The Journal of Organic Chemistry
Article
column chromatography (Hexane:Ethyl acetate = 1:1, Rf = 0.7) to
obtain 3a as a slightly yellowish liquid (1.28 g, 91%). H NMR (300
ethyl acetate (3 × 10 mL). The organic phases were combined,
washed with NaOH (1.0 M), brine, and dried over anhydrous
Na2SO4. The solvent was removed to afford 3f as a white solid (333
mg, 99%), m.p. 114−115 °C. 1H NMR (500 MHz, CDCl3): δ 6.92 (s,
2H), 3.81 (s, 3H), 3.78 (s, 3H), 3.74−3.72 (t, J = 5.0 Hz, 8H), 3.54
(s, 4H), 2.52 (s, 8H). 13C{1H} NMR (125 MHz, CDCl3): δ 155.5,
151.5, 132.1, 114.5, 67.2, 62.2, 57.1, 55.6, 53.7. HRMS-ESI (+) (m/
1
MHz, CDCl3): δ 6.90 (s, 2H), 5.15 (s, 4H), 3.78 (s, 6H), 2.11−2.10
(d, J = 3.0 Hz, 6H) [the NMR spectra were in agreement with those
reported].54 Different from the previous procedure (74% yield), 4-
dimethylaminopyridine was used as a catalyst instead of pyridine,
leading to a higher yield (91%)]. HRMS-ESI (+) (m/z): [M + Na]+
calcd. for C14H18O6Na+, 305.0996; found: 305.0985.
+
z): [M + H]+ calcd. for C18H29N2O4 , 337.2122; found: 337.2113.
2,5-Dimethoxy-1,3-bis(methoxymethyl)benzene (3b). To a sol-
ution of 7 (1.0 g, 5.04 mmol) in DMF (10 mL) was added NaH (605
mg, 60%, 15.12 mmol) at 0 °C. The reaction mixture was stirred at 0
°C for 10 min. Then, CH3I (2.86 g, 20.16 mmol) was added. The
reaction mixture was allowed to warm to rt, stirred for another 4 h,
quenched with water (20 mL), and extracted with ethyl acetate (3 ×
30 mL). The organic layers were combined, washed with brine, dried
over anhydrous Na2SO4, and concentrated. The residue was purified
by column chromatography (Hexane:Ethyl acetate = 1:1, Rf = 0.8) to
((2,5-Dimethoxy-1,3-phenylene)bis(methylene))bis-
(phenylsulfane) (3g). A solution of 1c (648 mg, 2.0 mmol) in DMF
(10 mL) was added thiophenol (661.2 mg, 6.0 mmol) followed by
trimethylamine (0.6 mL). The reaction mixture was stirred at 70 °C
overnight, quenched with water (20 mL), and extracted with ethyl
acetate (3 × 20 mL). The organic layers were combined, washed with
brine, dried over anhydrous Na2SO4, and concentrated. The residue
was purified by column chromatography (Hexane:ethyl acetate = 6:1,
Rf = 0.4) to afford 3g as a white solid (620 mg, 81%), m.p. 63−64 °C.
1H NMR (500 MHz, CDCl3): δ 7.40−7.38 (m, 4H), 7.33−7.30 (m,
4H), 7.25−7.22 (m, 2H), 6.74 (s, 2H), 4.18 (s, 4H), 3.86 (s, 3H),
3.66 (s, 3H). 13C{1H} NMR (125 MHz, CDCl3): δ 155.5, 150.2,
136.5, 131.6, 129.9, 129.0, 126.4, 115.0, 62.7, 55.5, 33.3. HRMS-ESI
(+) (m/z): [M + K]+ calcd. for C22H22O2S2K+, 421.0693; found:
421.0687.
((2,5-Dimethoxy-1,3-phenylene)bis(methylene))bis-
(phenylselane) (3h). A solution of diphenyl diselenide (624 mg, 2.0
mmol) in DMF (5.0 mL) was added NaBH4 (151 mg, 4.0 mmol) and
stirred at rt for 10 min. Then, 1c (324 mg, 1.0 mmol) in DMF (4.0
mL) was added. The resulting mixture was stirred overnight,
quenched with water (20 mL), and extracted with ethyl acetate (3
× 20 mL). The organic layers were combined, washed with brine,
dried over anhydrous Na2SO4, and concentrated. The residue was
purified by column chromatography (Hexane:DCM = 4:1, Rf = 0.5)
to afford 3h as a white solid (300 mg, 63%), m.p. 38−39 °C. 1H NMR
(500 MHz, CDCl3): δ 7.55−7.54 (m, 4H), 7.31−7.29 (t, J = 5.0 Hz,
6H), 4.16 (s, 4H), 3.86 (s, 3H), 3.59 (s, 3H). 13C{1H} NMR (125
MHz, CDCl3): δ 155.2, 149.8, 133.6, 132.9, 130.7, 129.1, 127.4,
114.9, 62.1, 55.4, 26.5. HRMS-ESI (+) (m/z): [M + K]+ calcd. for
C22H22O2Se2K+, 516.9586; found: 516.9580.
