Efficient microwave-assisted solvent-free synthesis of N-substituted aldimines

Article abstract of DOI:10.1055/s-2006-926429

Neat non-volatile amines react with various aromatic aldehydes in the absence of any catalyst, solid support, or solvent, to give imines after a reaction time of eight minutes under microwave irradiation by a clean and very efficient process (yields: 75-100%). In the case of volatile amine, methylamine, 1,3-dimethylurea dispersed on montmorillonite K10 is used as an amine precursor to prepare the corresponding imines. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-2006-926429

1652
PAPER
Efficient Microwave-Assisted Solvent-Free Synthesis of N-Substituted
Aldimines
M
icrowave-Ass
u
iste
d
Solven
d
t-Free Synth
o
esis of N-Sub
v
stituted
A
ld
i
imines c Paquin, Jack Hamelin, Françoise Texier-Boullet*
Synthèse et Electrosynthèse organique 3, UMR 6510, CNRS et Université de Rennes 1, Campus de Beaulieu, 35042 Rennes, France
Fax +33(2)23236374; E-mail: francoise.texier@univ-rennes1.fr
Received 8 September 2005; revised 5 January 2006
O
H
Ar
Abstract: Neat non-volatile amines react with various aromatic al-
dehydes in the absence of any catalyst, solid support, or solvent, to
give imines after a reaction time of eight minutes under microwave
irradiation by a clean and very efficient process (yields: 75–100%).
In the case of volatile amine, methylamine, 1,3-dimethylurea dis-
persed on montmorillonite K10 is used as an amine precursor to pre-
pare the corresponding imines.
+
R-NH2
Ar
N
– H2O
1a–k
2a–k
Scheme 1
Key words: solvent-free reactions, microwave activation, N-sub-
stituted imines, ureas
The development of simple, cheap, and clean processes in
the area of ‘green chemistry’ is of increasing interest.1–8
Some years ago, we reported an efficient synthesis of
electrophilic alkenes under microwave irradiation in a do-
mestic oven by the condensation of carbonyl derivatives
with active methylene compounds, without solvent and by
the addition of catalytic amounts of piperidine.9 The polar
water molecules eliminated after the reaction are immedi-
ately vaporized, avoiding the use of Dean–Stark appara-
tus. The synthesis of imines, a two step-process (addition
of the amine followed by the elimination of water), could
be performed in a dry medium coupled with microwave
irradiation.
Figure 1
The synthesis of imines has been reviewed many times in
recent years.10–12 Imines are important intermediates in
synthetic organic chemistry and pharmaceutical com-
pounds such as b-lactams.13–19 They have been prepared
using mineral supports, such as alumina20 without solvent,
in the presence of organic solvent with azeotropic distilla-
tion,21 or by elimination of water with magnesium sulfate
or molecular sieves.22 However, the reaction times are
long (1–7 d), environmentally toxic solvents are required,
and additional purification steps are necessary.
The results reported in Figure 2 and Table 1 show that a
quantitative yield was obtained after eight minutes, while
degradation of the final imine 2a was observed with long-
er reaction times.
We looked at the preparation of imines by microwave ir-
radiation. As a model reaction, an equimolar mixture of
neat diisopropylamineand benzaldehyde (Scheme 1) were
reacted and the factors, which govern this reaction were
carefully investigated.
First, the influence of the reaction time was studied.
Therefore, the model reaction was performed in an ice-
bath in a quartz reactor, irradiated23 at 100 °C24 with a
maximum power of 90 W (Figure 1).
Figure 2 Influence of the reaction time on the conversion of 1a and
the yield of 2a
In the same way, we studied the influence of the tempera-
ture on the reaction by irradiating the reaction vessel for
eight minutes at a range of temperatures from –30 °C to
160 °C (Figure 3).
SYNTHESIS 2006, No. 10, pp 1652–1656
x
x.
x
x
.
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0
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Advanced online publication: 07.04.2006
DOI: 10.1055/s-2006-926429; Art ID: Z16905SS
© Georg Thieme Verlag Stuttgart · New York

PAPER
Microwave-Assisted Solvent-Free Synthesis of N-Substituted Aldimines
1653
Table 2 Preparation of N-Substituted Imines 2a–k under Micro-
wave Irradiation
Table 1 Determination of the Optimal Reaction Time for the Prep-
aration of 2aa
Completion (%)b Yield (%)c
Ar
Amine (R)
2
Yield
(%)a
Mp (°C) or
bp/Torr
Entry
Time (min)
1
2
3
4
5
6
7
2
3
40
55
30
43
Ph
i-PrNH2
i-PrNH2
i-PrNH2
i-PrNH2
i-PrNH2
i-PrNH2
PrNH2
a
b
c
d
e
f
100
85b
99
97
98
95
99
96
95
96
96
34
4-MeOC6H4
4-ClC6H4
55/8 × 10–2
45/8 × 10–2
62
5
85
72
8
100
100
100
100
100
100
85
4-NO2C6H4
3,4,5-MeOC6H2
piperonyl
10
15
30
54
43/8 × 10–2
68/8 × 10–2
89
70
piperonyl
g
h
i
a Reactions were run at 100 °C (monitored temperature) under micro-
wave irradiation.
