2066
P. B. Thorat et al.
LETTER
(14) (a) Saha, B. K.; Jetti, R. K. R.; Reddy, S.; Aitipamula, S.;
Nangia, A. Cryst. Growth Des. 2005, 5, 887. (b) Saha, B. K.;
Aitipamula, S.; Banerjee, R.; Nangia, A.; Jetti, R. K. R.;
Boese, R.; Lam, C. K.; Mak, T. C. W. Mol. Cryst. Liq. Cryst.
2005, 440, 295. (c) Desiraju, G. R. Acc. Chem. Res. 2002,
35, 565.
G.; Bucherri, F.; Noto, R.; Gentile, M. J. Heterocycl. Chem.
1977, 14, 1385. (e) Guin, S.; Ghosh, T.; Rout, S. K.;
Banerjee, A.; Patel, B. K. Org. Lett. 2011, 13, 5976.
(f) Rostamizadeh, S.; Ghasem Housaini, S. A. Tetrahedron
Lett. 2004, 34, 8753.
(20) (a) Yang, R.-Y.; Dai, L.-X. J. Org. Chem. 1993, 58, 3381.
(b) Rao, V. S.; Sekhar, K. Synth. Commun. 2004, 34, 2153.
(c) Kumar, D.; Sundaree, S.; Johnson, E. O.; Shah, K.
Bioorg. Med. Chem. Lett. 2009, 19, 4492. (d) Prakash, O.;
Kumar, M.; Kumar, R.; Sharma, C.; Aneja, K. R. Eur. J.
Med. Chem. 2010, 4252. (e) Shang, Z.; Reiner, J.; Chang, J.;
Zhao, K. Tetrahedron Lett. 2005, 46, 2701. (f) Shang, Z.
Synth. Commun. 2006, 36, 2927. (g) Dobrota, C.;
Paraschivescu, C. C.; Dumitru, I.; Matache, M.; Baciu, I.;
Rut, L. L. Tetrahedron Lett. 2009, 50, 1886.
(15) Preparation of 2,4,6-Tris(4-iodophenoxy)-1,3,5-triazine
(11)
KOH (20 mmol, 1.12 g) was added to acetone (150 mL) and
stirred for 45 min. 4-Iodophenol (20 mmol, 4.4 g) was then
added to this solution and again stirred for 30 min. The
resulting mixture was cooled to 0 °C, cyanuric chloride
(5 mmol, 0.92 g) was added, and the mixture stirred for a
further 1 h at 0 °C. The reaction mixture was allowed to stir
for 48 h at r.t., poured into crushed ice, the resulting white
precipitate was filtered with suction and then washed with
MeOH to furnish 11 in 93% yield. White solid, mp 236–
238 °C. 1H NMR 400 MHz (CDCl3): δ = 6.88 (2 H, d,
(21) General Experimental Procedure for the Synthesis of
2,5-Disubstituted 1,3,4-Oxadiazoles 15 from Aldehyde
N-Acylhydrazones 14
J = 8.6 Hz, ArH), 7.66 (2 H, d, J = 8.6 Hz, ArH) ppm. 13
C
2,4,6-Tris(4-dichloroiodophenoxy)-1,3,5-triazine (8, 0.4
mmol) was added to a stirred solution of the appropriate
aldehyde N-acylhydrazone (1 mmol) in CH2Cl2 at r.t. The
progress of the reaction was monitored by TLC, and the
reaction was complete within 2–6 h. After completion, the
solvent was removed in vacuo followed by addition of
MeOH to precipitate out triiodide 11. The resulting
heterogeneous solution was filtered to recover 11 which was
subsequently subjected to chlorination at 0 °C in CHCl3 to
form 8. The filtrate, meanwhile, was concentrated in vacuo
to afford the crude product which was purified by column
chromatography on silica gel using PE–EtOAc (9:1) as
eluent to give 2,5-disubstituted 1,3,4-oxadiazoles in
excellent purity.
NMR 100 MHz (CDCl3): δ = 90.54, 123.56, 138.65, 151.26,
173.40 ppm. IR (neat): ν = 1589, 1562, 1480, 1378, 1358,
1204, 1172, 1055, 1008, 820, 803, 704 cm–1. ESI-MS: m/z
[M + H]+ calcd for C21H12I3N3O3: 735.05; found: 735.75.
