Microwave-assisted synthesis and antimicrobial evaluation of novel pyrazolines

Article abstract of DOI:10.1007/s10593-015-1790-6

A series of 6-(5-aryl-4,5-dihydro-1 H-pyrazol-3-yl)-2,2-dimethylchroman-7-ol and 6-(5-aryl-4,5-dihydro-1 H-pyrazol-3-yl)-2,2-dimethyl-chroman-5-ol derivatives have been synthesized from the corresponding chalcones and hydrazine hydrate in the presence of

Full text of DOI:10.1007/s10593-015-1790-6

DOI 10.1007/s10593-015-1790-6
Chemistry of Heterocyclic Compounds 2015, 51(10), 872–882
Microwave-assisted synthesis and antimicrobial evaluation
of novel pyrazolines
Ashok Dongamanti1*, Mohan Gandhi Devulapally1,
Vikas Kumar Aamate1, Srinivas Gundu1
1 Department of Chemistry, Osmania University,
Tamaka, Hyderabad 500 007, India; e-mail: ashokdou@gmail.com
Published in Khimiya Geterotsiklicheskikh Soedinenii,
2015, 51(10), 872–882
Submitted March 23, 2015
Accepted after revision October 21, 2015
A series of 6-(5-aryl-4,5-dihydro-1H-pyrazol-3-yl)-2,2-dimethylchroman-7-ol and 6-(5-aryl-4,5-dihydro-1H-pyrazol-3-yl)-2,2-dimethyl-
chroman-5-ol derivatives have been synthesized from the corresponding chalcones and hydrazine hydrate in the presence of sodium ace-
tate under microwave irradiation involving the Michael addition followed by cycloaddition. All the newly synthesized 18 compounds
were screened for their in vitro antimicrobial activity. Most of the compounds displayed very good to excellent antimicrobial activity in
comparison to standard drugs streptomycin and nystatin.
Keywords: chalcones, pyrazolines, antimicrobial activity, Michael addition, microwave irradiation.
Since resistance of pathogenic bacteria towards available
antibiotics is rapidly becoming a worldwide problem, the
design of new compounds to deal with resistant bacteria
has become one of the most important areas of antibacterial
research today. In addition, it is known that antifungal
drugs do not have selective activity because of the
biochemical similarity between human cell and fungi
forms.1 Therefore there are many studies focused on
antibacterial and antifungal compounds.2–3 Heterocyclic
compounds such as pyrazolines and chromans are well
known for their significant biological activities. Pyrazo-
lines and their derivatives have attracted considerable
attention due to their extensive biological activities such as
antimicrobial,4,5 antiamoebic,6 antidepressant,7 anticonvul-
sant,8 anti-inflammatory,9 and antitumor.10 Ibipinabant
(Fig. 1), a commercially available drug containing pyrazoline
nucleus, is a potent and highly selective CB1 antagonist.11
On the other hand, chromans are important oxygen-
containing fused heterocycles frequently encountered in
many natural products and exhibit significant biological
activities such as anticancer,12 neuroprotective,13 HIV
inhibitory,14 antimicrobial,15 and antioxidant.16 Vitamin E
(Fig. 1), a naturally occurring chroman, is very effective in
suppression of cellular membrane phospholipid degra-
dation.17 Microwave-assisted organic synthesis is becoming
very popular and is widely practiced by chemists,18 as the
rate of the reaction is accelerated under microwave (MW)
irradiation compared to conventional heating.
Inspired by the biological profile of pyrazolines, their
increasing importance in pharmaceutical and biological
fields, and in connection with our previous research on the
design and synthesis of pharmacologically important new
Figure 1. Examples of commercially available drug containing pyrazoline moiety and a natural product containing chroman ring.
0009-3122/15/5110-0872©2015 Springer Science+Business Media New York
872

Chemistry of Heterocyclic Compounds 2015, 51(10), 872–882
Scheme 1
heterocycles19–22 linked to chroman ring system, we planned
to synthesize pyrazoline compounds containing chroman
moiety by conventional and microwave irradiation methods
(Scheme 1). The constitution of all the compounds was
in THF and heptane.23 The Claisen–Schmidt condensation
of compounds 1 and 2 with the selected aryl aldehydes 3a–i
in the presence of powdered KOH under MW irradiation
produced chalcones – (E)-3-aryl-1-(7-hydroxy-2,2-dimethyl-
chroman-6-yl)prop-2-en-1-ones 4a–i and (E)-1-(5-hydroxy-
2,2-dimethylchroman-6-yl)-3-phenylprop-2-en-1-ones 6a–i,
respectively.24 The reaction of chalcones 4a–i and 6a–i
with hydrazine hydrate in DMF in the presence of sodium
acetate under thermal conditions gave the target pyrazolines
6-(5-aryl-4,5-dihydro-1H-pyrazol-3-yl)-2,2-dimethylchroman-
7-ols 5a–i and 6-(5-aryl-4,5-dihydro-1H-pyrazol-3-yl)-
2,2-dimethylchroman-5-ols 7a–i in low yields, and it took
several hours to complete the reaction (Table 1). Hence, to
investigate the advantages of microwave-assisted synthesis,
1
characterized using elemental analysis, FT-IR, H, 13C NMR,
and mass spectroscopy. The synthesized pyrazoline com-
pounds were evaluated for their in vitro antimicrobial activity.
In the present investigation we have synthesized novel
pyrazolines from the respective precursor chalcones. The
synthesis of new derivatives of pyrazoline was carried out
as outlined in Scheme 1. The starting materials 1-(7-hydroxy-
2,2-dimethylchroman-6-yl)ethanone (1) and 1-(5-hydroxy-
2,2-dimethylchroman-6-yl)ethanone (2) were prepared from
resacetophenone and isoprene using Amberlyst-15 as catalyst
Table 1. Substituents and yields of compounds 5a–i and 7a–i obtained with conventional heating and microwave irradiation
Conventional method*
Microwave method**
Com-
pound
R1
R2
R3
Time, h
Yield, %
Time, min
Yield, %
H
H
H
OMe
H
H
H
H
H
H
H
H
OMe
H
H
H
H
H
H
Me
OMe
OMe
Cl
Cl
i-Pr
H
NMe2
H
Me
OMe
OMe
Cl
Cl
i-Pr
H
H
H
H
OMe
H
Cl
H
NO2
H
H
H
H
OMe
H
Cl
H
4.0
5.0
5.0
7.0
7.0
6.0
7.0
8.0
7.0
4.0
5.0
5.0
6.0
7.0
7.0
6.0
8.0
7.0
68
62
64
56
62
62
60
58
66
66
64
62
58
60
64
62
58
64
2.0
2.5
3.0
3.5
3.0
3.0
3.0
5.0
3.5
2.5
3.0
3.0
3.5
3.5
3.0
2.5
5.0
3.5
90
86
88
86
86
86
88
60
85
90
88
88
86
86
88
84
80
82
5a
5b
5c
5d
5e
5f
5g
5h
5i
7a
7b
7c
7d
7e
7f
7g
7h
7i
NO2
H
NMe2
* Chalcone 4 or 6 (1.0 mmol), hydrazine hydrate (1.0 mmol), NaOAc (1.0 mmol) in DMF (5 ml) heated at 80–90°C.
** Chalcone 4 or 6 (1.0 mmol), hydrazine hydrate (1.0 mmol), NaOAc (1.0 mmol) in DMF (5 ml) irradiated with MW (180 W).
873

Chemistry of Heterocyclic Compounds 2015, 51(10), 872–882
we synthesized the target pyrazolines under MW irradiation.
subtilis (MTCC 441), Staphylococcus aureus (MTCC 737),
and two Gram-negative bacteria viz., Pseudomonas
aeruginosa (MTCC 741), Escherichia coli (MTCC 443).
Nutrient agar medium was used for the antibacterial
screening. The zone of inhibition (in mm) was compared
with standard drug streptomycin sulfate. Antifungal
activity was carried out against three fungi viz., Aspergillus
niger (ATCC 9029), Candida albicans (ATCC 2091), and
Aspergillus foetidus (NCIM 505). Sabouraud's agar
medium was used for the antifungal screening. Nystatin
was used as standard. The results are presented in Tables 2
and 3.
The investigation of antibacterial activity (Table 2)
revealed that compounds 5a,c,g, 7a,d,g,i (inhibition zone
>26 mm) showed excellent growth inhibition against
Bacillus subtilis as compared to streptomycin (21 mm) at
100 µg/ml concentration. In the case of Staphylococcus
aureus, compounds 5a,g, 7a,d (>27 mm) were found to be
exceedingly potent in comparison with the standard
(20 mm). Compounds 5b,d,f,i, 7b,c,d,f,g were found to
exhibit good activity against both Gram-positive bacterial
strains used in the test.
On the other hand, antibacterial activity evaluation
against Gram-negative bacteria Pseudomonas aeruginosa
revealed that all the tested compounds except 5e,h, 7e,h
showed excellent to moderate activity compared to the
standard drug streptomycin. Compounds 5b,c,g, 7a,d,f,g,i
(inhibition zone >27 mm) were found to exhibit higher
activity than the standard drug. Compounds 5c,g,i,
7a,d,f,g,i (>27 mm) were significantly more active than the
standard drug streptomycin (21 mm) against Escherichia
coli. Compounds 5b, 7b,c demonstrated activity compar-
able with that of streptomycin against Escherichia coli.
Chalcones 4a–i and 6a–i and hydrazine hydrate in DMF in
the presence of sodium acetate were irradiated at 180 W
power for 2–5 min to give pyrazole derivatives 5a–i and 7a–i
in high yields. Therefore, investigation results revealed that
applying MW irradiation to the reaction mixture provides
better yields and lesser reaction times.
