The Journal of Organic Chemistry
Article
Methyl (4-Benzamido-6-methoxy-1,3,5-triazin-2-yl)glycinate
145.3, 140.0, 137.3, 130.4, 130.0, 129.9, 128.4, 128.3, 125.5, 56.2,
21.8. HRMS-ESI (m/z) calculated for C20H18N8NaO4S+ [M + Na]+,
461.1002; found, 461.1010.
(3ac). The product (264 mg, 83%) was an orange solid, with
1
petroleum ether/EtOAc as the eluent (PE/EA = 1:1 v/v). H NMR
(400 MHz, chloroform-d): δ 8.56 (s, 1H), 7.86 (d, J = 8.4 Hz, 2H),
7.57 (t, J = 7.4 Hz, 1H), 7.48 (t, J = 7.6 Hz, 2H), 6.54 (s, 1H), 4.25
(d, J = 5.5 Hz, 2H), 3.92 (d, J = 2.6 Hz, 3H), 3.77 (d, J = 5.4 Hz, 3H).
13C{1H} NMR (101 MHz, chloroform-d): δ 171.3, 170.3, 167.8,
166.2, 164.7, 134.2, 132.6, 128.8, 127.8, 54.7, 52.4, 42.9. HRMS-ESI
2,4-Dimethoxy-6-(5-methyl-4-(phenylsulfonyl)-1H-1,2,3-triazol-
1
1-yl)-1,3,5-triazine (6c). The product was a light yellow solid. H
NMR (400 MHz, chloroform-d): δ 8.08 (d, J = 7.5 Hz, 2H), 7.62 (t, J
= 7.4 Hz, 1H), 7.54 (t, J = 7.6 Hz, 2H), 4.13 (s, 6H), 3.00 (s, 3H).
13C{1H} NMR (101 MHz, chloroform-d): δ 173.5, 164.4, 145.9,
140.6, 139.1, 134.1, 129.5, 128.0, 56.5, 11.6. HRMS-ESI (m/z)
calculated for C14H14N6NaO4S+ [M + Na]+, 385.0689; found,
385.0693.
+
(m/z) calculated for C14H15N5NaO4 [M + Na]+, 340.1016; found,
340.1023.
Dimethyl 2,2′-((6-Benzamido-1,3,5-triazine-2,4-diyl)bis(oxy)) di-
2,4-Dimethoxy-6-(5-methyl-4-tosyl-1H-1,2,3-triazol-1-yl)-1,3,5-
acetate (3ad). The product (154 mg, 41%) was a yellow solid, with
1
1
triazine (6d). The product was a light yellow solid. H NMR (400
petroleum ether/EtOAc as the eluent (PE/EA = 2:1 v/v). H NMR
MHz, chloroform-d): δ 7.95 (d, J = 8.3 Hz, 2H), 7.33 (d, J = 8.2 Hz,
2H), 4.13 (s, 6H), 2.99 (s, 3H), 2.41 (s, 3H). 13C{1H} NMR (101
MHz, chloroform-d): δ 173.5, 164.4, 146.2, 145.3, 138.8, 137.7130.1,
128.1, 56.5, 21.8, 11.5. HRMS-ESI (m/z) calculated for
C15H16N6NaO4S+ [M + Na]+, 399.0846; found, 399.0839.
(400 MHz, chloroform-d): δ 8.69 (s, 1H), 7.87 (d, J = 8.6 Hz, 2H),
7.59 (t, J = 7.4 Hz, 1H), 7.49 (t, J = 7.6 Hz, 2H), 4.93 (s, 4H), 3.78 (s,
6H). 13C{1H} NMR (101 MHz, chloroform-d): δ 172.1, 167.9, 166.2,
164.8, 133.5, 132.9, 128.8, 127.8, 63.8, 52.4. HRMS-ESI (m/z)
+
calculated for C16H16N4NaO7 [M + Na]+, 399.0911; found,
2-(4-((4-Chlorophenyl)sulfonyl)-5-methyl-1H-1,2,3-triazol-1-yl)-
4,6-dimethoxy-1,3,5-triazine (6e). The product was a light yellow
solid. 1H NMR (400 MHz, chloroform-d): δ 8.01 (d, J = 8.1 Hz, 2H),
7.52 (d, J = 8.1 Hz, 2H), 4.13 (s, 6H), 3.00 (s, 3H). 13C{1H} NMR
(101 MHz, chloroform-d): δ 173.5, 164.4, 145.5, 140.9, 139.2, 139.0,
129.8, 129.6, 56.5, 11.6. HRMS-ESI (m/z) calculated for
C14H13ClN6NaO4S+ [M + Na]+, 419.0300; found, 419.0306.
