Synthesis of primary amines and N-methylamines by the electrophilic amination of Grignard reagents with 2-imidazolidinone O-sulfonyloxime

Article abstract of DOI:10.1246/bcsj.76.1063

2-Imidazolidinone O-sulfonyloxime reacts with various aryl and alkyl Grignard reagents as an electrophilic amination reagent, giving N-alkylated imines. The resulting imines are transformed to primary amines and N-methyl secondary amines by hydrolysis with CsOH and LiAlH₄ reduction, respectively.

Full text of DOI:10.1246/bcsj.76.1063

Ó 2003 The Chemical Society of Japan
Bull. Chem. Soc. Jpn., 76, 1063–1070 (2003) 1063
Synthesis of Primary Amines and N-Methylamines by the Electrophilic
Amination of Grignard Reagents with 2-Imidazolidinone O-Sulfonyl-
oxime
ꢀ
Mitsuru Kitamura, Shunsuke Chiba, and Koichi Narasaka
Department of Chemistry, Graduate School of Science, The University of Tokyo,
7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033
(Received December 9, 2002)
2-Imidazolidinone O-sulfonyloxime reacts with various aryl and alkyl Grignard reagents as an electrophilic amina-
tion reagent, giving N-alkylated imines. The resulting imines are transformed to primary amines and N-methyl second-
ary amines by hydrolysis with CsOH and LiAlH4 reduction, respectively.
In general, primary amines are prepared by reduction of the
corresponding nitro compounds,1a imines,1b and azides.1c Al-
kylation of nucleophilic amination reagents such as phthali-
mide and trifluoroacetamide is another common method for
preparation of amino compounds,2 whereas this method cannot
be applied for the synthesis of aminoarene. Recently, a transi-
tion metal-mediated amination method has been developed,
and this is now regarded as an efficient method for the prepara-
tion of arylamines.3 While electrophilic amination has pro-
vided an alternative method,4 this has rarely been utilized in
organic synthesis, because electrophilic amination reagents
such as chloramine and O-sulfonylhydroxylamine derivatives
are not stable enough and not easy to handle due to their high
reactivity.5 Recently several electrophilic amination reactions
such as N-metal hydroxylamine derivatives,6 dialkyl
azodicarboxylates,7 oxaziridines,8 and some oxime de-
rivatives9 have been reported.
This particular benzophenone oxime 1 was designed to meet
the following conditions. There is no ꢀ-hydrogen to prevent
Neber reaction,11 and trifluoromethyl groups are introduced
to suppress Beckmann rearrangement.12 To apply this method
to the preparation of primary amines, it was desired to employ
simple oximes without bulky substituents like 3,5-bis(trifluor-
omethyl)phenyl group.
Since oximes of ureas and carbonates rarely undergo Beck-
mann rearrangement and Neber reaction, O-sulfonyl deriva-
tives of these compounds were employed for electrophilic
amination. We found that 1,3-dimethyl-2-imidazolidinone
O-sulfonyloxime reacted smoothly with Grignard reagents,
and the resulting N-alkylated imines were transformed to pri-
mary amines and secondary methylamines. In this paper, full
accounts of these results are described.
Results and Discussion
Recently, we have reported substitution reactions on oxime
nitrogen. One of the typical reaction is the electrophilic ami-
nation of Grignard reagents with benzophenone oxime
derivatives.10 For example, bis[3,5-bis(trifluoromethyl)phe-
nyl] ketone O-tosyloxime (1) reacts with aryl and alkyl
Grignard reagents at room temperature to give the correspond-
ing imines, which are hydrolyzed to afford primary amines
(Eq. 1).
The reactions of phenyl Grignard reagent with O-sulfony-
loximes of ureas and carbonates were screened. In the reaction
with diethyl carbonate O-tosyloxime (2)13 and phenylmagne-
sium bromide in toluene, the Grignard reagent attacked either
oxime carbon or the nitrogen atom to give a mixture of 3a–c
and 2 (Eq. 2).
ð2Þ
ð1Þ
Cyclic O-sulfonyloximes such as 2-imidazolidinone O-tosy-
loxime 4, 1,3-dioxolan-2-one O-tosyloxime (5), and 2-oxazoli-
dinone O-tosyloxime 6 were prepared as described in the
Scheme 1. Imidazolidinone oxime 4 was prepared from 2-
chloro-1,3-dimethyl-1-imidazolinium chloride (7)14 and O-tet-

1064 Bull. Chem. Soc. Jpn., 76, No. 5 (2003)
Electrophilic Amination by Using Oximes
Table 2. Transformation of Imine 10a, 11 to Amines
Yield/%
Run
1
X
Conditions
14a
95a)
15a
NMe 10a
0
CsOH H2O, ethylene glycol
ꢁ ꢂ
150 C, 1 h; HCl/Et2O
2
3
NMe 10a LiAlH4, Et2O, THF, rt, 12 h
NMe 10a
0
50c)
93b)
38c)
DIBAL-H, CH2Cl2
ꢁ
ꢃ78 C!rt, 12 h
1 M HCl, MeOH
rt, 30 min
4
O
11
41c),d)
0
a) Isolated as a HCl salt. b) Isolated yield. c) NMR yield. d)
2 steps yield from 5 [amination (Table 1, Run 4) and hydroly-
sis].
Scheme 1. Preparation of cyclic O-tosyloximes 4–6. a)
NaNO2, AcOH, H2O. b) TsCl, Pyridine; HO(CH2)2OH,
NaH. c) BnBr, Et3N; HO(CH2)2NHMe, NaH; H2,
Pd(OH)2-C; TsCl, Et3N.
lan-2-one oxime 5 was insoluble in toluene and less reactive
as compared to 2-imidazolidinone oxime 4, the reaction of
which with phenylmagnesium bromide in toluene gave imine
11 in 66% yield with the recovery of 19% of the starting ma-
terial 5 (run 3). By the reaction in CH2Cl2 in which 1,3-diox-
olan-2-one oxime 5 was completely soluble, 5 was consumed
within 1 h, but the yield of N-phenylimine 11 was 66%. (Z)-N-
Methyloxazolidinone O-sulfonyloxime 6 was scarcely soluble
in toluene, but the reaction with phenylmagnesium bromide in
toluene yielded the corresponding imine 1217 in high yield
(97%, run 5). Strangely in the reaction of stereoisomer (E)-
N-methyloxazolidinone oxime 6, Grignard reagent attacked
the oxime carbon instead of the nitrogen to yield amidoxime
13 in 70% yield (run 6).
