Synthesis of functionalized chromene and spirochromenes using L-proline-melamine as highly efficient and recyclable homogeneous catalyst at room temperature

Article abstract of DOI:10.1016/j.tetlet.2017.09.060

An efficient and recyclable homogeneous catalyst is developed using commercially cheap L-proline and melamine for the synthesis of chromenes and spirochromenes (spirooxindoles) via multicomponent reactions at room temperature. Systematic studies were conducted in order to achieve desired reactivity and recyclability of the catalyst using various α-amino acids and aromatic amines as donor-acceptor pairs. Among the screened combinations, L-proline and melamine (3:1 ratio; 3 mol% on total weight) was found to be best catalyst to give the desired products with excellent yields (up to 99%) in very short times (1–15 min) at room temperature in DMSO as solvent. The catalyst was recovered by adding EtOAc and reused up to 5 cycles without losing the catalytic activity.

Full text of DOI:10.1016/j.tetlet.2017.09.060

Accepted Manuscript
Synthesis of functionalized chromene and spirochromenes using L-Proline-
melamine as highly efficient and recyclable homogeneous catalyst at room
temperature
Sakkani Nagaraju, Banoth Paplal, Kota Sathish, Santanab Giri, Dhurke
Kashinath
PII:
S0040-4039(17)31196-6
https://doi.org/10.1016/j.tetlet.2017.09.060
TETL 49330
DOI:
Reference:
Tetrahedron Letters
To appear in:
Received Date:
Revised Date:
Accepted Date:
19 August 2017
19 September 2017
20 September 2017
Please cite this article as: Nagaraju, S., Paplal, B., Sathish, K., Giri, S., Kashinath, D., Synthesis of functionalized
chromene and spirochromenes using L-Proline-melamine as highly efficient and recyclable homogeneous catalyst
at room temperature, Tetrahedron Letters (2017), doi: https://doi.org/10.1016/j.tetlet.2017.09.060
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Graphical Abstract
Synthesis of functionalized chromene and
spirochromenes using L-Proline-melamine as
highly efficient and recyclable homogeneous
catalyst at room temperature
Leave this area blank for abstract info.
Sakkani Nagaraju,a Banoth Paplal,a Kota Sathish,a Santanab Giri,b and Dhurke Kashinatha*

1
Tetrahedron Letters
journal homepage: www.els evier.com
Synthesis of functionalized chromene and spirochromenes using L-Proline-melamine
as highly efficient and recyclable homogeneous catalyst at room temperature
Sakkani Nagaraju,a Banoth Paplal,a Kota Sathish,a Santanab Giri,b and Dhurke Kashinatha∗
aDepartment of Chemistry, National Institute of Technology, Warangal-506 004, India
bDepartment of Chemistry, National Institute of Technology, Rourkela-769 008, India
ARTICLE INFO
ABSTRACT
Article history:
Received
Received in revised form
Accepted
An efficient and recyclable homogeneous catalyst is developed using commercially cheap L-
proline and melamine for the synthesis of chromenes and spirochromenes (spirooxindoles) via
multicomponent reactions at room temperature. Systematic studies were conducted in order to
achieve desired reactivity and recyclability of the catalyst using various α-amino acids and
aromatic amines as donor-acceptor pairs. Among the screened combinations, L-proline and
melamine (3:1 ratio; 3 mol% on total weight) was found to be best catalyst to give the desired
products with excellent yields (up to 99%) in very short times (1 to 15 min) at room temperature
in DMSO as solvent. The catalyst was recovered by adding EtOAc and reused up to 5 cycles
without losing the catalytic activity.
