Microwave-assisted efficient synthesis of azlactones using zeolite NaY as a reusable heterogeneous catalyst

Article abstract of DOI:10.1080/15533174.2016.1212242

The efficient preparation of azlactones in the presence of zeolite NaY has been reported. This heterogeneous catalyst was used for efficient synthesis of azlactone derivatives with Ac2O as a condensing agent under microwave irradiation and solvent-free co

Full text of DOI:10.1080/15533174.2016.1212242

Synthesis and Reactivity in Inorganic, Metal-Organic, and
Nano-Metal Chemistry
ISSN: 1553-3174 (Print) 1553-3182 (Online) Journal homepage: http://www.tandfonline.com/loi/lsrt20
Microwave-Assisted Efficient Synthesis of
Azlactones Using Zeolite NaY as a Reusable
Heterogeneous Catalyst
Mohammad Ali Bodaghifard, Hassan Moghanian, Akbar Mobinikhaledi &
Fatemeh Esmaeilzadeh
To cite this article: Mohammad Ali Bodaghifard, Hassan Moghanian, Akbar Mobinikhaledi
& Fatemeh Esmaeilzadeh (2016): Microwave-Assisted Efficient Synthesis of Azlactones Using
Zeolite NaY as a Reusable Heterogeneous Catalyst, Synthesis and Reactivity in Inorganic, Metal-
Organic, and Nano-Metal Chemistry, DOI: 10.1080/15533174.2016.1212242
To link to this article: http://dx.doi.org/10.1080/15533174.2016.1212242
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Microwave-Assisted Efficient Synthesis of Azlactones Using Zeolite NaY as a Reusable
Heterogeneous Catalyst
Mohammad Ali Bodaghifard*a, Hassan Moghanianb, Akbar Mobinikhaledi a, Fatemeh
Esmaeilzadeha
aDepartment of Chemistry, Faculty of Science, Arak University, Arak 38156-8-8349, Iran
bDepartment of Chemistry, Dezful Branch, Islamic Azad University, Dezful, Iran
Email: mbodaghi2007@yahoo.com (m-bodaghifard@araku.ac.ir)
ABSTRACT
The efficient preparation of azlactones in the presence of zeolite NaY has been reported. This
heterogeneous catalyst was used for efficient synthesis of azlactone derivatives with Ac2O as
condensing agent under microwave irradiation and solvent-free conditions. The present method
offers advantages of good yields, short reaction time and simple work-up and catalyst reusability,
which makes this method mild and eco-friendly.
Keywords
Azlactone, Zeolite NaY, Heterogeneous catalyst, Erlenmeyer synthesis, Microwave irradiation.
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1. Introduction
Azlactones, or 2,4-disubstituted oxazolin-5-ones have attracted much interest because of their
wide range of biological and pharmaceutical properties.[1,2] They are appropriate building blocks
and valuable intermediates for the preparation of diverse biologically active molecules, including
amino acids,[3,4] heterocyclic compounds,[5] biosensors and photosensitive devices for proteins.[6]
Furthermore, these compounds are pharmaceutically active agent such as anticancer, antitumor,
antimicrobial, anti-inflammatory, anti-hypertensive, and inhibitor of central nervous system.[7-10]
After primary synthesis report in 1893 by Erlenmeyer,[11] several other dehydrating agent and
catalysts such as perchloric acid,[12] polyphosphoric acid,[13] Al2O3,[14] supported KF,[15]
Bi(OAc)3,[16]
Bi(OTf)3,[17]
Yb(OTf)3,[18]
Ca(OAc)2,[19]
organic--inorganic
hybrid
polyoxometalates,[20] TsCl-DMF,[21] and functionalized magnetic nanocatalyst[22] have been
employed in azlactones synthesis. However, some of these procedures have some
disadvantageous drawbacks, such as long reaction time, unsatisfactory yields, use of expensive,
corrosive and non-reusable catalysts and rigorous work-up procedures. Therefore, the
development of a mild, eco-friendly and more convenient method for synthesis of azlactones
without using any hazardous solvents and green catalyst is still in demand.
