Team:TU Darmstadt/Protocols/Synthesis of paranitrophenylesters with acyl chlorides in presence of triethylamine

Synthesis of paranitrophnylesters with acyl chlorides in presence of triethylamine

Theory

The synthesis of the esters was achieved by combining acyl chlorides with paranitrophenole in presence of triethylamine. Acetone was used as solvent. The reaction takes 2 h at 0 °C and inert conditions. Triethylamine is used as base to deprotonate paranitrophenol and to catalyze the attack of phenolate at the acyl chloride. It is dissipated by developing hydrogen chloride. Diparanitrophenyl succinate and paranitrophenyl dihydrocinnamate are synthesized.

Equation of diparanitrophenyl succinate synthesis

Equation of paranitrophenyl dihydrocinnamate synthesis

Mechanisms

Diparanitrophenyl succinate

Mechanism of diparanitrophenyl succinate synthesis

Paranitrophenyl dihydrocinnamate

Mechanism of paranitrophenyl dihydrocinnamate synthesis

Preparation

Diparanitrophenyl succinate

In a 250 mL triple-neck round-bottom flask with reflux 6.79 g (48.82 mmol/ 2.01 eq.) paranitrophenole and 5.16 g (51.01 mmol/ 2.10 eq.) triethylamine are dissolved in 100 mL acetone under inert conditions and kept at 0 °C using a water/ice mixture. A solution of 1.70 g (10.07 mmol/ 1.00 eq.) succinyl chloride in 50 mL acetone is added dropwise with stirring 2 h at 0 °C. The resulting ester is precipitated in 400 mL distilled water, recrystallized from ethyl acetate three times and dried at 60 °C in a cabinet dryer over night. The yield is 2.3381 g (26.73 % of the theory).

Paranitrophenyl dihydrocinnamate

In a 100 mL triple-neck round-bottom flask with reflux 1.41 g (10.17 mmol/ 1.01 eq.) paranitrophenole and 1.07 g (10.57 mmol/ 1.05 eq.) triethylamine are dissolved in 50 mL acetone under inert conditions and kept at 0 °C using a water/ice mixture. A solution of 3.76 g (24.29 mmol/ 1.00 eq.) dihydrocinnamoyl chloride in 20 mL acetone is added dropwise with stirring 2 h at 0 °C. The resulting ester is precipitated in 200 mL distilled water, filtrated washed with ice cold acetone, stirred in distilled water for 2 h and dried at 60 °C in a cabinet dryer over night. The yield is 1.0623 g (34.69 % of the theory).

Analysis (¹H-NMR-spectroscopy)

Diparanitrophenyl succinate

(300 MHz, CDCl₃): δ/ppm = 2.99 (2 H), 7.19-7.25 (2 H), 8.18-8.24 (2 H)

Paranitrophenyl dihydrocinnamate

(300 MHz, CDCl₃): δ/ppm = 2.94-2.97 (2 H), 3.07-3.10 (2 H), 7.18-7.21 (2 H), 7.26-7.35 (5 H), 8.24-8.28 (2 H)

Sources

• [http://patentscope.wipo.int/search/en/detail.jsf?docId=WO2009073541&recNum=1&maxRec=&office=&prevFilter=&sortOption=&queryString=&tab=PCT+Biblio: Thermoresponsive arginine-based hydrogels as biologic carriers 11.06.2009]