Hydrazonoyl halides as precursors for synthesis of novel bioactive thiazole and formazan derivatives

Article abstract of DOI:10.3184/174751912X13491094428620

A new series of substituted 4-methyl-5-(arylazo)-2-[N'-(6,7,8,9-tetrahydro- benzocyclohepten-5-ylidene)-hydrazino]-thiazoles and 5-(arylhydrazono)-2-[N'-(6, 7,8,9-tetrahydro-benzocyclohepten-5-ylidene)-hydrazino]-thiazol-4-one were prepared by reaction of hydrazonoyl chlorides with a thiosemicarbazone derivative. The tautomeric structures of the products were studied using electronic absorption and NMR spectroscopy. The site-selectivities of the reactions of hydrazonoyl halides with benzocyclohepten-5-one hydrazone were also investigated. In addition, the antimicrobial activity of some of the products was evaluated. Many derivatives have promising activities against antibacterial and antifungal species.

Full text of DOI:10.3184/174751912X13491094428620

660 RESEARCH PAPER
NOVEMBER, 660–664
JOURNAL OF CHEMICAL RESEARCH 2012
Hydrazonoyl halides as precursors for synthesis of novel bioactive
thiazole and formazan derivatives
Thoraya A. Farghalya* and Eman M.H. Abbasb
aDepartment of Chemistry, Faculty of Science, University of Cairo, Giza, Egypt
bDepartment of Chemistry, Natural and Microbial Products, National Research Center, Dokki, Cairo, Egypt
A new series of substituted 4-methyl-5-(arylazo)-2-[N’-(6,7,8,9-tetrahydro-benzocyclohepten-5-ylidene)-hydrazino]-
thiazoles and 5-(arylhydrazono)-2-[N’-(6,7,8,9-tetrahydro-benzocyclohepten-5-ylidene)-hydrazino]-thiazol-4-one were
prepared by reaction of hydrazonoyl chlorides with a thiosemicarbazone derivative. The tautomeric structures of the
products were studied using electronic absorption and NMR spectroscopy. The site-selectivities of the reactions of
hydrazonoyl halides with benzocyclohepten-5-one hydrazone were also investigated. In addition, the antimicrobial
activity of some of the products was evaluated. Many derivatives have promising activities against antibacterial and
antifungal species.
Keywords: thiosemicarbazone, hydrazone, thiazole, hydrazonoyl chlorides, formazan, antimicrobial activity
Our previous work with benzocycloheptenone (benzosuber-
one) has led to the synthesis of bioactive novel heterocyclic
compounds.1–3 Thiazole derivatives exhibit a number of
biological properties, such as antimicrobial,4 antiprotozoal,5
anti-inflammatory,4 anticonvulsant,6 cardiotonic,7 analgesic,
antithermic8 and anticancer9 properties. In addition to these
findings, formazans and heterocyclic hydrazones are known
for their diverse biological activities.10–12 As part of our
ongoing interests in the reactions of hydrazonoyl halides
with several heterocyclic compounds to synthesise bioactive
compounds,13–15 we investigated the reaction of hydrazonoyl
halides with benzocyclohepten-5-one thiosemicarbazones and
benzocyclohepten-5-one hydrazone to give new derivatives of
thiazole and substituted formazan which were expected to be
biologically active. We also elucidated the actual tautomeric
structures of such thiazole derivatives as they can have one or
more of eight possible tautomeric forms (Scheme 2 and Fig. 1).
chromophore.18 Furthermore, the spectrum of 5c, taken as a
typical example of the series studied, in solvents of different
polarities, showed little, if any, shift (Table 1). The small shift
in λmax of 5c in different solvents is due to solute–solvent inter-
action. This finding excludes the hydrazone tautomeric form
5A (Fig. 1). From our point of view, the most stable structure
is likely to be 5C due to the aromaticity of the thiazole ring.
