Synthesis of 5-aryl-3H-[1,3,4]oxadiazol-2-ones from N′-(chloro-aryl- methylene)-tert-butylcarbazates using basic alumina as an efficient and recyclable surface under solvent-free condition

Article abstract of DOI:10.1016/j.tetlet.2012.11.128

The synthesis of biologically important 5-aryl-3H-[1,3,4]oxadiazol-2-ones has been carried out by heating the easily synthesized N′-(chloro-aryl- methylene)-tert-butylcarbazates on basic alumina surface under solvent-free condition. The dual characteristic of basic alumina as a solid support as well as a nucleophile is successfully exploited in these reactions. The method provides special attributions such as reduced reaction times, easier work-up procedures, and good to excellent yields as well as increased purity of products and most importantly environmentally friendly protocols. The basic alumina is easily recovered and utilized for further reactions several times without serious loss of activity.

Full text of DOI:10.1016/j.tetlet.2012.11.128

Tetrahedron Letters 54 (2013) 896–899
Contents lists available at SciVerse ScienceDirect
Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Synthesis of 5-aryl-3H-[1,3,4]oxadiazol-2-ones
from N0-(chloro-aryl-methylene)-tert-butylcarbazates using basic alumina
as an efficient and recyclable surface under solvent-free condition
⇑
Kamalesh Debnath, Sudipta Pathak, Animesh Pramanik
Department of Chemistry, University of Calcutta, 92, A.P.C. Road, Kolkata 700 009, India
a r t i c l e i n f o
a b s t r a c t
Article history:
The synthesis of biologically important 5-aryl-3H-[1,3,4]oxadiazol-2-ones has been carried out by heat-
ing the easily synthesized N0-(chloro-aryl-methylene)-tert-butylcarbazates on basic alumina surface
under solvent-free condition. The dual characteristic of basic alumina as a solid support as well as a
nucleophile is successfully exploited in these reactions. The method provides special attributions such
as reduced reaction times, easier work-up procedures, and good to excellent yields as well as increased
purity of products and most importantly environmentally friendly protocols. The basic alumina is easily
recovered and utilized for further reactions several times without serious loss of activity.
Ó 2012 Elsevier Ltd. All rights reserved.
Received 25 September 2012
Revised 24 November 2012
Accepted 27 November 2012
Available online 13 December 2012
Keywords:
5-Aryl-3H-[1,3,4]oxadiazol-2-one
N0-(Chloro-aryl-methylene)-tert-
butylcarbazate
N-Chlorosuccinamide
Basic alumina as solid support
Solvent-free condition
Synthesis of novel oxadiazole derivatives and investigation of
their chemical and biological behaviors have gained immense sig-
nificance in the recent decades for new drug development. Com-
tivity on the solid surface.15a Solid supported reactions under sol-
vent-free conditions have emerged to be an effective route in
terms of product yields, reaction times and conditions, ease of
purification, and work-up procedures.15 Since the inorganic solid
supports are easily recyclable, organic reactions on such solid sup-
ports are environmentally acceptable.16 Alumina is one of the
examples of proficient catalyst and reagent due to its surface prop-
erty and well defined porosity17 along with its low cost and easy
availability and nontoxicity. Here we report a green synthesis of
5-aryl-3H-[1,3,4]oxadiazol-2-ones from easily synthesized N0-
(chloro-aryl-methylene)-tert-butylcarbazates employing basic alu-
mina as a solid support. To the best of our knowledge, this is the
first time the synthesis of 5-aryl-3H-[1,3,4]oxadiazol-2-ones on so-
lid support under solvent-free condition has been accomplished.