As a consequence of serious pollution problems, the adoption of “cleaner production” methods is
an urgent priority. Among the different strategies for achieving this goal, the use of
heterogeneous catalysts and solvent-free methods which extremely lead to milder experimental
conditions, an easier work-up, reusability of catalysts, has received special attentions.[23,24]
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In recent years, Zeolite has received considerable attention as an inexpensive, reusable without
any loss of activity, nontoxic, readily available catalyst for various organic transformations under
mild and convenient conditions to afford the corresponding products in excellent yields with
high selectivity.[25-27]
As a part of our research interest towards the development of efficient one-pot synthetic
methodologies in eco-friendly conditions,[22,28,29] herein we wish to explore an efficient
microwave-assisted synthesis of azlactone derivatives via the one-pot condensation of carbonyl
compounds and hippuric acid under solvent-free conditions using zeolite NaY as an efficient,
mild and environmentally benign catalyst (Scheme 1).
2. Experimental
All chemicals and solvents were obtained from commercial sources and used without further
purification. All known organic products were identified by comparison of their physical and
spectral data with those of authentic samples. Thin layer chromatography (TLC) was performed
on UV active precaoted plates of silica gel (TLC Silica gel60 F254).The FT-IR spectrum was
1
recorded on a Unicom Galaxy Series FT-IR 5030 spectrophotometer using KBr discs. The H
and 13C NMR spectra were recorded on a Brucker Avance spectrometer operating at 300 and 75
MHz respectively in DMSO-d6 or CDCl3 with TMS as an internal standard. Microwave
irradiation was carried out in a National Microwave Oven, Model No. NN-K571MF (2450
MHz).
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2.1. General procedure for the microwave-assisted synthesis of azlactone derivatives Catalyzed
by Zeolite NaY
The appropriate aldehyde or ketone (1 mmol), hippuric acid (1.1 mmol), Ac2O (1 ml) and
catalyst (0.1 g) was mixed in a test tube. Then, the reaction mixture was irradiated using the
microwave oven at a power output of 300W for the appropriate time according to Table 2. After
completion of the reaction as indicated by TLC, the reaction mixture was cooled to room
temperature. 3 ml cold ethanol/water (1:2) was added and the mixture was stirred for 15 min
until a yellow solid precipitated. An aqueous solution of NaHCO3 (10 ml, 20%) was added, the
solid products and the catalyst were filtered. The solid materials were dissolved in hot ethanol to
remove the catalyst. The solvent was allowed to cool in room temperature to obtain crude
products.
2.2. Spectral data for selected compounds
4-benzylidene-2-phenyloxazol-5(4H)-one (3a):
IR (KBr): max = 3070, 1789, 1651, 1552, 1450, 1305, 1158, 760, 657 cm1. 1H NMR (300 MHz,
CDCl3): δ = 2.27 (s, 1 H), 7.42--7.63 (m, 6 H), 8.18--8.21 (m, 4H). Anal Calcd for C16H11NO2:
C, 77.10; H, 4.45; N, 5.62. Found: C, 77.31; H, 4.53; N, 5.58.
4-(4-methylbenzylidene)-2-phenyloxazol-5(4H)-one (3b):
1
IR (KBr): max = 3065, 1796, 1653, 1607, 1557, 1491, 1298, 1161, 1001, 889, 775 cm1. H
NMR (300 MHz, CDCl3): δ = 2.41 (s, 3 H), 7.21--7.34 (m, 3 H), 7.50--7.62 (m, 3H), 8.11--8.19
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(m, 4H). Anal Calcd for C17H13NO2: C, 77.55; H, 4.98; N, 5.32. Found: C, 77.69; H, 5.08; N,
5.41.
4-(3,4-dimethoxybenzylidene)-2-phenyloxazol-5(4H)-one (3g):
IR (KBr): max = 3090, 3001, 2961, 2836, 1784, 1649, 1595, 1452, 1329, 1244, 1140, 1018, 866,
1
627 cm1; H NMR (300 MHz, CDCl3): δ = 8.16 (s, 1H), 8.11 (d, J = 8 Hz, 1H), 7.49-7.62 (m,
5H), 7.19 (s, 1H), 6.94 (d, J = 8.3 Hz, 1H) 4.03 (s, 3H), 3.96 (s, 3H); 13C NMR(75 MHz, CDCl3):
δ = 167.4, 161.9, 151.8, 148.8, 132.7, 131.6, 130.8, 128.7, 127.7, 127.6, 126.7, 125.6, 110.6,
55.7, 55.6; Anal Calcd for C18H15NO4: C, 69.89; H, 4.89; N, 4.53. Found: C, 69.84; H, 4.93; N,
4.61.