Available online
Keywords:
L-proline
Melamine
Recyclable catalyst
Homogeneous catalysis
Spirooxindole
4H-chromene
Homogeneous catalysis enjoys the advantage of product
selectivity and yields over heterogeneous catalysis depending on
the number of active sites in the catalyst. However, the separation
of the product, loss of the catalyst and regeneration of the catalyst
from the reaction mixture (which require tedious processes, thus
may not be suitable for sensitive products) is the main limitation
of homogeneous catalysis.1a-c Because of this, designing the
recyclable homogeneous catalysts with high activity, selectivity
and easy separation from the products is always a challenge. In
this regard, different approaches were adopted for the
development of recyclable homogeneous catalysts. The use of
homogeneous catalyst with covalently, non-covalently bonded or
immobilized silica or insoluble polymer/resin is most common
method for this purpose.1a,2a Along with these, the use of
organometallic complex and metallodendrimes,2b-c transforming a
homogeneous catalyst in to heterogeneous catalyst using
nanoparticles,2d solvent/temperature dependent solubility of the
catalyst during and after the reaction, (thermomorphic solvent
systems),1a,2e precipitation of the catalyst after completion of the
reaction,2f exposure to UV radiation,2g metals complexed with
macromolecules (self supported),2h tagged catalyst with ionic
liquids,2i are known in the literature.
complexes, and by modular designed organocatalysts.3d As a
result, last couple of decades have witnessed the use of L-Proline
and its derivatives as organocatalysts for different types of
reactions4a,b and synthesis complex products/biologically
important compounds.4c,d Along with these, L-proline has been
used for multicomponent reactions (MCRs) for the preparation of
functionalized
pyrans,
dihydropyridiines,
pyridones,
pyrazolo[3,4-b]quinolines,
4H-pyrano[2,3-c]pyrazoles,
naphtharidines, dicoumarols etc.5
2-Amino-4H-chromene-3-carbonitriles (chromenes)6 and 2'-
amino-2-oxospiro[indoline-3,4'-pyran]-3'-carbonitrile (spiro
chromenes/spirooxindoles)7 are known to show many biological
properties including anticancer, antioxidant and antimicrobial,
inhibitors of excitatory amino acid transporters etc. Currently,
these compounds are prepared by MCR approach using different
catalysts like urea,8a potassium phthalimide,8q organic bases
(TEA, DBU, DABCO, DMAP),8b-e inorganic salts (CaCl2,8h
NH4Cl,8j tungstic acid,8l cellulose–HClO4,8i NbCl5), alternative
reaction media (chitosan/ionic liquid,8k BnN(Et)3Cl surfactant,8n
sulfated choline based heteropolyanion salt,8o micellar media8p),
nanomaterials (nano-organocatalyst,8f,g γ-Fe2O3 nano particles8m)
amino acids (cysteine,8r) and catalyst free8s,t conditions. Along
with these methods, L-proline and supported proline derivatives9
also been used for the synthesis of purpose (Figure-1). However,
many of these methods (including L-proline) involve the use of
temperature, require more time for completion of reaction and
L-proline mediated reactions often take more time for
completion and give poor stereoselectivity. These limitations
have been addressed by using additives,3a co-catalysts,3b
incorporating covalently bonded functional groups,3c host-guest
———
∗ Corresponding author. Tel. +91-870- 246-2677; FAX No. +91-870-245-9547;
e-mail: kashinath@nitw.ac.in; kashinath.dhurke@gmail.com;

2
HO
limit to three or four types of nucleophiles in both simple
chemomene and spirooxindole case.
