472 Dandia, Singh, and Sharma
mixture (0.01 mol) of 5-methyl-indole-2,3-dione
1a and 2-trifluoromethyl aniline 2a was refluxed
in dry toluene for 4 h. Crystals separated out
on cooling were dried and recrystallized from
ethanol (yield = 70%; m.p. 165◦C [19]).
Synthesis of Mannich Base of Spiro
Compounds 7a/7b
A mixture of appropriate spiro compound 6a/6b
(1 mmol), formaldehyde (1.5 mmol, 40%), and mor-
pholine (1 mmol) was irradiated in a microwave oven
at power output at 640 W for the period indicated in
Table 2 (TLC). The resultant residue after crystalliza-
tion from methanol gave 7a/7b.
2. Synthesis of spiro product: To a well stirred
solution of 3a (0.005 mol) and triethylamine
(0.005 mol) in dry benzene (10 ml) was
added chloroacetyl chloride (0.005 mol) drop-
wise at room temperature. After the addition of
chloroacetyl chloride, the mixture was further
stirred for 3 days. The precipitated triethylamine
hydrochloride was filtered off and washed thor-
oughly with dry benzene. The solvent from the
filtrate was evaporated in vacuo and the residue
was recrystallized from benzene-pet-ether.
ACKNOWLEDGMENT
We are thankful to CDRI, Lucknow, India, for spec-
troscopic data and elemental analyses.
REFERENCES
[1] Manas, M. S.; Bose, A. K. Synthesis of Penicillin,
Cephalosporin and Analogs; Marcel Dekker, Inc.: New
York, 1969; p. 13.
[2] Doherty, J. B.; Down, C. P. PCT Int Appl WO
94,10,193, 1994; Chem Abstr 1995, 122, 160362k.
[3] Khalafallah, A. K.; Selim, M. A.; Abu, R. M.;
Elmaghraby, M. A.; Soleiman, H. A.; Raslan, M. A.
Indian J Chem 1995, 34B, 1060.
Microwave-Assisted Synthesis (Synthesis of 3a)
An equimolar mixture (0.01 mol) of 1a and 2a was
irradiated under microwave irradiation for 30 s at
640 W (monitored by TLC). The intermediate 3a was
so obtained in reasonable purity (TLC) (confirmed by
mixed mp with authentic sample), and used as such
for the next step for the synthesis of spiro[indole-
azetidine] 6a by following two methods to study the
role of power level, medium, and base.
Using the MORE technique: An equimolar
mixture (0.005 mol) of 3a, triethylamine, and
chloroacetyl chloride in o-dichlorobenzene (5 ml) in
an erlenmeyer flask was irradiated inside a domes-
tic microwave oven at power 30% (275 W) and 70%
(480 W) for 10 and 7 min respectively to check the ef-
fect of power level. Progress of the reaction was mon-
itored by TLC. Reaction mixture was cooled down
and the precipitate of triethylamine hydrochloride
was filtered off and washed thoroughly with benzene,
and the excess solvent was evaporated on a rotary-
evaporator to give a solid that was found to be pure
by TLC.
Using inorganic solid support: K2CO3 (2 mmol,
i.e., 376 g) was coground with 4 g of basic alumina
in an agate mortar. To this, a mixture of intermedi-
ate 3a (2 mmol) and chloroacetyl chloride 4 (3 mmol)
was added, mixed thoroughly, and irradiated under
microwave irradiation at 640 W for 6 min. The prod-
uct was obtained by desorption with methanol and
found to be pure by TLC.
The identity of compound 6a synthesized by
various methods, i.e., conventionally and under
microwave irradiation by changing power level,
medium, and base, was confirmed by mixed mps
and spectral studies. Other compounds 6b–g listed
in Table 2 were similarly prepared under solvent-free
conditions using (K2CO3–Al2O3) as support.
[4] Vashi, B. S.; Mehta, D. S.; Shah, V. H. Indian J Chem
1995, 34B, 802.
[5] Edmondson, S.; Danishefsky, J. S.; Sepp-Lorenzino,
L.; Rosen, N. J Am Chem Soc 1999, 121, 2147.
[6] Keplinger, K.; Wagner, H.; Kreutz-Kamp, B. PCT Int
86,00,524, 1986; Chem Abstr 1986, 105, 146231j.
[7] Joshi, K. C.; Jain, R.; Sharma, V. J Indian Chem Soc
1986, 63, 430.
[8] Filler, R. Chem Tech 1974, 4, 752.
[9] Whittle, B. A.; Youny, E. H. P. J Med Chem 1963, 6,
378.
[10] (a) Hassan, K. M.; El-Shavei, A. K.; El-Kashev, H.
S. Z Naturforsch B 1978, 33, 1515; (b) Joshi, K. C.;
Dandia, A.; Bhagat, S. J Fluorine Chem 1990, 48,
169; (c) Awad, I. M. A.; Abdel-Hafez, A. A.; Hassan,
K. M. Stud Org Chem 1988, 35, 201; (d) Kumar, R.;
Giri, S.; Nizamuddin, J. Agric Food Chem 1989, 37,
10946.
[11] (a) Bose, A. K.; Banik, B. K.; Manhas, M. S. Tetrahe-
dron Lett 1995, 36, 213; (b) Bose, A. K.; Jayaraman,
M.; Okawa, A.; Bari, S. S.; Robb, E. B.; Manhas, M.
S. Tetrahedron Lett 1996, 39, 6989; (c) Banik, B. K.;
Manhas, M. S.; Rebb, E. W.; Bose, A. K. Tetrahedron
Lett 1997, 44, 403.
[12] (a) Loupy, A.; Petit, A.; Hamelin, J.; Texier-Boullet,
F.; Jacquault, P.; Mathe, D. Synthesis 1998, 1231;
(b) Varma, R. S. Green Chem 1999, 1, 43.
[13] (a) Dandia, A.; Sachdeva, H.; Singh, R.; Sharma, C. S.
Indian J Chem 2003, 42, 140; (b) Dandia, A.; Sati, M.;
Arya, K.; Loupy, A. Heterocycles 2003, 60(3), 563; (c)
Dandia, A.; Sati, M.; Loupy, A. Green Chem 2002, 4,
599; (d) Dandia, A.; Singh, R.; Sachdeva, H.; Arya,
K. J Fluorine Chem 2001, 111, 61; (e) Dandia, A.;
Sachdeva, H.; Singh, R. J Chem Res (S) 2000, 272; (f)
Dandia, A.; Sachdeva, H.; Singh, R. Synth Commun
2000, 31, 87; (g) Dandia, A.; Saha, M.; Taneja, H. J
Fluorine Chem 1998, 90, 17; (h) Dandia, A.; Upreti,