Then, the transformations of the resulting imines to amines
were investigated under various conditions as shown in Table
2. The hydrolysis of 10a under acidic conditions failed. Treat-
ment of 10a with various hetero nucleophiles such as
NH2NH2, H2O2 under neutral or basic conditions, did not give
the desired amine 14a at all. Imidazolidinone imine 10a was
Table 1. Reaction of PhMgBr with Cyclic Oximes 4–6
Run
X
Y
Solvent Conditions
ꢁ
Yield/%
toluene 0 C, 15 min 10a 98a)
1
2
3
4
5
6
NMe NMe
NMe NMe
O
O
NMe
O
4
4
5
5
ꢁ
0 C, 2 days 10a 92b),c)
THF
toluene 0 C, 1 h
ꢁ
ꢁ
O
O
O
11 66b),d)
11 66b)
CH2Cl2 0 C, 1 h
(Z)-6 toluene rt,ꢁ30 min
12 97a),e)
NMe (E)-6 CH2Cl2 0 C, 30 min 12
0f)
a) Isolated yield. b) NMR yield. c) 4 was recovered in 6%
yield. d) 5 was recovered in 19% yield. e) See Ref. 17. f)
13 was isolated in 70% yield.
hydrolyzed by the treatment of CsOH H2O in ethylene glycol
ꢁ
ꢂ
at 150 C for 1 h to give aniline (14a) in 95% yield (run 1).
The reduction of 10a proceeded smoothly with LiAlH4, and
N-methylaniline (15a) was obtained as the sole product in
93% yield (run 2), whereas diisobutylaluminum hydride (DI-
BAL-H) reduction gave a mixture of aniline (14a) and N-
methylaniline (15a) (run 3). The results show that imines
formed by the reaction of 4 with Grignard reagents could be
selectively transformed to primary amines or monomethyl sec-
ondary amines.18 The imine 11 was hydrolyzed under acidic
conditions to give aniline (14a) in moderate yield (run 4).
Although imine 11 was hydrolyzed more easily under acidic
conditions as compared with imine 10a, the yield of imine
11 (66%) could not be improved (vide supra). The hydrolysis
of 12 was as difficult as that of 10a. Thus, it was concluded
that 2-imidazolidinone oxime 4 is most suitable for electrophi-
lic amination among 4–6, and we examined further by using 4
or its addition product 10.
rahydropyranylhydroxylamine15 by 3 steps.16 It was stable en-
ough to be stored at least for 3 months at 0 ꢁC. 1,3-Dioxolan-2-
one oxime 5 and 2-oxazolidinone oxime 6 were synthesized
from malononitrile (8) according to a modified literature
procedure.13
The results of the reactions of phenylmagnesium bromide
and cyclic urea and carbonate O-sulfonyloximes 4–6 are sum-
marized in Table 1. 2-Imidazolidinone O-tosyloxime 4 re-
acted smoothly with an equimolar amount of phenylmagne-
ꢁ
sium bromide (Et2O solution) in toluene at 0 C, giving N-
phenylimine 10a in 98% yield (run 1). In THF, the reaction
became much slower (run 2). Thus, 2-imidazolidinone oxime
4 was found to be more reactive in toluene as compared to
bis[3,5-bis(trifluoromethyl)phenyl] ketone oxime 1, the reac-
tion of which proceeded at room temperature.10 1,3-Dioxo-
The results of the amination of various Grignard reagents
with 4 are listed in Table 3. 2-Imidazolidinone O-tosyloxime

M. Kitamura et al.
Bull. Chem. Soc. Jpn., 76, No. 5 (2003) 1065
Table 3. Preparation of Various Primary Amines 14 and Mono-N-methylamines 15 by the Reaction of 4 with Grignard Reagents
Yield/%
14c)
Run
RMgBr
Conditions 1
Conditions 2
10b)
15c)
ꢁ
1
2
0 C, 15 min
rt, 12 h
rt, 12 h
10a
10b
98
99
14a
14b
95
98
15a
15b
93
81
ꢁ
0 C–rt, 30 min
ꢁ
3
4
0 C, 15 min
reflux, 8 h
10c
10d
96
85
14c
14d
36d),e)
0f)
15c
15d
89
ꢁ
0 C–rt, 30 min
reflux, 24 h
0f)
ꢁ
5
6
0 C–rt, 30 min
reflux, 3 h
rt, 12 h
10e
10f
96
88
14e
14f
55g)
0h)
15e
15f
70
0i)
ꢁ
0 C, 15 min
ꢁ
7
0 C, 30 min
reflux, 9 h
10g
> 99
14g
84d)
15g
92
ꢁ
8
9
0 C, 15 min
reflux, 1.5 h
rt, 12 h
10h
10i
84
94
14h
14i
0f)
93
15h
15i
68j)
73
ꢁ
ꢃ78 C, 15 min
ꢁ
10
ꢃ78 C, 15 min
rt, 12 h
10j
96
14j
96
15j
84
ꢁ
k)
11
12
ꢃ78 C, 15 min
reflux, 24 h
10k
10l
—
14k
14l
71
0
15k
55d),l)
ꢁ
m)
ꢃ78 C, 15 min
—
a) Oxime: Grignard reagent = 1:1. b) Isolated yield. c) Isolated yield (2 steps from 4). d) NMR yield. e) Hydrolysis was carried out
for 7.5 h, and 50% of imine 10c was recovered. f) Imine 10 was recovered. g) Hydrolysis was carried out for 3 h. h) See Eq. 3. i) A
mixture of 16 was isolated. j) 2-Aminothiophene 14h was isolated in 2%. When the reaction was carried out at room temperature for
12 h, 2-methylaminothiophene 15h and 2-aminothiophene 14h were obtained in 63% and 15%, respectively. k) Imine 10k was not
isolated. l) Imine 10k was recovered in 15%. m) Imine 10l is detected to be formed in low yield (< 8%) by NMR, but could not be
isolated and characterized.
ð3Þ
ꢁ
4 reacted with aryl Grignard reagents smoothly at 0 C–room
temperature (run 1–8), even with sterically hindered 2,6-di-
methylphenylmagnesium bromide, giving the corresponding
N-arylimines in high yields. The resulting imines 10, except
2,6-dimethylphenylimine 10d and p-trifluoromethylphenyli-
mine 10f, were hydrolyzed with CsOH to anilines and/or re-
duced with LiAlH4 to N-methylanilines. The difficulty of
the hydrolysis of 2,6-dimethylphenylimine 10d is due to the
sterical hindrance. 2-Thienyl Grignard reagent also reacted
with 4 to give imine 10h, which was converted to 2-N-methy-

1066 Bull. Chem. Soc. Jpn., 76, No. 5 (2003)
Electrophilic Amination by Using Oximes
with dichloromethane. The combined extracts were washed with
brine and dried over anhydrous sodium sulfate. The dichloro-
methane was removed in vacuo, and the crude materials were pur-
ified by flash column chromatography (silica gel; hexane/acetone
= 7/3) to give 1,3-dimethyl-2-imidazolidinone O-tetrahydropyra-
nyloxime (15.5 g, 88%). Colorless oil; 1H NMR (500 MHz,
CDCl3) ꢁ 1.52–1.68 (4H, m), 1.75–1.81 (2H, m), 2.65 (3H, s),
3.16 (3H, s), 3.05–3.22 (4H, m), 3.58–3.63 (1H, m), 3.92–3.97
(1H, m), 4.93–4.95 (1H, m); 13C NMR (125 MHz, CDCl3) ꢁ
20.3, 25.4, 29.3, 34.8, 38.1, 49.5, 51.2, 62.8, 100.8, 158.2.
laminothiophene 15h in 68% yield, but was not hydrolyzed at
all and 10h was recovered (run 7).