This choice is also based on the 13C NMR spectral data of com-
pounds 5Cc and 5Cd which revealed a signal near 170 ppm
for the carbon 2 in thiazole ring (S–C=N) while carbon 2 in
thiazole ring of compound 5B appears upfield of this value.19
On the other hand, reaction of hydrazonoyl chlorides 6
with thiosemicarbazone derivative 2 afforded the hydrazone
tautomeric structures 7B (Scheme 2 and Fig. 1). The structure
of these products was established on the basis of spectral data
and absorption spectra. For example, the mass spectra of the
latter products revealed in each case, the molecular ion peaks
at the expected m/z values and their elemental analysis data
were consistent with their assigned structures. Their IR spectra
showed, in each case, one carbonyl band in the region 1712–
1663 cm−1 and two NH bands in the region 3228–3151 and
3166–3066 cm−1. The observed wavenumber of the CO stretch-
ing band in the compounds 7 seems to result from the possible
strong hydrogen bonding with the hydrazone NH and conjuga-
tion with the C=N double bond as required by the hydrazone
form 7B (Fig. 1). The electronic absorption spectral data of the
studied compounds 7 are summarised in Table 1. Each of the
compounds 7 in dioxane exhibits two characteristic absorption
bands in the regions 391–366 and 306–296 nm. Such an
absorption pattern is similar to that of the typical hydrazone
chromophore.20 Furthermore, the spectra of 7c, taken as a
Results and discussion
The required starting compounds, benzocycloheptenone
thiosemicarbazone 2 and benzocycloheptanone hydrazone 3
were prepared according to the method reported previously16,17
(Scheme 1).
Reaction of benzocycloheptenone thiosemicarbazone 2 with
α-keto-hydrazonoyl chlorides 4a–d in dioxane in the presence
of triethylamine as a basic catalyst can lead to one or more of
three tautomeric structures 5A–C (Scheme 2). To elucidate the
actual tautomeric form(s) of these compounds, their electronic
absorption spectra were first studied. The spectra of the
compounds in dioxane showed in each case two absorption
bands in the regions 450–442 and 302–288 nm (Table 1). This
absorption pattern is analogous to that reported for the azo
Scheme 1 Synthesis of compounds 2 and 3.
Scheme 2 Reaction of compounds 2 with hydrazonoyl
chlorides 4 and 6.
* Correspondent. E-mail: thoraya-f@hotmail.com

JOURNAL OF CHEMICAL RESEARCH 2012 661
Fig. 1 Tautomeric structure of compounds 5 and 7.
Scheme 3
typical example of the series studied, in solvents of different
polarities showed little, if any, shift (Table 1). This finding
while it suggests that compounds 7 exist in one tautomeric
form, it excludes the azo tautomeric forms 7D and 7E and the
enol-hydrazone form 7C (Fig. 1). 13C NMR spectrum of 7f,
taken as a typical example of the series prepared, revealed the
signal of the carbonyl carbon of the pyrimidinone ring residue
at δ 179.52 ppm. Such a chemical shift value indicated the
presence of a carbonyl group adjacent to the N=C group.21 On
the basis of all the above data, the isolated products were
assigned the tautomeric form 7B.
Recently, it was reported that reaction of hydrazone deriva-
tive 8 with hydrazonoyl chlorides 4 at room temperature in
the presence of potassium carbonate gave the product 10 via
intermediate 9 (Scheme 3).22
Following the above report, we investigated the site-selectivity
of the reaction of hydrazonoyl halides 4 with hydrazone 3.
Thus, hydrazone 3 reacted with hydrazonoyl chlorides 4a–g
in ethanol in the presence of potassium carbonate at room
temperature or in ethanol in the presence of triethylamine as a
basic catalyst under reflux to give in all cases only one isolable
product (as indicated by TLC) and identified as a member of
the series 12 (Scheme 4). All attempts to cyclise these products
to give compound 13 failed. The structure of compounds 12
was established on the basis of spectral data (mass, IR and 1H
NMR) and elemental analysis. For example, IR spectra of
the products 12 showed absorption bands at ν 3380–3265,
3224–3150 and 1685–1666 cm−1 attributed to the two NH and
1
carbonyl group, respectively. H NMR spectra of compounds
12 revealed three singlet signals at δ 2.36–2.46, 8.88–9.12 and
11.70–12.28 ppm for the acetyl and two NH groups, respec-
tively. The above spectral data indicated that the reaction of
hydrazonoyl halides with hydrazone 3 proceeds via elimina-
tion of HX from NH2 group to give compounds 12 rather than
the different reaction course reported in the steroid series 922 to
give compounds 14 and/or 15.
Biological screening
In vitro anti-microbial screening of the series of compounds
(5, 7 and 12) prepared in this study was carried out using
four fungal strains, including Aspergillus fumigatus (RCMB
002003) (AF), Geotrichum candidum (RB 052006) (GC),
Candida albicans (RCMB 005002) (CA) and Syncephalastrum
racemosum (RCMB 005003) (SR), and four bacteria species,
including Gram positive Bacteria, Staphylococcus aureus
(RCMB 000106) (SA) and Bacillus subtilis (RCMB 000107)
(BS),GramnegativeBacteria,Pseudomonasaeruginosa(RCMB
000102 (PA)) and Escherichia coli (RCMB 000103) (EC).
