M.I.L. Soares, T.M.V.D. Pinho e Melo / Tetrahedron 71 (2015) 4227e4235
4233
3
2
CDCl
.90 (d, J¼14.5 Hz, 1H), 5.77 (pseudo-t, J¼4.1 Hz,1H), 6.98e7.00 (m,
of the crude product with diethyl ether gave compound 21d as
13
ꢀ
1
H), 7.20e7.28 (m, 6H), 7.70e7.72 (m, 1H). C NMR (100 MHz,
: 27.2, 42.8, 61.0, 109.8, 120.4, 122.5, 122.6, 127.5, 128.5,
a yellow solid (578 mg, 79%). Mp 150e151 C. H NMR (400 MHz,
CDCl
: 1.94 (d, J¼6.6 Hz, 3H), 4.52 (d, J¼16.2 Hz, 1H), 4.59 (d,
J¼16.2 Hz, 1H), 5.39 (q, J¼6.6 Hz, 1H), 7.36e7.42 (m, 3H), 7.81e7.83
3
)
d
3
) d
129.9, 132.1, 134.4, 148.9, 158.0. IR (KBr)
n
: 1522, 1452, 1410,
ꢂ1
þ
13
748 cm . HRMS (EI) m/z: calcd for C16
H
14
N
2
S [M] 266.0876,
3
(m, 1H); C NMR (100 MHz, CDCl ) d: 15.2, 49.3, 72.1, 110.0, 120.8,
found 266.0885.
123.8, 124.1, 131.7, 144.0, 144.5. IR (KBr)
n
: 1533, 1452, 1387, 1331,
ꢂ1
1
232, 1132, 1107, 752 cm . HRMS (EI) m/z: calcd for C10
H
10
N
2
O
2
S
þ
4
.5. General procedure for the synthesis of 1H,3H-thiazolo
[M] 222.0463, found 222.047.
[3,4-a]benzimidazole-2,2-dioxides
4
.5.5. 1-Benzyl-1H,3H-thiazolo[3,4-a]benzimidazole 2,2-dioxide
A mixture of Na
PO , (2.8 l, 1M solution in water), CH
l, 1M solution in methanol) and aqueous 30% H
was vigorously stirred at room temperature for 10 min. A solution
of the appropriate 1H,3H-thiazolo[3,4-a]benzimidazole
2.77 mmol) in ethyl acetate (10 mL) was slowly added to the re-
action mixture and the resulting solution was stirred at 45e50 C,
except where otherwise indicated. The reaction was monitored by
TLC. After the reaction was complete, it was cooled to room tem-
perature and 40% (w/v) aqueous sodium bisulfite solution was
added to the reaction mixture. The organic phase was separated,
2
WO
4
.2H
2
O (2.8
m
l, 1M solution in water),
N[(CH CH Cl
(1.0 mL)
(21e). Obtained from compound 8e (216 mg, 0.81 mmol) as de-
scribed in the general procedure (after 20 h of reaction, a new load
of catalysts and H O was added, reaction time: 27 h). Purification
2 2
of the crude product by flash chromatography [hexane/EtOAc (2:1),
then hexane/EtOAc (1:1)] gave compound 21e as a light yellow
C
6
H
5
m
3
H
2
m
3
2
O
)
7
3
]
3
(
2.8
2
2
8
ꢀ
1
(
solid (232 mg, 96%). Mp 182e184 C (from EtOAc/hexane). H NMR
(400 MHz, CDCl
ꢀ
3
)
d
: 3.37 (dd, J¼6.7 and 14.6 Hz, 1H), 3.71 (dd, J¼4.8
and 14.6 Hz,1H), 3.98 (d, J¼15.8 Hz,1H), 4.45 (d, J¼15.8 Hz,1H), 5.51
(pseudo-t, J¼5.8 Hz, 1H), 6.68 (d, J¼8.1 Hz, 1H), 7.02e7.03 (m, 2H),
13
7.17e7.33 (m, 6H), 7.77 (d, J¼8.1 Hz, 1H). C NMR (100 MHz, CDCl
3
)
d
: 37.4, 49.5, 74.2, 110.2, 120.6, 123.6, 124.0,128.2, 129.1, 130.0, 132.5,
dried over anhydrous Na
crude product was purified by crystallization or flash
chromatography.