b Estimated by 1H NMR spectroscopy of the crude reaction mixture.
c Isolated pure product.
piperonyl
H2NCH2Ph
PrNH2
3,4-MeOC6H3
3,5-MeOC6H3
4-OHC6H4
62/8 × 10–2
49
PrNH2
j
The reaction was run in a liquid nitrogen bath in a modi-
fied monomode Prolabo MX 350 to achieve a temperature
of –30 °C, both with and without irradiation. After a reac-
tion time of eight minutes, under microwave irradiation
the reaction was 60% complete (58% yield of isolated
PrNH2
k
120
a Yield of isolated pure product.
b Yield of isolated pure product after removal of unreacted amine.
pure imine after drying over MgSO4); in the absence of ir- Due to the high temperatures required this method is not
radiation the reaction went to only 15% completion (12% applicable to volatile amines such as methylamine. In the
yield of isolated pure imine).
case of methylamine, 1,3-dimethylurea24 was used as a
synthetic equivalent and the reaction was carried out in
the presence of solid clay-montmorillonite K10 (Scheme
2).
The results show that the reaction reached 100% comple-
tion after eight minutes at 100 °C. At this temperature the
water molecules formed are vaporized and eliminated
from the reaction mixture and the equilibrium is dis-
placed, favoring imine formation. At higher temperatures,
we observed a physical and chemical runaway of the reac-
tion. The thermal stability of pure imine was analyzed by
microwave irradiation of the imine at 150 °C (reached af-
ter 10 min) for 15 minutes and no degradation was ob-
served.
MeHN
NHMe
Ar
+
ArCHO
N
Me
– MeNH2
– CO2
O
2l–p
Scheme 2
Equimolar amounts of benzaldehyde with 1,3-dimethyl-
urea were dispersed on 3 g of clay and irradiated at 80 °C
(maximum power 120 W, reached after 3 min). The opti-
mal reaction time is ten minutes giving a 40% isolated
yield of imine 2l (Table 3, entry 4).
The reaction was extended to various aldehydes 1a–k
(Scheme 1) and the results are reported in Table 2.
Table 3 Influence of the Reaction Time on the Preparation of Imine
2l
Entry
Time (min)
Completion (%)a Yield (%)b
1
2
3
4
5
6
2
3
15
20
8
17
26
40
30
0
5
30
10
15
20
45
60
100
Figure 3 Influence of reaction temperature on the conversion of 1a
and the yield of 2a
a Estimated by 1H NMR spectroscopy of the crude reaction mixture.
b Isolated pure product.
Synthesis 2006, No. 10, 1652–1656 © Thieme Stuttgart · New York

1654
L. Paquin et al.
PAPER
cused system. All solvents and reagents were purchased from Acros
Organics and Aldrich Chimie and used without further purification
unless otherwise stated.
In order to optimize the yield of 2l we studied the influ-
ence of the reaction temperature (in the range 40–140 °C)
on the reaction. The results show the optimal temperature
is 120 °C (Table 3, entry 5); above this temperature we
observed a degradation of the final products and below
this temperature water elimination is disfavored and the
yield decreases.
For compounds 2c, 2e, 2i, and 2j although NMR spectra and HMR
were acceptable, elemental analyses were not satisfactory due to the
instability of these compounds during purification.
N-Substituted Aldimines 2a–k; General Procedure
An equimolar mixture of neat aldehyde (10 mmol) and amine (10
mmol) at 0 °C was placed in a quartz reactor and irradiated in a Syn-
thewave 402® oven23 at 100 °C (monitored temperature,24 reached
after 3 min) for 5 min. Imine 2 is generally obtained pure. In a few
cases, a small excess of amine is present, which was removed by
short-path distillation. This procedure was scaled up to 1 mol and a
Synthewave 1000®.
Table 4 Influence of the Temperature on the Preparation of Imine 2l
Entry
Temperature (°C) Completion (%)b
Yield (%)c
1
2
3
4
5
6
50
70
14
25
45
53
75
75
8
20
37
43
73
48
80
N-Methylaldimines 2l–p; General Procedure
An equimolar mixture of neat aldehyde and 1,3-dimethylurea (10
mmol) was dispersed on montmorillonite K10 clay (3 g), the result-
ing mixture was placed in a quartz reactor (diameter 3 cm), and ir-
radiated in a Synthewave 402® oven23 at 120 °C (monitored
temperature, reached after 3 min) for 7 min. The mixture was cooled
and extracted with CH2Cl2 (2 × 15 mL). The clay was removed by
filtration through celite, the solvent was removed under vacuum,
and the residual oil is purified by short-path distillation or crystalli-
zation from MeOH.
