ω-Nitro Acids and ω-Amino Acids by Ring Cleavage of α-Nitrocycloalkanones
6-Nitro-4-phenylhexanoic Acid (2k): IR (film): ν˜ ϭ 2960 cmϪ1
1720, 1560. Ϫ 1H NMR (CDCl3): δ ϭ 1.2Ϫ1.35 (m, 2 H), 1.8Ϫ2.3
(m, 2 H), 2.5 (t, 2 H, J ϭ 6.1 Hz), 4.2 (t, 2 H, J ϭ 7.1 Hz), 5.5 (m,
1 H), 7.1Ϫ7.3 (m, 5 H). Ϫ C12H15NO4 (237.1): calcd. C 60.75, H
6.37, N 5.90; found C 60.83, H 6.29, N 5.97.
FULL PAPER
1
,
cmϪ1, 1710. Ϫ H NMR (CDCl3): δ ϭ 1.2Ϫ1.4 (m, 6 H), 1.5Ϫ1.7
(m, 4 H), 2.15 (s, 3 H), 2.28 (t, 2 H, J ϭ 6.7 Hz), 2.4 (t, 2 H, J ϭ
7.3 Hz), 3.65 (s, 3 H). Ϫ MS; m/z (%) ϭ 200 [Mϩ], 185, 169, 143,
111, 83, 55, 43 (100). Ϫ C11H20O3 (200.1): calcd. C 65.97, H 10.07;
found C 66.03, H 10.13.
3,3,5,5-Tetramethyl-6-nitrohexanoic Acid (2l): IR (film): ν˜ ϭ 2970
1
cmϪ1, 1720, 1560. Ϫ H NMR (CDCl3): δ ϭ 1.1 (s, 3 H), 1.17 (s,
3 H), 1.23 (s, 3 H), 1.3 (s, 3 H), 1.5Ϫ1.7 (m, 2 H), 2.3Ϫ2.4 (m, 2
H), 4.27Ϫ4.38 (m, 2 H), 10.45 (s, 1 H). Ϫ C10H19NO4 (217.1):
calcd. C 55.28, H 8.81, N 6.45; found C 55.33, H 8.90, N 6.37.
Acknowledgments
This work was carried out in the framework of the National Project
“Stereoselezione in Sintesi Organica. Metodologie ed Applica-
zioni” supported by Ministero dellЈUniversita e della Ricerca
Scientifica e Tecnologica, Rome, and by the University of Came-
rino.
Synthesis of ω-Amino Acids 3: To a stirred solution of nitro acid 2
(5 mmol) and 10% Pd-C (0.25 g), in methanol (10 mL), anhydrous
ammonium formate (23 mmol) was added under N2, and the ob-
tained mixture was heated, at 80°C, for 30 min. The catalyst was
then filtered off, and the filtrate was concentrated to give the almost
pure amino acid 3. However, if necessary compond 3 can be puri-
fied by reversed-phase chromatography.
`
[1]
[1b]
[1a] R. H. Fisher, H. M. Weitz, Synthesis 1980, 261Ϫ282. Ϫ
G. Rosini, R. Ballini, M. Petrini, E. Marotta, P. Righi, Org.
Prep. Proc. Int. 1990, 22, 707Ϫ746
R. Ballini, M. Petrini, V. Polzonetti, Synthesis 1992, 355Ϫ357.
R. Ballini, E. Marcantoni, M. Petrini, G. Rosini, Synthesis
1988, 915Ϫ917.
R. Ballini, M. Petrini, G. Rosini, Tetrahedron 1990, 46,
7531Ϫ7538.
R. Ballini, G. Bartoli, R. Giovannini, E. Marcantoni, M. Pe-
trini, Tetrahedron Lett. 1993, 34, 3301Ϫ3304.
R. Ballini, M. Petrini, O. Polimanti, J. Org. Chem. 1996, 61,
5652Ϫ5655.
6-Aminohexanoic Acid (3b): M.p. 210Ϫ212°C. Ϫ IR (film): ν˜ ϭ
1
2970 cmϪ1, 1630, 1460. Ϫ H NMR (CD3OD): δ ϭ 1.35Ϫ1.45 (m,
[2]
[3]
2 H), 1.55Ϫ1.75 (m, 4 H), 2.25 (t, 2 H, J ϭ 7.2 Hz), 2.93 (t, 2 H,
J ϭ 7.4 Hz). Ϫ C6H13NO2 (131.1): calcd. C 54.94, H 9.99, N 10.68;
found C 55.01, H 10.06, N 10.57.
