WELCOME TO MY PRESENTATION

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WELCOME TO MY PRESENTATION
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Pyranochromene Pyranopyrimidine Derivatives
Green Synthesis and Biological Evaluation

Presented By

Pradeep Paliwal Basic Science Deptt.
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Introduction
Heterocycles, form the core of many biologically
or pharmaceutically interesting compounds.
Heterocyclic synthesis offers a powerful solution
to many problems like complex natural product
synthesis and drug molecule synthesis. Chemical
and pharmaceutical industries are facing
constraints regarding the environment and saving
energy. To overcome .. Handling of
waste Better yield reaction process Search of
environment tolerate procedure Ease of
reaction Time minimizing it would be much more
efficient, if one could form target molecules in
economical and environmental friendly way in
shorter reaction time.
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Introduction to titled compounds
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Dihydropyranochromene, Pyranopyrimidine
derivatives have recently attracted much
attention as important class of heterocycles to
their useful biological and pharmacological
properties. Since their innovation, they are
attracting many biological interests, because of
the close proximity of many functional groups in
their structure.
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Multi Component Reactions
Multi-component reactions (MCRs) are a
promising and vital field of chemistry
because, the synthesis of complicated
molecules can be achieved in a very fast,
efficient and time-saving manner without the
isolation of any intermediate. These reactions
offer a wide range of possibilities for
the efficient construction of highly complex
molecules in a single procedural step. As a
result, it requires minimum effort, which
minimizes the environmental loading and is
acceptable from a Green Chemistry point of
view. In recent years, the discovery of novel
MCRs has become an increasingly active area
of research, yielding novel chemical scaffolds
for drug discovery. Thus, the development of
new multi-component reaction is a popular area
of research in current organic chemistry. In
the past decade, there have been tremendous
development in three and four-component
reactions and great efforts continue to be made
to develop new MCRs.
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• Some of the reported procedures for the
  synthesis of pyranochromenes and
  pyranopyrimidines often suffer from certain
  drawbacks such as
• ? Long reaction times
• ? Carcinogenic solvents
• ? Hazardous by-products
• ? Microwave irradiations
• ? Use of metal triflates and
• ? Excess amount of base catalyst.
• The development of cleaner technologies is
  a major accent in green chemistry.
• Among the several aspects of green
  chemistry, the reduction/replacement of volatile
  organic solvents and/or catalysts from the
  reaction medium is of utmost importance. The
  search for a nonvolatile and recyclable
  alternative is thus holding a key role in this
  field of synthetic research.
• The use of fused organic salts, consisting
  of ions, is now emerging as a possible
  alternative.

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Ionic Liquids
Ionic Liquids are materials that are composed
solely of cations and anions. Ionic Liquids
(IL) are salts with a melting temperature below
the boiling point of water (100 C). Extremely
low vapor pressure Miscibility with water or
organic solvents Can act as acids, bases or
ligands Chiral IL for chiral synthesis Precursor
salts for the preparation of stable carbenes
Very large liquidus ranges up to 400 C Can be
used as surfactants More viscous than common
molecular solvents IL/IL mixtures can be stable
up to 250 C Electrically conductive
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Ionic Liquids in Organic Reactions Many
studies have reported on the application of ionic
liquids in different areas and, in particular, on
their use in organic reactions. On the other
hand, there are a few reports that provide a
clear discussion on questions such as how do
ionic liquids act in organic reactions? or are
ionic liquids solvents, catalysts, or both?
Perhaps for the synthetic organic chemist, these
questions are secondary, considering the
significant improvement in products yields,
reaction times, reaction work-up, etc., that they
confer.
Ionic Liquids as Solvent Solvent polarity is
the most commonly used for solvent
classification. The simplest qualitative
definition is that a polar solvent is one that
will dissolve and stabilize dipolar or charged
solutes. It is widely thought, though yet to be
generally demonstrated, that under this
definition, ionic liquids will be highly polar
solvents. It was generally found that the ionic
liquids could be considered to be polar phases
with the solvent properties being largely
determined by the ability of the salt to act as a
hydrogen bond donor or acceptor.