1
obtain 3b as a colorless liquid (1.10 g, 96%). H NMR (500 MHz,
CDCl3): δ 6.92 (s, 2H), 4.51 (s, 4H), 3.81 (s, 3H), 3.76 (s, 3H), 3.44
(s, 6H). 13C{1H} NMR (125 MHz, CDCl3): δ 156.0, 150.0, 132.3,
114.1, 69.4, 62.5, 58.3, 55.6. HRMS-ESI (+) (m/z): [M + Na]+ calcd.
for C12H18O4Na+, 249.1103; found: 249.1094.
1,3-Bis((allyloxy)methyl)-2,5-dimethoxybenzene (3c). A solution
of 7 (1.0 g, 5.04 mmol) in DMF (10 mL) was added NaH (605 mg,
60%, 15.12 mmol) at 0 °C and stirred for 10 min. Then, allyl iodide
(2.54 g, 15.12 mmol) was added. The reaction mixture was allowed to
warm to rt, stirred for 3 h, quenched with water (10 mL), and
extracted with ethyl acetate (3 × 30 mL). The organic layers were
combined, washed with brine, dried over anhydrous Na2SO4, and
concentrated. The residue was purified by column chromatography
(Hexane:Ethyl acetate = 3:1, Rf = 0.85) to obtain 3c as a colorless
1
liquid (1.20 g, 86%). H NMR (500 MHz, CDCl3): δ 6.95 (s, 2H),
6.03−5.96 (m, 2H), 5.37−5.33 (d, J = 20.0 Hz, 2H), 5.24−5.22 (d, J
= 10.0 Hz, 2H), 4.58 (s, 4H), 4.10−4.09 (d, J = 5.0 Hz, 4H), 3.81 (s,
3H), 3.76 (s, 3H). 13C{1H} NMR (125 MHz, CDCl3): δ 156.0,
150.1, 134.8, 132.4, 117.1, 114.2, 71.4, 67.0, 62.6, 55.6. HRMS-ESI
+
(+) (m/z): [M + H]+ calcd. for C16H23O4 , 279.1591; found:
279.1583.
((2,5-Dimethoxy-1,3-phenylene)bis(methylene))bis-
(triphenylphosphonium) Bromide (3i). A mixture of 1c (324 mg, 1.0
mmol) and triphenylphosphine (630 mg, 2.4 mmol) in dry toluene
(5.0 mL) was refluxed for 6 h under argon. The crude white powder
was obtained by filtration, which was washed with ether (3 × 20 mL)
((((2,5-Dimethoxy-1,3-phenylene)bis(methylene))bis(oxy))bis-
(methylene))dibenzene (3d). A solution of 7 (1.0 g, 5.04 mmol) in
DMF (10 mL) was cooled to 0 °C and added NaH (605 mg, 60%,
15.12 mmol). The resulting mixture was stirred for 10 min. Then,
benzyl chloride (1.91 g, 15.12 mmol) was added. The reaction
mixture was allowed to warm to rt, stirred for another 3 h, quenched
with water (10 mL), and extracted with ethyl acetate (3 × 30 mL).
The organic layers were combined, washed with brine, dried over
anhydrous Na2SO4, and concentrated. The residue was purified by
column chromatography (Hexane:Ethyl acetate = 3:1, Rf = 0.8) to
1
to afford 3i as a white foam (840 mg, 99%). H NMR (500 MHz,
CDCl3): δ 7.79−7.62 (m, 6H), 7.67−7.64 (m, 24H), 6.53 (s, 2H),
5.18−5.15 (d, J = 15.0 Hz, 4H), 3.17 (s, 3H), 2.86 (s, 3H): m.p. 270−
271 °C. 13C{1H} NMR (125 MHz, CDCl3): δ 151.5, 135.3, 134.2,
134.2, 134.1, 130.5, 130.5, 130.4, 123.3, 118.1, 117.9, 117.9, 117.9,
117.4, 55.5, 26.0, 25.6. HRMS-ESI (+) (m/z): [M − 2Br]2+ calcd. for
C46H42O2P22+, 344.1325; found: 344.1319.
