Transition Metal Catalyzed Oxidation, 10
FULL PAPER
1.70Ϫ1.85 (m, 2 H, 1-H, 3-H), 1.55Ϫ1.62 (m, 1 H, 4-H), 1.21 (s, 3
H, 8-H), 1.07 (d, J ϭ 7.15 Hz, 3 H, 10-H), 1.03 (s, 3 H, 9-H), 0.72
(d, J ϭ 9.96 Hz, 1 H, 7-H). Ϫ 13C NMR (75 MHz, CDCl3): δ ϭ
82.93 (t, CH2NO2), 47.24 (d, C-1), 40.86 (d, C-5), 39.80 (d, C-3),
38.44 (s, C-6), 35.18 (d, C-2), 33.66 (t, C-7), 31.53 (t, C-4), 27.63
(q, C-9), 22.71 (q, C-8), 21.03 (q, C-10). Ϫ C11H19NO2 (197.2):
calcd. C 66.97, H 9.71, N 7.10; found C 66.93, H 9.65, N 7.09.
17-H at δ ϭ 4.5 (β isomer 24b) and 4.7 (α isomer 24a). The
major β isomer 24b was easily purified by crystallization
and the axial β position of the nitro group was unequivo-
cally established by the absence of trans-diaxial relation-
ships of 17-H with the neighboring methylene protons in
the H-NMR spectrum. In addition, proton 17-H of the α
isomer 24a shows a distinct NOE effect with the neighbor-
1
1,1-Diethoxy-4-nitrobutane (15): IR (neat): ν˜ ϭ 2977 cmϪ1, 2932,
2881, 1556 (NO2), 1444, 1377 (NO2). Ϫ 1H NMR (200 MHz,
CDCl3): δ ϭ 4.32Ϫ4.46 (m, 3 H, 1-H, 4-H), 3.33Ϫ3.65 (m, 4 H,
OCH2), 1.94Ϫ2.09 (m, 2 H, 3-H), 1.57Ϫ1.68 (m, 2 H, 2-H), 1.12
(t, J ϭ 7.05 Hz, 6 H, CH3). Ϫ 13C NMR (50 MHz, CDCl3): δ ϭ
102.36 (d, C-1), 75,64 (t, C-4), 61.96 (t, OCH2), 30.58 (t, C-2), 22.84
(t, C-3), 15,54 (q, CH3). Ϫ C8H17NO4 (191.22): calcd. C 50.24, H
8.96, N 7.32; found C 50.28, H 8.88, N 7.39.
ing methyl group (C-18).
Careful analysis of the GC and H-NMR spectra in the
1
oxidation of the amino group on primary (entries 1Ϫ4) and
benzylic positions (entry 9) revealed the occurrence of small
amounts of the corresponding aldehydes or acetophenone
(5Ϫ21%). Evidently, oxidative cleavage of the nitro com-
pounds occurred to some extent with these sterically unhin-
dered substrates.[6] Accordingly, the yields were somewhat
lower compared to the sterically more hindered amino
group on secondary or tertiary carbon positions and the
procedure was also less effective for benzylic amines (entry
9). On the other hand, this observation offers the chance
for in situ Nef reactions for a one-pot conversion of amines
to carbonyl compounds. Initial results in this direction are
promising and the elaboration of such a procedure is un-
der investigation.
17β-Nitroestron Methyl Ether (24b): M.p. 169Ϫ170°C (CH2Cl2/
20
n-hexane); [α]D ϭ ϩ102.4 (c ϭ 0.5, CH2Cl2). Ϫ IR (KBr): ν˜ ϭ
3069 cmϪ1, 3018, 2978, 2950, 2935, 2928, 2915, 2879, 2865, 1607,
1541 (NO2), 1503, 1466, 1448, 1388, 1371 (NO2). Ϫ 1H NMR (200
MHz, CDCl3): δ ϭ 7.24 (d, J1,2 ϭ 8.55 Hz, 1 H, 1-H), 6.77 (dd,
J1,2 ϭ 8.55 Hz, J2,4 ϭ 2.70 Hz, 1 H, 2-H), 6.68 (d, J2,4 ϭ 2.56 Hz,
1 H, 4-H), 4.50 (t, J16,17 ϭ 8.82 Hz, 1 H, 17-H), 3.82 (s, 3 H,
OCH3), 2.79Ϫ3.02 (m, 2 H), 2.56Ϫ2.73 (m, 1 H), 2.06Ϫ2.46 (m, 4
H), 1.79Ϫ1.98 (m, 2 H), 1.32Ϫ1.74 (m, 6 H), 0.83 (s, 3 H, 18-H).
Ϫ
13C NMR (50 MHz, CDCl3): δ ϭ 158.04 (s, C-3), 138.08 (s, C-
We thank the Deutsche Forschungsgemeinschaft for financial sup-
port of this work.
