L.N. Makley et al.
Bioorganic & Medicinal Chemistry 34 (2021) 115990
4.6.3.7. 1-(2,4-difluorophenoxy)-2,4-dinitrobenzene (12). Compound 12
was recrystallized from iPrOH at 30 ◦C overnight to give yellow needles
(170 mg, 75%; a repeat reaction on a larger scale yielded 2.70 g, 62%):
1H NMR (400 MHz, d6-DMSO): δ 8.9 (d, J = 2.4 Hz, 1H), 8.43 (dd, J = 8,
2 Hz, 2H), 7.68,
4.6.3.16. 2,4-dichloro-1-(2,4-dinitrophenoxy)benzene (28). Compound
28 was recrystallized from iPrOH to give a pale yellow solid (230 mg,
100%): 1H NMR (400 MHz, d6-DMSO): δ 8.93 (d, J = 2.4 Hz, 1H), 8.43
(dd, J = 9.2, 2.4 Hz, 1H), 7.94 (d, J = 2 Hz, 1H), 7.63,7.53 (m, 2H), 7.18
(d, J = 9.2 Hz, 1H).
7.57 (m, 2H), 7.30,7.22 (m, 2H).
4.6.3.17. 2,4-dinitro 1-(4-(trifluoromethyl)phenoxy)-benzene (29).
Compound 29 was recrystallized from iPrOH to give iridescent yellow
crystals (132 mg, 52%): 1H NMR (400 MHz, d6-DMSO): δ 8.11 (s, 1H),
7.67 (d, J = 6 Hz, 1H), 7.07 (d, J = 5.2 Hz, 2H), 6.64 (d, J = 5.6 Hz, 2H),
6.58 (d, J = 6.4, 1H).
4.6.3.8. 2-(2,4-difluorophenoxy)-1,3-dinitrobenzene (13). Compound 13
was recrystallized from iPrOH to give a yellow powder (94 mg, 42%): 1H
NMR (400 MHz, d6-DMSO): δ 7.69 (d, J = 5.6 Hz, 2H), 6.98 (t, J = 5.6,
1H), 6.69,6.65 (m, 1H), 6.23,6.18 (m, 2H).
4.6.3.9. phenoxy-3-nitro-pyridine (19). Compound 19 was synthesized
according to an adapted protocol. To a solution of 2-chloro-5-nitropyri-
dine (0.476 g, 3 mmol, 1 eq) in acetone (20 mL) was added phenol (0.28
mL, 3 mmol, 1 eq) and potassium carbonate (0.350 g, 3.45 mmol, 1.15
eq). The reaction mixture was heated to reflux overnight and then
worked up according to the general protocol. The product was recrys-
tallized from EtOAc (313 mg, 48%): 1H NMR (400 MHz, d6-DMSO): δ
8.56 (dd, J = 8, 1.6 Hz, 1H), 8.39 (dd, J = 4.8, 1.6 Hz, 1H), 7.42 (t, J =
7.6, 2H), 7.36 (dd, J = 8, 4.8 Hz, 1H), 7.26 (t, J = 7.6 Hz, 1H), 7.20 (d, J
= 7.6 Hz, 2H).
4.6.3.18. 1-(2,4-dimethylphenoxy)-2,4-dinitrobenzene (30). Compound
30 was recrystallized from iPrOH to give fine yellow crystals (60 mg,
19%): 1H NMR (400 MHz, d6-DMSO): δ 8.89 (d, J = 2 Hz, 1H), 8.41 (dd,
J = 9.2, 2 Hz, 1H). 7.25 (s, 1H), 7.16 (d, J = 8 Hz, 1H), 7.09 (d, J = 8.4
Hz, 1H), 6.93 (d, J = 9.6 Hz, 1H).
4.6.3.19. 4-(2,4-dinitrophenoxy)benzaldehyde (31). Compound 31 was
recrystallized from iPrOH to give a pale yellow solid (154 mg, 69%): 1H
NMR (400 MHz, d6-DMSO): δ 10.01 (s, 1H), 8.94 (d, J = 2.8, 1H), 8.52
(dd, J = 9.6, 2.8 Hz, 1H), 8.05 (dd, J = 6.4, 2.0 Hz, 2H), 7.43 (m, 3H).
