One pot preparations N,N′-alkylidene bisamide derivatives catalyzed by Nano-TiCL4.SiO2 with antimicrobial studies of some products

Article abstract of DOI:10.4067/S0717-97072016000300005

Nano-TiCl₄.SiO₂ has been introduced to be an extremely efficient catalyst for the preparation of N,N′-alkylidene bisamides from various aldehydes and amides under mild conditions. We synthesized this solid Lewis acid catalyst by the

Full text of DOI:10.4067/S0717-97072016000300005

J. Chil. Chem. Soc., 61, Nº 3 (2016)
ONE POT PREPARATIONS N,N΄-ALKYLIDENE BISAMIDE DERIVATIVES CATALYZED BY NANO-TiCL4.SiO2
WITH ANTIMICROBIAL STUDIES OF SOME PRODUCTS
SOGHRA KHABNADIDEH,1 KAMIAR ZOMORODIAN,2 BI BI FATEMEH MIRJALILI,3 ELHAM IZADI1,
LEILA ZAMANI1*
1Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
2Center of Basic Researches in Infectious Diseases and Department of Medical Mycology and
Parasitology School of Medicine, Shiraz University of Medical Sciences, Post code 71348-45794, Shiraz, Iran
3Department of Chemistry, College of Science, Yazd University, Yazd, PO Box 8915813149, I. R. Iran
ABSTRACT
Nano-TiCl4.SiO2 has been introduced to be an extremely efficient catalyst for the preparation of N,N’-alkylidene bisamides from various aldehydes and amides
under mild conditions. We synthesized this solid Lewis acid catalyst by the reaction of nano-SiO and TiCl4. The processor was simple and environmentally benign
with high to excellent yields. Our method has the advantages of high yields, simple methodolo2gy, and easy work-up. The antimicrobial and antifungal activities
of some of the synthetic compounds were determined by broth microdilution methods as recommended by Clinical Laboratory Standard Institute. Further studies
still needed to investigate the other biological activities of the compounds.
Keywords: Nano-TiCl4.SiO2, Heterogeneous catalyst, N,N’-Alkylidene bisamides, Antifungal, Antibacterial.
antibacterial activities of the above compounds against standard species of
Staphylococcus aureus (ATCC 25923), Enterococcus faecalis (ATCC 11700),
Escherichia coli (ATCC 25922) and Pseudomonas aeruginosa (ATCC 27853)
were also determined in this study. The susceptibility of all clinical isolates of
fungi against select compounds was examined by microdilution and disk dif-
fusion methods.17,18
INTRODUCTION
Amide and bisamide compounds are main part of many peptidomimetic1
and they play a major role in the expansion and composition of biological and
pharmacological systems. They are of considerable interest in the synthesis
of pharmacological materials such as peptidomimetic compounds2,3 and gem-
diaminoalkyl residues in retro-inverso pseudopeptide derivatives4 by treating
the corresponding amide with iodobenzene bistrifluoroacetate.5 Generally sym-
metrical alkylidene bisamides are synthesized by the direct reaction of alde-
hydes with the corresponding amides under suitable catalytic condition. In this
topic, let us examine the various conditions of the catalysts such as sulfuric
acid6, sulfonic acid7, triflic acid8, p-toluene sulfonic acid9, SiO2-MgCl210, hydro-
chloric acid11, CC- or DCMT activatd DMSO12, phosphotungstic acid13, boric
acid 14, silica coated magnetic NiFe2O4 nanoparticle supported polyphosphoric
acid15 and p-toluenesulfonic acid.16 Our studies towards the development of
more efficient methods accompanied with higher yields for the synthesis of
N,N’-Alkylidene bisamides in the presence of nano-TiCl4.SiO2. In addition,
the antimicrobial and antifungal activities of some of the synthetic compounds
were evaluated by broth microdilution methods.
