8172
M. Bella et al. / Tetrahedron 66 (2010) 8169e8174
5.3. Quantum-chemical calculations
Dry products were recrystallized from dimethylsulfoxide without
addition of charcoal and filtration.
Standard geometry optimizations of the compounds under study
at DFT level of theory using hybrid B3LYP functional28 and cc-pVDZ
basis sets29,30 have been performed using Gaussian03 program
package.31 Their stability (i.e., that the geometry corresponds to
a minimum of a potential energy surface) has been confirmed by
vibrational frequencies calculations (no imaginary vibrations).
Frontier electron densities (FED) of individual atoms in the highest
occupied molecular orbital (HOMO) and in the lowest unoccupied
molecular orbital (LUMO) have been evaluated as the corresponding
net electron populations and used as reactivity indices of these
atoms in nucleophilic and electrophilic reagents, respectively.
5.5.1. 5-[(2,1,3-Benzoselenadiazol-4-ylamino)methylene]-2,2-di-
methyl-1,3-dioxane-4,6-dione (8a). Yellow needles (90%); mp
239e244 ꢀC; 1H NMR (300 MHz, CDCl3):
d
1.79 (s, 6H, 2ꢂCH3), 7.30
(d, 3J¼7.0 Hz, 1H, 5-H), 7.55 (dd, 3J¼9.1 Hz, 7.1 Hz, 1H, 6-H), 7.72 (dd,
3J¼9.1 Hz, 4J¼0.8 Hz, 1H, H-7), 9.09 (d, 3J¼14.1 Hz, 1H, ]CHe), 12.11
(br d, 1H, NH); 13C NMR (75 MHz, CDCl3):
d 27.1, 89.2, 105.4, 111.4,
120.5, 129.4, 130.9, 151.5, 153.5, 160.5, 163.4, 165.1. IR (KBr): 3448,
1730, 994, 925 cmꢁ1. Anal. Calcd for C13H11N3O4Se (352.21): C,
44.33; H, 3.15; N, 11.93. Found: C, 44.42; H, 3.17; N, 11.90.
5.5.2. Dimethyl 2-[(2,1,3-benzoselenadiazol-4-ylamino)methylene]-
propanedioate (8b). Yellow needles (74%); mp 213e215 ꢀC; 1H
5.4. 4-Amino-2,1,3-benzoselenadiazole (4)
NMR (300 MHz, CDCl3):
d 3.84 (s, 3H, OCH3), 3.94 (s, 3H, OCH3),
7.14 (d, 3J¼7.1 Hz, 1H, 5-H), 7.49 (dd, 3J¼9.0 Hz, 7.1 Hz, 1H, 6-H),
Method
A (via 1,2,3-triaminobenzene (3)). Tin(II) chloride
7.56 (dd, 3J¼9.0 Hz, 4J¼0.7 Hz, 1H, 7-H), 8.76 (d, 3J¼13.7 Hz, 1H,
dihydrate (22.2 g, 98.4 mmol) was suspended in concentrated
hydrochloric acid (33 mL) and to this suspension 2,6-dinitroani-
line (1) (2.0 g, 11.0 mmol), 4-nitro-2,1,3-benzoselenadiazole (5)
(2.5 g, 11.0 mmol) or 4-nitro-2,1,3-benzothiadiazole (6) (1.99 g,
11.0 mmol) was added portionwise. After the addition was
completed, the reaction mixture was refluxed for 5 h. In case of
using nitro derivative 5, elementary selenium was filtered off
while hot. The reaction mixture or filtrate was cooled to room
temperature. Yellowish crystals were collected by suction,
washed with ethanol and dried. Dihydrochloride 2 was dissolved
in 10% NaOH solution (5 mL gꢁ1) and the resulting brown colored
solution was extracted with ethyl acetate (4ꢂ25 mL). Combined
extracts were dried over anhydrous Na2SO4 and evaporated to
dryness under reduced pressure to afford free triamine 3. This
triamine was immediately dissolved in ethanol (30 mL gꢁ1) and
a stoichiometric amount of SeO2 in water (1 g/20 mL) was added
dropwise at room temperature while orange crystals were
formed. After the addition was completed, the reaction mixture
was stirred for an additional 10 min. Then water (50 mL) was
added to the reaction mixture and orange needles were separated
by suction, washed with water and dried. Yield 1.63 g (75%)
starting from 1; 1.26 g (58%) starting from 5; 1.61 g (74%) starting
from 6.
