chapter 4 an efficient organic synthesis using metal...
TRANSCRIPT
135
CHAPTER-4
AN EFFICIENT ORGANIC SYNTHESIS USING METAL OXIDE AND
METAL SULPHIDE NANOPARTICLES
Metal oxides and metal sulphides are used as a catalyst in many organic
transformations. They have catalytic activity due to, i) the redox properties,
ii) coordination of surface atoms, and iii) oxidation state. In the metal oxides or metal
sulphides s, p, d or f outer electrons are in their valence shell and therefore these act as
a catalyst. The acid/base and redox properties are interrelated with each other362
. The
nanoparticles have high activities, and selectivity due to their large surface area and
these catalysts can be recycled363, 364
. These nanoparticles are used as nanocatalysts in
reduction, oxidation, decomposition, and coupling reactions365, 366
. Heterogeneous
catalysis is being widely used in fine chemical industry due to its environmentally
friendly production technology. The nanomaterials have high specific active sites on
its surface, and exhibit more catalytic activity367
.
Nanocatalysis is a rapidly growing field involves the use of nanomaterials as
catalysts for a variety of homogeneous and heterogeneous reactions. Heterogeneous
catalysis represents one of the commercial practices of nanoscience, nanoparticles of
metals, semiconductors, oxides, and other compounds have been widely used for
important chemical reactions. They are promising, can be expected decrease in the
energy usage in chemical processes, and resulted greener chemical industry.
Significance of nanocatalysts:
The nanoctystalline material has many advantages some of are listed below:
i) Nanomaterials increases selectivity, activity by controlling pore size and particle
characteristics as compared to bulk material in catalysis. The nanocatalysts are
136
more efficient because they have large surface area which acts as active centers in
catalysis.
ii) Recently, the precious metal catalyst replaced by nanoscale catalyst thus improving
chemical reactivity and reducing process cost, therefore it is possible to achieve
cost effectiveness.
iii) The nanoscale catalytic material can remove unwanted molecules from gases or
liquids by controlling their properties so they are environmentally friendly
catalyst.
iv) Some of the nanocatalyst can develop partial and net charges that help in process
of making and braking bonds at more efficient scale.
v) The nanocatalyst minimizes the usage of fossil fuels and reduces the energy
consumption.
vi) The nanocrystalline catalyst gives high yields with high quality and increased the
atom economy of the process.
Nowadays, the development of environmentally benign protocol is gaining the
importance in chemical processes. Generally, reactions are carried out using organic
acids such as H2SO4, HCl, HNO3, and in another hand the use of Lewis acid like HF
and BF3. Despite its high selectivity these homogeneous acid catalyst have several
disadvantages such as high toxicity, corrosive nature, generating maximum waste,
difficulty in recovery, and reusability. In view of enviro-economical aspects it is
necessary to replace these toxic acid catalyst by newer solid metal oxides and metal
sulphide catalyst as an excellent alternative source over this conventional acid catalyst
as they can be inexpensive, non-toxic, non-corrosive, easy to recover, and reuse.
Metal oxide or metal sulphide based catalysts are active over a wide range of
temperature, and more resistant to thermal excursion.
137
In the present work, efforts are made for the synthesis, characterization, and
catalytic application of metal oxide or metal sulphide solid catalysts for chemical
synthesis. The noticeable advantage of the present work is to introduce simple and
eco-friendly procedure for the preparation of organic compounds, and their
derivatives.
Chapter 4 is divided into five sections,
Section-A: An efficient synthesis of benzylidene malononitrile and
tetrahydrobenzopyrans using PbO nanoparticles.
Section-B: An efficient synthesis of acridinediones using CdO nanoparticles as
catalyst under solvent free condition.
Section-C: PbS nanoparticles as an effective catalyst for the one pot synthesis of
amidoalkyl naphthols under solvent free condition.
Section-D: ZnS nanoparticles as an efficient solid catalyst for synthesis of 5-arylidene
barbituric acids under solvent free condition.
Section-E: Comparative study on catalytic efficiency of synthesized nanoparticles
towards synthesis of pyranopyrazoles.
138
Section-A
I) Synthesis of Benzylidene Malononitriles using PbO Nanoparticles as an
Efficient and Reusable Catalyst
4.1A. Introduction:
Benzylidene malononitriles are the main products of the condensation of
substituted benzaldehyde with malononitrile. Derivatives of benzylidene
malononitriles have important applications in chemotherapeutic treatment of
cancer368
. Moreover, benzylidene malononitriles were used as cytotoxic agents
against tumours or as riot control agents369
, and have been reported to be effective
anti-fouling agents, fungicides, and insecticides370
. The small molecules have been
found to possess inhibitory activity to HER2, including compounds belonging to the
benzylidene malononitrile family371
. The derivatives of benzylidene malononitriles
possess antimicrobial activity372
and used as potent tyrosine kinase inhibitors373
. The
benzylidene malononitrile derivatives also used for the treatment of leukemia374
.
Several methods used for the synthesis of substituted benzylidene
malononitrile, Heravi et al375
have reported the Na2S/Al2O3 catalyzed condensation
between various aldehydes and active methylene compounds in a heterogeneous
system (Scheme 1).
R2
O
R1+
R3
CN R1
R2 R3
CNNa2S(20mol%),Al 2O3(0.05gm)
CH2Cl 2
Scheme 1
139
Bhuiyan et al372
have reported the condensation reaction of malononitrile with
aromatic aldehydes in presence of ammonium acetate (NH4OAc) using microwave
irradiation under solvent free condition (Scheme 2).
Scheme 2
Balalaie et al376
have reported the condensation reaction between aromatic
aldehydes and active methylene compounds in presence of ammonium acetate
(NH4OAc) basic alumina (Scheme 3).
Scheme 3
Verma et al377
have been reported the use of p-methoxyphenyltellurium
trichloride as an efficient catalyst for condensation reaction of active methylene with
aromatic aldehydes (Scheme 4).
Scheme 4
Ye et al378
have reported the condensation of aromatic aldehydes with active
methylene using diethylamine functionalized polyethylene glycol-600 (PEG-600) at
room temperature without solvent (Scheme 5).
Scheme 5
Ar
H
O
+CN
CN NH4OAc
MWI CN
CNAr
H
Ar
H
O
+CN
CN NH4OAc
basic alumina CN
CNAr
H
Ar
H
O
+R
CN
R
CNAr
H
R' TeCl 3
900C-100
0C
R1
H
O
+CN
R2
CN
R2
R1
H
PEG-600
solvent free
140
Gupta et al379
have reported the hydroxyapatite supported cesium carbonate in
water as an efficient catalyst for condensation reaction of active methylene with
aromatic aldehydes (Scheme 6).
Scheme 6
Mogilaiah et al380
have reported ammonium sulphamate catalyzed
condensation of aromatic aldehydes with active methylene in solvent free condition
under microwave irradiation (Scheme 7).
Scheme 7
Bhaumik et al381
have reported highly efficient mesoporous base catalyzed
Knoevenagel condensation of different aromatic aldehydes with malononitrile by
amine functionalized mesoporous silica (Scheme 8).
Scheme 8
Su et al382
have reported deprotonated mesoporous graphite carbon nitride
(mpg-C3N4) as a solid base catalyst for condensation of aromatic aldehydes with
malononitrile (Scheme 9).
Scheme 9
R
H
O
+CN
X
CN
XR
H
HAP-Cs 2CO3, 80-1000C
reflux, H 2O
Ar
H
O
+R
CN
R
CNAr
H
NH2SO3NH4
MW
Ar
H
O
+CN
CN
CN
CNAr
H
amine functionalized
mesoporus silica
Ar
H
O
+CN
CN
CN
CNAr
H
mpg-C3N4
141
Reddy et al383
have reported sulfate ion promoted ZrO2 catalyst for
condensation of aliphatic, aromatic, and heterocyclic aldehydes with malononitrile
under solvent free condition (Scheme 10).
Scheme 10
Yuan et al384
have reported MgC2O4/SiO2 catalyst for condensation of
aldehydes with malononitrile under microwave irradiation and solvent free condition
(Scheme 11).
Scheme 11
Shi et al385
have reported triethylbenzylammonium chloride (TEBA) catalyzed
condensation of aromatic aldehydes with malononitrile in presence of water at 70oC
(Scheme 12).
Scheme 12
However, many of these methods suffered from drawbacks such as low yield,
long reaction time, drastic reaction condition, and tedious work up. Therefore, there is
a scope for generation of new methodology with mild reaction condition, better yield,
short reaction time, and environment friendliness. Recently, metal or metal oxides are
also used as catalyst in organic reactions, and have more advantages over organic
catalyst386
.
The present work reports the use of efficient and reusable PbO nanoparticles
as a catalyst for the synthesis of benzylidene malononitriles. The PbO nanoparticles
Ar
H
O
+CN
CN
CN
CNAr
H
sulfate ion-ZrO 2
Ar
H
O
+CN
CN
CN
CNAr
H
MgC2O4/SiO2
MWI
Ar
H
O
+R
CN
R
CNAr
H
H2O, TEBA
700C, 5h
142
have gained more importance in organic transformations due to high thermal stability,
large surface area, easy recovery, good ability to perform organic reactions at room
temperature without solvent and enviro-economic factors387
.
4.2A. Present work:
Here we are reported the synthesis of benzylidene malononitrile derivatives by
Knoevenagel condensation of substituted benzaldehyde and malononitrile using PbO
nanoparticles catalyst under solvent free condition by grinding (Scheme 13).
1 2 3 (a-i)
Scheme 13: Synthesis of benzylidene malononitriles
4.3A: Synthesis of benzylidene malononitriles:
In a clean mortar, substituted aromatic aldehyde (1.0 mmol), malononitrile
(1.0 mmol), and PbO nanoparticles (40 mg) were grinded in presence of sunlight. The
reaction was monitored by TLC. After completion of reaction, reaction mixture was
stir, filtered, and the residue was washed with distilled water. The crude product was
dried, extracted by diethyl ether and used PbO nanoparticles catalyst was recovered.
The organic layer on evaporation yielded product which was recrystallized using
ethanol/water afforded pure products. The recovered catalyst was dried, and reused
further in successive reactions. All the products were characterized by IR, 1H NMR,
13C NMR, and mass spectrometry.
4.4A. Results and Discussion:
The reaction of various aromatic aldehydes with malononitrile was carried out
successfully at room temperature without solvent using grinding method. The high
CHO
R
+ CN
NC PbO nanoparticles
CN
CN
R
grinding
143
conversions, and rapid reaction rates was achieved in all reactions (Table 4.1). Both
electron rich and electron deficient aldehyde worked very well giving high yield of
benzylidene malononitriles. Electron deficient aldehyde furnished excellent yield of
the corresponding benzylidene malononitriles in a short reaction time, whereas
electron rich aldehydes resulted in comparatively low yield, and required longer time.
In order to optimize the amount of catalyst the condensation reaction of
benzaldehyde (1.0 mmol), and malononitrile (1.0 mmol) was used as model reaction
using PbO nanoparticles as a catalyst. The reaction mixture was grounded at room
temperature in presence of sunlight. The reaction was optimized by varying
concentration of catalyst such as 10, 20, 30, 40, 50, 60, and 70 mg (Table 4.2). It was
observed that the 40 mg of the catalyst was sufficient to promote the reaction.
In order to study the reusability of catalyst, it was filtered, washed with
ethanol, and heated at 100oC in oven for 2 hrs. The reusability of the catalyst was
checked for several successive run under identical reaction condition. The catalyst
was stable and reusable even after five consecutive cycles without appreciable loss in
activity (Table 4.3). Moreover, the reusability of this catalyst makes the method cost
effective.
The structure of the entire synthesized compound was confirmed by
spectroscopic techniques including IR, 1H NMR,
13C NMR, and mass spectrometry.
Typical 1H NMR spectrum of compound 3g showed the presence of C=CH, and
aromatic protons which confirms the formation of 2-(4-chlorobenzylidene)
malononitrile (Fig. 4.1). 13
C NMR showed peaks at 139.58, 112.47, and 113.51 δ due
to carbon attached to -Cl group, carbon attached to -CN group and -CN carbon
confirms the formation of compound 3g (Fig. 4.2). The structure of 3c compound was
confirmed by mass spectrum which shows the (M+1)+ peak at 200 (Fig. 4.3).
144
Table 4.1. Synthesis of benzylidene malononitriles in presence of PbO nanoparticles
Entry Product
(R group)
Time (min) Yield (%) M. P. (oC)
3a H 09 91 88
3b 4-OCH3 13 92 115
3c 3-NO2 19 95 102
3d 4-OH 25 93 185
3e 3-OCH3 24 96 108
3f 2-CH3 12 94 107
3g 4-Cl 13 92 162
3h 2-NO2 18 90 139
3i 3-CH3 14 92 75
Table 4.2. Effect of amount of PbO nanoparticles catalyst
Entry Catalyst (mg) Time (min) Yield (%)
1 10 21 76
2 20 16 81
3 30 12 87
4 40 07 91
5 50 07 91
6 60 07 90
7 70 07 90
Table 4.3. Reusability of the catalyst
Cycles Time (min) Yield (%)
1 9 91
2 9 90
3 9 89
4 9 89
5 9 88
145
Similarly the formation of all other compounds was confirmed on the basis of spectral
data.
4.5A. Spectral data:
2-(Benzylidene) malononitrile (3a): mp: 88oC, Yield: 91 %, IR (KBr): 3182, 2224,
1691, 1592, 1090 cm-1
, 1H NMR (400 MHz, DMSO-d6): δ 7.91 (d, 2H,
J = 7.60 Hz), 7.64 (t, 1H, J = 7.60 Hz), 7.27 (t, 2H, J = 7.60 Hz), 7.12
(s, 1H), 13
C NMR (100 MHz, DMSO): δ 160.06, 134.68, 130.96,
130.77, 129.66, 113.77, 112.62, M. F: C10H6N2, M. W: 154, MS (m/z): 155 (M +1)+.