2-phenyl-4-(3,4,5-trimethoxybenzylidene)oxazol-5(4H)-one (3h):
IR (KBr): max = 2999, 2942, 2841, 1784, 1761, 1655, 1578, 1506, 1452, 1329, 1256, 1126,
1
1003, 966, 851, 687 cm1; H NMR (300 MHz, CDCl3): δ = 8.14 (d, J = 7.8 Hz, 2H), 7.55-7.57
(m, 5H), 7.18 (s, 1H), 3.99 (s, 6H), 3.96 (s, 3H); 13C NMR(75 MHz, CDCl3): δ = 167.3, 162.9,
153.0, 141.1, 133.1, 132.2, 131.5, 128.9, 128.8, 128.0, 125.5, 109.7, 60.9, 56.0; Anal Calcd for
C19H17NO5: C, 67.25; H, 5.05; N, 4.13. Found: C, 67.34; H, 5.10; N, 4.19.
4-(2,6-dichlorobenzylidene)-2-phenyloxazol-5(4H)-one (3j):
1
IR (KBr): max = 3084, 1797, 1759, 1672, 1564, 1427, 1321, 1165, 981, 866, 777, 698 cm1; H
NMR (300 MHz, CDCl3): δ = 8.12 (d, J = 7.9 Hz, 2H), 7.62 (t, J = 7.4 Hz, 1H), 7.50 (t, J = 7.5
Hz, 2H), 7.44 (d, J = 8.0 Hz, 2H), 7.37 (s, 1H), 7.33(t, J = 7.5 Hz, 1H);13C NMR(75 MHz,
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CDCl3): δ = 165.8, 164.5, 137.8, 135.1, 133.7, 131.3, 130.4, 128.8, 128.6, 128.2, 126.4, 125.3;
Anal Calcd for C16H9Cl2NO2: C, 60.40; H, 2.85; N, 4.40. Found: C, 60.51; H, 2.91; N, 4.37.
N-acetyl-N-(1,3-dioxo-1,3-dihydrobenzo[c]oxepin-4-yl)benzamide (3n):
IR (KBr): max = 3080, 1811, 1772, 1682, 1651, 1604, 1410, 1309, 1197, 1089, 995, 1028, 995,
1
763, 686 cm1; H NMR (300 MHz, DMSO-d6): δ = 8.20 (d, J = 8.0, 1H), 8.07 (d, J = 7.8, 1H),
7.93 (t, J = 8.0, 1H), 7.87 (s, 1H), 7.70-7.77 (m, 3H), 7.48-7.53 (m, 3H), 2.27 (s, 3H); 13C
NMR(75 MHz, CDCl3): δ = 168.2, 160.1, 157.6, 135.8, 133.6, 133.4, 130.7, 130.0, 128.9, 128.6,
128.5, 128.2, 126.0, 125.8, 108.0, 21.7; Anal Calcd for C19H13NO5: C, 68.06; H, 3.91; N, 4.18.
Found: C, 68.15; H, 3.97; N, 4.27.
4-cyclopentylidene-2-phenyloxazol-5(4H)-one (3p):
IR (KBr): max = 3054, 2962, 2874, 1778, 1676, 1568, 1450, 1323, 1249, 1147, 881, 777, 700
1
cm1; H NMR (300 MHz, CDCl3): δ = 8.07 (d, J = 7.6 Hz, 2H), 7.46-7.56 (m, 3H), 2.96(t, J =
7.2 Hz, 4H), 1.86-1.93 (quin, J = 5.6 Hz, 4H); 13C NMR(75 MHz, CDCl3): δ = 165.5, 164.8,
160.0, 132.4, 128.8, 128.5, 127.6, 126.1, 34.0, 32.5, 26.5, 25.6; Anal Calcd for C14H13NO2: C,
73.99; H, 5.77; N, 6.16. Found: C, 74.08; H, 5.83; N, 6.11.