R
S
O
O
O
O
N
H2N
COOH
N
N
N
N
H
COOH
H
OH
H
H
R
OH
H
OH
1a
1b ; R = H
1e
1f ; R = NH2
1g ; R = OCH3
1h
1i
1c ; R = CH3
1d ; R = CH2Ph
NH2
NH2
NH2
NH2
OH
N
NH2
N
N
Cl
2a
2b
2c
2d
2e
NH2
N
N
NH2 Cl-
S
N
NH2
N
NH
2 H2N
N
NH2
H2N
NH2
H2N
N
NH2
N
2f
2g
2h
2i
2j
Figure 2. Different α-amino acids and aromatic amines used in the
present study for the development of recyclable homogeneous catalyst
Scheme 1. Catalyst screening for the multicomponent
reaction of isatin (3a), dimedone (4a) and malononitrile (5a)
Figure-1. Closely related literature methods for the synthesis of
chromenes and spirochromenes and present study
Melamine 2j (1,3,5-Triazine-2,4,6-triamine) with pKa 5 and
66% nitrogen content is a unique molecule that has hydrogen
donor-acceptor-donor sites (donor to donor distance of 4.8 A°
units) to form self-assembly supramolecular networks via inter-
molecular non-covalent interactions [hydrogen bonding, aromatic
(π-π)] etc.12,13 Melamine unit has been extensively used for the
preparation of functional materials, nano-structures, liquid
crystals and biologically active products.14 However, limited
reports are available for its applications in organic synthesis for
MCRs and other reactions.15
Though the use of small molecules as additives or co-catalysts
is known concept,3b the use of commercially available small
organic molecules (other than L-proline) as recyclable
homogeneous catalysts is rare.10 Thus, considering the biological
importance chromenes, recyclable homogeneous catalysis and in
continuation with our efforts in developing simple synthetic
methods,11 here in we report L-proline-melamine combination as
highly efficient recyclable homogeneous catalyst for the
synthesis of chromenes and spirochromenes via MCR approach.
Towards this, we envisaged the use of commercially available
small organic molecules with hydrogen bonding donor-donor and
donor-acceptor sites as additives in combination with α-amino
acid derivatives.3,12 In order to achieve the desired reactivity,
active catalyst systems, initially the catalyst systems were
prepared by mixing L-proline (1a) with different aromatic and
heteroaromatic amines (2a-2e) in MeOH (RT, overnight).
Evaporation of the solvent gave active catalysts as white powder
(see ESI for detailed procedure) which were used (3 mol%) for
multicomponent reaction of isatin (3a) with dimedone (4a) and
malononitrile (5a) to desired spirochromene (6a) in 50-70% yield
(Scheme 1;Table-1; entries 1-10). It is interesting to note that all
the catalyst systems are giving the desired product with moderate
yields compare to the reaction of L-proline (30 mmol) (Table-1;
entry 1). Also, entry 4 indicate that the structural features (1,3-
relationship of the nitrogen; charged species of pyridinium ion)
of the aromatic amines are important for faster kinetics of the
reaction. Considering this, further investigation was continued
using different heteroaromatic amines (2f-2h) and guanidine (2i).
Among these, the combination of L-proline (1a) and 2-
aminopyrazine (2f)/guanidine (2i) are slightly better in terms of
reactivity which may be due to distant donor-acceptor atoms and
their ratio/increased pKa values of catalyst system because of the
presence of extra nitrogen.
Keeping in view of the above results and considering the
structural features of melamine 2j (with respect to 2-
aminopyridine, 2-aminopiperazine and guanidine) and with the
intension of improving the reaction conditions further, melamine
2j was selected for present study. Thus, the catalyst system was
prepared using similar procedure with melamine:L-proline (1:1,
1:2 and 1:3 ratios) as white powder. The resulting catalysts were
used (3 mol% by weight) for the multicomponent reaction as
shown in Scheme-1. Surprisingly this combination of L-proline
and melamine combination [1a + 2j] gave better yields (85%,
90% and 99% respectively) (Table-1; entries 11, 12 and 13)
compare to all the screened combinations described above.
After successfully obtaining the expected reactivity, efforts
were made to characterize catalyst system (for IR, mass spectra,
see ESI) and study its stability using computational methods. All
the studied molecules were optimized using B3LYP16a,b
functional with 6-311+G(d,p) in the form of basis set. Vibrational
frequency were also analyzed at the same level of theory and
basis set to ensure ground state geometries. Positive vibrational
frequencies for all of our catalyst systems indicate that all of
them are on the local minimum of their respective potential
energy surfaces. The optimized geometries along with their
Cartesian coordinates are given in supporting information (see
ESI). To find the stability of 1:1, 1:2 and 1:3 (melamine:L-
Proline catalyst systems) we have calculated the formation

3
energies (∆Ef) by using the expression ∆Ef = EM-P – (EM + EP).