4.6.3.10. 6-(2,4-difluorophenoxy)pyridine-3-amine (20). Compound 20
was synthesized from 2-(2,4,-ifluorophenoxy-5-nitropyridine using the
same procedure used to prepare 4 and recrystallized from iPrOH to give
21 (90.6 mg, 23%): 1H NMR (400 MHz, d6-DMSO): δ 7.41,7.34 (m, 2H),
7.24 (dd, J = 14.8, 9.2 Hz, 1H), 7.10,7.06 (m, 2H), 6.82 (d, J = 8.8, 1H),
5.04 (s, 2H).
4.6.3.20. 4-(2,4-dinitrophenoxy)benzoic acid (32). Compound 32 was
purified by silica gel column chromatography using 50:50 hexanes:
EtOAc, then recrystallized from iPrOH to give a yellow solid (62 mg,
21%): 1H NMR (400 MHz, d6-DMSO): 13.08 (s, 1H), 8.95,8.90 (m, 1H),
8.53,8.46 (m, 1H), 8.26 (t, J = 8.8 Hz, 2H), 8.05 (m, 3H).
4.6.3.21. 2-(2,4-dinitrophenoxy-naphthalene (34). Compound 34 was
recrystallized from iPrOH to give yellow crystals (137 mg, 40%): 1H
NMR (400 MHz, d6-DMSO): δ 8.93 (d, J = 2.4 Hz, 1H), 8.43 (dd, J = 8.8
Hz, 2.4, 1H), 8.10 (d, J = 8.8 Hz, 1H), 8.0 (d, J = 7.6 Hz, 1H), 7.9 (d, J =
7.6 Hz, 1H), 7.81 (s, 1H), 7.61,7.54 (m, 2H), 7.45 (dd, J = 8.8, 2 Hz, 1H),
7.25 (d, J = 9.2 Hz, 1H).
4.6.3.11. 2-phenoxypyridin-3-amine (23). Compound 23 was synthe-
sized from 3-nitro-phenoxypyridine using the same procedure used to
prepare 4 and was used without further purification (24.7 mg, 22%): 1H
NMR (400 MHz, d6-DMSO): δ 7.37 (t, J = 7.6 Hz, 2H), 7.31 (dd, J = 4.8,
1.2 Hz, 1H), 7.14 (t, J = 7.2 Hz, 1H), 7.07 (m, 3H), 6.86 (dd, J = 7.6, 4.8
Hz, 1H), 5.23 (s, 2H).
4.6.3.22. 1-(2,4-dinitrophenoxy)naphthalene (35). Compound 35 was
synthesized on a smaller scale from 1-napthol (38 mg, 0.26 mmol, 1 eq)
and 1-chloro-2,4-dinitrobenzene (53 mg, 0.26 mmol, 1 eq) with cesium
carbonate (98 mg, 0.3 mmol, 1.15 eq) and worked up as described in the
general procedure. The product was recrystallized from iPrOH to give a
yellow-orange solid (39 mg, 48%): 1H NMR (400 MHz, d6-DMSO): δ 8.97
(d, J = 2.4 Hz, 1H), 8.37 (dd, J = 9.2, 2.8 Hz, 1H), 8.10 (d, J = 8 Hz, 1H),
7.98 (d, J = 8 Hz, 1H), 7.92 (d, J = 8 Hz, 1H), 7.65,7.61 (m, 3H), 7.45 (d,
J = 7.2 Hz, 1H), 7.01 (d, J = 9.6 Hz, 1H).