1
The H NMR spectrum of the representative compound
5a in CDCl3 solution showed three characteristic signals
due to the diastereotopic protons CHA and CHB, as well as
CHX proton at the chiral carbon atom of the pyrazoline
ring.25,26 The CHA proton, which is cis-oriented relative to
CHX proton resonated as doublet of doublets at a higher
field (3.10 ppm, JAB = 16.4, JAX = 8.8 Hz) than the CHB
proton which is trans-oriented (3.51 ppm, JBA = 16.4,
J
BX = 10.8 Hz). The CHX proton (4.83 ppm) signal had both
matching vicinal spin-spin interaction constants (8.8 and
10.8 Hz).
The proposed structure of compound 5a was further
supported by the 13C NMR spectrum, in which the signals
at 41.7 and 61.9 ppm could be attributed to C-4 and C-5
carbons of the pyrazoline ring, respectively, based on the
close agreement of those values with the reported values
for the respective carbons in analogous structures.27,28 The
ESI mass spectrum of 5a showed the principal ion peak at
the expected m/z value (323) for protonated molecular ion
1
[M+H]+. The combination of H and 13C NMR and mass
spectral data thus provides a strong evidence in support of
the structures assigned to pyrazoline derivatives 5a–i, 7a–i.
All new 18 pyrazoline compounds 5a–i, 7a–i were
screened for their antibacterial and antifungal activity by
the cup-plate agar diffusion method.29 Antibacterial activity
was tested against two Gram-positive bacteria viz., Bacillus
Table 2. Antibacterial activity of compounds 5a–i and 7a–i expressed as zone of inhibition (mm)*
Gram-positive strains
Gram-negative strains
Com-
pound
Bacillus subtilis
Staphylococcus aureus
Pseudomonas aeruginosa
Escherichia coli
(MTCC 443)
(MTCC 441)
(MTCC 737)
(MTCC 741)
26
25
26
25
–**
25
28
–
28
24
26
24
–
26
27
–
26
27
27
24
–
26
28
–
25
23
27
26
–
25
30
–
5a
5b
5c
5d
5e
5f
5g
5h
25
29
25
22
27
–
24
27
24
22
27
–
26
28
26
22
30
–
28
28
24
22
29
–
5i
7a
7b
7c
7d
7e
24
26
–
28
21
26
25
–
2
20
27
29.5
–
27
23
27
28
–
28
21
7f
7g
7h
7i
Streptomycin
* The compounds were tested at 200 µg/ml concentration.
** Not active.
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Chemistry of Heterocyclic Compounds 2015, 51(10), 872–882
Overall, among the target molecules, only four compounds
of the compounds against on various bacterial and fungal
strains. Different electronic environments on the phenyl
ring were produced by combination of different functional
groups. Both electron-donating and electron-withdrawing
groups were chosen as substituents for the design and
synthesis of the target molecules (Table 1).
5e,h, 7e,h did not respond to any of the bacterial strains,
whereas compounds 5a,c,d,g,i and 7a,c,d,g,i showed
excellent zones of inhibition against all bacterial strains.
All the synthesized pyrazolines 5a–i, 7a–i were screened
in vitro for their antifungal activity against Aspergillus
niger (ATCC 9029), Candida albicans (ATCC 2091), and
Aspergillus foetidus (NCIM 505). Sabouraud's agar
medium was used for the antifungal screening. Zone of
inhibition (in mm) was compared with that of standard
drug nystatin. The results are presented in Table 3.
From the antibacterial and antifungal data available in
the report, it can be concluded that, as a trend, electron-
donating functional groups like OMe, Me, i-Pr, and
N,N-dimethylamino in the para-position of the phenyl
group, as well as 3,4,5-trimethoxyphenyl group, caused
larger zone of inhibition than the electron-withdrawing
groups like 4-Cl, 3-NO2 on the phenyl group, or
3,4-dichlorophenyl group. Compounds 5b,c,d,g,i and
7b,c,d,g,i possesing electron-donating groups at para-
position showed excellent activity against all bacterial
strains and moderate activity against fungal strains. It was
also observed that compounds 5e,f,h and 7e,f,h possesing
electron-withdrawing groups showed moderate to poor
inhibition of the growth of bacterial with respect to the
standard. The antibacterial, as well as antifungal activities
for the compounds 5a and 7a are well pronounced even in
the absence of any substitution in the phenyl ring.
Compounds without substituent(s) on phenyl ring showed
very good antimicrobial activity compared to those with
substituent(s) (electron-donating or electron-withdrawing)
on the phenyl ring. Overall, the presence of electron-
donating groups like methyl or methoxy group as
substituents on phenyl ring in the synthesized molecules
helps to increase the antimicrobial potency. From these
results, we hypothesized that the compounds with electron-
donating groups are predominantly involved in the
From the antifungal activity data it can be observed that
compounds 5a,c,d,g, 7a,b,c,d,g,i (inhibition zone >25 mm)
exhibited excellent zone of inhibition when employed
against Aspergillus niger as compared to the standard drug
nystatin (22 mm). Other compounds 5b,f, 7f showed
moderate zone of inhibition values, while compounds 5e,h,
7e,h were showing no activity against Aspergillus niger.
When the synthesized compounds were tested against
C. albicans, compounds 5a,g,i, 7a–d,g,i (>25 mm) were
found to exhibit excellent zone of inhibition values compared
to the standard drug (21 mm). Compounds 5b–d,f, 7f were
also found to exhibit good to moderate zone of inhibition
against C. albicans compared to the standard drug.
Compounds 5a,g, 7a,d,g (>27 mm) were significantly more
active against Aspergillus foetidus compared to nystatin
(20 mm). Compounds 5b–d,i, 7b,c,i also showed higher
activity compared to the standard while compounds 5e,f,h,
7e,f,h showed moderate to low activity against the fungal
strain Aspergillus foetidus.
The structure–activity relationship analysis revealed the
effect of different substituents at phenyl ring on the activity
Table 3. Antifungal activity of compounds 5a–i and 7a–i expressed as zone of inhibition (mm)*
Compound
Aspergillus niger (ATCC 9029)
Candida albicans (ATCC 2091)
Aspergillus foetidus (NCIM 505)
26
22
26
28
–**
16
26
–
26
22
24
24
–
27
25
25
24
–
5a
5b
5c
5d
5e
20
27
–
17
27
–
5f
5g
5h
5i
22
28
25
27
29
–
26
27
26
26
28
–
24
28
25
24
28
–
7a
7b
7c
7d
7e
15
29
–
21
29
–
14
28
–
7f
7g
7h
7i
Nystatin
25
22
25
21
23
20
* The compounds were tested at 200 µg/ml concentration.
** Not active.
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Chemistry of Heterocyclic Compounds 2015, 51(10), 872–882
inhibition of protein synthesis of the bacteria and thus stop
spectrum, δ, ppm (J, Hz): 1.36 (6H, s, 2CH3); 1.85 (2H, t,
J = 6.8, CH2); 2.78 (2H, t, J = 6.8, CH2); 6.37 (1H, s, H-5);
7.42–7.65 (6H, m, H Ar, α-CH); 7.66–7.88 (2H, m, H-8,
β-CH); 13.00 (1H, s, OH). 13C NMR spectrum, δ, ppm:
22.3; 26.8; 32.7; 79.8; 103.4; 112.5; 118.2; 119.3; 126.8;
127.8; 128.5; 131.5; 134.8; 144.5; 161.1; 164.3; 191.4.
Mass spectrum, m/z (Irel, %): 309 [M+H]+ (100). Found, %:
C 70.85; H 6.59. C20H20O3. Calculated, %: C 70.90; H 6.54.
(E)-1-(7-Hydroxy-2,2-dimethylchroman-6-yl)-3-(4-methyl-
phenyl)prop-2-en-1-one (4b). Yield 96%, pale-yellow
solid, mp 164–166°C (mp 167–168°C30). IR spectrum,
ν, cm–1: 2934, 2853, 1638, 1568, 1356, 1289, 1151, 818.
1H NMR spectrum, δ, ppm (J, Hz): 1.37 (6H, s, 2CH3);
1.85 (2H, t, J = 6.8, CH2); 2.42 (3H, s, CH3); 2.79 (2H, t,
J = 6.8, CH2); 6.39 (1H, s, H-5); 7.18–7.26 (2H, m, H Ar);
7.54–7.68 (4H, m, α-CH, H-8, H Ar); 7.88 (1H, d, J = 15.8,
β-CH); 13.00 (1H, s, OH). 13C NMR spectrum, δ, ppm:
21.3; 22.3; 26.8; 32.7; 76.8; 104.1; 112.5; 119.3; 126.8;
128.5; 129.4; 131.5; 132.6; 138.5; 144.5; 161.1; 164.3;
192.4. Mass spectrum, m/z (Irel, %): 323 [M+H]+ (100).
Found, %: C 78.26; H 6.83. C21H22O3. Calculated, %:
C 78.23; H 6.88.
or slow down the growth or proliferation of bacterial
cells.22 Thus, in the future combination of different electron-
donating groups on the phenyl ring together with
pyrazoline moiety will be tried out for generating better
lead entities as potent antibacterial and antifungal agents.