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Ionic Liquids as Catalyst An ionic liquid can
be useful if the cation or anion of the ionic
liquid can act as a catalyst, catalyst activator,
or co-catalyst for a reaction. In some of the
more recent examples found in the literature, the
ionic liquid is deliberately prepared so that one
of the ions serves as the catalyst for the
reaction
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Objective of the proposed work
The syntheses of chromene and its derivatives
have attracted great interest due to their
biological and pharmacological activities. The
4H-chromene derivatives show various
pharmacological properties such as spasmolytic,
diuretic, anti-coagulant, anti-cancer, anti-HIV,
antitumor, anti-malarial activities, anti-
alzheimer, anti-leukemic, antibacterial,
anti-malarial activities, emetic, and
anti-anaphylactic activities. The derivatives
of pyrano2,3-dpyrimidines have been reported to
display biological activities, especially
antipyretic, anti-inflammatory and
gastroprotective. Growing concern about
environmental damage leads to an urgent
requirement for the development of eco-friendly
technology and economic processes. It is of great
practical importance to synthesize Pyran
derivatives by the MCRs by using ILs. Ease of
handling, recycling of the catalyst and
environmental compatibility are main advantages
of this work.
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Fenisorex Anorectic agent Chem. Abstr. 1973, 79,
126
Morellin Antitubecular agent Moroccan patent,
2004,No. 2769.
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Antihypertensive agent J.Med.Chem. 1991, 34, 806
Adrenoceptor-selective antagonist J.Med.Chem.
1999, 42, 4764
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Ionic Liquid used in this work
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A proper choice of cations and anions is
required to achieve ionic salts that are liquids
at room temperature. (RTILs) Triethylammonium
acetate (TEAA), a cheap and easy to synthesize
IL, was chosen as solvent system as well as
catalyst and successfully employed to synthesize
target compounds under conventional conditions.
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Ionic Liquid used in this work
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Chemical Name___________ Tri Ethyl Ammonium
Acetate (TEAA) Molecular weight_________
161.25g/mol Appearance ______________Colourless
liquid Odor
___________________ Odorless
Water Solubility___________Water
Soluble pH______________________7.0
Specific gravity___________ 1.007mL/g
Refractive index___________ 1.355

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Proposed Methodology
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General procedure for the synthesis of heteroaryl
substituted pyrano(c)chromene or
pyrano2,3-dpyrimidine 5-memberd heteroaryl
aldehyde, malononitrile, 5,5-dimethyl-cyclohexane
-1,3-dione/barbituric acid in equimolar ratio and
TEAA (5 mL) were added to a R.B. flask. The
reaction mixture was stirred for appropriate time
at room temp. The completion of the reaction was
monitored by TLC. After completion of the
reaction, water (5 mL) was added in reaction
mixture, precipitation of product is occurred.
The pure product (6/7) was obtained by
recrystallization. Products (6/7) thus obtained
were in high yields.
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Proposed Mechanism for the formation of titled
compounds
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Graphical Representation of Recycle data
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The reaction of Heteroaryl Aldehyde,
Malanonitrile, Dimidone/Barbuteric acid Using
TEAA
The filtrate of ionic liquid was recovered
for reuse by drying at 80C several hours
in a vacuum. The ionic liquid can be recycled
for five times. Even in the fifth run the yield
of the product is fairly good.