Initially a series of carbo-tert-butoxyhydrazones (3a–m) are
prepared by the condensation of aromatic aldehydes (1a–m) with
tert-butylcarbazate (2). Subsequently, compounds 3 are treated
with N-chlorosuccinamide in dry DMF medium to get N0-(chloro-
aryl-methylene)-tert-butylcarbazates (4a–m) in very high yields
(Scheme 1, Table 1).18a Although the chlorination of oxime com-
pounds using N-chlorosuccinamide in dry DMF medium is well
known in the literature,19 this is the first time the synthesis of
chlorinated compounds 4a–m starting from carbo-tert-butoxyhyd-
razones of aromatic aldehydes has been carried out. Interestingly,
compounds 4a–m, in absorbed condition on the basic alumina sur-
face, are easily converted into 5-aryl-3H-[1,3,4]oxadiazol-2-ones
(5a–m) in good to excellent yields (81–99%) upon heating around
pounds bearing 1,3,4-oxadiazole nucleus possess
a
wide
spectrum of medicinal activities such as antiedema and anti-
inflammatory activities,1–3 analgesic,2,3 antimicrobial,4 antituber-
cular,5 anticonvulsant,6 anti-hepatitis B viral activities,7 and a pop-
ular bioisostere for improving the pharmacological profile of
biologically active amides, esters, and ureas.8 So far, several meth-
ods of synthesis of 5-aryl-3H-[1,3,4]oxadiazol-2-ones have been
reported in the literature.9–13 Although these methods are helpful
for the construction of 3H-[1,3,4]oxadiazol-2-one nucleus, still all
these reactions have some significant drawbacks such as the use
of hazardous and toxic reagents like phosgene or milder phosgene
equivalents9 and lead tetraacetate,10 metal catalyst,11 laborious
reaction procedures with longer reaction times,10–12 harsh reaction
conditions, and low to moderate percentage of yield10,13 which are
not desirable for the synthesis of such biologically important het-
erocyclic compounds. Therefore an efficient, safer, and environ-
mentally friendly method is required within the frame of Green
Chemistry principles.14
Organic synthesis on porous solid materials possesses a lot of
advantages over the conventional solution phase synthesis because
of the homogenous dispersion of active sites and associated selec-
⇑
Corresponding author. Tel.: +91 33 2484 1647; fax: +91 33 2351 9755.
E-mail address: animesh_in2001@yahoo.co.in (A. Pramanik).
0040-4039/$ - see front matter Ó 2012 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tetlet.2012.11.128

K. Debnath et al. / Tetrahedron Letters 54 (2013) 896–899
897
H
H
Cl1
C7
O
H
N
N
O
O3
C9
O
Ar
N
H2N
+
Ar
H
C8
O
O
O2
N2
N3
3a-m
C2
2
1a-m
C1
O4
C12
C11
N1
Dry DMF,
NCS
C6
C3
Stirring at rt
O1
C5
O
C10
Cl
O
C4
Basic alumina
85°C
H
N
NH
O
Ar
N
N
Ar
O
Figure 1. ORTEP diagram of compound 4c with atom numbering scheme. Thermal
ellipsoids are shown at 50% probability.
4a-m
5a-m
Scheme 1. Synthesis of 5-aryl-3H-[1,3,4]oxadiazol-2-ones from aromatic
aldehydes.
O2
C5
O1
C6
Table 1
Preparation of 4a–m from 3a–m using N-chlorosuccinamide
C1
C9
Entry
1
Ar
Adduct
Yielda (%)
Melting point (°C)
4a
94
79–80
C7
C8
C4
C2
c
N2
2
3
4b
4c
90
96
73–74
C3
N1
152–153
Figure 2. ORTEP diagram of compound 5b with atom numbering scheme. Thermal
O2N
O2N
ellipsoids are shown at 50% probability.
4
5
4d
4e
91
85
141–142
99–100
At the beginning of our investigation we focused on the system-
atic evaluation of a wide range of solid supports including molec-
ular sieves, sea sand, celite-545, silica gel, NaOH beads, K2CO3,
and different types of alumina where basic alumina was found to
be the most effective solid support for the formation of 5a under
solvent-free condition (Table 2). However, the remarkable differ-
ence of efficiency between two forms of alumina might be due to
the compositional and structural differences which account for
their different surface and catalytic reactivity.
F
6
4f
87
84–85
Cl
7
8
9
4g
4h
4i
85
88
91
90–91
95–96
72–73
Cl
Cl
Next, we focus on the development of an optimum set of reaction
conditions using basic alumina where a maximum yield of product
can be obtained. Initially, when N0-(chloro-phenyl-methylene)-
Table 2
Br
Optimization studies with 4a using different solid supports in the reaction
Entry
Medium
Yield of 5aa (%)
10
4j
80
80–81
1
2
3
4
5
6
7
8
Molecular sieves 4 Å
Neutral alumina
Basic alumina
Sea sand
Silica gel (60–120 mesh)
Celite-545
22c
35c
99d
12c
40b
5
Br
Br
11
12
13
4k
4l
83
90
84
77–78
NC
149–150
104–105
K2CO3
NaOH
—
—
e
MeO
4m
a
Optimization studies are carried out with 0.5 mmol 4a and 500 mg of solid
support at 85 °C for 15 min.
a
Isolated yield.
b
Although silica gel gives moderate yield of product 5a, the reaction mixture is
turned into reddish brown on maintaining the same reaction condition; colored
impurities are obtained in considerable amount.
c
85 °C for 8–15 min (Scheme 1).18b Hydrolysis and cyclization of
4a–m take place efficiently on the solid surface of basic alumina
under the solvent-free condition to produce the final products
5a–m. The formation of compounds 4 and 5 are confirmed by IR,
1H, 13C, and X-ray diffraction studies (Figs. 1 and 2)20 and also com-
paring the melting points of 5 with the reported values.