General Procedures for the Synthesis of Diazo Compounds
(7m, 7n, 8a, and 9a). To a solution of active methylene compounds
(1 mmol, 1.0 equiv) in DMSO (4 mL) was added K2CO3 (0.4 mmol,
0.4 equiv) and stirred at 25 °C for 3−5 min. Then, azide (1 mmol, 1.0
equiv) was added in one portion. The reaction mixture was stirred
and monitored by TLC. After 15 min, the reaction mixture was
poured into water (10 mL) and extracted with EtOAc (10 mL × 3).
The combined organic phase was washed with brine (10 mL), dried
over Na2SO4, and evaporated under reduced pressure to provide the
crude product. The residue was purified by flash column
chromatography on silica gel (EA/PE) to afford the desired
compound if necessary.
399.0919.
Methyl 2-((4-Benzamido-6-methoxy-1,3,5-triazin-2-yl)thio) Ac-
etate (3ae). The product (160 mg, 48%) was a yellow solid, with
petroleum ether/EtOAc as the eluent (PE/EA = 2:1 v/v). H NMR
1
(400 MHz, chloroform-d): δ 8.41 (s, 1H), 7.90−7.85 (m, 2H), 7.61
(t, J = 7.4 Hz, 1H), 7.51 (t, J = 7.6 Hz, 2H), 4.02 (s, 3H), 3.96 (s,
2H), 3.77 (s, 3H). 13C{1H} NMR (101 MHz, chloroform-d): δ 183.2,
170.3, 169.1, 164.8, 163.7, 133.6, 133.1, 129.0, 127.8, 55.5, 53.0, 32.8.
HRMS-ESI (m/z) calculated for C14H14N4NaO4S+ [M + Na]+,
357.0628; found, 357.0634.
Dimethyl 2,2′-((6-Benzamido-1,3,5-triazine-2,4-diyl)bis-
(sulfanediyl))diacetate (3af). The product (118 mg, 29%) was a
yellow solid, with petroleum ether/EtOAc as the eluent (PE/EA =
1
2.5:1 v/v). H NMR (400 MHz, chloroform-d): δ 8.37 (s, 1H), 7.86
(d, J = 8.6 Hz, 2H), 7.60 (d, J = 7.4 Hz, 1H), 7.51 (t, J = 7.6 Hz, 2H),
3.94 (s, 4H), 3.78 (s, 6H). 13C{1H} NMR (101 MHz, chloroform-d):
δ 180.8, 169.0, 164.6, 160.7, 133.5, 133.2, 129.1, 127.8, 53.0, 32.7.
+
HRMS-ESI (m/z) calculated for C16H16N4NaO5S2 [M + Na]+,
431.0454; found, 431.0463.
4-Diazo-2,6-dimethylheptane-3,5-dione (7m). The product (173
mg, 95%) was a pale yellow liquid, with petroleum ether/EtOAc as
the eluent (PE/EA = 19:1 v/v). 1H NMR (400 MHz, chloroform-d):
δ 3.24 (hept, J = 6.8 Hz, 2H), 1.14 (d, J = 6.8 Hz, 12H). 13C{1H}
NMR (101 MHz, chloroform-d): δ 195.6, 81.5, 38.1, 18.6.
2-Diazo-1-phenylethan-1-one (4a). The product was a yellow
solid, with petroleum ether/EtOAc as the eluent (PE/EA = 9:1 v/v).
1H NMR (400 MHz, chloroform-d): δ 7.75 (d, J = 7.3 Hz, 2H), 7.53
(t, J = 7.4 Hz, 1H), 7.43 (t, J = 7.6 Hz, 2H), 5.91 (s, 1H). 13C{1H}
NMR (101 MHz, chloroform-d): δ 186.4, 136.7, 132.8, 128.7, 126.8,
54.3.