2-(4-Methoxybenzylidene) malononitrile (3b): mp: 115oC, Yield: 92 %, IR (KBr):
3117, 2222, 1605, 1561, 1217, 1026 cm-1
, 1H NMR (400 MHz, DMSO-
d6): δ 7.90 (d, 2H, J = 8.0 Hz), 7.64 (s, 1H), 7.00 (d, 2H, J = 8.0 Hz),
3.91 (s, 3H), 13
C NMR (100 MHz, DMSO): δ 164.87, 158.96, 133.49,
124.03, 115.17, 114.49, 113.41, 55.84, M. F: C11H8N2O, M. W: 184,
MS (m/z): 185 (M +1)+.
2-(3-Nitrobenzylidene) malononitrile (3c): mp: 102oC, Yield: 95 %, IR (KBr): 3107,
2225, 1610, 1595, 1529, 1479 cm-1
, 1H NMR (400 MHz, DMSO-
d6): δ 8.45-8.33 (m, 3H), 8.31 (s, 1H,), 7.86 (s, 1H), 13
C NMR
(100 MHz, DMSO): δ 159.74, 149.81, 136.96, 133.99, 132.00,
128.89, 125.99, 114.53, 113.52, M. F: C10H5N3O2, M. W: 199, MS (m/z): 200
(M +1)+.
2-(4-Hydroxybenzylidene) malononitrile (3d): mp: 185oC, Yield: 93 %, IR (KBr):
3654, 3150, 2223, 1569, 1511, 1365, 1208 cm-1
, 1H NMR 400 MHz,
DMSO-d6): δ 12.50 (s, 1H), 7.99 (s, 1H), 7.89 (d, 2H, J = 8.0 Hz), 7.03
(d, 2H, J = 8.0 Hz), 13
C NMR (100 MHz, DMSO): δ 165.34, 160.98,
134.99, 124.51, 117.46, 115.90, 114.95, M. F: C10H6N2O, M. W: 170,
CN
CN
OCH3
CN
CN
CN
CN
O2N
CN
CN
OH
146
MS (m/z): 171 (M +1)+.
2-(3-Methoxybenzylidene)-malononitrile (3e): mp: 108oC, Yield: 96 %, IR (KBr):
3088, 2225, 1593, 1567, 1161 cm-1
, 1H NMR (400 MHz, DMSO-
d6): δ 8.16 (s, 1H), 7.54 (s, 1H), 7.51 (t, 1H, J = 7.32 Hz), 7.45
(d, 1H, J = 8.0 Hz), 7.21 (d, 1H, J = 8.0 Hz), 3.84 (s, 3H).
13C NMR (100 MHz, DMSO): δ 161.90, 161.49, 133.93, 131.51,
124.51, 121.75, 115.61, 115.07, 114.04, 56.03, M. F: C11H8N2O, M. W: 184,
MS (m/z): 185 (M +1)+.
2-(2-Methylbenzylidene) malononitrile (3f): mp: 107oC, Yield: 94 %, IR (KBr):
3043, 2229, 1584, 1501 cm-1
, 1H NMR (400 MHz, DMSO-d6): δ 8.47
(s, 1H), 8.01 (d, 1H, J = 7.70 Hz), 7.50 (d, 1H, J = 7.90 Hz), 7.35
(t, 2H, J = 7.30 Hz), 2.44 (s, 3H), 13
C NMR (100 MHz, DMSO): δ
160.73, 141.30, 134.77, 132.32, 131.83, 129.23, 127.66, 114.93, 113.88, 19.65,
M. F: C11H8N2, M. W: 168, MS (m/z): 169 (M +1)+.
2-(4-Chlorobenzylidene) malononitrile (3g): mp: 162oC, Yield: 92 %, IR (KBr):
3183, 2195, 1604, 1584, 1014 cm-1
, 1H NMR (400 MHz, DMSO-d6): δ
8.34 (s, 1H), 7.90 (d, 2H, J = 8.0 Hz), 7.52 (d, 2H, J = 8.0 Hz),
13C NMR (100 MHz, DMSO): δ 159.2, 139.58, 131.88, 129.61, 129.41,
113.51, 112.47, M. F: C10H5ClN2, M. W: 189, MS (m/z): 190 (M +1)+.
2-(2-Nitrobenzylidene) malononitrile (3h): mp: 139oC, Yield: 90 %, IR (KBr): 3110,
2228, 1613, 1595, 1482 cm-1
, 1H NMR (400 MHz, DMSO-d6): δ
8.47 (s, 1H), 8.34 (d, 1H, J = 8.0 Hz), 7.90-7.89 (m, 1H), 7.82-
7.79 (m, 2H), 13
C NMR (100 MHz, DMSO): δ 158.91, 146.74,
134.95, 133.43, 130.41, 126.64, 125.80, 112.24, 110.97, M. F: C10H5N3O2, M. W:
199, MS (m/z): 200 (M +1)+.
CN
CN
H3CO
CN
CN
CN
CN
Cl
CN
CN
O2N
147
2-(3-Methylbenzylidene) malononitrile (3i): mp: 75oC, Yield: 92 %, IR (KBr): 3093,
2229, 1595, 1501 cm-1
, 1H NMR (400 MHz, DMSO-d6): δ 7.72
(d, 2H, J = 5.50 Hz), 7.69 (s, 1H), 7.43 (m, 1H), 7.40 (t, 1H, J = 7.80
Hz), 2.43 (s, 3H), 13
C NMR (100 MHz, DMSO): δ 160.17, 139.59,
135.55, 131.26, 130.89, 129.47, 127.88, 113.81, 112.62, 21.24, M. F: C11H8N2,
M. W: 168, MS (m/z): 169 (M +1)+.
CN
CN
148
Fig. 4.1: 1H NMR spectrum of 3g compound
Fig. 4.2: 13
C NMR spectrum of 3g compound
CN
CN
Cl
H1
H2
H3H3
H2
CN
CN
Cl
12
34
56
4'
5'
149
Fig. 4.3: Mass spectrum of 3c compound
CN
CN
O2N
150
II) Synthesis of Tetrahydrobenzopyrans Using PbO Nanoparticles as an Efficient
and Reusable Catalyst
4.6A. Introduction:
Benzopyran and their derivatives have shown several pharmacological and
biological properties like diuretic, spasmolytic, antisterlity, antianaphylactin, and
anticancer agents388, 389
. The derivatives of benzopyrans constitute a structural unit of
series of natural products which are used as pigments, cosmetics, and biodegradable
agrochemicals390
. They have been also used as cognitive enhancer for the treatment of
neurogenerative disease including Alzheimer disease, Parkinson‟s disease, and for the
treatment of AIDS associated dementia, Downs‟s syndrome, neurodegenerative
disease, schizophrenia, and myoclonus391
. The derivatives of tetrahydrobenzopyran
are useful as photoactive materials392
. Due to their applications, the synthesis of
heterocyclic derivatives of these ring systems has great importance in medicinal
chemistry and organic synthesis. Several methods used for the synthesis of tetrahydro-
benzo[b]pyrans.
Sandhu et al393
have reported the LiBr catalyzed facile, and efficient method
for the tetrahydrobenzo[b]pyrans under solvent free and microwave heating condition
(Scheme 14).
Scheme 14
O
O
+R
CN
+
CHO
O
R
NH2
O
LiBr
MW
151
Balalaie et al394
have reported a greener method to synthesize
tetrahydrobenzo[b]pyrans from dimedone, aldehyde, and malononitrile under neutral
condition by the use of s-proline as a catalyst (Scheme 15).
Scheme 15
Feng et al395
have reported the synthesis of tetrahydrobenzo[b]pyrans by
microwave assisted multi component one pot reactions in PEG-400 (Scheme 16).
Scheme 16
Lian et al396
have reported the synthesis of tetrahydrobenzo[b]pyrans through
N-methylimidazole as organo catalyst (Scheme 17).
Scheme 17
Li et al397
have reported the synthesis of tetrahydrobenzo[b]pyran derivatives
in aqueous media using trisodium citrate as a catalyst (Scheme 18).
O
O
+R
CN
+
CHO
O
R
NH2
O
(s)-proline (5 mol%)
O
O
+R
CN
+
CHO
O
R
NH2
O
PEG-400
O
O
+R
CN
+
CHO
O
R
NH2
O
N-methyl imidazole
152
Scheme 18
Ranu et al398
have reported the synthesis of tetrahydrobenzo[b]pyrans through
basic ionic liquid (1-butyl-3-methyl imidazolium hydroxide) at room temperature by
condensation reaction of dimedone, aldehyde, and malononitrile (Scheme 19).
Scheme 19
Mobinikhaledi et al399
have reported tetrabutylammonium bromide (TBAB) as
a catalyst for the synthesis of tetrahydrobenzo[b]pyrans in water as a solvent
(Scheme 20).
Scheme 20
Tabatabaeian et al400
have reported Ru (II) complexes bearing tertiary
phosphine ligands a novel and efficient homogeneous catalyst for one pot
condensation of aldehydes, malononitrile, and dimedone for the synthesis of
tetrahydrobenzo[b]pyran derivatives (Scheme 21).
O
O
+R
CN
+
CHO
O
R
NH2
O
trisodium citrate
O
O
+R
CN
+
CHO
O
R
NH2
O
basic ionic liquid
O
O
+R
CN
+
CHO
O
R
NH2
O
TBAB/H2O
ref lux
153
Scheme 21
Kolekar et al401
have reported the synthesis of tetrahydrobenzo[b]pyran
derivatives using basic ionic liquid and 4-amino-1-(2, 3-dihydroxypropyl) pyridinium
hydroxide under mild condition (Scheme 22).
Scheme 22
Patra et al402
have reported the synthesis of tetrahydrobenzo[b]pyran
derivatives in excellent yield using trioctylmethylammonium chloride (Aliquat®336)
as a phase transfer catalyst in water under microwave irradiation (Scheme 23).
Scheme 23
Hilmy Elnagdi et al403
have reported the synthesis of polysubstituted
tetrahydrobenzo[b]pyran derivatives using l-proline as a catalyst in presence of
ethanol or by grinding at room temperature (Scheme 24).
O
O
+R
CN
+
CHO
O
R
NH2
O
Ru(II) complexes
O
O
+R
CN
+
CHO
O
R
NH2
O
(ADPPY)(OH)
O
O
+R
CN
+
CHO
O
R
NH2
O
aliquat-R-336/H2O
MWI
154
Scheme 24
The nanoporous solid acid like catalyst sulfonic acid functionalized silica
(SiO2-Pr-SO3H)404
also used in the synthesis of tetrahydrobenzo[b]pyran derivatives.
In multicomponent reaction the complex molecules could be synthesized with
maximum simplicity405
. However because of wide range of biological activities of
tetrahydrobenzo[b]pyran derivatives, the synthesis of this derivatives are carried out
to explore the catalytic activity of the nanocrystalline PbO as heterogeneous
catalyst387
towards the synthesis of tetrahydrobenzopyran derivatives.
4.7A. Present work:
The present study deals with simple and efficient method for the synthesis of
tetrahydrobenzopyrans under solvent free condition using grinding method at room
temperature. The reaction between aromatic aldehyde, malononitrile, and dimedone
using nanocrystalline PbO as a catalyst provided good yield of tetrahydrobenzopyran
derivatives (Scheme 25).
1 2 3 4 (a-j)
Scheme 25: Synthesis of tetrahydrobenzopyrans
+CN
CNAr CHO +
O
O O
CN
NH2
O
L-proline(10%mol)
EtOH, ref lux, 4h
CHO
R
+ CN
NCPbO nanoparticles
grinding
O
O+
O
O NH2
CN
R
155
4.8A. Synthesis of tetrahydrobenzopyrans:
The substituted aromatic aldehydes (1.0 mmol), malononitrile (1.0 mmol),
dimedone (1 mmol), PbO nanoparticles (50 mg) were mixed, and homogenized in a
beaker. The resulting reaction mixture was grounded in presence of sunlight at room
temperature, and the reaction was monitored by TLC technique. After completion of
reaction, the crude product was washed with distilled water, dried, and recrystallized
from ethanol/water system to afford pure product. The recovered catalyst was washed
with ethanol, dried, heated at 100oC in oven for 2 hrs, and reused further in successive
reactions. All the products were characterized by IR, 1H NMR,
13C NMR, and mass
spectrometry.
4.9A. Results and Discussion:
Using optimized reaction conditions a range of substituted tetrahy-
drobenzopyran derivatives were synthesized at room temperature without solvent by
simple grinding technique. All these reactions are found to be very fast (10-18 min),
and gives high yields (82-92 %) without side product (Table 4.4). In all cases
aromatic aldehydes substituted with either electron donating or electron withdrawing
groups undergoes smooth reaction and gave the products in good yields under the
optimized reaction condition. The aromatic aldehydes with hydroxyl substituents
disfavored the reaction, which gives a comparative lower yield and required longer
time for the completion of the reaction. The yields and reaction time depends on the
structure of aromatic aldehydes. The aromatic aldehydes containing electron donating
groups have taken longer reaction time with low yields whereas the reaction time is
less for the aldehyde containing electron withdrawing groups with high yields.