For all the cases, we have found that the formation energy is
negative. For 1:1 complex the formation energy is found to be -
14.85 kcal/mol. For 1:2 and 1:3 complexes, two types of
formation energy can be possible. The stepwise and direct. If we
look at the direct complex formation for 1:2 (-29.49 kcal/mol)
and 1:3 (-44.55 kcal/mol), we have found that the formation
energy gradually increases from 1:1 complex. This suggest that
1:3 complex formation is preferable among the other two. The
stability can also be analyzed in view of the number of H-bonds
present in the complex. Optimized geometries of the catalyst
complexes reveals that there exist H- bond between melamine
and Proline as shown in Figures 3 and 4. We have found that the
H bond distances ranges from 1.6 to 1.9 Å depending on the
centers involve for H-bond formation. More number of H-bonds
makes 1:3 complex superior than other two complexes. All the
computational work has been performed in G09W suits
program.16c
Table-1. Screening of the catalysts for the MCR of isatin
(3a) dimedone (4a), and malononitrile (5a)
S. No.
Catalyst combination Reaction time (h)
Isolated Yield (%)a
1
2
3
4
5
6
7
8
1a (30 mol%) + no additive
1a + 2a (1:1)
1a + 2b (1:1)
1a + 2c (1:1)
1a + 2d (1:1)
1a + 2e (1:1)
1a + 2f (1:1)
1a + 2g (1:1)
1a + 2h (1:1)
1a + 2i (1:1)
1a + 2j (1:1)
1a + 2j (2:1)
1a + 2j (3:1) (3 mol%)
Only 2j
2b + 2j
2c + 2j
2d + 2j
2e + 2j
2f + 2j
2g + 2j
2h + 2j
2i + 2j
24
5
4
4
5
6
3
8
25
60
65
70
60
50
80
60
75
80
85
90
99
9
5
3
10
11
12
13
14
15
16
17
18
19
20
21
22
23
40 min
25 min
5 min
24
6
24
24
24
24
24
ND
70
30
35
20
Trace
ND
ND
ND
Trace
24
24
1a + 2j (in water)
Reaction conditions:aAll the reactions were performed at 1
mmol scale using 3 mol% of the catalyst in DMSO solvent at RT
and given as isolated yields.
Meanwhile, simultaneous attempts were made to simplify the
reaction protocol and recovery of the catalyst as precipitate.
Thus, different combinations of solvents were added to the
reaction mixture in order to get the products and catalyst
separately. Among all, addition of EtOAc was found to be best
solvent system to give the product in solution and catalyst as
precipitate as shown in Scheme-2. Further, to find the reactivity
of the regenerated catalyst, the precipitate (catalyst system)
obtained from above reaction was washed with EtOAc (in order
to remove impurity traces), air dried to get the catalyst as fine
powder. This regenerated catalyst system (1a + 2j) was used (3
mol%) for above reaction up to 5 cycles to give the desired
products in good yields (Table-2).
Figure-3. Possible interactions of L-proline (1a) with melamine (2j) to
give stable catalyst
E= -401.27804454 a.u
E = -847.94060246 a.u
E= -446.63887465 a.u
E = -1249.24227537 a.u
Scheme 2. Schematic representation for the catalyst recovery
after the multicomponent reaction
Table-2. Recyclability studies of the catalyst system
S. No.
Cycle No.
