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Synlett 2002(12): 2092-2094
DOI: 10.1055/s-2002-35602
LETTER
© Georg Thieme Verlag Stuttgart · New York

A Novel and Efficient Oxidation of 1,2-Amino Alcohols to Dialkylamides

María García-Valverde*a, Rafael Pedrosa*b, Martina Vicenteb
a Departamento de Química, Facultad de Ciencias, Universidad de Burgos, Pza. Misael Bañuelos s/n 09001-Burgos, Spain
Fax: +34(947)258087; e-Mail: magaval@ubu.es;
b Departamento de Química Orgánica, Facultad de Ciencias, Universidad de Valladolid, Dr. Mergelina s/n 47011-Valladolid, Spain
Further Information

Publication History

Received 22 August 2002
Publication Date:
20 November 2002 (online)

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Abstract

The oxidation of 1,2-amino alcohols and α-amino ketones can be efficiently performed using potassium hydroxide in the presence of air. This novel procedure affords carboxylic derivatives in excellent yields and high purity.

Key words

1,2-amino alcohols - α-amino ketones - oxidations - potassium hydroxide - radical reactions

    References

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    4h: (2-Dibutylamino-1-phenyl-1-propanone): Pyridinium chlorochromate (1.29 g, 6 mmol) was added in small portions to a stirred solution of amino alcohol 1h (0.39 g, 1.5 mmol) in CH2Cl2 (30 mL) over 4 Å sieves. The resulting mixture was stirred at r.t. for 6 h and filtered. The solvent was evaporated under reduced pressure. The residue was dissolved in an aqueous solution of NaOH (15% w/v, 10 mL) and extracted with ether. The organic layer was separated, washed with brine and dried (Na2SO4). Removal of the solvent left a residue, which was purified by column chromatography (hexane/EtOAc, 6:1) to yield amino ketone 4h (67%). Colorless liquid. bp 82-84 (0.2 mmHg). IR (neat, cm-1): 1685. 1H NMR (CDCl3, 200 MHz): 0.79 (t, 6 H, J = 12 Hz); 1.04-1.21 (m, 7 H), 1.22-1.38 (m, 4 H); 2.40 (t, 4 H, J = 12 Hz); 4.31 (q, 1 H, J = 9.0 Hz); 7.22-7.50 (m, 3 H); 7.94-8.00 (m, 2 H). 13C NMR (CDCl3, 50 MHz): 9.2 (CH3); 14.0 (CH3); 20.4 (CH2); 30.7 (CH2); 50.7 (CH2); 60.4 (CH); 128.1 (CHAr);128.9 (CHAr); 132.4 (CHAr); 137.0 (CAr); 201.8 (CO). MS (m/z, %): 260 (M+ - 1, 1), 156(100). Anal. Calcd for C17H27NO: C, 78.11; H, 10.41; N, 5.36. Found: C, 78.22; H, 10.63; N, 5.27.
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9

Typical experimental procedure: The amino alcohol (1a-k) (0.1 g) was added to a stirred suspension of KOH (1.0 g) in diethyl ether (20 mL). The stirring was continued for the proper time (Table [1] ) at room temperature. The solid was filtered off and washed with ether. The solvent was removed to yield the amide. The solid was dissolved in water and the solution acidified with HCl and extracted with ether. The organic layer was dried and the solvent was removed to yield the corresponding carboxylic acid.

15

The EPR studies were made on the reaction mixtures without filtration. Moreover, the evolution of the EPR spectra taken at different reaction times showed the presence of mixtures of radicals as intermediates in these reactions.

17

NOESY experiments showed that the angular oxazolidine proton at C-7a was trans to the proton at C-6, indicating an S configuration at this carbon. (2S,3R,6S,7aR)-6-Benzyl-2-phenyl-3-methyl-5-oxo-2,3,5,6,7,7a-hexahydro-pyrrolo-[2,1-b]-oxazole (5). White solid, mp 101-103 ºC. [α]23 D +34.6 (c 1.6, CHCl3). IR (neat, cm-1) 1700. 1H NMR (CDCl3, 300 MHz): 1.00 (d, J = 6.8 Hz, 3 H), 2.19-2.23 (m, 2 H), 2.88 (dd, J = 13.2 Hz, 8.2 Hz, 1 H), 3.06-3.18 (m, 2 H), 3.95 (qd, J = 6.9 Hz, 6.8 Hz, 1 H), 4.95 (t, J = 5.4 Hz, 1 H), 5.19 (d, J = 7.1 Hz, 1 H), 7.20-7.37 (m, 5 H, HAr). 13C NMR (CDCl3, 75 MHz): 13.4 (CH3), 30.7 (CH2), 37.6 (CH2), 48.6 (CH), 54.7 (CH), 85.3(CH), 91.2 (CH), 126.6 (CHAr), 128.0 (CHAr), 128.3 (CHAr), 128.5 (CHAr), 129.1 (CHAr), 136.3 (CAr), 138.5 (CAr), 175.5 (CO). Anal.calcd for C20H21NO2: C, 78.15; H, 6.89; N, 4.56. Found: C, 77.77; H, 7.08; N, 4.35.

18

Two isomers were observed at room temperature. (R)-1-Acetyl-2-benzyl pyrrolidine (2m). Colorless oil. [α]D 23 +25.54 (c 1.1, CHCl3), IR (neat, cm-1) 1650. MS (m/z, %): 203 (M+, 32), 91(28), 43(100). 1H NMR (CDCl3, 300 MHz): 1.53-1.75 (m, 2 H), 1.95-2.05 (m, 8 H), 2.41-2.52 (m, 2 H), 2.62-2.69 (m, 4 H), 3.03-3.12 (m, 2 H), 3.33-3.58 (m, 4 H), 3.61-3.68 (m, 2 H), 7.14-7.33 (m, 5 H, HAr). 13C NMR (CDCl3, 75 Mz): 22.2 (CH3), 22.4 (CH3), 30.4 (CH2), 31.7 (CH2), 39.0 (CH2), 39.6 (CH), 41.1 (CH), 45.1 (CH2), 46.9 (CH2), 50.7 (CH2), 52.5 (CH2), 126.2 (CHAr), 126.3 (CHAr), 128.4 (CHAr), 128.5 (CHAr), 128.6 (CHAr), 139.9 (CAr), 169.2 (CO). Anal. Calcd for C13H17NO: C, 76.81; H, 8.43; N, 6.89. Found: C, 76.70; H, 8.62; N, 6.76.