The condensation reaction between benzaldehyde (1.0 mmol), malononitrile
(1.0 mmol), and dimedone (1.0 mmol) was used as model reaction using PbO
156
nanoparticles as a catalyst to optimize the amount of catalyst. The reaction mixture
was grind at room temperature in presence of sunlight and the reaction was optimized
by varying the concentration of catalyst in the range of 20 to 70 mg (Table 4.5). It was
observed that the 50 mg of the catalyst was sufficient to perform the reaction. Increase
in amount of catalyst does not show any significant increase in the yield of products.
The reusability of the catalyst was checked for several successive runs under identical
reaction condition. The catalyst was found to be stable and reusable even after five
consecutive cycles without appreciable loss in activity (Table 4.6).
The structure of all the synthesized compound was confirmed by IR, 1H NMR,
13C NMR, and mass spectrometry. Typical
1H NMR spectrum of compound 4a
showed the presence of -C=O, -NH2, -CH3, and aromatic protons which confirms the
formation of 2-amino-3-cyano-4-(phenyl)-7, 7-dimethyl-5-oxo-4H-5, 6, 7, 8-tetrahy-
drobenzo[b]pyran (Fig. 4.4). 13
C NMR showed peaks at 195.32, 113.01, 28.52, and
27.00 δ due to -C=O carbon, -CN carbon, and -CH3 carbon confirms the formation of
compound 4a (Fig. 4.5). The structure of 4d compound was confirmed by mass
spectrum which shows the (M+1)+ peak at 330 (Fig. 4.6). Similarly the formation of
all other compounds was confirmed on the basis of their spectral data.
157
Table 4.4. PbO nanoparticles catalyzed synthesis of tetrahydrobenzopyran
Entry Product
(R group)
Time (min) Yield (%) M. P. (oC)
4a H 15 83 229
4b 4-Cl 12 90 212
4c 4-OCH3 18 85 201
4d 2-Cl 15 86 202
4e 4-NO2 10 91 180
4f 4-OH 15 82 208
4g 3-NO2 15 85 212
4h 2-NO2 13 88 227
4i 3-Cl 15 87 230
4j 4-CH3 12 92 214
Table 4.5. Effect of amount of PbO nanoparticles catalyst
Entry Catalyst (mg) Time (min) Yield (%)
1 20 32 63
2 30 21 75
3 40 18 81
4 50 15 83
5 60 15 83
6 70 15 83
Table 4.6. Result of the reaction using recycled PbO nanoparticles catalyst
Cycles Time (min) Yield (%)
1 15 83
2 15 81
3 15 79
4 15 77
5 15 75
158
4.10A. Spectral data:
2-Amino-3-cyano-4-(phenyl)-7, 7-dimethyl-5-oxo-4H-5, 6, 7, 8-tetrahydrbenzo[b]-
pyran (4a): mp: 229oC, Yield: 83 %, IR (KBr): 3396, 2960,
2200, 1685, 1617, 1214 cm-1
, 1H NMR (400 MHz, DMSO-d6):
δ 7.25-7.22 (m, 2H), 7.19-7.12 (m, 3H), 6.59 (s, 2H), 4.22
(s, 1H), 2.46 (s, 2H), 2.19 (d, 1H, J = 16.0 Hz), 2.08 (d, 1H,
J = 16.0 Hz), 1.06 (s, 3H), 0.98 (s, 3H), 13
C NMR (100 MHz, DMSO): δ 195.32,
161.93, 158.35, 144.32, 128.01, 127.08, 126.34, 119.54, 113.01, 58.83, 50.13, 35.49,
31.68, 28.52, 27.00, M. F: C18H18N2O2, M. W: 294, MS (m/z): 295 (M +1)+.
2-Amino-3-cyano-4-(4-chloro-phenyl)-7, 7-dimethyl-5-oxo-4H-5, 6, 7, 8-tetrahydro-
benzo[b]pyran (4b): mp: 212oC, Yield: 90 %, IR (KBr): 3373,
2994, 2246, 1653, 1613, 1490 cm-1
, 1H NMR (400 MHz,
DMSO-d6): δ 7.34 (d, 2H, J = 8.40 Hz), 7.16 (d, 2H, J = 8.40
Hz), 7.07 (s, 2H), 4.18 (s, 1H), 2.48 (m, 2H), 2.26 (d, 1H,
J = 15.90 Hz), 2.10 (d, 1H, J = 15.90 Hz), 1.01 (s, 3H), 0.92 (s, 3H), 13
C NMR (100
MHz, DMSO): δ 196.17, 163.09, 158.93, 144.19, 131.55, 129.56, 128.74, 120.01,
117.13, 112.75, 58.20, 50.37, 35.54, 32.25, 28.75, 27.29, M. F: C18H17ClN2O2,
M. W: 329, MS (m/z): 330 (M +1)+.
2-Amino-3-cyano-4-(4-methoxy-phenyl)-7, 7-dimethyl-5-oxo-4H-5, 6, 7, 8-tetra-
hydrobenzo[b]pyran (4c): mp: 201oC, Yield: 85 %, IR (KBr):
3395, 2990, 2204, 1680, 1510, 1252 cm-1
, 1H NMR (400 MHz,
DMSO-d6): δ 7.15 (d, 2H, J = 8.70 Hz), 6.97 (s, 2H), 6.84
(d, 2H, J = 8.70 Hz), 4.37 (s, 1H), 3.78 (s, 3H), 2.43 (s, 2H),
2.22 (d, 1H, J = 16.0 Hz), 2.09 (d, 1H, J = 16.0 Hz), 1.04 (s, 3H), 0.97 (s, 3H),
13C NMR (100 MHz, DMSO): δ 195.60, 162.02, 158.47, 136.81, 128.15, 125.11,
O
O
CN
NH2
O
O
CN
NH2
Cl
O
O
CN
NH2
OCH3
159
119.72, 118.17, 113.61, 113.03, 58.65, 54.91, 50.06, 35.10 31.71, 28.37, 26.74,
M. F: C19H20N2O3, M. W: 324, MS (m/z): 325 (M + 1)+.
2-Amino-3-cyano-4-(2-chloro-phenyl)-7, 7-dimethyl-5-oxo-4H-5, 6, 7, 8-tetrahydro-
benzo[b]pyran (4d): mp: 202oC, Yield: 86 %, IR (KBr): 3379,
2994, 2195, 1682, 1481 cm-1
, 1H NMR (400 MHz, DMSO-d6):
δ 7.36-7.13 (m, 4H), 7.01 (s, 2H), 4.67 (s, 1H), 2.48 (m, 2H),
2.26 (d, 1H, J = 15.90 Hz), 2.07 (d, 1H, J = 15.90 Hz), 1.03 (s, 3H), 0.96 (s, 3H),
13C NMR (100 MHz, DMSO): δ 196.04, 163.62, 159.12, 142.02, 132.52, 130.40,
129.90, 128.67, 127.89, 119.70, 115.10, 112.21, 50.37, 45.77, 33.28, 32.21, 28.85,
27.31, M. F: C18H17ClN2O2, M. W: 329, MS (m/z): 330 (M + 1)+.
2-Amino-3-cyano-4-(4-nitro-phenyl)-7, 7-dimethyl-5-oxo-4H-5, 6, 7, 8-tetrahydro-
benzo[b]pyran (4e): mp: 180oC, Yield: 91 %, IR (KBr): 3394,
2970, 2193, 1683, 1523, 1365 cm-1
, 1H NMR (400 MHz,
DMSO-d6): δ 8.18-8.16 (m, 2H), 7.46-7.44 (m, 2H), 7.20 (s, br,
2H), 4.39 (s, 1H), 2.57 (m, 2H), 2.30 (d, 1H, J = 16.0 Hz), 2.14
(d, 1H, J = 16.0 Hz), 1.06 (s, 3H), 0.99 (s, 3H), 13
C NMR (100 MHz, DMSO): δ
196.21, 163.54, 159.07, 146.72, 129.06, 124.14, 121.71, 119.75, 115.12, 112.12,
57.47, 50.34, 40.42, 39.44, 32.20, 28.77, 27.46, M. F: C18H17N3O4, M. W: 339,
MS (m/z): 340 (M +1)+.
2-Amino-3-cyano-4-(4-hydroxy-phenyl)-7, 7-dimethyl-5-oxo-4H- 5, 6, 7, 8-tetra-
hydrobenzo[b]pyran (4f): mp: 208oC, Yield: 82 %, IR (KBr):
3464, 3364, 2192, 1663, 1491 cm-1
, 1H NMR (400 MHz,
DMSO-d6): δ 11.59 (s, 1H), 7.22 (s, 2H), 6.91 (d, 2H, J = 7.0
Hz), 6.78 (d, 2H, J = 7.0 Hz), 4.35 (s, 1H), 2.48 (m, 2H), 2.19
(s, 2H), 1.00 (s, 3H), 0.925 (s, 3H), 13
C NMR (100 MHz, DMSO): δ 195.95, 156.10,
O
O
CN
NH2
OH
O
O
CN
NH2
Cl
O
O
CN
NH2
NO2
160
140.19, 135.61, 129.45, 128.45, 126.13, 115.01, 114.02, 112.11, 50.69, 45.10, 34.78,
32.07, 28.10, 27.52, M. F: C18H18N2O3, M. W: 310, MS (m/z): 311 (M + 1)+.
2-Amino-3-cyano-4-(3-nitro-phenyl)-7, 7-dimethyl-5-oxo-4H-5, 6, 7, 8-tetrahydro-
benzo[b]pyran (4g): mp: 212oC, Yield: 85 %, IR (KBr): 3313,
3003, 2200, 1683, 1513, 1355 cm-1
, 1H NMR (400 MHz,
DMSO-d6): δ 8.02-7.61 (m, 4H), 7.18 (s, br, 2H), 4.42 (s, 1H),
2.55 (m, 2H), 2.28 (d, 1H, J = 16.0 Hz), 2.13 (d, 1H, J = 16.0
Hz), 1.06 (s, 3H), 0.96 (s, 3H), 13
C NMR (100 MHz, DMSO): δ 196.34, 163.63,
159.09, 148.23, 147.44, 134.63, 130.48, 122.23, 122.09, 121.21, 119.80, 112.23,
53.66, 50.32, 35.86, 32.28, 28.77, 27.19, M. F: C18H17N3O4, M. W: 339, MS (m/z):
340 (M +1)+.
2-Amino-3-cyano-4-(2-nitro-phenyl)-7, 7-dimethyl-5-oxo-4H-5, 6, 7, 8-tetrahydro-
benzo[b]pyran (4h): mp: 227oC, Yield: 88 %, IR (KBr): 3302,
3195, 2193, 1687, 1664, 1596, 1524 cm-1
, 1H NMR (400 MHz,
DMSO-d6): δ 7.82 (d, 1H, J = 8.40 Hz), 7.68-7.64 (m, 1H),
7.44-7.41 (m, 1H), 7.38 (d, 1H, J = 8.40 Hz), 7.20 (s, br, 2H),
4.93 (s, 1H), 2.55 (m, 2H), 2.24 (d, 1H, J = 16.0 Hz), 2.04 (d, 1H, J = 16.0 Hz), 1.02
(s, 3H), 0.91 (s, 3H), 13
C NMR (100 MHz, DMSO): δ 196.32, 163.24, 159.65, 149.41,
135.15, 130.72, 128.35, 124.11, 120.13, 119.55, 114.12, 112.74, 50.06, 42.51, 35.46,
32.37, 28.72, 27.11, M. F: C18H17N3O4, M. W: 339, MS (m/z): 340 (M +1)+.
2-Amino-3-cyano-4-(3-chloro-phenyl)-7, 7-dimethyl-5-oxo-4H-5, 6, 7, 8-tetrahydro-
benzo[b]pyran (4i): mp: 230oC, Yield: 87 %, IR (KBr): 3391,
3182, 2192, 1662, 1630, 1600, 1483 cm-1
, 1H NMR (400 MHz,
DMSO-d6): δ 7.32-7.10 (m, 4H), 7.09 (s, 2H), 4.21 (s, 1H),
2.53 (m, 2H), 2.27 (d, 1H, J = 15.90 Hz), 2.25 (d, 1H, J = 15.90
O
O
CN
NH2
NO2
O
O
CN
NH2
NO2
O
O
CN
NH2
Cl
161
Hz), 1.11 (s, 3H), 1.07 (s, 3H), 13
C NMR (100 MHz, DMSO): δ 196.22, 163.34,
159.01, 147.66, 140.27, 135.37, 130.72, 127.54, 126.40, 120.12, 119.91, 112.55,
50.33, 42.54, 36.40, 32.36, 28.71, 27.23, M. F: C18H17ClN2O2, M. W: 329, MS (m/z):
330 (M + 1)+.
2-Amino-3-cyano-4-(4-methyl-phenyl)-7, 7-dimethyl-5-oxo-4H-5, 6, 7, 8-tetrahydro-
benzo[b]pyran (4j): mp: 214oC, Yield: 92 %, IR (KBr): 3324,
2957, 2193, 1684, 1602, 1480 cm-1
, 1H NMR (400 MHz,
DMSO-d6): δ 7.09 (d, 2H, J = 8.0 Hz ), 7.02 (d, 2H, J = 8.0
Hz), 6.97 (s, 2H), 4.34 (s, 1H), 2.51 (m, 2H), 2.24 (s, 3H), 2.26
(d, 1H, J = 16.0 Hz), 2.11 (d, 1H, J = 16.0 Hz), 1.03 (s, 3H), 0.94 (s, 3H), 13
C NMR
(100 MHz, DMSO): δ 196.12, 162.73, 158.94, 142.27, 136.13, 129.35, 127.51,
120.20, 118.31, 113.34, 50.43, 41.51, 37.44, 32.22, 28.87, 27.23, 21.04, M. F:
C19H20N2O2, M. W: 308, MS (m/z): 309 (M + 1)+.