We have reported an easy, high yielding, and convenient
method for the synthesis of 2,2-dimethyl-6-(5-aryl-4,5-di-
hydro-1H-pyrazol-3-yl)chroman-7-ol derivatives and 2,2-di-
methyl-6-(5-aryl-4,5-dihydro-1H-pyrazol-3-yl)chroman-5-ol
derivatives from suitable chalcones (E)-3-aryl-1-(7-hydr-
oxy-2,2-dimethylchroman-6-yl)prop-2-en-1-ones and
(E)-3-aryl-1-(5-hydroxy-2,2-dimethylchroman-6-yl)prop-
2-en-1-ones under microwave irradiation method. All the
final compounds were investigated for their in vitro anti-
microbial activity. Several compounds showed promising
antibacterial activity when compared to streptomycin and
good antifungal activity compared to nystatin. We observed
that compounds with electron-donating groups on phenyl
ring showed better antimicrobial activity than those with
electron-withdrawing groups.
Experimental
(E)-1-(7-Hydroxy-2,2-dimethylchroman-6-yl)-3-(4-meth-
oxyphenyl)prop-2-en-1-one (4c). Yield 97%, pale-yellow
solid, mp 145–146°C (mp 146–147°C30). IR spectrum, ν, cm–1:
2929, 1634, 1602, 1558, 1423, 1358, 1293, 1247, 1151,
IR spectra were recorded on a Shimadzu FT-IR 8400 S
spectrometer in KBr pellets. 1H and 13C NMR spectra were
recorded on a Bruker Avance-400 spectrometer (400 and
100 MHz, respectively) in CDCl3 using TMS as internal
standard. Mass spectra (ESI) were recorded on a Shimadzu
GCMS-QP 1000 spectrometer. Elemental analyses were
recorded on a Karlo Erba 1106 elemental analyzer. Melting
points were taken in open capillary tubes and are
uncorrected. Microwave reactions were carried out in a
Milestone multi SYNTH series ATC-FO 300 multimode
microwave reactor with a twin magnetron (2×800 W,
2.45 GHz) with a maximum delivered power of 1000 W in
10 W increments (pulsed irradiation). Analytical TLC was
performed on Merck precoated 60 F254 silica gel plates.
Visualization was done by exposing to iodine vapor and
UV. All the reagents and solvents were purchased from
commercial sources.
1
1028, 831, 761; H NMR spectrum, δ, ppm (J, Hz): 1.30
(6H, s, 2CH3); 1.70 (2H, t, J = 6.8, CH2); 2.75 (2H, t, J = 6.8,
CH2); 6.39 (1H, s, H-5); 3.64 (3H, s, OCH3); 6.87–6.92
(2H, m, H Ar); 7.59–7.62 (3H, m, H Ar, α-CH); 7.76 (1H,
s, H-8); 7.83 (1H, d, J = 15.8, β-CH); 13.1 (1H, s, OH). 13
C
NMR spectrum, δ, ppm: 22.3; 26.8; 32.7; 56.2; 75.8; 108.8;
111.6; 112.5; 118.5; 126.8; 128.5; 129.5; 131.5; 139.5;
144.5; 161.1; 164.3; 191.4. Mass spectrum, m/z (Irel, %):
339 [M+H]+ (100). Found, %: C 74.50; H 6.51. C21H22O4.
Calculated, %: C 74.54; H 6.55.
(E)-1-(7-Hydroxy-2,2-dimethylchroman-6-yl)-3-(3,4,5-
trimethoxyphenyl)prop-2-en-1-one (4d). Yield 98%, pale-
yellow solid, mp 107–110°C. IR spectrum, ν, cm–1: 2926,
1
2865, 1647, 1565, 1376, 1268, 1150, 889, 762. H NMR
Synthesis of chalcones 4a–i and 6a–i (General
method). A mixture of 1-(7-hydroxy-2,2-dimethylchroman-
6-yl)-ethanone (1) or 1-(5-hydroxy-2,2-dimethylchroman-
6-yl)-ethanone (2) (0.194 g, 1.0 mmol), an aromatic
aldehyde 3a–i (1.0 mmol), and powdered KOH (0.224 g,
4 mmol) in ethanol (10 ml) was taken into a quartz tube
and inserted into a screw-capped Teflon vial and then
subjected to microwave irradiation for 2 or 3 periods of
5 min at 180 W (90°C) with 30 s time interval between
them. The progress of the reaction was monitored by TLC
(eluent petroleum ether–AcOEt, 4:1). After completion of
the reaction, the reaction mixture was neutralized with
dilute HCl, the solid obtained was filtered off, washed with
water, dried, and recrystallized from chloroform to yield
pure chalcones 4a–i or 6a–i.
spectrum, δ, ppm (J, Hz): 1.37 (6H, s, 2CH3); 1.85 (2H, t,
J = 6.8, CH2); 2.79 (2H, t, J = 6.8, CH2); 3.91 (3H, s,
OCH3); 3.93 (6H, s, 2OCH3); 6.37 (1H, s, H-5); 6.87 (2H,
s, H Ar); 7.43 (1H, d, J = 15.8, α-CH); 7.62 (1H, s, H-8);
7.78 (1H, d, J = 15.8, β-CH); 13.20 (1H, s, OH). 13C NMR
spectrum, δ, ppm: 22.4; 27.0; 32.9; 56.7; 60.7; 75.9; 108.8;
111.6; 112.5; 118.5; 120.3; 126.8; 131.5; 139.5; 144.5;
156.6; 161.1; 164.3; 191.4. Mass spectrum, m/z (Irel, %):
399 [M+H]+ (100). Found %: C 69.35; H 6.55. C23H26O6.
Calculated, %: C 69.33; H 6.58.
(E)-3-(4-Chlorophenyl)-1-(7-hydroxy-2,2-dimethyl-
chroman-6-yl)prop-2-en-1-one (4e). Yield 98%, pale-
yellow solid, mp 170–172°C. IR spectrum, ν, cm–1: 2928,
2864, 1632, 1566, 1358, 1209, 1086, 811. 1H NMR
spectrum, δ, ppm (J, Hz): 1.37 (6H, s, 2CH3); 1.83 (2H, t,
J = 6.8, CH2); 2.72 (2H, t, J = 6.8, CH2); 6.38 (1H, s, H-5);
7.36–7.39 (2H, m, H Ar); 7.53–7.58 (3H, m, H Ar, α-CH);
7.68 (1H, s, H-8); 7.78 (1H, d, J = 15.8, β-CH); 12.90 (1H,
s, OH). 13C NMR spectrum, δ, ppm: 22.3; 26.7; 32.3; 76.9;
(E)-1-(7-Hydroxy-2,2-dimethylchroman-6-yl)-3-phenyl-
prop-2-en-1-one (4a). Yield 98%, pale-yellow solid,
mp 192–193°C (mp 194–195°C30). IR spectrum, ν, cm–1:
2938, 2855, 1637, 1570, 1357, 1151, 973. 1H NMR
876

Chemistry of Heterocyclic Compounds 2015, 51(10), 872–882
109.3; 112.7; 114.5; 118.9; 128.5; 129.4; 130.5; 133.4;
(100). Found, %: C 75.25; H 7.20. C22H25NO3. Calculated,
133.6; 145.2; 161.0; 165.2; 192.4. Mass spectrum, m/z (Irel, %):
343 [M+H]+ (100). Found, %: C 70.12; H 5.65. C20H19ClO3.
Calculated, %: C 70.07; H 5.59.
%: C 75.19; H 7.17.
(E)-1-(5-Hydroxy-2,2-dimethylchroman-6-yl)-3-phenyl-
prop-2-en-1-one (6a). Yield 98%, pale-yellow solid,
mp 129–130°C (mp 128–129°C30). IR spectrum, ν, cm–1:
(E)-3-(3,4-Dichlorophenyl)-1-(7-hydroxy-2,2-dimethyl-
chroman-6-yl)prop-2-en-1-one (4f). Yield 98%, pale-
yellow solid, mp 100–102°C. IR spectrum, ν, cm–1: 2929,
1
2979, 1633, 1571, 1359, 1279, 1220, 1112, 867. H NMR
spectrum, δ, ppm (J, Hz): 1.36 (6H, s, 2CH3); 1.83 (2H, t,
J = 6.8, CH2); 2.78 (2H, t, J = 6.8, CH2); 6.39 (1H, d,
J = 8.8, H-7); 6.86–6.92 (2H, m, H Ar); 7.33–7.43 (3H, m,
H Ar); 7.59–7.62 (1H, m, H Ar, α-CH); 7.66 (1H, d,
J = 8.6, H-8); 7.94 (1H, d, J = 15.5, β-CH); 13.00 (1H, s,
OH). 13C NMR spectrum, δ, ppm: 16.3; 26.9; 32.7; 79.8;
108.4; 112.5; 115.2; 119.3; 127.3; 128.5; 129.5; 131.5;
135.8; 144.5; 163.1; 165.3; 192.4. Mass spectrum, m/z (Irel, %):
309 [M+H]+ (100). Found, %: C 70.85; H 6.59. C20H20O3.
Calculated, %: C 70.90; H 6.54.
1
2858, 1590, 1433, 1360, 1295, 1157, 1090, 821. H NMR
spectrum, δ, ppm (J, Hz): 1.30 (6H, s, 2CH3); 1.77 (2H, t,
J = 6.8, CH2); 2.74 (2H, t, J = 6.8, CH2); 6.68 (1H, s, H-5);
7.24 (1H, s, H Ar); 7.36–7.59 (3H, m, H Ar, α-CH); 7.94
(1H, s, H-8); 8.06 (1H, d, J = 15.8, β-CH); 13.40 (1H, s,
OH). 13C NMR spectrum, δ, ppm: 22.3; 26.8; 32.7; 76.5;
104.3; 112.7; 119.8; 127.3; 127.5; 128.5; 129.2; 130.1;
132.4; 133.5; 135.3; 145.2; 161.0; 164.2; 190.4. Mass
spectrum, m/z (Irel, %): 378 [M+H]+ (100). Found, %:
C 63.60; H 4.78. C20H18Cl2O3. Calculated, %: C 63.67;
H 4.81.
