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PAPER
the catalyst), and the cotton plug was washed with EtOAc (2 × 1
mL). The combined EtOAc filtrates were concentrated on a rotary
evaporator; this afforded 1-(benzoyloxy)-4-(1,1-dimethoxymeth-
yl)benzene.
The cotton plug retaining the recovered catalyst was put in a round-
bottomed flask (25 mL) and dried in a rotary evaporator, where the
catalyst separated out from the cotton; yield: 87 mg (87%). The cat-
alyst was activated on heating under reduced pressure (10 Torr) at
80 °C for 24 h. The repetition of the reaction of 4-(benzoyl-
oxy)benzaldehyde (1.16 g, 5 mmol) with TMOF (0.58 g, 5.5 mmol,
1.1 equiv) in the presence of the recovered HBF4-SiO2 (40 mg, 0.05
mmol, 1 mol%) afforded 1-(benzoyloxy)-4-(1,1-dimethoxymeth-
yl)benzene; yield: 1.09 g (80%); this is identical (spectral data) with
an authentic sample.4e
Yield: 0.58 g (85%); colorless oil.
IR (neat): 2955, 1734, 1598, 1261, 1100 cm–1.
1H NMR (300 MHz, CDCl3): d = 3.3 (s, 6 H), 5.43 (s, 1 H), 7.23 (d,
J = 8.6 Hz, 2 H), 7.56 (d, J = 2 Hz, 4 H), 7.65 (t, J = 7.6 Hz, 1 H),
8.2 (d, J = 7.5 Hz, 2 H); this is identical with an authentic sample.4e
To demonstrate the applicability on larger scale, HBF4-SiO2 (200
mg, 0.25 mmol, 1 mol%) was added to a mixture of 4-methylbenz-
aldehyde (3 g, 25 mmol) and TMOF (2.9 g, 27.5 mmol, 1.1 equiv),
and the mixture was stirred at 25–30 °C. After complete consump-
tion of the aldehyde (20 min, TLC), the reaction mixture was diluted
with EtOAc (10 mL) and filtered through a plug of cotton (to sepa-
rate the catalyst), and the cotton plug was washed with EtOAc (2 ×
5 mL). The combined EtOAc filtrates were concentrated on a rotary
evaporator; this afforded (1,1-dimethoxymethyl)-4-methylbenzene;
yield: 3.7 g (90%); colorless oil.
(1,1-Dimethoxymethyl)-4-cyanobenzene (Table 1, entry 15);
Typical Procedure for Synthesis of a Dimethyl Acetal in a
Solvent (Method B)
To a magnetically stirred mixture of 4-cyanobenzaldehyde (0.33 g,
2.5 mmol) and TMOF (0.290 g, 2.75 mmol, 1.1 equiv) in anhyd
MeOH (1 mL) was added HBF4-SiO2 (20 mg, 0.025 mmol, 1
mol%). The reaction mixture was stirred at 25–30 °C until con-
sumption of the aldehyde was completed (15 min, TLC). The reac-
tion mixture was diluted with EtOAc (2 mL) and filtered through a
plug of cotton (to separate the catalyst), and the cotton plug was
washed with EtOAc (2 × 1 mL). The combined EtOAc filtrates were
The cotton plug retaining the recovered catalyst was put in a round-
bottomed flask (25 mL) and dried in a rotary evaporator, where the
catalyst separated out from the cotton; yield: 80 mg (90%). The cat-
alyst was activated on heating under reduced pressure (10 Torr) at
80 °C for 24 h. The repetition of the reaction of 4-methylbenzalde-
hyde (1.2 g, 10 mmol) with TMOF (1.16 g, 11 mmol, 1.1 equiv) in
the presence of the recovered HBF4-SiO2 (80 mg, 0.1 mmol, 1
mol%) afforded (1,1-dimethoxymethyl)-4-methylbenzene [yield:
1.4 g (90%)] and the recovered catalyst after the usual workup.
concentrated on
a rotary evaporator; this afforded (1,1-
dimethoxymethyl)-4-cyanobenzene.
Yield: 0.42 g (96%); colorless oil.
IR (neat): 3545, 2938, 2292, 1611, 1445, 1352, 1209, 1102, 988,
822 cm–1.
1H NMR (300 MHz, CDCl3): d = 3.32 (s, 6 H), 5.44 (s, 1 H), 7.58
(d, J = 8.3 Hz, 2 H), 7.68 (d, J = 1.6 Hz, 2 H); this is identical with
an authentic sample.4e
(1,1-Dimethoxymethyl)-4-methylbenzene
IR (neat): 2936, 2821, 1613, 1516, 1444, 1311, 1199, 1103, 1054
(1,1-Diethoxymethyl)benzene; Typical Procedure for Synthesis
of a Diethyl Acetal in a Solvent (Method B)
cm–1.