4-(4-(tert-butyl)cyclohexylidene)-2-phenyloxazol-5(4H)-one (3r):
IR (KBr): max = 3051, 2970, 2945, 2866, 1786, 1755, 1660, 1572, 1450, 1321, 1151, 977, 883,
1
781, 702 cm1; H NMR (300 MHz, CDCl3): δ = 8.05 (d, J = 8.2 Hz, 2H), 7.46-7.58 (m, 3H),
4.05 and 3.59 (AB system, J = 12.5 Hz, 2H), 2.07-2.20 (m, 4H), 1.24-1.41 (m, 3H), 0.91 (s, 9H);
13C NMR(75 MHz, CDCl3): δ = 165.5, 161.2, 159.2, 132.3, 128.75, 128.72, 127.6, 126.1, 47.4,
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32.5, 31.9, 28.9, 27.5; Anal Calcd for C19H23NO2: C, 76.73; H, 7.80; N, 4.71. Found: C, 76.85;
H, 7.85; N, 4.70.
3. Results and discussion
Initially, as a model, the condensation reaction of benzaldehyde, hippuric acid and acetic
anhydride was examined in the presence of zeolite NaY in different solvents and solvent-free
condition under microwave irradiation (Table 1). As shown in Table 1, it was found that
microwave-assisted solvent-free condition is a more efficient (Table 1, entry 5) over the organic
solvents. When the reaction was carried out in the presence of different amounts of catalyst, the
highest yield was obtained with 0.1g of catalyst under microwave-assisted solvent-free condition
after 10 minutes. Increasing the amount of catalyst to 0.2g did not affect the product yield (Table
1, entry 7). Moreover, the catalyst is essential and in the absence of the catalyst, only 20% of the
corresponding azlactone was produced (Table 1, entry 8). The recyclability of zeolite NaY was
investigated. The catalyst was recovered easily by simple filtration, washed with hot ethanol and
dried under vacuum and reused in a subsequent reaction. As seen in Table 1, entry 6, the catalyst
showed no substantial reduction in the activity even after four runs.
After optimization of condition for azlactones synthesis and in order to investigate the generality
of this procedure, a variety of aromatic aldehydes bearing electron-withdrawing and electron-
donating groups and heterocyclic aldehydes were reacted with hippuric acid and Ac2O in the
presence of zeolite NaY under microwave-assisted solvent-free conditions. The results (Table 2)
indicated that the corresponding azlactones were synthesized in 70-92% isolated yield in 10-15
min. In order to further expand the scope of this catalytic system, cyclic ketones such as
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cyclopentanone, cyclohexanone and 4-(t-Bu)-cyclohexanone were used and successfully
converted to their corresponding azlactone derivatives with moderate yields (Table 2, entries 15-
17). Aliphatic aldehydes and ketones were also examined under the same conditions, but the
corresponding products were not isolated.
A proposed mechanism for the formation of azlactones catalyzed by zeolite NaY depicted in
Scheme 3. We assumed that the reaction proceeds via the initial activation of the carbonyl group
of acetic anhydride, followed by nucleophilic addition of hippuric acid and cyclization at the
oxygen center, with eliminaton of acetic acid and water, to form 2-phenyl-5-oxazolone
intermediate. Then zeolite-assisted deprotonation of intermediate, produce oxazolone anion
which adds to the activated carbonyl compounds and form the corresponding product. It seems
that microwave irradiation accelerates the intermediates formation and therefore, accelerates the
reaction accordingly.
It is noteworthy that, the condensation of 2-formylbenzoic acid and hippuric acid under
optimized reaction conditions was produced benzo[c]oxepine-1,3-dione derivative as an
unexpected product (Table 1, entry 14). Possible route for the formation of this product proposed
previously,[22] and illustrated in the Scheme 4. Condensation of the 2-formylbenzoic acid and
hippuric acid in the presence of the catalyst affords the corresponding azlactone as an
intermediate. The possible re-cyclization of azalactone ring by carboxylic acid group and
formation of the fused oxepine ring, followed by acetylation of NH group produce a novel
1
product. The structure of this compound was confirmed with FT-IR, H-NMR and 13C-NMR
specteroscopy.