(E)-1-(5-Hydroxy-2,2-dimethylchroman-6-yl)-3-(4-me-
thylphenyl)prop-2-en-1-one (6b). Yield 97%, pale-yellow
solid, mp 150–151°C (mp 152–153°C30). IR spectrum, ν,
cm–1: 2934, 2856, 1625, 1573, 1363, 1284, 1220, 1109,
(E)-1-(7-Hydroxy-2,2-dimethylchroman-6-yl)-3-(4-iso-
propylphenyl)prop-2-en-1-one (4g). Yield 98%, pale-
yellow solid, mp 95–98°C. IR spectrum, ν, cm–1: 2932,
2854 1598, 1463, 1352, 1260, 1167, 1108, 1032, 759.
1H NMR spectrum, δ, ppm (J, Hz): 1.26 (6H, d, J = 7.0,
(CH3)2)CH); 1.36 (6H, s, 2CH3); 1.84 (2H, t, J = 6.8, CH2);
2.78 (2H, t, J = 6.8, CH2); 2.91–2.93 (1H, m, (CH3)2CH);
6.37 (1H, s, H-5); 7.28–7.30 (2H, m, H Ar); 7.52–7.60 (3H,
m, H Ar, α-CH); 7.62 (1H, s, H-8); 7.85 (1H, d, J = 15.6,
β-CH); 13.00 (1H, s, OH). 13C NMR spectrum, δ, ppm:
22.3; 23.3; 26.8; 32.3; 33.5; 76.6; 109.3; 112.7; 118.6;
119.8; 126.5; 128.6; 131.4; 135.3; 145.2; 147.8; 161.0;
164.2, 192.4. Mass spectrum, m/z (Irel, %): 351 [M+H]+
(100). Found, %: C 78.85; H 7.45. C23H26O3. Calculated, %:
C 78.83; H 7.48.
(E)-1-(7-Hydroxy-2,2-dimethylchroman-6-yl)-3-(3-nitro-
phenyl)prop-2-en-1-one (4h). Yield 98%, pale-yellow
solid, mp 145–147°C (mp 147–148°C30). IR spectrum,
ν, cm–1: 2926, 2852, 1641, 1570, 1354, 1275, 1154, 890.
1H NMR spectrum, δ, ppm (J, Hz): 1.32 (6H, s, 2CH3);
1.77 (2H, t, J = 6.8, CH2); 2.75 (2H, t, J = 6.8, CH2); 6.39
(1H, s, H-5); 7.69–7.72 (2H, m, H Ar, β-CH); 7.82 (1H, s,
H-8); 8.00–8.08 (3H, m, H Ar, α-CH); 8.25 (1H, s, H Ar);
13.00 (1H, s, OH). 13C NMR spectrum, δ, ppm: 22.3; 27.0;
32.4; 78.5; 104.5; 112.7; 118.5; 119.7; 123.5; 124.6; 128.5;
129.4; 131.1; 137.7; 142.2; 148.0; 162.0; 163.2; 192.5.
Mass spectrum, m/z (Irel, %): 354 [M+H]+ (100). Found, %:
C 67.94; H 5.36. C20H19NO5. Calculated, %: C 67.98;
H 5.42.
1
883. H NMR spectrum, δ, ppm (J, Hz): 1.37 (6H, s,
2CH3); 1.85 (2H, t, J = 6.8, CH2); 2.42 (3H, s, CH3); 2.79
(2H, t, J = 6.8, CH2); 6.40 (1H, d, J = 8.8, H-7); 7.20–7.24
(2H, m, H Ar); 7.44–7.63 (3H, m, α-CH, H Ar); 7.69 (1H,
d, J = 8.6, H-8); 7.86 (1H, d, J = 15.1, β-CH); 14.00 (1H, s,
OH). 13C NMR spectrum, δ, ppm: 16.3; 21.5; 26.7; 31.8;
75.8; 109.1; 109.3; 112.8; 119.5; 128.5; 129.7; 129.8;
132.2; 141.0; 143.9; 160.8; 164.1; 191.9. Mass spectrum,
m/z (Irel, %): 323 [M+H]+ (100). Found, %: C 78.26;
H 6.83. C21H22O3. Calculated, %: C 78.23; H 6.88.
(E)-1-(5-Hydroxy-2,2-dimethylchroman-6-yl)-3-(4-meth-
oxyphenyl)prop-2-en-1-one (6c). Yield 98%, pale-yellow
solid, mp 107–109°C (mp 106–107°C30). IR spectrum, ν,
cm–1: 2926, 2853, 1598, 1514, 1354, 1286, 1224, 1171,
1
1111, 891, 764. H NMR spectrum, δ, ppm (J, Hz): 1.30
(6H, s, 2CH3); 1.70 (2H, t, J = 6.8, CH2); 2.75 (2H, t,
J = 6.8, CH2); 3.65 (3H, s, OCH3); 6.39 (1H, d, J = 8.8,
H-7); 6.87 (2H, d, J = 8.7, H Ar); 7.49 (1H, d, J = 15.5,
α-CH); 7.61 (2H, d, J = 8.7, H Ar); 7.72 (1H, d, J = 8.6,
H-8); 7.82 (1H, d, J = 15.5, β-CH); 14.00 (1H, s, OH). 13
C
NMR spectrum, δ, ppm: 16.2; 26.8; 32.7; 55.8; 76.8; 107.1;
114.6; 115.5; 123.3; 129.5; 130.4; 131.4; 132.2; 139.5;
144.5; 156.6; 160.1; 191.4. Mass spectrum, m/z (Irel, %):
339 [M+H]+ (100). Found, %: C 74.50; H 6.51. C21H22O4.
Calculated, %: C 74.54; H 6.55.
(E)-1-(5-Hydroxy-2,2-dimethylchroman-6-yl)-3-(3,4,5-
trimethoxyphenyl)prop-2-en-1-one (6d). Yield 98%, pale-
yellow solid, mp 98–100°C. IR spectrum, ν, cm–1: 2979,
1635, 1578, 1498, 1359, 1221, 1112, 867. 1H NMR
spectrum, δ, ppm (J, Hz): 1.38 (6H, s, 2CH3); 1.85 (2H, t,
J = 6.8, CH2); 2.74 (2H, t, J = 6.8, CH2); 3.87 (3H, s,
OCH3); 3.90 (6H, s, 2OCH3); 6.38 (1H, d, J = 8.8, H-7);
6.87 (2H, s, H Ar); 7.47 (1H, d, J = 15.2, α-CH); 7.71 (1H,
d, J = 8.6, H-8); 7.80 (1H, d, J = 15.2, β-CH); 13.80 (1H, s,
OH). 13C NMR spectrum, δ, ppm: 16.3; 26.8; 32.7; 56.6;
60.7; 75.8; 103.8; 107.1; 112.6; 115.5; 118.5; 131.5; 139.5;
144.5; 155.7; 156.6; 161.1; 164.3; 191.4. Mass spectrum,
m/z (Irel, %): 399 [M+H]+ (100). Found, %: C 69.33;
H 6.55. C23H26O6. Calculated, %: C 69.30; H 6.58.
(E)-3-[4-(Dimethylamino)phenyl]-1-(5-hydroxy-2,2-di-
methylchroman-6-yl)prop-2-en-1-one (4i). Yield 98%,
pale-yellow solid, mp 170–172°C. IR spectrum, ν, cm–1:
1
2928, 1589, 1432, 1355, 1164, 1108, 1062, 846. H NMR
spectrum, δ, ppm (J, Hz): 1.36 (6H, s, 2CH3); 1.84 (2H, t,
J = 6.8, CH2); 2.78 (2H, t, J = 6.8, CH2); 3.06 (3H, s,
NCH3); 6.41 (1H, s, H-5); 6.61–6.64 (2H, m, H Ar); 7.58–
7.62 (3H, m, H Ar, α-CH); 7.61 (1H, s, H-8); 7.85 (1H, d,
J = 15.8, β-CH); 13.10 (1H, s, OH). 13C NMR spectrum,
δ, ppm: 22.3; 26.8; 33.0; 41.5; 77.1; 108.3; 111.7; 112.7;
115.3; 118.8; 122.5; 128.5; 130.1; 145.2; 156.2; 163.0;
165.2; 191.3. Mass spectrum, m/z (Irel, %): 352 [M+H]+
877

Chemistry of Heterocyclic Compounds 2015, 51(10), 872–882
(E)-3-(4-Chlorophenyl)-1-(5-hydroxy-2,2-dimethyl-
1109, 791. 1H NMR spectrum, δ, ppm (J, Hz): 1.36 (6H, s,
2CH3); 1.84 (2H, t, J = 6.8, CH2); 2.78 (2H, t, J = 6.8,
CH2); 3.06 (6H, s, N(CH3)2); 6.42 (1H, d, J = 8.8, H-7);
6.61–6.64 (2H, m, H Ar); 7.56–7.60 (3H, m, H Ar, α-CH);
7.64 (1H, d, J = 8.6, H-8); 7.84 (1H, d, J = 15.8, β-CH).
13.0 (1H, s, OH). 13C NMR spectrum, δ, ppm: 16.4; 26.7;
31.9; 40.1; 75.6; 108.8; 109.2; 111.8; 113.0; 114.9; 122.7;
128.2; 130.4; 144.8; 152.0; 160.2; 163.9; 191.9. Mass
spectrum, m/z (Irel, %): 352 [M+H]+ (100). Found, %: C 75.25;
H 7.20. C22H25NO3. Calculated, %: C 75.19; H 7.17.