Determination of minimum inhibitory concentration
MICs were determined using the broth microdilution method recommend-
ed by the CLSI with some modifications.17,18 Briefly, for determination of an-
timicrobial activities against fungi, serial dilutions of the synthetic compounds
(1–1024 µg/mL) were prepared in 96-well microtiter plates using RPMI-1640
media (Sigma, St. Louis, MO, USA) buffered with MOPS (Sigma). Stock in-
oculums were prepared by suspending three colonies of the examined yeast in
5 mL sterile 0.85% NaCl, and adjusting the turbidity of the inoculums to 0.5
McFarland standards at 530 nm wavelengths (this yields stock suspension of
1-5 × 106 cells/mL). For moulds (Aspergillus spp. and dermatophytes), conidia
were recovered from the 7-day old cultures grown on potato dextrose agar by
a wetting loop with tween-20. The collected conidia were transferred in sterile
saline and their turbidity was adjusted to OD=0.09-0.11 that yields 0.4-5 × 106
conidia/mL. Working suspension was prepared by making a 1/50 and 1/1000
dilution with RPMI of the stock suspension for moulds and yeasts, respec-
tively. Working inoculums (0.1 mL) were added to the microtiter plates, which
were incubated in a humid atmosphere at 30ºC for 24–48 h. Uninoculated me-
dium (200 μL) was included as a sterility control (blank). In addition, growth
controls (medium with inoculums but without antibiotics or the synthetic com-
pounds) were also included. The growth in each well was compared with that
of the growth in the control well.
EXPERIMENTAL
The chemicals were purchased from Merck Company and used without
any additional purification. The products were characterized by FT-IR (ATR),
1H-NMR, and a comparison of their physical properties with those reported in
the literature. FT-IR (ATR) spectra were run on a Bruker, Eqinox 55 spectrom-
eter. A Bruker (DRX-400 Avance) NMR was used to record the 1H NMR spec-
tra. Spectrophotometer (Company BAUSCH & LOMB, US), Vortex mixer
(Company Lab net), Tween 20 (Company Roche, Germany).
RESULTS AND DISCUSSION
General experimental procedure for the synthesis of N,N′-alkylidene
bisamide
TiCl4.SiO 19-26 is an efficient and reusable acidic catalyst. This catalyst is
synthesized vi2a reaction of nano-silica gel with TiCl4 in chloroform at room
temperature. In continue of our investigations on solid acid application in
organic synthesis, we tried to develop new synthetic method to prepare N,N‘-
alkylidene bisamides and find the best reaction conditions. The reaction of
benzamide and benzaldehyde was examined under various conditions and
different quantities of TiCl4.SiO2 and nano-TiCl4.SiO (Table 1). According to
our results, the best condition is the reaction in solven2t free condition using 0.1
g of TiCl4.SiO2 or 0.04 g of nano-TiCl .SiO2. The results showed an improved
reaction rate and yield (Table 1, Entrie4s 2, 11).
A mixture of aldehyde (1 mmol), amide (2 mmol), n-hexane (5 ml) and
nano-TiCl4.SiO2 (0.04 g) was refluxed for appropriate time. The progress of the
reaction was monitored by TLC. After completion of the reaction, the mixture
was cooled to room temperature and filtered. The catalyst was separated from
the reaction mixture by boiling ethanol. The crude solid product was purified
by recrystallization procedure in ethanol:water, 80:20.
Biological study
Microorganisms
The antifungal activities of the synthetic compounds against some Ameri-
can Type Culture Collection (ATCC) strains of fungi, including Candida albi-
cans (ATCC 10261), Candida tropicalis (ATCC 750), Candida krusei (ATCC
6258), Candida glabarata (ATCC 90030), Candida dubliniensis (CBS 8501),
Aspergillus flavus (ATCC 64025), and Aspergillus fumigatus (ATCC 14110)
as well as two clinical isolates of yeasts identified by PCR-RFLP were de-
termined. The susceptibility of all clinical isolates of fungi against selected
antibiotics was examined by microdilution and disk diffusion methods The
Once the scope of the reaction condition was established, the reusability
of catalyst was examined. After performing the reaction, the catalyst was
separated, washed with acetone, dried and re-used up to 3 times in reaction
without losing its activity (Figure 1).
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e-mails: l.zamani2008@gmail.com

J. Chil. Chem. Soc., 61, Nº 3 (2016)
attaching to aromatic ring (Table 2).
In all cases, aromatic aldehydes containing electron-withdrawing groups
gave higher yield of products in shorter time than aromatic aldehydes
containing electron-withdrawing groups (Table 2, entries 3 and 9). In methyl
carbamate, the nucleophilicity of nitrogen is higher than acetamide. Thus,
methyl carbamates produce a good yield of product in shorter time than
acetamides (Table 2, entries 4).