100
120
140
a Reaction time: 10 min.
b Estimated by 1H NMR spectroscopy of the crude reaction mixture.
c Isolated pure product.
N-(2-Propyl)benzylideneamine (2a)25
White solid; mp 34 °C.
Finally, we prepared N-methylimines 2l–p by adsorption
onto an excess of montmorillonite K10, without solvent
under microwave irradiation for ten minutes at 120 °C
(Table 5).
1H NMR (300 MHz, CDCl3): d = 1.32 [d, 3J = 6.3 Hz, 6 H,
(CH3)2CH], 3.56 (hept, J = 6.29 Hz, 1 H, CHN=C), 7.34–7.79 (m, 5
H, Ph), 8.27 (s, 1 H, N=CH).
13C NMR (75 MHz, CDCl3): d = 24.2 [q, J = 121 Hz, NCH(CH3)2],
61.7 [d, J = 140 Hz, NCH(CH3)2], 128.0 [d, J = 118 Hz, Ph(C-3),
Ph(C-5)], 128.5 [d, J = 160 Hz, Ph(C-2), Ph(C-6)], 130.4 [d,
J = 143 Hz, Ph(C-4)], 136.5 [s, Ph(C-1)], 158.4 (d, J = 155 Hz,
C=N).
Table 5 Preparation of N-Methylimines 2l–p
Ar
2
l
Yield (%)a
Bp (°C)/Torr
72/0.024
65/0.035
50/0.04
Ph
73
60b
65
48
55
HMRS: m/z calcd for C10H13N: 147.10480; found: 147.1045.
4-MeOC6H4
4-ClC6H4
4-NO2C6H4
4-Me
m
n
o
p
N-(2-Propyl)-4-methoxybenzylideneamine (2b)
Yellow liquid; bp 55 °C (8 × 10–2 Torr).
48b
1H NMR (300 MHz, CDCl3): d = 1.21 [d, 3J = 6.34 Hz, 6 H,
3
(CH3)2CH], 3.53 (hept, J = 6.30 Hz, 1 H, CHN=C), 3.73 (s, 3 H,
OCH3), 6.75–7.25 (m, 4 H, Ph), 8.18 (s, 1 H, N=CH).
25/0.034
a Yield of isolated pure product after short-path distillation.
b After crystallization (MeOH).
13C NMR (75 MHz, CDCl3): d = 24.2 [q, J = 121.1 Hz, CH2(CH3)2],
55.5 (q, J = 144.1 Hz, OCH3), 61.5 [d, J = 115.9 Hz, CH(CH3)2],
114.0 [d, J = 164.7 Hz, Ph(C-3), Ph(C-5)], 129.6 [d, J = 148.7 Hz,
Ph(C-2), Ph(C-6)], 131.9 [s, Ph(C-1)], 157.7 (d, J = 154.7 Hz,
C=N), 161.4 [s, Ph(C-4)].
In conclusion, we report a useful, expeditious, and eco-
friendly method for the synthesis of N-substituted imines,
which is simpler than methods previously reported.
HMRS: m/z calcd for C11H15NO: 177.11536; found: 177.1153.
Anal. Calcd for C11H15NO: C, 74.54; H, 8.53; N, 7.90. Found: C,
74.68; H, 8.55; N, 7.90.
Melting points were determined on a Kofler melting point apparatus
and are uncorrected. IR spectra were taken with a Perkin-Elmer
1420 spectrometer. 1H NMR spectra were recorded on Bruker ARX
200 (200 MHz), Bruker AC 300 P (300 MHz) spectrometers and 13C
NMR spectra on Bruker AC 300 P (75 MHz) spectrometer. Chem-
ical shifts are expressed in parts per million downfield from tetram-
ethylsilane as an internal standard. Mass spectra (MS) were taken
on a Varian MAT 311 at 70 eV at the Centre de Mesures Physiques
de l’Ouest (CRMPO, Rennes). Elemental analyses were performed
at the Laboratoire Central de Microanalyses-CNRS (Lyon) and
Centre de Mesures Physiques de l’Ouest (CRMPO, Rennes). Reac-
tions under microwave irradiation were performed in a Prolabo
Synthewave 402® (2.45 GHz) microwave reactor23 with a single fo-
N-(2-Propyl)-4-chlorobenzylideneamine (2c)
Colorless liquid; bp 45 °C (8 × 10–2 Torr).
