4
Tetrahedron
ACCEPTED MANUSCRIPT
spectrometer. Column chromatography was carried out with
White solid; mp 269–270 °C; 1H NMR (DMSO-d6, 500
Silica Gel 60 N (spherical, neutral) from Kanto Chemical Co.,
Inc. Deionized water from a Millipore Milli-Q machine (Gradient
A 10) was used as solvent without further treatment. All organic
solvents used were commercially available anhydrous solvents,
which were distilled appropriately under an argon atmosphere or
were stored over molecular sieves prior to use. All reagents used
as substrates were either distilled or recrystallized before use.
Centrifugation was performed with a Kokusan H-36 centrifuge at
3,500 rpm. X-ray diffraction was recorded with a Rigaku
Miniflex 300/600 diffractometer machine with Cu Kα (λ
=0.15406 nm) radiation at 40 kV and 40 mA. Na+-Mont was
purchased from Kunipia F, Kunimine Industry Co. Ltd. Ion-
exchanged Zeolite was prepared from JRC H-beta-zeolite 150,
(Si/Al = 150). 4-Amino-6-chloro-m-benzenedisulfonamide (1)
was provided by Towa Pharmaceutical Co. Ltd. Ion-exchanged
montmorillonites were prepared from 1.5 g of Na+-Mont by
stirring in 100 mL of aqueous M(OTf)3 solution (5.0 × 10–3 M) at
50 °C for 24 h, and subsequent centrifugation at 3,500 rpm for 5
min, repeated washing with distilled water, and drying at 110 °C.
Metal loading in Montmorillonite catalyst was determined by
inductively coupled plasma (ICP) analysis with Shimadzu ICPS-
7510 equipment, as follows. Catalyst (10-15 mg) was dissolved
in 2–3 mL of hydrofluoric acid (CAUTION) at room
temperature. When the catalyst was completely dissolved, the
solution was diluted to 50 mL with pure water.
MHz): δ = 0.99 (t, J = 7.4, 3H), 1.71-1.84 (m, 2H), 4.67 (s,
1H), 6.98 (s, 1H), 7.49 (s, 2H), 7.74 (brs, 1H). 7.91 (s, 1H), 7.97
(s, 1H); 13C NMR (DMSO-d6, 125 MHz): δ = 9.1, 26.5, 67.2,
117.1, 118.2, 125.6, 128.1, 134.4, 146.6; HRMS (ESI): m/z calcd
for C9H12ClN3O4S2 [M+H]+ 326.0036, found 326.0046.
4.2.4.
6-Chloro-3-propyl-3,4-dihydro-2H-
benzo[e][1,2,4]thiadiazine-7-sulfonamide 1,1-dioxide)
(Prothiazide, 2d)25
White solid; mp 253–257 °C; 1H NMR (DMSO-d6, 500
MHz): δ = 0.99-1.01 (m, 3H), 1.73-1.82 (m, 2H), 4.65-4.69 (m,
1H), 6.98 (s, 1H), 7.49 (s, 2H), 7.74 (d, J = 11.7, 2H). 7.91 (s,
1H), 7.97 (s, 1H); 13C NMR (DMSO-d6, 150 MHz): δ = 9.1, 26.5,
67.2, 117.0, 118.2, 125.5, 128.1, 134.3, 146.6; HRMS (ESI): m/z
calcd for C10H14ClN3O4S2 [M+H]+ 340.0193, found 340.0174.
4.2.5.
6-Chloro-3-(chloromethyl)-3,4-dihydro-2H-
benzo[e][1,2,4]thiadiazine-7-sulfonamide 1,1-dioxide (2e)26
White solid; mp 249–253 °C; IR (neat): ν = 736, 964, 1063,
1155, 1342, 1496, 1595, 3182, 3349, 3423 cm–1; 1H NMR
(DMSO-d6, 600 MHz): δ = 3.87 (d, J = 5.67 Hz, 2H), 4.99-5.04
(m, 1H), 7.06 (s, 1H), 7.54 (s, 2H), 7.99 (s, 1H), 8.10 (d, J = 11.3
Hz, 1H), 8.16 (s, 1H); 13C NMR (DMSO-d6, 125 MHz): δ = 43.7,
66.4, 117.3, 118.4, 125.2, 128.8, 134.6, 146.1; HRMS (ESI): m/z
calcd for C8H9Cl2N3O4S2 [M+H]+ 345.9490, found 345.9519.
4.2. General procedure for cyclocondensation catalyzed by Yb3+-
Mont in water
4.2.6.
2-Methyl-2,3-dihydroquinazolin-4(1H)-one (2f)27
1
White solid; mp 137–141 °C; H NMR (CDCl3, 600 MHz): δ
= 1.40-1.43 (m, 3H), 4.29 (s, 1H), 4.97 (d, J = 4.0, 1H) 6.60 (d, J
= 7.9, 1H), 6.78 (t, J = 7.4, 1H), 6.87 (s, 1H), 7.20-7.24 (m, 1H),
7.81 (d, J = 4.0, 1H); 13C NMR (CDCl3, 125 MHz): δ = 21.7,
61.6, 114.7, 115.9, 119.4, 128.5, 133.7, 147.6, 165.7.