As compared with aryl Grignard reagents, alkyl Grignard
ꢁ
reagents reacted with 4 at lower temperature, ꢃ78 C, within
15 min, giving N-alkylimines 10 in high yields, regardless of
the primary, secondary, or tertiary alkyl Grignard reagents ex-
cept tert-butylmagnesium bromide (run 9–12). Hydrolysis un-
der alkali conditions and the reduction with LAH of primary
and secondary-alkylimines 10 proceeded in high yields (run
9, 10), whereas the yield of adamantylamine was moderate
(run 11).
1,3-Dimethyl-2-imidazolidinone Oxime: To a solution of
1,3-dimethyl-2-imidazolidinone O-tetrahydropyranyloxime (15.5
g, 72.7 mmol) in methanol (50 mL) was added 1.0 M HCl (75
mL, 75 mmol), and this mixture was stirred at 80 ꢁC for 30
min. After the reaction was quenched with 1.0 M NaOH (100
mL, 100 mmol) at 0 ꢁC, the mixture was extracted five times with
dichloromethane and washed with brine. The extracts were dried
over anhydrous sodium sulfate, and the dichloromethane was re-
moved in vacuo to give 1,3-dimethyl-2-imꢁidazolidinone oxime
(7.7 g, 82%). White powder; mp 121–122 C; IR (ZnSe) 3249,
3176, 2940, 2867, 1664, 1497, 1438, 1390, 1288, 1039, 971,
In conclusion, various primary amines and N-methyl sec-
ondary amines are prepared by the reaction of 2-imidazolidi-
none O-tosyloxime with aryl and alkyl Grignard reagents
and the successive hydrolysis and LiAlH4 reduction, respec-
tively.
Experimental
General. 1H NMR (500 and 270 MHz) spectra were recorded
on Bruker DRX 500, Bruker AVANCE 500, and JEOL AL 270
spectrometers in CDCl3 [using tetramethylsilane (for 1H, ꢁ ¼ 0)
as internal standard] or DMSO-d6 [using DMSO (for 1H,
ꢁ ¼ 2:49) as internal standard]. 13C NMR (125 and 67.5 MHz)
spectra were recorded on Bruker DRX 500, Bruker AVANCE
500, and JEOL AL 270 spectrometers in CDCl3 [using CHCl3
(for 13C, ꢁ ¼ 77:00) as internal standard] or DMSO-d6 [using
DMSO (for 13C, ꢁ ¼ 39:70) as internal standard]. IR spectra were
recorded on a Horiba FT 300-S by ATR method. High-resolution
mass spectra were obtained with a JEOL MS-700P mass
spectrometer. The melting points were uncorrected. Elemental
analyses were carried out at The Elemental Analysis Laboratory,
Department of Chemistry, Faculty of Science, the University of
Tokyo. Flash column chromatography was performed on silica
gel [Kanto Chemical Co., Inc. Silica gel 60N (spherical, neutral)]
and preparative thin-layer chromatography was carried out using
Wakogel B-5F. Tetrahydrofuran (THF) and diethyl ether (Et2O)
were purchased from Kanto Chemical Co., Inc and used without
purification. Toluene was distilled, and water was azeotropically
removed. Dichloromethane was distilled twice from P2O5 then
from CaH2, and stored over molecular sieves 4A. Triethylamine
was distilled from CaH2 and stored over KOH. 2-Chloro-1,3-di-
methyl-1-imidazolinium chloride was purchased from Nacalai
Tesque, Inc., Japan. t-Butylmagnesium chloride was purchased
from Aldrich Chemical Co., Inc., and was titrated by the literature
procedure.19 Phenylmagnesium bromide, 1-naphthylmagnesium
bromide, 2-methylphenylmagnesium bromide, 2,6-dimethylphe-
nylmagnesium bromide, 2-methoxyphenylmagnesium bromide,
2,4-dimethoxyphenylmagnesium bromide, 4-trifluoromethylphe-
nylmagnesium bromide, 2-thienylmagnesium bromide, phenethyl-
magnesium bromide, 1-methyl-3-phenylpropylmagnesium bro-
mide, and 1-adamantylmagnesium bromide20 were prepared
according to the references and titrated by the literature
procedure.19
927, 761, 688 cmꢃ1 1H NMR (500 MHz, CDCl3) ꢁ 2.60 (3H,
;
s), 3.13–3.17 (4H, m), 3.18 (3H, s), 7.79 (1H, br); 13C NMR
(125 MHz, CDCl3) ꢁ 34.5, 37.6, 49.5, 51.1, 157.5; Anal. Found:
C, 46.42; H, 8.58; N, 32.50%. Calcd for C5H11N3O: C, 46.50;
H, 8.58; N, 32.53%.
1,3-Dimethyl-2-imidazolidinone O-p-Tosyloxime (4): To an
ice cold solution of 1,3-dimethyl-2-imidazolidinone oxime (2.02
g, 15.7 mmol) and triethylamine (7.0 mL, 50.2 mmol) in dichlor-
omethane (20 mL) was slowly added p-toluenesulfonyl chloride
(3.06 g, 16.1 mmol), and this mixture was stirred at the same tem-
perature for 10 min. After the reaction was quenched with water,
the mixture was extracted three times with ethyl acetate. The
combined extracts were washed with brine and dried over anhy-
drous sodium sulfate. The ethyl acetate was removed in vacuo,
and the crude materials were purified by flash column chromato-
graphy (silica gel; hexane/acetone = 7/3) to give 1,3-dimethyl-2-
imidazolidinone O-tosyloxime (4.21 g, 95%). White powder; mp
ꢁ
70–75 C (dec.); IR (ZnSe) 2950, 2857, 1596, 1494, 1353, 1292,
1
1172, 1095, 1037, 875, 825, 757, 665 cmꢃ1; H NMR (500 MHz,
CDCl3) ꢁ 2.44 (3H, s), 2.57 (3H, s), 3.13 (3H, s), 3.16 (2H, t, J ¼
7:7 Hz), 3.24 (2H, t, J ¼ 7:7 Hz), 7.31 (2H, d, J ¼ 8:2 Hz), 7.87
(2H, d, J ¼ 8:2 Hz); 13C NMR (125 MHz, CDCl3) ꢁ 21.5, 33.6,
37.2, 48.7, 51.0, 128.8, 129.1, 132.6, 144.1, 161.6; Anal. Found:
C, 50.86; H, 5.95; N, 14.87%. Calcd for C12H17N3O3S: C,
50.87; H, 6.05; N, 14.83%.
Typical Procedure for the Preparation of Imine by the Re-
action of 2-Imidazolidinone Oxime 4 with Grignard Reagents
(Table 1, Run 1): To a solution of 1,3-dimethyl-2-imidazolidi-
none O-tosyloxime (4, 843 mg, 2.98 mmol) in toluene (20 mL)
was added dropwise an ether solution of phenylmagnesium bro-
ꢁ
mide (1.00 M, 3.0 mL) at 0 C under an argon atmosphere, and
this mixture was stirred at the same temperature foꢁr 15 min. After
the reaction was quenched with pH 9 buffer at 0 C, the mixture
was extracted three times with ethyl acetate, and the combined ex-
tracts were washed with brine. The solution was dried over anhy-
drous sodium sulfate, and the ethyl acetate was removed in vacuo.