(16) Synthesis of 2,4,6-Tris(4-dichloroiodophenoxy)-1,3,5-
triazine (8)
2,4,6-Tris(4-iodophenoxy)-1,3,5-triazine was dissolved in
CHCl3, and chlorine gas was passed through this solution at
0 °C with stirring for 2 h. 2,4,6-Tris(4-dichloroiodophenoxy)-
1,3,5-triazine precipitated out as yellow, stable, micro-
crystalline solid. The reaction mixture was kept under
refrigeration for 24 h, then filtered and washed with CHCl3
to produce 8 in 94% yield. Yellow solid, mp 232–234 °C. IR
(neat): ν = 1586, 1561, 1479, 1380, 1360, 1212, 1176, 1002,
838, 807, 749 cm–1.
(22) (a) Yan, M.; Chen, Z.; Zheng, Q. J. Chem. Research, Synop.
2003, 618. (b) Cheng, D.-P.; Chen, Z.-C. Synth. Commun.
2002, 32, 2155. (c) Patil, P. C.; Bhalerao, D. S.; Dangate, P.
S.; Akamanchi, K. G. Tetrahedron Lett. 2009, 50, 5820.
(23) The same reaction in CH2Cl2 resulted in the formation of few
other side products as revealed by TLC.
(24) General Procedure for 1,2,4-Thiazoles 17
2,4,6-Tris(4-dichloroiodophenoxy)-1,3,5-triazine (8, 0.947
g, 1 mmol) was added to a stirred solution of appropriate
thiobenzamide (3 mmol) in MeOH at r.t. The progress of the
reaction was monitored by TLC, and the reaction was
complete within 2 h. After completion of reaction, the
mixture was filtered, and the resulting white precipitate was
washed several times with MeOH to recover 11 which was
subsequently subjected to chlorination at 0 °C in CHCl3 to
form 8. The original filtrate was concentrated in vacuo to
afford the crude product which was purified by column
chromatography on silica gel using PE–EtOAc (9:1) as
eluent to give the substituted 1,2,4-thiazole in excellent
purity.
(17) General Procedure for Nuclear Chlorination of Arenes
Reagent 8 (0.5 mmol) was added to a stirred solution of the
appropiate activated arene (1 mmol) in CH2Cl2 (3 mL). The
reaction mixture was stirred at r.t. for the period of time
given in Table 1, and progress of reaction was monitored by
TLC. When the substrate was consumed, the CH2Cl2 was
evaporated under reduced pressure. MeOH was added to the
reaction mass, and the white precipitate was isolated by
filtration. The residue was washed several times with small
aliquote of MeOH and air-dried to recover 2,4,6-tris(4-
iodophenoxy)-1,3,5-triazine in 93% yield. The filtrate was
concentrated in vacuo to afford the crude product which was
purified by column chromatography on silica gel using PE–
EtOAc (9:1) as eluent to give the chlorinated product in
excellent purity.
(18) (a) Tully, W. R.; Gardner, C. R.; Gillespie, R. J.; Westwood,
R. J. Med. Chem. 1991, 34, 2060. (b) Chen, C.; Senanayake,
C. H.; Bill, T. J.; Larsen, R. D.; Verhoeven, T. R.; Reider, P.
J. J. Org. Chem. 1994, 59, 3738. (c) Chan, L.-H.; Lee, R.-H.;
Hsieh, C.-F.; Yeh, H.-C.; Chen, C.-T. J. Am. Chem. Soc.
2002, 124, 6469. (d) Lee, Y.-Z.; Chen, X.; Chen, S.-A.; Wei,
P.-K.; Fann, W.-S. J. Am. Chem. Soc. 2001, 123, 2296.
(19) (a) Dabiri, M.; Salehi, P.; Baghbanzadeh, M.; Bahramnejad,
M. Tetrahedron Lett. 2006, 47, 6983.
(25) The measured solubilities of the coproduced triiodide 11, a
reduced form of the 2,4,6-tris[(4-dichloroiodo)phenoxy]-
1,3,5-triazine (8) reagent, in several (mixed) solvents at
25 °C are as follows: 0.02 mg·mL–1 (MeOH); 0.02 mg·mL–1
(i-PrOH); 0.2 mg·mL–1 (MeCN); 4.1 mg·mL–1 (EtOAc); 4.3
mg·mL–1 (acetone); 0.04 mg·mL–1 (MeOH–EtOAc = 10:1);
0.06 mg·mL–1 (MeOH–EtOAc = 5:1); 0.6 mg·mL–1 (MeOH–
EtOAc = 1:1).
(b) Mruthyunjayaswamy, B. H. M.; Shanthaveerappa, B. K.
Indian J. Heterocycl. Chem. 1998, 8, 31. (c) Milcent, R.;
Barbier, G. J. Heterocycl. Chem. 1983, 20, 77. (d) Werber,
Synlett 2013, 24, 2061–2066
© Georg Thieme Verlag Stuttgart · New York