crystalline solid was collected, washed one time with DMF,
and then with petroleum ether until absence of PPh3 in the
organic solvent (checked by TLC). The solid was dried in
vacuum for 24 h.
Benzyltriphenylphosphonium Chloride (16). Reagents:
benzyl chloride (19.0 g, 150 mmol), PPh3 (40.0 g, 153 mmol).
Solvent: DMF (300.0 mL). TLC: Rf ) 0.05 (SiO2, developing
solvent, CH2Cl2/MeOH (90:10); detection λ ) 254 nm). Yield
50.2 g (86%). Mp > 300.0 °C. 1H NMR (DMSO-d6) δ (ppm):
5.20 (d, 2H, J ) 15.7 Hz), 6.99 (m, 2H), 7.25 (t, 2H), 7.32 (m,
1H), 7.65–7.77 (m, 12H), 7.91 (m, 3H). MS (ESI) m/z: 353
(M+• - 35). Anal. (C25H22ClP) C, H, N.
K2CO3 (9.8 g, 71 mmol), and 18-crown-6 (0.2 g, 0.7 mmol).
Solvent: toluene (355.0 mL). Reaction time: 2.5 h. Isolation:
the brown solid was collected and washed with toluene (∼100.0
mL), and the organic layer was evaporated in vacuo. The residue
was a mixture of E and Z isomers, ratio 1:2 ) 2.2. Prepurifi-
cation: the residue was prepurified by column chromatography
(SiO2 flash, petroleum ether/EtOAc (90:10 to 80:20). 1 (E-
isomer): fractions corresponding to the product (10.0 g, 59%)
were crystallized from petroleum ether/EtOAc (85:15) to give
7.4 g (44%) as orange needles. Mp 143.8–145.5 °C. TLC: Rf
) 0.75 (SiO2, developing solvent, petroleum ether/EtOAc (85:
15), detection λ ) 254 nm). HPLC: tR ) 13.86 min (to ) 2.29
min). 1H NMR (CDCl3) δ: 7.09 (d, J ) 16.3 Hz, 1H), 7.21 (d,
J ) 16.3 Hz, 1H), 7.34 (t, J ) 7.2 Hz, 1H), 7.40 (t, J ) 7.6
Hz, 2H), 7.54 (d, J ) 7.3 Hz, 2H), 7.60 (br s, 3H). MS (EI)
m/z (%): 238 (M+•, 90), 222 (16), 192 (16), 178 (100), 149 (3).
IR ν (cm-1): 1614, 1572, 1525, 1485, 962, 758, 735. Anal.
(C14H10N2O2) C, H, N. 2 (Z-isomer): the fractions corresponding
to the product (4.5 g, 27%) were crystallized from petroleum
ether to give 3.5 g (21%) as a pale yellow solid. Mp 61.5–62.9
°C. TLC: Rf ) 0.85 (SiO2, developing solvent, petroleum ether/
EtOAc (85:15), detection λ ) 254 nm). HPLC: tR ) 12.30 min
(4-Chlorobenzyl)triphenylphosphonium Chloride (17).
Reagents: 4-chlorobenzyl chloride (35.4 g, 221 mmol), PPh3
(64.0 g, 244 mmol). Solvent: DMF (430.0 mL). TLC: Rf )
0.05 (SiO2, developing solvent, CH2Cl2/MeOH (90:10); detec-
1
tion λ ) 254 nm). Yield 61.5 g (67%). Mp > 300.0 °C. H
NMR (DMSO-d6) δ (ppm): 5.26 (d, 2H, J ) 15.8 Hz), 6.99
(m, 2H), 7.33 (d, 2H), 7.68–7.76 (m, 12H), 7.92 (m, 3H). MS
(ESI) m/z: 387 (M+• - 35). Anal. (C25H21Cl2P) C, H, N.
(3,4-Methylendioxobenzyl)triphenylphosphonium Chlo-
ride (18). Reagents: 5-(chloromethyl)benzo[d]1,3-dioxole, 15,
(22.0 g, 129 mmol), PPh3 (37.0 g, 142 mmol). Solvent: DMF
(200.0 mL). TLC: Rf ) 0.05 (SiO2, developing solvent, CH2Cl2/
MeOH (90:10), detection λ ) 254 nm). Yield 52.0 g (93%).
Mp > 300.0 °C. 1H NMR (DMSO-d6) δ (ppm): 5.09 (d, 2H,
J ) 15.1 Hz), 5.97 (s, 2H), 6.48 (m, 2H), 6.80 (d, 1H),
1
(to ) 2.29 min). H NMR (CDCl3) δ: 6.74 (d, J ) 12.2 Hz,
1H), 6.94 (d, J ) 12.2 Hz, 1H), 7.18 (br s, 1H), 7.33 (br s,
5H), 7.42 (br s, 2H). MS (EI) m/z (%): 238 (M+•, 3), 222 (30),
192 (25), 178 (26), 149 (40). IR ν (cm-1): 1610, 1570, 1520,
1480. Anal. (C14H10N2O2) C, H, N.
7.65–7.76 (m, 12H), 7.91 (m, 3H). MS (ESI) m/z: 397 (M+•
-
5-[2(E and Z)-(4-Chlorophenyl)ethenyl]benzo[1,2-c]1,2,5-
oxadiazole N1-Oxide (3 and 4). Reagents: 5-formylbenzo-
furoxan (8.2 g, 50 mmol), phosphonium salt 17 (21.2 g, 50
mmol), K2CO3 (6.9 g, 50 mmol), and 18-crown-6 (0.1 g, 0.5
mmol). Solvent: toluene (250.0 mL). Reaction time: 2.0 h.