Synthesis of pyrazolines 5a–i and 7a–i (General
method). Conventional method. Sodium acetate (0.08 g,
1.0 mmol) and hydrazine hydrate (0.03 g, 1.0 mmol) were
added to a solution of an appropriate chalcone 4a–i, 6a–i
(1.0 mmol) in DMF (5 ml), and the reaction mixture was
heated at 80–90°C for 4–8 h. The progress of the reaction
was monitored by TLC (hexane–AcOEt, 4:1). After the
completion of the reaction, ice water was added. The
separated solid product was filtered off, washed with water,
dried, and recrystallized from the mixture CHCl3–MeOH,
1:1.
Microwave method. A mixture of an appropriate
chalcone 4a–i, 6a–i (1.0 mmol), hydrazine hydrate (0.03 g,
1.0 mmol), and sodium acetate (0.08 g, 1.0 mmol) in DMF
(5 ml) was taken in a quartz tube (10 ml) and inserted into
a screw-capped Teflon vial and then subjected to
microwave irradiation for 2–5 min using an irradiation
power of 180 W (90°C). The progress of the reaction was
monitored by TLC for every 30 s. After completion of the
reaction, ice water was added. The separated solid product
was filtered off, washed with water, dried, and recrys-
tallized from mixture CHCl3–MeOH, 1:1.
chroman-6-yl)prop-2-en-1-one (6e). Yield 98%, pale-
yellow solid, mp 138–140°C. IR spectrum, ν, cm–1: 2943,
1638, 1585, 1488, 1223, 1112, 874, 792. 1H NMR
spectrum, δ, ppm (J, Hz): 1.39 (6H, s, 2CH3); 1.83 (2H, t,
J = 6.8, CH2); 2.78 (2H, t, J = 6.8, CH2); 6.38 (1H, d,
J = 8.8, H-7); 7.40–7.49 (2H, m, H Ar); 7.52–7.68 (4H, m,
H Ar, α-CH, H-8); 7.80 (1H, d, J = 15.6, β-CH); 12.90 (1H,
s, OH). 13C NMR spectrum, δ, ppm: 16.1; 26.7; 33.0; 76.9;
108.3; 112.7; 114.5; 118.9; 128.5; 129.4; 130.5; 133.4;
133.6; 145.2; 161.0; 165.2; 192.4. Mass spectrum, m/z (Irel, %):
343 [M+H]+ (100). Found, %:
C20H19ClO3. Calculated, %: C 70.07; H 5.59.
C 70.12; H 5.65.
(E)-3-(3,4-Dichlorophenyl)-1-(5-hydroxy-2,2-dimethyl-
chroman-6-yl)prop-2-en-1-one (6f). Yield 98%, pale-
yellow solid, mp 92–94°C. IR spectrum, ν, cm–1: 2979,
1
1627, 1526, 1426, 1212, 1108, 792. H NMR spectrum,
δ, ppm (J, Hz): 1.30 (6H, s, 2CH3); 1.77 (2H, t, J = 6.8,
CH2); 2.74 (2H, t, J = 6.8, CH2); 6.69 (1H, d, J = 8.8, H-7);
7.23 (1H, s, H Ar); 7.36–7.55 (3H, m, H Ar, α-CH); 7.88
(1H, d, J = 8.8, H-8); 8.06 (1H, d, J = 15.5, β-CH); 13.4
(1H, s, OH). 13C NMR spectrum, δ, ppm: 16.3; 26.8; 32.9;
76.5; 107.5; 112.7; 114.5; 119.8; 127.5; 128.6; 129.2;
129.6; 130.1; 132.4; 133.5; 135.3; 145.2; 161.0; 164.2;
190.4. Mass spectrum, m/z (Irel, %): 377 [M+H]+ (100).
Found, %: C 63.60; H 4.78. C20H18Cl2O3. Calculated, %:
C 63.67; H 4.81.
(E)-1-(5-Hydroxy-2,2-dimethylchroman-6-yl)-3-(4-iso-
propylphenyl)prop-2-en-1-one (6g). Yield 98%, yellow
solid, mp 90–92°C. IR spectrum, ν, cm–1: 2930, 1594,
1
1430, 1351, 1157, 1114, 1058, 671. H NMR spectrum,
δ, ppm (J, Hz): 1.27 (6H, d, J = 7.0, (CH3)2)CH); 1.36 (6H,
s, 2CH3); 1.84 (2H, t, J = 6.8, CH2); 2.78 (2H, t, J = 6.8,
CH2); 2.91–2.93 (1H, m, (CH3)2CH); 6.39 (1H, d, J = 8.8,
H-7); 7.24–7.28 (2H, m, H Ar); 7.56–7.60 (3H, m, H Ar,
α-CH); 7.64 (1H, d, J = 8.7, H-8); 7.85 (1H, d, J = 15.5,
β-CH); 13.00 (1H, s, OH). 13C NMR spectrum, δ, ppm:
16.1; 23.3; 26.9; 32.8; 33.0; 77.1; 108.3; 112.7; 115.3;
119.8; 127.5; 129.2; 130.1; 132.4; 145.2; 147.5; 163.0;
165.2; 191.3. Mass spectrum, m/z (Irel, %): 351 [M+H]+
(100). Found, %: C 78.80; H 7.44. C23H26O3. Calculated,
%: C 78.83; H 7.48.
2,2-Dimethyl-6-(5-phenyl-4,5-dihydro-1H-pyrazol-
3-yl)-chroman-7-ol (5a). Pale-yellow solid, mp 120–122°
C. IR spectrum, ν, cm–1: 3422, 2927, 1632, 1493, 1294,
1
1118, 822, 700. H NMR spectrum, δ, ppm (J, Hz): 1.33
(3H, s, CH3); 1.35 (3H, s, CH3); 1.78 (2H, t, J = 6.7, CH2);
2.68 (2H, t, J = 6.7, CH2); 3.10 (1H, dd, JAB = 16.4, JAX = 8.8,
CHAHB); 3.51 (1H, dd, JBA = 16.4, JBX = 10.8, CHAHB);
4.83 (1H, dd, JXA = 8.8, JXB = 10.8, CHX); 6.42 (1H, s,
H-5); 6.83 (1H, s, H-8); 7.30–7.35 (5H, m, H Ar).
13C NMR spectrum, δ, ppm: 21.8; 26.9; 33.0; 41.7;
61.9; 74.8; 104.8; 109.8; 112.0; 114.3; 126.5; 127.5;
128.5; 134.5; 156.0; 157.6; 159.3. Mass spectrum, m/z
(Irel, %): 323 [M+H]+ (100). Found, %: C 74.45; H 6.83;
N 8.64. C20H22N2O2. Calculated, %: C 74.51; H 6.88;
N 8.69.
(E)-1-(5-Hydroxy-2,2-dimethylchroman-6-yl)-3-(3-nitro-
phenyl)prop-2-en-1-one (6h). Yield 98%, yellow solid,
mp 128–130°C. IR spectrum, ν, cm–1: 2924, 2855, 1643,
1565, 1342, 1154, 844. 1H NMR spectrum, δ, ppm (J, Hz):
1.34 (6H, s, 2CH3); 1.82 (2H, t, J = 6.8, CH2); 2.75 (2H, t,
J = 6.8, CH2); 6.38 (1H, d, J = 8.5, H-7); 7.75–7.78 (2H, m,
H Ar, β-CH); 7.86 (1H, d, J = 8.5, H-8); 7.99–8.13 (3H, m,
H Ar, α-CH); 8.25 (1H, s, H Ar); 13.0 (1H, s, OH).
13C NMR spectrum, δ, ppm: 16.1; 26.9; 32.3; 76.5; 109.3;
111.7; 114.6; 118.7; 122.5; 123.6; 129.4; 130.1; 135.3;
137.7; 141.2; 147.8; 161.0; 164.2; 192.4. Mass spectrum,
m/z (Irel, %): 354 [M+H]+ (100). Found, %: C 67.90;
H 5.38. C20H19NO5. Calculated, %: C 67.98; H 5.42.
2,2-Dimethyl-6-[5-(4-methylphenyl)-4,5-dihydro-1H-
pyrazol-3-yl]chroman-7-ol (5b). White solid, mp 125–
129°C. IR spectrum, ν, cm–1: 3342, 2937, 1634, 1509,
1
1260, 1151, 751. H NMR spectrum, δ, ppm (J, Hz): 1.34
(6H, s, 2CH3); 1.80 (2H, t, J = 6.8, CH2); 2.39 (3H, s,
CH3); 2.73 (2H, t, J = 6.8, CH2); 3.10 (1H, dd, JAB = 16.4,
JAX = 8.8, CHAHB); 3.51 (1H, dd, JBA = 16.4, JBX = 10.8,
CHAHB); 4.83 (1H, dd, JXA = 8.8, JXB = 10.8, CHX); 6.40
(1H, s, H-5); 6.79 (2H, d, J = 8.5, H Ar); 6.94 (1H, s, H-8);
7.23–7.24 (2H, m, H Ar); 11.40 (1H, s, OH). 13C NMR
spectrum, δ, ppm: 21.8; 22.3; 26.9; 33.0; 41.7; 61.9; 74.8;
104.6; 109.4; 112.0; 114.3; 127.5; 128.5; 134.5; 152.6;
(E)-3-[4-(Dimethylamino)phenyl]-1-(5-hydroxy-2,2-di-
methylchroman-6-yl)prop-2-en-1-one (6i). Yield 98%,
pale-yellow solid, mp 135–136°C (mp 136–137°C31).