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TEAA Catalyzed Synthesis of dihydro Pyranoc
Chromenes
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6b Yield 94, M.P205-207
6a Yield 90, M.P216-218
6c Yield 84, M.P178-180
6d Yield 95, M.P208-210
6f Yield 97, M.P217-219
6e Yield 95, M.P214-215
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TEAA Catalyzed Synthesis of dihydro Pyranoc
Chromenes
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7b Yield 94, M.P284-286
7a Yield 92, M.P280-282
7c Yield 86, M.P191-193
7d Yield 95, M.P274-275
7f Yield 97, M.P298-300
7e Yield 96, M.P289-291
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Spectral data for dihydropyranocchromenes
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6a
2-Amino-3-cyano-4-(furan-2-yl)-7,7-dimethyl-5-oxo-
4H-5,6,7,8-tetrahydrobe nzo-b pyran 6a white
solid, m.p. 216-218C, IR (KBr) 3355, 3208(NH2),
2941 (C-H), 2202(CN), 1680(CO), 1652(CC) cm-1
1H NMR(300 MHz, DMSO-d6) d 0.99 (s, 3H, CH3),
1.05 (s, 3H,CH3), 2.17 (m, 2H, CH2), 2.48 (m, 2H,
CH2), 4.33 (s, 1H, CH), 6.05 (s, 1H), 6.32 (s,
1H), 7.07 (s, 2H), 7.48 (s, 1H) ppm EI-MS (m/z)
284 (M). C16H16N2O3 calcd C, 67.59 H, 5.67
N, 9.85. Found C, 67.88 H, 5.56 N, 9.63.
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6b
2-Amino-7,7-dimethyl-4-(5-methyl-furan-2-yl)-5-oxo
-5,6,7,8-tetrahydro-4H-chromene-3-carbonitrile
6b yellow solid, m.p. 205-207, IR (KBr) cm-1
3396, 3210 (NH2), 2966 (C-H), 2196 (CN), 1680
(CO), 1660 (CC) cm-1 1H NMR (DMSO- d6), 2.17
(s, 3H,CH3), 6.32-6.33 (dd, 1H, Ar-H), 6.05 (d,
1H, Ar-H), 7.08(s, 2H, NH2), 4.33 (s, 1H), 2.50
(s, 2H, CH2), 2.30 (d, 1H,CH2), 2.15 (d, 1H),
1.04 (s, 3H, CH3), 0.99 (s, 3H, CH3)ppm EI-MS
(m/z) 298(M) C17H18N2O3 (298.34) calcd C,
68.44 H, 6.08 N, 9.39. Found C, 68.40 H,
6.10 N, 9.41
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2-Amino-7,7-dimethyl-5-oxo-4-(1H-pyrrol-2-yl)-5,6,
7,8tetrahydro-4H-chromene-3- carbonitrile 6c
white solid, m.p. 178-180C. IR(KBr) 3355,
3208(NH2), 2941(C-H), 2212(CN), 1675(CO),
1658(CC) cm-1 1H NMR (DMSO- d6) d 0.99 (s,
3H, CH3), 1.08 (s, 3H, CH3), 2.22 (m, 2H), 2.42
(m, 2H), 4.31(s, 1H), 5.21(s, 1H, NH), 6.05 (s,
1H, Ar-H), 5.91(s, Ar-H), 6.32 (s, Ar-H),7.07 (s,
2H, NH2) EI-MS (m/z) 283(M) C16H17N3O2
(283.33) Calcd. C, 67.83 H, 6.05 N, 14.83.
Found C, 67.88 H, 5.99 N, 14.84. 2-Amino-7,7-d
imethyl-4-(thiophen-2-yl)-5-oxo-5,6,7,8-tetrahydro
-4H-chromene-3-carbonitrile 6d yellow solid,
m.p. 208-210C IR (KBr) 3402, 3212 (NH2), 2977
(C-H), 2206 (CN), 1678 (CO), 1662 (CC) cm-1 1H
NMR (DMSO- d6), d 6.32-6.33 (dd, 1H, Ar-H), 6.15
(d, 1H, Ar-H), 6.05 (d, 1H, Ar-H) , 7.08 (s, 2H,
NH2), 4.33 (s, 1H, CH), 2.50 (m, 2H, CH2), 2.30
(m, 2H, CH2), 1.04 (s, 3H, CH3), 0.99 (s, 3H,
CH3) EI-MS (m/z) 300(M) C16H16N2O2S (300.09)