To the crude imine was added aqueous 1.0 M HCl (5 mL, 5
mmol), and the mixture was washed with ether. To the aqueous
layer was added 1.0 M NaOH (8 mL, 8 mmol), and the mixture
was extracted twice with dichloromethane. The combined ex-
tracts were washed with brine and dried over anhydrous sodium
1,3-Dimethyl-2-imidazolidinone
O-Tetrahydropyranyl-
oxime: To a solution of O-tetrahydropyranylhydroxylamine15
(10.2 g, 87.2 mmol) and triethylamine (35.0 mL, 251 mmol) in
acetonitrile (75 mL) was slowly added 2-chloro-1,3-dimethyl-1-
imidazolinium chloride (14.1 g, 83.1 mmol) in acetonitrile (75
mL) at ꢃ20 ꢁC under an argon atmosphere, and this mixture
was stirred at room temperature for 30 min. After the reaction
was quenched with water, the mixture was extracted three times

M. Kitamura et al.
Bull. Chem. Soc. Jpn., 76, No. 5 (2003) 1067
sulfate; then the dichloromethane was removed in vacuo to give
1,3-dimethyl-2-(phenylimino)imidazolidine (10a, 553 mg, 98%).
Spectral Data. 1,3-Dimethyl-2-(phenylimino)imidazolidine
(10a): Pale yellow oil; IR (ZnSe) 2937, 2850, 1629, 1581, 1479,
1390, 1270, 1226, 1031, 966, 775, 692 cmꢃ1; 1H NMR (500 MHz,
CDCl3) ꢁ 2.64 (6H, s), 3.28 (4H, s), 6.84 (1H, t, J ¼ 7:4 Hz), 6.87
(2H, d, J ¼ 7:4 Hz), 7.17 (2H, t, J ¼ 7:4 Hz); 13C NMR (125
MHz, CDCl3) ꢁ 35.4, 48.6, 120.1, 122.5, 128.5, 150.0 155.8;
Anal. Found: C, 69.82; H, 8.10; N, 22.06%. Calcd for C11H15N3:
C, 69.81; H, 7.99; N, 22.20%.
m=z 240.1467. Calcd for C15H18N3: (M + H)þ, 240.1501.
1,3-Dimethyl-2-(2-thienylimino)imidazolidine (10h): Pale
purple oil; IR (ZnSe) 3396, 3062, 2937, 2854, 1635, 1496,
1
1440, 1276, 1139, 1025, 966, 844, 806, 786, 667 cmꢃ1; H NMR
(500 MHz, CDCl3) ꢁ 2.74 (6H, s), 3.30 (4H, s), 6.21 (1H, dd,
J ¼ 3:3, 0.8 Hz), 6.63 (1H, dd, J ¼ 5:0, 0.8 Hz), 6.72 (1H, dd,
J ¼ 5:0, 3.3 Hz); 13C NMR (125 MHz, CDCl3) ꢁ 35.0, 48.4,
112.9, 114.7, 125.5, 154.9, 157.0; Anal. Found: C, 55.46; H,
6.83; N, 21.38%. Calcd for C9H13N3S: C, 55.35; H, 6.71; N,
21.52%.
1,3-Dimethyl-2-(2-methoxyphenylimino)imidazolidine
(10b): Pale yellow oil; IR (ZnSe) 2937, 2834, 1635, 1583, 1484,
1,3-Dimethyl-2-(phenethylimino)imidazolidine (10i): Pale
yellow oil; IR (ZnSe) 2931, 2834, 1652, 1481, 1436, 1382,
;
1353, 1263, 1022, 956, 748, 723, 698 cmꢃ1 1H NMR (500
1436, 1390, 1276, 1234, 1110, 1024, 966, 740, 694, 646 cmꢃ1
;
1H NMR (500 MHz, CDCl3) ꢁ 2.64 (6H, s), 3.27 (4H, s), 3.82
(3H, s), 6.78–6.85 (4H, m); 13C NMR (125 MHz, CDCl3) ꢁ
34.9, 48.5, 55.6, 110.9, 120.6, 120.8, 123.3, 139.4, 151.8, 155.8;
FABHRMS Found: m=z 220.1448. Calcd for C12H18ON3: (M
+ H)þ, 220.1450.
1,3-Dimethyl-2-(2-methylphenylimino)imidazolidine (10c):
Pale yellow oil; IR (ZnSe) 2937, 2844, 2362, 1635, 1590, 1479,
1436, 1388, 1276, 1228, 1027, 966, 769, 728, 647 cmꢃ1; 1H NMR
(500 MHz, CDCl3) ꢁ 2.15 (3H, s), 2.59 (6H, s), 3.25 (4H, s), 6.77–
6.82 (2H, m), 7.02 (1H, t, J ¼ 7:5 Hz), 7.06 (1H, d, J ¼ 7:5 Hz);
13C NMR (125 MHz, CDCl3) ꢁ 18.5, 35.0, 48.6, 120.5, 122.4,
125.9, 129.6, 129.7, 148.6, 154.2; Anal. Found: C, 70.99; H,
8.44; N, 20.55%. Calcd for C12H17N3: C, 70.90; H, 8.43; N,
20.67%.
MHz, CDCl3) ꢁ 2.79 (6H, br), 2.86 (2H, t, J ¼ 7:9 Hz), 3.14
(4H, s), 3.60 (2H, t, J ¼ 7:9 Hz), 7.16–7.20 (1H, m), 7.25–7.29
(4H, m); 13C NMR (125 MHz, DMSO-d6, 80 ꢁC) ꢁ 35.5 (br),
39.4, 48.3, 48.6 (br), 125.1, 127.5, 128.5, 141.1, 155.4; Anal.
Found: C, 71.63; H, 8.79; N, 19.16%. Calcd for C13H19N3: C,
71.85; H, 8.81; N, 19.34%.
1,3-Dimethyl-2-(1-methyl-3-phenylpropylimino)imidazoli-
dine (10j): Pale yellow oil; IR (ZnSe) 2923, 2844, 1652, 1479,
1452, 1378, 1259, 1197, 1035, 746, 698, 636 cmꢃ1; 1H NMR (500
MHz, CDCl3) ꢁ 1.18 (3H, d, J ¼ 6:2 Hz), 1.65–1.68 (2H, m), 2.55
(1H, ddd, J ¼ 14:5, 9.3, 6.6 Hz), 2.68 (1H, ddd, J ¼ 14:5, 9.3, 6.6
Hz), 2.77 (6H, br), 3.20–3.26 (2H, m), 3.02–3.08 (2H m), 3.66
(1H, ddq, J ¼ 6:2, 6.2, 6.2 Hz), 7.15 (1H, t, J ¼ 7:3 Hz), 7.19
(2H, d, J ¼ 6:9 Hz), 7.25 (2H, dd, J ¼ 7:3, 6.9 Hz); 13C NMR
ꢁ
1,3-Dimethyl-2-(2,6-dimethylphenylimino)imidazolidine
(10d): Pale yellow crystals; mp 65–66 ꢁC; IR (ZnSe) 2935, 2844,
1652, 1587, 1482, 1434, 1386, 1274, 1238, 1029, 966, 757, 713,
(125 MHz, DMSO-d6, 80 C) ꢁ 23.6, 32.1, 35.7 (br), 41.8, 48.2,
48.6 (br), 124.9, 127.7, 127.9, 142.7; FABHRMS Found: m=z
246.1990. Calcd for C15H24N3: (M+H)þ, 246.1970.
1,3-Dimethyl-2-(1-adamantylimino)imidazolidine (10k):
1H NMR (500 MHz, CDCl3) ꢁ 1.67 (6H, s), 2.03 (6H, s), 2.14 (3H,
s), 3.22 (6H, s), 3.75 (4H, s); 13C NMR (125 MHz, CDCl3) ꢁ 29.7,
35.6, 37.5, 43.5, 48.5, 58.4, 161.8.
