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V. Benin, A. T. Yeates, D. Dudis
Vol 45
Stirring was continued for 18 h at ambient temperature, the
resultant brown solid was filtered through a fine fritted funnel
and the filter cake suspended in an aqueous solution of NaHSO3.
The resultant mixture was stirred for 0.5 h, filtered and the white
solid washed with water, followed by THF. The solid was then
suspended in water (200 mL), the suspension cooled in an ice –
water bath while conc. HCl was added to a pH of 0 – 1. The
mixture was left standing for 0.5 h, filtered, the white solid
washed with small amount of cold water and air-dried for 12 h
to yield 2.73 g (85%) of 2,5-thiazolo[5,4-d]thiazoledicarboxylic
acid 5. Mp 208 – 209 °C (Lit. 212 °C).[9]
[5,4-d]thiazole 3b; Fraction #2: 3,5-dibromopyridine, identified
by comparison with literature NMR data; Fraction #3: 2-
bromothiazolo[5,4-d]thiazole 2b; Fraction #4: thiazolo[5,4-d]-
thiazole 1, identified by TLC analysis and comparison with
authentic NMR data. Substances were isolated after removal of
the solvents under reduced pressure.
2-Bromothiazolo[5,4-d]thiazole (2b). Isolated as a colorless
solid (0.35 g, 35% yield).
Further purification via
recrystallization from methanol at – 30 °C yields colorless
needles. Mp 52 – 53 °C. 1H NMR (CDCl3) δ 8.94 (s, 1H); 13C
NMR (CDCl3) δ 137.9, 147.7, 152.1, 154.2; MS m/e 222
([M+2]+, 48), 220 (M+, 40), 88 (100), 70 (85). Anal. Calcd. for
C4HBrN2S2: C, 21.73; H, 0.46; N, 12.67. Found: C, 21.94; H,
0.47; N, 12.58.
2,5-Dibromothiazolo[5,4-d]thiazole (3b). Isolated as a
bluish solid (0.19 g, 14% yield). Further purification via
recrystallization from toluene at – 30 °C yields bluish needles.
Mp 153 – 154 °C. 13C NMR (CDCl3) δ 137.7, 149.1; MS m/e
302 ([M+4]+, 30), 300 ([M+2]+, 48), 298 (M+, 26), 88 (80), 70
(100). Anal. Calcd. for C4Br2N2S2: C, 16.01; N, 9.34. Found:
C, 16.24; N, 9.31.
Thiazolo[5,4-d]thiazole (1). 2,5-Thiazolo[5,4-d]thiazole
dicarboxylic acid 5 (2.73 g, 10.26 mmol) was suspended in 96%
ethanol (200 mL) and the resultant mixture stirred at reflux for
24 h. The solution was cooled to ambient temperature and the
solvent removed under reduced pressure. The solid residue was
dissolved in small amount of CH2Cl2 and passed through a short
silica gel column (Eluent CH2Cl2). The solvent was removed
under reduced pressure to yield 1.16 g (79%) of thiazolo[5,4-d]-
thiazole 1 as a white solid. Mp 149 – 150 °C (Lit. 150 – 151
1
°C).[9] H NMR (CDCl3) δ 8.95 (s, 2H).
Chlorination of thiazolo[5,4-d]thiazole. Thiazolo[5,4-d]-
thiazole 1 (0.20 g, 1.41 mmol) was dissolved in CCl4 (15 mL).
Trichloroisocyanuric acid, TCICA (3.27 g, 14.08 mmol) was
added in one portion and the resultant mixture stirred at reflux
for 7 days. TLC indicated complete conversion of the starting
material. The mixture was vacuum filtered and the solid washed
with CCl4 (15 mL). The filtrate was concentrated under reduced
pressure, the residue was re-dissolved in a small amount of
hexane/CH2Cl2 mixture (3:1), and placed on a short silica gel
column. The column was successively eluted with hexane,
hexane:CH2Cl2 = 1:1 (collection of 3a) and CH2Cl2 (collection
of 2a). Products were isolated after removal of the solvents
under reduced pressure.
