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Synlett 2010(14): 2083-2086  
DOI: 10.1055/s-0030-1258526
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

Straightforward Conversion of Arene Carboxylic Acids into Aryl Nitriles by Palladium-Catalyzed Decarboxylative Cyanation Reaction

Kahina Ouchaou, Dominique Georgin, Frédéric Taran*
CEA, iBiTecS, Service de Chimie Bioorganique et de Marquage, Gif sur Yvette 91191, France
Fax: +33(1)69087991; e-Mail: frederic.taran@cea.fr;
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Publikationsverlauf

Received 16 June 2010
Publikationsdatum:
27. Juli 2010 (online)

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Abstract

A one-pot procedure to convert aromatic carboxylic acids into aromatic nitriles is described. The methodology is based on a palladium(II)-catalyzed decarboxylative cyanation reaction using cyanohydrins as soluble cyanide sources. The described reaction worked on a panel of substrates and is additionally of particular interest for the straightforward preparation of ¹³C- or ¹4C-labeled compounds.

Key words

palladium - cyanation - arene carboxylic acids - cyanohydrin - decarboxylation

19

General Procedure for the Preparation of Aryl Nitriles 2
Arene carboxylic acid (250 mg, 1 equiv), Ag2CO3 (3 equiv), and palladium trifluoroacetate (0.2 equiv) were suspended in DMSO-DMF (95:5, 5 mL) under air. The reaction mixture is heated at 100 ˚C, then, cyclohexanone cyanohydrin
(1 equiv) diluted in DMSO-DMF (95:5, 5 mL) was added dropwise with a syringe pump. The reaction mixture rapidly turned black, was further heated for 1 h, then was cooled, poured into EtOAc, and filtered. The filtrate was washed sequentially with aq NaHCO3 (1 M), H2O and brine, then was dried over MgSO4, filtered, and concentrated. Chromatography of the residue on silica gel (EtOAc-heptane) gave the desired product. Compounds 2a-l are known compounds.
Compound 2m: white solid, mp 69.6 ˚C. ¹H NMR (400 MHz, CDCl3): δ = 2.47 (s, 3 H), 3.84 (s, 3 H), 3.88 (s, 3 H), 6.30 (s, 1 H), 6.38 (s, 1 H) ppm.¹³C NMR (100 MHz, CDCl3): δ = 20.81, 55.51, 55.90, 94.67, 95.70, 106.87, 116.05, 145.25, 163.81, 164.51 ppm. IR (NaCl): 2972, 2212, 1606, 1577, 1468, 1425, 1336, 1304, 1238, 1209, 1153, 1095, 1053, 935, 853, 830 cm-¹. HRMS: m/z calcd for [M + H]+:178.0868; found:178.0863.
Compound 2n: white solid, mp 168.8 ˚C. ¹H NMR (400 MHz, CDCl3): δ = 3.96 (s, 3 H), 3.97 (s, 3 H), 6.46 (s, 1 H), 7.68 (s, 1 H) ppm.¹³C NMR (100 MHz, CDCl3): δ = 56.28, 56.47, 94.68, 95.68, 102.20, 116.12, 138.78, 160.41, 162.52. IR (NaCl): 2989, 2224, 1595, 1561, 1492, 1471, 1433, 1386, 1317, 1284, 1221, 1161, 1020, 896, 838, 780 cm-¹. HRMS: m/z calcd for [M + Na]+:263.9636; found:263.9644.

20

Procedure for the Preparation of 3h
¹³C-Labeled 9-anthracenecarboxylic acid was prepared in two steps. ¹³C-Labeled 9-anthracenecarbonitrile was first prepared from ¹³C-labeled cyclohexanone cyanohydrin according to the procedure described above. After purification, the ¹³C-labeled nitrile was hydrolyzed under basic conditions: ¹³C-labeled nitrile (1 mmol) was reacted overnight at 80 ˚C with aq KOH (10 mL, 40% w/w) and abs. EtOH (10 mL). The mixture was acidified to pH 3 (HCl solution) and extracted by EtOAc. The organic phase was concentrated, and the residue was purified by reversed-phase chromatography with MeOH-H2O (70:30) to afford product 3h; mp 212-214 ˚C. ¹H NMR (400 MHz, CDCl3): δ = 8.61 (s, 1 H), 8.34 (d, 2 H, J = 8.8 Hz), 8.07 (d, 2 H, J = 8.8 Hz), 7.62 (t, 2 H, J = 7.2 Hz), 7.54 (t, 2 H, J = 7.2 Hz) ppm. ¹³C NMR (100 MHz, CDCl3): δ = 171.38 (¹³CO2H), 131.23, 130.96, 129.96, 128.47, 127.68, 126.80, 125.50, 124.96 ppm. IR (KBr): 3200-2700, 2761, 2623, 1680, 1626, 1557, 1523, 1487, 1447, 1425, 1399, 1343, 1319, 1292, 1266, 1254, 1229, 1177, 1154, 1142, 1020, 992, 917, 891, 857, 847, 793, 738, 723, 639, 596, 559, 513 cm-¹. HRMS: m/z calcd for C14 ¹³CH10O2Na: 246.0578; found: 246.0581.