Organic Process Research & Development
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detector: temp: 250 °C; mode: constant flow; H2 flow: 30 mL/
min; air flow: 300.0 mL/min; makeup flow: 10 mL/min (N2).
Quantitative product analysis was calculated using the following
method: a 0.10 mL solution of biphenyl (10 mg/L) containing
a standard of the specific compound of interest (0.05 mL) in
MeOH (1.00 mL). The retention times of commercial
standards and pure products: (min) anisole, 2.00; benzene,
0.63; phenol, 3.28; cresol, 4.80; toluene, 1.13; 3-methylanisole,
5.80; 3-methoxybenzyl alcohol, 8.96; 3-methoxybenzaldehyde,
8.09; 2,4,6-tris(2-methoxyphenoxy)-1,3,5-triazine, 19.86.
General Information. All reagents and solvents were
obtained from commercial suppliers and used as supplied
unless stated otherwise. All yields refer to chromatographically
and spectroscopically pure products unless stated otherwise. All
NMR spectra were recorded on Bruker DPX-300 and DRX-500
spectrometers in the solvents specified. Infrared spectra were
recorded neat on NaCl plates or as a solid on a diamond
transmission accessory using a PerkinElmer FT-IR spectrom-
eter; details are reported as νmax in cm−1. Mass spectra were
carried out using a Microsmass LCT (ES mode), Bruker
Daltonic (ES mode), and Waters GCT Premier (EI and FI
mode) apparatus and are reported as values in atomic mass
units followed by the peak intensity relative to the base peak
(100%). Elemental analysis was done using a Carlo Erba 1108
elemental analyzer apparatus. Crystal and molecular structures
were determined using single crystal X-ray diffraction using
Nonius KappaCCD and Bruker-Nonius FR591/X8Apex
apparatus. Melting points were measured using a Griffin
melting point apparatus and are uncorrected. Sulfonylated
phenols used were synthesized and hydrogenolyzed using
standard procedures; see SI. Tetrazoylguaicol was synthesized
using the method of Alves et al.;11 see SI.
General Method for the Synthesis of 1,3,5-Triaryloxy-
2,4,6-triazines 1−10. A solution of cyanuric chloride (1
equiv) in acetone (300 mL) was added dropwise to a solution
of the phenol (3 equiv) in water (300 mL) with NaOH (3
equiv) and the resulting solution stirred at room temperature
for 3 h. The reaction mixture was filtered; the resulting solid
was washed with water (2 × 100 mL) and crystallized.
1,3,5-Triphenoxy-2,4,6-triazine (1). 1 was recrystallized
from MeOH to give a white solid (2.26 g, 6.32 mmol, 89%).
1H NMR (500 MHz, CDCl3): δ = 7.35 (ddd, J = 8.3, 7.4, 0.9
Hz, 9H, C3H/C4H/C5H), 7.16−7.10 (m, 6H, C2H/C6H). Lit
1H NMR: δ = 7.25−6.60 (m). 13C NMR (125 MHz, CDCl3): δ
= 173.68, 151.61, 129.44, 126.03, 121.39. HRMS (ES+ mode):
m/z = 380.1020 [100%, MNa+]; calculated for C21H15N3O3
requires [MNa+]: m/z = 380.1006. Mpt. (MeOH) 230−232
°C; Lit.21 Mpt. (CHCl3/hexane) 230−231 °C.
solid (2.34 g, 5.24 mmol, 92%). 1H NMR (501 MHz, CDCl3) δ
= 7.24 (s, 3H, C5H), 6.75 (dddd, J = 16.1, 8.1, 2.4, 0.8 Hz, 6H,
C5H/C6H), 6.69 (t, J = 2.3 Hz, 3H, C2H), 3.76 (s, 9H,
OCH3). 13C NMR (126 MHz, CDCl3) δ = 173.63, 160.49,
152.45, 129.80, 113.59, 111.88, 107.52, 55.41. LC-MS: m/z =
448.20 [100%, MH+]; calculated for C24H21N3O6 requires
[MH+]: m/z = 448.15. IR υmax/ cm−−1 (film): 3011, 2840,
1576, 1269, 1146, 1040, 776. Mpt. 145−147 °C.
1,3,5-Tri(4-methoxyphenoxy)-2,4,6-triazine (4). 4 was
recrystallized from MeOH to give the title product as a white
1
solid (3.08 g, 6.97 mmol, 85%). H NMR as described in the
literature.23 13C NMR (125 MHz, CDCl3): 190.9, 173.6, 156.0,
134.8, 131.7, 122.6. HRMS (ES+ mode): m/z = 464.0870
[100%, MNa+]; calculated for C24H15N3O6 requires [MNa+]:
m/z = 464.0853. Mpt. (MeOH) 168−170 °C; Lit.24 Mpt.
(EtOAc) 174−176 °C.
1,3,5-Tri(4-formylphenoxy)-2,4,6-triazine (5). 5 was filtered
to give the product as a yellow solid (2.84 g, 6.35 mmol, 92%).
