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Reduction of Phenolic Nitrostyrenes by Lithium Aluminum Hydride

By F. A. Ramirez1 & A. Burger, J. Am. Chem. Soc. 72, 2781-2782 (1950)

The literature records the reduction of two β-nitrostyrenes to phenethylamines by lithium aluminum hydride2. We have found that this method affords an excellent route to phenolic phenethylamines. For the preparation of appreciable amounts of these compounds, none of the methods so far described3 has been found suitable.

4-Hydroxy-3-methoxy-, 3-hydroxy-4-methoxy- and 2-hydroxy-3-methoxyphenethylamines were prepared from the corresponding β-nitrostyrenes and isolated as their picrates in yields of 80%, 68% and 81%, respectively. The picrates were in turn converted to the stable hydrochlorides. In view of the amphoteric nature as well as the physical properties of the phenolic amines, this method of isolation was found very suitable.

The required β-nitrostyrenes were easily obtained by condensation of commercially available phenolic aldehydes with nitromethane using methylamine3d or ammonium acetate4 as condensing agents.



A mixture of 7g of methylamine hydrochloride, 10g of sodium carbonate and 100 mL of methanol was stirred well, filtered and added to a solution of 219 g of vanillin and 85 ml. of nitromethane in 600 mL of methanol. The solution was kept at room temperature in the dark for 72 hours and the β-nitrostyrene which crystallized out was collected and washed with cold methanol. The yield of yellow needles melting at 166-168°C was 225 g (81%); reported@3d melting point 167-168°C.


To a well-stirred mixture of 53 g. of lithium aluminum hydride and 2500 ml. of absolute ether was added by the Soxhlet extractor technique6 55 g. of 4-hydroxy-3-methoxy-β-nitrostyrene over a period of 59 hours. Stirring and refluxing can be stopped and resumed at any time. The flask was cooled well and 3000 mL of ice-cold 1.5 N sulfuric acid was added dropwise with stirring. The water layer was separated and its pH adjusted to 6 with solid lithium carbonate. The solution was heated to boiling. and the aluminum hydroxide which precipitated was filtered off with the aid of filter-cel; the clear, hot filtrate was mixed with a solution of 70g. of picric acid in the minimum amount of hot ethanol. Upon standing overnight at room temperature. 89.2g (80%) of deep yellow needles of the picrate melting at 194-197°C was obtained. Recrystallization from water raised the melting point to 198-199°C (dec.); reported3d mp 198-199°C.

A solution of 88 g of the picrate in 2 L of boiling water was mixed with 400 mL of concentrated hydrochloric acid. The picric acid which precipitated on cooling was filtered, the filtrate was extracted with nitrobenzene and then with ether. The aqueous solution was concentrated under reduced pressure until crystals of the hydrochloride appeared. Thirty-six grams of tan crystals melting at 211-213°C was collected. By evaporation of the filtrate to dryness and recrystallization of the residue from methanol-ethyl acetate. another 4g was isolated. making a total yield of 90%. The pure salt melted at 213-214°C; reported3a mp 210-211°C. The dibenzoyl derivative prepared from the hydrochloride melted at 131-132°C; reported3b mp 129°C.


This compound was prepared from 3.0 g. of isovanillin and 1.2 mL of nitromethane by the same procedure as described above. The mixture was allowed to stand for 50 hours, and an 87% yield of yellow needles, mp 156-159°C, was obtained. The product crystallized from methanol and melted at 161-162°C. Hahn and Rumpf3c, who prepared this compound in 40.6% yield using potassium hydroxide as condensing agent, reported a mp of 154°C.


Using the same procedure as described above, 1.24 g of 3-hydroxy-4-methoxy-β-nitrostyrene was added over a period of 6 hours to 1.1 g of lithium aluminum hydride in 150 ml. of ether. The yield of picrate melting at 196-198°C (dec.) was 1.70 g (68%). After one recrystallization from water the picrate melted at 201-203°C (dec.) ; reported3c mp 203-204°C (dec.). The hydrochloride was obtained from the picrate as colorless needles mp 206-207° (from methanol-ethyl acetate).


A solution of 5.0 g. of freshly distilled 2-hydroxy-3-methoxybenzaldehyde, 2.5 ml. of nitromethane and 2 g. of ammonium acetate in 20 ml of glacial acetic acid was refluxed for 2 hours. The cooled dark mixture was poured into water and the gummy product allowed to crystallize. The crude solid was recrystallized from benzene, with the aid of Norit. The yield of yellow needles, melting at 115-122°C was 2.32 g (37%). The analytical sample melted at 129-130°C.

Using a methanolic solution of methylamine as condensing agent only 18% of the nitrostyrene was obtained after seven days. The reaction failed using potassium hydroxide as condensing agent.


The yield of the picrate of the amine obtained from 1.0g of 2-hydroxy-3-methoxy-β-nitrostyrene was 1.62 g (81%), mp 168-170°C; reported3b mp 170°C. The hydrochloride crystallized from methanol-ethyl acetate as colorless plates, mp 177-178°C; reported3b mp 175°C.



  1. Robert Earll McConnell Post-Doctorate Fellow.
  2. Nystrom and Brown, J. Am. Chem. Soc. 70, 3738 (1948); Hamlin and Weston, J. Am. Chem. Soc. 71, 2210 (1949).
    1. Kobayashi, Sci. Papers Inse. Phys. Chem. Research (Tokyo), 6, 149 (1927); C. A., 22, 1345 (1928);
    2. Buck, J. Am. Chem. Soc. 66, 3388 (1933);
    3. Hahn and Rumpf, Ber., 71, 2141 (1938);
    4. Hahn and Stiehl, Ber, 71, 2154 (1938).
  4. Raiford and Fox, J. Org. Chem., 9, 170 (1944).
  5. Microanalyses by Clark, Microanalytical Laboratory, Urbana, Ill. All melting points are corrected.
  6. Nystrom and Brown, J. Am. Chem. Soc. 69, 1197 (1947).