Table 2. Preparation of N,N′-alkylidene bisamide derivatives in the
presence of nano-TiCl4.SiO2a
M.P. °C Yield(%)b
Entry
R1
R2
Products
(Lit)Ref
/Time (h)
H
H
Ph
N
N
Ph
210-211
(214-
O
O
B1
Ph
Ph
87/1.5
216)13
H
H
CH=CH2
H2C=CH
N
N
222-223
(224-
O
O
CH2=
CH
B2
B3
3-NO2-Ph
4-NO2-Ph
90/5
96/2
226)13
NO2
Fig. 1. Reusability of nano-TiCl4.SiO2 catalyst.
H
H
Ph
N
N
Ph
239-240
(242-
O
O
Table 1. Synthesis of N, N’-(4-nitrophenylmethylene) dibenzamide under
various conditions
Ph
244)13
NO2
Yield(%)a /
Time (h)
H
H
N
Entry
Catalyst (g)
Solvent/T °C
Reference
MeO
N
OMe
O
O
B4
4-NO2-Ph
OCH3
196-198
91/0.9
Solvent-
free/100
1
2
TiCl4.SiO2 (0.1)
TiCl4.SiO2 (0.1)
3/85
2/89
-
-
NO2
H
H
MeO
N
N
OMe
n-Hexane/
reflux
O
O
2,4-
Dichloro-ph
Cl
B5
B6
OCH3
Ph
248-250
236-237
87/1
4
5
TiCl4.SiO2 (0.1)
TiCl4.SiO2 (0.1)
EtOAc/reflux
CHCl3/reflux
3.5/75
4/78
-
-
Cl
H
H
Ph
N
N
Ph
O
O
Toluene/
reflux
3-NO2-Ph
83/1.5
6
7
TiCl4.SiO2 (0.1)
TiCl4.SiO2 (0.1
5/30
2/0
-
NO2
S.F./mixer
b
-
mill
H
H
H3
C
N
N
CH3
O
Cl
O
EtOAc/
sonication
2,4-
Dichloro-ph
c
8
9
TiCl4.SiO2 (0.1)
TiCl4.SiO2 (0.1)
1/32
0.5/50
1/90
-
B7
CH3
264-265
72/5
Cl
d
S.F./M.W.
-
Nano-TiCl4.SiO2
n-Hexane/
reflux
10
-
-
H
H
(0.08)
Ph
N
N
Ph
B8
B9
n-propyl
3-NO2-Ph
PhCH2-CH2
Ph
OCH3
Ph
172-173
184-185
76/2.5
93/2.3
72/4.5
O
O
Nano-TiCl4.
SiO2(0.04)
n-Hexane/
reflux
C3H7
11
12
13
14
15
16
17
1.5/90
1.5/85
1.5/79
2.5/73
3/71
H
H
OMe
N
N
OMe
Nano-TiCl4.SiO2
n-Hexane/
reflux
O
O
-
(0.04), 2nd run
NO2
Nano-TiCl4.SiO2
n-Hexane/
reflux
-
(0.04), 3rd run
253-254
(248-
NHCOPh
B10
Solvent-
free/100
NHCOPh
249)9
SiO2-MgCl2 (0.025)
10
12
13
14
CC(1.2 equiv)-
DMSO(7.0 equiv)
Toluene/r.t.
NHCOPh
to 70
B11
B12
PhCH=CH
Ph
Ph
199-201
177-179
68/2.3
70/3.5
NHCOPh
Phosphotungstic
acid (0.3 mmol)
Toluene/
reflux
20-70
H
H
N
N
Ph
Ph
Boric acid (0.3
mmol)
O
OH
O
Microwave
40 min/80
2-OH-phenyl
a Isolated yield.
b Using mixer mill (MM 400) in 25 Hz frequency.
c Using BANDELIN Sonopulse HD 3200 ultrasonic apparatus with power
aReaction conditions: amide (2 mmol), aldehyde (1 mmol), nano-TiCl4.
SiO2 (0.04 g).
equal to 20 KHz.
bIsolated yield.
d Using microwave oven Kenwood, 1300W
This protocol is effective special for primary amides but secondary amides
or primary sulfonamides (Scheme 1and 2).
Next, the scale of this procedure was explored using a wide range of
aldehydes containing electron-donating or electron-withdrawing groups
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J. Chil. Chem. Soc., 61, Nº 3 (2016)
Scheme 1. The selectivity of protocol for primary amides versus secondary
amides
Scheme 2. The selectivity of protocol for primary amides versus
sulfonamides
Nano-TiCl4.SiO2 catalyzes the reaction of benzaldehyde with urea to
produce corresponding bisamides and imines with different yields (Scheme 3).