2-Chlorothiazolo[5,4-d]thiazole (2a). Isolated as a white
solid (0.10 g, 40% yield). Further purification via recrystal-
lization from methanol at – 30 °C yields colorless needles. Mp
57 – 59 °C. 1H NMR (CDCl3) δ 8.92 (s, 1H); 13C NMR (CDCl3)
δ 150.4, 153.3, 154.0; MS m/e 178 ([M+2]+, 30), 176 (M+, 90),
115 (35), 88 (100), 70 (50). Anal. Calcd. for C4HClN2S2: C,
27.20; H, 0.57; N, 15.86. Found: C, 27.50; H, 0.52; N, 15.81.
2,5-Dichlorothiazolo[5,4-d]thiazole (3a). Isolated as a white
solid (0.13 g, 44% yield). Further purification via recrystal-
lization from toluene at – 30 °C yields colorless needles. Mp
175 – 177 °C (Lit. 171 – 172 °C)[33]. 13C NMR (CDCl3) δ
145.3, 151.8; MS m/e 214 ([M+4]+, 15), 212 ([M+2]+, 65), 210
(M+, 85), 88 (100), 70 (80). Anal. Calcd. for C4Cl2N2S2: C,
22.76; N, 13.27. Found: C, 22.98; N, 13.02.
Bromination of thiazolo[5,4-d]thiazole. Thiazolo[5,4-d]-
thiazole 1 (0.65 g, 4.58 mmol) was dissolved in CCl4 (30 mL).
Pyridine (0.54 g, 6.87 mmol, 0.56 mL) was added, followed by
bromine (1.10 g, 6.87 mmol, 0.35 mL). The resultant solution
was stirred at reflux for 2 h, followed by addition of more
pyridine (0.18 g, 2.29 mmol, 0.19 mL) and bromine (1.10 g,
6.87 mmol, 0.35 mL), and the stirring was continued at reflux
for additional 2 h. The resultant mixture was poured into aq.
NaHSO3 to quench the excess bromine, the organic layer was
separated and the aqueous layer extracted with CH2Cl2 (30 mL).
The combined organic extract was dried (MgSO4) and the
solvent removed under reduced pressure. The residue was
separated on a silica gel column (Eluent CH2Cl2) with four
major fractions collected. Fraction #1: 2,5-dibromothiazolo-
Dibromination of thiazolo[5,4-d]thiazole. Thiazolo[5,4-d]-
thiazole 1 (0.46 g, 3.24 mmol) was dissolved in CCl4 (20 mL).
Pyridine (0.51 g, 6.48 mmol, 0.52 mL) was added, followed by
bromine (5.18 g, 32.40 mmol, 1.66 mL). The resultant solution
was stirred at reflux for 4 h and TLC analysis indicated complete
consumption of the starting material. The mixture was poured
into aq. NaHSO3 and stirred until all excess bromine was
reacted. The organic layer was separated and the aqueous layer
extracted with CH2Cl2 (30 mL). The combined organic extract
was dried (MgSO4) and the solvent removed under reduced
pressure. The residue was separated on a silica gel column
(Eluent CH2Cl2) to yield 0.56 g (58%) of 3b as a bluish solid.
Physical and spectral characteristics matched those of the
sample obtained in the previous experiment.
Acknowledgements. We gratefully acknowledge the DoD
High Performance Computing office for a grant of computer
time and resources, for some of the computational results
reported herein. Funding for V. Benin was provided by the
American Society for Engineering Education, as part of the Air
Force Summer Faculty Fellowship program (Summer 2006).
Supporting Information Available. Crystallographic data
(excluding structure factors) for the structures in this paper have
been deposited with the Cambridge Crystallographic Data Centre
as supplementary publication numbers CCDC 625746 and
625747. Copies of the data can be obtained, free of charge, on
application to CCDC, 12 Union Road, Cambridge CB2 1EZ, UK
Calculated energies and thermodynamic parameters of
optimized global minimum structures of compounds 2a,b and
3a,b are summarized in Table S1. Calculated energies and
thermodynamic parameters of stationary points for the processes
of pyridine-catalyzed chlorination of compounds 1 and 2a are
summarized in Tables S2 and S3.
REFERENCES
*
Corresponding author. Phone: 937-229-4762; Fax: 937-
229-2635; E-mail: vladimir.benin@notes.udayton.edu
[1] Peng, Q.; Peng, J.-B.; Kang, E. T.; Neoh, K. G.; Cao, Y.
Macromolecules 2005, 38, 7292 - 7298.