Data in Table 2 revealed that most of the compounds have
superior antibacterial potency relative to antifungal and anti-
bacterial potency. Of the thiazole derivatives 5a,b and 7a–d,
compounds 5a and 7d are highly active against all microorgan-
isms used. However, compound 5b has excellent activity
against all microorganisms except Syncephalastrum racemo-
sum (SR) and Pseudomonas aeruginosa (PA). These results
indicated that the presence of the electron donating group
of the phenyl group at position 5 of the thiazole ring increases
Table 1 UV spectra of compounds 5 and 7 in dioxane
Compd
λmax (log ε)
5a
5b
5ca
5d
7cb
7d
7e
7f
442 (4.83), 292 (4.94)
444 (4.80), 296 (4.77)
444 (4.61), 288 (4.69)
450 (4.36), 302 (4.92)
366 (4.25), 298 (4.82)
373 (4.35), 296 (4.68)
369 (4.50), 306 (4.84)
391 (4.60), 298 (5.01)
a Solvent: λmax (log ε): acetic acid 438 (5.08), 306 (4.80); DMF 454
(4.31), 300 (4.90); ethanol 434 (4.84), 298 (5.08).
b Solvent: λmax (log ε): acetic acid 376 (4.21), 288 (4.35); DMF 365
(4.05), 289 (4.31); ethanol 366 (4.28), 298 (4.56).

662 JOURNAL OF CHEMICAL RESEARCH 2012
the activity. On the other hand, for the formazan derivatives,
the most reactive compounds were 12a and 12b against all
microorganisms except SR and PA. While, compound 12c
shows significant activity against gram positive bacteria and
gram negative bacteria.
Conclusion
In conclusion, we report the synthesis of new derivatives of
thiazole and formazan incorporated with the benzocyclohep-
tene unit via reaction of thiosemicarbazone and hydrazone
derivatives. The structures of the newly synthesised com-
pounds were established on the basis of spectral data (mass,
IR, 1H NMR, 13C NMR and UV) and elemental analyses. Also,
some of the newly synthesised compounds were evaluated
for antimicrobial activity and the results showed that some
compounds showed excellent activity against the tested
microorganisms.
Experimental
All melting points were determined on an electrothermal Gallenkamp
apparatus. Solvents were distilled and dried by standard literature pro-
cedures prior to use. The IR spectra were measured on a Pye-Unicam
1
sp 300 instrument in potassium bromide disks. The H NMR and
13C NMR spectra were recorded on a Varian spectrometer (300 MHz
1
for H NMR and 100 MHz for 13C NMR) and the chemical shifts
were related to those of the solvent DMSO-d6. The mass spectra were
recorded on GCMS-Q1000-EX Shimadzu and GCMS 5988-A HP
spectrometers, the ionising voltage was 70 eV. Elemental analyses
were carried out by the Microanalytical Center of Cairo University,
Giza, Egypt. Hydrazonoyl halides 4 and 6 were prepared as previously
described.23,24
Scheme 4 Reaction of hydrazone derivative 3 with
hydrazonoyl halides.
Table 2 Anti-microbial activities of compounds 5, 7 and 12
Microorganism
Fungi
5a
5b
7c
7d
7e
12a
ST (30 µg mL-1)
Itraconazole
Clotrimazole
AF
22.1
19.6
19.5
NA
21.5
18.5
16.5
10.6
15.2
17.4
13.2
NA
21.3
18.2
14.5
9.4
14.2
11.5
12.0
NA
23.8
21.2
20.1
NA
28.5
27.1
26.1
23.1
GC
CA
SR
26.1
18.3
22.3
20.5
Gram positive bacteria
SA
BS
Gram negative bacteria
PA
EC
Penicillin G
29.4
Streptomycin
25.1
23.1
26.4
22.0
23.6
16.2
19.8
22.9
22.1
10.5
13.2
20.8
25.0
32.5
29.1
Penicillin G
28.3
Streptomycin
24.3
NA
22.6
13.4
20.5
NA
10.1
21.0
15.7
NA
8.6
NA
23.0
33.5
25.6
The experiment was carried out in triplicate and average zone of inhibition was calculated; NA, no activity.