Scheme 6. The suggested mechanism for bisamide formation from
aldehyde and amide
Scheme 3. Reaction of benzaldehyde with urea
N,N,N′,N’-(1, 5-pentylene)tetrabenzamide was also produced via the
reaction of 1 mmol of glutardialdehyde with 4 mmol of benzamide in the
presence of Nano-TiCl4.SiO2 (Scheme 4).
None of the selected compounds exhibited antifungal activity against the
examined fungi at the tested concentrations (Table 3). Moreover, the examined
compounds failed to inhibit the growth of the Gram-positive and gram-
negative bacteria at the concentration up to and including 256µg/mL (Table
4). Further studies still needed to investigate other biological activities of these
compounds.
SPECTROSCOPIC DATA
N,N’-(phenylmethylene)dibenzamide (Table 2, B1)
Scheme 4. Synthesis of N,N,N′,N’-(1, 5-pentylene)tetrabenzamide from
glutardialdehyde and benzamide
N,N’-(methylene)dibenzamide was produced via the reaction of 1, 3,
5-trioxane with benzamide in the presence of nano-TiCl4.SiO2 (Scheme 5).
FT-IR: ῡ (ATR, neat, cm-1): 3275 (N-H stretch), 1650 (C=O stretch), 1480
(N-H bend), 715, 799 (C-H bend); 1H NMR (DMSO-d6, ppm): δ 9.01 (d, J=7.7
Hz, 2H, N-H),7.92 (d, J=7.8 Hz, 4H),7.56 (t, J=7.09 Hz, 2H),7.49 (t, J=7.5
Hz, 6H),7.39 (t, J=7.5 Hz, 2H),7.32 (t, J=7.07 Hz, 1H), 7.05 (t, J=7.72 Hz,
1H, CH).
Elemental analysis. Found, %: С 76.55; H 5.38; N 8.38. С21H18N2O2.
Calculated, %: С 76.34; H 5.49; N 8.48.
N,N’-(3-nitrophenylmethylene)diacrylamide (Table 2, B2):
FT-IR: ῡ (ATR, neat, cm-1): 3242 (N-H stretch), 1664 (C=O stretch), 1628
(C=C stretch), 1346, 1528 (N=O stretch), 1520 (N-H bend), 966, 703, 667
Scheme 5. Synthesis of N,N’-(methylene)dibenzamide from 1, 3,
5-trioxane with benzamide
1
(C-H bend); H NMR (DMSO-d6, ppm): δ 9.22 (d, J=7.4 Hz, 2H, N-H), 8.20
(d, J=1.74 Hz, 2H), 7.82 (d, J=7.78 Hz, 1H), 7.70 (t, J=8.03 Hz, 1H), 6.74 (t,
J=7.49 Hz, 1H, CH), 6.35 (dd, J=17.09 Hz, 10.19, 2H), 6.17 (dd, J=17.10 Hz,
1.73, 2H), 5.68 (dd, J =10.17 Hz, 1.78, 2H). Elemental analysis. Found, %: С
56.56; H 4.58; N 15.38. С13H13N3O4. Calculated, %: С 56.72; H 4.76; N 15.27.
N,N’-(4-nitrophenylmethylene)dibenzamide (Table 2, B3):
The chemo-selectivity of bisamide preparation was examined via reaction
of 4-nitrobenzaldehyde with benzamide and acetamide in one vessel in the
presence of nano-TiCl4.SiO2. The preparation of mixed products approves
no chemo selectivity between aromatic and aliphatic amides. Reaction
of benzamide with 3-phenylpropione aldehyde and benzaldehyde in one
vessel and producing a mixture of corresponding bisamides show no chemo
selectivity between aromatic and aliphatic aldehydes. Previously, two types
of mechanisms were reported for bisamide formation from aldehyde and
amide.13,14
FT-IR: ῡ (ATR, neat, cm-1): 3256 (N-H stretch), 1649 (C=O stretch), 1343,
1
1507 (N=O stretch), 1546 (N-H bend), 852 (C-H bend); HNMR (DMSO-d6,
ppm): δ 9.2 (d, J=5.0 Hz, 2H, N-H), 8.26(d, J=6.9 Hz, 2H), 7.93(d, J=5.6 Hz,
4H), 7.75(d, J=6.9 Hz, 2H), 7.58(s, 2H), 7.50(m, 4H), 7.09 (brs, 1H, CH).13C-
NMR (DMSO-d6, ppm): 166.7, 134.41, 132.62, 129.21, 128.91, 128.47,
124.38. Elemental analysis, Found, %: С 66.99; H 4.78; N 11.15. С21H17N3O4.
Calculated, %: С 67.19; H 4.56; N 11.19.