IR spectrum, ν, cm–1: 2912, 2853, 1609, 1555, 1364, 1228,
878

Chemistry of Heterocyclic Compounds 2015, 51(10), 872–882
156.1; 157.6; 159.3. Mass spectrum, m/z (Irel, %): 337 [M+H]+
spectrum, δ, ppm: 21.8; 27.0; 33.0; 41.5; 61.9; 74.7; 104.6;
108.9; 112.0; 114.3; 127.5; 128.2; 128.5; 129.4; 130.1;
134.7; 156.0; 156.9; 159.3. Mass spectrum, m/z (Irel, %):
392 [M+H]+ (100). Found, %: C 61.30; H 5.13; N 7.15.
C20H20Cl2N2O2. Calculated, %: C 61.39; H 5.15; N 7.16.
6-[5-(4-Isopropylphenyl)-4,5-dihydro-1H-pyrazol-3-yl]-
2,2-dimethylchroman-7-ol (5g). Yellow solid, mp 139–
142°C. IR spectrum, ν, cm–1: 3346, 2962, 1636, 1512,
(100). Found, %: C 74.85; H 7.15; N 8.30. C21H24N2O2.
Calculated, %: C 74.97; H 7.19; N 8.33.
6-[5-(4-Methoxyphenyl)-4,5-dihydro-1H-pyrazol-3-yl]-
2,2-dimethylchroman-7-ol (5c). White solid, mp 140–
142°C. IR spectrum, ν, cm–1: 3340, 2936, 1636, 1509,
1
1250, 1151, 827, 747. H NMR spectrum, δ, ppm (J, Hz):
1.33 (6H, s, 2CH3); 1.79 (2H, t, J = 6.8, CH2); 2.69 (2H, t,
J = 6.8, CH2); 3.75 (1H, dd, JAB = 16.4, JAX = 8.8, CHAHB);
3.46 (1H, dd, JBA = 16.4, JBX = 10.8, CHAHB); 3.80 (3H, s,
OCH3); 4.78 (1H, dd, JXA = 8.8, JXB = 10.8, CHX); 5.75
(1H, br. s, NH); 6.42 (1H, s, H-5); 6.85 (2H, d, J = 7.9,
H Ar); 6.88 (1H, s, H-8); 7.27 (2H, d, J = 8.1, H Ar); 11.00
(1H, br. s, OH). 13C NMR spectrum, δ, ppm: 21.7; 26.8;
32.9; 41.7; 55.3; 61.8; 74.7; 104.3; 109.8; 111.9; 114.2;
127.4; 128.4; 134.4; 154.5; 156.1; 157.5; 159.3. Mass
spectrum, m/z (Irel, %): 353 [M+H]+ (100). Found, %:
C 71.52; H 6.84; N 7.92. C21H24N2O3. Calculated, %:
C 71.57; H 6.86; N 7.95.
1
1276, 1156, 805. H NMR spectrum, δ, ppm (J, Hz): 1.25
(6H, d, J = 6.6 (CH3)2CH); 1.34 (6H, s, 2CH3); 1.80 (2H, t,
J = 6.8, CH2); 2.73 (2H, t, J = 6.8, CH2); 2.95–2.97 (1H, m,
(CH3)2CH); 3.11 (1H, dd, JAB = 16.4, JAX = 8.8, CHAHB);
3.51 (1H, dd, JBA = 16.4, JBX = 10.8, CHAHB); 4.80 (1H,
dd, JXA = 8.8, JXB = 10.8, CHX); 6.40 (1H, s, H-5); 6.80
(1H, s, H-8); 7.15–7.20 (3H, m, H Ar); 7.28 (1H, s, H Ar);
11.40 (1H, s, OH). 13C NMR spectrum, δ, ppm: 21.7; 23.8;
27.0; 32.9; 33.8; 41.7; 61.9; 74.8; 104.5; 108.6; 112.3;
114.5; 127.3; 128.4; 134.5; 156.1; 156.3; 157.6. Mass
spectrum, m/z (Irel, %): 365 [M+H]+ (100). Found, %:
C 75.72; H 7.72; N 7.64. C23H28N2O2. Calculated, %:
C 75.79; H 7.74; N 7.69.
2,2-Dimethyl-6-[5-(3,4,5-trimethoxyphenyl)-4,5-dihydro-
1H-pyrazol-3-yl]chroman-7-ol (5d). Yellow solid, mp
155–157°C. IR spectrum, ν, cm–1: 3457, 2943, 1656, 1596,
1534, 1439, 1116, 846. 1H NMR spectrum, δ, ppm (J, Hz):
1.50 (6H, s, 2CH3); 1.95 (2H, t, J = 6.8, CH2); 2.85 (2H, t,
J = 6.8, CH2); 3.22 (1H, dd, JAB = 16.4, JAX = 8.8, CHAHB);
3.68 (1H, dd, JBA = 16.4, JBX = 10.8, CHAHB); 3.89 (3H, s,
OCH3); 4.02 (6H, s, 2OCH3); 4.95 (1H, dd, JXA = 8.8,
2,2-Dimethyl-6-[5-(3-nitrophenyl)-4,5-dihydro-1H-
pyrazol-3-yl]chroman-7-ol (5h). Yellow solid, mp 157–
160°C. IR spectrum, ν, cm–1: 3342, 2935, 1645, 1536,
1
1501, 1350, 1281, 1160, 794. H NMR spectrum, δ, ppm
(J, Hz): 1.34 (6H, s, 2CH3); 1.81 (2H, t, J = 6.8, CH2); 2.79
(2H, t, J = 6.8, CH2); 3.05 (1H, dd, JAB = 16.4, JAX = 8.8,
CHAHB); 3.62 (1H, dd, JBA = 16.4, JBX = 10.8, CHAHB);
4.97 (1H, dd, JXA = 8.8, JXB = 10.8, CHX); 6.40 (1H, s,
H-5); 6.91 (1H, d, J = 8.8, H Ar); 7.53 (1H, t, J = 8.8,
H Ar); 7.65 (1H, s, H-8); 8.16 (1H, d, J = 8.1, H Ar); 8.25
(1H, s, H Ar). 13C NMR spectrum, δ, ppm: 21.8; 26.9; 32.8;
41.7; 61.9; 74.8; 104.5; 112.0; 114.3; 126.4; 127.5; 1280.1;
128.5; 129.8; 130.5; 134.5; 156.1; 157.6; 159.3. Mass
spectrum, m/z (Irel, %): 368 [M+H]+ (100). Found, %:
C 65.30; H, 5.72; N 11.40. C20H21N3O4. Calculated, %:
C 65.38; H 5.76; N 11.44.
JXB = 10.8, CHX); 6.59 (1H, s, H-5); 6.78 (1H, s, H-8); 7.00
(1H, s, H Ar); 7.43 (1H, s, H Ar). 13C NMR spectrum,
δ, ppm: 21.7; 26.8; 32.9; 42.2; 56.2; 60.8; 62.8; 74.7;
103.2; 104.3; 109.6; 112.0; 128.4; 137.8; 150.4; 153.5;
156.1; 157.5; 159.4. Mass spectrum, m/z (Irel, %): 413
[M+H]+ (100). Found, %: C 66.91; H 6.80; N 6.75.
C23H28N2O5. Calculated, %: C 66.97; H 6.84; N 6.79.
6-[5-(4-Chlorophenyl)-4,5-dihydro-1H-pyrazol-3-yl]-
2,2-dimethylchroman-7-ol (5e). White solid, mp 160–
162°C. IR spectrum, ν, cm–1: 3344, 2947, 1630, 1496,
1275, 1170, 1045, 815. 1H NMR spectrum, δ, ppm (J, Hz):
1.34 (6H, s, 2CH3); 1.79 (2H, t, J = 6.8, CH2); 2.69 (2H, t,
J = 6.8, CH2); 3.04 (1H, dd, JAB = 16.4, JAX = 8.8, CHAHB);
3.52 (1H, dd, JBA = 16.4, JBX = 10.8, CHAHB); 4.81 (1H,
dd, JXA = 8.8, JXB = 10.8, 1-CHX); 5.86 (1H, br. s, NH);
6.43 (1H, s, H-5); 6.83 (1H, s, H-8); 7.31–7.33 (4H, m,
H Ar); 10.80 (1H, br. s, OH). 13C NMR spectrum, δ, ppm:
21.8; 26.9; 27.1; 32.8; 41.5; 74.8; 104.5; 109.6; 112.0;
114.3; 127.8; 128.3; 129.2; 133.6; 153.4; 156.1; 159.2.
Mass spectrum, m/z (Irel, %): 357 [M+H]+ (100). Found, %:
C 67.30; H 5.90; N 7.83. C20H21ClN2O2. Calculated, %:
C 67.32; H, 5.93; N 7.85.
6-{5-[4-(Dimethylamino)phenyl]-4,5-dihydro-1H-py-
razol-3-yl}-2,2-dimethylchroman-7-ol (5i). Yield 85%,
yellow solid, mp 118–120°C. IR spectrum, ν, cm–1: 3344,
2927, 1634, 1521, 1285, 1152, 880, 758. 1H NMR
spectrum, δ, ppm (J, Hz): 1.33 (6H, s, 2CH3); 1.79 (2H, t,
J = 6.8, CH2); 2.69 (2H, t, J = 6.8, CH2); 2.94 (6H, s,
2CH3); 3.10 (1H, dd, JAB = 16.4, JAX = 8.8, CHAHB); 3.43
(1H, dd, JBA = 16.4, JBX = 10.8, CHAHB); 4.74 (1H, dd,
JXA = 8.8, JXB = 10.8, CHX); 5.85 (1H, br. s, NH); 6.42
(1H, s, H-5); 6.69 (2H, d, J = 8.2, H Ar); 6.85 (1H, s, H-8);
7.19 (2H, d, J = 8.2, H Ar); 10.90 (1H, s, OH). 13C NMR
spectrum, δ, ppm: 21.7; 26.8; 32.9; 40.5; 41.4; 61.9; 74.6;
104.3; 111.9; 112.7; 125.4; 127.8; 128.3; 130.0; 150.3;
154.6; 156.0; 157.5. Mass spectrum, m/z (Irel, %): 366
[M+H]+ (100). Found, %: C 72.26; H 7.43; N 11.42.