Table 3 Anti-microbial activities of compounds 5, 7 and 12
Microorganism
Fungi
12b
12c
12d
12e
12f
12g
ST (30 µg mL-1)
Itraconazole
Clotrimazole
AF
23.4
23.1
16.2
NA
NA
NA
NA
NA
18.5
17.4
15.2
NA
NA
NA
NA
NA
14.6
19.0
11.2
NA
10.4
9.8
10.1
NA
28.5
27.1
26.1
23.1
GC
CA
SR
26.1
18.3
22.3
20.5
Gram positive bacteria
SA
BS
Gram negative bacteria
PA
EC
Penicillin G
29.4
Streptomycin
25.1
22.8
28.3
22.6
23.4
16.2
14.3
NA
NA
10.6
12.1
9.5
12.1
32.5
29.1
Penicillin G
28.3
Streptomycin
24.3
NA
23.1
21.9
19.9
NA
NA
NA
NA
NA
8.0
NA
NA
33.5
25.6
The experiment was carried out in triplicate and average zone of inhibition was calculated; NA, no activity.

JOURNAL OF CHEMICAL RESEARCH 2012 663
Reaction of hydrazonoyl chlorides 4 or 6 with thiosemicarbazone
derivative 2; general procedure
5-[(4-Bromo-phenyl)-hydrazono]-2-[N′-(6,7,8,9-tetrahydro-benzo-
cyclohepten-5-ylidene)-hydrazino]-thiazol-4-one (7Be): Yellow solid,
(87% yield), m.p. 130–132 °C (EtOH); IR (KBr) νmax 3200, 3151
(2NH), 1708 (C=O) cm−1; 1H NMR (DMSO-d6) δ 1.25–1.66 (m, 4H,
2CH2), 2.65–3.05 (m, 4H, 2CH2), 7.12–7.27 (m, 8H, ArH), 10.09 (s,
1H, NH), 10.44 (s, 1H, NH); MS m/z (%) 457 (M++2, 53), 456 (M++1,
45), 455 (M+, 30), 454 (43), 284 (30), 200 (33), 199 (40), 170 (72),
156 (42), 129 (100), 104 (32), 91 (57), 77 (60). Anal. Calcd for
C20H18BrN5OS (455.04): C, 52.64; H, 3.98; N, 15.35. Found: C, 52.45;
H, 4.08; N, 15.18%.
5-[(4-Nitro-phenyl)-hydrazono]-2-[N′-(6,7,8,9-tetrahydro-benzo-
cyclohepten-5-ylidene)-hydrazino]-thiazol-4-one (7Bf): Orange solid,
(80% yield), m.p. 122 °C (EtOH/dioxane); IR (KBr) νmax 3151, 3066
(2NH), 1712 (C=O) cm−1; 1H NMR (DMSO-d6) δ 1.07–1.83 (m, 4H,
2CH2), 2.64–3.06 (m, 4H, 2CH2), 7.13–8.29 (m, 8H, ArH), 10.10 (s,
1H, NH), 11.0 (s, 1H, NH); 13C NMR (DMSO-d6) δ 21.48, 25.77,
28.13, 31.40 (4CH2), 113.95, 125.82, 126.54, 126.85, 127.82, 128.54,
129.10, 129.62, 131.05, 138.27, 139.36 (10ArC + =C), 155.94 (C=N),
171.0 (S–C=N), 179.52 (C=O). MS m/z (%) 423 (M++1, 37), 422 (M+,
90), 259 (34), 156 (46), 143 (77), 130 (100), 116 (96), 91 (57), 89
(50), 77 (61), 76 (56). Anal. Calcd for C20H18N6O3S (422.46): C,
56.86; H, 4.29; N, 19.89. Found: C, 56.64; H, 4.08; N, 19.71%.
Triethylamine (0.35 mL) was added to a stirred solution of thiosemi-
carbazone derivative 2 (0.47 g, 2 mmol) and the appropriate hydra-
zonoyl chloride 4 or 6 (2 mmol) in dioxane (30 mL), and the mixture
was refluxed for 5 h. The precipitated triethylamine hydrochloride
was filtered off, and the filtrate was evaporated under reduced
pressure. The residue was triturated with methanol. The solid product,
so formed in each case, was collected by filtration, washed with water,
dried, and crystallised from the appropriate solvent to afford the
corresponding thiazole derivatives 5 or 7, respectively.