According to our knowledge, we have proposed a mechanism for formation
of bisamides in the presence of nano-TiCl4.SiO2 (Scheme 6).
N,N’-(4-nitrophenylmethylene)dimethylcarboxamide (Table 2, B4):
FT-IR: ῡ (ATR, neat, cm-1): 3306 (N-H stretch), 1706 (C=O stretch),
1600 (C=C stretch), 1349, 1530 (N=O stretch), 1550 (N-H bend), 1251, 1195
(C-O stretch), 871 (C-H bend); 1H NMR (DMSO-d6, ppm): δ 8.2(d, J=7.5 Hz,
2H), 8.1 (brs, 2H, N-H), 7.6(d, J=7.6 Hz, 2H), 6.24(brs, 1H, CH), 3.58 (s, 6H,
OMe); 13C-NMR (DMSO-d6, ppm): 156.6, 148.1, 147.9, 128.7, 124.3, 61.9,
52.5. Elemental analysis, Found, %: С 46.50; H 4.70; N 14.90. С11H13N3O6.
Calculated, %: С 46.65; H 4.63; N 14.84.
N,N’-(2,4-dichlorophenylmethylene)dimethylcarboxamide (Table 2,
B5):
FT-IR: ῡ (ATR, neat, cm-1): 3309 (N-H stretch), 1708 (C=O stretch), 1550
1
(N-H bend), 720, 699 (C-H bend), 643 (C-Cl stretch); H NMR (DMSO-d6,
ppm): δ 8.04 (sbr, 2H, N-H), 7.61 (d, J=2 Hz, 1H), 7.57 (d, J=8.45 Hz, 1H),
6.24 (dd, J=8.42 Hz, 1.9, 1H), 6.24(t, J=7.55 Hz, 1H, CH), 3.55(s, 6H, OMe);
13C-NMR (DMSO-d6, ppm): 156.3, 137.5, 134.1, 133.8, 130.3, 129.5, 128.1,
59.8, 52.4. Elemental analysis, Found, %: С 42.92; H 3.90; N 9.08; Cl 23.02.
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J. Chil. Chem. Soc., 61, Nº 3 (2016)
С11H12N2O4Cl2. Calculated, %: С 43.02; H 3.94; N 9.12; Cl 23.09.
N,N’-(3-nitrophenylmethylene)dibenzamide (Table 2, B6):
size some effective derivatives of bisamides with different biological activities.
FT-IR: ῡ (ATR, neat, cm-1): 3250 (N-H stretch), 1646 (C=O stretch),1340
(N-H bend), 1339, 1533 (N=O stretch), 1505 (C=C stretch), 715, 695 (C-H
bend);1H NMR (DMSO-d6, ppm): δ 9.2 (d, J=7.4 Hz, 2H, N-H), 8.35 (sbr, 1
H), 8.2 (dd, J=6.9 Hz, 1.37, 1H), 7.96(s, IH), 7.93(d, J=8.4 Hz, 4H), 7.71(t,
J=7.9 Hz, 1 H), 7.58(t, J=7.2 Hz, 2H), 7.5(t, J=7.8 Hz, 4H), 7.09 (t, J=7.3 Hz,
1H, CH). Elemental analysis, Found, %: С 66.89; H 4.67; N 11.39. С21H17N3O4.
Calculated, %: С 67.19; H 4.56; N 11.19.
ACKNOWLEDGEMENTS
The Research Council of Yazd University is gratefully acknowledged for
the financial support of design and synthesis of compounds. The antifungal
activities of the synthetic compounds were evaluated in Shiraz University of
Medical Sciences.