]CHe), 12.0 (br d, 1H, NH); 13C NMR (CDCl3, 75 MHz):
d 51.7,
52.1, 95.6, 108.4, 118.3, 129.9, 132.3, 149.7, 153.4, 160.5, 165.7,
168.8. IR (KBr): 3447, 1689, 1098, 995 cmꢁ1. Anal. Calcd for
C12H11N3O4Se (340.20): C, 42.37; H, 3.26; N, 12.35. Found: C,
42.34; H, 3.27; N, 12.38.
5.5.3. Diethyl
2-[(2,1,3-benzoselenadiazol-4-ylamino)methylene]-
propanedioate (8c). Ochre needles (75%); mp 153e157 ꢀC; 1H NMR
(300 MHz, CDCl3):
d
1.36 (s, 3J¼7.1 Hz, 3H, OCH2CH3), 1.41 (t,
3J¼7.1 Hz, 3H, OCH2CH3), 4.30 (q, 3J¼7.1 Hz, 2H, OCH2CH3), 4.41 (q,
3J¼7.1, 2H, OCH2CH3), 7.12 (d, 3J¼7.1 Hz, 1H, 5-H), 7.49 (dd, 1H,
3J¼9.0 Hz, 7.1 Hz, 6-H), 7.55 (dd, 3J¼9.0 Hz, 4J¼0.7 Hz, 1H, 7-H), 8.73
(d, 3J¼13.6 Hz, 1H, ]CHe), 11.92 (br d, 1H, NH); 13C NMR (75 MHz,
CDCl3):
d 14.3, 14.4, 60.4, 60.8, 96.4, 108.2, 118.1, 130.0, 132.4, 149.2,
153.5, 160.5, 165.5, 168.4. IR (KBr): 3442, 1683, 1013, 977 cmꢁ1. Anal.
Calcd for C14H15N3O4Se (368.25): C, 45.66; H, 4.11; N, 11.57. Found:
C, 45.52; H, 4. 09; N, 11.62.
5.5.4. 3-[(2,1,3-Benzoselenadiazol-4-ylamino)methylene]pentane-
2,4-dione (8d). Brownish solid (82%); mp 215e218 ꢀC, 1H NMR
(300 MHz, CDCl3):
d 2.46 (s, 3H, CH3), 2.61 (s, 3H, CH3), 7.16 (d,
3J¼7.2 Hz, 1H, 5-H), 7.51 (dd, 3J¼9.0 Hz, 7.2 Hz, 1H, 6-H), 7.64 (dd,
3J¼9.0 Hz, 4J¼0.7 Hz, 1H, 7-H), 8.82 (d, 3J¼12.6, 1H, ]CHe), 13.45
Method
B (via 1,2,3-triaminobenzene dihydrochloride (2)).
(br d, 1H, NH); 13C NMR (75 MHz, CDCl3):
d 27.4, 32.2, 111.0, 114.5,
Dihydrochloride 2 (4.26 g, 21.7 mmol) was dissolved in water
(42 mL). To this solution, an aqueous solution of SeO2 (2.41 g,
21.7 mmol) was added dropwise at room temperature while
orange crystals were formed. After the addition was finished,
reaction mixture was stirred for 15 min and then alkalized with
30% NaOH solution while cooling in an ice bath. Orange needles
were separated by suction, washed with water and dried to give
compound 4 (4.17 g (97%)).
