K. Wimalasena, H. B. Wickman, M. P. D. Mahindaratne
FULL PAPER
N-Benzyl-N-cyclopropyl-N-phenylamine: This compound was syn-
thesized according to the procedure of Chaplinski and de Meijere[7]
with minor modifications. A solution of N-benzylformanilide
J ϭ 3.3, 6.6 Hz, 1 H), 4.10Ϫ4.20 (br. s, 1 H), 6.73 (t, J ϭ 7.3 Hz,
1 H), 6.79 (dd, J ϭ 1.1, 8.4 Hz, 2 H), 7.19 (dd, J ϭ 7.3, 8.4 Hz, 2
H). Ϫ 13C NMR (100.5 MHz): δ ϭ 7.4 (t), 25.2 (d), 113.1 (d), 117.7
(5.1 g, 21.2 mmol) in freshly distilled THF (125 mL) was treated (d), 129.1 (d), 148.7 (s).
with Ti(OiPr)4 (8 mL, 27.1 mmol) and the resulting mixture was
N-(1-Methylcyclopropyl)-N-phenylamine (2a): This compound was
stirred under N2 for 5 min. A 2.0 solution of ethylmagnesium
bromide in THF (20 mL, 40 mmol) was then added dropwise and
the mixture was stirred for 24 h. The reaction was then quenched
by the addition of saturated aqueous ammonium chloride solution
(75 mL). The resulting mixture was filtered and the filtrate was ex-
tracted with CH2Cl2. The combined organic layers were concen-
trated in vacuo and the residue was subjected to chromatography
obtained in 58% yield by catalytic debenzylation of N-benzyl-N-(1-
methylcyclopropyl)-N-phenylamine according to the same proced-
ure as that described above for N-cyclopropyl-N-phenylamine. Ϫ
1H NMR (400 MHz): δ ϭ 0.62 (dd, J ϭ 4.4, 6.2 Hz, 2 H), 0.77
(dd, J ϭ 4.4, 6.2 Hz, 1 H), 1.35 (s, 3 H), 4.09 (br. s, 1 H), 6.69 (tt,
J ϭ 1.1, 7.3 Hz, 1 H), 6.73 (dd, J ϭ 1.1, 8.4 Hz, 2 H), 7.17 (ddd,
J ϭ 1.8, 7.3, 8.4 Hz, 2 H). Ϫ 13C NMR (100.5 MHz): δ ϭ 15.2 (t),
21.7 (q), 30.2 (s), 113.5 (d), 117.1 (d), 129.1 (d), 147.1 (s).
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yielding 3.8 g (80%) of the product. Ϫ H NMR (300 MHz): δ ϭ
0.64Ϫ0.70 (m, 2 H), 0.77Ϫ0.84 (m, 2 H), 2.59 (tt, J ϭ 3.8, 6.5 Hz,
1 H), 4.60 (s, 2 H), 6.73 (t, J ϭ 7.3 Hz, 1 H), 6.92 (d, J ϭ 8.7 Hz,
2 H), 7.12Ϫ7.29 (m, 7 H). Ϫ 13C NMR (75.4 MHz): δ ϭ 8.9 (t),
32.7 (d), 56.2 (t), 113.9 (d), 117.4 (d), 126.3 (d), 126.6 (d), 128.4
(d), 128.8 (d), 139.9 (s), 149.8 (s). Ϫ C16H17N (223.32): calcd. C
86.06, H 7.67; found C 86.27, H 7.72.
N-(trans-2-Methylcyclopropyl)-N-phenylamine (3a): This compound
was obtained in 45% yield by catalytic debenzylation of N-benzyl-
N-(trans-2-methylcyclopropyl)-N-phenylamine according to the
same procedure as that described above for N-cyclopropyl-N-
1
phenylamine. Ϫ H NMR (400 MHz): δ ϭ 0.49 (ddd, J ϭ 5.1, 5.5,
6.6 Hz, 1 H), 0.67 (ddd, J ϭ 3.7, 4.8, 8.8 Hz, 1 H), 0.84 (dddq, J ϭ
2.9, 5.9, 8.8, 6.2 Hz, 1 H), 1.14 (d, J ϭ 6.2 Hz, 3 H), 2.09 (dt, J ϭ
6.6, 3.3 Hz, 1 H), 4.05Ϫ4.15 (br. s, 1 H), 6.70Ϫ6.74 (m, 3 H), 7.18
(dddd, J ϭ 1.1, 1.8, 7.3, 8.1 Hz, 2 H). Ϫ 13C NMR (100.5 MHz):
δ ϭ 15.5 (d), 15.5 (t), 17.1 (q), 33.3 (d), 113.0 (d), 117.5 (d), 129.1
(d), 148.5 (s).