N,N’-(2,4-dichlorophenylmethylene)diacetamide (Table 2, B7):
FT-IR: ῡ (ATR, neat, cm-1): 3285 (N-H stretch), 1665 (C=O stretch), 1425
(C=C stretch), 1518 (N-H bend), 856, 749 (C-H bend), 643 (C-Cl stretch); 1H
NMR (DMSO-d6, ppm): δ 8.54 (d, J=7.19 Hz, 2H, N-H), 7.62 (d, J=1.6 Hz,
1H), 7.5 (m, 2H), 6.6 (t, J=7.55 Hz, 1H, CH), 1.84(s, 6H, CH3). Elemental
analysis, Found, %: С 47.90; H 4.48; N 10.08; Cl 25.62. С11H12N2O2Cl2.
Calculated, %: С 48.02; H 4.40; N 10.18; Cl 25.77.
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1
1484, 1600 (C=C stretch), 1530 (N-H bend); H NMR (DMSO-d , ppm): δ
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1
1508, 1579 (C=C stretch), 1545 (N-H bend), 690, 756 (C-H bend); H NMR
(DMSO-d6, ppm): δ 8.64 (d, J=7.5 Hz, 2H, N-H), 7.88 (d, J=7.22 Hz, 4H),
7.54(t, J=7.31 Hz, 2H), 7.48 (t, J=7.69 Hz, 4H), 7.28 (m, 4H), 7.17 (m, 1H),
5.85 (m, 1H, CH), 2.69 (t, J=8.15 Hz, 2H, CH ), 2.17 (dd, J=15.4 and 7.31 Hz,
2H, CH2). Elemental analysis, Found, %: С 762.89; H 6.24; N 7.95. С23H22N2O2.
Calculated, %: С 77.07; H 6.19; N 7.82.
N,N’-(3-phenyl-2-ene-propylene)dibenzamide (Table 2, B11):
FT-IR: ῡ (ATR, neat, cm-1): 3274(N-H stretch), 1647 (C=O stretch),
1
1484,1504 (C=C stretch), 1543 (N-H bend), 690, 756 (C-H bend); H NMR
(DMSO-d6, ppm): δ 8.87 (d, J=6.8 Hz, 2H, N-H), 7.92 (d, J=7.36 Hz, 4H),
7.86 (t, J=7.92 Hz, 2H), 7.56 (t, J=7.2 Hz, 2H), 7.48 (m, 4H), 7.35 (m, 2H),
7.28 (t, J=7.32 Hz, 1H), 6.69 (d, J=14.7 Hz, 1H, CH), 6.65 (m, 2H). Elemental
analysis, Found, %: С 77.99; H 5.37; N 7.59. С23H20N2O2. Calculated, %: С
77.51; H 5.66; N 7.86.
N,N’-(2-hydroxyphenyl-methylene)dibenzamide (Table 2, B12):
FT-IR: ῡ (ATR, neat, cm-1): 3406-3268(O-H and N-H stretch), 1639 (C=O
stretch), 1425 (C=C stretch), 1126 (C-N bend), 758 (C-H bend);1H NMR
(DMSO-d6, ppm): δ 9.02 (d, J=7.39 Hz, 2H, N-H), 8.03 (d, J=7.27 Hz, 2H),
7.81(d, J=7.31 Hz, 3H), 7.69 (m, 1H), 7.52 (m, 3H), 7.45 (m, 5H), 7.35 (m,
1H), 7.26 (t, J=7.34 Hz, 1H, CH). Elemental analysis, Found, %: С 72.99; H
5.17; N 7.99. С21H18N2O . Calculated, %: С 72.82; H 5.24; N 8.09.
N,N’-(methylene)di3benzamide (Scheme 5):
19. B.F. Mirjalili, A. Bamoniri, L. Zamani, Scientia Iranica, C 19, 565, (2012).
20. B.F. Mirjalili, A. Bamoniri, L. Zamani, Lett. Org. Chem., 9, 338, (2012).
21. B.F. Mirjalili, L. Zamani, S. Afr. J. Chem., 67, 21, (2014).
22. L. Zamani, B.F. Mirjalili, M. Namazian, Chemija 24, 312, (2013).
23. L. Zamani, B.F. Mirjalili, K. Zomorodian, S. Zomorodian, S. Afr. J.
Chem., 68, 133, (2015).
24. L. Zamani, B.F. Mirjalili, Chem. Heterocycl. Compd., 51, 578, (2015).
25. L. Zamani, B. F.Mirjalili, K. Zomorodian, M. Namazian, S. Khabnadideh,
E. FaghihMirzaei, Farmacia, 62, 467, (2014).
26. B.F. Mirjalili, L. Zamani, K. Zomorodian, S. Khabnadideh, Z. Haghighijoo,
Z. Malakotikhah, S.A. Ayatollahi Mousavi, Sh. Khojasteh, J. Mol. Struct.,
1116, 102 (2016).