[4]
[5]
[6]
[7]
7-Aminoheptanoic Acid (3c): M.p. 193Ϫ195°C. Ϫ IR (film): ν˜ ϭ
1
2970 cmϪ1, 1640, 1460. Ϫ H NMR (CD3OD): δ ϭ 1.3Ϫ1.45 (m,
4 H), 1.55Ϫ1.75 (m, 4 H), 2.1Ϫ2.4 (m, 2 H), 2.95 (t, 2 H, J ϭ 7.5
Hz). Ϫ C7H15NO2 (145.2): calcd. C 57.90, H 10.41, N 9.65; found
C 57.82, H 10.33, N 9.57.
A. K. Saikia, M. Hazarika, N. C. Barua, M. S. Bezbarua, R.
P. Sharma, A. C. Ghosh, Synthesis 1996, 981Ϫ985.
R. Ballini, L. Barboni, L. Pintucci, Synlett 1997, 1389Ϫ1390.
R. Ballini, G. Bosica, Tetrahedron 1997, 53, 16131Ϫ16138.
H. Stach, M. Hesse, Tetrahedron 1988, 44, 1573Ϫ1590.
[8]
[9]
12-Aminododecanoic Acid (3g): M.p. 184Ϫ186°C. Ϫ IR (film): ν˜ ϭ
[10]
1
2980 cmϪ1, 1640, 1440. Ϫ H NMR (CD3OD): δ ϭ 1.25Ϫ1.35 (m,
[11] [11a] . Ballini, G. Bosica, Tetrahedron Lett. 1996, 37, 8027Ϫ8030.
[11b]
14 H), 1.45Ϫ1.7 (m, 4 H), 2.10Ϫ2.2 (m, 2 H), 2.85Ϫ2.95 (m, 2 H).
Ϫ C12H25NO2 (215.2): calcd. C 66.93, H 11.70, N 6.50; found C
66.96, H 11.78, N 6.42.
Ϫ
Ϫ
R. Ballini, G. Bosica, J. Org. Chem. 1997, 62, 425Ϫ427.
[11c] R. Ballini, G. Bosica, Eur. J. Org. Chem. 1998, 355Ϫ357.
[12]
[13]
G. Rosini, R. Ballini, Synthesis 1988, 833Ϫ847.
R. Ballini, in Studies in Natural Products Chemistry (Ed.: Atta-
ur-Rahman), Elsevier, Amsterdam, 1997, vol. 19, p. 117Ϫ184.
15-Aminopentadecanoic Acid (3h): M.p. 180Ϫ182°C. Ϫ IR (film):
[14] [14a]
[14b]
1
ν˜ ϭ 2980 cmϪ1, 1640, 1460. Ϫ H NMR (CD3OD): δ ϭ 1.3Ϫ1.45
J. T. Sparrow, J. Org. Chem. 1976, 41, 1350Ϫ1353. Ϫ
A. B. Tabor, Tetrahedron 1996, 52, 2229Ϫ2234.
(m, 20 H), 1.5Ϫ1.75 (m, 4 H), 2.15Ϫ2.20 (m, 2 H), 2.85Ϫ2.95 (m,
2 H). Ϫ C15H31NO2 (257.2): calcd. C 69.99, H 12.14, N 5.44; found
C 70.06, H 12.13, N 5.38.
[15]
[15a]
See for example:
A. Keiichi, Y. Mutsunori, E. Yoshiaki,
Jpn. Kokai Tokkyo Koho JP 62 01,748, 1985, Unitika Ltd.;
Chem. Abstr. 1987, 106, 214962. Ϫ [15b] E. Schmid, G. Stoeppel-
mann, Eur. Pat. Appl. EP 409,115, 1991, A.-G. Ems-Inventa;
[15c]
6-Nitro-9-oxodecanoate (7): To a mixture of α-nitrocyclohexanone
(1b) (10 mmol) and 0.05 NaOH (12 mmol), methyl vinyl ketone
(4) (11 mmol) and CTACl (1 mmol) were added at 0°C. The mix-
ture was stirred at 0°C for 8 h, and at 80°C for another 8 h. After
cooling, the solution was saturated with NaCl and extracted with
EtOAc (4 ϫ 20 mL), and dried (MgSO4). Removal of the solvent
afforded the crude product 6 which was dissolved in methanol (30
mL) and stirred for 18 h in the presence of Amberlyst 15 ion ex-
change resin (1 g). The resin was removed by filtration, and then,
after evaporation of the solvent, the crude ester was purified by
flash chromatography (EtOAc/cyclohexane, 3:7), affording 1.67 g
(68%) of pure 7. Ϫ Oil. Ϫ IR (film): ν˜ ϭ 1740 cmϪ1, 1715, 1540.
