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o-formylation of 4-hydroxybenzonitrile in trifluoroacetic acid; 3-formyl-4-hydroxhybenzonitrile

SyntheticPage 648
DOI: 10.1039/SP648
Submitted Jul 23, 2013, published Jul 24, 2013
Lihong Li (Lihongli0707@yahoo.com), Pratik Gurnani (pratik.gurnani@warwick.ac.uk)
A contribution from Scott group, Warwick University


			Reaction Scheme: <IMG src="/images/empty.gif">o-formylation of <SPAN id=csm1374663269996 class=csm-chemical-name title=4-hydroxybenzonitrile grpid="1">4-hydroxybenzonitrile</SPAN> in trifluoroacetic acid<IMG src="/images/empty.gif">

Chemicals Used

4-hydroxybenzonitrile (Aldrich)
Trifluoroacetic acid (TFA) (Aldrich)
Hexamethylenetetramine (Aldrich)

Procedure

A 25 mL round bottom flask with a stirrer bar was charged with 4-hydroxybenzonitrile (1.19 g, 10.0 mmol) and TFA (8 mL). To the reaction mixture was added hexamethylenetetramine (2.8 g, 20 mmol) all at once while stirring. After the heat evolution had ceased, the reaction mixture was heated to 90 °C and kept stirring for 8 h. TFA and other volatiles were removed on a rotary evaporator. The mixture was then cooled in an ice bath, and 50 % sulfuric acid (5 mL) and water (30 mL) were added. The reaction mixture was kept stirring for 30 min at room temperature. This was followed by extraction with diethyl ether (4 × 25 mL). The ether fractions were combined, washed with water (5 × 25 mL ), saturated NaCl (aq.) (3 × 20 mL) and the organic layer dried over anhydrous NaSO4 followed by filtration. All volatiles were removed under reduced pressure to yield a pale solid.

The pure product was isolated as white solid by flash column (EtOAc : hexane = 5 : 1 then 2 :1). (0.97 g, 33 %).

Author's Comments

Procedure was carried out under argon by using a dual manifold vacuum/argon line and standard Schlenk techniques.
This phenol being electron poor is difficult to formylate, but this method is reproducible and reasonably efficient.

Data

1H NMR (300 MHz, CDCl3): δ ppm 11.40 (s, 1H, ArOH), 9.88 (s, 1H, HC=O), 7.90 (d, 1H, Ar-CH), 7.73 (dd, 1H, Ar-CH), 7.07 (d, 1H, Ar-CH).

MS (EI): m/z 147 [M+H]+.


Lead Reference

Y. Suzuki and H. Takahashi, Chem. Pharm. Bull, 1983, 31, 1751-1753.
http://dx.doi.org/10.1248/cpb.31.1751

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Keywords: addition, alcohols, aldehydes, amines, aromatics/arenes, carboxylic acids, formylation, ortho

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