1H NMR (300 MHz, CDCl3): d = 3.34 (s, 3 H), 3.3 (s, 6 H), 5.36 (s,
1 H), 7.17 (d, J = 7.7 Hz, 2 H), 7.33 (d, J = 7.6 Hz, 2 H); this is iden-
tical with an authentic sample.18
To a magnetically stirred mixture of benzaldehyde (0.267 g, 2.5
mmol, 1 equiv) and TEOF (0.407 g, 2.75 mmol, 1.1 equiv) in anhyd
EtOH (1 mL) was added HBF4-SiO2 (20 mg, 0.025 mmol, 1 mol%)
and the reaction mixture was stirred at 25–30 °C until completion
consumption of the aldehyde (10 min, TLC). The reaction mixture
was diluted with EtOAc (2 mL) and filtered through a plug of cotton
(to separate the catalyst), and the cotton plug was washed with
EtOAc (2 × 1 mL). The combined EtOAc filtrates were concentrat-
ed on a rotary evaporator; this afforded (1,1-diethoxymethyl)ben-
zene.
4-Cyanobenzaldehyde (Table 2, entry 4); Typical Procedure for
Deprotection of a Dimethyl Acetal
To a magnetically stirred mixture of 1-cyano-4-(1,1-dimethoxy-
methyl)benzene (0.44 g, 2.5 mmol) and MeOH–H2O (1:1, 2.5 mL)
was added HBF4-SiO2 (20 mg, 0.025 mmol, 1 mol%) and the reac-
tion mixture was stirred at 25–30 °C until consumption of the acetal
was completed (20 min, TLC). The reaction mixture was diluted
with EtOAc (2 mL) and filtered through a plug of cotton (to separate
the catalyst), and the cotton plug was washed with EtOAc (2 × 1
mL). The combined EtOAc filtrates were dried (Na2SO4), filtered,
and concentrated on a rotary evaporator; this afforded 4-cyanobenz-
aldehyde.
Yield: 0.39 g (95%); colorless oil.
IR (neat): 3033, 2976, 1607, 1493, 1371, 1207, 1114, 1054, 934,
834 cm–1.
1H NMR (300 MHz, CDCl3): d = 1.24 (t, J = 7.19 Hz, 6 H), 3.56 (m,
4 H), 5.50 (s, 1 H), 7.28 (m, 3 H), 7.36 (d, J = 1.9 Hz, 2 H); this is
identical (spectral data) with an authentic sample.17
Yield: 0.29 g (90%); this is identical (spectral data) with an authen-
tic sample.19
1-(Benzoyloxy)-4-(1,1-dimethoxymethyl)benzene (Table 1,
entry 8 and Table 2, entry 13) and (1,1-Dimethoxymethyl)-4-
methylbenzene (Table 1, entry 9 and Table 2, entry 15); Typi-
cal Procedure for Large-Scale Acetal Formation (Method A)
and Catalyst Reuse
To a magnetically stirred mixture of 4-(benzoyloxy)benzaldehyde
(2.26 g, 10 mmol) and TMOF (1.16 g, 11 mmol, 1.1 equiv) was add-
ed HBF4-SiO2 (80 mg, 0.1 mmol, 1 mol%), and the reaction mixture
was stirred at 25–30 °C. After complete consumption of the alde-
hyde (60 min, TLC), the reaction mixture was diluted with EtOAc
(5 mL) and filtered through a plug of cotton (to separate the cata-
lyst), and the cotton plug was washed with EtOAc (2 × 2.5 mL). The
combined EtOAc filtrates were concentrated on a rotary evaporator;
this afforded 1-(benzoyloxy)-4-(1,1-dimethoxymethyl)benzene;
yield: 2.18 g (80%).
Reactions of 1-(Benzoyloxy)-4-(1,1-dimethoxymethyl)benzene
and (1,1-Dimethoxymethyl)-4-methylbenzene; Typical Proce-
dures for Large-Scale Deprotection of Dimethyl Acetals
To a magnetically stirred mixture of 1-(benzoyloxy)-4-(1,1-
dimethoxymethyl)benzene (2.72 g, 10 mmol) and MeOH–H2O
(1:1, 10 mL) was added HBF4-SiO2 (80 mg, 0.1 mmol, 1 mol%) and
the reaction mixture was stirred at 25–30 °C until consumption of
the acetal was completed (50 min, TLC). The reaction mixture was
diluted with EtOAc (10 mL) and filtered through a plug of cotton
(to separate the catalyst), and the cotton plug was washed with
EtOAc (2 × 5 mL). The combined EtOAc filtrates were dried
(Na2SO4) and concentrated on a rotary evaporator; this afforded 4-
(benzoyloxy)benzaldehyde.
Synthesis 2008, No. 8, 1249–1256 © Thieme Stuttgart · New York