N-Benzyl-N-(1-methylcyclopropyl)-N-phenylamine: This compound
was synthesized according to a procedure analogous to that de-
scribed above for N-benzyl-N-cyclopropyl-N-phenylamine using N-
benzylacetanilide; it was obtained in 40% yield after purification.
Ϫ 1H NMR (400 MHz): δ ϭ 0.96Ϫ0.98 (br. s, 2 H), 0.99Ϫ1.01 (br.
s, 2 H), 1.37 (s, 3 H), 4.51 (br. s, 2 H), 6.68 (t, J ϭ 7.3 Hz, 1 H),
6.80 (dd, J ϭ 1.10, 8.8 Hz, 2 H), 7.12Ϫ7.22 (m, 5 H), 7.24Ϫ7.30
(m, 2 H). Ϫ 13C NMR (100.5 MHz): δ ϭ 18.8 (q), 21.9 (t), 29.7
(t), 38.1 (s), 54.6 (t), 113.7 (d), 116.5 (d), 127.7 (d), 128.5 (d), 128.8
(d), 140.2 (s), 147.8 (s). Ϫ C17H19N (237.34): calcd. C 86.03, H
8.07; found C 86.16, H 8.11.
N-(cis-2-Methylcyclopropyl)-N-phenylamine (4a): This compound
was obtained in 55% yield by catalytic debenzylation of N-benzyl-
N-(cis-2-methylcyclopropyl)-N-phenylamine according to the same
procedure as that described above for N-cyclopropyl-N-
phenylamine. Ϫ 1H NMR (400 MHz): δ ϭ 0.13 (dt, J ϭ 5.5,
4.4 Hz, 1 H), 0.91 (dt, J ϭ 4.8, 7.0 Hz, 1 H), 1.00 (ddpent, J ϭ 6.6,
6.2, 5.9 Hz, 1 H), 1.10 (d, J ϭ 5.9 Hz, 3 H), 2.42 (dt, J ϭ 4.0,
7.0 Hz, 1 H), 3.09Ϫ4.05 (br. s, 1 H), 6.72 (t, J ϭ 7.3 Hz, 1 H), 6.78
(d, J ϭ 8.3 Hz, 2 H), 7.18 (dd, J ϭ 7.3, 8.4 Hz, 2 H). Ϫ 13C NMR
(100.5 MHz): δ ϭ 11.9 (q), 12.5 (t), 13.5 (d), 29.8 (d), 112.9 (d),
117.4 (d), 129.1 (d), 149.1 (s).
N-Benzyl-N-(cis- and trans-2-methylcyclopropyl)-N-phenylamine:
This compound was synthesized as a mixture of cis and trans iso-
mers according to a procedure analogous to that described above
for N-benzyl-N-cyclopropyl-N-phenylamine using propylmagnes-
ium bromide; it was obtained in 68% yield after purification. The
two isomers were separated by column chromatography on silica
gel. Ϫ cis Isomer: 1H NMR (400 MHz): δ ϭ 0.30 (dt, J ϭ 5.9,
4.8 Hz, 1 H), 0.90 (ddd, J ϭ 5.5, 7.3, 8.4 Hz, 1 H), 1.10 (d, J ϭ
5.9 Hz, 3 H), 1.16 (dddq, J ϭ 4.8, 6.5, 8.4, 5.9 Hz, 1 H), 2.61 (ddd,
J ϭ 4.4, 6.6, 7.3 Hz, 1 H), 4.52 (d, J ϭ 17.2 Hz, 1 H), 4.70 (d, J ϭ
16.9 Hz, 1 H), 6.74 (tt, J ϭ 1.1, 7.3 Hz, 1 H), 6.97 (dd, J ϭ 1.1,
7.7 Hz, 2 H), 7.16Ϫ7.30 (m, 7 H). Ϫ 13C NMR (100.5 MHz): δ ϭ
12.7 (q), 13.3 (t), 15.7 (d), 38.3 (d), 56.5 (t), 114.3 (d), 117.5 (d),
126.50 (d), 126.8 (d), 128.3 (d), 139.9 (s), 150.7 (s). Ϫ trans Isomer:
1H NMR (400 MHz): δ ϭ 0.57 (dt, J ϭ 6.6, 5.5 Hz, 1 H), 0.84
(ddd, J ϭ 3.7, 4.8, 8.8 Hz, 1 H), 1.02 (dddq, J ϭ 3.3, 5.9, 8.8,
6.2 Hz, 1 H), 1.16 (d, J ϭ 6.2 Hz, 3 H), 2.28 (dt, J ϭ 6.6, 3.3 Hz,