2
SO
4
and the solvent evaporated off. The
132.5, 144.1, 144.5. IR (KBr)
746 cm . HRMS (ESI) m/z: calcd for C16
299.08487, found 299.08483.
n
: 1541, 1452, 1327, 1203, 1140, 1128,
ꢂ1
S [MþH]þ
H
15
N
2
O
2
4
.5.1. 1-Phenyl-1H,3H-thiazolo[3,4-a]benzimidazole-2,2-dioxide
(
21a). Obtained from compound 8a (420 mg, 1.67 mmol) as de-
4.6. General procedures for generation and cycloaddition
reactions of benzo-2,5-diazafulvenium methide 22
scribed in the general procedure (the reaction was carried out at
room temperature, reaction time: 22 h). Purification of the crude
product by flash chromatography [hexane/EtOAc (1:2)] gave com-
pound 21a (260 mg, 55%) as a white solid. Mp 211e212 C (from
diethyl ether). H NMR (400 MHz, CDCl
Method A. A solution of 3-methyl-1H,3H-thiazolo[3,4-a]benz-
imidazole-2,2-dioxide (21c) (100 mg, 0.45 mmol) and dipolarophile
(2 equiv, 0.90 mmol) in 1,2,4-trichlorobenzene (2 mL) was heated at
ꢀ
1
3
)
d
: 4.65 (s, 2H), 6.28 (s, 1H),
ꢀ
6
1
.84 (d, J¼8.1 Hz, 1H), 7.18e7.23 (m, 3H), 7.35 (pseudo-t, J¼7.6 Hz,
230 C under dry nitrogen for the time indicated in each case. After
1
3
H), 7.45e7.99 (m, 2H), 7.52e7.56 (m, 1H), 7.85 (d, J¼8.1 Hz, 1H).
C
cooling to room temperature, the mixture was purified by flash
chromatography (hexane) to remove 1,2,4-trichlorobenzene fol-
lowed by elution with ethyl acetate/hexane to obtain the corre-
sponding products.
NMR (100 MHz, CDCl
1
1
3
) d
: 49.6, 79.5, 110.9, 120.7, 123.9, 124.1, 127.1,
28.3, 129.5, 131.3, 131.8, 144.5, 144.7. IR (KBr)
215, 1137 cm . HRMS (EI) m/z: calcd for C15H N O S [M]
n
: 1534, 1450, 1336,
ꢂ1
þ
12 2 2
2
84.0619, found 284.0620.
Method B. A solution of 3-methyl-1H,3H-thiazolo[3,4-a]benz-
imidazole-2,2-dioxide (21c) (100 mg, 0.45 mmol) and dipolarophile
(2 equiv, 0.90 mmol) in 1,2,4-trichlorobenzene (1 mL) was irradi-
4
.5.2. 1H,3H-Thiazolo[3,4-a]benzimidazole-2,2-dioxide
ꢀ
(21b). Obtained from compound 8b (197 mg, 1.12 mmol) as de-
ated in the microwave reactor at 250 C over a period of 15 min.
scribed in the general procedure (reaction time: 4.5 h). Trituration
of the crude product with diethyl ether gave compound 21b as
After cooling to room temperature, the mixture was purified by
flash chromatography (hexane) to remove 1,2,4-trichlorobenzene
followed by elution with ethyl acetate/hexane to obtain the corre-
sponding products.
ꢀ
a white solid (94 mg, 40%). Mp 228e229 C (with decomposition).