5), 132.27 (s, C-10), 126.74 (d, C-1), 114.27 (d, C-4), 112.01 (d, C-
2), 94.87 (d, C-17), 55.65 (q, OCH3), 52.49 (d, C-14), 46.48 (s, C-
13), 43.99 (d, C-9), 39.21 (d, C-8), 37.68 (t, C-6)*, 30.08 (t,
C-16)*, 27.75 (t, C-12)*, 26.80 (t, C-7)*, 25.16 (t, C-11)*, 23.84 (t,
C-15)*, 12.62 (q, C-18). Ϫ C19H25NO3 (315.41): calcd. C 72.35, H
7.99, N 4.44; found C 72.36, H 7.95, N 4.47.
Experimental Section
For general methods and instructions see ref.[30]. Ϫ Interchang-
able assignments in the 13C-NMR spectra are marked by *.
Oxidation of Primary Aliphatic Amines to Nitro Compounds. Ϫ
General Procedure: All reactions were conducted at 22°C under dry
nitrogen in a 100-ml dry two-necked vessel equipped with magnetic
stirring bar, gas inlet and septum. With exception of 7, 8a/8b and
12a/12b all primary amines (see Table 1) were commercially avail-
able and used without further purification. The amino hydrochlo-
rides (2, 4 and 10) were converted to the bases by usual NaOH (2
and 10) or Na2CO3 (4) treatment. The mixture (43:57) of the cis-
and trans-4-tert-butylcyclohexylamines (8a/8b) was obtained by
Schmidt degradation of the commercially available cis/trans-4-tert-
butylcyclohexanecarboxylic acid.[31]
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[6]
H. H. Baer, L. Urbas in The Chemistry of The Nitro and Nitroso
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[7]
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[8]
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[9]
H. O. Larson in The Chemistry of The Nitro and Nitroso Groups,
A solution of the amine (10.0 mmol) in dry CH2Cl2 (20 ml) was
treated successively with freshly activated powdered molecular
Part 1 (Ed.: H. Feuer), Interscience Publishers, New York 1969,
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[10]
E. Keinan, Y. Mazur, J. Org. Chem. 1977, 42, 844Ϫ847.
˚
sieves (3 A, 1.5 g) and Zr(O t-Bu)4 (0.4 ml, 1.0 mmol). After stirring
[11]
F. M. Menger, C. Lee, Tetrahedron Lett. 1981, 22, 1655Ϫ1656.
for 30 min, a solution of TBHP in CH2Cl2 (c ϭ 3.66 mol/l, 16.0
ml, 59 mmol) was added within 2Ϫ5 min. After complete consump-
tion of the starting material (GC control, 1Ϫ8 h, see Table 1) the
reaction was quenched by addition of water (10Ϫ20 ml). The mix-
ture was filtered and the molecular sieves washed carefully with
CH2Cl2 (50 ml). The organic phase was stirred overnight in pres-
ence of a Na2SO3 solution (5%, 50 ml) to reduce the excessive
TBHP. The organic phase was separated, dried (Na2SO4) and puri-
fied by column chromatography on silica gel followed by bulb-to-
bulb destillation or crystallization (for yields and boiling points see
Table 1).
[12]
N. Kornblum, R. J. Clutter, W. J. Jones, J. Am. Chem. Soc. 1956,
78, 4003Ϫ4004.
[13]
W. D. Emmons, J. Am. Chem. Soc. 1957, 79, 5528Ϫ5530.
[14]
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[15] [15a] C. H. Robinson, L. Milewich, P. Hofer, J. Org. Chem. 1966,
[15b]
31, 524Ϫ528. Ϫ
For the oxidation of organonitrogen com-
pounds by the methyltrioxorhenium/hydrogen peroxide system
see: R. W. Murray, K. Iyanar, J. Chen, J. T. Wearing, Tetra-
hedron Lett. 1996, 37, 805Ϫ808. We thank a referee for drawing
our attention to this reference.
[16]
[17]
[18]
R. W. Murray, S. N. Rajadhyaksha, L. Mohan, J. Org. Chem.
1989, 54, 5783Ϫ5788.
R. W. Murray, R. Jeyaraman, L. Mohan, Tetrahedron Lett.
1986, 27, 2335Ϫ2336.
20
3-(Nitromethyl)-cis-pinane (14): [α]D ϭ ϩ19.7 (c ϭ 0.98,
T. L. Gilchrist in Comprehensive Organic Synthesis, vol. 7, (Ed.
B. M. Trost, I. Fleming), Pergamon Press, Oxford 1991, p.
736Ϫ737.
CH2Cl2). Ϫ IR (neat): ν˜ ϭ 2911 cmϪ1, 2873, 1549 (NO2), 1472,
1455, 1431, 1379 (NO2). Ϫ 1H NMR (300 MHz, CDCl3): δ ϭ
4.19Ϫ4.41 (m, 2 H, CH2NO2), 2.49Ϫ2.62 (m, 1 H, 2-H), 2.32Ϫ2.40
(m, 1 H, 7-H), 2.17Ϫ2.27 (m, 1 H, 4-H), 1.93Ϫ1.99 (m, 1 H, 5-H),
[19]
N. Kornblum, H. O. Larson, R. K. Blackwood, D. D. Moob-
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Eur. J. Org. Chem. 1998, 679Ϫ682
681