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DOI: 10.1055/s-0029-1219575
Metal-Free One-Pot Conversion of Electron-Rich Aromatics into Aromatic Nitriles
Publication History
Publication Date:
10 March 2010 (online)
Abstract
Various electron-rich aromatics could be smoothly converted into the corresponding aromatic nitriles in good to moderate yields by treatment of electron-rich aromatics with POCl3 and DMF, followed by treatment with molecular iodine in aqueous ammonia. The present reaction is a novel metal-free one-pot method for the preparation of aromatic nitriles from electron-rich aromatics.
Key words
aromatics - aromatic N,N-dimethyliminium salt - aromatic nitrile - Vilsmeier-Haack reaction - molecular iodine - aqueous ammonia
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References and Notes
Typical Experimental
Procedure: To a flask containing 1,3,5-trimethoxybenzene (1009.1
mg, 6 mmol) were added POCl3 (1011.9 mg, 6.6 mmol) and
DMF (1754.1 mg, 24 mmol) at 0 ˚C. After being stirred for
3 h at 40 ˚C, I2 (3045.7 mg, 12 mmol) and aq
ammonia (12 mL, 28-30%) were added to the reaction
mixture. The obtained mixture was stirred for 3 h at r.t. After
the reaction, the mixture was poured into aq sat. Na2SO3 solution
and extracted with CHCl3 (3 × 20 mL). The organic
layer was dried over Na2SO4, filtered, and
evaporated to provide almost pure 2,4,5-trimethoxybenzonitrile (1156.1
mg) in 99% yield. If it was necessary, it was recrystallized
from a mixture of hexane and EtOAc (1:1).
Most aromatic
nitriles mentioned in this work are commercially available and were
identified by comparison with the authentic samples.
2,4-Dimethoxybenzonitrile: mp 93-94 ˚C
(commercial, mp 93-94 ˚C). IR: 2219 cm-¹. ¹H
NMR (500 MHz, CDCl3): δ = 3.86 (s,
3 H), 3.90 (s, 3 H), 6.46 (s, 1 H), 6.51 (d, J = 8.5 Hz,
1 H), 7.48 (d, J = 8.5 Hz, 1
H).
2,4,6-Trimethoxybenzonitrile:
mp 139-140 ˚C (commercial, mp 143-145 ˚C).
IR: 2212 cm-¹. ¹H
NMR (500 MHz, CDCl3): δ = 3.86 (s,
3 H), 3.89 (s, 6 H), 6.07 (s, 2 H).
2,3,4-Trimethoxybenzonitrile:
mp 55-56 ˚C (commercial, mp 56-57 ˚C).
IR: 2226 cm-¹. ¹H
NMR (400 MHz, CDCl3): δ = 3.87 (s,
3 H), 3.92 (s, 3 H), 4.06 (s, 3 H), 6.70 (d, J = 8.7 Hz,
1 H), 7.29 (d, J = 8.7 Hz, 1
H).
3-Cyanoindole: mp 177-179 ˚C
(commercial, mp 179-182 ˚C). IR: 2227 cm-¹. ¹H
NMR (500 MHz, CDCl3): δ = 7.28-7.36
(m, 2 H), 7.48 (d, J = 7.6 Hz,
1 H), 7.73 (s, 1 H), 7.78 (d, J = 7.3
Hz, 1 H), 8.91 (s, 1 H).
N
-Methyl-3-cyanolindole: mp 60-61 ˚C
(lit. ¹² mp 60.5-61.5 ˚C).
IR: 2219 cm-¹. ¹H
NMR (500 MHz, CDCl3): δ = 3.75 (s,
3 H), 7.25 (t, J = 6.4 Hz, 1
H), 7.28-7.35 (m, 2 H), 7.44 (s, 1 H), 7.68 (d, J = 7.9 Hz, 1 H).
4-Methoxy-1-cyanonaphthalene: mp 100-102 ˚C (commercial,
mp 100-102 ˚C). IR: 2213 cm-¹. ¹H
NMR (400 MHz, CDCl3): δ = 4.07 (s,
3 H), 6.84 (d, J = 8.2 Hz, 1 H),
7.59 (t, J = 8.2 Hz, 1 H), 7.69
(t, J = 8.2 Hz, 1 H), 7.86 (d, J = 8.2 Hz, 1 H), 8.17 (d, J = 8.2 Hz, 1 H), 8.32 (d, J = 8.2 Hz, 1 H).
2-Methoxy-1-cyanonaphthalene: mp 96-97 ˚C
(lit.¹³ mp 95-96 ˚C).