Isolation: the brown solid (E- isomer, checked by TLC) was
collected and washed with toluene (∼100.0 mL), acetone
(∼200.0 mL), and EtOH (∼300.0 mL). The mixture of the
organic layer together with the reaction solvent was evaporated
in vacuo. The residue was a mixture of E and Z isomers. Pre-
purification: the residue was prepurified by column chroma-
tography (Al2O3, petroleum ether/EtOAc (90:10 to 80:20). Ratio
3:4 ) 3.6. 3 (E-isomer): the brown solid, together with the
fractions from the chromatographic column corresponding to
the product (8.9 g, 65%) were crystallized from EtOH to give
6.3 g (54%) as an orange solid. Mp 173.0–174.0 °C. TLC Rf
) 0.70 (SiO2, developing solvent, petroleum ether/EtOAc (85:
15), detection λ ) 254 nm). HPLC: tR ) 14.52 min (to ) 1.71
min). 1H NMR (CDCl3) δ: 7.45 (d, J ) 16.2 Hz, 1H), 7.47 (d,
J ) 8.5 Hz, 2H), 7.55 (d, J ) 16.0 Hz, 1H), 7.55–7.61 (br s,
1H), 7.72 (d, J ) 8.5 Hz, 2H), 7.88–7.90 (br s, 2H). MS (EI)
m/z (%): 272 (M+ ., 100), 256 (24), 226 (8), 212 (64), 177 (46),
149 (9). IR ν (cm-1): 1611, 1522, 957, 843, 689. Anal.
(C14H9N2O2Cl) C, H, N. 4 (Z-isomer): the fractions from
chromatographic column corresponding to the product (2.5 g,
18%) were crystallized from petroleum ether:EtOAc
(90:10) to give 1.8 g (13%) as yellow solid. mp 116.0–117.0
°C. TLC Rf ) 0.75 (SiO2, developing solvent: petroleum ether:
EtOAc (85:15), detection: λ ) 254 nm). HPLC: tR ) 12.00
35). Anal. (C26H22ClO2P) C, H, N.
5-Formylbenzo[1,2-c]1,2,5-oxadiazole N1-Oxide (19). A
mixture of 4-chloro-3-nitrobenzaldehyde (19.0 g, 102 mmol)
and NaN3 (6.3 g, 97 mmol) in DMSO (90.0 mL) was heated at
60–75 °C during 0.5 h and subsequently at 90–100 °C during
1.5 h. The residue was treated with H2O (250.0 mL) and brine
(250.0 mL) and extracted with EtOAc (4 × 100.0 mL). After
the workup the organic layer was dried with Na2SO4 and
evaporated in vacuo. The residue was purified by chromato-
graphic column (Al2O3, petroleum ether/EtOAc (90:10 to
80:20)). The product was crystallized from petroleum ether/
EtOAc (85:15) to give 19 as a yellow solid (10.4 g, 65%). Mp
68.0–69.0 °C. TLC: Rf ) 0.60 (SiO2, developing solvent,
1
petroleum ether/EtOAc (90:10), detection λ ) 254 nm). H
NMR (CDCl3) δ (ppm): 7.71 (br s, 1H), 7.83 (br s, 1H), 7.99
(br s, 1H), 10.03 (s, 1H). MS (EI) m/z (%): 164 (M+•, 100),
148 (7), 103 (37). IR ν (cm-1): 1699, 1605, 1537, 1485. Anal.
(C7H4N2O2) C, H, N.
General Procedure for the Synthesis of Arylethenylben-
zofuroxan Derivatives (1–6). A mixture of 5-formylbenzo-
furoxan 19 (1.0 equiv), phosphonium salt (16, 17, or 18, 1.0
equiv), K2CO3 (1.0 equiv), 18-crown-6 (0.01 equiv), and dry
toluene (5.0 mL/mmol of 19) as solvent was stirred at reflux
until the aldehyde 19 was not present (TLC, SiO2, petroleum
ether/EtOAc (80:20)). The reaction mixture was allowed to
reach room temperature, and the crude was purified as indicated
in each case.
5-[2(E- and Z)-Phenylethenyl]benzo[1,2-c]1,2,5-oxadi-
azole N1-Oxide (1 and 2). Reagents: 5-formylbenzofuroxan
(11.7 g, 71 mmol), phosphonium salt 16 (27.6 g, 71 mmol),
1
min (to ) 1.71 min). H NMR (CDCl3) δ: 6.62 (d, J ) 12.2
Hz, 1H), 6.81 (d, J ) 12.2 Hz, 1H), 7.00–7.05 (br s, 1H), 7.18
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