O
O
CN
NH2
162
Fig. 4.4: 1H NMR spectrum of 4a compound
Fig. 4.5: 13
C NMR spectrum of 4a compound
O
CN
NH2
O
CH3CH3
H1
H3
H2
H1
H2
H4
6
5
O
CN
NH2
O
CH3CH3
H1
H3
H2
H1
H2
H4
6
5
163
Fig. 4.6: Mass spectrum of 4d compound
O
O
CN
NH2
Cl
164
Section-B
An Efficient Synthesis of Acridinediones Using CdO Nanoparticles as Catalyst
Under Solvent Free Condition
4.1B. Introduction:
Acridinediones and their derivatives are polyfunctionalized 1, 4-
dihydropyridine derivatives which are bioactive compounds such as vasodilator,
bronchodilator, anti-atherosclerotic, anti-cancer, and antidiabetic agents406, 407
.
Derivatives of 1, 4-dihydropyridine are employed as potential drug for the treatment
of congestive heart failure408
. Acridinediones and their derivatives possess a wide
range of pharmaceutical activities including antitumor409
, antimicrobial410
,
antibacterial411
, antimalarial412
, DNA binding413
, and fungicidal properties414
. In
addition acridinediones exhibit important properties like high fluorescence efficiency
allowing them to be used as laser dyes415
. 1, 4-Dihydropyridine derivatives show very
high lasing efficiency therefore used as photoinitiators416
, and important core for
many bioactive compounds417
. It has antiaggregatory activity so used in Alzheimer
disease418
and also have calcium channel blocking activity419
. Due to importance of
such activities and properties a number of methods for the synthesis of acridinedione
derivatives have been reported.
Sangshetti et al420
have reported the water mediated oxalic acid catalyzed one
pot synthesis of 1, 8-dioxodecahydroacridines from condensation of aromatic
aldehydes, cyclic diketones, and ammonium acetate (Scheme 26).
165
Scheme 26
Wang et al421
have reported the synthesis of acridinediones under thermal
heating condition from the condensation reaction of aromatic aldehydes, dimedone,
and ammonium acetate (Scheme 27).
Scheme 27
Moeinpour et al422
have reported synthesis of 1, 8-dioxodecahydroacridines
via one pot three component condensation reaction using silica gel supported
polyphosphoric acid (Scheme 28).
Scheme 28
To et al423
have reported efficient one pot synthesis of acridinediones through
the reaction between dimedone, aromatic aldehyde, and ammonium acetate or anilline
using Indium (III) triflate as catalyst (Scheme 29).
CHO
R
+
O
OR2
R3
2 + NH4OAc
NH
R2R3R3
R2
O O
R
oxalic acid (20 mol %)
ref lux ( 60-80 min)
CHO
R
+
O
OR2
R3
2 + NH4OAc
NH
R2R3R3
R2
O O
R
solvent f ree
1200C, 1.5h
CHO
R
+
O
OR2
R3
2 + NH4OAc
NH
R2R3R3
R2
O O
R
PPA-SiO 2
solvent f ree, 1000C
166
Scheme 29
Davoodnia et al424
have reported carbon based solid acid (CBSA) as reusable,
and efficient catalyst for the synthesis of 1, 8-dioxodecahydroacridines under solvent
free condition (Scheme 30).
Scheme 30
Ziarani et al425
have reported as an efficient catalyst for the synthesis of 1, 8-
dioxodecahydroacridines under solvent free condition using sulfonic acid
functionalized silica catalyst (Scheme 31).
Scheme 31
Vahdat et al426
have reported synthesis of 1, 8-dioxodecahydroacridines under
ambient temperature in ethanol solvent using Indium (III) chloride as catalyst
(Scheme 32).
CHO
R
+
O
OR
R
2 + NH4OH or Ar-NH2
NRR
R
R
O O
R1
R
In(OTf )3
heating
CHO
R
+
O
O
2 + NH4OAc or Ar-NH2
N
O O
R
R
CBSA
solv ent f ree
CHO
R
+
O
O
2 + NH4OAc or R-NH2
N
O O
R
R
SiO2-Pr-SO3H
solv ent f ree
167
Scheme 32
Balalaie et al415
have reported synthesis of 1, 8-dioxodecahydroacridine
derivatives using ammonium chloride or Zn(OAc)2 2H2O or l-proline in water
(Scheme 33).
Scheme 33
The silica gel supported ferric chloride427
, ceric ammonium nitrate in presence
of polyethylene glycol419
, and silica bonded s-sulfonic acid428
are used as a catalyst
for the synthesis of 1, 8-dioxodecahydroacridine derivatives. However, many of these
methods suffered from some drawbacks such as low yield, long reaction time, drastic
reaction conditions, and tedious work up. Occurrence of several side reaction and in
some cases more than one step is involved in the synthesis of compound. Therefore,
there is a need for generation of new methodology with mild reaction conditions,
better yields, short reaction time, and environment friendliness. Now a day‟s metal
oxide nanoparticles are known to be promising material for the heterogeneous catalyst
in a variety of condensation reactions386
. The nanocrystalline CdO also reported as a
catalyst in a few organic transformations429
.
CHO
R2
+
O
O
2 + NH4OAc or R3-NH2
N
O O
R3
R2
InCl3, 1 mol %
C2H5OH, rt
CHO
R
+
O
O
2 + NH4OAc
N
O O
H
R
NH4Cl or Zn(OAc)2.2H2O
or L-proline
168
The CdO nanoparticles were used as catalyst for the synthesis of acridinedione
derivatives from condensation reaction between aromatic aldehydes, dimedone, and
ammonium acetate. The CdO nanoparticles have gained more importance in organic
transformations due to high thermal stability, large surface area, easy recovery, and
good ability to perform organic reactions at room temperature without solvent.
4.2B. Present work:
An efficient method for the synthesis of acridinedione derivatives was
developed under solvent free condition. The reaction between aromatic aldehydes,
dimedone, and ammonium acetate using synthesized nanocrystalline CdO as a
catalyst provided good yield of acridinedione derivatives (Scheme 34).
+
CHO
CdO nanoparticles
R1 2 3
4(a-i)
RO
O
+ NH4OAc
NH
O O
solvent free
1200C
Scheme 34: Synthesis of acridinediones
4.3B. Synthesis of acridinediones:
A mixture of dimedone (2.0 mmol), aromatic aldehyde (1.0 mmol),
ammonium acetate (1.0 mmol), and CdO nanoparticles (60 mg) were heated in an oil
bath at 120oC (Scheme 34). The reaction was monitored by thin layer
chromatography. After completion of reaction, the crude product was collected after
cooling to room temperature and recrystallized from ethanol to furnish compounds
4 (a-i) in high yields. The formation of product was confirmed by comparison of their
physical and spectral data with the authentic samples reported in literature. The
catalyst was separated by filtration, dried at 100oC, and reused for similar reaction.
All the products were characterized by IR, 1H NMR, and mass spectrometry.
169
4.4B. Results and Discussion:
Initially, the three component reaction of dimedone (2.0 mmol), benzaldehyde
(1.0 mmol), and ammonium acetate (1.0 mmol) was carried out in presence of CdO
nanoparticles used as a model reaction to optimize the amount of catalyst. No product
was obtained in the absence of the catalyst even after 60 mins indicating that the
catalyst is necessary for the reaction. It was observed that with increase in amount of
catalyst, the reaction rate, and yield of products was increased. The optimum amount
of the catalyst was found to be 60 mg to proceeds the reaction (Table 4.7). The
increase in the amount of the catalyst beyond optimum amount did not increase the
yield noticeably.
The reaction was carried out in different solvents, under solvent free condition
to study the effect of solvents and temperature on the reaction (Table 4.8). The yield
of reaction under solvent free reaction condition was greater, and short time was
required for completion of reaction. The reaction under solvent free condition was
carried out at different temperatures such as 80o, 100
o, and 120
oC. The best result was
obtained at 120oC for 8 mins under solvent free condition. A series of acridinedione
derivatives was synthesized by using CdO nanoparticles as a catalyst under solvent
free reaction condition (Table 4.9). In all cases aromatic aldehydes with substituents
carrying either electron donating or electron withdrawing groups reacted successfully,
and gave the expected product in excellent yield, and shorter reaction time. The
aromatic aldehydes with electron withdrawing groups react faster than electron
donating groups.
The catalytic efficiency was also checked by its reusability. The catalyst was
recovered, and used four times in a model reaction [dimedone (2.0 mmol),
benzaldehyde (1.0 mmol), and ammonium acetate (1.0 mmol) in presence of CdO]
170
Table 4.7. Optimization of catalyst amount
Entry Amount of catalyst (mg) Time (min) Yield (%)
1 20 10 84
2 40 9 89
3 60 8 92
4 80 8 92
5 100 8 92
Table 4.8. Effect of solvent, and temperature on the synthesis of acridinediones
Entry Solvent Temperature (oC) Time (min) Yield
(%)
1 MeOH 60 210 80
2 EtOH 70 207 82
3 CH3CN 82 202 70
4 H2O 100 194 60
5 Solvent free 80 12 81
6 Solvent free 100 10 89
7 Solvent free 120 8 92
171
Table 4.9. Synthesis of acridinediones in presence of CdO nanoparticles
Entry Product
(R)
Time (min) Yield (%) M. P. (oC)
4a H 8 92 278
4b 2-Cl 16 91 221
4c 4-Cl 4 93 300
4d 2-OCH3 14 88 294
4e 4-OCH3 12 90 272
4f 2-NO2 12 90 288
4g 4-NO2 4 95 286
4h 4-CH3 16 91 269
4i 4-OH 8 89 285
Table 4.10. Reusability of CdO nanoparticles
Cycles Time (min) Yield (%)
1 8 92
2 8 92
3 8 92
4 8 91
172
It was found that catalyst showed good results after four turns, and it showed the same
activity as fresh catalyst without any significant loss in its activity (Table 4.10).
The structure of all the synthesized compound was confirmed by IR, 1H NMR,
and mass spectrometry. Typical 1H NMR spectrum of compound 4g showed the
presence of -NH, -C=O, -CH3, and aromatic protons, which confirms the 3, 3, 6, 6-
tetramethyl-1, 8-dioxo-9-(4-nitrophenyl)-decahydroacridine compound (Fig. 4.7). The
structure of 4g compound was also confirmed by mass spectrum which shows the
(M+1)+
peak at 395 (Fig. 4.8). Similarly the formation of all other compounds was
confirmed on the basis of spectral data.
4.5B. Spectral data:
3, 3, 6, 6-Tetramethyl-1, 8-dioxo-9-(phenyl)-decahydroacridine (4a): mp: 278oC,
Yield: 92 %, IR (KBr): 3474, 2958, 1641, 1617, 1513 cm-1
,
1H NMR (400 MHz, DMSO-d6): δ 9.41 (s, 1H), 7.16-7.03
(m, 5H), 4.83 (s, 1H), 2.48-1.84 (m, 8H), 1.01 (s, 6H), 0.84
(s, 6H), M. F: C23H27NO2, M. W: 349, MS (m/z): 350
(M+1)+.
3, 3, 6, 6-Tetramethyl-1, 8-dioxo-9-(2-chlorophenyl)-decahydroacridine (4b): mp:
221oC, Yield: 91 %, IR (KBr): 3295, 1662, 1601, 1499,
1387, 1221 cm-1
, 1H NMR (400 MHz, DMSO-d6): δ 11.60
(s, 1H), 7.35-7.09 (m, 4H), 5.22 (s, 1H), 2.35-1.80 (m, 8H),
1.16 (s, 6H), 0.98 (s, 6H), M. F: C23H26ClNO2, M. W: 384,
MS (m/z): 385 (M+1)+.
NH
O O
NH
O OCl
173
3, 3, 6, 6-Tetramethyl-1, 8-dioxo-9-(4-chlorophenyl)-decahydroacridine (4c): mp:
300oC, Yield: 93 %, IR (KBr): 3250, 2960, 1653, 1608,
1489, 1367, 1223 cm-1
, 1H NMR (400 MHz, DMSO-d6): δ
11.78 (s, 1H), 7.28 (d, 2H, J = 8.0 Hz), 7.19 (d, 2H, J = 8.0
Hz), 5.22 (s, 1H), 2.23-1.99 (m, 8H), 1.11 (s, 6H), 0.96
(s, 6H), M. F: C23H26ClNO2, M. W: 384, MS (m/z): 385
(M+1)+.
3, 3, 6, 6-Tetramethyl-1, 8-dioxo-9-(2-methoxyphenyl)-decahydroacridine (4d):
mp: 294oC, Yield: 88 %, IR (KBr): 3310, 3032, 1637, 1605,
1486, 1364, 1224 cm-1
, 1H NMR (400 MHz, DMSO-d6): δ
11.30 (s, 1H), 7.01-6.76 (m, 4H), 5.25 (s, 1H), 3.80 (s, 3H),
2.30-2.02 (m, 8H), 1.03 (s, 6H), 0.92 (s, 6H), M. F:
C24H29NO3, M. W: 379, MS (m/z): 380 (M+1)+.
3, 3, 6, 6-Tetramethyl-1, 8-dioxo-9-(4-methoxyphenyl)-decahydroacridine (4e):
mp: 272oC, Yield: 90 %, IR (KBr): 3202, 2980, 1642, 1609,
1450, 1362, 1221 cm-1
, 1H NMR (400 MHz, DMSO-d6): δ
11.92 (s, 1H), 6.98 (d, 2H, J = 8.0 Hz), 6.78 (d, 2H, J = 8.0
Hz), 5.48 (s, 1H), 3.76 (s, 3H), 2.28-2.01 (m, 8H), 1.22
(s, 6H), 1.09 (s, 6H), M. F: C24H29NO3, M. W: 379, MS
(m/z): 380 (M+1)+.
