H
OCH3
N
9;
H
H
H
H
N
H
10;
11;
12;
R1
R1
13; Cl
N
H
14;
H
R2
R2
15;
H
CH3
(9-15)
Scheme 1 Synthetic routes of compounds 9–15
Antibacterial activity
3''
2''
NH2
The newly synthesized compounds were screened for their
in vitro antibacterial activity by disc diffusion method.
MIC values were determined by twofold serial dilution
method (Dhar et al., 1968). Streptomycin was used as a
4''
O
1''
5''
6''
7
N
8
N
H
6
9
R1
R1
5
4
1
2
NH2
O
3
N
2'
4'
C
H
R2
R2
N
H
N
Fig. 1 Numbering the bicyclo[3.3.1]nonane
region of 3070–2800 cm-1 are ascribed to aromatic and
aliphatic C–H stretching frequencies.
H
H
In the 1H NMR spectra of the target hydrazones, a broad
and more downfield D2O exchangeable singlet at 10.50 ppm
was characteristic of the NH amide group. The broad sin-
glet signal appeared at 4.31 ppm, corresponding to two
protons integrals. These two signals are attributed to ben-
zylic protons H-2 and H-4, respectively. However, signals
that appeared at 3.25 and 3.57 ppm should be due to
the bridgehead protons H-1 and H-5, respectively. The
bridgehead protons H-1 merged with the solvent signal.
H
a
H
a
H
a
H
a
H
e
H
Ar
Ar
e
H
e
N
H
H
a
Fig. 2 Conformation of the molecule
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Med Chem Res (2012) 21:345–350
S. aureus. Compound 11 demonstrated strong activ-
ity against B. subtilis at 25 lg/ml. However, unsubstitut-
ed compound 9 showed a noticeable activity against
K. pneumoniae.
Table 1 Physical constant of the synthesized compounds 9–15
Compound R1 R2
Yield m.p. M.F
(%)
M.W
(°C)
9
H
H
H
H
Cl
H
H
H
Br
F
62
61
64
64
58
210
208
200
190
202
212
195
C27H28N4O
424.30
The results obtained revealed that the nature of sub-
stituents and substitution pattern on the aryl ring may have
a considerable impact on the antibacterial activities of the
target hydrazone. In this context, para-substituted com-
pounds appear to be more beneficial for antibacterial
activity than the ortho-substituted pattern.
10
11
12
13
14
15
C
C
C
C
27H26N4OBr 502.20
27H26N4OF 441.30
Cl
H
27H26N4OCl 457.75
27H26N4OCl 457.75
OCH3 62
CH3 60
C30H33N3O3
C30H33N3O
483.60
451.60
Antifungal activity
standard for the comparison of antibacterial activity, and
the MIC results are summarized in Table 2. Streptomycin
was used as an antibiotic against mycobacterium tubercu-
losis and dermatological diseases (Ruiz et al., 2002 and
references cited therein).
All the synthesized compounds were screened for in vitro
antifungal activity. The antifungal activities were evaluated
against different fungal strains, such as Candida albicans,
Fusarium oxysporum, Aspergillus flavus, Aspergillus niger,
and Cryptococcus neoformans. MIC values were deter-
mined by twofold serial dilution method (Dhar et al.,
1968). Amphotericin B was used as a standard for the
comparison of antifungal activity. DMSO was used as
solvent control. MIC values of the tested compounds are
presented in Table 3. From the antifungal activity data
Ortho choloro-substituted compound 13 demonstrated
good activities against S. typhimurium, V. cholerae, and
K. pneumoniae, whereas para chloro-substituted com-
pound 12 demonstrated strong activity against E. coli,
B. subtilis, and S. aureus. Bromo- and fluoro-substituted
compounds 10 and 11 demonstrated good activity against
Table 2 In vitro antibacterial activities of compounds 9–15
Compd. Entry
R1
S. typhimurium E. coli V. cholerae S. typhi P. aeruginosa K. pneumoniae B. subtilis S. aureus
R2
9
H
H
200
200
100
200
50
200
100
100
50
100
200
50
200
50
200
50
50
200
50
100
200
25
200
50
10
H
p-Br
p-F
p-Cl
H
11
H
100
200
100
100
100
25
200
100
100
200
200
50
50
12
H
100
50
200
50
50
50
13
o-Cl
H
100
100
100
50
200
100
100
200
100
200
25
14
p-OCH3 200
50
200
200
20
15
H
p-CH3
200
25
200
50
Strept.
12.5
Strept. Streptomycin
Table 3 In vitro antifungal activities of compounds 9–15
Compd.
