Print version Print setup

Amide hydrolysis of 2-bromo-4,5-dimethylacetanilide; 2-bromo-4,5-dimethylaniline

SyntheticPage 933
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: Amide hydrolysis of 2-bromo-4,5-dimethylacetanilide<!--  /* Font Definitions */  @font-face 	{font-family:"Cambria Math"; 	panose-1:2 4 5 3 5 4 6 3 2 4; 	mso-font-charset:0; 	mso-generic-font-family:roman; 	mso-font-pitch:variable; 	mso-font-signature:3 0 0 0 1 0;}  /* Style Definitions */  p.MsoNormal, li.MsoNormal, div.MsoNormal 	{mso-style-unhide:no; 	mso-style-qformat:yes; 	mso-style-parent:""; 	margin:0in; 	line-height:115%; 	mso-pagination:widow-orphan; 	font-size:11.0pt; 	font-family:"Arial",sans-serif; 	mso-fareast-font-family:Arial; 	mso-ansi-language:EN-GB; 	mso-fareast-language:ZH-CN;} .MsoChpDefault 	{mso-style-type:export-only; 	mso-default-props:yes; 	font-size:11.0pt; 	mso-ansi-font-size:11.0pt; 	mso-bidi-font-size:11.0pt; 	font-family:"Arial",sans-serif; 	mso-ascii-font-family:Arial; 	mso-fareast-font-family:Arial; 	mso-hansi-font-family:Arial; 	mso-bidi-font-family:Arial; 	mso-ansi-language:EN-GB; 	mso-fareast-language:ZH-CN;} .MsoPapDefault 	{mso-style-type:export-only; 	line-height:115%;}size:8.5in 11.0in; 	margin:1.0in 1.0in 1.0in 1.0in; 	mso-header-margin:.5in; 	mso-footer-margin:.5in; 	mso-paper-source:0;} div.WordSection1 	{page:WordSection1;}--><!--  /* Font Definitions */  @font-face 	{font-family:"Cambria Math"; 	panose-1:2 4 5 3 5 4 6 3 2 4; 	mso-font-charset:0; 	mso-generic-font-family:roman; 	mso-font-pitch:variable; 	mso-font-signature:3 0 0 0 1 0;}  /* Style Definitions */  p.MsoNormal, li.MsoNormal, div.MsoNormal 	{mso-style-unhide:no; 	mso-style-qformat:yes; 	mso-style-parent:""; 	margin:0in; 	line-height:115%; 	mso-pagination:widow-orphan; 	font-size:11.0pt; 	font-family:"Arial",sans-serif; 	mso-fareast-font-family:Arial; 	mso-ansi-language:EN-GB; 	mso-fareast-language:ZH-CN;} .MsoChpDefault 	{mso-style-type:export-only; 	mso-default-props:yes; 	font-size:11.0pt; 	mso-ansi-font-size:11.0pt; 	mso-bidi-font-size:11.0pt; 	font-family:"Arial",sans-serif; 	mso-ascii-font-family:Arial; 	mso-fareast-font-family:Arial; 	mso-hansi-font-family:Arial; 	mso-bidi-font-family:Arial; 	mso-ansi-language:EN-GB; 	mso-fareast-language:ZH-CN;} .MsoPapDefault 	{mso-style-type:export-only; 	line-height:115%;}size:8.5in 11.0in; 	margin:1.0in 1.0in 1.0in 1.0in; 	mso-header-margin:.5in; 	mso-footer-margin:.5in; 	mso-paper-source:0;} div.WordSection1 	{page:WordSection1;}-->

Chemicals Used

2-bromo-4,5-dimethylacetanilide 932

NaOH (Spectrum Chemical)

Acetic Acid (Fisher Scientific)

Ethyl Acetate (99%, Alfa Aesar)

MgSO4 (EMD Millipore)

Procedure

2-bromo-4,5-dimethylacetanilide (0.24 g, 1 mmol) and 3 M NaOH (10 mL) were added into a 50 mL round bottom flask. The reaction was stirred at high speed and heated under reflux conditions overnight at 120°C, then cooled to room temperature. Acetic acid was added to neutralize the reaction to pH 7. The mixture was extracted with ethyl acetate (20 mL X 3) and water (20 mL).  Then, MgSO4 was added to the combined ethyl acetate, filtered, then concentrated via rotary evaporation to give a crude product.  Flash column chromatography (1:19 EtOAc/Hex) followed by vacuum concentration and drying provided a white solid product (0.14 g, 68 %)

Author's Comments

This is a simple and user-friendly procedure.

Data

mp =  83.8°C - 85.0°C

Rf = 0.603 (1:9 EtOAc/Hex)

1 H NMR (400 MHz, CDCl3): δ 7.16 (s, 1H), 6.58 (s, 1H), 3.86 (s, 2H), 2.14 (s, 6H)

13 C NMR (100 MHz, CDCl3): δ 141.64, 136.80, 132.85, 127.94, 117.24, 106.13, 19.42, 18.48


Lead Reference

Claffey, Michelle Marie; Goldstein, Steven Wayne; et al. Aryl-​substituted imidazo[1,​2-​a]​pyridine derivatives as C3a receptor antagonists, their preparation, pharmaceutical compositions, and use in therapy. Patent WO 2007034282, A2, March 29, 2007.

Supplementary Information

1H NMR (YRO-H1-Amide hydrolysis.pdf)
13C NMR (YRO-C13-Amide Hydrolysis.pdf)
IR (2-bromo-4,5-dimethylaniline(IR).pdf)

This page has been viewed approximately 162 times since records began.

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

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

Post new comment
Loading ...