3, 3, 6, 6-Tetramethyl-1, 8-dioxo-9-(2-nitrophenyl)-decahydroacridine (4f): mp:
288oC, Yield: 90 %, IR (KBr): 3233, 2985, 1649, 1596,
1530, 1316, 1218 cm-1
, 1H NMR (400 MHz, DMSO-d6): δ
11.85 (s, 1H), 8.13-7.30 (m, 4H), 5.45 (s, 1H), 2.20-1.87
(m, 8H), 1.22 (s, 6H), 1.11 (s, 6H), M. F: C23H26N2O4,
NH
O O
Cl
NH
O OOCH3
NH
O O
OCH3
NH
O ONO2
174
M. W: 394, MS (m/z): 395 (M+1)+.
3, 3, 6, 6-Tetramethyl-1, 8-dioxo-9-(4-nitrophenyl)-decahydroacridine (4g): mp:
286oC, Yield: 95 %, IR (KBr): 3245, 2930, 1636, 1600,
1575, 1350, 1222 cm-1
, 1H NMR (400 MHz, DMSO-d6): δ
11.79 (s, 1H), 8.10 (d, 2H, J = 8.0 Hz), 7.22 (d, 2H, J = 8.0
Hz), 5.52 (s, 1H), 2.49-2.29 (m, 8H), 1.19 (s, 6H), 1.09
(s, 6H), M. F: C23H26N2O4, M. W: 394, MS (m/z):
395 (M+1)+.
3, 3, 6, 6-Tetramethyl-1, 8-dioxo-9-(4-methylphenyl)-decahydroacridine (4h): mp:
269oC, Yield: 91 %, IR (KBr): 3235, 2960, 1660, 1603,
1487, 1301, 1203 cm-1
, 1H NMR (400 MHz, DMSO-d6): δ
11.80 (s, 1H), 7.40 (d, 2H, J = 8.0 Hz), 7.01 (d, 2H, J = 8.0
Hz), 5.34 (s, 1H), 2.23 (s, 3H), 2.12-1.81 (m, 8H), 1.02
(s, 6H), 0.96 (s, 6H), M. F: C24H29NO2, M. W: 363, MS
(m/z): 364 (M+1)+.
3, 3, 6, 6-Tetramethyl-1, 8-dioxo-9-(4-hydroxyphenyl)-decahydroacridine (4i): mp:
285oC, Yield: 89 %, IR (KBr): 3201, 3005, 1614, 1512,
1472, 1371, 1222 cm-1
, 1H NMR (400 MHz, DMSO-d6): δ
12.25 (s, 1H), 11.01 (s, 1H), 6.81 (d, 2H, J = 8.0 Hz), 6.51
(d, 2H, J = 8.0 Hz), 4.60 (s, 1H), 2.42-2.04 (m, 8H), 1.09
(s, 6H), 0.98 (s, 6H), M. F: C23H27NO3, M. W: 365, MS
(m/z): 366 (M+1)+.
NH
O O
NO2
NH
O O
NH
O O
OH
175
Fig. 4.7: 1H NMR spectrum of 4g compound
Fig. 4.8: Mass spectrum of 4g compound
NH
O O
CH3 CH3CH3CH3
H1
NO2
H1
H2H2
H3
44
55
NH
O O
CH3 CH3CH3CH3
H1
NO2
H1
H2H2
H3
44
55
176
Section-C
PbS Nanoparticles as an Effective Catalyst for the One Pot Synthesis of
Amidoalkyl Naphthols Under Solvent Free Condition
4.1C. Introduction:
The biologically active 1-aminomethyl-2-naphthol derivatives can be obtained
from 1-amidomethyl-2-naphthols by amide hydrolysis reaction, which have activities
like hypotensive and brady cardiac effects430
. This 1-aminoalkyl alcohol type ligand is
used as catalyst and in asymmetric synthesis431
. Amidoalkyl naphthols are precursors
for the synthesis of oxazines which are present in variety of biologically important
natural products, potent drugs including a number of nucleoside antibiotics, HIV
protease inhibitors such as ritonavir, and lipinavir432-435
. 1-Amidoalkyl-2-naphthols
can be converted into 1, 3-oxazine derivatives which have potentially different
biological activities including antipsychotic436
, antimalarial437
, antihypertensive438
,
antibiotic, antitumor, and antirheumatic properties439
. Due to the importance of such
activities and properties a number of methods for the synthesis of amidoalkyl
naphthols have been reported in the literature.
Gokavi et al440
have reported the silicotungstic acid (H4SiW12O40) catalyzed
one pot synthesis of amidoalkyl naphthols from condensation of aromatic aldehydes,
2-naphthol, and acetamide (Scheme 35).
Scheme 35
Shinde et al441
have reported synthesis of amidoalkyl naphthols using oxalic
acid as catalyst under solvent free condition (Scheme 36).
OH
+ ArCHO + R CONH2OH
Ar NHCOR
5 mol%, H4SiW12O40
1100C
177
Scheme 36
Xie et al442
have reported one pot multi component synthesis of amidoalkyl
naphthols in presence of potassium hydrogen sulfate under solvent free condition
(Scheme 37).
Scheme 37
Khodaei et al443
have reported synthesis of amidoalkyl naphthols by
condensation reaction of aromatic aldehydes, 2-naphthol, and amides in the presence
of p-toluene sulfonic acid in 1, 2-dichloroethane at room temperature or under solvent
free condition (Scheme 38).
Scheme 38
Ashalua et al444
have reported synthesis of amidoalkyl naphthols using
magnesium sulphate as an efficient Lewis acid catalyst (Scheme 39).
Scheme 39
Hazeri et al445
have reported a one pot three component synthesis of
amidoalkyl naphthols catalyzed by succinic acid (Scheme 40).
OH
+ ArCHO + R CONH2OH
Ar NHCOR
oxalic acid (10 mol%)
solvent free, 1250C
OH
+ R1CHO + R2 CONH2OH
R1 NHCOR2
KHSO4
solvent free, 1000C
OH
+ ArCHO + R CONH2OH
Ar NHCOR
p-TSA
ClCH2-CH2Cl, rt
or neat conditions, 1250C
OH
+ R1CHO + R2 CONH2OH
R1 NHCOR2
MgSO4.7H2O
solvent free, 1000C
178
Scheme 40
Shaterian et al446
have reported synthesis of amidoalkyl naphthols and
carbamatoalkyl naphthols using P2O5/SiO2 as catalyst under solvent free condition
(Scheme 41).
Scheme 41
Aswin et al447
have reported synthesis of amidoalkyl naphthols under solvent
free conditions by ZrOCl2.8H2O recyclable catalyst (Scheme 42).
Scheme 42
Maheria et al448
have reported one pot synthesis of amidoalkyl naphthols using
zeolite H-BEA as heterogeneous catalyst (Scheme 43).
Scheme 43
Several Lewis, and Bronsted acids have been applied to catalyze this
transformation are such as silica gel supported-SO3H functionalized benzimidazolium
based ionic liquid449
, bismuth nitrate450
, amberlite IR-120451
, 1-hexanesulphonic
sodium salt452
, and sodium hydrogen sulfate453
etc. However, some of this catalyst
OH
+ ArCHO + R CONH2OH
Ar NHCOR
succinic acid (5 mol%)
solvent free, 1200C
OH
+ ArCHO + R CONH2OH
Ar NHCOR
P2O5/SiO2
solvent free, 1000C
OH
+ ArCHO + R2 CONH2OH
Ar NHCOR2
ZrOCl2.8H2O (2mol%)
solvent free, 800C
OH
+ ArCHO + OH
Ar NHCOCH3
CH3CONH2
zeolite H-BEA
179
suffers from the drawback of long reaction time, low yields, and use of solvents.
Therefore, the clean process, and heterogeneous green catalysts which can be simply
recycled at the end of the reaction have been under permanent attention.
An efficient and recyclable PbS nanocrystalline catalyst is used for the
synthesis of amidoalkyl naphthols from condensation reaction between aromatic
aldehydes, β naphthol, and acetamide under solvent free reaction condition at 120oC.
4.2C. Present work:
Amidoalkyl naphthol was synthesized using PbS nanoparticles under solvent
free condition by the reaction of aromatic aldehydes, β naphthol, and acetamide. A
series of amidoalkyl naphthols was synthesized in good yield (Scheme 44).
Scheme 44: Synthesis of amidoalkyl naphthols
4.3C. Synthesis of amidoalkyl naphthols:
To a mixture of β naphthol (1.0 mmol), aldehydes (1.0 mmol), and acetamide
(1.2 mmol) the PbS nanoparticles was added as a catalyst. The mixture was stirred
under solvent free condition at 120oC in oil bath for few minutes (Scheme 44). The
reaction was monitored by TLC. The crude product was collected after cooling, and
recrystallized from ethanol to give products 4(a-j) in high yields. The catalyst was
separated by filtration, dried at 100oC for 2 hrs, and reused for similar reaction. All
the products were characterized by IR, 1H NMR, and mass spectrometry. The
formation of product was confirmed by comparison of their physical, and spectral
data with the authentic samples reported in literature.
CHO
R
+OH
+NH2
OOH
NH
O
R
PbS nanoparticles
solvent free, 1200C
1 2 3
4(a-j)
180
4.4C. Results and Discussion:
A series of amidoalkyl naphthol derivatives were prepared by using PbS
nanoparticles as a catalyst (Table 4.11) with excellent yields (85-95 %). An ortho
substituted aromatic aldehydes decrease the yield of the reaction due to the steric
effect while meta and para substituted aromatic aldehydes gave good results. In all the
cases aromatic aldehydes with electron withdrawing groups or electron donating
groups reacted successfully and gave the products in high yields. It was shown that
the aromatic aldehydes with electron withdrawing groups reacted faster than the
aromatic aldehydes with electron releasing group. The reactions proceeds smoothly
and no undesirable side products were observed.
The three component one pot reaction of β naphthol (1.0 mmol), benzaldehyde
(1.0 mmol), acetamide (1.2 mmol), and PbS nanoparticles was used as a model
reaction to optimize amount of the catalyst. The reaction rate and yield was increased
with the amount of catalyst. It was found that 40 mg of the catalyst was appropriate
amount for completion of reaction (Table 4.12). Small amount of catalyst gave low
yield even after a long reaction time while more amounts did not cause a significant
increase in the yield of product.
The reusability of the catalyst is one of the most important benefits, and makes
it useful for commercial applications. The reusability of the PbS nanoparticles catalyst
was checked for model condition. The catalyst was found to be recovered and reused
for five times for a model reaction (Table 4.13).
The structure of all the synthesized compound was confirmed by IR, 1H NMR,
and mass spectrometry. Typical 1H NMR spectrum of compound 4a showed the
presence of -CH3, -NH, and phenolic -OH protons which confirms the formation of
181
Table 4.11. Synthesis of amidoalkyl naphthols in presence of PbS nanoparticles
Entry Product
(R)
Time (min) Yield (%) M. P.(oC)
4a H 6 95 242
4b 4-CH3 8 90 223
4c 4-Cl 5 92 224
4d 4-OCH3 8 89 185
4e 4-NO2 4 85 249
4f 3-NO2 5 89 240
4g 2-Cl 7 87 214
4h 2-NO2 9 86 181
4i 2-CH3 9 89 201
4j 3-OCH3 9 93 202
Table 4.12. Optimization of catalyst amount
Entry Amount of catalyst (mg) Time (min) Yield (%)
1 20 9 81
2 30 8 89
3 40 6 95
4 50 6 94
5 60 6 93
Table 4.13. Reusability of the catalyst
Cycles Yield (%)
1 95
2 95
3 95
4 94
5 93
182
N-[phenyl-(2-hydotroxynapthalen-1-yl)-methyl]-acetamide compound (Fig. 4.9). The
structure of 4e compound was confirmed by mass spectrum which shows the (M+1)+
peak at 337 (Fig. 4.10). Similarly the formation of all other compounds was
confirmed on the basis of their spectral data.
4.5C. Spectral data:
N-[Phenyl-(2-hydroxynapthalen-1-yl)-methyl]-acetamide (4a): mp: 242oC, Yield:
95 %, IR (KBr): 3406, 3243, 3067, 1642, 1587, 1511, 1374, 1067,
804, 746 cm-1
, 1H NMR (400 MHz, DMSO-d6): δ 9.85 (s, 1H),
8.29 (d, 1H, J = 8.50 Hz), 7.94-7.69 (m, 3H), 7.39-7.12 (m, 9H),
2.02 (s, 3H), M. F: C19H17NO2, M. W: 291, MS (m/z): 292
(M+1)+.
N-[(4-Methylphenyl-(2-hydroxynapthalen-1-yl)-methyl]-acetamide(4b): mp: 223oC,
Yield: 90 %, IR (KBr): 3418, 3315, 3068, 1620, 1597, 1560,
1467, 1394, 1057, 940, 884 cm-1
, 1H NMR (400 MHz, DMSO-
d6): δ 9.92 (s, 1H), 8.37 (d, 1H, J = 8.0 Hz), 7.83 (br, 1H), 7.79
(d, 1H, J = 8.0 Hz), 7.75 (d, 1H, J = 8.0 Hz), 7.35 (m, 1H), 7.25
(t, 1H, J = 7.10 Hz), 7.20 (d, 1H, J = 8.0 Hz), 7.09-7.03 (m, 5H), 2.21 (s, 3H), 1.96
(s, 3H), M. F: C20H19NO2, M. W: 305, MS (m/z): 306 (M+1)+.