Reaction time (min) Isolated yield (%)a
1
2
3
4
5
Cycle-1
Cycle-2
Cycle-3
Cycle-4
Cycle-5
5 min
5 min
5 min
8 min
10
99
99
99
98
98
E = -1650.54373801 a.u
H-bond distances in Å: 1:N-H 1.66; O-H 1.93 2. N-H 1.67;
O-H 1.91 3: N-H: 1.69; O-H: 1.90
aReactions were performed at 1 mmol of isatin as control in
Figure-4. Optimized geometries of the catalyst complexes (which reveals
that there exist H- bond between melamine and L-proline)
DMSO solvent using 3 mol% of the catalyst [1a + 2j]

4
Having successfully demonstrating the regeneration and
recyclability of the catalyst after the above reaction, nucleophiles
(4b-4h) with variable ring systems were reacted with isatins 3a
(Scheme 3) using DMSO as reaction medium. It is noteworthy to
mention all the nucleophiles are equally reactive giving the
desired products (6a-6h) within short period of time (1-15 min)
with excellent yields (up to 99%) and catalyst recovery as
described above in every case (Model study; see ESI).18 Later,
many functionalized (aromatic ring and N-substituted) isatins
were treated with malononitrile/ethylcyanoacetate and
nucleophiles to give library of chromene-spirooxindole
derivatives as shown in Scheme-3; Figure-5. In the similar lines,
different nucleophiles were reacted with p-nitrobenzaldehyde and
malononitrile as model study to give desired products in short
reactions times with excellent yields (Model study; See ESI). In
this case, the reactions of 4-hydroxy coumarin and 2-hydroxy
naphthoquinone and EAA required more time (20 min) for the
completion with the aromatic aldehydes with electron
withdrawing groups as substituents. Subsequently, same protocol
was extended for the generation of library of compounds under
optimized conditions (Scheme-4), (Figure-6). Here also the
catalyst was recovered in all cases by adding EtOAc to the
reaction mixture as described above.
Figure-6. Various chromene derivatives prepared under optimized
conditions (the physical and spectral data (1H- , 13C-NMR and Mass) is given
in ESI
In continuation with above, with the intension of generating
more structural variation and testing the ability of the catalyst for
more complex systems, the bis-isatins were prepared from simple
alkylation of isatin and corresponding dibromides. Then the
resulting bis-isatins (23a-23c) were treated with different
nucleophiles and malononitrile
/ ethylcyanoacetate (under
optimized conditions) to give the expected bis-spirooxindole-
chromenes (24a-24r) in good yields (80-98%) (Scheme-5)
Scheme-3. MCRs of isatin and malononitrile with different
nucleophiles in presence of [1a + 2j] (3 mol%) in DMSO at
RT).
Scheme-5. Preparation of bis-spirooxindole derivatives (24a-
24r) using the optimized reaction conditions.
Figure-5. Various spirooxindole derivatives prepared under optimized
conditions (the physical and spectral data (1H- , 13C-NMR and Mass) is given
in ESI
Conclusion
In conclusion, we have developed a simple method for
recyclable homogeneous catalysis using commercially cheap L-
proline (1a) and melamine (2j) as donor-acceptor pair. This is the
first example for recyclable homogeneous catalyst without any
support for the materials used as catalyst. Also this is first
examples for fast multicomponent reactions without heating
under simple experimental procedures (with broad substrate
scope, excellent yields). Further this catalyst system is working
well for other reactions which will be reported in due course of
time.
Scheme-4. MCRs of aromatic aldehydes and malononitrile
with different nucleophiles in presence of [1a + 2j] (3 mol%)
in DMSO at RT).

5
Liu JQ, Guo FL, Liu Y. Tetrahedron. 2010;66:339; (o)
Acknowledgments
Rostamnia S, Nuri A, Xin H, Pourjavadi A, Hosseini SH.
Tetrahedron Lett. 2013;54:3344; (p) Baghernejad M,
Khodabakhshi S, Tajik S. New J Chem. 2016;40:2704; (q) Gupta
A, Jamatia R, Pal AK. New J Chem. 2015;39:5636; (r) Khalafi-
Nezhad A, Nourisefat M, Panahi F. Org Biomol Chem.
