Green and reusable nanocatalyst for the synthesis of 1,5-benzodiazepines and its derivatives under solvent-free conditions

Article abstract of DOI:10.1246/cl.150663

Novel, reusable, and efficient (Cd, Zn) S nanocatalysts were prepared by simple and economical chemical bath deposition using a greener approach. The as-synthesized catalysts were characterized by XRD, SEM, TEM, and FT-IR spectroscopy. The catalytic activ

Full text of DOI:10.1246/cl.150663

Received: July 15, 2015 | Accepted: August 17, 2015 | Web Released: September 3, 2015
CL-150663
Green and Reusable Nanocatalyst for the Synthesis of 1,5-benzodiazepines
and Its Derivatives under Solvent-free Conditions
1
2
1
Kandregula Veera Venkata Satyanarayana, Matangi Ravi Chandra, Parimi Atchuta Ramaiah,
1
3
3
Yellajyosula Lakshmi Narasimha Murthy, Yoon Soon Gil, and Sri Venkata Narayana Pammi*
1
Department of Organic Chemistry Foods, Drugs and Water, College of Science and Technology, Andhra University,
Visakhapatnam 530003, India
2
Advanced Analytical Laboratory, DST-PURSE Programme, Andhra University, Visakhapatnam 530003, India
3
Department of Materials Science and Engineering, Chungnam National University, Daeduk Science Town, 305-764, Daejeon, Korea
(
E-mail: venkat@cnu.ac.kr)
Novel, reusable, and efficient (Cd, Zn) S nanocatalysts were
prepared by simple and economical chemical bath deposition
using a greener approach. The as-synthesized catalysts were
characterized by XRD, SEM, TEM, and FT-IR spectroscopy. The
catalytic activity of as-prepared nanocatalysts were examined for
the synthesis of 1,5-benzodiazepines and its derivatives under
solvent-free conditions without using any toxic materials. It has
been observed that CdS nanocatalyst shows superior catalytic
activity and is recyclable and reusable for ten runs without any
significant loss.
Scheme 1.
Benzodiazepines and their derivatives have received signifi-
cant attention due to their remarkable central nervous system
depressant activity and are now known to be one of the most
1
widely prescribed classes of psychotropics. They are broadly
used as antibiotics, and in various diseases such as cancer, viral
infection (HIV), and cardiovascular disorders and also useful in
the treatment of anxiety, insomnia, agitation, seizures, muscle
spasms, alcohol withdrawal and as a premedication for medical
2
,3
or dental procedures. The 1,5-benzodiazepine core is found
in compounds active against a variety of target types such as
peptide hormones, interleukin converting enzymes, and potassium
blockers. Furthermore, benzodiazepines also act as valuable
intermediates in the synthesis of fused ring compounds such
as triazolo-, oxadiazolo-, oxazino-, and furanobenzodiazepines.4
Figure 1. XRD patterns for ZnS and CdS nanoparticles.
ZnS and CdS nanoparticles were synthesized by simple chem-
ical bath deposition of Zn(CH3COO)2 (zinc acetate)/cadmium
acetate dihydrate (Cd(OAc)2)¢2H2O, trisodium citrate, NaOH and
thiourea solution and ethylene glycol containing PVP near room
temperature (ca. 35 °C). The product was separated from the
reaction mixture by centrifugation, washed several times with
ethanol and finally treated with 0.1 M HNO3. The detailed
experimental method is given in Supporting Information (SI).
The morphological, structural, chemical, and optical properties
of ZnS and CdS nanoparticles were analyzed with SEM, XRD,
EDAX, TEM, and FTIR techniques.
The XRD pattern (Figure 1) of ZnS nanoparticles exhibits
diffraction peaks which are significantly broadened because of
very small crystalline size. The ZnS nanoparticles exhibit
hexagonal structure (JCPDS No. 80-0007) with preferred orienta-
tion (002) along with (110), and (112) directions. The crystalline
size of ZnS nanoparticles and CdS nanoparticles was calculated
using the Scherrer formula and was found to be about 5 and 8 nm
respectively, indicating their nanocrystalline nature. On the other
hand, XRD pattern of CdS nanoparticles exhibits cubic phase with
preferred orientation (111) along with (220), (311) directions. No
metal or other phases were detected by XRD for ZnS and CdS
nanoparticles.
1
,5-Benzodiazepines are generally synthesized by acid-catalyzed
condensation of o-phenylenediamines with ketones. From the
reported literature, the synthesis of benzodiazepines includes usage
of various metal salts, CAN, heteropolyacids, ionic liquids, etc.5
However, most of these processes have certain limitations, such as
prolonged reaction time, use of strong acid or organic solvents,
generation of by-products, anhydrous conditions, poor yields,
and tedious work-up procedures. Therefore, improvements in this
synthesis have been sought continuously. In recent years, there
has been an upsurge of interest on the usage of heterogeneous
nanocatalyst because of their quantum size effect that leads to
increase in relative number of surface atoms and thus improvement
­8
9
in catalytic activity. The usage of ZnS and CdS semiconductor
nanoparticles in biomedical applications has been studied.10
However, there are very few reports on the synthesis of 1,5-
benzodiazepines and their derivatives using nanocatalyst.11
In this article, we report the synthesis and characterization of
ZnS and CdS nanoparticles and examined the feasibility of catalytic
activity in the synthesis of 1,5-benzodiazepines and their deriva-
tives using the process of condensation of σ-phenylenediamine
with various ketones under solvent-free conditions (Scheme 1).
Chem. Lett. 2015, 44, 1589–1591 | doi:10.1246/cl.150663
© 2015 The Chemical Society of Japan | 1589