Yb3+-Mont was pretreated at 200 °C under vacuum for 2 h,
immediately before the reaction. To pretreated Yb3+-Mont (50
mg, 3 mol% based on Yb3+) were added 4-amino-6-chloro-m-
benzenedisulfonamide (1) (142.9 mg, 0.5 mmol), acetaldehyde
(66.1 mg, 3.0 equiv.), and water (10 mL), and the mixture was
stirred for 12 h at room temperature. The catalyst was separated
by filtration and washed with ethyl acetate. Brine was added to
the filtrate and the aqueous layer was extracted with ethyl acetate
(3 × 100 mL). The combined organic layers were dried over
Na2SO4 and concentrated under reduced pressure. During
optimization of the reaction conditions, yields were determined
based on the characteristic peak of the product using
dibromomethane as an internal standard. Isolated yields are given
unless otherwise noted.
4.2.7.
2-Methyl-1,2,3,4-tetrahydroquinazoline (2g)28
1
Yellow solid; mp 62–69 °C; H NMR (DMSO-d6, 600 MHz):
δ = 1.14-1.16 (m, 3H), 3.70 (d, J = 16.5 Hz, 1H), 3.86 (d, J =
16.5 Hz, 1H), 4.06 (q, J = 5.7 Hz, 1H), 5.69 (s, 1H), 6.41-6.48
(m, 2H), 6.76 (d, J = 7.6 Hz, 1H), 6.84 (t, J = 7.6 Hz, 1H); 13C
NMR (DMSO-d6, 150 MHz): δ = 22.8, 45.8, 62.2, 113.8, 115.8,
120.5, 123.9, 126.5 144.7.
4.2.8.
2-Ethyl-1,2,3,4-tetrahydroquinazoline (2h)29
Yellow solid; mp 84–88 °C; 1H NMR (CDCl3, 600 MHz): δ =
0.97 (t, J = 7.6 Hz, 3H), 1.53-1.57 (m, 2H), 3.88 (d, J = 16.5 Hz,
1H), 4.01 (t, J = 5.8 Hz, 1H), 4.06 (d, J = 16.5 Hz, 1H), 6.44 (d, J
= 8.3 Hz, 1H), 6.60 (t, J = 7.6 Hz, 1H), 6.82 (d, J = 7.6 Hz, 1H),
6.93 (t, J = 7.6 Hz, 1H); 13C NMR (DMSO-d6, 150 MHz): δ =
9.2, 29.4, 46.5, 68.0, 114.9, 117.9, 121.5, 126.1, 127.1, 143.7.
4.2.1.
6-Chloro-3,4-dihydro-2H-benzo[e][1,2,4]thiadiazine-7-
sulfonamide 1,1-dioxide) (Hydrochlorothiazide, 2a)24
White solid; mp 273–276 °C; 1H NMR (DMSO-d6, 600
MHz): δ = 4.75 (s, 2H), 7.00 (s, 1H), 7.53 (brs, 2H) 8.02-8.04 (m,
2H); 13C NMR (DMSO-d6, 125 MHz): δ = 54.3, 117.0, 118.5,
125.5, 127.9, 134.3, 146.6.
4.3. General procedure for recovery and reuse experiments
4.2.2.
6-Chloro-3-methyl-3,4-dihydro-2H-
benzo[e][1,2,4]thiadiazine-7-sulfonamide 1,1-dioxide)
(Methiazide, 2b)25
After the first run, catalyst was filtered and washed with a
small amount of distilled water. Half the amount of filtrate was
taken out and, after sulfuric acid (1 mL) was added, the resulting
solution was diluted in pure water (50 mL) and submitted to ICP
analysis. The other half was used to determine the yield of the
reaction. To this aqueous solution was added ethyl acetate (5–10
mL) and the mixture was stirred vigorously. The organic phase
was extracted and this procedure was repeated until no substrate
remained in the aqueous layer. The recovered catalyst was dried
under vacuum for 6 h at room temperature, pretreated at 200 °C
for 2 h and was reused for the next run.
White solid; mp 258–261 °C; 1H NMR (DMSO-d6, 600
MHz): δ = 1.45 (d, J = 6.2 Hz, 3H), 4.88-4.93 (m, 1H), 6.94 (s,
1H), 7.50 (s, 2H), 7.85 (d, J = 11.7 Hz, 1H), 7.98 (s, 1H), 8.01 (s,
1H); 13C NMR (DMSO-d6, 150 MHz): δ = 19.7, 62.6, 116.9,
117.9, 125.5, 128.1, 134.4, 146.6; HRMS (ESI): m/z calcd. for
C8H10ClN3O4S2 [M+H]+ 311.9880, found 311.9896.
4.2.3.
6-Chloro-3-ethyl-3,4-dihydro-2H-
benzo[e][1,2,4]thiadiazine-7-sulfonamide 1,1-dioxide)
(Ethiazide, 2c)25
Acknowledgments