622 cmꢃ1
;
1H NMR (500 MHz, CDCl3) ꢁ 2.13 (6H, s), 2.56
(6H, s), 3.22 (4H, s), 6.73 (1H, t, J ¼ 7:4 Hz), 6.93 (1H, d,
J ¼ 7:4 Hz); 13C NMR (125 MHz, CDCl3) ꢁ 18.9, 34.4, 48.6,
120.4, 127.2, 129.3, 147.2, 152.8; Anal. Found: C, 71.76; H,
8.69; N, 19.17%. Calcd for C13H19N3: C, 71.85; H, 8.81; N,
19.34%.
Typical Procedure for the Preparation of Amine Hydro-
chloride by the Reaction of Imidazolidinone Oxime 4 with
Grignard Reagents (Table 2, Run 1): To a solution of 1,3-di-
methyl-2-imidazolidinone O-tosyloxime (4, 283 mg, 1.00 mmol)
in toluene (8 mL) was added dropwise an ether solution of phenyl-
1,3-Dimethyl-2-(2,4-dimethoxyphenylimino)imidazolidine
(10e): Pale yellow oil; IR (ZnSe) 2937, 2832, 1633, 1498, 1488,
1434, 1390, 1274, 1199, 1151, 1122, 1025, 966, 829, 713, 636
1
ꢁ
cmꢃ1; H NMR (500 MHz, CDCl3) ꢁ 2.63 (6H, s), 3.24 (4H, s),
magnesium bromide (1.00 M, 1.0 mL) at 0 C under an argon at-
3.77 (3H, s), 3.80 (3H, s), 6.37 (1H, dd, J ¼ 8:5, 2.7 Hz), 6.43
(1H, d, J ¼ 2:7 Hz), 6.73 (1H, d, J ¼ 8:5 Hz); 13C NMR (125
MHz, CDCl3) ꢁ 34.9, 48.6, 55.4, 55.6, 110.9, 120.6, 120.8,
123.3, 139.4, 151.8, 155.8; FABHRMS Found: m=z 250.1556.
Calcd for C13H20N3O2: (M + H)þ, 250.1556.
mosphere, and this mixture was stirred at the same temperature for
15 min. After the reaction was quenched with pH 9 buffer at 0 ꢁC,
the mixture was extracted three times with ethyl acetate, and the
combined extracts were washed with brine. The solution was
dried over anhydrous sodium sulfate, and the ethyl acetate was re-
moved in vacuo. The crude imine was dissolved in ethylene gly-
col (3 mL); then cesium hydroxide monohydrate (1.52 g, 9.05
mmol) was added to the solution. After the suspension was stirred
at 150 ꢁC for 1 h under an argon atmosphere, the mixture was
1,3-Dimethyl-2-(4-trifluoromethylphenylimino)imidazoli-
dine (10f): Pale yellow oil; IR (ZnSe) 2940, 2861, 1639, 1585,
1317, 1278, 1153, 1097, 1058, 1029, 968, 840, 728, 701 cmꢃ1
;
1H NMR (500 MHz, CDCl3) ꢁ 2.66 (6H, s), 3.33 (4H, s), 6.90
(2H, d, J ¼ 8:4 Hz), 7.40 (2H, d, J ¼ 8:4 Hz); 13C NMR (125
MHz, CDCl3) ꢁ 35.3, 48.5, 121.4 (q, J ¼ 32 Hz), 122.0, 125.0
(q, J ¼ 269 Hz), 125.7 (q, J ¼ 4 Hz), 153.8, 156.6; Anal. Found:
C, 56.25; H, 5.64; N, 16.27%. Calcd for C12H14F3N3: C, 56.03; H,
5.49; N, 16.33%.
ꢁ
cooled to 0 C. After 4.0 M HCl (3 mL, 12.0 mmol) was added
to the solution, the mixture was extracted with ether. To the aqu-
eous phase was added 2.0 M NaOH (2 mL, 4.0 mmol) and the
mixture was extracted twice with dichloromethane. The com-
bined extracts were washed with brine and dried over anhydrous
magnesium sulfate. After the dichloromethane was removed in
vacuo, the resulting crude materials were dissolved in ether (3
mL). To the solution was added 2.0 M HCl in ether (1.0 mL,
2.0 mmol) to form a white precipitate, which was collected by fil-
tration to give aniline hydrochloride (14a, 123 mg, 95%).
Spectral Data. o-Toluidine and Naphthylamine are known
compounds, and their spectral data are in good agreement with
those of authentic samples.21
1,3-Dimethyl-2-(1-naphthylimino)imidazolidine (10g): Pale
yellow oil; IR (ZnSe) 3046, 2937, 2844, 1623, 1567, 1482, 1386,
1276, 1226, 1139, 1072, 1024, 962, 773, 696, 653 cmꢃ1; 1H NMR
(500 MHz, CDCl3) ꢁ 2.59 (6H, s), 3.31 (4H, s), 6.90 (1H, d, J ¼
7:4 Hz), 7.31 (1H, dd, J ¼ 7:4, 7.4 Hz), 7.37–7.43 (3H, m), 7.76
(1H, d, J ¼ 7:4 Hz), 8.09 (1H, d, J ¼ 7:4 Hz), 13C NMR (125
MHz, CDCl3) ꢁ 35.0, 48.6, 116.6, 120.2, 124.4, 124.6, 125.5,
126.0, 127.6, 129.0, 134.3, 146.8, 155.1; FABHRMS Found:

1068 Bull. Chem. Soc. Jpn., 76, No. 5 (2003)
Electrophilic Amination by Using Oximes
Aniline Hydrochloride (14a):21
White powder; 1H NMR
umn chromatography (silica gel, hexane/ethyl acetate = 9/1) to
give 2-methoxy-N-methylaniline (15b, 111 mg, 81%).
Spectral Data. N-Methylaniline (15a):21 Pale yellow oil;
1H NMR (500 MHz, CDCl3) ꢁ 2.83 (3H, s), 3.68 (1H, br), 6.61
(2H, dd, J ¼ 8:5, 0.8 Hz), 6.71 (1H, tt, J ¼ 7:3, 0.8 Hz), 7.19
(2H, dd, J ¼ 8:5, 7.3 Hz); 13C NMR (125 MHz, CDCl3) ꢁ 30.7,
112.4, 117.2, 129.2, 149.3.
