The Reaction of Acetylenic Amines with Tetraethylammonium Carbonate and Hydrogen Carbonate; Synthesis of 5-Methylene-1,3-oxazolidin-2-ones

Abstract

The reaction of acetylenic amines 1 with electrochemically generated tetraethylammonium carbonate (TEAC) or chemically generated tetraethylammonium hydrogen carbonate (TEAHC) is reported. Unsubstituted or substituted 5-methylene-1,3-oxazol­idin-2-ones 2 are obtained in moderate to very high yields according to the reaction conditions adopted and to the nature of the substrate.

alkynes - amines - cyclizations - carboxylations - oxazol­idin-2-ones

References

1a Feroci M. Inesi A. Rossi L. In Novel Trends in Electroorganic Synthesis   Torii S. Springer-Verlag; Tokio: 1998. and references cited therein

1b Inesi A. Mucciante V. Rossi L. J. Org. Chem.  1998,  63:  1337 

1c Feroci M. Inesi A. Mucciante V. Rossi L. Tetrahedron Lett.  1999,  40:  6059 

1d Mucciante V. Rossi L. Feroci M. Sotgiu G. Synth. Commun.  2002,  32:  1205 

2 Ager DJ. Prakash I. Schaad DR. Chem. Rev.  1996,  96:  835 ; and references cited therein

3 Dimroth P, and Pasedach H. inventors; (BASF) DE Pat  1164411.  ; Chem. Abstr. 1964, 60, 14510

4a Mitsudo T. Hori Y. Yamakawa Y. Watanabe Y. Tetrahedron Lett.  1987,  28:  4417 

4b Shi M. Shen Y.-M. J. Org. Chem.  2002,  67:  16 

5a Costa M. Chiusoli GP. Rizzardi M. Chem. Commun.  1996,  1699 

5b Costa M. Chiusoli GP. Taffurelli D. Dalmonego G. J. Chem. Soc., Perkin Trans. 1  1998,  1541 

6 Shi M. Shen Y.-M. Chen Y.-J. Heterocycles  2002,  57:  245 

7 TEAHC is simply obtained by saturating a methanol solution of tetraethylammonium hydroxide with CO₂, see: Venturello C. D’Aloisio R. Synthesis  1985,  33 

For further details concerning electrogeneration of TEAC, see:

8a Casadei MA. Inesi A. Micheletti Moracci F. Rossi L. Chem. Commun.  1996,  2575 

8b Casadei MA. Inesi A. Rossi L. Tetrahedron Lett.  1997,  38:  3565 

9a Imada Y. Yuasa M. Nakamura I. Murahashi S.-I. J. Org. Chem.  1994,  59:  2282 

9b

N -[2-(3,4-Dimethoxy-phenyl)ethyl]-2-methylbut-3-yn-2-amine ( 1d): ¹H NMR (200 MHz, CDCl₃): δ = 1.36 (s, 6 H), 1.56 (br s, 1 H), 2.26 (s, 1 H), 2.78 (t, 2 H), 2.98 (t, 2 H), 3.87 (s, 3 H), 3.88 (s, 3 H), 6.65-6.85 (m, 5 H) ppm. ¹³C NMR (50.3 MHz, CDCl₃): δ = 29.4, 35.9, 45.2, 49.6, 55.8, 55.9, 69.7, 88.8, 111.2, 111.8, 120.6, 132.2, 147.4, 148.8 ppm. Anal. Calcd: C, 72.84; H, 8.56. Found: C, 72.79; H, 8.54.

10a Austin WB. Bilow N. Kelleghan WJ. Lau KSY. J. Org. Chem.  1981,  46:  2280 

10b

Synthesis of 1-{4-[3-(benzylamino)-3-methylpent-1-ynyl]phenyl}ethanone ( 1f): To a solution of 1c (1 g, 5.34 mmol) in DMF (2 mL), and Et₃N (4 mL) were added 1-(4-iodophenyl)ethanone (1.315 g, 5.34 mmol), palladium diacetate (0.024 g, 0.107 mmol) and PPh₃ (0.056 g, 0.213 mmol). The mixture was stirred under N₂ at 50 °C for 16 h, then 0.5 M NH₄Cl (100 mL) was added and the mixture extracted with Et₂O (3 × 50 mL). The combined organic phase was dried (Na₂SO₄) and evaporated under reduced pressure. Silica gel chromatography (hexanes-EtOAc 90:10) afforded 1f (1.265 g, 78% yield). ¹H NMR (200 MHz, CDCl₃): δ = 1.08 (t, 3 H), 1.45 (s, 3 H), 1.48 (br s, 1 H), 1.74 (dq, 2 H), 2.59 (s, 3 H), 3.94 (s, 2 H), 7.20-7.45 (m, 5 H), 7.70 (AA′XX′, 4 H) ppm. ¹³C NMR (50.3 MHz, CDCl₃): δ = 8.9, 26.3, 26.6, 34.6, 48.7, 54.7, 82.9, 97.5, 127.0, 128.2, 128.4, 128.5, 131.8, 135.9, 140.7, 197.4 ppm. Anal. Calcd: C, 82.58; H, 7.59. Found: C, 82.55; H, 7.56.