Table 1. Comparison of various bulk catalysts with nanocatalyst for
the condensation of o-phenylenediamine with acetone (ketone) under
a
solvent-free conditions (Scheme1)
Time
Yield
/%
Entry
Catalyst
b
/
min
1
2
3
4
5
6
7
8
9
ZnSO4
CdSO4
25
25
25
30
30
25
20
20
16
57
61
67
69
73
88
92
98
98
Bulk ZnO commercial
Bulk ZnS commercial (100 nm)
Bulk CdS commercial (100 nm)
Nano-ZnS 5%
Nano-CdS 5%
Nano-CdS 10%
Nano-CdS 20%
aReaction conditions: o-phenylenediamine (1 mmol), acetone as ketone
2 mmol), and catalyst (10 mol %), solvent free, temperature 90 °C.
(
b
Based on isolated yield.
¹
1
3
1
600 cm representing (OH) stretching vibrations and bands at
¹1
620 cm due to (HOH) bending vibrations seems to be in good
12
agreement with the reported values. In addition, the group of
peaks around 1000 cm was an indicative of sulfate groups, which
has been previously reported for water on bulk sulphides. There
were medium to strong absorption bands at 613 and 723 cm
¹1
1
3
¹1
which have been assigned to Cd­S stretching.14 However, there
has been no evidence of distinct ZnO and/or CdO phase from
diffraction data and the FTIR data, thereby indicating that the
oxidized groups were confined to the nanoparticle surface.
This study was initiated by testing the catalytic activity of ZnS
and CdS nanoparticles in comparison with commercial catalysts
for the synthesis of 1,5-benzodiazepines by condensation of σ-
phenylenediamine with acetone as ketone under solvent-free con-
dition as shown in Table 1. Commercial salts i.e., ZnSO4¢7H2O
and CdSO4¢7H2O catalysts with an amount of 5% (Table 1,
Entries 1 and 2) exhibit poor yield and, bulk ZnO, ZnS, and CdS
(commercial, size ca. 0.1 ¯m) giving (Entries 3­5) moderate
yields. It has been observed that among the bulk commercial
catalyst CdS shows higher yield compared to ZnO and ZnS. On
the other hand, ZnS and CdS nanocatalysts (prepared in our lab,
Entries 6­8) show excellent yield in short reaction time. The
increased catalytic activity of nanoparticles over commercial
catalyst may be attributed to higher surface area, thus resulting in
higher surface concentration of the reactive sites. The theoretically
calculated surface area of bulk CdS and nano CdS are 12.42 and
Figure 2. (a), (b) SEM, (c), (d) TEM, and (e), (f) HRTEM images of
ZnS and CdS nanoparticles respectively.
The surface morphology and chemical composition of the ZnS
and CdS nanoparticles (Figures 2a and 2b) were observed by
scanning electron microscopy (SEM). Figure 2a shows ZnS
nanospheres having rough surface composed of agglomerated
nanoparticles with an average diameter of about 70 nm. The
presence of some larger particles attributes to aggregation or
overlapping of smaller particles. Figure 2b shows the spherical-
shaped CdS nanoparticles aggregated with small particles due to
growth and assembly of CdS nuclei. The chemical composition
of synthesized ZnS and CdS nanoparticles were analyzed by EDS
which was given in Figures 1 and 2 in SI.
2
¹1
On further investigation, the sizes of ZnS and CdS nano-
particles were analyzed by TEM (Figures 2c and 2e) and it reveals
that the ZnS nanoparticles (Figure 2c) were 3­5 nm in diameter.
From HRTEM image, the interplanar spacing was about 0.35 nm
155.27 m g respectively. However, there was no significant
improvement in yield when above 10 mol % (Entry 9) amount of
catalyst was used in the reaction.
To study the viability of the synthetic method for preparing
benzodiapine derivatives, different ketones were readily reacted
with o-phenylenediamine. The scope and generality of this process
was illustrated with various cyclic and acyclic ketones, and the
results were summarized in Table 2. Based on electrophilic nature,
the alkyl, cyclic, and aromatic ketones gives higher yields
(Table 2). For instance, treatment of phenylenediamine with
different cyclic and alkyl-substituted ketones, acetone exhibits
higher yields (Table 2, Entry 1) compared to remaining alkyl-
substituted ketones because of the more electrophilic centre of
acetone for the nucleophilic o-phenylenediamine. For the same
reason, aromatic methyl-substituted ketones, phenyl acetone
exhibits higher yields (Table 2, Entry 7) compared to remaining
ketones.
(
Figure 2e) and it represents (002) lattice plane of hexagonal
wurtzite structure of ZnS nanoparticles. Figure 2d indicates the
TEM images of CdS nanoparticles. TEM image clearly revealed
that the synthesized CdS nanoparticles (Figure 2d) have particle
size of 6­8 nm. From HRTEM image, the interplanar spacing was
known to be about 0.33 nm (Figure 2f) and it represents (111)
lattice plane of cubic structure of CdS nanoparticles. The sizes of
CdS and ZnS nanoparticles were corroborated with XRD results.
The reason for the appearance of aggregates of both sulfide (CdS
and ZnS) nanoparticles was possibly due to static attraction of
their surface groups. Figure 3 in SI, shows the FTIR spectra of
synthesized CdS nanoparticles, which were prepared by chemical
bath deposition. From the FTIR data, bands around 3000­
1590 | Chem. Lett. 2015, 44, 1589–1591 | doi:10.1246/cl.150663
© 2015 The Chemical Society of Japan