2015;13:7772; (s) Zhang M, Fu QY, Gao G, He HY, Zhang
Y, Wu YS, Zhang ZH. ACS Sustainable Chem Eng. 2017;5:6175
(t) Satasia SP, Kalaria PN, Avalani JR, Raval DK. Tetrahedron.
2014;70:5763.
SN thanks, UGC-New Delhi for the fellowship. SG thanks
DST (IFA 14-CH-151) and NIT Rourkela for financial support
and computational facilities. DK thanks, DST (SERB), New
Delhi for the financial support (SB/FT/CS-136/2012 and
SB/EMEQ-103/2014).
References and notes
9. (a) Li Y, Chen H, Shi C, Shi D, Ji S. J Comb Chem. 2010;2:231;
(b) Karamthulla S, Pal S, Parvinb T, Choudhury LH. RS Adv.
2014;4:15319.
10. Zolfigol MA, Tavasoli M, Moosavi-Zare AR, Moosavi P, Kruger
HG, Shirid M, Khakyzadeha V. RSC Adv. 2013;3:25681.
1. (a) Recoverable and Recyclable Catalysts, Benaglia M, Ed 2009
John Wiley & Sons, Ltd, (b) Cole-Hamilton DJ. Homogeneous
Catalysis-New Approaches to Catalyst Separation, Recovery, and
Recycling. Science. 2003;299:1702. (c) Astruc D, Lu F, Aranzaes
JR. Angew Chem Int Ed. 2005;44:7852; (d) Gladysz JA. Chem
Rev. 2002;102:3215; (e) Trindade AF, Gois PMP, Afonso CAM.
Chem Rev. 2009;109:418.
2. (a) Corma A, Garcia H. Adv Synth Catal. 2006;348:1391; (b)
Cornils B, Herrmann WA, Beller M, Paciello R, Eds. Applied
Homogeneous Catalysis with Organometallic Compounds: A,
VCH, Germany, 2017; (c) Van Klink GPM, Dijkstra HP, Van
Koten GCR. Chimie. 2003;6:1079; (d) Gladysz JA. Curran DP.
11. (a) Nagaraju S, Sathish K, Paplal B, Kashinath D. Tetrahedron
Lett. 2017;58:2865; (b) Paplal B, Nagaraju S, Sridhar B,
Kashinath D. Catal Commun. 2017;99:115; (c) Paplal B. Nagaraju
S, Palakollu V, Kanvah S, Kumar B.V, Kashinath D. RSC Adv.
2015;5:57842; (d) Paplal B, Nagaraju S, Palakollu V, Sujatha K,
Kanvah S, Kumar B.V, Kashinath D. RSC Adv. 2014;4: 54168; (e)
Nagaraju S, Satyanarayana N, Paplal B, Vasu AK, Kanvah S,
Kashinath D. RSC Adv. 2015;5:81768; (f) Nagaraju S.
Satyanarayana N, Paplal B, Vasu AK, Kanvah S, Sridhar B,
Prabhakar S, Kashinath D. RSC Adv. 2015;5:94474; (g) Nagaraju
S, Perumal P. O, Divakar K, Paplal B, Kashinath D. New J Chem.
2017;41:8993 (a) Arduini M, Crego-Calama M, Timmerman P,
Reinhoudt DN. J Org Chem. 2003;68:1097; (b) Leung FKC, Cui
JF, Hui TW, Zhou ZY, Wong MK. RSC Adv. 2014;4:26748.
12. (a) Russell KC, Lehn JM, Kyritsakas N, DeCian A, Fischer J. New
J Chem.1998;22:123; (b) Ikonen S, Nonappa, Kolehmainen E.
Cryst Eng Comm. 2010;12:4304; (c) Saha A, Roy B, Garai A,
Nandi AK. Langmuir. 2009;25:8457; (d) Seetha Lekshmi S, Guru
Row TN. Cryst Eng Comm. 2011;13:4886.