11

Some representative examples are reported:
4,4-Dimethyl-5-methylene-3-(3-phenylpropyl)-1,3-oxazolidin-2-one ( 2b): ¹H NMR (200 MHz, CDCl₃): δ = 1.29 (s, 3 H), 1.80-2.00 (m, 2 H), 2.58 (t, 3 H), 3.11 (t, 3 H), 4.13 (dd, 1 H), 4.55 (dd, 1 H), 7.10-7.30 (m, 5 H) ppm. ¹³C NMR (50.3 MHz, CDCl₃): δ = 27.5, 29.6, 30.9, 33.1, 40.0, 61.3, 83.9, 126.0, 128.2, 128.4, 141.0, 154.3, 160.6 ppm. Anal. Calcd: C, 73.44; H, 7.81. Found: C, 73.49; H, 7.73.
3-Benzyl-4-ethyl-4-methyl-5-methylene-1,3-oxazolidin-2-one ( 2c): ¹H NMR (200 MHz, CDCl₃): δ = 0.65 (t, 3 H), 1.17 (s, 3 H), 1.30-1.55 (m, 1 H) 1.60-1.80 (m, 1 H), 4.09 (d, 1 H), 4.32 (AB, 2 H), 4.65 (d, 1 H), 7.15-7.35 (m, 5 H) ppm. ¹³C NMR (50.3 MHz, CDCl₃): δ = 7.6, 27.3, 32.2, 44.0, 65.4, 84.5, 127.8, 128.1, 128.6, 137.4, 155.4, 158.8 ppm. Anal. Calcd: C, 72.70; H, 7.41. Found: C, 72.63; H, 7.29.
3-[2-(3,4-Dimethoxyphenyl)ethyl]-4,4-dimethyl-5-methylene-1,3-oxazolidin-2-one ( 2d): ¹H NMR (200 MHz, CDCl₃): δ = 1.22 (s, 6 H), 2.75-2.95 (m, 2 H), 3.15-3.35 (m, 2 H), 3.78 (s, 3 H), 3.80 (s, 3 H), 4.12 (d, 1 H), 4.55 (d, 1 H), 6.60-6.80 (m, 3 H) ppm. ¹³C NMR (50.3 MHz, CDCl₃): δ = 27.2, 34.5, 42.3, 55.8, 61.2, 84.0, 111.2, 112.0, 120.7, 130.9, 147.6, 148.8, 154.1, 160.5 ppm. Anal. Calcd: C, 65.96; H, 7.27. Found: C, 65.88; H, 7.14.
(5 Z )-3-Benzyl-5-(4-methoxybenzylidene)-4,4-dimethyl-1,3-oxazolidin-2-one ( 2h): ¹H NMR (200 MHz, CDCl₃):
δ = 1.27 (s, 6 H), 3.71 (s, 3 H), 4.41 (s, 2 H), 5.31 (s, 1 H), 6.70-6.85 (m, 2 H), 7.10-7.30 (m, 5 H), 7.40-7.55 (m, 2 H) ppm. ¹³C NMR (50.3 MHz, CDCl₃): δ = 27.7, 44.0, 55.2, 62.3, 100.1, 113.8, 126.2, 127.7, 128.6, 129.5, 137.5, 151.6, 154.9, 158.3 ppm. Anal. Calcd: C, 74.28; H, 6.55. Found: C, 74.11; H, 6.38.
Methyl 3-[(3-Benzyl-4-ethyl-4-methyl-2-oxo-1,3-oxazolidin-5-ylidene)methyl]benzoate ( 2i): ¹H NMR (200 MHz, CDCl₃): δ = 0.66 (t, 3 H), 1.18 (s, 3 H), 1.40-1.65 (m, 1 H), 1.70-1.95 (m, 1 H), 3.84 (s, 3 H), 4.38 (AB, 2 H), 5.37 (s, 1 H), 7.15-7.40 (m, 6 H), 7.75-8.10 (m, 3 H) ppm. ¹³C NMR (50.3 MHz, CDCl₃): δ = 7.7, 27.3, 29.7, 44.1, 52.2, 66.3, 100.1, 127.8, 127.9, 128.1, 128.7, 129.4, 130.3, 132.5, 133.9, 137.2, 152.7, 155.1, 166.8 ppm. Anal. Calcd: C, 72.31; H, 6.34. Found: C, 72.39; H, 6.42.