The Journal of Organic Chemistry
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(4.02 g, 88%): mp 99−101 °C; FT-IR (ν, cm−1, KBr) 3062, 3023,
8.8 Hz, 1H), 4.58−4.53 (d, J = 8.8 Hz, 2H), 3.15 (s, 6H); 13C NMR
(100 MHz, CDCl3) δ 155.1, 138.1, 127.1, 126.0, 125.8, 66.9, 38.1;
HRMS (ESI) m/z [M + H]+ calcd for C8H13N4OS, 213.08101; found,
213.08115.
1
2980, 2933, 2903, 1651, 1598, 1427; H NMR (400 MHz, CDCl3) δ
7.80 (s, 1H), 7.73 (s, 1H), 7.64−7.58 (m, 4H), 7.31−7.25 (m, 6H),
4.12−4.04 (q, J = 7.1 Hz, 2H), 3.47 (s, 3H), 1.34−1.29 (t, J = 7.0 Hz,
3H); 13C NMR (100 MHz, CDCl3) δ 158.0, 138.5, 137.3, 135.2,
135.1, 129.0, 128.8, 128.41, 128.36, 126.9, 126.8, 39.6, 33.0, 11.1;
HRMS (ESI) m/z [M + H]+ calcd for C18H21N4O, 309.17154; found,
309.17245.
2,4-Dibenzyl-6-phenyl-1,2,4,5-tetrazinan-3-one (14). Carbo-
di(N′-benzylidene-N-benzylhydrazide) (3) (1.50 g) was reacted
according to the general methanolysis and ring-closure procedure to
yield white needle-like crystals (1.09 g, 91%): mp 147−150 °C; FT-IR
1
(ν, cm−1, KBr) 3256, 3249, 3227, 1594, 1501, 1449; H NMR (400
Carbo-N′-benzylidene-N-methylhydrazide(N′-benzylidene-
N-propylhydrazide) (10). Carbo-N′-benzylidene(N′-benzylidene-N-
propylhydrazide) (11) (2.00 g, 6.49 mmol) was added to a 250 mL
round-bottom flask and dissolved in 40 mL of anhydrous toluene with
stirring. Dimethylsulfate (1.4 equiv, 1.15 g, 0.86 mL, 9.08 mmol) was
added, followed by a slow addition of 2.2 equiv of sodium hydride
(340 mg, 14.3 mmol). The solution was heated to 85 °C and allowed
to react for 2 h. The reaction mixture was allowed to cool to 0 °C, the
unreacted sodium hydride was quenched by the slow addition of
methanol, and the solution volume was reduced in vacuo. This
solution was then taken up in 75 mL of EtOAc and washed three times
with 50 mL of water. The crude extract was dried over anhydrous
sodium sulfate, and the solvent was evaporated in vacuo. The crude
product was filtered through a short silica gel column (1:99 methanol
in DCM as the eluent) to yield a light yellow oil (1.67 g, 80%): FT-IR
(ν, cm−1, KBr) 3059, 3027, 2962, 2932, 2874, 1666, 1598, 1572, 1422;
1H NMR (400 MHz, CDCl3) δ 7.74 (s, 1H), 7.65 (s, 1H), 7.63−7.56
MHz, CDCl3) δ 7.45−7.24 (m, 15H), 4.82−4.67 (m, 5H), 4.23−4.17
(d, J = 10.8 Hz, 2H); 13C NMR (100 MHz, CDCl3) δ 154.0, 137.6,
134.8, 128.6, 128.4, 128.3, 127.3, 126.1, 69.5, 53.1; HRMS (ESI) m/z
[M + H]+ calcd for C22H23N4O, 359.18719; found, 359.18893.
2,4-Diethyl-6-phenyl-1,2,4,5-tetrazinan-3-one (15). Carbo-di-
(N′-benzylidene-N-ethylhydrazide) (4) (347 mg) was reacted
according to the general methanolysis and ring-closure procedure to
yield white needle-like crystals (252 mg, 82%): mp 70−72 °C; FT-IR
(ν, cm−1, KBr) 3231, 3063, 3034, 2972, 2930, 2868, 1600, 1496, 1452,
1
1421; H NMR (400 MHz, CDCl3) δ 7.56−7.52 (m, 2H), 7.43−7.34
(m, 3H), 4.94−4.86 (t, J = 11.2 Hz, 1H), 4.19−4.13 (d, J = 11.3 Hz,
2H), 3.73−3.63 (sextet, J = 7.0 Hz, 2H), 3.56−3.45 (sextet, J = 7.0 Hz,
2H), 1.23−1.18 (t, J = 7.0 Hz, 6H); 13C NMR (100 MHz, CDCl3) δ
154.4, 135.4, 128.8, 128.7, 126.3, 70.4, 44.6, 12.4; HRMS (ESI) m/z
[M + H]+ calcd for C12H19N4O, 235.15589; found, 235.15581.