(500 MHz, DMSO-d6) ꢁ 7.36–7.39 (3H, m), 7.47 (2H, t,
J ¼ 7:5 Hz), 10.37 (3H, br); 13C NMR (125 MHz, DMSO-d6) ꢁ
123.3, 128.0, 129.9, 132.5; Anal. Found: C, 55.67; H, 6.38; N,
10.76%. Calcd for C6H8ClN: C, 55.61; H, 6.22; N, 10.81%.
2-Methoxyaniline Hydrochloride (14b): White powder; mp
228–230 ꢁC (dec.); IR (ZnSe) 2794, 2618, 2360, 1629, 1496,
1324, 1294, 1263, 1025, 643 cmꢃ1
;
1H NMR (500 MHz,
2-Methoxy-N-methylaniline (15b):
(ZnSe) 3432, 2892, 2813, 1606, 1585, 1513, 1471, 1301, 1263,
Pale yellow oil; IR
DMSO-d6) ꢁ 3.82 (3H, s), 6.99 (1H, dd, J ¼ 7:6, 7.5 Hz), 7.16
(1H, d, J ¼ 8:2 Hz), 7.34 (1H, dd, J ¼ 8:2, 7.6 Hz), 7.53 (1H,
d, J ¼ 7:5 Hz), 10.35 (3H, br); 13C NMR (125 MHz, DMSO-d6)
ꢁ 56.4, 112.8, 120.7, 121.0, 124.5, 129.7, 152.7; Anal. Found:
C, 52.87; H, 6.35; N, 8.54%. Calcd for C7H10ClNO: C, 52.67;
H, 6.31; N, 8.78%.
1
1166, 1043, 742 cmꢃ1; H NMR (500 MHz, CDCl3) ꢁ 2.86 (3H,
s), 3.84 (3H, s), 4.23 (1H, br), 6.60 (1H, dd, J ¼ 7:7, 1.0 Hz),
6.67 (1H, ddd, J ¼ 7:7, 7.7, 1.0 Hz), 6.76 (1H, dd, J ¼ 7:7, 1.0
Hz), 6.89 (1H, ddd, J ¼ 7:7, 7.7, 1.0 Hz); 13C NMR (125 MHz,
CDCl3) ꢁ 30.3, 55.3, 109.2, 109.3, 116.2, 121.3, 139.3, 146.8;
Anal. Found: C, 70.13; H, 8.08; N, 10.07%. Calcd for C8H11NO:
C, 70.04; H, 8.08; N, 10.21%.
2-Methyl-N-methylaniline (15c): Pale yellow oil; IR (ZnSe)
3432, 2910, 2813, 1606, 1585, 1513, 1471, 1446, 1427, 1301,
1263, 1166, 1043, 742, 715 cmꢃ1 1H NMR (500 MHz, CDCl3)
;
ꢁ 2.13 (3H, s), 2.89 (3H, s), 3.55 (1H, br), 6.61 (1H, d, J ¼ 8:0
Hz), 6.66 (1H, dd, J ¼ 7:6, 7.4 Hz), 7.05 (1H, d, J ¼ 7:4 Hz),
7.06 (1H, dd, J ¼ 8:0, 7.6 Hz); 13C NMR (125 MHz, CDCl3) ꢁ
17.4, 30.7, 109.1, 116.8, 121.9, 127.2, 129.9, 147.2; Anal. Found:
C, 79.02; H, 9.15; N, 11.41%. Calcd for C8H11N: C, 79.29; H,
9.15; N, 11.56%.
2,4-Dimethoxy-N-methylaniline (15e): Pale purple oil; IR
(ZnSe) 3415, 2937, 2930, 1594, 1511, 1452, 1284, 1228, 1201,
;
1029, 917, 829, 788, 617 cmꢃ1 1H NMR (500 MHz, CDCl3) ꢁ
2,4-Dimethoxyaniline Hydrochloride (14e):21 White pow-
der; 1H NMR (500 MHz, DMSO-d6) ꢁ 3.77 (3H, s), 3.86 (3H,
s), 6.58 (1H, dd, J ¼ 8:6, 2.4 Hz), 6.74 (1H, d, J ¼ 2:4 Hz),
7.38 (1H, d, J ¼ 8:6 Hz), 9.98 (3H, br); 13C NMR (125 MHz,
DMSO-d6) ꢁ 56.0, 56.6, 100.0, 105.4, 113.4, 125.0, 153.8,
160.5; Anal. Found: C, 50.48; H, 6.39; N, 7.26%. Calcd for
C8H12ClNO2: C, 50.67; H, 6.38; N, 7.39%.
Phenethylammonium Chloride (14i):21
White powder;
1H NMR (500 MHz, DMSO-d6) ꢁ 2.89 (2H, t, J ¼ 7:8 Hz), 2.99
(2H, br), 7.22–7.26 (3H, m), 7.32 (2H, t, J ¼ 7:4 Hz), 8.20 (3H,
br); 13C NMR (125 MHz, DMSO-d6) ꢁ 33.1, 40.1, 126.9,
128.81, 128.84, 137.7; Anal. Found: C, 61.18; H, 7.72; N,
8.70%. Calcd for C8H12ClN: C, 60.95; H, 7.67; N, 8.89%.
1-Methyl-3-phenylpropylammonium Chloride (14j): White
powder; mp 139–141 ꢁC (dec.); IR (ZnSe) 2879, 2373, 2318,
2.83 (3H, s), 3.76 (3H, s), 3.82 (3H, s), 3.88 (1H, br), 6.44 (1H,
dd, J ¼ 8:3, 2.7 Hz), 6.45 (1H, d, J ¼ 2:7 Hz), 6.51 (1H, d,
J ¼ 8:3 Hz); 13C NMR (125 MHz, CDCl3) ꢁ 31.1, 55.4, 55.8,
99.0, 103.6, 109.5, 133.8, 148.0, 151.8; Anal. Found: C, 64.61;
H, 7.89; N, 8.15%. Calcd for C9H13NO2: C, 64.65; H, 7.84; N,
8.38%.
1716, 1540, 1508, 765, 744, 700 cmꢃ1 1H NMR (500 MHz,
;
DMSO-d6) ꢁ 1.22 (3H, d, J ¼ 6:5 Hz), 1.67–1.75 (1H, m),
1.85–1.93 (1H, m), 2.58–2.69 (2H, m), 3.08–3.12 (1H, m),
7.17–7.21 (3H, m), 7.29 (2H, t, J ¼ 7:5 Hz), 8.05 (3H, br);
13C NMR (125 MHz, DMSO-d6) ꢁ 18.2, 31.0, 36.1, 46.6, 126.2,
128.4, 128.7, 141.2; Anal. Found: C, 64.76; H, 8.74; N, 7.35%.
Calcd for C10H16ClN: C, 64.68; H, 8.68; N, 7.54%.
1-Adamantylammonium Chloride (14k):10b White powder;
1H NMR (500 MHz, DMSO-d6) ꢁ 1.57 (3H, d, J ¼ 12:1 Hz), 1.66
(3H, d, J ¼ 12:1 Hz), 1.81 (6H, s), 2.08 (3H, s), 8.09 (3H, br);
13C NMR (125 MHz, DMSO-d6) ꢁ 28.5, 35.3, 40.2, 51.2; Anal.