4-Methyl-5-(4-methylphenylazo)-2-[N′-(6,7,8,9-tetrahydro-benzo-
cyclohepten-5-ylidene)-hydrazino]-thiazole (5Ca): Pink solid, (82%
1
yield), m.p. 80–82 °C (EtOH); IR (KBr) νmax 3359 (NH) cm−1; H
NMR (DMSO-d6) δ 1.17–1.76 (m, 4H, 2CH2), 2.26 (s, 3H, CH3), 2.57
(s, 3H, CH3), 2.79–2.91 (m, 4H, 2CH2), 7.12 (d, J = 8Hz, 2H, ArH),
7.23–7.38 (m, 4H, ArH), 7.59 (d, J = 8Hz, 2H, ArH), 10.42 (s, 1H,
NH); MS m/z (%) 390 (M++1, 15), 389 (M+, 35), 232 (31), 158 (42),
130 (54), 129 (50), 117 (50), 104 (39), 91 (100), 77 (46). Anal. Calcd
for C22H23N5S (389.52): C, 67.84; H, 5.95; N, 17.98. Found: C, 67.65;
H, 5.84; N, 17.72%.
4-Methyl-5-(3-methylphenylazo)-2-[N′-(6,7,8,9-tetrahydro-benzo-
cyclohepten-5-ylidene)-hydrazino]-thiazole (5Cb): Dark orange crys-
tals, (80% yield), m.p. 70–73 °C (EtOH); IR (KBr) νmax 3190 (NH)
Reaction of hydrazonoyl chlorides 4 with hydrazone derivative 3
Method A: Triethylamine (0.35 mL) was added to a stirred solution
of hydrazone derivative 3 (0.35g, 2 mmol) and the appropriate
hydrazonoyl chloride 4 (2 mmol) in absolute ethanol (30 mL), and the
mixture was refluxed for 5 h. The precipitated triethylamine hydro-
chloride was filtered off, and the filtrate was evaporated under reduced
pressure. The residue was triturated with methanol. The solid product,
so formed in each case, was collected by filtration, washed with water,
dried, and crystallised from ethanol to afford the corresponding
formazan derivatives 12.
1
cm−1; H NMR (DMSO-d6) δ 1.62–1.78 (m, 4H, 2CH2), 2.29 (s, 3H,
CH3), 2.46 (s, 3H, CH3), 2.65–2.90 (m, 4H, 2CH2), 6.81–7.63 (m, 8H,
ArH), 10.43 (s, 1H, NH); MS m/z (%) 390 (M++1, 24), 389 (M+, 44),
231 (24), 158 (48), 130 (60), 116 (48), 91 (100), 77 (48). Anal. Calcd
for C22H23N5S (389.52): C, 67.84; H, 5.95; N, 17.98. Found: C, 67.75;
H, 6.0; N, 17.80%.
4-Methyl-5-(phenylazo)-2-[N′-(6,7,8,9-tetrahydro-benzocyclohep-
ten-5-ylidene)-hydrazino]-thiazole (5Cc): Dark red solid, (80% yield),
1
m.p. 100–102 °C (EtOH); IR (KBr) νmax 3359 (NH) cm−1; H NMR
Method B: A mixture of hydrazone derivative 3 (0.87 g, 0.005 mol)
and hydrazonoyl halide (0.005 mol) in absolute ethanol (30 ml)
containing K2CO3 (0.69 g, 0.005 mol) was stirred for 24 h, at room
temperature. The reaction mixture was poured onto ice/water and
the resulting solid was collected by filtration and crystallised from
ethanol to afford the corresponding formazan derivatives 12 which are
identical in all respects with those produced by method A.
3-Acetyl-5-phenyl-1-[N′-(6,7,8,9-tetrahydro-benzocyclohepten-5-
ylidene)]-1,2-dihydroformazan (12a): Red solid, (86% yield), m.p.
160 °C; IR (KBr) νmax 3380, 3224 (2NH), 1670 (C=O) cm−1; 1H NMR
(DMSO-d6) δ 1.59–1.77 (m, 4H, 2CH2), 2.36 (s, 3H, CH3), 2.51–2.74
(m, 4H, 2CH2), 6.81–7.52 (m, 9H, ArH), 8.93 (s, 1H, NH), 11.78 (s,
1H, NH); MS m/z (%) 335 (M++1, 7), 334 (M+, 11), 206 (43), 158
(23), 143 (31), 128 (32), 115 (34), 104 (31), 93 (48), 77 (100). Anal.