2-Benzyl-4-methyl-6-phenyl-1,2,4,5-tetrazinan-3-one (16).
Carbo-N′-benzylidene-N-benzylhydrazide(N′-benzylidene-N-methyl-
hydrazide) (6) (6.10 g) was reacted according to the general
methanolysis and ring-closure procedure to yield white needle-like
crystals (2.11 g, 45%): mp 98−100 °C; FT-IR (ν, cm−1, KBr) 3238,
(m, 4H), 7.24−7.17 (m, 6H), 4.98−4.91 (t, J = 7.4 Hz, 2H), 3.37 (s,
3H), 1.79−1.68 (sextet, J = 7.4 Hz, 2H), 1.00−0.93 (t, J = 7.4 Hz,
3H); 13C NMR (100 MHz, CDCl3) δ 158.2, 138.3, 137.3, 135.3,
135.2, 129.0, 128.8, 128.42, 128.37, 126.89, 126.85, 46.3, 33.0, 19.2,
11.2; HRMS (ESI) m/z [M + H]+ calcd for C19H23N4O, 323.1866;
found, 323.1866.
1
3030, 2909, 1687, 1597, 1514; H NMR (400 MHz, CDCl3) δ 7.48−
7.27 (m, 10H), 4.99−4.92 (t, J = 10.4 Hz, 1H), 4.79−4.73 (d, J = 14.5
Hz, 1H), 4.69−4.63 (d, J = 14.5 Hz, 1H), 4.35−4.30 (d, J = 10.4 Hz,
1H), 4.24−4.19 (d, J = 10.3 Hz, 1H), 3.21 (s, 3H); 13C NMR (100
MHz, CDCl3) δ 154.4, 137.7, 134.9, 128.62, 128.57, 128.5, 128.3,
127.2, 126.2, 69.4, 53.5, 37.9; HRMS (ESI) m/z [M + H]+ calcd for
C16H19N4O, 283.15589; found, 283.15616.
Carbo-N′-benzylidene(N′-benzylidene-N-propylhydrazide)
(11). Carbo-di-N-benzylhydrazide (2.50 g, 9.39 mmol) was added to a
500 mL round-bottom flask and dissolved in 100 mL of dried THF
with stirring. Iodopropane (1.2 equiv, 1.92 g, 1.1 mL, 11.3 mmol) was
added, followed by a slow addition of 2 equiv of sodium hydride (451
mg, 18.8 mmol). The solution was heated to reflux and allowed to
react for 24 h. The reaction mixture was allowed to cool to 0 °C, and
the unreacted sodium hydride was quenched by the slow addition of
methanol. This solution was then taken up in 100 mL of EtOAc and
washed three times with 75 mL of water. The crude extract was dried
over anhydrous sodium sulfate, and the solvent was evaporated in
vacuo. The crude product was filtered through a short silica gel column
(2:98 methanol in DCM as the eluent) and recrystallized from 1:9
EtOAc in hexanes to yield off-white crystals (2.14 g, 74%): mp 114−
116 °C; FT-IR (ν, cm−1, KBr) 3327, 2960, 2937, 2874, 1695, 1608,
1511, 1402; 1H NMR (400 MHz, CDCl3) δ 9.88 (s, 1H), 8.05 (s, 1H),
7.77−7.73 (m, 2H), 7.67−7.63 (m, 2H), 7.61 (s, 1H), 7.45−7.31 (m,
6H), 4.02−3.96 (t, J = 7.5 Hz, 2H), 1.70−1.59 (sextet, J = 7.5 Hz,
2H), 1.00−0.95 (t, J = 7.4 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ
152.1, 145.1, 137.1, 134.2, 134.0, 129.6, 128.7, 128.4, 127.2, 126.7,
42.1, 18.9, 11.0; HRMS (ESI) m/z [M + H]+ calcd for C18H21N4O,
309.17154; found, 309.17177.
2-Benzyl-4-ethyl-6-phenyl-1,2,4,5-tetrazinan-3-one (17).
Carbo-N′-benzylidene-N-benzylhydrazide(N′-benzylidene-N-ethylhy-
drazide) (7) (290 mg) was reacted according to the general
methanolysis and ring-closure procedure to yield an orange oil (154
mg, 69%): FT-IR (ν, cm−1, KBr) 3234, 3062, 3030, 2971, 2927, 1613,
1
1495, 1451; H NMR (400 MHz, CDCl3) δ 7.46−7.20 (m, 10H),
4.82−4.56 (m, 3H), 4.35−4.27 (m, 2H), 3.73−3.62 (sextet, J = 7.0 Hz,
1H), 3.46−3.36 (sextet, J = 7.0 Hz, 1H), 1.19−1.14 (d, J = 7.0 Hz,
3H); 13C NMR (100 MHz, CDCl3) δ 154.0, 137.8, 135.1, 128.5,
128.4, 128.3, 127.2, 126.2, 69.8, 53.5, 44.6, 12.3; HRMS (ESI) m/z [M
+ H]+ calcd for C17H21N4O, 297.17154; found, 297.17162.