119.3, 129.6, 132.2, 150.6, 153.5, 160.7, 195.2, 201.5. IR (KBr): 3445,
1623, 989, 969 cmꢁ1. Anal. Calcd for C12H11N3O2Se (308.20): C,
46.77; H, 3.60; N, 13.63. Found: C, 46.74; H, 3.67; N, 13.57.
5.5.5. (E/Z)-Ethyl
2-[(2,1,3-benzoselenadiazol-4-ylamino)methy-
lene]-3-oxobutanoate (8e). Yellow-orange crystals (84%,); mp
215e218 ꢀC; E/Z¼4:1; 1H NMR (300 MHz, CDCl3,): E-isomer:
d 1.38
(t, 3J¼7.1 Hz, 3H, OCH2CH3), 2.61 (s, 3H, CH3), 4.31 (q, 3J¼7.1 Hz, 2H,
OCH2CH3), 7.19 (d, 3J¼7.2 Hz, 1H, 5-H), 7.50 (dd, 3J¼9.0 Hz, 7.2 Hz,
1H, 6-H), 7.60 (d, 3J¼9.0 Hz, 1H, 7-H), 8.77 (d, 3J¼13.1 Hz, 1H, ]
CHe), 13.48 (br d, 1H, NH); 13C NMR (75 MHz, CDCl3): E-isomer:
Compound 4: orange needles; mp 162e164 ꢀC (Ref. 15 mp
160e161 ꢀC). 1H NMR (300 MHz, DMSO-d6):
d 5.87 (br s, 2H, NH2),
6.38 (dd, 3J¼7.2 Hz, 4J¼0.7 Hz, 1H, 5-H), 6.96 (dd, 3J¼8.9 Hz,
4J¼0.8 Hz, 1H, 7-H), 7.27 (dd, 3J¼8.9 Hz, 7.2 Hz, 1H, 6-H); 13C NMR
d
14.5, 31.6, 60.3, 104.9, 109.8, 119.0, 129.8, 132.4, 149.3, 153.5, 160.5,
(75 MHz, DMSO-d6):
d 102.8, 109.0, 131.6, 141.3, 153.6, 160.5.
166.6, 200.5. IR (KBr): 3444, 1703, 1629, 1027, 979 cmꢁ1. Anal. Calcd
for C13H13N3O3Se (338.23): C, 46.16; H, 3.89; N, 12.42. Found: C,
46.28; H, 3.91; N, 12.38.
5.5. General procedure for the preparation of
(benzoselenadiazol-4-ylamino)methylene derivatives (8)
5.5.6. (E/Z)-Ethyl 3-(2,1,3-benzoselenadiazol-4-ylamino)-2-cyano-
A mixture of 4-aminobenzoselenadiazole 4 (1.98 g, 10 mmol)
and corresponding alkoxymethylene derivative 7aei (11 mmol)
was refluxed in methanol or ethanol (60 mL) until all amine 4 was
consumed (TLC monitoring, eluent CHCl3/MeOH, 100:1). Product 8c
crystallized from the cooled solution, while compounds 8a, b and
8dei precipitated during reflux. After cooling, the precipitate was
collected by suction, washed with methanol or ethanol and dried.
prop-2-enoate (8f). Yellow powder (65%); mp 239e243 ꢀC; E/
Z¼4:1; 1H NMR (300 MHz, DMSO-d6): E-isomer:
d¼1.33 (t,
3J¼7.1 Hz, 3H, OCH2CH3), 4.32 (q, 3J¼7.1 Hz, 2H, OCH2CH3),
7.65e7.45 (m, 3H, AreH), 8.78 (d, 3J¼13.6 Hz, 1H, ]CHe) 11.51 (br
d, 1H, NH); 13C NMR (75 MHz, DMSO-d6): E-isomer:
d 13.6, 60.4,
76.0, 109.9, 116.7, 118.2, 129.2, 130.6, 151.7, 152.1, 159.2, 165.8. IR
(KBr): 3451, 2214, 1672, 1032, 985 cmꢁ1
.
Anal. Calcd for