A New Heterogeneous One-Pot Process for Both Nitroaldol (Henry) and Michael Reactions from Primary Haloalkanes via Nitroalkanes

Abstract

At room temperature, one equivalent of primary haloalkane and aldehyde, or conjugated enone, in the presence of IRA-402 nitrite and Amberlyst A-21, gave β-nitroalkanols or γ-nitro ketones, respectively, via a one-pot tandem S_N2-nitroaldol (Henry) or S_N2-Michael reactions.

one-pot process - haloalkanes - nitroalkanes - nitroaldol reaction - Henry reaction - Michael addition - heterogeneous process

References and Notes

1a Rosini G. Ballini R. Synthesis  1988,  833 

1b Ono N. The Nitro Group in Organic Synthesis   Wiley; New York: 2001. 

1c Nitro Compounds: Recent Advances in Synthesis and Chemistry   Feuer H. Nielsen AT. Wiley-VCH; Weinheim: 1990. 

1d The Chemistry of Amino, Nitroso, Nitro and Related Groups   Patai S. Wiley; Chichester: 1996. 

1e Adams JP. J. Chem. Soc., Perkin Trans. 1  2002,  2586 

2a Rosini G. In Comprehensive Organic Synthesis   Vol. 2:  Trost BM. Pergamon; Oxford: 1991.  p.321 

2b Luzzio FA. Tetrahedron  2001,  57:  915 

3 Ballini R. Bosica G. Fiorini D. Palmieri A. Petrini M. Chem. Rev.  2005,  105:  933 

See for example:

4a Ballini R. In Studies in Natural Products Chemistry   Vol. 19:  . Elsevier; Amsterdam: 1997.  p.117 

4b Ballini R. Petrini M. Tetrahedron  2004,  60:  1017 

5a Kornblum N. Org. React. (N. Y.)  1962,  12:  101 

5b Feuer H. Leston G. Org. Synth., Coll. Vol. IV   Wiley; New York: 1963.  p.368 

6a Amato J. Science  1993,  259:  1538 

6b Broadwater SJ. Roth SL. Price KE. Kobaslija M. McQuade DT. Org. Biomol. Chem.  2005,  3:  2899 

See for example:

7a Ballini R. Bosica G. Fiorini D. Palmieri A. Synthesis  2004,  1938 

7b Ballini R. Bosica G. Parrini M. Tetrahedron Lett.  1998,  39:  7963 

7c Rosini G. Galanarini R. Marotta E. Righi P. J. Org. Chem.  1990,  55:  781 

7d Ballini R. Synthesis  1993,  687 

7e Ballini R. Palmieri A. Righi P. Tetrahedron  2007,  63:  12099 

8 Gelbard G. Colonna S. Synthesis  1977,  113 

9

Preparation of Amberlite IRA-402 Nitrite: To a stirred solution of NaNO₂ (3 g) in H₂O (30 mL), Amberlite IRA-402 (Fluka; 3 g) was added and the heterogeneous mixture was heated at 40 °C for 30 min. Then, H₂O was separated from Amberlite by decantation, and the resin was washed with MeOH (2 × 15 mL) and with Et₂O (2 × 15 mL). Finally the exchanged resin was dried under vacuum.

10

General Procedure for the One-Pot Preparation of β-Nitroalkanols 6 and γ-Nitro Ketones 7: In a round-bottomed flask the resins IRA-402 nitrite (800 mg) and Amberlyst A-21 (600 mg), were added to a solution of DMF (2 mL), haloalkane 1 (1 mmol) and the appropriate electrophilic species 4 or 5 (1 mmol). The resulting mixture was stirred for the appropriate time (Table [1] ), then filtered and washed with Et₂O (20 mL). The organic layer was washed with cold H₂O (20 mL), dried (Na₂SO₄), filtered and evaporated yielding a crude product that was purified by flash chromatography (cyclohexane-EtOAc as eluent), giving the pure compound 6 or 7.