N-[(4-Chlorophenyl-(2-hydroxynapthalen-1-yl)-methyl]-acetamide(4c): mp: 224oC,
Yield: 92 %, IR (KBr): 3391, 3350, 2961, 1636, 1577, 1491,
1437, 1374, 1091, 820, 746 cm-1
, 1H NMR (400 MHz, DMSO-
d6): δ 9.95 (s, 1H), 8.23 (d, 1H, J = 8.0 Hz), 7.71-7.61 (m, 3H),
7.67 (d, 1H, J = 8.0 Hz), 7.30-7.21 (m, 5H), 7.16-7.12 (m, 2H),
2.04 (s, 3H), M. F: C19H16ClNO2, M. W: 326, MS (m/z): 327 (M+1)+.
OH
NH
O
OH
NH
O
OH
NH
OCl
183
N-[(4-Methoxyphenyl)-(2-hydroxynapthalen-1-yl)-methyl]-acetamide (4d): mp:
185oC, Yield: 89 %, IR (KBr): 3393, 3252, 3065, 1692,
1584, 1511, 1434, 1374, 1083, 984 cm-1
, 1H NMR (400
MHz, DMSO-d6): δ 9.45 (s, 1H), 8.31 (d, 2H, J = 8.0 Hz),
7.80-7.74 (m, 2H), 7.51 (t, 2H, J = 7.30 Hz), 7.45-7.31
(m, 3H), 6.68 (s, 1H), 6.61 (d, 2H, J = 8.0 Hz), 3.52 (s, 3H), 2.01 (s, 3H), M. F:
C20H19NO3, M. W: 321, MS (m/z): 322 (M+1)+.
N-[(4-Nitrophenyl)-(2-hydroxy-napthalen-1-yl)-methyl]-acetamide (4e): mp: 249oC,
Yield: 85 %, IR (KBr): 3375, 3260, 3094, 1677, 1571, 1544,
1457, 1091, 837 cm-1
, 1H NMR (400 MHz, DMSO-d6): δ
9.82 (s, 1H), 8.50 (d, 1H, J = 8.0 Hz), 8.00-7.88 (m, 3H),
7.73 (d, 2H, J = 8.0 Hz), 7.64-7.55 (m, 2H), 7.31-7.14 (m,
4H), 2.05 (s, 3H), M. F: C19H16N2O4, M. W: 336, MS (m/z): 337 (M+1)+.
N-[(3-Nitrophenyl)-(2-hydroxy-napthalen-1-yl)-methyl]-acetamide (4f): mp: 240oC,
Yield: 89 %, IR (KBr): 3373, 3224, 2921, 1647, 1573, 1438,
1374, 1039, 1002, 924, 809 cm-1
, 1H NMR (400 MHz, DMSO-d6):
δ 10.11 (s, 1H), 8.54 (d, 1H, J = 8.0 Hz), 7.79-7.77 (m, 5H), 7.64
(d, 1H, J = 8.0 Hz), 7.20-7.16 (m, 5H), 2.07 (s, 3H), M. F:
C19H16N2O4, M. W: 336, MS (m/z): 337 (M+1)+.
N-[(2-Chlorophenyl)-(2-hydroxy-napthalen-1-yl)-methyl]-acetamide (4g):
mp: 214oC, Yield: 87 %, IR (KBr): 3325, 3062, 1647, 1513, 1267,
809 cm-1
, 1H NMR (400 MHz, DMSO-d6): δ 9.77 (s, 1H), 8.50
(s, 1H), 8.00 (t, 1H, J = 7.0 Hz), 7.77 (d, 1H, J = 7.0 Hz), 7.71
(d, 1H, J = 7.0 Hz), 7.54-7.07 (m, 8H), 1.92 (s, 3H), M. F: C19H16ClNO2, M. W: 326,
MS (m/z): 327 (M+1)+.
OH
NH
OH3CO
OH
NH
OO2N
OH
NH
O
NO2
OH
Cl
NH
O
184
N-[(2-Nitrophenyl)-(2-hydroxy-napthalen-1-yl)-methyl]-acetamide (4h): mp: 181oC,
Yield: 86 %, IR (KBr): 3370, 3234, 3104, 1677, 1573, 1312,
1039 cm-1
, 1H NMR (400 MHz, DMSO-d6): δ 9.71 (s, 1H), 8.52
(d, 1H, J = 8.30 Hz), 8.04 (d, 1H, J = 8.30 Hz), 7.91 (d, 1H,
J = 8.30 Hz), 7.83-7.71 (m, 4H), 7.40-7.12 (m, 5H), 2.02 (s, 3H),
M. F: C19H16N2O4, M. W: 336, MS (m/z): 337 (M+1)+.
N-[(2-Methylphenyl-(2-hydroxynapthalen-1-yl)-methyl]-acetamide (4i): mp: 201oC,
Yield: 89 %, IR (KBr): 3384, 3264, 2933, 1677, 1570, 1507,
1316, 1050 cm-1
, 1H NMR (400 MHz, DMSO-d6): δ 9.84 (s, 1H),
8.38 (d, 1H, J = 8.0 Hz), 7.78-7.60 (m, 4H), 7.22-6.48 (m, 7H),
2.23 (s, 3H), 1.97 (s, 3H), M. F: C20H19NO2, M. W: 305, MS
(m/z): 306 (M+1)+.
N-[(3-Methoxyphenyl)-(2-hydroxynapthalen-1-yl)-methyl]-acetamide(4j):
mp: 202oC, Yield: 93 %, IR (KBr): 3382, 3262, 3081, 1682,
1566, 1237, 1025 cm-1
, 1H NMR (400 MHz, DMSO-d6): δ 9.84
(s, 1H), 8.10-8.07 (m, 2H), 7.77-7.71 (m, 2H), 7.32-6.93 (m, 7H),
6.74 (s, 1H), 3.60 (s, 3H), 2.05 (s, 3H), M. F: C20H19NO3, M. W:
321, MS (m/z): 322 (M+1)+.
OH
NH
O
OCH3
OH
NH
O
OH
NO2
NH
O
185
Fig. 4.9: 1H NMR spectrum of 4a compound
Fig. 4.10: Mass spectrum of 4e compound
OH
H1
H2H3
H4
H5
H8
H9
H10
CH3
H6
NH
O H11
H7
H12
OH
NH
OO2N
186
Section-D
ZnS Nanoparticles as an Efficient Solid Catalyst for Synthesis of 5-Arylidene
Barbituric Acid Under Solvent Free Condition
4.1D. Introduction:
The 5-alkylidene or arylidene barbituric acid derivatives are important
members of the pyrimidine family. The barbituric acids are an excellent target
compound for organic and medicinal chemists due to their diverse biological activity
and coverage of a broad chemical space454
. Due to their ready availability and various
functionalization possibilities, the parent barbituric acid and 2-thiobarbituric acid are
convenient starting compounds for the preparation of different fused heterocycles and
their derivatives which are pharmacologically the most important class of barbituric
acid-based compounds455, 456
. Barbitals (5, 5-diethyl barbituric acid) possess sedative
and hypnotic activity457
.
Arylidene-pyrimidine-2, 4, 6-trione, arylidene-2-thioxodihydropyrimidine-4,
6-dione, and its derivatives are compounds which have variety of pharmacological
activities458
. They also possess biological activities such as hypotensive, tranquilizer,
and good antibacterial agents459
. Some barbituric acid derivatives have been widely
used as anticonvulsant, antispasmodic, and local anaesthetic agents460
. Benzylidene
barbituric acids are useful as potential organic oxidizers461
, unsymmetrical synthesis
of disulfides458
, and they have been recently studied as non linear optical materials462
.
Benzylidene barbiturates are also used as a safe tyrosinase inhibitors463
. Thus the
synthesis of arylidene barbituric acid derivatives is recently of very much importance.
There are several reported methods in the literature for the synthesis of arylidene
barbituric acid derivatives.
187
Khalafi-Nezhad et al464
have reported the basic alumina catalyzed synthesis of
arylidene barbituric acid derivatives in presence of microwave irradiation
(Scheme 45).
Scheme 45
Kikelj et al465
have reported the synthesis of arylidene barbituric acid
derivatives in presence of water at reflux condition (Scheme 46).
Scheme 46
Mashaly et al466
have reported condensation of thiobarbituric, and barbituric
acids with aromatic aldehydes in water using ethanolamine or sodium p-toluene
sulfonate as catalyst (Scheme 47).
Scheme 47
Thirupathi et al467
has reported synthesis of barbituric and thiobarbituric acid
derivatives using an efficient L-tyrosine as a catalyst in aqueous medium at room
temperatute (Scheme 48).
ArCHO +NHNH
O O
O
MW irradiation
basic alumina, 3-5 min
NHNH
O O
O
Ar
ArCHO +NHNH
O O
O
NHNH
O O
O
Ar
water, reflux 12 h
ArCHO +NHNH
O O
O
NHNH
O O
O
Ar
H2O, EA
stirr, rt
188
ArCHO +NHNH
O O
O
NHNH
O O
O
Ar
w ater / 8-16 min.
L-tyrosine / R T
X= O / S X= O / S
Scheme 48
Delgado et al468
have reported synthesis of benzylidene barbituric acids
promoted by infrared irradiation under solvent free condition (Scheme 49).
Scheme 49
Rathod et al469
have reported synthesis of 5-arylidine barbituric acid
derivatives in microwave using metal oxides containing cerium, Mg, and Zr metals
[Ce1MgxZr1-xO2] as solid heterogeneous catalyst (Scheme 50).
Scheme 50
Li et al
470 have reported synthesis of the derivatives of 5-arylidene barbituric
acid catalyzed by aminosulfonic acid with grinding method (Scheme 51).
Scheme 51
ArCHO +NHNH
O O
O
NHNH
O O
O
Ar
IR lamp
ArCHO +NHNH
O O
O
NHNH
O O
O
Ar
CMZO (1:0.6:0.4)
450 W
ArCHO +NHNH
O O
O
NHNH
O O
O
Ar
H2NSO3H, rt
grinding
189
Bhuyan et al471
have reported synthesis of 5-alkylated barbituric acids through
microwave assisted three component reaction in solvent free condition using Hantzsch
1, 4-dihydropyridines as reducing agents (Scheme 52).
Scheme 52
Several catalysts have been applied to catalyze this transformation such as
SiO2.12WO3.24H2O472
, ionic liquid473
, nickel nanoparticles474
, and LaCl3.7H2O475
etc.
However, some of these catalysts suffers from the drawback of long reaction time,
low yields, and are toxic. Therefore, solvent free clean process, and heterogeneous
green catalysts which can be simply recycled at the end of the reactions have been
under permanent attention.
Nanoparticles have the potential for improving the efficiency, selectivity, and
yield of catalytic processes. Recently, nanocrystalline ZnS was used as a catalyst in
organic synthesis476
. To explore the catalytic activity of ZnS nanoparticles in organic
synthesis, herein a simple synthesis of 5-arylidene barbituric acid derivatives using
ZnS nanoparticles as reusable catalyst under solvent free condition with grinding at
room temperature has been reported.
4.2D. Present work:
An efficient method for the synthesis of 5-arylidene barbituric acid derivatives
is developed under solvent free condition by grinding method at room temperature
using ZnS nanoparticles. The reaction between aromatic aldehydes, and barbituric
acid using synthesized nanocrystalline ZnS as a catalyst provided good yield of the
products (Scheme 53).
CHO
R
+NHNH
O
O O
NHNH
O
O O
Ar
dihydropyridines
MW
190
+
CHO
ZnS nanoparticles
catalystgrinding, rt
R1 2 3(a-i)
NHNH
O O
O NHNH
O O
O
R
Scheme 53: Synthesis of 5-arylidene barbituric acid derivatives
4.3D. Synthesis of 5-arylidene barbituric acids:
Aromatic aldehydes (1.0 mmol) and barbituric acid (1.0 mmol) were mixed
with ZnS nanoparticles as a catalyst (40 mg) in a beaker at room temperature. The
reaction mixture was grounded, and progress of reaction was monitored by thin layer
chromatography technique. The crude product was collected and recrystallized from
ethanol to give pure products 3(a-i) in high yields. The catalyst was separated by
filtration, dried at 110oC for 2 hrs and reused for similar reaction. All the products
were characterized by IR, 1H NMR,
13C NMR, and mass spectrometry.
4.4D. Results and Discussion:
The reaction between benzaldehyde (1.0 mmol) and barbituric acid (1.0 mmol)
was used as a model reaction to optimize the amount of catalyst. It was found that 40
mg of ZnS nanoparticles was the appropriate quantity of the catalyst to offer the
reaction (Table 4.14). All reactions were performed by grinding method at room
temperature, and were completed within 2-7 mins. A blank reaction of benzaldehyde
and barbituric acid was performed to confirm the effectiveness of ZnS nanoparticles.
In absence of ZnS nanoparticles the reaction was incomplete even after 2 hrs. After
optimizing the reaction conditions a variety of aromatic aldehydes were reacted with
barbituric acid under similar reaction condition to evaluate the scope of this reaction.
A series of 5-arylidene barbituric acid derivatives were prepared by using ZnS
nanoparticles as a catalyst (Table 4.15) with excellent yields (89-96 %) at room
191
temperature. The reaction proceeds smoothly and no undesirable side reactions were
observed. The nature of substituents on the aromatic ring does not affect on the
condensation reaction. The condensation reactions of aromatic aldehydes carrying
electron donating or electron drawing groups were also successfully carried out with
this method in excellent yields and short reaction time.