13. (a) Roy B, Bairia P, Nandi AK. RSC Adv. 2014;4:1708; (b)
Bretterbauer K, Schwarzinger C. Curr Org Synth. 2012;9:342; (c)
Bucos M, Sierra T, Golemme A, Termine R, Barber J, Giménez R,
Serrano JL, Romero P, Marcos M. Chem Eur J. 2014;20:10027.
14. (a) Kundu SK, Bhaumik A. RSC Adv. 2015;5:32730; (b) Mondal
J, Modak A, Nandi M, Uyama H, Bhaumik A. RSC Adv. 2012;2:
11306; (c) Tan MX, Gu L, Li N, Ying JY, Zhang Y. Green Chem.
2013;15;1127; (d) Ghorbani‐Choghamarani A, Rashidimoghadam
S. Chin J Cat. 2014;35:1024; (e) Mansoor SS, Aswin K, Logaiya
K, Sudhan SPN. J King Saud Uni. Science. 2013;25:191.
Fluorous Chemistry: From biphasic catalysis to
a parallel
chemical universe and beyond. Tetrahedron. 2002;58:3823; (e)
Färber T, Riechert O, Zeiner T, Sadowski G, Behr A, Vorholt AJ.
Chemical Engg Research and Design. 2016:12:263; (f) Dioumaev
VK, Bullock RM. NATURE. 2000;424:530; (g) Zhang G, Lang R,
Wang W, Lv H, Zhao L, Xia C, Lia F. Adv Synth Catal.
2015;5:917; (h) Bissessar D; Achard T; Bellemin-Laponnaza S.
Adv Synth Catal. 2016;358:1982; (i) Sebesta R, Kmentova´b I,
Toma S. Green Chem. 2008;10:484.
3. (a) Yu L, Luan J, Xu L, Ding Y, Xu Q. Tetrahedron Lett. 2015;56:
6116; (b) Xu L, Wang F, Huang J, Yang C, Yu L, Fan Y.
Tetrahedron. 2016;72:4076; (c) Chen H, Wang Y, Weia S; Sun J.
Tetrahedron: Asymmetry. 2007;18:1308; (d) Cobb AJA, Shaw
DM, Longbottom DA, Gold JB, Ley SV. Org Biomol Chem.
2005;3:84; (e) Reis O, Eymur S, Reis B, Demir AS. Chem
Commun. 2009;0:1088; (f) Martinez-Castaneda A, Kedziora K,
Lavandera I, Rodriguez-Solla H, Concellon C, Amo VD. Chem
Commun. 2014;50:2598; (g) Perera S, Sinha D, Rana NK, Trieu-
Do V, Zhao JCG. J Org Chem. 2013;78:10947; (h) Rana NK,
Huang H, Zhao J CG. Angew Chemie. 2014;53:7619.
15. (a) Lee C, Yang W, Parr GR. Phys Rev B. 1988;37:785; (b) Becke
AD. Phys Rev A. 1988;38:3098; (c) Frisch MJ. Trucks GW,
Schlegel HB, Scuseria GE, Robb MA, et.al. Gaussian 09, Revision
A.02 Gaussian, Inc., Wallingford CT, 2016.
4. (a) Herna´ ndez JG, Juaristi E. Chem Commun. 2012;48:5396; (b)
Gruttadauria M, Giacalone F, Noto R. Chem Soc Rev. 2008;
37:1666; (c) Raja M, Singh VK. Chem Commun. 2009;0:6687 (d)
Marqués-López
E,
Herrera
RP,
In
Comprehensive
16. General procedure for the multicomponent reaction using L-
proline-melamine catalyst system: To a solution of L-proline-
melamine complex (3 mol%) in DMSO (2 mL) was added
Dimedone 0.025 mg (0.178 mmol), malononitrile (1 equiv) and
benzaldehyde / isatin (1 equiv) and stirred at room temperature for
1-20 min. After completion of the reaction (monitored by TLC),
ethyl acetate was added stirring and continued for another 5 min.