4-Diazo-2,2,6,6-tetramethylheptane-3,5-dione (7n). The product
(180 mg, 86%) was a yellow solid, with petroleum ether/EtOAc as the
General Procedures for the Synthesis of Triazine Com-
pounds (6a−6e). To a solution of active methylene compounds 5 (1
mmol, 1.0 equiv) (were commercially purchased from Sigma-Aldrich)
in DMSO/H2O (4 mL, v:v = 1:1) was added K2CO3 (0.4 mmol, 0.4
equiv) and stirred at 25 °C for 3−5 min. Then, azide 1 (1 mmol, 1.0
equiv) was added in one portion. The reaction mixture was stirred
and monitored by TLC. After completion, the reaction mixture was
poured into water (10 mL) and extracted with EtOAc (10 mL × 3).
The combined organic phase was washed with brine (10 mL), dried
over Na2SO4, and evaporated under reduced pressure to provide the
crude product. The residue was purified by flash column
chromatography on silica gel (EA/PE) to afford the desired
compound if necessary.
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eluent (PE/EA = 19:1 v/v). H NMR (400 MHz, chloroform-d): δ
1.27 (s, 18H). 13C{1H} NMR (101 MHz, chloroform-d): δ 97.1, 80.1,
45.4, 26.7.
2-Diazo-1,3-diphenylpropane-1,3-dione (8a). The product (238
mg, 95%) was a yellow solid, with petroleum ether/EtOAc as the
1
eluent (PE/EA = 5:1 v/v). H NMR (400 MHz, chloroform-d): δ
7.59−7.54 (m, 4H), 7.44 (t, J = 7.5 Hz, 2H), 7.35−7.29 (m, 4H).
13C{1H} NMR (101 MHz, chloroform-d): δ 186.6, 137.1, 132.8,
128.5, 128.5, 84.6.
2-Diazo-1-phenyl-2-(phenylsulfonyl)ethan-1-one (9a). The prod-
uct (248 mg, 87%) was a yellow solid, with petroleum ether/EtOAc as
the eluent (PE/EA = 5:1 v/v). 1H NMR (400 MHz, chloroform-d): δ
8.06 (dd, J = 8.4, 1.2 Hz, 2H), 7.69−7.64 (m, 1H), 7.56 (ddd, J = 6.0,
4.2, 3.0 Hz, 5H), 7.47−7.42 (m, 2H). 13C{1H} NMR (101 MHz,
chloroform-d): δ 182.7, 141.5, 135.9, 134.3, 133.2, 129.3, 129.0,
128.3, 127.6, 83.5.
2,4-Dimethoxy-6-(5-phenyl-4-(phenylsulfonyl)-1H-1,2,3-triazol-
1-yl)-1,3,5-triazine (6a). The product was a light yellow solid, with
petroleum ether/EtOAc as the eluent (PE/EA = 4:1 v/v). H NMR
1
(400 MHz, chloroform-d): δ 7.79 (dd, J = 8.4, 1.2 Hz, 2H), 7.60−
7.55 (m, 1H), 7.53−7.49 (m, 1H), 7.46−7.41 (m, 4H), 7.29 (dd, J =
7.6, 1.9 Hz, 2H), 3.75 (s, 6H). 13C{1H} NMR (101 MHz,
chloroform-d): δ 173.4, 163.9, 147.0, 140.3, 140.3, 134.1, 130.4,
130.0, 129.3, 128.4, 128.2, 125.5, 56.2. HRMS-ESI (m/z) calculated
for C19H16N6NaO4S+ [M + Na]+, 447.0846; found, 447.0840.
2,4-Dimethoxy-6-(5-phenyl-4-tosyl-1H-1,2,3-triazol-1-yl)-1,3,5-
triazine (6b). 1H NMR (400 MHz, chloroform-d): δ 7.68 (d, J = 8.1
Hz, 2H), 7.51 (d, J = 7.5 Hz, 1H), 7.46 (d, J = 7.4 Hz, 2H), 7.31 (d, J
= 7.3 Hz, 2H), 7.24 (d, J = 8.0 Hz, 2H), 3.76 (s, 6H), 2.40 (s, 3H).
13C{1H} NMR (101 MHz, chloroform-d): δ 173.3, 163.9, 147.2,
ASSOCIATED CONTENT
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* Supporting Information
The Supporting Information is available free of charge at
Calculation details, characterization data, X-ray crystal-
lography data of 1a, and H and 13C NMR spectra of
1
G
J. Org. Chem. XXXX, XXX, XXX−XXX