The catalytic efficiency of ZnS nanoparticles was also checked by its
reusability. It was found that catalyst showed good results after four successive runs
without any significant loss in its activity (Table 4.16).
The structure of all of the synthesized compound was confirmed by IR, 1H
NMR, 13
C NMR, and mass spectrometry. Typical 1H NMR spectrum of compound 3e
showed the presence of -NH, phenolic -OH, and aromatic protons which confirms the
formation of 5-(4-hydroxybenzylidene) barbituric acid (Fig. 4.11). 13
C NMR showed
peaks at 164.01, 163.16, and 162.02 δ due to –C=O carbon and 156.25 δ due to
carbon attached to phenolic -OH group which confirms the formation of compound 3e
(Fig. 4.12). The structure of 3a compound was confirmed by its mass spectrum which
shows the (M+1)+ peak at 217 (Fig. 4.13). Similarly the formation of all other
compounds was confirmed on the basis of their spectral data.
192
Table 4.14. Optimization of catalyst amount
Entry Amount of catalyst (mg) Time (min) Yield (%)
1 10 5 87
2 20 4 89
3 30 3 91
4 40 2 92
5 50 2 92
6 60 2 92
Table 4.15. Synthesis of 5-arylidene barbituric acids using ZnS nanoparticles
Entry Product
(R group)
Time (min) Yield (%) M. P. (oC)
3a H 2 92 263
3b 4-Cl 3 94 299
3c 4-CH3 7 93 279
3d 4-Br 2 95 293
3e 4-OH 3 96 >300
3f 3-NO2 4 88 246
3g 4-NO2 2 94 294
3h 4-OCH3 3 89 277
3i 2-Cl 3 90 253
Table 4.16. Reusability of ZnS nanoparticles catalyst
Cycles Yield (%)
1 92
2 92
3 91
4 89
193
4.5D. Spectral data:
5-Benzylidenebarbituric acid (3a): mp: 263oC, Yield: 92 %, IR (KBr): 3459, 3219,
3062, 1747, 1565 cm-1
, 1H NMR (400 MHz, DMSO-d6): δ 11.22
(s, 1H), 11.10 (s, 1H), 10.58 (s, 1H), 8.33-8.27 (m, 3H), 6.85
(d, 2H, J = 7.10 Hz), 13
C NMR (100 MHz, DMSO): δ 163.6, 162.2,
155.7, 150.4, 133.7, 133.3, 132.4, 128.3, 119.2, M. F: C11H8N2O3,
M. W: 216, MS (m/z): 217 (M+1)+.
5-(4-Chlorobenzylidene) barbituric acid (3b): mp: 299oC, Yield: 94 %, IR (KBr):
3430, 3214, 3087, 1752, 1675, 1578, 1090 cm-1
, 1H NMR (400
MHz, DMSO-d6): δ 11.37 (s, 1H), 11.20 (s, 1H), 8.24 (d, 2H,
J = 8.0 Hz), 8.07 (s, 1H), 7.51 (d, 2H, J = 8.0 Hz), 13
C NMR (100
MHz, DMSO): δ 163.6, 162.1, 153.4, 150.1, 137.5, 135.3, 132.1,
128.3, 120.2, M. F: C11H7ClN2O3, M. W: 251, MS (m/z): 252 (M+1)+.
5-(4-Methylbenzylidene) barbituric acid (3c): mp: 279oC, Yield: 93 %, IR (KBr):
3490, 3350, 3092, 1729, 1679, 1658, 1574 cm-1
, 1H NMR (400
MHz, DMSO-d6): δ 11.43 (s, 1H), 11.26 (s, 1H), 8.34 (s, 1H),
8.13-7.38 (m, 4H), 2.15 (s, 3H), 13
C NMR (100 MHz, DMSO): δ
163.8, 162.1, 155.7, 150.6, 143.8, 134.5, 130.2, 129.4, 118.1,
21.6, M. F: C12H10N2O3, M. W: 230, MS (m/z): 231 (M+1)+.
5-(4-Bromobenzylidene) barbituric acid (3d): mp: 293oC, Yield: 95 %, IR (KBr):
3495, 3360, 3090, 1737, 1672, 1561 cm-1
, 1H NMR (400 MHz,
DMSO-d6): δ 11.41 (s, 1H), 11.24 (s, 1H), 8.24 (s, 1H), 8.01-7.77
(m, 4H), 13
C NMR (100 MHz, DMSO): δ 165.11, 160.2, 153.2,
150.2, 134.5, 131.8, 131.1, 127.6, 119.7, M. F: C11H7BrN2O3,
M. W: 295, MS (m/z): 296 (M+1)+.
NHNH
O O
O
NHNH
O O
O
Cl
NHNH
O O
O
NHNH
O O
O
Br
194
5-(4-Hydroxybenzylidene) barbituric acid (3e): mp: >300oC, Yield: 96 %, IR (KBr):
3542, 3418, 3260, 3080, 1742, 1660, 1581, 1527, 1281 cm-1
,
1H NMR (400 MHz, DMSO-d6): δ 11.22 (s, 1H), 11.10 (s, 1H),
10.58 (s, 1H), 8.33-8.27 (m, 3H), 6.85 (d, 2H, J = 8.80 Hz),
13C NMR (100 MHz, DMSO): δ 164.01, 163.16, 162.02,
156.25, 150.09, 138.57, 123.65, 115.37, 113.45, M. F: C11H8N2O4, M. W: 232,
MS (m/z): 233 (M+1)+.
5-(3-Nitrobenzylidene) barbituric acid (3f): mp: 246oC, Yield: 88 %, IR (KBr): 3442,
3240, 3095, 1780, 1697, 1596, 1537, 1435 cm-1
, 1H NMR (400
MHz, DMSO-d6): δ 11.45 (s, 1H), 11.30 (s, 1H), 8.90 (s, 1H), 8.34
(s, 1H), 8.31-8.28 (m, 1H), 8.23-8.21 (m, 1H), 7.73 (t, 1H, J = 8.0
Hz), 13
C NMR (100 MHz, DMSO): δ 165.0, 162.4, 152.3, 150.4,
150.1, 145.0, 135.0, 133.4, 132.4, 131.2, 118.1, M. F: C11H7N3O5,
M. W: 261, MS (m/z): 262 (M+1)+.
5-(4-Nitrobenzylidene) barbituric acid (3g): mp: 294oC, Yield: 94 %, IR (KBr):
3323, 3242, 3095, 1742, 1692, 1596, 1517 cm-1
, 1H NMR (400
MHz, DMSO-d6): δ 11.46 (s, 1H), 11.30 (s, 1H), 8.31 (s, 1H),
8.23 (d, 2H, J = 8.70 Hz), 8.01 (d, 2H, J = 8.70 Hz), 13
C NMR
(100 MHz, DMSO): δ 165.2, 162.0, 157.3, 150.2, 136.4,
136.2, 135.1, 134.4, 118.1, M. F: C11H7N3O5, M. W: 261, MS (m/z): 262 (M+1)+.
5-(4-Methoxybenzylidene) barbituric acid (3h): mp: 277oC, Yield: 89 %, IR (KBr):
3401, 3233, 3094, 1712, 1672, 1546, 1206 cm-1
, 1H NMR
(400 MHz, DMSO-d6): δ 11.32 (s, 1H), 11.17 (s, 1H), 8.30
(s, 1H), 8.12-7.35 (m, 4H), 3.84 (s, 3H), 13
C NMR (100
MHz, DMSO): δ 164.4, 163.6, 162.7, 155.2, 150.2, 137.5,
NHNH
O O
O
OH
NHNH
O O
O
NO2
NHNH
O O
O
O2N
NHNH
O O
O
H3CO
195
125.4, 115.7, 114.2, 56.2, M. F: C12H10N2O4, M. W: 246, MS (m/z): 247 (M+1)+.
5-(2-Chlorobenzylidene) barbituric acid (3i): mp: 253oC, Yield: 90 %, IR (KBr):
3360, 3230, 3075, 1732, 1657, 1547 cm-1
, 1H NMR (400 MHz,
DMSO-d6): δ 11.56 (s, 1H), 11.29 (s, 1H), 8.33 (s, 1H), 7.77 (d, 1H,
J = 7.60 Hz), 7.72 (d, 1H, J = 7.60 Hz), 7.49 (d, 1H, J = 7.60 Hz),
7.38 (d, 1H, J = 7.60 Hz), 13
C NMR (100 MHz, DMSO): δ 162.7,
161.1, 150.9, 150.1, 133.6, 132.4, 132.1, 130.9, 129.4, 126.7, 122.3, M. F:
C11H7ClN2O3, M. W: 251, MS (m/z): 252 (M+1)+.
NHNH
O O
O
Cl
196
Fig. 4.11: 1H NMR spectrum of 3e compound
Fig. 4.12: 13
C NMR Spectrum of 3e compound
N
NO
O
O
H
H
H1
H2
H2' H3
H3' OH
N
NO
O
O
H
H
H1
H2
H2' H3
H3' OH
197
Fig. 4.13: Mass spectrum of 3a compound
NHNH
O O
O
198
Section-E
Comparative Study on Catalytic Efficiency of Synthesized Nanoparticles
Towards Synthesis of Pyranopyrazoles
4.1E Introduction:
Pyranopyrazoles and their derivatives are important class of heterocyclic
compounds due to their pharmacological and biological properties477
. They are widely
used in biodegradable agrochemicals and pharmaceutical ingredients478
.
Pyranopyrazoles exhibit biological properties such as anti-inflammatory, anticancer,
antimicrobial, analgesic activity, and act as a hypoglycemic, hypotensive, and
vasodilators agents479, 480
. The derivatives of pyranopyrazole have an affinity toward
A1 and A2a adenosine receptors481
. They also exhibits molluscicidal activity and used
as a screening kit for Chk1kinase inhibitor482
. Substituted pyranopyrazoles derivatives
have been found to be effective antiplatelet agents483
. Therefore, the synthesis of
pyranopyrazole derivatives is recently of much interest. There are several methods
reported in the literature for the synthesis of pyranopyrazoles.
Otto et al484
have reported a base catalyzed two component Michael type
reaction between 4-arylidiene-1-phenyl-1H-pyrazol-5-one and malononitrile for the
synthesis of various 4-aryl-4H-pyrano[2,3-c] pyrazoles (Scheme 54).
Scheme 54
O
NN
CN
NH2Ph
+CN
CN
R
N
N
OPh
R
EtOH
base
199
Shestopalov et al485, 486
have reported the synthesis of spiropyrazolopyran by
three component condensation between pyrazol-5-one, N-methylpiperidone and
malononitrile in absolute ethanol by heating or electrochemical method under an inert
atmosphere (Scheme 55).
Scheme 55
Bihani et al487
have reported the synthesis of dihydropyrano [2, 3-c] pyrazoles
by a four component reaction of ethyl acetoacetate, hydrazine hydrate, aldehyde, and
malononitrile in boiling water (Scheme 56).
Scheme 56
Pasha et al488
have reported synthesis of pyranopyrazoles at 25oC using iodine
as a catalyst through four component reaction of ethyl acetoacetate, hydrazine
hydrate, malononitrile, and aldehydes (Scheme 57).
Scheme 57
Mohammadi et al489
have reported synthesis of dihydropyranopyrazole
derivatives through a four component reaction of benzaldehyde, ethyl acetoacetate,
+CN
CNN
NH
O
+N
O
electrochemical
or heatingO
NNH
CN
NH2
N
NH2 NH2 +O
OEt
O
+ R CHO+CN
CN
O
NNH
R
CN
NH2
boiling water
NH2 NH2 +O
OEt
O
+ +CN
CN
O
NNH
CN
NH2
R
CHO
R
H2O
Iodine
200
hydrazine hydrate, and malononitrile in the presence of 3-methyl-1-(4-sulphonic acid)
butyl imidazolium hydrogen sulphate as a catalyst under solvent free condition
(Scheme 58).
Scheme 58
Bandgar et al490
have reported synthesis of pyranopyrazoles through one pot
four component reaction of ethyl acetoacetate, hydrazine hydrate, aldehydes, and
malononitrile in the presence of silicotungstic acid under solvent free condition
(Scheme 59).
Scheme 59
Peng et al491
have reported two component reaction involving pyran
derivatives, and hydrazine hydrate to obtain pyranopyrazoles in water using
combination of microwave, and ultrasonic irradiation (Scheme 60).
Scheme 60
Patel et al492
have reported microwave assisted multi component synthesis of
3 indolyl substituted pyranopyrazole derivatives, and their antimicrobial activity
(Scheme 61).
NH2 NH2 +O
OEt
O
+ R CHO+CN
CN ((CH2)4SO3HMIM)(HSO 4)
solvent f ree, rtO
NNH
R
CN
NH2
NH2 NH2 +O
OEt
O
+ R CHO+CN
CN
O
NNH
R
CN
NH2
silicotungstic acid
neat, 600C
NH2 NH2 +O
NNH
CN
NH2O
OEt
OCN
NH2
w ater, CMUI
piperidine
201
Scheme 61
However, some of these methods suffer from the drawback of long reaction
time, and low yield. Therefore, use of solvent free condition, heterogeneous, and
green catalysts is under permanent attention. Recently, nanocrystalline metal oxide,
and metal sulphide are used as a catalyst in organic synthesis476
. To explore the
catalytic activity of metal oxide and metal sulphide nanoparticle in organic synthesis,
the synthesis of pyranopyrazole derivatives using metal oxide, and metal sulphide
nanoparticles catalyst under solvent free condition with grinding at room temperature
has been reported.