The precipitate formed was filtered. Evaporation of solvent gave
the crude product which was recrystallized using ethanol to give
the pure compound.
Enantioselective Organocatalysis: Catalysts, Reactions, and
Applications, Ed. Dalko PI, Wiley-VCH Verlag GmbH & Co.
KGaA, 2013; (e) Sun BF. Tetrahedron Lett. 2015;56:2133.
(a) Sarita K, Yogesh KT, Mahendra K. Current Organocatalysis.
2016;3:176; (b) Mecadon H, Rohman MdR, Kharbangar I, Laloo
BM, Kharkongor I, Rajbangshi M, Myrboh B. Tetrahedron Lett.
2011;52:3228; (c) Li M, Zhanga B, Gu Y. Green Chem.
2012;14:2421.
5.
6.
(a) Doshi JM, Tian D, Xing C. J Med Chem. 2006;49:7731; (b)
Aridoss G, Zhou B, Hermanson DL, Bleeker NP, Xing C. J Med
Chem. 2012;55:5566
7. (a) Pavlovska TL, Redkin RG, Lipson VV, Atamanuk DV. Mol
Diversity. 2016;20:299; (b) Hostetler G, Dunn D, McKenna B. A,
Kopec K, Chatterjee S. Chem Biol Drug Des.2014;83:149; (c)
Vintonyak VV, Warburg K, Kruse H, Grimme S, Hübel K, Rauh
D,Waldmann H. Angew Chem Int Ed. 2010;49:5902
8. (a) Brahmachari G, Banerjee B. ACS Sustainable Chem Eng.
2014;2:411; (b) Dekamin MG, Eslami M. Green Chem.
2014;16:4914; (c) Khurana JM, Nand B, Saluja P. Tetrahedron.
2010;6:5637; (d) Davarpanah J, Kiasat AR. RSC Adv.
2014;4:4403; (e) Feng J, Ablajan K, Sali A. Tetrahedron.
2014;70:484; (f) Litvinov YM, Mortikov VY, Shestopalov AM.
Supplementary Material
Electronic supplementary information (1H- 13C-NMR and
Mass spectral data and spectra) can be found for this article.
J
Comb Chem. 2008;10:741; (g) Safaei HR, Shekouhy M,
Shirinfeshan A, Rahmanpur S. Mole Diversity. 2012;16:669; (h)
Dabiri M, Bahramnejad M, Baghbanzadeh M. Tetrahedron.
2009;65:9443; (i) Khalafi-Nezhad A, Divar M, Panahi F. RSC
Adv. 2015;5:2223; (j) Khan T, Siddiqui ZN. New J Chem.
2014;38:4847; (k) Rai P, Srivastava M, Singh J, Singh J. New J
Chem. 2014;38:3181; (l) Zhu SL, Jia SJ, Zhang Y. Tetrahedron.
2007;63:9365; (m) Satasia SP, Kalaria PN, Avalani JR, Raval DK.
Tetrahedron. 2014;70:5763 (n) Wang LM, Jiao N, Qiu J, Yu JJ,

6
Synthesis of functionalized chromene and
spirochromenes using L-Proline-melamine as
highly efficient and recyclable homogeneous
catalyst at room temperature
Sakkani Nagaraju,a Banoth Paplal,a Kota Sathish,a
Santanab Giri,b and Dhurke Kashinatha*
aDepartment of Chemistry, National Institute of
Technology, Warangal-506 004, India
bDepartment of Chemistry, National Institute of
Technology, Rourkela-769 008, India
Highlights:
1. Highly
efficient
and
recyclable
homogeneous catalyst
2. α-amino acids and aromatic amines as
donor-acceptor pairs
3. Catalyst recovery and reuse up to 6 cycles
4. Efficient for 8 types of nucleophiles