C22H27N3O2. Calculated, %: C 72.30; H 7.45; N 11.50.
2,2-Dimethyl-6-(5-phenyl-4,5-dihydro-1H-pyrazol-3-yl)-
chroman-5-ol (7a). White solid, mp 97–100°C. IR spectrum,
ν, cm–1: 3335, 2931, 1627, 1595, 1498, 1350, 1275, 1232,
1162, 761. 1H NMR spectrum, δ, ppm (J, Hz): 1.34 (6H, s,
2CH3); 1.82 (2H, t, J = 6.8, CH2); 2.75 (2H, t, J = 6.8,
CH2); 3.12 (1H, dd, JAB = 16.4, JAX = 8.8, CHAHB); 3.52
6-[5-(3,4-Dichlorophenyl)-4,5-dihydro-1H-pyrazol-
3-yl]-2,2-dimethylchroman-7-ol (5f). Yield 86%, yellow
solid, mp 142–145°C. IR spectrum, ν, cm–1: 3346, 2934,
1
1636, 1596, 1485, 1285, 1175, 845. H NMR spectrum,
δ, ppm (J, Hz): 1.34 (6H, s, 2CH3); 1.80 (2H, t, J = 6.8,
CH2); 2.73 (2H, t, J = 6.8, CH2); 3.02 (1H, dd, JAB = 16.4,
JAX = 8.8, CHAHB); 3.52 (1H, dd, JBA = 16.4, JBX = 10.8,
CHAHB); 4.78 (1H, dd, JXA = 8.8, JXB = 10.8, CHX); 6.40
(1H, s, H-5); 6.80 (1H, s, H-8); 7.21 (1H, d, J = 7.8, H Ar);
7.40–7.46 (2H, m, H Ar); 11.40 (1H, s, OH). 13C NMR
879

Chemistry of Heterocyclic Compounds 2015, 51(10), 872–882
(1H, dd, JBA = 16.4, JBX = 10.8, CHAHB); 4.82 (1H, dd,
(J, Hz): 1.34 (6H, s, 2CH3); 1.82 (2H, t, J = 6.8, CH2); 2.75
(2H, t, J = 6.8, CH2); 3.04 (1H, dd, JAB = 16.4, JAX = 8.8,
CHAHB); 3.52 (1H, dd, JBA = 16.4, JBX = 10.8, CHAHB);
4.80 (1H, dd, JXA = 8.8, JXB = 10.8, CHX); 5.84 (1H, br. s,
NH); 6.36 (1H, d, J = 8.53, H-7); 6.93 (1H, d, J = 8.78,
H-8); 7.28–7.33 (4H, m, H Ar); 11.30 (1H, s, OH).
13C NMR spectrum, δ, ppm: 16.8; 26.8; 33.0; 41.7; 61.9;
74.8; 108.4; 109.7; 126.5; 127.4; 128.1; 128.5; 130.9;
142.2; 153.4; 156.2; 156.6. Mass spectrum, m/z (Irel, %):
357 [M+H]+ (100). Found, %: C 67.30; H 5.90; N 7.83.
C20H21ClN2O2. Calculated, %: C 67.32; H 5.93; N 7.85.
6-[5-(3,4-Dichlorophenyl)-4,5-dihydro-1H-pyrazol-3-yl]-
2,2-dimethylchroman-7-ol (7f). Yield 88%, white solid,
mp 125–127°C. IR spectrum, ν, cm–1: 3328, 2925, 1627, 1593,
JXA = 8.8, JXB = 10.8, CHX); 5.86 (1H, br. s, NH); 6.36
(1H, d, J = 8.5, H-7); 6.94 (1H, d, J = 8.8, H-8); 7.29–7.31
(1H, m, H Ar); 7.34–7.35 (4H, m, H Ar); 11.40 (1H, s,
OH). 13C NMR spectrum, δ, ppm: 16.9; 26.6; 26.7; 32.2;
41.7; 62.3; 74.6; 108.2; 108.4; 109.1; 125.9; 126.3; 127.9;
128.9; 142.4; 155.0; 156.0; 156.7. Mass spectrum, m/z (Irel, %):
323 [M+H]+ (100). Found, %: C 74.45; H 6.83; N 8.64.
C20H22N2O2. Calculated, %: C 74.51; H 6.88; N 8.69.
2,2-Dimethyl-6-[5-(4-methylphenyl)-4,5-dihydro-1H-
pyrazol-3-yl]chroman-7-ol (7b). Pale-yellow solid, mp
115–117°C. IR spectrum, ν, cm–1: 3327, 2931, 1627, 1503,
1
1275, 1161, 795. H NMR spectrum, δ, ppm (J, Hz): 1.33
(3H, s, CH3); 1.34 (3H, s, CH3); 1.82 (2H, t, J = 6.8, CH2);
2.33 (3H, s, CH3); 2.75 (2H, t, J = 6.8, CH2); 3.10 (1H, dd,
JAB = 16.4, JAX = 8.8, CHAHB); 3.49 (1H, dd, JBA = 16.4,
JBX = 10.8, CHAHB); 4.79 (1H, dd, JXA = 8.8, JXB = 10.8,
CHX); 6.35 (1H, d, J = 8.5, H-7); 6.94 (1H, d, J = 8.6, H-8);
7.14 (2H, d, J = 8.1, H Ar); 7.23 (2H, d, J = 8.11, H Ar);
11.40 (1H, br. s, OH). 13C NMR spectrum, δ, ppm: 16.8;
22.4; 26.5; 33.0; 41.7; 61.9; 74.5; 108.2; 108.4; 109.5;
125.5; 127.5; 128.5; 142.5; 155.1; 156.6; 156.9. Mass
spectrum, m/z (Irel, %): 337 [M+H]+ (100). Found, %:
C 74.85; H 7.15; N 8.30. C21H24N2O2. Calculated, %:
C 74.97; H 7.19; N 8.33.
1
1471, 1274, 1161, 797. H NMR spectrum, δ, ppm (J, Hz):
1.34 (3H, s, CH3); 1.36 (3H, s, CH3); 1.84 (2H, t, J = 6.8, CH2);
2.75 (2H, t, J = 6.8, CH2); 3.02 (1H, dd, JAB = 16.4, JAX = 8.8,
CHAHB); 3.53 (1H, dd, JBA = 16.4, JBX = 10.8, CHAHB); 4.78
(1H, dd, JXA = 8.8, JXB = 10.8, CHX); 6.36 (1H, d, J = 8.8,
H-7); 6.91 (1H, d, J = 8.8, H-8); 7.21 (1H, d, J = 8.7, H Ar);
7.40–7.48 (2H, m, H Ar); 11.20 (1H, s, OH). 13C NMR
spectrum, δ, ppm: 16.9; 26.6; 32.1; 42.0; 61.3; 74.7; 107.9;
108.5; 109.2; 124.5; 125.9; 128.5; 130.8; 131.8; 132.9; 142.5;
154.9; 156.2; 156.7. Mass spectrum, m/z (Irel, %): 392 [M+H]+
(100). Found, %: C 61.30; H 5.13; N 7.15. C20H20Cl2N2O2.
Calculated, %: C 61.39; H 5.15; N 7.16.
6-[5-(4-Methoxyphenyl)-4,5-dihydro-1H-pyrazol-3-yl]-
2,2-dimethylchroman-7-ol (7c). Yellow solid, mp 138–
140°C. IR spectrum, ν, cm–1: 3133, 2935, 1626, 1597,
1512, 1245, 1164, 811. 1H NMR spectrum, δ, ppm (J, Hz):
1.34 (6H, s, 2CH3); 1.82 (2H, t, J = 6.8, CH2); 2.75 (2H, t,
J = 6.8, CH2); 3.08 (1H, dd, JAB = 16.4, JAX = 8.8, CHAHB);
3.48 (1H, dd, JBA = 16.4, JBX = 10.8, CHAHB); 3.80 (3H, s,
OCH3); 4.78 (1H, dd, JXA = 8.8, JXB = 10.8, CHX); 6.36
(1H, d, J = 8.5, H-7); 6.87 (2H, d, J = 8.0, H Ar); 6.94 (1H,
d, J = 8.8, H-8); 7.25–7.28 (2H, m, H Ar). 13C NMR
spectrum, δ, ppm: 16.9; 26.9; 32.2; 41.6; 55.3; 61.8; 74.5;
108.3; 109.1; 125.9; 127.5; 128.6; 129.1; 130.5; 142.1;
155.2; 156.6; 156.8. Mass spectrum, m/z (Irel, %): 353
[M+H]+ (100). C21H24N2O3. Found, %: C 71.52; H 6.84;
N 7.92. Calculated, %: C 71.57; H 6.86; N 7.95.