4.2E. Present work:
A simple method for the synthesis of pyranopyrazole derivatives is developed
under solvent free condition by grinding method at room temperature using
synthesized PbO/CdO/PbS/ZnS nanoparticles, to compare the catalytic efficiency of
synthesized PbO/CdO/PbS/ZnS nanoparticles. The reaction between aromatic
aldehydes, hydrazine hydrate, ethyl acetoacetate, and malononitrile using synthesized
nanoparticles (PbO/CdO/PbS/ZnS) as a catalyst provided good yields of the products
(Scheme 62).
O
NNH
CN
NH2
NH2 NH2 +O
OEt
O
+
CHO
+CN
CN ZnS nanoparticles
catalystgrinding, rt
R
R1 2 3 4 5(a-h)
Scheme 62: Synthesis of pyranopyrazoles
+CN
CNN
NH
O
+ Ar CHO
O
NNH
CN
NH2
Ar
MWI
202
4.3E. Synthesis of pyranopyrazoles:
To compare the catalytic activity of synthesized nanoparticles the model
reaction was carried out in presence of PbO/CdO/PbS/ZnS nanoparticles catalyst. In a
model reaction mixture of hydrazine hydrate (1.0 mmol), ethyl acetoacetate
(1.0 mmol), catalyst (50 mg), aromatic aldehyde (1.0 mmol), and malononitrile
(1.0 mmol) was grinded at room temperature. The products were recrystallized using
hot ethanol to obtain the pure products. All the products were characterized by IR,
1H NMR, and mass spectrometry.
After optimization of the catalytic efficiency of PbO/CdO/PbS/ZnS
nanoparticles, a series of pyranopyrazoles was synthesized. To a mixture of hydrazine
hydrate (1.0 mmol) and ethyl acetoacetate (1.0 mmol), ZnS nanoparticle (50 mg) was
added, and stirred for few minutes. Then aldehyde (1.0 mmol) and malononitrile
(1.0 mmol) was added to it and the reaction mixture was grinded at room temperature.
After completion of reaction, the crude product was recrystallized from hot ethanol to
afford the pure products 5(a-h) in high yields. The catalyst was separated by filtration,
dried at 110oC for 2 hrs and reused for similar reaction. All the products were
characterized by IR, 1H NMR, and mass spectrometry.
4.4E. Results and Discussion:
The model reaction in presence of synthesized PbO/CdO/PbS/ZnS
nanoparticles reveals that among all these synthesized nanoparticles efficiency
towards synthesis of pyranopyrazoles, ZnS nanoparticles has more catalytic activity.
The catalytic activity of synthesized nanoparticles has order PbO < CdO < PbS < ZnS
for the synthesis of pyranopyrazoles (Table 4.17). This is due to average particle size
of the synthesized nanoparticles, and the average particle size of the synthesized
nanoparticles has order of PbO < CdO < PbS < ZnS (Table 4.18).
203
After optimizing the reaction conditions a variety of aromatic aldehydes with
hydrazine hydrate, ethyl acetoacetate, and malononitrile were employed under same
reaction condition to evaluate the scope of this reaction. A series of pyranopyrazoles
were prepared by using ZnS nanoparticles as a catalyst (Table 4.19) with excellent
yields at room temperature with grinding at solvent free condition. The reaction
proceeds efficiently by either electron releasing or electron withdrawing substituents
on aryl ring of aldehyde. In case of aromatic aldehydes the nature of substituents of
aromatic aldehydes did not have appreciable effect on overall yields of the product.
The electron deficient aldehydes gave excellent yield of products. The position (o, m
and p) of the substituted aromatic aldehydes did not show any noticeable effect on
either the reaction time or the yield.
The catalyst was filtered after completion of the reaction, washed with
ethanol, and heated at 120oC in oven for 2 hrs. The recovered catalyst was further
used in several successive runs under identical reaction condition. The catalyst shows
a good catalytic activity and stable even after five times (Table 4.20).
The structure of all the synthesized compound was confirmed by spectroscopic
techniques including IR, 1H NMR,
13C NMR, and mass spectrometry. Typical
1H NMR spectrum of compound 5a showed the presence of -NH, -NH2, and aromatic
protons which confirms the presence of 6-amino-3-methyl-4-phenyl-2, 4-
dihydropyrano [2, 3-c] pyrazoles-5-carbonitrile compound (Fig. 4.14). 13
C NMR
spectrum shows peaks at 154.72 and 120.75 δ due to carbon attached to -NH2 group,
and –CN carbon confirms the formation of compound 5a (Fig. 4.15). The structure of
5b compound was confirmed by its mass spectrum which shows the (M+1)+ peak at
298 (Fig. 4.16). Similarly the formation of all other compoundas was confirmed on
the basis of their spectral data.
204
Table 4.17. Comparison of catalytic activity of synthesized nanoparticles
Entry Synthesized
nanoparticles
Product
(R group)
Time
(min)
Yield
(%)
M. P.(oC)
5a
PbO
H 17 85 244
5b 4-OCH3 34 81 211
5c 4-NO2 10 92 195
5a
CdO
H 14 88 244
5b 4-OCH3 30 83 211
5c 4-NO2 8 94 195
5a
PbS
H 11 90 244
5b 4-OCH3 25 86 211
5c 4-NO2 7 96 195
5a
ZnS
H 8 92 244
5b 4-OCH3 21 88 211
5c 4-NO2 5 97 195
Table 4.18. Comparison between synthesized nanoparticles
Sr.
No.
Synthesized
nanoparticles
BET surface area
(m2/gm)
Band gap
energy
(eV)
Average
particle
size (nm)
1 PbO 29.38 3.13 69
2 CdO 29.71 3.64 47
3 PbS 15.65 4.20 31
4 ZnS 36.30 4.07 20
205
Table 4.19. Synthesis of pyranopyrazoles in presence of ZnS nanoparticles
Entry Product
(R group)
Time (min) Yield (%) M. P (oC)
5a H 8 92 244
5b 3-NO2 10 94 193
5c 4-NO2 5 97 195
5d 4-Br 11 96 206
5e 4-OCH3 21 88 211
5f 4-CH3 20 87 202
5g 4-OH 16 93 225
5h 4-Cl 20 96 175
Table 4.20. Reusability of ZnS catalyst
Cycles Yield (%)
1 92
2 92
3 92
4 91
5 90
206
4.5E. Spectral data:
6-Amino-3-methyl-4-phenyl-2,4-dihydropyrano[2,3-c]pyrazole-5-carbonitrile(5a):
mp: 244oC, Yield: 92 %, IR (KBr): 3370, 3307, 2190, 1609, 1591,
1441 cm-1
, 1H NMR (400 MHz, DMSO-d6): δ 12.08 (s, 1H), 7.33-
7.15 (m, 5H), 6.85 (s, 2H), 4.58 (s, 1H), 1.78 (s, 3H), 13
C NMR
(100 MHz, DMSO): δ 160.82, 154.72, 144.39, 135.51, 128.36,
127.43, 126.67, 120.75, 97.56, 57.15, 36.24, 9.71, M. F: C14H12N4O, M. W: 252, MS
(m/z): 253 (M+1)+.
6-Amino-3-methyl-4-(3-nitrophenyl)-2, 4-dihydropyrano [2, 3-c]pyrazole-5-carboni-
trile (5b): mp: 193oC, Yield: 94 %, IR (KBr): 3381, 3288, 2192,
1626, 1510, 1451 cm-1
, 1H NMR (400 MHz, DMSO-d6): δ 12.11
(s, 1H), 7.87 (s, 1H), 7.75 (d, 1H, J = 8.40 Hz), 7.46-7.40 (m, 2H),
6.91 (s, 2H), 4.95 (s, 1H), 1.81 (s, 3H), 13
C NMR (100 MHz,
DMSO): δ 165.1, 147.5, 145.8, 141.2, 135.1, 134.6, 130.5, 127.2, 124.1, 121.8, 98.1,
59.1, 32.0, 9.71, M. F: C14H11N5O3, M. W: 297, MS (m/z): 298 (M+1)+.
6-Amino-3-methyl-4-(4-nitrophenyl)-2, 4-dihydropyrano [2, 3-] pyrazole-5-carboni-
trile (5c): mp: 195oC, Yield: 97 %, IR (KBr): 3471, 3278, 3114,
2191, 1648, 1598, 1508, 1489 cm-1
, 1H NMR (400 MHz, DMSO-
d6): δ 12.21 (s, 1H), 8.25 (d, 2H, J = 8.70 Hz), 7.43 (s, 2H), 7.41
(d, 2H, J = 8.70 Hz), 4.87 (s, 1H), 1.78 (s, 3H), 13
C NMR (100
MHz, DMSO): δ 161.3, 154.2, 151.3, 146.7, 135.3, 128.1, 123.2,
120.7, 96.1, 35.1, 9.3, M. F: C14H11N5O3, M. W: 297, MS (m/z): 298 (M+1)+.
O
NNH
CN
NH2
O
N
NH
CN
NH2
NO2
O
N
NH
CN
NH2
NO2
207
6-Amino-3-methyl-4-(4-bromo)-2,4-dihydropyrano[2,3-c]pyrazole-5-carbonitrile
(5d): mp: 206oC, Yield: 96 %, IR (KBr): 3409, 3368, 2192, 1515,
1450 cm-1
, 1H NMR (400 MHz, DMSO-d6): δ 11.96 (s, 1H), 7.88-
6.96 (m, 4H), 6.83 (s, 2H), 4.97 (s, 1H), 1.62 (s, 3H), 13
C NMR
(100 MHz, DMSO): δ 161.3, 156.3, 148.7, 138.2, 137.2, 135.3,
130.3, 121.7, 97.6, 57.6, 27.4, 10.3, M. F: C14H11BrN4O, M. W:
331, MS (m/z): 332 (M+1)+.
6-Amino-4-(4-methoxyphenyl)-3-methyl-2,4-dihydropyrano[2,3-c]pyrazole-5-carbo-
nitrile (5e): mp: 211oC, Yield: 88 %, IR (KBr): 3478, 3247, 2180,
1596, 1448 cm-1
, 1H NMR (400 MHz, DMSO-d6): δ 12.13 (s, 1H),
7.12 (s, 2H), 6.82 (d, 2H, J = 8.20 Hz), 6.81 (d, 2H, J = 8.20 Hz),
4.64 (s, 1H), 3.86 (s, 3H), 1.74 (s, 3H), 13
C NMR (100 MHz,
DMSO): δ 160.1, 156.6, 155.1, 144.7, 136.2, 118.1, 114.8, 112.8,
107.8, 57.2, 54.7, 36.7, 10.5, M. F: C15H14N4O2, M. W: 282, MS (m/z): 283 (M+1)+.
6-Amino-4-(4-methyl)-3-methyl-2,4-dihydropyrano[2,3-c]pyrazole-5-carbonitrile
(5f): mp: 202oC, Yield: 87 %, IR (KBr): 3412, 3371, 2184, 1598,
1482 cm-1
, 1H NMR (400 MHz, DMSO-d6): δ 12.10 (s, 1H), 7.13
(d, 2H, J = 8.0 Hz), 7.06 (d, 2H, J = 8.0 Hz), 6.80 (s, 2H), 4.56
(s, 1H), 2.24 (s, 3H), 1.76 (s, 3H), 13
C NMR (100 MHz, DMSO):
δ 160.6, 154.3, 141.7, 135.2, 128.5, 124.3, 120.1, 118.6, 97.2, 57.6, 35.7, 20.5, 9.5, M.
F: C15H14N4O, M. W: 266, MS (m/z): 267 (M+1)+.
O
N
NH
CN
NH2
Br
O
NNH
CN
NH2
OCH3
O
N
NH
CN
NH2
208
6-Amino-4-(4-hydroxy)-3-methyl-2,4-dihydropyrano[2,3-c]pyrazole-5-carbonitrile
(5g): mp: 225oC, Yield: 93 %, IR (KBr): 3374, 3305, 2182, 1595,
1492 cm-1
, 1H NMR (400 MHz, DMSO-d6): δ 12.06 (s, 1H), 9.25
(s, 1H), 6.97 (d, 2H, J = 8.30 Hz), 6.81 (s, 2H), 6.70 (d, 2H,
J = 8.30 Hz), 4.46 (s, 1H), 1.78 (s, 3H), 13
C NMR (100 MHz,
DMSO): δ 160.4, 155.8, 154.6, 135.3, 134.3, 128.4, 120.6, 115.2,
97.7, 57.7, 35.5, 9.6, M. F: C14H12N4O2, M. W: 268, MS (m/z): 269 (M+1)+.
6-Amino-4-(4-chloro)-3-methyl-2,4-dihydropyrano[2,3-c]pyrazole-5-carbonitrile
(5h): mp: 175oC, Yield: 96 %, IR (KBr): 3372, 3225, 2183, 1621,
1520, 1486 cm-1
, 1H NMR (400 MHz, DMSO-d6): δ 12.12 (s, 1H),
7.35 (d, 2H, J = 8.30 Hz), 7.22 (d, 2H, J = 8.30 Hz), 6.91 (s, 2H),
4.63 (s, 1H), 1.80 (s, 3H), 13
C NMR (100 MHz, DMSO): δ 160.6,
154.4, 143.5, 135.4, 131.2, 129.1, 128.4, 120.2, 97.2, 57.1, 35.4,
9.7, M. F: C14H11ClN4O, M. W: 287, MS (m/z): 288 (M+1)+.
O
NNH
CN
NH2
OH
O
N
NH
CN
NH2
Cl
209
Fig. 4.14: 1H NMR spectrum of 5a compound
Fig. 4.15: 13
C NMR spectrum of 5a compound
O
NNH
CN
NH2
O
NNH
CN
NH2
210
Fig. 4.16: Mass spectrum of 5b compound
O
NNH
CN
NH2
NO 2