Chem. Abstr. 1991, 114, 248054. Ϫ
T. Sakashita, Y. Zeni-
tani, A. Ikeda, Jpn. Kokai Tokkyo Koho JP 62,156,130,1985,
Mitsui Petrochemical Industries, Ltd.; Chem. Abstr. 1987, 107,
237563. Ϫ [15d] T. Motoi, Y. Ido, M. Oguchi, Jpn. Kokai Tokkyo
Koho JP 62,161,828, 1987, Toyobo Co. Ltd.; Chem. Abstr. 1988,
108, 38653. Ϫ [15e] T. Shimada, M. Tamaya, Jpn. Kokai Tokkyo
Koho JP 63 43,953, 1986, Daicel Chemical Industried Ltd.;
Chem. Abstr. 1988, 108, 222636. Ϫ [15f] B. Frimlova, J. Taticek,
P. Marek, O. Hajicek, O. Marek, Czech. CS 241,391,1987;
Chem. Abstr. 1988, 109, 74512. Ϫ [15g] Y. Isegawa, M. Watanabe,
Ger. Offen. DE 3,738,876, 1988, Mitsubishi Monsanto Chemical
Co.; Chem. Abstr. 1988, 109, 150929. Ϫ [15h] A. Okada, M. Ka-
wasumi, M. Kohaki, M. Fujimoto, Y. Kojima, T. Kurauchi, O.
Kamigaito, Ger. Offen. DE 3,808,623, 1988, Toyota Central Re-
search and Development Laboratories, Inc.; Chem. Abstr. 1989,
1
[15i]
Ϫ H NMR (CDCl3): δ ϭ 1.1Ϫ1.3 (m, 2 H), 1.35Ϫ1.45 (m, 2 H),
110, 115982. Ϫ
A. Okada, M. Kawasumi, M. Kohaki, M.
Fujimoto, Y. Kojima, T. Kurauchi, O. Kamigaito, Ger. Offen.
DE 3,808,623, 1988, Toyota Central Research and Development
Laboratories, Inc.; Chem. Abstr. 1989, 110, 115982.
T. Ichino, E. Sakai, Y. Takei, Jpn. Kokai Tokkyo Koho JP 03
15,851, 1989, Konika Co.; Chem. Abstr. 1991, 115, 38651.
I. Saiki, J. Iida, J. Murata, R. Ogawa, N. Nishi, K. Sugimura,
S. Tokura, I. Azuma, Cancer Res. 1989, 49, 3815Ϫ3822; Chem.
Abstr. 1989, 111, 108493.
P. Roger, J. P. Fournier, A. Martin, J. Choay, Eur. Pat. Appl. EP
238,401, 1986, SANOFI; Chem. Abstr. 1988, 108, 21494.
A. Cordi, C. Gillet, J. Roba, P. Niebes, D. P. Janssesn, G. Lam-
belin, Belg. BE 897,566, 1982, MIDIT; Chem. Abstr. 1984,
100, 210422.
2.15 (s, 3 H), 2.28 (t, 2 H, J ϭ 7.3 Hz), 2.48 (t, 2 H, J ϭ 6.9 Hz),
3.65 (s, 3 H), 4.4Ϫ4.6 (m, 1 H). Ϫ C11H19NO5 (245.3): calcd. C
53.87, H 7.81, N 5.71; found C 53.96, H 7.75, N 5.80.
[16]
[17]
Methyl 9-Oxodecanoate (8): A dried, N2-flushed flask was charged
with compound 7 (1.2 g, 4.9 mmol) and AIBN (312 mg, 1.92 mmol)
in dry toluene (12 mL). Tri-n-butyltin hydride (24 mmol) was added
and the resulting solution refluxed for 3 h. After that, the solvent
was evaporated and the crude product was purified by flash chro-
matography (EtOAc/cyclohexane, 2:8) yielding 0.39 g (40%) of the
pure compound 8. Ϫ B.p. 70°C/0.4 Torr. Ϫ IR (film): ν˜ ϭ 1735
[18]
[19]
Eur. J. Org. Chem. 1999, 87Ϫ90
89