Found: C, 63.77; H, 9.46; N, 7.17%. Calcd for C10H18ClN: C,
63.99; H, 9.67; N, 7.46%.
Typical Procedure for the Preparation of N-Methylamine
(Table 3, Run 2): To a solution of 1,3-dimethyl-2-imidazolidi-
none O-tosyloxime (4, 283 mg, 1.00 mmol) in toluene (8 mL) was
added dropwise an ether solution of 2-methoxyphenylmagnesium
bromide (1.22 M, 0.82 mmol) at 0 ꢁC under an argon atmosphere,
and this mixture was stirred at the same temperature for 15 min.
After the reaction was quenched with pH 9 buffer at 0 ꢁC, the mix-
ture was extracted three times with ethyl acetate, and the com-
bined extracts were washed with brine. The solution was dried
over anhydrous sodium sulfate, and the ethyl acetate was removed
in vacuo. The crude imine was dissolved in ether (3 mL); then
lithium aluminum hydride in tetrahydrofuran (1.0 M, 1.0 mL)
was added to the solution at 0 ꢁC. After the resulting solution
was stirred at room temperature for 12 h, the ꢁmixture was
quenched with 1.0 M HCl (5 mL, 5.0 mmol) at 0 C. After the
mixture was washed with ether, to the resulting aqueous layer
was added 2 M NaOH (3 mL, 6.0 mmol). The mixture was ex-
tracted twice with ether and washed with brine. The ether solution
was dried over anhydrous magnesium sulfate, and ether was re-
moved in vacuo. The crude materials were purified by flash col-
N-Methyl-1-naphthylamine (15g):22
Pale yellow oil;
1H NMR (270 MHz, CDCl3) ꢁ 2.99 (3H, s), 4.40 (1H, br), 6.59
(1H, d, J ¼ 7:0 Hz), 7.23 (1H, d, J ¼ 8:2 Hz), 7.36 (1H, d,
J ¼ 8:2 Hz), 7.37–7.46 (2H, m), 7.73–7.80 (2H, m); 13C NMR
(67.5 MHz, CDCl3) ꢁ 31.0, 103.7, 117.2, 119.7, 123.3, 124.6,
125.7, 126.6, 128.6, 134.2, 144.5.
1
2-Methylaminothiophene (15h):23 Purple oil; H NMR (500
MHz, CDCl3) ꢁ 2.87 (3H, s), 6.00 (1H, dd, J ¼ 3:6, 1.3 Hz), 6.45
(1H, dd, J ¼ 5:4, 1.3 Hz), 6.73 (1H, dd, J ¼ 5:4, 3.6 Hz);
13C NMR (125 MHz, CDCl3) ꢁ 34.3, 103.1, 110.2, 126.3, 156.4.
N-Methylphenethylamine (15i):21
Colorless oil; 1H NMR
(270 MHz, CDCl3) ꢁ 2.45 (3H, s), 2.78–2.89 (4H, m), 7.20–
7.33 (5H, m); 13C NMR (67.5 MHz, CDCl3) ꢁ 36.1, 36.3, 53.1,
126.1, 128.5, 128.7, 140.0.
N-Methyl-(1-methyl-3-phenylpropyl)amine (15j): Colorless
oil; IR (ZnSe) 3303, 2964, 2933, 2856, 1658, 1494, 1454, 1376,
1155, 1078, 1029, 786, 746, 696 cmꢃ1 1H NMR (500 MHz,
;
CDCl3) ꢁ 1.11 (3H, d, J ¼ 6:2 Hz), 1.61 (1H, dddd, J ¼ 6:6,
6.6, 10.1, 13.4 Hz), 1.78 (1H, dddd, J ¼ 5:9, 5.9, 9.9, 13.4 Hz),
2.41 (3H, s), 2.57 (1H, ddq, J ¼ 5:9, 6.6, 6.2 Hz), 2.60–2.69
(2H, m), 7.16–7.20 (3H, m), 7.28 (2H, t, J ¼ 7:5 Hz); 13C NMR
(125 MHz, CDCl3) ꢁ 19.8, 32.3, 33.8, 38.5, 54.4, 125.7, 128.29,
128.32, 142.4; FABHRMS Found: m=z 164.1461. Calcd for
C11H18N: (M + H)þ, 164.1439.
1-(N-Methylamino)adamantane (15k):24
1H NMR (500
MHz, CDCl3) ꢁ 1.66–1.70 (12H, m), 2.09 (3H, brs), 2.36 (3H,
s), 2.55 (1H, br).
2-Benzyloxyiminomalononitrile: To a solution of malononi-

M. Kitamura et al.
Bull. Chem. Soc. Jpn., 76, No. 5 (2003) 1069
trile (906 mg, 13.7 mmol) in acetic acid (2 mL) and water (5mL)
was slowly added sodium nitrite (1.42 g, 20.6 mmol) at 0 ꢁC, and
this mixture was stirred at the same temperature for 30 min. After
quenching the reaction with 2 M HCl (10 mL), the mixture was
extracted three times with ether. The extracts were dried over an-
hydrous sodium sulfate, and the ether was removed in vacuo. To a
solution of the crude materials and benzyl bromide (1.8 mL, 15
mmol) in dichloromethane (10 mL) was slowly added triethyla-
mine (5.7 mL, 41 mmol) at 0 ꢁC. This mixture was stirred at
the same temperature for 15 min, and the reaction was quenched
with water. The mixture was extracted three times with ethyl ace-
tate, and the combined extracts were washed with brine and dried
over anhydrous sodium sulfate. Volatile materials were removed
in vacuo, and the crude materials were purified by flash column
chromatography (silica gel; hexane/ethyl acetate = 95/5) to give
2-benzyloxyiminomalononitrile (1.66 g, 65%). Pale yellow oil;
1H NMR (500 MHz, CDCl3) ꢁ 5.51 (2H, s), 7.35–7.40 (2H, m),
7.41–7.44 (3H, m); 13C NMR (125 MHz, CDCl3) ꢁ 82.4, 105.6,
108.5, 109.0, 129.0, 129.3, 129.8, 133.2.
1,3-Dioxolan-2-one O-Tosyloxime (5):13
Color needles;
1H NMR (500 MHz, CDCl3) ꢁ 2.44 (3H, s), 4.52–4.54 (2H, m),
4.58–4.60 (2H, m), 7.33 (2H, d, J ¼ 8:1 Hz), 7.85 (2H, d,
J ¼ 8:1 Hz); 13C NMR (125 MHz, CDCl3) ꢁ 23.9, 66.1, 66.9,
122.8, 123.4, 125.6, 137.6, 156.1.
1
Fig. 1. X-ray analysis of (Z)-6.
2-(Phenylimino)-1,3-dioxolane (11): Colorless oil; H NMR
(500 MHz, CDCl3) ꢁ 4.49 (4H, brs), 7.06 (1H, t, J ¼ 7:4 Hz), 7.09
(2H, d, J ¼ 8:2 Hz), 7.28 (2H, dd, J ¼ 7:4, 8.2 Hz); 13C NMR
(125 MHz, CDCl3) ꢁ 64.8, 66.6, 123.0, 123.4, 128.6, 145.3, 153.5.
