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Synlett 2010(7): 1067-1070  
DOI: 10.1055/s-0029-1219575
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

Metal-Free One-Pot Conversion of Electron-Rich Aromatics into Aromatic Nitriles

Sousuke Ushijima, Hideo Togo*
Graduate School of Science, Chiba University, Yayoi-cho 1-33, Inage-ku, Chiba 263-8522, Japan
Fax: +81(43)2902792; e-Mail: togo@faculty.chiba-u.jp;
Further Information

Publication History

Received 18 January 2010
Publication Date:
10 March 2010 (online)

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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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11

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).