IR: 2211 cm-¹. ¹H
NMR (400 MHz, CDCl3): δ = 4.08 (s,
3 H), 7.28 (d, J = 8.7 Hz, 1
H), 7.45 (t, J = 8.0 Hz, 1 H),
7.64 (t, J = 8.0 Hz, 1 H), 7.83
(d, J = 8.0 Hz, 1 H), 8.04 (d, J = 8.7 Hz, 1 H), 8.09 (d, J = 8.0 Hz, 1 H).
4,8-Dimethoxy-1-cyanonaphthalene: mp 126-129 ˚C.
IR: 2211 cm-¹. ¹H
NMR (400 MHz, CDCl3): δ = 4.05 (s,
6 H), 6.85 (d, J = 8.2 Hz, 1
H), 6.99 (d, J = 7.7 Hz, 1 H),
7.47 (t,
J = 7.7 Hz,
1 H), 7.86 (d, J = 8.2 Hz, 1
H), 7.89 (d, J = 7.7 Hz, 1 H).
HRMS (ESI): m/z calcd
for C13H11O2N: 213.0784; found:
21.0780.
4-Cyano-
N
,
N
-dimethylaniline:
mp 74-75 ˚C (commercial, mp 75 ˚C). IR:
2210 cm-¹. ¹H NMR
(500 MHz, CDCl3): δ = 3.04 (s, 6 H),
6.64 (d, J = 9.1 Hz, 2 H), 7.47
(d, J = 9.1 Hz, 2 H).
9-Cyanoanthracene: mp 173-175 ˚C
(commercial, mp 173-177 ˚C). IR: 2212 cm-¹. ¹H
NMR (500 MHz, CDCl3):
δ = 7.59
(t, J = 8.5 Hz, 2 H), 7.73 (t, J = 8.5 Hz, 2 H), 8.09 (d, J = 8.5 Hz, 2 H), 8.43 (d, J = 8.5 Hz, 2 H), 8.69 (s, 1
H).
2-Cyano-
N
-benzylpyrrole: oil. IR: 2215 cm-¹. ¹H
NMR (400 MHz, CDCl3): δ = 5.19 (s,
2 H), 6.19 (dd, J = 2.9, 2.7 Hz,
1 H), 6.80-6.86 (m, 2 H), 7.18 (d, J = 7.4
Hz, 2 H), 7.31-7.38 (m, 3 H). HRMS (FAB): m/z [M + H]+ calcd
for C12H11N2: 183.0922; found:
183.0927.
3-Cyano-
N
-benzylpyrrole:
oil. IR: 2224 cm-¹. ¹H
NMR (500 MHz, CDCl3): δ = 5.06 (s,
2 H), 6.44 (d, J = 1.7 Hz,
1
H), 6.65 (s, 1 H), 7.11-7.17 (m, 3 H), 7.33-7.41
(m, 3 H). HRMS (FAB): m/z [M + H]+ calcd
for C12H11N2: 183.0922; found:
183.0927.
2-Cyanothiophene: oil.
IR: 2222 cm-¹. ¹H
NMR (500 MHz, CDCl3): δ = 7.14 (dd, J = 5.2, 3.7 Hz, 1 H), 7.62
(d, J = 5.2 Hz, 1 H), 7.64 (d, J = 3.7 Hz, 1 H).
5-Decyl-2-cyanothiophene: oil. IR: 2218
cm-¹. ¹H NMR (500
MHz, CDCl3): δ = 0.88 (t, J = 7.1 Hz, 3 H), 1.23-1.38 (m,
14 H), 1.67 (quint, J = 7.5
Hz, 2 H), 2.83 (t, J = 7.5 Hz, 2
H), 6.78 (d, J = 3.6 Hz, 1 H),
7.43 (d, J = 3.6 Hz, 1 H). HRMS
(FAB): m/z [M + H]+ calcd
for C15H24NS: 250.1629; found: 250.1636.
5-Decyl-2-cyanofuran: oil. IR: 2229 cm-¹. ¹H
NMR (500 MHz, CDCl3): δ = 0.88 (t, J = 7.0 Hz, 3 H), 1.21-1.38
(m, 14 H), 1.65 (quint, J = 7.1
Hz, 2 H), 2.66 (t, J = 7.1 Hz,
2 H), 6.11 (d, J = 3.4 Hz, 1
H), 6.99 (d, J = 3.4 Hz, 1 H).
HRMS (FAB): m/z [M + H]+ calcd
for C15H24NO: 234.1858; found: 234.1861.
3-Cyanobenzofuran: mp 90-91 ˚C
(commercial, mp 93 ˚C). IR: 2211 cm-¹. ¹H
NMR (500 MHz, CDCl3): δ = 7.35 (t, J = 7.5 Hz, 1 H), 7.44 (s, 1
H), 7.48-7.56 (m, 2 H), 7.67 (d, J = 9.1
Hz, 1 H).