Print version Print setup

Amidation of acetic anhydride with 3,4-dimethylaniline; 3,4-dimethylacetanilide

SyntheticPage 931
Submitted Sep 09, 2020, published Sep 22, 2020
Steven Kennedy (Steven.Kennedy@millersville.edu), Yongyu Ou (yoou@millersville.edu)
A contribution from Kennedy Group, Millersville University


			Reaction Scheme: Amidation of acetic anhydride with 3,4-dimethylaniline

Chemicals Used

3,4-dimethylaniline (>99.0%, TCI America)

Acetic anhydride (97+%, Alfa Aesar)

Pyridine (99.0%, EMD Millipore)

Hexane (99%, VWR Chemicals)

Ethyl acetate (99%, Alfa Aesar)

Ammonium chloride (Fisher Scientific)

Magnesium sulfate (EMD Millipore)


Procedure

3,4-dimethylaniline (2.4 g, 20 mmol) was dissolved in pyridine (36 mL) and acetic anhydride (9.4 mL, 100 mmol) was added at room temperature. The reaction was stirred at 60 °C for 2 hours. The solvent was removed in vacuo. The crude product was extracted with ethyl acetate (4 X 50 mL) and washed with saturated aqueous ammonium chloride solution (60 mL). The combined ethyl acetate layers were dried over anhydrous magnesium sulfate, filtered, and concentrated by rotary evaporation, leaving a white solid product (3.15 g, 96.6%).

Author's Comments

This is a simple and user-friendly procedure.

Data

mp = 96.3°C – 96.9°C

Rf = 0.12 (1:2 EtOAc/Hex)

1 H NMR (400 MHz, CDCl3): δ 7.27 (m, 1H), 7.20 (d, J = 8.0 Hz, 1H), 7.06 (d, J = 8.4 Hz, 1H), 2.22 (d, J = 8.4 Hz, 6H), 2.15 (s, 3H)

13 C NMR (100 MHz, CDCl3): δ 168.2, 137.2, 135.6, 132.6, 129.9, 121.4, 117.5, 24.5, 19.9, 19.2


Lead Reference

Guo, Liangqin; He, Shuwen; et al. Preparation of Cycloalkylcarbonyl or heterocycloalkylcarbonyl-substituted spiropiperidines as melanocortin-4 receptor agonists for the treatment of conditions such as Obesity. Patent WO 2004089307 A2, October 21, 2014.

Supplementary Information

1H NMR (YRO-I-003-H1(Amide Formation).pdf)
13C NMR (YRO-I-003-C13(Amide Formation).pdf)
IR (dimethylacetanilide IR.pdf)

This page has been viewed approximately 270 times since records began.

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

Keywords: amide formation; nucleophilic acyl substitution, amides, amines, aromatics/arenes, substitution

Post new comment
Loading ...