Many spots, along with the spots of starting material and product are found in
TLC monitoring which suggests that the reaction is not clean in the presence of
these solid supports.
d
Single spot for required product only in TLC.
Upon heating, the reaction mixture is turned into dark pink immediately
e
without giving any desirable product. It suggests that drastic condition is not
suitable for the reaction.

898
K. Debnath et al. / Tetrahedron Letters 54 (2013) 896–899
tert-butylcarbazate 4a (0.5 mmol) is soaked on the solid surface of
100 mg of basic alumina at room temperature, no product is ob-
tained. But, gratifyingly, 99% yield of compound 5a is achieved with-
in 15 min using 500 mg of basic alumina for 0.5 mmol of 4a and on
heating at 85 °C (Table 3, entry 8). At higher temperature the reac-
tion mass is partially decomposed and the yield of the desired prod-
uct decreases significantly. Apart from that, on heating after 20 min
at 85 °C with lesser amount of basic alumina (200 mg) the reaction
mixture is turned into dark pink from white with considerable
amount of formation of side products. Therefore, it can be concluded
that the maintenance of the proper reaction conditions such as reac-
tion time (15 min), temp (85 °C), and amount of basic alumina
(500 mg) is necessary for obtaining the maximum yield of the final
product. Similar optimization is also carried out with other solid
supports such as neutral alumina and silica gel. But in both cases
the yield and purity of the final product are always observed to be
considerably less than that of basic alumina. After the optimization
of the reaction conditions for the best possible yields we have carried
out the reaction for a series of differently substituted 4 with basic
alumina to get the products 5 (Table 4).
The formation of 5-aryl-3H-[1,3,4]oxadiazol-2-ones 5 from
intermediate N0-(chloro-aryl-methylene)-tert-butylcarbazates
4
comprises of an interesting mechanistic pathway (Scheme 2). The
remarkable performance of basic alumina can be ascribed to the
presence of Al–Oꢀ groups on the alumina surface21 that plays a
key role in the nucleophilic substitutions to form the cyclic inter-
mediate 6 followed by the intramolecular cyclization to furnish
the final compounds 5-aryl-3H-[1,3,4]oxadiazol-2-ones 5. The
intramolecular cyclization of intermediate 6 is facilitated probably
due to the close proximity of the attacking nucleophilic oxygen
atom and the electrophilic carbonyl carbon of the cyclic ester on
the basic alumina surface and also for the formation of a stable five
membered ring in the final product.
Furthermore, a recovering and reusability test of basic alumina
in the formation of 5a is performed up to six times without any
serious loss of its activity or efficiency. After heating N0-(chloro-
phenyl-methylene)-tert-butylcarbazate 4a with basic alumina at
85 °C for 15 min, the product 5a is simply extracted with ethyl ace-
tate. Then the solid phase is separated and dried under vacuum and
the recovered basic alumina is reused directly for a new reaction
cycle. The yield of the product 5a varies from 99% to 97% after
six successive cycles (Fig. 3).22
Table 3
Optimization of reaction conditions using 4a
Entry
Basic aluminaa (mg)
Temperature (°C)
Yield of 5a (%)
1
2
3
4
5
6
7
8
9
100
100
100
100
200
300
400
500
500
rt
None
20
33
40
48
55
80
99
57
50
80
85
85
85
85
85
100
In conclusion, we have successfully developed a new and
efficient route for the synthesis of biologically important 5-
aryl-3H-[1,3,4]oxadiazol-2-ones from N0-(chloro-aryl-methylene)-
tert-butylcarbazates using basic alumina as a solid support under
solvent-free condition. The significant advantages of this method-
ology are cost effectiveness, operational simplicity, good to excel-
lent yields of the products, and easy availability and reusability
a
Basic alumina dried under vacuum is used.