1 H), 4.54 (d, J ϭ 16.9 Hz, 1 H), 4.62 (d, J ϭ 16.9 Hz, 1 H), 6.73
(tt, J ϭ 1.1, 7.3 Hz, 1 H), 6.85 (dd, J ϭ 1.1, 8.8 Hz, 2 H), 7.14Ϫ7.23
(m, 5 H), 7.24 (m, 2 H). Ϫ 13C NMR (100.5 MHz): δ ϭ 16.6 (q),
16.7 (t), 17.2 (d), 40.7 (d), 55.9 (t), 113.7 (d), 117.2 (d), 126.3 (d),
126.6 (d), 128.4 (d), 128.8 (d), 139.9 (s), 149.7 (s). Ϫ C17H19N
(237.34; analyzed as cis/trans mixture): calcd. C 86.03, H 8.07;
found C 86.19, H 8.07.
Oxidation of N-Cyclopropyl-N-phenylamine and Its Derivatives with
tert-Butyl Peroxide: A solution of N-cyclopropyl-N-phenylamine
(20 mg, 0.15 mmol) and tert-butyl peroxide (50 mg, 0.34 mmol) in
CHCl3 (25 mL) was stirred for 1Ϫ2 h in a vessel open to the atmo-
sphere while irradiating with light of wavelength 254 nm from a 4-
W UV lamp. The solution was subsequently concentrated in vacuo
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and its composition was analyzed by H NMR spectroscopy.
Oxidation of N-Cyclopropyl-N-phenylamine and Its Derivatives with
Benzoyl Peroxide: A solution of N-cyclopropyl-N-phenylamine
(15 mg, 0.11 mmol) and benzoyl peroxide (27.3 mg, 0.11 mmol) in
CHCl3 (10 mL) was stirred in the dark for 45 min in a vessel open
to the atmosphere. The solution was subsequently washed with
aqueous Na2CO3 solution, concentrated in vacuo, and analyzed by
1H NMR spectroscopy.
Oxidation of N-Cyclopropyl-N-phenylamine and Its Derivatives with
Tris(1,10-phenanthroline)iron(III) Hexafluorophosphate: A solution
of N-cyclopropyl-N-phenylamine (25 mg, 0.19 mmol) and a cata-
lytic amount of [(phen)3FeIII](PF6)3 (ca. 1 mg, 0.6 mol %) in CHCl3
(25 mL) was stirred for 1 h in a vessel open to the atmosphere at
room temperature. The solution was subsequently filtered through
N-Cyclopropyl-N-phenylamine (1a): A solution of N-benzyl-N-
cyclopropyl-N-phenylamine (1.0 g) in methanol (200 mL) and gla-
cial acetic acid (1 mL) was hydrogenated (4 bars) for 4 h in the
presence of 10% Pd/C catalyst (100 mg). The reaction mixture was
filtered, concentrated, basified, and extracted with CH2Cl2. Puri-
fication of the crude product by column chromatography on silica
gel yielded 62% of N-cyclopropyl-N-phenylamine (1a). Ϫ 1H NMR
1
a plug of silica, concentrated in vacuo, and analyzed by H NMR
spectroscopy.
N-(1,2-Dioxolan-3-yl)-N-phenylamine (1f): 1H NMR (400 MHz):
(400 MHz): δ ϭ 0.48Ϫ0.52 (m, 2 H), 0.69Ϫ0.74 (m, 2 H), 2.41 (tt, δ ϭ 2.39 (dddd, J ϭ 3.4, 8.1, 8.4, 12.9 Hz, 1 H), 3.05 (dddd, J ϭ
3816 Eur. J. Org. Chem. 2001, 3811Ϫ3817