Radical Trapping with Monomers. Compound 3i (100 mg,
0.118 mmol) in CH3CN (1.5 mL) was added TEMPO (184 mg, 1.18
mmol) under stirring at rt. The resulting mixture was irradiated under
UV (350 nm) for 5 days and concentrated. The residue was purified
by chromatography (DCM:MeOH = 10:1) to afford compound 11c
as a white foam (24 mg, 31%). 1H NMR (300 MHz, CDCl3): δ 7.74−
7.61 (m, 15 H), 6.97 (s, 1H), 6.69 (s, 1H), 5.23−5.19 (d, J = 12.0 Hz,
2H), 4.58 (s, 2H), 3.52−3.49 (d, J = 9 Hz, 6H), 1.47 (s, 4H), 1.34 (s,
2H), 1.15−1.11 (d, J = 12.0 Hz, 12H). 13C{1H} NMR (75 MHz,
CDCl3): δ 155.7, 155.7, 134.9, 134.4, 134.2, 130.1, 129.9, 121.1,
121.0, 118.7, 117.5, 116.5, 114.7, 72.9, 62.0, 60.0, 55.7, 39.7, 32.9,
20.7, 17.0. HRMS-ESI (+) (m/z): [M − Br]+ calcd. for
C37H45NO3P+, 582.3132; found: 582.3115.
1
afford 3d as a colorless liquid (1.52 g, 80%). H NMR (500 MHz,
CDCl3): δ 7.45−7.33 (m, 10H), 7.03 (s, 2H), 4.66 (s, 8H), 3.84 (s,
3H), 3.74 (s, 3H). 13C{1H} NMR (125 MHz, CDCl3): δ 156.0,
150.2, 138.3, 132.4, 128.5, 127.9, 127.7, 114.4, 72.6, 67.1, 62.6, 62.6,
55.7, 55.6. HRMS-ESI (+) (m/z): [M + Na]+ calcd. for
C24H26O4Na+, 401.1723; found: 401.1717.
1,1′-(2,5-Dimethoxy-1,3-phenylene)bis(N,N-dimethylmethan-
amine) (3e). A solution of 1c (500 mg, 1.54 mmol) in ethyl acetate (5
mL) was added dimethylamine solution (2.0 M in methanol) (3.85
mL, 7.7 mmol) and stirred at rt for 2 h. The solvent was removed.
Then, water (5 mL) was added. The resulting mixture was extracted
with ethyl acetate (3 × 10 mL), washed with NaOH (1.0 M), brine,
and dried over anhydrous Na2SO4. The solvent was removed to afford
1
3e as a slightly yellowish gel (350 mg, 90%). H NMR (500 MHz,
CDCl3): δ 6.85 (s, 2H), 3.76 (s, 3H), 3.69 (s, 3H), 3.42 (s, 4H), 2.24
(s, 12H). 13C{1H} NMR (75 MHz, CDCl3): δ 155.7, 151.1, 132.5,
114.6, 61.9, 57.9, 55.6, 45.4. HRMS-ESI (+) (m/z): [M + H]+ calcd.
Carbocation Trapping with Monomers. A solution of
MeONH2·HCl (394 mg, 4.72 mmol) in DMF (2 mL) was added
trimethylamine (567 mg, 5.20 mmol) and stirred at rt for 30 min.
Then, 3i (100 mg, 0.118 mmol) in DMF (1 mL) was added. The
resulting mixture was stirred for 20 min, irradiated with 350 nm light
for 2 days, quenched with water, and extracted with ethyl acetate (3 ×
3 mL). The combined organic phases were combined, washed with
+
for C14H25N2O2 , 253.1911; found: 253.1905.
4,4′-((2,5-Dimethoxy-1,3-phenylene)bis(methylene))-
dimorpholine (3f). A solution of 1c (324 mg, 1.0 mmol) in ethyl
acetate (4 mL) was added morpholine (871 mg, 10.0 mmol), stirred
at rt overnight, diluted with water (5 mL), and then extracted with
K
J. Org. Chem. XXXX, XXX, XXX−XXX