Calcd for C20H22N4O (334.42): C, 71.83; H, 6.63; N, 16.75. Found: C,
71.65; H, 6.50; N, 16.58%.
(DMSO-d6) δ 1.15–1.75 (m, 4H, 2CH2), 2.49 (s, 3H, CH3), 2.79–3.09
(m, 4H, 2CH2), 6.98–7.62 (m, 9H, ArH), 10.10 (s, 1H, NH); 13C NMR
(DMSO-d6) δ 16.94 (CH3), 22.68, 26.04, 29.95, 32.33 (4CH2), 113.33,
114.95, 124.25, 126.72, 128.39, 129.38, 129.77, 130.18, 130.36,
138.32, 138.55 (10 ArC + =C), 140.51 (N–C=C), 144.26 (C=N),
171.45 (S–C=N). MS m/z (%) 376 (M++1, 15), 375 (M+, 42), 374 (30),
342 (21), 158 (28), 139 (56), 130 (51), 117 (34), 115 (30), 91 (37), 77
(100). Anal. Calcd for C21H21N5S (375.49): C, 67.17; H, 5.64; N,
18.65. Found: C, 67.08; H, 5.49; N, 18.52%.
5-(4-Chlorophenylazo)-4-methyl-2-[N′-(6,7,8,9-tetrahydro-benzo-
cyclohepten-5-ylidene)-hydrazino]-thiazole (5Cd): Dark red solid,
(82% yield), m.p. 110–112 °C (EtOH/dioxane); IR (KBr) νmax 3254
(NH) cm−1; 1H NMR (DMSO-d6) δ 1.64–1.76 (m, 4H, 2CH2), 2.59 (s,
3H, CH3), 2.79–2.91 (m, 4H, 2CH2), 7.24–7.62 (m, 8H, ArH), 10.57
(s, 1H, NH); 13C NMR (DMSO-d6) δ 15.98 (CH3), 22.45, 25.25, 29.16,
31.27 (4CH2), 113.57, 115.49, 124.15, 126.20, 128.23, 130.01, 130.28,
131.28, 133.31, 138.01, 138.45 (10 ArC + =C),140.11 (N–C=C),
142.35 (C=N), 170.28 (S–C=N). MS m/z (%) 411 (M++2, 26), 410
(M++1, 25), 409 (M+, 66), 408 (58), 375 (32), 158 (66), 143 (39), 130
(84), 116 (100), 111 (65), 89 (35), 77 (31).Anal. Calcd for C21H20ClN5S
(409.94): C, 61.53; H, 4.92; N, 17.08. Found: C, 61.41; H, 4.83; N,
17.00%.
5-(Phenylhydrazono)-2-[N′-(6,7,8,9-tetrahydro-benzocyclohepten-
5-ylidene)-hydrazino]-thiazol-4-one (7Bc): Yellow solid, (88% yield),
m.p. 185–186 °C (EtOH); IR (KBr) νmax 3200, 3151 (2NH), 1708
(C=O) cm−1; 1H NMR (DMSO-d6) δ 1.14–1.66 (m, 4H, 2CH2), 2.63–
2.84 (m, 4H, 2CH2), 7.12–7.53 (m, 9H, ArH), 10.09 (s, 1H, NH),
10.38 (s, 1H, NH); MS m/z (%) 377 (M+, 28), 376 (14), 159 (39), 130
(72), 120 (31), 91 (89), 90 (39), 77 (100). Anal. Calcd for C20H19N5OS
(377.46): C, 63.64; H, 5.07; N, 18.55. Found: C, 63.55; H, 5.00; N,
18.41%.
5-[(4-Chlorophenyl)-hydrazono]-2-[N′-(6,7,8,9-tetrahydro-benzo-
cyclohepten-5-ylidene)-hydrazino]-thiazol-4-one (7Bd): Red solid,
(91% yield), m.p. 125–126 °C (EtOH); IR (KBr) νmax 3228, 3166
(2NH), 1663 (C=O) cm−1; 1H NMR (DMSO-d6) δ 1.17–1.72 (m, 4H,
2CH2), 2.65–2.69 (m, 4H, 2CH2), 7.15–7.58 (m, 8H, ArH), 10.08 (s,
1H, NH), 10.40 (s, 1H, NH); 13C NMR (DMSO-d6) δ 20.54, 25.17,
28.29, 30.98 (4CH2), 113.48, 124.99, 126.16, 126.28, 127.59, 128.09,
129.68, 130.54, 131.25, 137.12, 139.49 (10ArC + =C), 154.28 (C=N),
172.11 (S–C=N), 178.97 (C=O). MS m/z (%) 413 (M++2, 38), 412
(M++1, 37), 411 (M+, 100), 285 (52), 200 (26), 158 (32), 143 (62), 126
(63), 128 (34), 125 (51), 116 (53), 111 (43), 91 (30), 75 (37). Anal.
