Org. Synth. 2006, 83, 45
DOI: 10.15227/orgsyn.083.0045
SUZUKI-MIYAURA CROSS-COUPLING: PREPARATION OF 2'-VINYLACETANILIDE
[N-(2-Ethenylphenyl)acetamide]
Submitted by Bertrand Cottineau, Albane Kessler, and Donal F. O'Shea
1.
Checked by Anuradha Gupta and Marvin J. Miller.
1. Procedure
A 500-mL, two-necked, round-bottomed flask covered in tin-foil and is equipped with a stirring bar, a reflux condenser fitted with a nitrogen inlet, and a stopper. The flask is charged with N-(2-bromophenyl)acetamide (10.0 g, 46.6 mmol, Note 1), ethylene glycol dimethyl ether (180 mL) (Note 2), and tetrakis(triphenylphosphine)palladium(0) (1.08 g, 0.9 mmol) (Note 3). The apparatus is maintained under an atmosphere of nitrogen during the course of the reaction. The mixture is stirred at room temperature for 20 min then potassium carbonate (6.44 g, 46.6 mmol) (Note 4) dissolved in distilled water (55 mL) is added via funnel, followed by 2,4,6-trivinylcyclotriboroxane-pyridine complex (5.6 g, 23.3 mmol) (Note 5). The reaction mixture is stirred and heated at reflux in an oil bath for 20 h, then cooled to ambient temperature. Distilled water (75 mL) is added via a funnel, and the resulting mixture is filtered on a Büchner funnel. The filtrate is transferred to a separatory funnel and extracted with diethyl ether (3 × 100 mL) (Note 6). The combined organic phases are dried over sodium sulfate, filtered on filter paper and concentrated to dryness by rotory evaporation (30 °C, 25 mmHg). The resulting yellow solid is purified by column chromatography (Note 7) affording N-(2-vinylphenyl)acetamide (5.9 g, 37.3 mmol) as a pale yellow solid. The solid is dissolved in a hot mixture of cyclohexane:dicholoromethane (4:1) (55 mL) and the warm mixture is filtered through a Büchner funnel. The filtrate is allowed to cool to room temperature for 20 min. The flask is immersed for 30 min in an ice bath in order to complete precipitation. The resulting crystals are collected by suction filtration on a Büchner funnel, washed with cyclohexane (10 mL), and dried under reduced pressure (15 h at 0.1 mmHg) to provide N-(2-vinylphenyl)acetamide (5.30 g, 71%) as a white solid (Note 8).
2. Notes
1.
N-(2-Bromophenyl)acetamide (96%) was purchased from Aldrich Chemical Company, Inc. and was used without purification.
2.
Ethylene glycol dimethyl ether (DME) was purchased from Aldrich Chemical Company, Inc. and passed through a column of Merck aluminium oxide 90 (30 g) immediately prior to use.
3.
Tetrakis(triphenylphosphine)palladium(0) was used as received from Aldrich Chemical Company, Inc.4.
Potassium carbonate (99%) was used as received from Aldrich Chemical Company, Inc.5.
2,4,6-Trivinylcyclotriboroxane-pyridine complex (purity not indicated) was used as received from Frontier Scientific, Inc.6.
Diethyl ether was used as received from Aldrich Chemical Company, Inc. (HPLC grade).
7.
The yellow solid, dissolved in
20 mL of dichloromethane, was applied to 4.5 cm diameter column packed with
600 g of flash silica gel (Merck silica 60 mesh 0.040–0.063 mm). The product was eluted with
diethyl ether/cyclohexane (9:1) (3.5 L). R
f of
2'-vinylacetanilide: 0.26 using the same eluting solvent and TLC aluminium sheets with
silica gel 60F254 (received from Aldrich Chemical Company, Inc.).
Dichloromethane, diethyl ether and cyclohexane were used as received from Aldrich Chemical Company, Inc. (HPLC grade).
8.
Analytical data:
1H NMR
pdf (500 MHz, DMSO-
d6) δ: 2.05 (s, 3H), 5.30 (dd,
J = 11.0, 1.1 Hz, 1 H), 5.77 (dd,
J = 17.5, 1.1 Hz, 1 H), 6.89 (dd,
J = 17.5, 11.0 Hz, 1 H), 7.16–7.27 (m, 2 H), 7.37 (d,
J = 7.9 Hz, 1 H), 7.61 (d,
J = 7.8 Hz, 1H), 9.52 (bs, 1H);
13C NMR (125 MHz, DMSO-
d6) δ: 23.1, 115.3, 125.2, 125.4, 126.2, 127.9, 131.5, 132.4, 135.1, 168.5; mp:
94–95 °C (lit.