100
80
60
40
20
0
Table 4
Formation of 5a–m from 4a–m at 85 °C on solid basic alumina
Entry
Adduct
Product
Time
(min)
% of
Lit. mp/observed mp (°C)
yielda
1
2
3
4
5
6
7
8
4a
4b
4c
4d
4e
4f
4g
4h
4i
5a
5b
5c
5d
5e
5f
5g
5h
5i
15
8
99
82
87
84
88
90
80
82
98
83
89
85
81
138–13912a/138–139
16112a/160–162
12
10
15
10
11
10
12
15
13
15
15
190–19212a/193–194
251–25312a/250–251
159–160b
165–16612a/166–167
158–15912a/158–159
234–23512a/236-237
150–151b
9
10
11
12
13
4j
4k
4l
5j
5k
5l
185–1869g/184–185
244–24512b/242–243
205–206b
1
2
3
4
5
6
4m
5m
193.1–193.89g/191–192
Number of Runs
a
Isolated yield.
b
In the literature, melting points of these compounds are not reported.
Figure 3. Reuse of basic alumina in the synthesis of 5a.
O
Ar
O
Ar
O
O
O
Ar
O
N
N
Cl
N
-
NH
O
- Cl
NH
Al O
SiO3
+
2
2
O
O
Al2O3
- tBuO
-
ASliOO
NH
2
23
O
O
O
O
O
5
O
O
O
O
O
O
4
6
Scheme 2. Plausible reaction mechanism for the formation of compounds 5.

K. Debnath et al. / Tetrahedron Letters 54 (2013) 896–899
899
15. (a) Varma, R. S. Green Chem. 1999, 1, 43; (b) Varma, R. S. Clean Prod. Processes
1999, 1, 132; (c) Loupy, A.; Petit, A.; Hamelin, J.; Texier-Boullet, F.; Jacquault, P.;
Mathe´, D. Synthesis 1998, 1213; (d) Bram, G.; Loupy, A.; Villemin, D. Solid
Supports and Catalysts in Organic Synthesis In Smith, K., Ed.; Ellis Horwood
Prentice Hall: Chichester, 1992; p 302. Chapter 12.
of the solid support. Therefore this may be a very attractive meth-
od for the synthesis of 5-aryl-3H-[1,3,4]oxadiazol-2-ones in chem-
ical and pharmaceutical industries within the green chemistry
protocols.
16. (a) Bram, G.; Loupy, A.; Majdoub, M.; Petit, A. Chem. Ind. 1991, 11, 396; (b)
Bougrin, K.; Soufiaoui, M. Tetrahedron Lett. 1995, 36, 3683.
Acknowledgements
17. (a) Sánchez-Valente, J.; Hernández-Beltrán, F.; Guzmán-Castillo, M. L.; Fripiat, J.
J.; Bokhimi, X. J. Mater. Res. 2004, 19, 1499; (b) Keshavarz, A. R.; Rezaei, M.;
Yaripour, F. Power Tech. 2010, 199, 176; (c) Ionescu, A.; Allouche, A.; Aycard, J.-
P.; Rajzmann, M.; Hutschka, F. J. Phys. Chem. B 2002, 106, 9359; (d) Maggi, R.;
Ballini, R.; Sartori, G.; Sartorio, R. Tetrahedron Lett. 2004, 45, 2297; (e) Blass, B.
E. Tetrahedron 2002, 58, 9301. and the references cited therein.
K.D. and S.P. thank UGC and CSIR, New Delhi, India, respectively,
for offering them Junior Research Fellowship (JRF). The financial
assistance of CSIR, New Delhi is gratefully acknowledged [Major
Research Project, No. 02(0007)/11/EMR-II]. Crystallography was
performed at the DST-FIST, India-funded Single Crystal Diffractom-
eter Facility at the Department of Chemistry, University of Calcutta.
18. (a) General procedure for the synthesis of N0-(chloro-aryl-methylene)-tert-
butylcarbazates (4): Aromatic aldehydes
1
(1.00 mmol) and tert-
butylcarbazate 2 (1.00 mmol) are placed in a 50 ml round bottomed flask
where condensation between 1 and 2 takes place instantaneously to form the
carbo-tert-butoxyhydrazones 3. In the case of solid aldehydes, 5.0 ml of
methanol is required to add to the mixture of 1 and 2 and heated slightly on a
water bath to furnish the condensation. Subsequently, N-chlorosuccinamide
Supplementary data
(1.00 mmol) is added to the dry DMF (10 ml) solution of compounds
3
Supplementary data (IR, 1H, 13C data of compounds 4 and 5)
associated with this article can be found, in the online version, at
http://dx.doi.org/10.1016/j.tetlet.2012.11.128.