1
3
H NMR (400 MHz, CDCl ) d: 4.61 (s, 2H), 5.25 (s, 2H), 7.37e7.40 (m,
13
3
H), 7.83e7.84 (m, 1H). C NMR (100 MHz, CDCl
3
)
d
: 50.9, 65.2,
: 1533, 1441,
398, 1331, 1157, 1144, 742 cm . HRMS (EI) m/z: calcd for
1
1
C
09.9, 120.7, 124.0, 124.4, 132.2, 144.3, 145.1. IR (KBr)
n
4.6.1. 4-Methyl-2-phenyl-3a,4,11,11a-tetrahydro-1H-benzo[4,5]imi-
ꢂ1
dazo[1,2-a]pyrrolo[3,4-d]pyridine-1,3(2H)-dione (23a). Method
(reaction time: 4 h). Obtained from compound 21c (100 mg,
.45 mmol) as described in the general procedure. Purification by
A
þ
H
9 8
N
2
O
2
S [M] 208.0306, found 208.0306.
0
4
.5.3. 3-Methyl-1H,3H-thiazolo[3,4-a]benzimidazole-2,2-dioxide
flash chromatography [hexane, hexane/EtOAc (2:1), hexane/EtOAc
(1:1), then EtOAc] gave compound 23a (23 mg, 15%).
Method B. Obtained from compound 21c (100 mg, 0.45 mmol) as
described in the general procedure. Purification by flash chroma-
tography [hexane, hexane/EtOAc (2:1), then EtOAc] gave compound
23a (41 mg, 28%).
(21c). Obtained from compound 8c (527 mg, 2.77 mmol) as de-
scribed in the general procedure (reaction time: 5 h). Purification
of the crude product by flash chromatography [hexane/EtOAc
(
1:1), then hexane/EtOAc (1:2)] gave compound 21c as a yellow
ꢀ
1
3
solid (554 mg, 90%). Mp 181e182 C. H NMR (400 MHz, CDCl ) d:
1
5
.89 (d, J¼7.1 Hz, 3H), 4.52 (q, J¼7.1 Hz, 1H), 5.18 (d, J¼10.2 Hz, 1H),
13
.21 (d, J¼10.2 Hz, 1H), 7.37e7.39 (m, 3H), 7.82e7.84 (m, 1H).
C
4.6.1.1. 4-Methyl-2-phenyl-3a,4,11,11a-tetrahydro-1H-benzo[4,5]
NMR (100 MHz, CDCl
3
)
d
: 11.1, 55.7, 63.7, 109.9, 120.7, 123.9, 124.3,
imidazo[1,2-a]pyrrolo[3,4-d]pyridine-1,3(2H)-dione
(23a). Light
brown solid. Mp 205e2007 C (from EtOAc). H NMR (400 MHz,
CDCl
: 1.74 (d, J¼7.2 Hz, 3H), 3.28 (dd, J¼5.3 and 9.5 Hz, 1H),
3.61e3.66 (m, 1H), 3.70e3.77 (m, 1H), 4.53 (dd, J¼6.6 and 13.4 Hz,
H), 4.58 (dd, J¼5.5 and 13.4 Hz, 1H), 7.13e7.15 (m, 2H), 7.27e7.42
ꢂ1
ꢀ
1
132.3, 144.1, 150.0. IR (KBr)
n
: 1535, 1398, 1327, 1140, 744 cm
.
þ
HRMS (EI) m/z: calcd for C10
H
10
N
2
O
2
S [M] 222.0463, found
3
) d
2
22.0461.
1
1
3
4
.5.4. 1-Methyl-1H,3H-thiazolo[3,4-a]benzimidazole-2,2-dioxide
(m, 8H), 7.75e7.77 (m, 1H). C NMR (100 MHz, CDCl
39.7, 40.1, 45.1, 108.8, 119.8, 122.7, 122.9, 126.2, 129.0, 129.2, 131.2,
134.2, 142.5, 153.2, 175.5, 176.0. IR (KBr) : 1707, 1496, 1456, 1400,
3
) d: 18.7, 31.7,
(21d). Obtained from compound 8d (625 mg, 3.29 mmol) as de-
scribed in the general procedure (reaction time: 24 h). Trituration
n