Table 2. The condensation of o-phenylenediamine with ketones in
the presence of nano-CdSa
b
Reaction Yield
S.No Diamine Ketone
Product
time/min
/%
NH
NH
2
1
O
NH
N
20
98
2
NH
NH
2
2
3
O
NH
N
25
20
93
95
2
NH
NH
2
O
NH
N
2
Figure 3. Reusability of CdS nanoparticles.
O
NH
NH
2
2
4
5
6
NH
N
20
20
25
94
95
88
of catalytic activity, These results proved that CdS nanocatalyst
provides the development of green synthesis of 1,5-benzodiaze-
pines and their derivatives under solvent-free conditions, fast
reaction rates, mild reaction conditions, good yields, and the
reaction seems to be economically and potentially valuable for
industrial applications.
NH
2
O
O
NH
N
NH
2
NH
NH
2
2
NH
N
We are thankful to Bk21 plus Project for their funding of
preparation of catalyst and the DST-PURSE Programme, Analyt-
ical Laboratory, Andhra University for their support in carrying out
in this research work regarding SEM-EDX and XRD analysis.
NH
NH
2
2
Ph
O
7
8
16
20
96
93
NH
Ph
N
Ph
NH
NH
2
2
O
Cl
NH
N
Cl
Supporting Information is available electronically on J-STAGE.
References and Notes
Cl
NH
NH
2
2
O
OMe
9
30
88
NH
N
1
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MeO
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(
b
Based on isolated yield.
2.00006-0.
3
4
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benzodiazepines by condensation of σ-phenylenediamine with
ketone under solvent-free conditions was studied. After comple-
tion of the condensation of dimethyl ketone with o-phenylenedi-
amine, the reaction mixture was diluted with ethyl acetate and the
catalyst was recovered by filtration. The solid-supported catalyst
was dried in an oven and reused for subsequent experiments under
similar reaction conditions.
The catalyst maintained its good level of efficiency even after
being reused for ten runs (Figure 3). The product was obtained
in 98, 95, 93, 92, and 91% yields after successive cycles. The
observed fact was that yields of the product remained comparable
in these experiments and established the recyclability and
reusability of the catalyst without any significant loss in activity.
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loss of catalyst during the handling i.e., recovering, washing, and
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morphology and size of the CdS nanoparticles before reaction and
after nine cycles (Figure 4, SI).
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9
1
0
11
In conclusion, we have synthesized CdS nanoparticles as a
new heterogeneous catalyst for the synthesis of xanthenes and
their derivatives without using acidic catalyst, solvent, or toxic
materials with superior catalytic activity in short reaction time.
In addition, nano CdS offers the competitive advantage of easy
workup and easy separation from the reaction mixture to be reused
and the recyclability of the catalyst without significant degradation
12
13
14
Chem. Lett. 2015, 44, 1589–1591 | doi:10.1246/cl.150663
© 2015 The Chemical Society of Japan | 1591