4.6.3.12. 2-(4-iodophenoxy)-3-nitropyridine (24). Compound 24 was
synthesized according to an adapted protocol. To a solution of 2-chloro-
5-nitropyridine (0.476 g, 3 mmol, 1 eq) in acetone (20 mL) was added 4-
iodophenol (0.66 g, 3 mmol, 1 eq) and potassium carbonate (0.350 g,
3.45 mmol, 1.15 eq). The reaction mixture was heated to reflux over-
night and then worked up according to the general protocol. The
product was recrystallized from iPrOH (412 mg, 40%). 1H NMR (400
MHz, d6-DMSO): δ 8.59 (d, J = 8 Hz, 1H), 8.42 (d, J = 4.8 Hz, 1H), 7.79
(d, J = 8.8 Hz, 2H), 7.4 (dd, J = 8, 4.8 Hz, 1H), 7.07 (d, J = 8.4, 2H).
4.6.3.23. 5-(2,4-dinitrophenoxy)-1H-indole (36). Compound 36 was
purified by column chromatography in 100% CH2Cl2 which gave
incomplete separation. Only fractions that appeared to contain pure
product (by TLC) were pooled, from which the product was isolated (42
mg, 18% purified yield): 1H NMR (400 MHz, d6-DMSO): 9.12 (s, 1H),
8.94 (s, 1H), 8.66,8.63 (m, 1H), 8.05 (dd, J = 8.8, 1.6 Hz, 1H), 7.45 (t, J
= 2.8, 1H), 7.05 (d, J = 8.4, 1H), 6.98 (s, 1H), 6.7 (d, J = 8.8, 1H), 6.66
(s, 1H).
4.6.3.13. 1-(3-fluorophenoxy)-2,4-dinitrobenzene (25). Compound 25
was recrystallized from iPrOH to give pale peach crystals (126 mg,
41%):(1H NMR 400 MHz, d6-DMSO): δ 8.90 (d, J = 2.8 Hz, 1H), 8.47
(dd, J = 9.2, 2.8 Hz, 1H), 7.57 (dd, J = 15.2, 8 Hz, 1H), 7.31,7.19 (m,
3H), 7.13 (d, J = 7.6 Hz, 1H).
4.6.3.14. 1-(2,4-dinitrophenoxy)-2,3,4-trifluorobenzene
(26). Com-
pound 26 was slowly recrystallized from iPrOH overnight at 30 ◦C to
give pale yellow crystals (165 mg, 47%): 1H NMR (400 MHz, d6-DMSO):
δ 8.92 (d, J = 2.8 Hz, 1H), 8.44 (dd, J = 9.2, 2.8 Hz, 1H), 7.55,7.39 (m,
3H).
4.6.3.24. 2-(2,4-dinitrophenoxy)-6-methylpyridine (39). Compound 39
was recrystallized from iPrOH to give pale yellow needles (159 mg,
75%): 1H NMR (400 MHz, d6-DMSO): δ 8.86 (d, J = 2.8 Hz, 1H), 8.70
(dd, J = 9.2 Hz, 2.4 Hz, 1H), 7.86 (t, J = 7.6 Hz, 1H), 7.70 (d, J = 9.2 Hz,
1H), 7.11 (d, J = 7.6 Hz, 1H), 7.07 (d, J = 8.4 Hz, 1H), 2.26 (s, 3H).
4.6.3.15. 3-(2,4-dinitrophenoxy)-1,2,4,5-tetrafluorobenzene (27). Com-
pound 27 was recrystallized from iPrOH to give cream colored crystals
(88 mg, 43%): 1H NMR (400 MHz, d6-DMSO): δ 8.95 (d, J = 2.8 Hz, 1H),
8.46 (dd, J = 9.6, 2.8 Hz, 1H), 8.11,8.02 (m, 1H), 7.65 (d, J = 9.6 Hz,
1H).
4.6.3.25. 1-(3,5-dimethylphenoxy)-2,4-difluorobenzene (40). Compound
40 was synthesized via a Chan-Lam coupling. To a stirring suspension of
copper (II) acetate monohydrate (300 mg, 1.5 mmol, 1.5 eq) in CH2Cl2
(10 mL) containing molecular sieves was added 2,4-difluorophenol (95
11