1H NMR and Mpt. are as described in the literature.25
1,3,5-Tri(2-methoxy-4-formylphenoxy)-2,4,6-triazine (6). 6
was recrystallized from MeOH to give the title product as a
1
white solid (2.16 g, 4.07 mmol, 62%). H NMR (500 MHz,
CDCl3): δ = 10.01 (s, 1H, CHO), 7.50 (d, J = 1.8 Hz, 1H,
C5H), 7.49 (d, J = 1.8 Hz, 1H, C3H), 7.30 (d, J = 8.4 Hz, 1H,
C6H), 3.86 (3H, s, OCH3). 13C NMR (125 MHz, CDCl3): δ =
190.79, 173.70, 151.70, 145.04, 135.73, 124.72, 122.71, 111.48,
56.26. HRMS (ES+ mode): m/z = 554.1176 [100%, MNa+];
calculated for C27H21N3O9 requires [MNa+]: m/z = 554.1170.
IR υmax/ cm−1 (film): 3012, 2835, 2563, 2097, 1694, 1593,
1466, 1263, 1202, 1174, 812, 732. Mpt. (MeOH) 238−240 °C.
1,3,5-Tri(4-methoxycarbonylphenoxy)-2,4,6-triazine (7). 7
was recrystallized from CH2Cl2 to give the title product as
1
white solid (1.54 g, 2.90 mmol, 66%). H NMR (501 MHz,
CDCl3): δ = 8.05 (d, J = 8.7 Hz, 6H, C3H/C5H), 7.19 (d, J =
8.8, 6H, C2H/C6H), 3.93 (3H, s, COOCH3). 13C NMR (125
MHz, CDCl3): δ = 173.10, 166.80, 159.74, 131.92, 122.87,
115.89, 51.89. HRMS (ES+ mode): m/z = 554.1176 [100%,
MNa+]; calculated for C27H21N3O9 requires [MNa+]: m/z =
554.1170. IR υmax/ cm−1 (film): 2986, 1726, 1538, 1357, 1286,
1117, 739. Mpt. 148−151 °C.
1,3,5-Tri(2-methoxy-4-methoxycarbonylphenoxy)-2,4,6-
triazine (8). 8 was recrystallized from CH2Cl2 to give the title
1
product as a white solid (0.19 g, 0.30 mmol, 33%). H NMR
(500 MHz, CDCl3): δ = 7.67 (dd, J = 8.3, 1.9 Hz, 3H, C5H),
7.62 (d, J = 1.9 Hz, 3H, C3H), 7.16 (d, J = 8.3 Hz, 3H, C6H),
3.93 (s, 9H, OCH3), 3.83 (s, 9H, COOCH3). 13C NMR (125
MHz, DMSO-d6): δ = 166.71, 164.10, 150.84, 142.00, 129.16,
124.62, 117.64, 112.29, 56.19, 52.07. LC-MS: m/z = 622.22
[100%, MH+]; calculated for C30H27N3O12 requires [MH+]: m/
z = 622.16. IR υmax/ cm−1 (film): 2975, 1718, 1538, 1357, 1291,
1174, 739. Mpt. 251−253 °C.
1,3,5-Tri(2-methoxyphenoxy)-2,4,6-triazine (2). 2 was
recrystallized from MeOH to give a white crystalline product
(19.68 g, 44.03 mmol, 78%). 1H NMR (500 MHz, DMSO-d6):
δ = 7.22 (ddd, J = 8.2, 7.4, 1.6 Hz, 3H, C5), 7.13 (ddd, J = 30.5,
8.1, 1.5 Hz, 6H, C4/C6), 6.93 (td, J = 7.7, 1.4 Hz, 3H, C3),
3.85 (s, 9H, OCH3). 13C NMR (125 MHz, DMSO-d6): δ =
173.62, 151.16, 140.86, 126.80, 122.35, 120.60, 112.66, 55.79.
HRMS (ES+ mode): m/z = 448.1509 [100%, MH+]; calculated
1,3,5-Tri(4-benzoyloxy)-2,4,6-triazine (9). After filtration
and vacuum drying, the product was obtained as a white
1
solid (1.54 g, 3.15 mmol, 76%). H NMR was as described in
the literature.26 13C NMR (126 MHz, DMSO-d6): δ = 172.70,
166.41, 154.53, 130.90, 128.59, 121.61. HRMS (ES+ mode):
m/z = 490.0883 [100%, MH+]; calculated for C24H15N3O9
requires [MH+]: m/z = 490.0881. Mpt. 329−331 °C; lit.26 mpt.
> 300 °C.
for C24H22N3O6 requires [MH+]: m/z = 448.1506. IR υmax
/
cm−1 (film): 3017, 2836, 2097, 1695, 1596, 1476, 1253, 1202,
1166, 743. Analysis calculated (%) for C24H21N3O6: C, 64.42;
H, 4.73; N, 9.39. Found: C, 64.15; H, 4.75; N, 9.25. Mpt.
(MeOH) 139−141 °C; Lit.22 Mpt. 145 °C.
1,3,5-Tri(2-methoxy-4-carboxy)-2,4,6-triazine (10). After
filtration and vacuum drying, the product was obtained as a
1
1,3,5-Tri(3-methoxyphenoxy)-2,4,6-triazine (3). 3 was
recrystallized from MeOH to give the product as a white
yellow solid (1.40 g, 2.41 mmol, 71% yield). H NMR (501
MHz, DMSO-d6): δ = 13.04 (brs, 3H, COOH), 7.61−7.50 (m,
E
Org. Process Res. Dev. XXXX, XXX, XXX−XXX