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4. Conclusions
The Zeolite NaY catalyst has been successfully used for microwave-assisted synthesis of
azlactone derivatives via the condensation of hippuric acid with a wide variety of aromatic,
heteroaromatic and cyclic ketones under solvent-free conditions. Short reaction times, removal
of the solvent, the simple experimental and work-up procedure combined with the reusability of
catalyst, generality and good yields make this method as a mild and eco-friendly protocol for
azlactones synthesis.
Acknowledgment
We gratefully acknowledge the financial support from the Research Council of Arak University.
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References
1. Takenaka, K.; Tsuji, T. J. Heterocycl. Chem. 1996, 33, 1367.
2. Mohammed Khan, K.; Mughal, M. R.; Hassan Khan, M. T.; Ullah, Z.; Perveen, S.;
Choudhary, M. E. Bioorg. Med. Chem. 2006, 14, 6027.
3. Gottwald, K.; Seebach, D. Tetrahedron 1999, 55, 723.
4. Konkel, J. T.; Fan, J.; Jayachandran, B.; Kirk, K. L. J. Fluorine Chem. 2002, 115, 27.
5. Ivanov, I. Ch.; Glasnov, T. N.; Heber, D. J. Heterocycl. Chem. 2005, 42, 857.
6. Hermanson, G. T.; Mattson, G. R.; Krohn, R. I. J. Chromatogr. A 1995, 691, 113.
7. Sanchez, C.; Mendez, C.; Salas, J. A. Nat. Prod. Rep. 2006, 23, 1007.
8. Siddiqui, S. A.; Bhusare, S. R.; Jarikote, D. V.; Pawar, R. P.; Vibhute, Y. B. Bull. Korean
Chem. Soc. 2001, 22, 1033.
9. Goksen, U. S.; Kelekci, N. G.; Goktas, O.; Koysal, Y.; Kilic, E.; Isik, S.; Aktay, G.; Ozalp, M.
Bioorg. Med. Chem. 2007, 15, 5738.
10. Urano, K.; Tornioka, Y.; Okubo, K.; Yarnazaki, K.; Nagamatsu, A. 1989, JP 01 29369 189
29, 3691.
11. Erlenmeyer, E. Annalen. 1893, 275, 1.
12. Boyd, G.; Wright, P. J. Chem. Soc., Perkin Trans. 1, 1972, 909.
10
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13. Rao, Y. J. Org. Chem. 1996, 41, 722.
14. Conway, P. A.; Devine, K.; Paradisi, F. Tetrahedron 2009, 65, 2935.
15. Bautista, F. M.; Campelo, J. M.; García, A.; Luna, D.; Marinas, J. M.; Romero, A. A. J.
Chem. Soc., Perkin Trans. 2, 2002, 227.
16. Monk, K. A.; Sarapa, D.; Mohan, R. S. Synth. Commun. 2000, 30, 3167.
17. Khodaei, M. M.; Khosropour, A. R.; Jomor, S. J. H. J. Chem. Res. (S) 2003, 638.
18. Yu, C.; Zhou, B.; Su, W.; Xu, Z. Synth. Commun. 2006, 36, 3447.
19. Paul, S.; Nanda, P.; Gupta, R.; Loupy, A. Tetrahedron Lett. 2004, 45, 425.
20. Rostami, M.; Khosropour, A. R.; Mirkhani, V.; Moghadam, M.; Tangestaninejad, Sh.;
Mohammadpoor-Baltork, I. Appl. Catal., A: General 2011, 397, 27.
21. Moghanian, H.; Shabanian, M.; Jafari, H. C. R. Chim. 2012, 15, 346.
22. Mobinikhaledi, A.; Moghanian, H.; Pakdel, S. Chin. Chem. Lett. 2015, 26, 557.
23. Tanaka, K.; Toda, F. Chem. Rev. 2000, 100, 1025.
24. Sheldon, R. A. Green Chem. 2005, 7, 267.
25. Zendehdel, M.; Mobinikhaledi, A.; Asgari, A. J. Inclusion Phenom. Mol. Recognit. Chem.
2008, 60, 353.
26. Balalaie, S.; Arabanian, A. Green Chem. 2000, 2, 274.
11
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27. Djakovitch, L.; Koehler, K. J. Am. Chem. Soc. 2001, 123, 5990.
28. Bodaghifard, M. A.; Solimannejad, M.; Asadbegi, S.; Dolatabadifarahani, S. Res. Chem.
Intermed. 2015, DOI: 10.1007/s11164-015-2079-1.