Calcd for C20H18ClN5OS (411.91): C, 58.32; H, 4.40; N, 17.00. Found:
C, 58.21; H, 4.20; N, 16.92%.
3-Acetyl-5-(4-methylphenyl)-1-[N′-(6,7,8,9-tetrahydro-benzocy-
clohepten-5-ylidene)]-1,2-dihydroformazan (12b): Red crystals, (95%
yield), m.p. 132 °C; IR (KBr) νmax 3332, 3224 (2NH), 1666 (C=O)
1
cm−1; H NMR (DMSO-d6) δ 1.60–1.75 (m, 4H, 2CH2), 2.22 (s, 3H,
CH3), 2.46 (s, 3H, CH3), 2.56–2.70 (m, 4H, 2CH2), 6.91 (d, J = 9Hz,
2H, ArH), 7.06 (d, J = 9Hz, 2H, ArH), 7.22–7.46 (m, 4H, ArH), 8.88
(s, 1H, NH), 11.70 (s, 1H, NH); MS m/z (%) 349 (M++1, 9), 348 (M+,
33), 190 (25), 160 (40), 159 (23), 158 (23), 121 (30), 119 (23), 106
(23), 91 (100), 77 (42). Anal. Calcd for C21H24N4O (348.44): C, 72.39;
H,6.94; N, 16.08. Found: C, 72.17; H, 6.87; N, 16.12%.
3-Acetyl-5-(3-chlorophenyl)-1-[N′-(6,7,8,9-tetrahydro-benzocyclo-
hepten-5-ylidene)]-1,2-dihydroformazan (12c): Orange solid, (84%
yield), m.p. 86–88 °C; IR (KBr) νmax 3320, 3150 (2NH), 1685 (C=O)
1
cm−1; H NMR (DMSO-d6) δ 1.50–1.74 (m, 4H, 2CH2), 2.36 (s, 3H,
CH3), 2.57–2.70 (m, 4H, 2CH2), 6.85–7.38 (m, 8H, ArH), 8.95 (s, 1H,
NH), 11.83 (s, 1H, NH); MS m/z (%) 370 (M++2, 20), 369 (M++1, 21),
368 (M+, 63), 367 (55), 269 (26), 240 (27), 209 (40), 160 (100), 140
(72), 130 (71), 111 (54), 91 (43), 77 (32).Anal. Calcd for C20H21ClN4O
(368.86): C, 65.12; H, 5.74; N, 15.19. Found: C, 65.03; H, 5.64; N,
15.06%.
3-Acetyl-5-(4-chlorophenyl)-1-[N′-(6,7,8,9-tetrahydro-benzocyclo-
hepten-5-ylidene)]-1,2-dihydroformazan (12d): Red crystals, (90%
yield), m.p. 140–142 °C; IR (KBr) νmax 3265, 3210 (2NH), 1685
(C=O) cm−1; 1H NMR (DMSO-d6) δ 1.59–1.76 (m, 4H, 2CH2), 2.36 (s,
3H, CH3), 2.57–2.72 (m, 4H, 2CH2), 7.06 (d, J = 9Hz, 2H, ArH), 7.20
(d, J = 9Hz, 2H, ArH), 7.23–7.49 (m, 4H, ArH), 8.93 (s, 1H, NH),
11.77 (s, 1H, NH); MS m/z (%) 370 (M++2, 5), 369 (M++1, 11), 368
(M+, 22), 210 (24), 160 (42), 140 (29), 130 (24), 105 (100), 77 (15).

664 JOURNAL OF CHEMICAL RESEARCH 2012
Anal. Calcd for C20H21ClN4O (368.86): C, 65.12; H, 5.74; N, 15.19.
Found: C, 65.08; H, 5.58; N, 15.27%.