3a 89–90 °C); IR (KBr) cm
−1: 3228.8, 1648. MS (ES
−)
m/z 160.1; Anal. required for C
10H
11NO: C, 74.51; H, 6.88; N, 8.69; Found: C, 74.44; H, 6.99; N, 8.61. HPLC analysis [column: Atlantis™ C
18 5 µm 4.6 × 250 mm, elution:
80% CH3CN 20% H
2O (pH = 4, adjusted with 100 µL of HCO
2H in 1.1 L of water), 1 mL/min, 1300 psi, retention time 3.6 min] gives 100% purity at 200 and 254 nm.
Handling and Disposal of Hazardous Chemicals
The procedures in this article are intended for use only by persons with prior training in experimental organic chemistry. All hazardous materials should be handled using the standard procedures for work with chemicals described in references such as "Prudent Practices in the Laboratory" (The National Academies Press, Washington, D.C., 2011 www.nap.edu). All chemical waste should be disposed of in accordance with local regulations. For general guidelines for the management of chemical waste, see Chapter 8 of Prudent Practices.
These procedures must be conducted at one's own risk. Organic Syntheses, Inc., its Editors, and its Board of Directors do not warrant or guarantee the safety of individuals using these procedures and hereby disclaim any liability for any injuries or damages claimed to have resulted from or related in any way to the procedures herein.
3. Discussion
We have previously reported a synthetic methodology for the generation of substituted styrene derivatives using
2,4,6-trivinylcyclotriboroxane-pyridine complex as the vinyl source in a Suzuki-Miyaura cross-coupling protocol.
2 Functionalized styrenes are of considerable synthetic importance as key synthetic intermediates and for the generation of new polymeric materials. Specifically
N-(2-vinylphenyl)-acetamide is an intermediate used for the synthesis of the indole ring system.
3Numerous
palladium-catalyzed methods have been described in which aryl halides are utilized as starting substrates in reactions with a variety of reagents as sources of the alkene functionality. To date the most commonly utilized approaches have been the Heck
4 and Stille
5 methodologies, which use ethene and
tributyl(vinyl)tin, respectively, as the vinyl provider.
Vinylmagnesium bromide,
6 trimethylvinylsilane,
7 vinyltrimethylsiloxane,
8 vinylpolysiloxanes,
9 potassium vinyltrifluoroborate,
10 vinylboronic acid dibutyl ester,
11 trivinylindium,
12 vinylbromide,
13 and
divinylaluminium-2-dimethylaminoethanolate14 have also been demonstrated as coupling reagents.
Aryl halides with
ortho-subsituents are known to be challenging substrates for cross-coupling reactions of boronic acids, therefore we chose
N-(2-bromophenyl)acetamide as a test substrate.
15 The target product has been previously synthesised by the coupling of ethene with
N-(2-bromophenyl)acetamide using a high pressure Heck protocol.
3aIn our reaction the cross-coupling proceeds efficiently by using a standard coupling procedure without the need of specialized catalysts. The reaction is successful with 0.5 mole equivalent of the trivinylboronic anhydride indicating that the anhydride provides more than one of the vinyl groups for reaction. In summary, 2,4,6-trivinylcyclotriboroxane-pyridine complex serves as a versatile coupling partner with aryl halides for the generation of substituted styrenes.
Appendix
Chemical Abstracts Nomenclature (Collective Index Number);
(Registry Number)
N-(2-Bromophenyl)acetamide; (614-76-6)
Tetrakis(triphenylphosphine)palladium(0); (14221-01-3)
2,4,6-Trivinylcyclotriboroxane-
pyridine complex:
Boron, ethenyl[(ethenylboronic acid-κO) bimol. monoanhydridato(2-)] (pyridine)-; (95010-17-6)
N-(2-Vinylphenyl)acetamide:
Acetamide, N-(2-ethenylphenyl)-; (29124-68-3)
Copyright © 1921-, Organic Syntheses, Inc. All Rights Reserved