29. Bodaghifard, M. A.; Mobinikhaledi, A.; Hamidinasab, M. Synth. React. Inorg. Met.-Org.
Chem. 2014, 44, 567.
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Table 1: Optimization of reaction conditions for synthesis of 4-benzylidene-2-phenyloxazol-
5(4H)-one (Table 2, entry 1)a.
Entry Catalyst (mg)
Solvent
Condition
Time
(min)
100
85
Yield (%)b
1
2
3
4
5
6
Zolite NaY
CHCl3
Reflux
Reflux
Reflux
MW
38
53
49
60
86
Zolite NaY
DMF
Zolite NaY
THF
100
10
Zolite NaY (0.05)
Zolite NaY (0.1)
Zolite NaY (0.1)
-
-
-
MW
10
MW
10
86, 87, 83,
82c
87
7
8
Zolite NaY (0.2)
-
-
-
MW
MW
10
10
25
aBenzaldehyde (1 mmol), hippuric acid (1.1 mmol), Ac2O (1 ml).
bIsolated yields.
CCatalyst reused in four consecutive reactions.
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Table 2: Synthesis of azlactone derivatives catalyzed by zeolite NaY under microwave
irradiation.
M.P. (°C)
Aldehydeor
Ketone (R, R’)
Yield
(%)a
Entry
Time(min)
Product
Reported
[Lit.]
Foundb
165-
166
140-
143
192-
194
171-
173
194-
195
103-
105
152-
154
199-
202
216-
218
159-
160
163-
165
167-
169
152-
155
195-
197
137-
140
113-
116
167-168
[14]
143-144
[14]
188-189
[22]
171-172
[22]
1
C6H5CHO
10
15
12
12
15
15
10
12
10
12
12
10
12
10
15
15
15
86
87
83
92
82
81
76
70
85
80
85
88
90
89
42
48
40
3a
3b
3c
3d
3e
3f
2
4-MeC6H4CHO
4-ClC6H4CHO
3-NO2C6H4CHO
4-BrC6H4CHO
3-MeOC6H4CHO
3
4
197-199
[22]
5
6
99-102 [14]
3,4-
150-152
[19]
203-204
[22]
212-214
[21]
153-155
[22]
168-169
[14]
170-171
[22]
145-147
[15]
198-199
[22]
7
3g
3h
3i
(MeO)2C6H3CHO
3,4,5-
(MeO)3C6H2CHO
8
9
4-N(Me)2C6H4CHO
2,6-Cl2C6H4CHO
Pyridine-2-CHO
Thiophene-2-CHO
10
11
12
13
14
15
16
17
3j
3k
3l
5-(Me)-Thiophene-2-
CHO
3m
3n
3o
3p
3r
2-Formylbenzoic
acidc
Cyclohexanone
Cyclopentanone
128 [15]
116 [22]
4-(t-Bu)-
Cyclohexanone
126-
128
124-125
[22]
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aIsolated yields.
bMelting points are not corrected.
cScheme 4.
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O
R
O
O
O
Zeolite NaY
Ac2O, MW
N
N
COOH
R'
+
H
R
R'
3 a-r
1
2
Scheme 1: The Zeolite NaY catalyzed Erlenmeyer azlactones synthesis.
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O
O
CHO
O
N
+
N
COOH
H
Scheme 2: Optimization of reaction condition.
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zeolite
O
O
O
HO
H3C
O
O
N
Ph
O
O
O
H3C
O
CH3
H
O
O
H3C
O
CH3
N
Ph
H
- CH3COOH
- CH3COOH
- H2O
zeolite
Ph
N
O
O
H
H
zeolite
R'
zeolite
O
R'
O
R
R
R
HO
R'
O
zeolite
O
O
N
H
H
O
N
O
- H2O
N
Ph
Ph
Ph
Scheme 3: Plausible mechanism for azlactone formation in the presence of zeolite NaY.
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O
Ph
CHO
O
Ph
Ph
O
CH3
NH
N
Ac2O
N
COOH
O
Ac2O
Cat.
O
+
O
O
O
O
O
OH
Ph
N
COOH
O
H
O
O
3n
Scheme 4: Proposed route for condensation of hippuric acid and 2-formylbenzoic acid.
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