Entry
R1
C. albicans
F. oxysporum
A. flavus
A. niger
C. neoformans
R2
9
H
H
200
100
50
200
100
200
100
200
50
10
H
p-Br
p-F
200
100
100
200
200
200
25
50
100
50
100
200
200
100
200
100
25
11
H
12
H
p-Cl
H
200
100
100
100
25
13
o-Cl
H
100
100
100
50
14
p-OCH3
p-CH3
15
H
200
50
Amp. B
Amp. B Amphotericin B
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Med Chem Res (2012) 21:345–350
349
2r,4c-Bis(p-bromophenyl)-3-azabicyclo[3.3.1]nonan-
9-one-4-aminobenzoyl hydrazone (10)
(Table 3), it can be observed that the compounds 10 and 11
are the most active among all the synthesized compounds
compared with all the tested organisms except Crypto-
coccus neoformans. It is seen that 9 shows no activity
compared with A. niger and C. neoformans even at a
concentration of 200 lg/ml. However, it shows antifungal
activity compared to all the other tested fungi in the range
50–200 lg/ml. Compounds 9–15 which have substituents
in the C-2 and C-4 aryl groups are more active than the
unsubstituent compound 9 compared with all the tested
fungi. The o-chloro compound 13 is less active than
the p-chloro compound 12 compared with C. albicans,
A. flavus, and A. niger. The results suggest that the anti-
bacterial and antifungal activities are markedly influenced
by the aromatic substituents. Thus, 9–15 with electron-
withdrawing substituents in the aromatic ring show greater
antibacterial activity.
White solid: m.p. 208°C, and yield 61%. IR (KBr) (cm-1):
3060, 2924, and 2854 (C–H stretching); 1632, 1605 (C=C
ring stretching); and 3334 (N–H stretching). 1H NMR
(400 MHz—DMSO-d6 ppm). d: 10.40 (s, 1H, amide NH);
8.81 (d, 2H, H-300); 6.60 (d, 2H, H-200); 7.71 (q, 4H, ortho);
7.42 (q, 4H, meta); 4.62 (d, 2H, H-2a); 4.48 (d, 2H, H-4a);
2.99 (s, 1H, H-5e); 2.78 (m, 1H, H-7a); 1.68 (m, H, H-8e);
1.53 (m, 1H, H-6a); 1.44 (m, 2H, H-6e, H-8a); 1.25 (m, 1H,
H-7e); 2.77 (s, 1H, ring NH); and 5.81 (s, 2H, p-NH2). 13
C
NMR (400 MHz): 62.3 (C-2); 60.6 (C-4); 42.3 (C-1); 28.1
(C-6); 21.0 (C-7); 165.7 (C-9); 164.0 (NHCO); 152.9
(C-400); 113.1 (C-200); 119.7 (C-100); and 139.9, and 139.8
(C-20, and C-40). Anal found (Cal.) for C27H26N4Obr (%):
C, 64.50 (64.51); H, 5.16 (5.18); and N, 11.14 (11.15).
2r,4c-Bis(p-fluorophenyl)-3-azabicyclo[3.3.1]nonan-
9-one-4-aminobenzoyl hydrazone (11)
Experimental section
White solid: m.p. 200°C, and yield 64%. IR (KBr) (cm-1):
3335 (N–H stretching); 3061, 2925, and 2855 (C–H
stretching); 1627 (C=N stretching); and 1605 (C=O
stretching). 1H NMR (400 MHz—DMSO-d6 ppm). d:
10.47 (s, 1H, amide NH); 7.7 (d, 2H, H-300); 6.6 (d, 2H,
H-200); 7.63 (q, 4H, ortho); 7.23 (q, 4H, meta); 4.29 (d, 2H,
H-2a, H-4a); 3.2 (s, 1H, H-5e); 2.7 (m, 1H, H-7a); 1.60 (m,
1H, H-8e); 1.45 (m, 3H, H-6a, H-6e, H-8a); 1.26 (m, 1H,
General procedure for synthesis of 2r,4c-diaryl-
3-azabicyclo[3.3.1]nonan-9-one-4-aminobenzoyl
hydrazones (9–15)
A mixture of 2,4-diaryl-3-azabicyclo[3.3.1]nonan-9-one
(1–7) (1 mmol), 4-aminobenzoic acid hydrazide (1.5 mmol)
in methanol and chloroform (1:1 v/v), and a few drops of
acetic acid was added and refluxed for 2–4 h. On com-
pletion of the reaction time, a solid mass was formed,
which was then cooled to room temperature. The precipi-
tate was filtered off and washed with ice-cooled water–
ethanol mixture. The crude product was recrystallized from
ethanol.
H-7e); and 2.94 (m, 1H, ring NH); 5.67 (s, 2H, p-NH2). 13
C
NMR (400 MHz): 64.2 (C-2); 61.9 (C-4); 46.2 (C-1); 28.5
(C-8); 27.2 (C-6); 21.3 (C-7); 170.0 (C-9); 162.0 (NHCO);
152.4 (C-400); 130.1 (C-300); 112.9 (C-200); 121.0 (C-100);
139.5, and 139.4 (C-20, and C-40). Anal found (Cal.) for
C27H26N4OF (%): C, 73.39 (73.42); H, 5.87 (5.89); and N,
12.65 (12.69).