2,2-Dimethyl-6-[5-(3,4,5-trimethoxyphenyl)-4,5-dihydro-
1H-pyrazol-3-yl]chroman-7-ol (7d). White solid, mp 120–
122°C. IR spectrum, ν, cm–1: 3431, 2934, 1665, 1593,
1504, 1419, 1126, 801. 1H NMR spectrum, δ, ppm (J, Hz):
1.36 (6H, s, 2CH3); 1.85 (2H, t, J = 6.8, CH2); 2.77 (2H, t,
J = 6.8, CH2); 3.24 (1H, dd, JAB = 16.4, JAX = 8.8, CHAHB);
3.80 (3H, s, OCH3); 3.82 (6H, s, 2OCH3); 3.87 (1H, dd,
JBA = 16.4, JBX = 10.8, CHAHB); 5.46 (1H, dd, JXA = 8.8,
6-[5-(4-Isopropyphenyl)-4,5-dihydro-1H-pyrazol-3-yl]-
2,2-dimethylchroman-7-ol (7g). Pale-yellow solid, mp
170–172°C. IR spectrum, ν, cm–1: 3340, 2957, 1630, 1503,
1
1275, 1161, 795. H NMR spectrum, δ, ppm (J, Hz): 1.25
(6H, d, J = 6.6, (CH3)2CH); 1.34 (3H, s, CH3); 1.35 (3H, s,
CH3); 1.82 (2H, t, J = 6.8, CH2); 2.75 (2H, t, J = 6.8, CH2);
2.86–2.92 (1H, m, (CH3)2CH); 3.11 (1H, dd, JAB = 16.4,
JAX = 8.8, CHAHB); 3.49 (1H, dd, JBA = 16.4, JBX = 10.8,
CHAHB); 4.79 (1H, dd, JXA = 8.8, JXB = 10.8, CHX); 5.81
(1H, br. s, NH); 6.35 (1H, d, J = 8.5, H-7); 6.94 (1H, d,
J = 8.8, H-8); 7.18–7.20 (3H, m, H Ar); 7.27 (1H, s, H Ar);
11.43 (1H, s, OH). 13C NMR spectrum, δ, ppm: 16.9; 23.9;
26.6; 26.7; 29.7; 32.2; 33.8; 41.6; 62.1; 74.8; 108.3; 109.1;
125.9; 126.2; 126.9; 139.7; 148.7; 155.0; 156.0; 156.7.
Mass spectrum, m/z (Irel, %): 365 [M+H]+ (100). Found, %:
C 75.72; H 7.72; N 7.64. C23H28N2O2. Calculated, %:
C 75.79; H 7.74; N 7.69.
2,2-Dimethyl-6-[5-(3-nitrophenyl)-4,5-dihydro-1H-pyrazol-
3-yl]-chroman-7-ol (7h). Orange solid, mp 120–122°C.
IR spectrum, ν, cm–1: 3328, 2927, 1626, 1531, 1496, 1348,
1
1273, 1160, 802. H NMR spectrum, δ, ppm (J, Hz): 1.34
(3H, s, CH3); 1.36 (3H, s, CH3); 1.82 (2H, t, J = 6.8, CH2);
2.75 (2H, t, J = 6.8, CH2); 3.05 (1H, dd, JAB = 16.4,
JAX = 8.8, CHAHB); 3.62 (1H, dd, JBA = 16.4, JBX = 10.8,
CHAHB); 4.97 (1H, dd, JXA = 8.8, JXB = 10.8, CHX); 6.36
(1H, d, J = 8.5, H-7); 6.91 (1H, d, J = 7.1, H Ar); 7.54 (1H,
t, J = 8.8, H Ar); 7.75 (1H, d, J = 8.8, H-8); 8.16 (1H, d,
J = 7.1, H Ar); 8.26 (1H, s, H Ar). 13C NMR spectrum,
δ, ppm: 16.9; 26.6; 26.7; 29.6; 32.1; 42.2; 61.6; 74.6;
107.8; 108.5; 109.2; 121.7; 122.8; 125.9; 129.9; 132.5;
144.3; 154.9; 156.3; 156.7. Mass spectrum, m/z (Irel, %):
368 [M+H]+ (100). Found, %: C 65.30; H 5.72; N 11.40.
C20H21N3O4. Calculated, %: C 65.38; H 5.76; N 11.44.
J
XB = 10.8, CHX); 6.40–6.42 (3H, m, H Ar, H-7); 6.97 (1H,
d, J = 8.8, H-8); 10.67 (1H, s, OH). 13C NMR spectrum,
δ, ppm: 16.8; 26.6; 26.7; 31.9; 42.9; 56.1; 58.3; 60.7; 75.1;
102.5; 103.3; 109.3; 109.5; 126.8; 137.1; 153.6; 156.7;
157.0; 157.6; 167.7. Mass spectrum, m/z (Irel, %): 413
[M+H]+ (100). Found, %: C 66.91; H 6.80; N 6.75.
C23H28N2O5. Calculated, %: C 66.97; H 6.84; N 6.79.
6-[5-(4-Chlorophenyl)-4,5-dihydro-1H-pyrazol-3-yl]-
2,2-dimethylchroman-7-ol (7e). Yield 86%, yellow solid,
mp 170–173°C. IR spectrum, ν, cm–1: 3308, 2932, 1626,
1
1595, 1272, 1162, 1058, 874. H NMR spectrum, δ, ppm
880

Chemistry of Heterocyclic Compounds 2015, 51(10), 872–882
used for the antifungal screening contained 20.0 g of agar
6-{5-[4-(Dimethylamino)phenyl]-4,5-dihydro-1H-
pyrazol-3-yl}-2,2-dimethylchroman-7-ol (7i). Yellow
solid, mp 140–143°C. IR spectrum, ν, cm–1: 3318, 2927,
in addition to the composition of Sabouraud's broth. The
corning sterile Petri dishes were used for investigation. The
molten Sabouraud's agar medium (about 20 ml) was poured
in each of the sterilized Petri dishes and 24 h old broth
cultures of fungal strains (0.5 ml each) was added to the
respective Petri dishes. The contents of the Petri dishes
were mixed thoroughly by rotary motion. After
solidification of the medium, four cups (diameter 8 mm)
were made with the help of a sterile borer at equal
distances. the Sabouraud's agar dishes were incubated at
28°C for 48 h. The presence of a definite zone of inhibition
surrounding the cups indicated antifungal activity. The
diameter of the zone of inhibition31 was recorded. The
experiments were performed at least in triplicate.
1
1622, 1523, 1351, 1275, 1163, 795. H NMR spectrum,
δ, ppm (J, Hz): 1.34 (6H, s, 2CH3); 1.82 (2H, t, J = 6.8,
CH2); 2.75 (2H, t, J = 6.8, CH2); 2.93 (6H, s, N(CH3)2);
3.10 (1H, dd, JAB = 16.4, JAX = 8.8, CHAHB); 3.44 (1H, dd,
JBA = 16.4, JBX = 10.8, CHAHB); 4.59 (1H, dd, JXA = 8.8,
JXB = 10.8, CHX); 5.83 (1H, br. s, NH); 6.35 (1H, d,
J = 8.5, H-7); 6.68 (2H, d, J = 8.1, H Ar); 6.95 (1H, d,
J = 8.8, H-8); 7.20 (2H, d, J = 8.1, H Ar);11.44 (1H, s,
OH). 13C NMR spectrum, δ, ppm: 16.9; 26.6; 26.7; 30.9;
32.2; 40.6; 41.4; 61.9; 74.5; 108.3; 108.5; 109.0; 112.8;
125.9; 127.1; 150.3; 155.2; 155.9; 156.7. Mass spectrum,
m/z (Irel, %): 366 [M+H]+ (100). Found, %: C 72.25;
H 7.48; N 11.45. C22H27N3O2. Calculated, %: C 72.30;
H 7.45; N 11.50.
Antibacterial activity investigation. The test solutions
of the samples were prepared in dimethyl formamide. The
commercial drug streptomycin, used as standard, was
dissolved in sterile distilled water. The microorganisms
employed in this study were two Gram-positive bacteria
such as Bacillus subtilis (MTCC 441), Staphylococcus
aureus (MTCC 737), and two Gram-negative bacteria such
as Pseudomonas aeruginosa (MTCC 741), Escherichia coli
(MTCC 443). Nutrient broth (pH 7.2) was used for the
preparation of inoculum of bacteria. Nutrient agar medium
used for the antibacterial screening contained 20.0 g of agar
in addition to the composition of nutrient broth. The agar
medium was sterilized by autoclaving at 120°C for 15 min.
The Petri dishes and pipettes were sterilized by dry heat in
a hot-air oven at 150°C for 1 h. The molten agar medium
(about 20 ml) was poured in each of sterilized Petri dishes
and 24 h old broth cultures (0.5 ml each) of bacterial strains
were added to the respective Petri dishes. The contents of
the Petri dishes were mixed thoroughly by rotary motion.
After solidification of the medium, four cups (diameter
8 mm) were made with the help of a sterile borer at equal
distances. Accurately measured test samples (200 µg/ml,
0.1 ml) and standard antibiotics (200 µg/ml, 0.1 ml) were
added into the cups and labelled accordingly. The dishes
were kept undisturbed in a cool place for 1 h to allow the
solutions to diffuse into the medium. The nutrient agar
dishes were then incubated at 37°C for 24 h. . The presence
of a definite zone of inhibition surrounding the cups
indicated antibacterial activity. The diameter of the zone of
inhibition31 was recorded. The experiments were performed
at least in triplicate.
Supporting material to this article containing of 1H NMR,
13C NMR, and mass spectra of the synthesized compounds is
available online at http://link.springer.com/journal/10593.
We thank the Head of Department of Chemistry,
Osmania University, Hyderabad, for providing laboratory
facilities. One of the authors (MGD) is grateful to
University Grants Commission, New Delhi, for the award
of Senior Research Fellowship. We also thank the CFRD
analytical team, Osmania University, for providing
spectral analysis facilities.
References
1. Williams, D. A.; Lemke, T. L. Foye's Principles of Medicinal
Chemistry; 5th ed.; Lippincott Williams and Wilkins, 2002,
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