Calcd. C, 63.98 H, 5.37 N, 9.33 Found C,
63.92 H, 5.34 N, 9.42.
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Spectral data for dihydro Pyrano2,3-d
Pyrimidines
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7a
7-Amino-5-furan-2-yl-2,4-dioxo-1,3,4,5-tetrahydro-
2H-pyrano2,3-dpyrimidine-6-carbonitrile 7a
dark yellow solid, m.p. 280-282C. IR (KBr)
3391, 3302 (NH2), 3188 (NH), 3072(C-H),
2197(CN), 1718(CO), 1665(CC) cm-1 1H NMR
(DMSOd6) dH 4.26 (s, CH), 7.20 (br s, 2H, NH2
), 7.22 (1H, d, H-Ar), 6.59 (1H, m, HAr),
6.51(1H,d, HAr), 11.12 (1H, br s, NH), 12.14
(1H, br s,NH) EI-MS (m/z) 272 (M) C12H8N4O4
(272.22) calcd C,52.95 H, 2.96 N, 20.58.
Found C, 52.94 H, 2.93 N, 20.47.
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7b
7-Amino-5-(5-methyl-furan-2-yl)-2,4-dioxo-1,3,4,5-
tetrahydro-2H-pyrano2,3-d pyrimidine-6-carbonitr
ile 7b dark yellow solid, m.p. 284-286C. IR
(KBr) 3402, 3299(NH2), 3178(NH), 2989(C-H),
2202(CN), 1715(CO), 1460(CC) cm-1 1H NMR
(DMSOd6) dH 4.12 (1H, s, CH), 7.16 (2H, br s,
NH2 ), 2.15 (3H, s, CH3), 6.59 (1H, m, HAr),
6.51(1H,d, HAr), 11.12(1H, br s, NH), 12.14 (1H,
br s, NH) EI-MS (m/z) 286(M)
C13H10N4O4(286.24) calcd C, 54.55 H, 3.52
N,19.57. Found C, 54.46 H, 3.56 N, 19.59.
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7-Amino-2,4-dioxo-5-(1H-pyrrol-2-yl)-1,3,4,5-tetra
hydro-2H-pyrano2,3-dpyrimidine-6-carbonitrile
7c pale-yellow solid, m.p. 191-193C. IR (KBr)
3402, 3299(NH2), 3168(NH), 2989(C-H), 2202(CN),
1708(CO),1460(CC) cm-1 1H NMR (DMSOd6) dH
4.19 (1H, s,CH), 7.10(2H, br s, NH2), 6.97(1H,d,
H-Ar), 6.59(1H, m, HAr), 6.51(1H,d, HAr),
11.12(1H, br s, NH), 12.14(1H, br s, NH) EI-MS
(m/z) 271(M) C12H9N5O3 (271.23) calcd C,
53.14 H, 3.34 N, 25.82. Found C, 53.07 H,
3.28 N, 25.89. 7-Amino-5-(thiophen-2-yl)-2,4-dio
xo-1,3,4,5-tetrahydro-2H-pyrano2,3-dpyrimidine-6
-carbonitrile 7d dark yellow solid, m.p.
274-275C. IR (KBr) 3390, 3306(NH2), 3188(NH),
3072(C-H), 2197(CN), 1708(CO), 1459(CC) cm-1
1H NMR (DMSOd6) dH 4.21 (1H, s), 7.38(2H, br s,
NH2), 7.02(1H, d, H-Ar), 6.57 (1H, m, HAr),
6.49(1H,d, HAr), 11.42(1H, br s, NH), 12.09(1H,
br s, NH) EI-MS (m/z) 288(M)
C12H8N4O3S(288.28) calcd C, 50.00 H, 2.80 N,
19.43. Found C, 49.89 H, 2.84 N,19.46.
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Antimicrobial Activity
All test micro organisms were obtained from
Microbiology Department, Lokmanya Tilak College
Ujjain and were as follows Citrobactor fruendi,
Klebsiella pneumoniae, Bacillus megaterium,
Escherichia coli, Pseudomonas aeruginosa and
Salmonella typhi. Antibacterial activity of the
prepared compounds 67 a-f was tested by the disk
diffusion method. Whattman No. 1 filter paper
disks were sterilized by autoclaving for one hour
at 140C. All the synthesized compounds were
dissolved in DMSO for dilution to prepare stock
solutions of 20mg/mL for antimicrobial assay.
