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Amine diazotization, in situ nucleophilic aromatic substitution and [3+2] cycloaddition reaction of azide compound; 5-Methyl-1-(4-methoxyphenyl)-1,2,3-triazol-4-carboxylic acid

SyntheticPage 411
DOI: 10.1039/SP411
Submitted May 25, 2010, published May 26, 2010
YOIHICIRO HIROSE (yhirose@chemgenesis.com)


			Reaction Scheme: Amine diazotization, in situ nucleophilic aromatic substitution and [3+2] cycloaddition reaction of azide compound

Chemicals Used

p-Anisidine (TCI)
Sodium Nitrite (Wako)
Sodium Azide (Wako)
Ethyl acetoacetate (TCI)
Sodium hydride (Wako)

Procedure

To a cold solution of p-anisidine (10 g, 80 mmol) in hydrochloric acid (2 mol/L, 100 mL) was added sodium nitrite (6.3g, 91mmol) dissolved in water (25 mL) dropwise. After being stirred for 30 min at the same temperature, sodium azide (5.4 g, 83 mmol) dissolved in water (25 mL) was added dropwise and the mixture was stirred for one h. The solution was diluted with toluene (50 mL). The organic phase separated was dried over sodium sulfate, filtered and washed with toluene (50 mL). To the filtrate was added ethanol (100 mL), ethyl acetoacetate (10mL, 80 mmol) and sodium hydride (5g, 60% dispersion, 125 mmol) portionwise. After being stirred for 20 h at 80 oC, the mixture was evaporated. Hydrochloric acid (2 mol/L, 100 mL) was added to the residue and precipitated solid was filtered, washed with water (100 mL) and dried in vacuo to give the product (15.4 g, 40 mmol, 50%).

Author's Comments

The intermediate “4-methoxyphenylazide” is explosive so we used that as a solution without concentration after extraction. Instead of sodium hydride, sodium ethoxide or sodium metal may be used. Sodium ethoxide is not so stable and it is difficult to store for long. Sodium metal is highly reactive. Sodium hydride is much stable and easy to use, but the product contains some mineral oil.

Data

1H NMR 400 MHz (CDCl3) d ppm 7.54 (d, 2H, J = 8.7 Hz), 7.16 (d, 2H, J = 8.7 Hz), 3.86 (s, 3H), 2,46 (s, 3H). 


Lead Reference

Otto Dimroth, Chemische Berichte, 1902, 1031

Supplementary Information

HNMR Spectrum of Product

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Get structure file (.cdx, .sk2, .mol)

Keywords: aromatics/arenes, azides, carboxylic acids, cyclization, substitution, triazoles

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