References
1
T.A. Farghaly, N.A. Abdel Hafez, E.A. Ragab, H.M. Awad and
3-Acetyl-5-(3-nitrophenyl)-1-[N′-(6,7,8,9-tetrahydro-benzocyclo-
hepten-5-ylidene)]-1,2-dihydroformazan (12e): Brown solid, (85%
yield), m.p. 130–131 °C; IR (KBr) νmax 3354, 3221 (2NH), 1684
(C=O) cm−1; 1H NMR (DMSO-d6) δ 1.60–1.75 (m, 4H, 2CH2), 2.39 (s,
3H, CH3), 2.59–2.71 (m, 4H, 2CH2), 7.22–7.77 (m, 8H, ArH), 8.99 (s,
1H, NH), 12.01 (s, 1H, NH); MS m/z (%) 379 (M+, 38), 378 (69), 349
(50), 333 (63), 279 (75), 250 (75), 223 (69), 191 (88), 151 (81), 101
(100), 77 (63). Anal. Calcd for C20H21N5O3 (379.41): C, 63.31; H,
5.58; N, 18.46. Found: C, 63.08; H, 5.42; N, 18.28%.
3-Acetyl-5-(4-nitrophenyl)-1-[N′-(6,7,8,9-tetrahydro-benzocyclo-
hepten-5-ylidene)]-1,2-dihydroformazan (12f): Red crystals, (95%
yield), m.p. 190–192 °C; IR (KBr) νmax 3290, 3159 (2NH), 1678
(C=O) cm−1; 1H NMR (DMSO-d6) δ 1.58–1.88 (m, 4H, 2CH2), 2.36 (s,
3H, CH3), 2.51–2.71 (m, 4H, 2CH2), 7.07 (d, J = 9Hz, 2H, ArH), 7.21–
7.53 (m, 4H, ArH), 8.13 (d, J = 9Hz, 2H, ArH), 9.12 (s, 1H, NH),
12.28 (s, 1H, NH); MS m/z (%) 379 (M+, 89), 378 (66), 221 (32), 160
(92), 144 (33), 130 (100), 115 (39), 91 (45), 77 (33). Anal. Calcd for
C20H21N5O3 (379.41): C, 63.31; H, 5.58; N, 18.46. Found: C, 63.08; H,
5.42; N, 18.28%.
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3-Thienyl-5-phenyl-1-[N′-(6,7,8,9-tetrahydro-benzocyclohepten-
5-ylidene)]-1,2-dihydroformazan (12g): Red crystals, (90% yield),
m.p. 170–172 °C; IR (KBr) νmax 3321, 3205 (2NH), 1601 (C=O) cm−1;
1H NMR (DMSO-d6) δ 1.59–1.77 (m, 4H, 2CH2), 2.51–2.74 (m, 4H,
2CH2), 6.87–8.13 (m, 12H, ArH), 9.21 (s, 1H, NH), 12.02 (s, 1H,
NH); MS m/z (%) 403 (M++1, 2), 402 (M+, 6), 245 (19), 159 (19), 111
(81), 110 (100), 104 (16), 91 (13), 77 (39).Anal. Calcd for C23H22N4OS
(402.51): C, 68.63; H, 5.51; N, 13.92. Found: C, 68.48; H, 5.35; N,
13.88%.
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17 Khanna, M. Jatinder, I.M. Chak and N.Anand, Indian J. Chem., 1967, 5,
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Agar diffusion well method to determine the antimicrobial activity
The microorganism inoculums were uniformly spread using a sterile
cotton swab on a sterile Petri dish containing malt extract agar (for
fungi) and nutrient agar (for bacteria). Each sample (100 µL) was
added to each well (6 mm diameter holes cut in the agar gel, 20 mm
apart from one another). The systems were incubated for 24–48 h at
37 °C (for bacteria) and at 28 °C (for fungi). After incubation, micro-
organism growth was observed. Inhibition of the bacterial and fungal
growth were measured in mm. Tests were performed in triplicate.25
18 R. Jones, A.J. Ryan, S. Sternhell and S.E. Wright, Tetrahedron, 1963, 19,
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19 H.M. Hassaneen, O.A. Miqdad, N.M. Abunada and A.A. Fares, Nat. Sci.,
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20 E.M.H. Abbas and T.A. Farghaly, Monatsh Chem., 2010, 141, 661.
21 W.W. Wardkhan, M.A. Youssef, F.I. Hamed and S.A. Ouf, J. Chinese
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22 M.M. Abdelhalim, E.M. Kamel, S.T. Rabie and N.R. Mohamed, Steroids,
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Received 30 July 2012; accepted 18 September 2012
Paper 1201441 doi: 10.3184/174751912X13491094428620
Published online: 12 November 2012

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