Agar plates were uniformly surface inoculated
with fresh broth culture of C. sruendi, K.
pneumoniae, B. megaterium, E. coli, P. aeruginosa
and S. typhi. The impregnated disks were placed
on the medium suitably spaced apart and the
plates were incubated at 30 C for 1 h to permit
good diffusion and were then transferred to an
incubator at 372 C for 24 h. The zones of
inhibition were measured on mm scale. Ampicillin
was used as standard antimicrobial drug.
Dimethylsulphoxide was used as solvent control.
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Comparative antibacterial activity of
Dihydropyrano(c)chromenes
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Graphical Representation
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Comparative antibacterial activity of
Pyrano2,3-dpyrimidines
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Graphical Representation
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Conclusion
In conclusion, we developed a simple, efficient
and environmental friendly method for
biologically potent molecules in a single flask.
All synthesized compounds shown good to excellent
yield against different bacterial
stains.(Anticancer activity is under
investigation) Room temperature Ionic liquid
TEAA is Cheap and easy to synthesis Can be
reused several times Good yields of the products
In shorter reaction time compare to earlier
reported procedures. Thus, we believe that
this simple and Green Methodology will be a
practical alternative to the existing
procedures. The simplicity of the system, ease
of separation/reuse of the catalyst, excellent
yields of the products and ease of work-up
fulfill the triple bottom line philosophy of
Green Chemistry and make the present methodology
environmentally benign.
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Publications

• DABCO promoted one-pot synthesis of
  dihydropyrano(c)chromene and pyrano2,3dpyrimidin
  e derivatives and their biological activities
• Shubha Jain, Neelaiah Babu G.,Anjna B.,
  Pradeep Paliwal
• Journal of Saudi Chem. Soc. 2011, doi
  10.1016/j.jscs.2011.10.023
• 2. An uncatalysed Knoevengal condensation
  Synthesis, Characterization
• and Biological activities
• Shubha Jain, Neelaiah Babu G, Pradeep
  Paliwal.
• Int. J. of Chem Tech Research 2011 (In
  Press)
• 3. Green approach towards the facile synthesis
  of pyrano(c)chromene
• and pyrano2,3-dpyrimidine derivatives
  and their biological activities
• Shubha Jain, Neelaiah Babu G and Pradeep K.
  Paliwal
• Med Chem Res 2011, (In Revision)
• 4. pH dependent photooxygenation of guanine by
  singlet molecular
• oxygen in presence of rose Bengal
• Neelaiah Babu, Shubha Jain, Archana Kushwah,
  Pradeep Paliwal
• Int. J. Chem. Sci. 8(2), 2010, 763-768.

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• 5. DABCO promoted cyclocondensation of
  vinylmalononitriles and
• heteroarylnitroolefins An efficient
  synthesis of heteroaryl
• substituted benzenes.
• Shubha Jain, Neelaiah Babu G., Anjna
  Jaiswal, Pradeep Paliwal
• Can. J. Pur.App.Chem., 2011, In Revision.
• 6. Photooxygenation of Adenosine by singlet
  molecular oxygen in
• different conditions.
• Shubha Jain, Archana Kushwah, Neelaiah
  Babu, Pradeep Paliwal
• Asian J. Of Research in chemistry, 3(1),
  110-112, 2010.
• 7. An efficient One-Pot Green Protocol for the
  Synthesis of 5
• Unsubstituted 3, 4-Dihydropyrimidin-2(1H)-on
  es Using
• Recyclable Amberlyst 15 DRY as a
  Heterogeneous Catalyst
•   Shubha Jain, Anjna Jaiswal, Srinivasarao
  J.,Pradeep Paliwal
• J.Iran.Chem.Soc., 2011. Under Review
• 8. Fused heterocycles DABCO catalyzed
  synthesis and their
• biological activity

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THANKS