27.
FT-IR: ῡ (ATR, neat, cm-1): 3308 (N-H stretch), 1634 (C=O stretch), 1487,
1578 (C=C stretch), 1526 (N-H bend), 1448 (CH2 bend); 1HNMR (DMSO-d6,
ppm): δ 9.03 (t, J=5.5 Hz, 2H, N-H), 7.9 (d, J=7.14 Hz, 4H), 7.55 (t, J=7.15 Hz,
2H), 7.48(t, J=7.14 Hz, 4H), 4.84(t, J=5.5 Hz, 2H, CH2). Elemental analysis,
Found, %: С 69.99; H 4.97; N 11.48. С15H14N2O2. Calculated, %: С 70.85; H
5.55; N 11.02.
CONCLUSION
We have demonstrated simple methods for the synthesis of preparation of
N,N′-alkylidene bisamides with using nano-TiCl4.SiO2 as eco-friendly and ef-
ficient catalyst in a one-pot procedure that has been developed. Short reaction
times, high yields, a clean process, simple methodology, easy work-up and
green conditions are advantages of this protocol. Even at this time our com-
pounds didn’t show antifungal and antibacterial activity but we suppose these
negative results probably related to undesirable pharmacokinetic properties.
Maybe some structural modifications could improve the pharmacokinetic prop-
erties of our compounds. We hope in future studies we could be able to synthe-
3037

J. Chil. Chem. Soc., 61, Nº 3 (2016)
Table 3. Minimum inhibitory and fungicidal concentrations of the synthetic compounds (µg/mL) against the examined fungi.
B1
B2
B3
B5
B6
B7
B9
B10
B12
Fluconazole
MIC
MFC MIC MFC MIC MFC MIC MFC MIC MFC MIC MFC MIC MFC MIC MFC MIC MFC MIC MFC
C.
albicans
ATCC10261
>256 >256 >256 >256 >256 >256 >256 >256 >256 >256 >256 >256 >256 >256 >256 >256 >256 >256
>256 >256 >256 >256 >256 >256 >256 >256 >256 >256 >256 >256 >256 >256 >256 >256 >256 >256
>256 >256 >256 >256 >256 >256 >256 >256 >256 >256 >256 >256 >256 >256 >256 >256 >256 >256
>256 >256 >256 >256 >256 >256 >256 >256 >256 >256 >256 >256 >256 >256 >256 >256 >256 >256
>256 >256 >256 >256 >256 >256 >256 >256 >256 >256 >256 >256 >256 >256 >256 >256 >256 >256
>256 >256 >256 >256 >256 >256 >256 >256 >256 >256 >256 >256 >256 >256 >256 >256 >256 >256
>256 >256 >256 >256 >256 >256 >256 >256 >256 >256 >256 >256 >256 >256 >256 >256 >256 >256
3.3
8
84.44
256
32
C.
ropicalis
ATCC750
C.
krusei
ATCC6258
16
C.
glabrata
ATCC90030
2.8
1.4
128
128
32
C.
dubliniensis
CBS8501
8
A.
flavus
ATCC64025
128
256
A.
fumigatus
ATCC14110
Table 4. MIC and MFC (µg/mL) values for the synthetic compounds against bacteria.
B1 B2 B3 B5 B6
B7
B9
B10
B12
MIC MFC MIC MFC MIC MFC MIC MFC MIC MFC MIC MFC MIC MFC MIC MFC MIC MFC
S.aureus
ATCC25923
>256 >256 >256 >256 >256 >256 >256 >256 >256 >256 >256 >256 >256 >256 >256 >256 >256 >256
E.fecalis
ATCC1299
>256 >256 >256 >256 >256 >256 >256 >256 >256 >256 >256 >256 >256 >256 >256 >256 >256 >256
>256 >256 >256 >256 >256 >256 >256 >256 >256 >256 >256 >256 >256 >256 >256 >256 >256 >256
>256 >256 >256 >256 >256 >256 >256 >256 >256 >256 >256 >256 >256 >256 >256 >256 >256 >256
E. coli
ATCC25922
P.aeruginosa
ATCC27853
3038