3-Methyl-2-oxazolidinone O-Benzyloxime: To an ice cold
solution of sodium hydride (485 mg, 20.2 mmol) in tetrahydrofur-
an (10 mL) was slowly added 2-(methylamino)ethanol (1.44 g,
19.2 mmꢁol) in tetrahydrofuran (10 mL) and this mixture was stir-
red at 0 C for 20 min. To the sꢁolution was added O-benzylhy-
droxyiminomalononitrile at ꢃ78 C, and the mixture was stirred
at 60 ꢁC for 5 h. The reaction was quenched with water at 0
ꢁC, and the mixture was extracted three times with ethyl
acetate. The combined extracts were washed with brine and dried
over anhydrous sodium sulfate. Volatile materials were removed
in vacuo, and the crude materials were purified by flash column
chromatography (silica gel; hexane/acetone = 7/3) to give 3-
methyl-2-oxazolidinone O-benzyloxime (372 mg, 22%). Pale yel-
low oil; IR (ZnSe) 2910, 2852, 1654, 1494, 1452, 1402, 1363,
cuo, and the crude materials were purified by flash column chro-
matography (silica gel; hexane/acetone = 1/1) to give 3-methyl-2-
oxazolidinone O-tosyloxime. The configuration of (Z)-6 was de-
termined by the X-ray analysis (Fig. 1).
(Z)-6 (278 mg, 57%); Colorless crystal; mp 125–126 ꢁC; IR
(ZnSe) 2973, 2358, 1637, 1500, 1351, 1292, 1186, 1172, 1043,
900, 804, 669, 566 cmꢃ1 1H NMR (500 MHz, CDCl3) ꢁ 2.44
;
(3H, s), 2.73 (3H, s), 3.48 (2H, ddd, J ¼ 7:7, 7.4, 1.1 Hz), 4.36
(2H, ddd, J ¼ 7:7, 7.4, 1.1 Hz), 7.31 (2H, d, J ¼ 8:2 Hz), 7.86
(2H, d, J ¼ 8:2 Hz); 13C NMR (125 MHz, CDCl3) ꢁ 21.6, 31.9,
49.5, 66.8, 128.9, 129.2, 132.8, 144.3; Anal. Found: C, 49.14;
H, 5.33; N, 10.15%. Calcd for C11H14N2O4S: C, 48.88; H, 5.22;
N, 10.36%.
(E)-6 (49.8 mg, 10%); 1H NMR (500 MHz, CDCl3) ꢁ 2.40 (3H,
s), 2.95 (3H, s), 3.63 (2H, dd, J ¼ 9:3, 8.3 Hz), 4.52 (2H, dd,
J ¼ 9:3, 8.3 Hz), 7.25 (2H, d, J ¼ 8:1 Hz), 7.85 (2H, d, J ¼ 8:1
Hz); 13C NMR (125 MHz, CDCl3) ꢁ 21.4, 31.8, 47.4, 66.3,
126.9, 129.0, 140.1, 142.2, 158.5.
1282, 1045, 825, 736, 696, 592 cmꢃ1 1H NMR (500 MHz,
;
CDCl3) ꢁ 2.74 (3H, s), 3.37 (2H, t, J ¼ 7:1 Hz), 4.33 (2H, t, J ¼
7:1 Hz), 7.27 (1H, tt, J ¼ 7:2, 1.4 Hz), 7.33 (2H, dd, J ¼ 7:2, 7.1
Hz), 7.41 (2H, dd, J ¼ 7:1, 1.4 Hz); 13C NMR (125 MHz, CDCl3)
ꢁ 32.7, 49.7, 66.1, 127.5, 127.8, 128.1, 128.5, 138.0, 157.8;
FABHRMS Found: m=z 207.1149. Calcd for C11H15N2O2: (M
+ H)þ, 207.1134.
N-Methyl-2-oxazolidinone O-Tosyloxime (6): In the pre-
sence of palladium hydroxide (119 mg, 20 wt% Pd on carbon),
a suspension of 3-methyl-2-oxazolidinone O-benzyloxime (372.7
mg, 1.81 mmol) in ethanol (5 mL) was stirred at room temperature
under hydrogen atmosphere for 5 h. After purging with argon, the
mixture was filtered through a celite pad, and the solvent was re-
moved in vacuo. To a solution of the crude materials and triethy-
lamine (0.75 mL, 5.4 mmol) in dichloromethane (4 ꢁmL) was
slowly added tosyl chloride (360 mg, 1.89 mmol) at 0 C. After
the mixture was stirred for 30 min, the reaction was quenched with
water. The mixture was extracted three times with ethyl acetate,
and the combined extracts were washed with brine and dried over
anhydrous sodium sulfate. The ethyl acetate was removed in va-
3-Methyl-2-(phenylimino)oxazolidine (12):17 To a solution
of (Z)-3-methyl-2-oxazolidinone O-tosyloxime (113 mg, 0.418
mmol) in toluene (5 mL) was added dropwise an ether solution
of phenylmagnesium bromide (1.00 M, 0.42 mL) at room tem-
perature under an argon atmosphere, and this mixture was stirred
at the same temperature for 30 min. After the reaction was
quenched with pH 9 buffer at 0 ꢁC, the mixture was extracted three
times with ethyl acetate, and the combined extracts were washed
with brine and dried over anhydrous sodium sulfate. After the vo-
latile material was removed in vacuo, the residues were purified
by the flash column chromatography (silica gel; hexane/acetone
= 7/3) to give N-methyl-2-(phenylimino)oxazolidine (71.7 mg,
97%). Pale yellow oil; IR (ZnSe) 2906, 2865, 1660, 1585,
1477, 1400, 1265, 1213, 1024, 962, 748, 709 cmꢃ1 1H NMR
;
(500 MHz, CDCl3) ꢁ 2.98 (3H, s), 3.50 (2H, t, J ¼ 7:6 Hz),
4.30 (2H, t, J ¼ 7:6 Hz), 6.96 (1H, t, J ¼ 8:1 Hz), 7.04 (2H, d,
J ¼ 7:7 Hz), 7.24 (2H, dd, J ¼ 8:1, 7.7 Hz); 13C NMR (125
MHz, CDCl3) ꢁ 32.4, 48.3, 64.2, 122.0, 123.4, 128.5, 147.9,

1070 Bull. Chem. Soc. Jpn., 76, No. 5 (2003)
Electrophilic Amination by Using Oximes
153.8; FABHRMS Found: m=z 177.1011. Calcd for C10H13N2O:
(M + H)þ, 177.1028.
29, 3989 (1999). e) E. Erdik and T. Daskapan, J. Chem. Soc., Per-
kin Trans. 1, 1999, 3139.
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1997, 317. b) H. Tsutsui, T. Ichikawa, and K. Narasaka, Bull.
Chem. Soc. Jpn., 72, 1869 (1999).
This research was supported by a Grant-in-Aid for Scientific
Research on Priority Areas (A) ‘‘Exploitation of Multi-Ele-
ment Cyclic Molecules’’ from the Ministry of Education, Cul-
ture, Sports, Science and Technology.
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