2-Ethyl-4-methyl-6-phenyl-1,2,4,5-tetrazinan-3-one (18).
Carbo-N′-benzylidene-N-ethylhydrazide(N′-benzylidene-N-methylhy-
drazide) (9) (200 mg) was reacted according to the general
methanolysis and ring-closure procedure to yield white needle-like
crystals (70 mg, 49%): mp 78−80 °C; FT-IR (ν, cm−1, KBr) 3251,
3226, 2972, 2932, 2871, 1593, 1490, 1450, 1430; 1H NMR (400 MHz,
CDCl3) δ 7.54−7.48 (m, 2H), 7.40−7.28 (m, 3H), 4.89−4.81 (t, J =
10.0 Hz, 1H), 4.78−4.72 (d, J = 10.0 Hz, 1H), 4.64−4.58 (d, J = 10.0
Hz, 1H), 3.75−3.55 (sextet, J = 7.0 Hz, 1H), 3.41−3.30 (sextet, J = 7.0
Hz, 1H), 3.10 (s, 3H), 1.18−1.10 (t, J = 6.9 Hz, 3H); 13C NMR (100
MHz, CDCl3) δ 154.6, 135.3, 128.4, 126.4, 69.7, 44.5, 37.8, 12.4;
HRMS (ESI) m/z [M + H]+ calcd for C11H17N4O, 221.14024; found,
221.13961.
2,4-Dimethyl-6-phenyl-1,2,4,5-tetrazinan-3-one (12). Carbo-
di(N′-benzylidene-N-methylhydrazide) (1) (5.00 g) was reacted
according to the general methanolysis and ring-closure procedure to
yield white needle-like crystals (3.07 g, 88%): mp 103−105 °C; FT-IR
1
(ν, cm−1, KBr) 3254, 3218, 2967, 2938, 2877, 1598, 1506, 1451; H
NMR (400 MHz, CDCl3) δ 7.55−7.51 (d, J = 7.3 Hz, 2H), 7.42−7.34
(m, 3H), 5.09−5.02 (t, J = 9.9 Hz, 1H), 4.40−4.35 (d, J = 10.0 Hz,
2H), 3.17 (s, 6H); 13C NMR (100 MHz, CDCl3) δ 155.4, 135.2,
128.72, 128.67, 126.5, 69.4, 38.1; HRMS (ESI) m/z [M + H]+ calcd
for C10H15N4O, 207.12459; found, 207.12373.
2,4-Dimethyl-6-(thiophen-2-yl)-1,2,4,5-tetrazinan-3-one
(13). Carbo-di(N′-2-thienylidene-N-methylhydrazide) (2) (193 mg)
was reacted according to the general methanolysis and ring-closure
procedure to yield white needle-like crystals (82 mg, 62%): mp 123−
125 °C; FT-IR (ν, cm−1, KBr) 3246, 2970, 2923, 2875, 1602, 1507,
1434; 1H NMR (400 MHz, CDCl3) δ 7.32−7.29 (d, J = 4.9 Hz, 1H),
7.16−7.13 (m, 1H), 7.04−7.00 (t, J = 4.5 Hz, 1H), 5.24−5.18 (t, J =
2-Methyl-6-phenyl-4-propyl-1,2,4,5-tetrazinan-3-one (19).
Carbo-N′-benzylidene-N-methylhydrazide(N′-benzylidene-N-propyl-
hydrazide) (10) (500 mg) was reacted according to the general
methanolysis and ring-closure procedure to yield a yellow-orange oil
(262 mg, 72%): FT-IR (ν, cm−1, KBr) 3235, 3061, 3032, 2961, 2930,
1
2873, 1690, 1616, 1451; H NMR (400 MHz, CDCl3) δ 7.54−7.48
(m, 2H), 7.40−7.28 (m, 3H), 4.92−4.84 (t, J = 9.9 Hz, 1H), 4.77−
4.69 (d, J = 10.1 Hz, 1H), 4.62−4.54 (d, J = 9.9 Hz, 1H), 3.55−3.44
(m, 1H), 3.37−3.26 (m, 1H), 3.11 (s, 3H), 1.68−1.55 (sextet, J = 7.3
Hz, 2H), 0.93−0.84 (t, J = 7.3 Hz, 3H); 13C NMR (100 MHz, CDCl3)
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dx.doi.org/10.1021/jo300027b | J. Org. Chem. 2012, 77, 2415−2421