(1.00 mmol) at cold condition (temperature around 0 °C) and then stirred for
3 h at room temperature. The progress of the reaction is monitored by TLC
analysis. After completion of the reaction, the reaction mixture is poured into
ice-cold water and the solid residue 4 is filtered out, which is washed several
times with distilled water, dried in open air and then crystallized from acetone.
(b) General procedure for the synthesis of 5-aryl-3H-[1,3,4]oxadiazol-2-ones
References and notes
(5): Compound
4 (0.50 mmol) is dissolved in a minimum quantity of
chloroform in a round bottomed flask and basic alumina (500 mg) is added
to it. The thoroughly mixed reaction mixture is dried under vacuum and then
heated around 85 °C on a water bath for the time indicated in Table 4. The
progress of the reaction is monitored by TLC analysis. After completion of the
reaction, the reaction mixture is cooled to room temperature and extracted
with ethyl acetate. Pure white powdered product is obtained by the
1. Omar, F. A.; Mahfouz, N. M.; Rahman, M. A. Eur. J. Med. Chem. 1996, 31, 819.
2. Narayana, B.; Vijayaraj, K. K.; Ashlatha, B. V.; Kumari, N. S. Arch. Pharm.
(Weinheim) 2005, 338, 373.
3. Amir, M.; Kumar, S. Acta Pharm. 2007, 57, 31.
4. Gaonkar, S. L.; Rai, K. M. L.; Prabhuswamy, B. Eur. J. Med. Chem. 2006, 41, 841.
5. Ali, M. A.; Shaharyar, M. Bioorg. Med. Chem. Lett. 2007, 17, 3314.
6. Zarghi, A.; Tabatabai, S. A.; Faizi, M.; Ahadian, A.; Navabi, P.; Zanganeh, V.;
Shafiee, A. Bioorg. Med. Chem. Lett. 2005, 15, 1863.
7. Tan, T. M. C.; Chen, Y.; Kong, K. H.; Bai, J.; Li, Y.; Lim, S. G.; Ang, T. H.; Lam, Y.
Antiviral Res. 2006, 71, 7.
evaporation of ethyl acetate under vacuum. Then the compound
crystallized from a mixture of petroleum ether and ethyl acetate.
5 is
Representative spectral data of compounds: N0-(Chloro-phenyl-methylene)-tert-
butylcarbazate (4a): 1H NMR (300 MHz, CDCl3):
J = 5.7 Hz, ,2H), 7.45–7.43 (m, 3H), 1.54 (s, 9H); 13C NMR (75 MHz, CDCl3): d
152.1, 142.8, 133.6, 130.6, 128.8, 126.9, 80.8, 28.0; IR (KBr): 3168, 1720 cmꢀ1
d 10.23 (s,1H), 7.78 (t,
8. (a) Borg, S.; Estenne-Bouhtou, G.; Luthman, K.; Csoeregh, I.; Hesselink, W.;
Hacksell, U. J. Org. Chem. 1995, 60, 3112; (b) Poulain, R. F.; Tartar, A. L.; Déprez,
B. P. Tetrahedron Lett. 2001, 42, 1495; (c) Poindexter, G. S.; Bruce, M. A.;
Breitenbucher, J. G.; Higgins, M. A.; Sit, S.-Y.; Romine, J. L.; Martin, S. W.; Ward,
S. A.; McGovern, R. T.; Clarke, W.; Russell, J.; Antal-Zimanyi, I. Bioorg. Med.
Chem. Lett. 2004, 12, 507; (d) Elzein, E.; Ibrahim, P.; Koltun, D. O.; Rehder, K.;
Shenk, K. D.; Marquart, T. A.; Jiang, B.; Li, X.; Natero, R.; Li, Y.; Nguyen, M.;
Kerwar, S.; Chu, N.; Soohoo, D.; Hao, J.; Maydanik, V. Y.; Lustig, D. A.; Zeng, D.;
Leung, K.; Zablocki, J. A. Bioorg. Med. Chem. Lett. 2004, 14, 6017.
9. (a) Smith, A. E. W. Science 1954, 119, 514; (b) Stempel, A.; Zelauskas, J.;
Aeschlimann, J. A. J. Org. Chem. 1955, 20, 412; (c) Rosen, G. M.; Popp, F. D.;
Gemmill, F. Q., Jr. J. Heterocycl. Chem. 1971, 8, 659; (d) Chau, N.; Saegusa, Y.;
Iwakura, Y. J. Heterocycl. Chem. 1982, 19, 541; (e) Thompson, S. K.; Smith, W.