11

Selected Analytical Data for Compounds 6b,c and 7a,b: Compound 6b: yellow oil. IR (neat): 1456, 1916, 3354 cm^-1. ¹H NMR (400 MHz, CDCl₃): δ = 0.86-0.92 (m, 3 H), 1.21-1.40 (m, 4 H), 1.60-1.93 (m, 3 H), 1.96-2.17 (m, 1 H), 2.32 (d, J = 8.1 Hz, 0.6 H), 2.45 (d, J = 4.3 Hz, 0.4 H), 2.65-2.80 (m, 1 H), 2.82-2.96 (m, 1 H), 3.82-3.94 (m, 0.6 H), 3.97-4.06 (m, 0.4 H), 4.40-4.49 (m, 1 H), 7.16-7.34 (m, 5 H). ¹³C NMR (100 MHz): δ = 13.9, 14.0, 22.3, 22.4, 27.9, 28.0, 28.3, 30.4, 31.8, 32.1, 35.0, 35.5, 71.4, 71.7, 92.5, 93.1, 126.5, 128.7, 128.8, 141.0. Anal. Calcd for C₁₄H₂₁NO₃: C, 66.91; H, 8.42; N, 5.57. Found: C, 67.24; H, 8.66; N, 5.38.
Compound 6c: yellow oil. IR (neat): 1730, 3404 cm^-1. ¹H NMR (400 MHz, CDCl₃): δ = 0.96-1.04 (m, 3 H), 1.37-1.94 (m, 5 H), 2.03-2.21 (m, 1 H), 2.43 (d, J = 7.7 Hz, 0.5 H), 2.54 (d, J = 5.1 Hz, 0.5 H), 3.63-3.83 (m, 2.5 H), 3.88-3.96 (m, 0.5 H), 4.49-4.61 (m, 1 H), 7.68-7.74 (m, 2 H), 7.79-7.85 (m, 2 H). ¹³C NMR (100 MHz): δ = 10.0, 10.2, 25.2, 25.3, 26.6, 26.8, 27.7, 37.0, 37.1, 73.6, 73.8, 91.4, 91.9, 123.6, 132.1, 134.4, 168.6. Anal. Calcd for C₁₅H₁₈N₂O₅: C, 58.82; H, 5.92; N, 9.15. Found: C, 59.14; H, 6.18; N, 8.89.
Compound 7a: yellow oil. IR (neat): 1442, 1577, 1732 cm^-1. ¹H NMR (400 MHz, CDCl₃): δ = 0.84-0.92 (m, 3 H), 1.23-1.40 (m, 4 H), 1.68-2.20 (m, 4 H), 2.25 (s, 3 H), 2.45-2.53 (m, 2 H), 4.43-4.52 (m, 1 H). ¹³C NMR (100 MHz): δ = 13.9, 22.2, 27.5, 28.0, 30.2, 33.8, 39.1, 88.1, 206.7. EI-MS (70 eV): m/z = 187, 157, 141, 123, 97, 83, 71, 55, 43 (100). Anal. Calcd for C₉H₁₇NO₃: C, 57.73; H, 9.15; N, 7.48. Found: C, 57.44; H, 8.91; N, 7.70.
Compound 7b: yellow oil. IR (neat): 1168, 1364, 1736 cm^-1. ¹H NMR (400 MHz, CDCl₃): δ = 1.58-1.67 (m, 2 H), 1.72-1.81 (m, 1 H), 1.96-2.11 (m, 3 H), 2.02 (s, 3 H), 2.12 (s, 3 H), 2.43-2.52 (m, 2 H), 3.96-4.10 (m, 2 H), 4.47-4.56 (m, 1 H). ¹³C NMR (100 MHz): δ = 21.1, 25.2, 27.6, 30.3, 30.7, 39.1, 63.4, 87.6, 171.2, 206.6. EI-MS (70 eV): m/z = 43 (100), 81, 125, 141, 185, 231. Anal. Calcd for C₁₀H₁₇NO₅: C, 51.94; H, 7.41; N, 6.06. Found: C, 52.23; H, 7.61; N, 5.88.

12a Mélot J.-M. Texier-Boullet F. Foucaud A. Tetrahedron Lett.  1986,  27:  493 

12b Rosini G. Ballini R. Petrini M. Marotta E. Righi P. Org. Prep. Proced. Int.  1990,  22:  707 

12c Ballini R. Bosica G. Fiorini D. Palmieri A. Tetrahedron  2005,  61:  8971 

13a Barret AGM. Graboski GG. Chem. Rev.  1986,  86:  751 

13b Kabalka GW. Varma RS. Org. Prep. Proced. Int.  1987,  19:  283 

13c Ballini R. Castagnani R. Petrini M. J. Org. Chem.  1992,  57:  2160