2r,4c-Diphenyl-3-azabicyclo[3.3.1]nonane-9-one-
4-aminobenzoyl hydrazone (9)
2r,4c-Bis(p-chlorophenyl)-3-azabicyclo[3.3.1]nonan-
9-one-4-aminobenzoyl hydrazone (12)
White solid: m.p. 210°C, and yield 62%. IR (KBr) (cm-1):
3032, 2922, and 2859 (C–H stretching); 1636 (C=N
stretching); 1603 (C=C ring stretching); and 3335 (N–H
stretching). 1H NMR (400 MHz—DMSO-d6 ppm). d:
10.50 (s, 1H, amide NH); 7.60 (d, 2H, Ph-a); 6.62 (d, 2H,
Ph-b); 7.66 (q, 4H, ortho); 7.41 (q, 4H, meta); 7.29 (q, 2H,
para); 4.31 (d, 2H, H-2a, H-4a); 3.25 (s, 1H, H-5e); 2.76
(m, 1H, H-7a); 1.64 (m, H, H-8e); 1.45 (m, 3H, H-6a,
H-6e); 1.51 (m, 3H, H-8a); 1.26 (m, 1H, H-7e); 2.84 (s, 1H,
ring NH); and 5.69 (s, 2H, p-NH2). 13C NMR (400 MHz):
65.0 (C-2); 62.7 (C-4); 46.4 (C-1); 28.6 (C-8); 27.3 (C-6);
21.4 (C-7); 167.7 (C-9); 152.4(C-400); 130.1 (C-300);
113.0 (C-200); 121.4 (C-100); 143.5 (C-20, C-40); and 165.6
(NH–CO). Anal found (cal.) for C27H28N4O (%): C, 76.33
(76.36); H, 5.56 (6.59); and N, 13.17 (13.20).
White solid: m.p. 190°C, and yield 65%. IR (KBr) (cm-1):
3332 (N–H stretching); 3034, 2923, and 2855 (C–H
stretching); 1634 (C=N stretching); and 1598 (C=O
stretching). 1H NMR (400 MHz—DMSO-d6 ppm), d:
10.44 (s, 1H, amide NH); 7.67 (d, 2H, H-300); 6.6 (d, 2H,
H-200); 7.60 (q, 4H, ortho); 7.45 (q, 4H, meta); 4.28 (d, 2H,
H-2a, H-4a); 3.2 (s, 1H, H-5e); 2.6 (m, 1H, H-7a); 1.60 (m,
1H, H-8e); 1.44 (m, 3H, H-6a, H-6e, H-8a); 1.25 (m, 1H,
H-7e); 3.01 (m, 1H, ring NH); and 5.66 (s, 2H, p-NH2). 13
C
NMR (400 MHz): 63.6 (C-2); 61.4 (C-4); 45.6 (C-1); 28.5
(C-8); 26.7 (C-6); 20.8 (C-7); 170.2 (C-9); 162.1
(NHCO);151.9 (C-400); 129.6 (C-300); 112.5 (C-200); 120.5
(C-100); and 141.8 (C-20, C-40). Anal found (Cal.) for
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Eisa HM, Tantawy AS, El-Kerdawy MM (1991) Synthesis of certain
2-aminoadamantane derivatives as potential antimicrobial
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C27H26N4Ocl (%): C, 70.76 (70.78); H, 5.65 (5.68); and
N, 12.21 (12.23).
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hydrazones derived from cyclic b-diketone from cytotoxic and
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2r,4c-Bis(o-chlorophenyl)-3-azabicyclo[3.3.1]nonan-
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White solid: m.p. 202°C, and yield 58%. IR (KBr) (cm-1):
3331 (N–H stretching); 3035, 2926, and 2855 (C–H stretch-
1
ing); and 1630 (C=N stretching). H NMR (400 MHz—
DMSO-d6 ppm), d: 10.46 (s, 1H, amide NH); 7.66 (d, 2H,
H-300); 6.6 (d, 2H, H-200); 7.59 (q, 4H, ortho); 7.46 (q, 4H,
meta); 4.27 (d, 2H, H-2a, H-4a); 3.20 (s, 1H, H-5e); 2.65
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1.45 (m, 2H, H-6e, H-8a); 1.25 (m, 1H, H-7e); 3.04 (s, 1H,
ring NH); and 5.68 (s, 2H, p-NH2). 13C NMR (400 MHz):
64.2 (C-2); 61.9 (C-4); 46.0 (C-1); 28.5 (C-8); 27.2 (C-6);
21.3 (C-7); 171.0 (C-9); 169.9 (NHCO); 152 (C-400); 113
(C–200); 121.0(C-100); and 142.8 (C-20, C-40). Anal found
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2r,4c-Diaryl-3-azabicyclo[3.3.1]-nonan-9-one-4-amino-
benzoyl hydrazones 9–15 adopt twin-chair conformation
with equatorial orientations of the aryl groups. All the
newly synthesized compounds were screened for their
preliminary antibacterial and antifungal activities. Most
of the compounds show good antibacterial and anti-
fungal activities. However, the antibacterial and antifungal
activities are significantly influenced by the aromatic
substituents.
Acknowledgments The authors would like to thank the NMR
Research Centre, IISC-Bangalore, and the SAIF-IIT, Madras, for the
recordings of the NMR spectra. The authors extend their thanks to the
RMMCH, Annamalai University for the antimicrobial studies. One of
the authors, Mr. John is thankful to the UGC, India for the award of
UGC-SAP Fellowship.
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