W.; Zhao, B.; Halbert, S. M.; Tomaszek, T. A.; Tew, D. G.; Levy, M. A.; Janson, C.
A.; DAlessio, K. J.; McQueney, M. S.; Kurdyla, J.; Jones, C. S.; DesJarlais, R. L.;
Abdel-Meguid, S. S.; Veber, D. F. J. Med. Chem. 1998, 41, 3923; (f) Yamada, N.;
Kataoka, Y.; Nagami, T.; Hong, S.; Kawai, S.; Kuwano, E. J. Pestic. Sci. 2004, 29,
205; (g) Levins, C. G.; Wan, Z.-K. Org. Lett. 2008, 10, 1755; (h) Zampieri, D.;
Mamolo, M. G.; Laurini, E.; Fermeglia, M.; Posocco, P.; Pricl, S.; Banfi, E.;
Scialino, G.; Vio, L. Bioorg. Med. Chem. Lett. 2009, 17, 4693.
;
Anal Calcd for C12H15Cl1N2O2: C, 56.59; H, 5.94; N, 11.00%. Found C, 56.53; H,
5.90; N, 10.96%.
N0-(Chloro-p-tolyl-methylene)-tert-butylcarbazate (4b): 1H NMR (300 MHz,
CDCl3): d 8.185 (s, 1H), 7.67 (d, J = 7.8 Hz, 2H), 7.03 (d, J = 7.8 Hz, 2H), 1.41 (s,
9H); 13C NMR (75 MHz, CDCl3): d 151.7, 140.7, 130.5, 129.4, 127.0, 125.5, 82.1,
28.0, 21.1; IR(KBr): 3208, 1699 cmꢀ1; Anal Calcd for C13H17Cl1N2O2: C, 58.10;
H, 6.38; N, 10.42. Found C, 58.05; H, 6.34; N, 10.36.
19. (a) Gucma, M.; Gołe˛biewski, W. M.; Morytz, B.; Charville, H.; Whiting, A. Lett.
Org. Chem. 2010, 7, 502; (b) Patent: W.O. 2010085581 A1, 2010.; (c) Patent:
W.O. 2011017578 A1, 2011.; (d) Patent: W.O. 2011059784 A1 2011.
20. Crystallographic data for the structure 4c and 5b in this Letter have been
deposited with Cambridge Crystallographic Data Centre as supplementary
publication no. CCDC 898547, 898548, respectively. Copies of the data can be
obtained, free of charge on application to CCDC, 12 Union Road, Cambridge CB2
1EZ, UK. Fax: +44 01223 336033 or e-mail: deposit@ccdc.cam.ac.uk.
21. (a) Saha, P.; Naskar, S.; Paira, P.; Hazra, A.; Sahu, K. B.; Paira, R.; Banerjee, S.;
Mondal, N. B. Green Chem. 2009, 11, 931; (b) Paira, R.; Maity, A.; Mondal, S.;
Naskar, S.; Sahu, K. B.; Saha, P.; Hazra, A.; Padmanaban, E.; Banerjee, S.;
Mondal, N. B. Tetrahedron Lett. 2011, 52, 1653.
22. Reusability study of basic alumina: The aforementioned procedure18b is
10. Baumgarten, H. E.; Hwang, D. R.; Rao, T. N. J. Heterocycl. Chem. 1986, 23, 945.
11. Liu, Q.; Wu, P.; Yang, Y.; Zeng, Z.; Liu, J.; Yi, H.; Lei, A. Angew. Chem., Int. Ed.
2012, 51, 4666.
12. (a) Davidson, J. S. Monatsh. Chem. 1988, 119, 1027; (b) Ioannisyan, E. M.;
Chernitsa, B. V.; Yakovlev, V. V. J. Russian Org. Chem. 2006, 42, 1089.
13. Golfier, M.; Milcent, R. Synthesis 1979, 946.
employed
with
N0-(chloro-phenyl-methylene)-tert-butylcarbazate
4a
(0.50 mmol) and basic alumina (500 mg). After the completion of the
reaction, the solid basic alumina is treated with ethyl acetate to extract the
product 5a and the basic alumina is separated by filtration, dried under
vacuum and reused in further reactions without any purification.
14. Anastas, P. T.; Warner, J. C. Green Chemistry: Theory and Practice; Oxford
University Press: Oxford, 1998.