1H NMR (300 MHz, CDCl3): d = 1.22 [d, 3J = 6.3 Hz, 6 H,
(CH3)2CH], 3.48 (hept, 3J = 6.3 Hz, 1 H, CHN=C), 7.28–7.63 (m, 4
H, Ph), 8.16 (s, 1 H, N=CH).
13C NMR (75 MHz, CDCl3): d = 24.1 [q, J = 120.6 Hz, CH2(CH3)2],
61.7 [d, J = 132.4 Hz, CH(CH3)2], 128.8 [d, J = 164.9 Hz, Ph(C-3),
Ph(C-5),], 129.3 [d, J = 164.9 Hz, Ph(C-2), Ph(C-6)], 134.9 [s,
Ph(C-1)], 136.3 [s, Ph(C-4)], 156.9 (d, J = 161 Hz, C=N).
HMRS: m/z calcd for C10H1235ClN: 181.06583; found: 181.0648.
Synthesis 2006, No. 10, 1652–1656 © Thieme Stuttgart · New York

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Microwave-Assisted Solvent-Free Synthesis of N-Substituted Aldimines
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N-(2-Propyl)-4-nitrobenzylideneamine (2d)
Brown solid; mp 62 °C.
N-Benzylpiperonylideneamine (2h)
Yellow solid; mp 89 °C.
1H NMR (300 MHz, CDCl3): d = 1.24 [d, 3J = 6.3 Hz, 6 H,
(CH3)2CH], 3.57 (hept, 3J = 6.3 Hz, 1 H, CHN=C), 6.76–8.22 (m, 4
H, Ph), 8.36 (s, 1 H, N=CH).
1H NMR (300 MHz, CDCl3): d = 4.83 (d, J = 1.0 Hz, 2 H, CH2Ph),
6.04 (s, 2 H, OCH2O), 6.88 (d, J = 8.0 Hz, 1 H), 7.17–7.47 (m, 8 H,
Ar), 8.32 (s, 1 H, =CH).
13C NMR (75 MHz, CDCl3): d = 23.9 [q, J = 125 Hz, CH2(CH3)2],
61.9 [d, J = 133.1 Hz, CH(CH3)2], 123.7 [d, J = 168 Hz, Ph(C-3),
Ph(C-5)], 128.7 [d, J = 157 Hz, Ph(C-2), Ph(C-6)], 142.1 [s, Ph(C-
1)], 149.0 [s, Ph(C-4)], 156.0 (d, J = 158 Hz, C=N).
13C NMR (75 MHz, CDCl3): d = 65.2 (tm, J = 156 Hz, CH2), 101.9
(t, J = 175 Hz, OCH2O), 107.1 (d, J = 165 Hz, Ph), 108.5 (d,
J = 175 Hz, Ph), 125.0 [d, J = 155.1 Hz, Ar(C-2)], 127.4 (m, Ph),
128.4 [d, J = 161.3 Hz, Ar(C-6)], 131.5 [d, J = 162.4 Hz, Ar(C-5)],
139.9 [s, Ar(C-4)], 148.7 [s, Ar(C-1)], 150.3 [s, Ar(C-3)], 161.5 (d,
J = 151.8 Hz, C=N).
HMRS: m/z calcd for C10H12N2O2: 192.08988; found: 192.0890.
Anal. Calcd for C10H12N2O2: C, 62.49; H, 6.29; N, 14.57. Found: C,
62.57; H, 6.38; N, 14.45.
HMRS: m/z calcd for C15H13NO2: 239.0946; found: 239.0932.
Anal. Calcd for C15H13NO2: C, 75.30; H, 5.48; N, 5.85. Found: C,
75.08; H, 5.57; N, 5.67.
N-(2-Propyl)-3,4,5-trimethoxybenzylideneamine (2e)
Light-brown solid; mp 54 °C.
N-Propyl-3,4-dimethoxybenzylideneamine (2i)
Yellow liquid; bp 62 °C (8 × 10–2 Torr).
1H NMR (300 MHz, CDCl3): d = 1.22 [d, 3J = 6.3 Hz, 6 H,
3
(CH3)2CH], 3.52 (hept, J = 6.3 Hz, 1 H, CHN=C), 3.88 (s, 9 H,
OCH3), 6.99 (s, 2 H, Ph), 8.18 (s, 1 H, N=CH).
1H NMR (300 MHz, CDCl3): d = 0.61 (t, J = 7.3 Hz, 3 H,
NCH2CH2CH3), 1.36 (sext, J = 7.2 Hz, 2 H, NCH2CH2CH3), 3.18 (t,
J = 6.9 Hz, 2 H, NCH2CH2CH3), 3.49 (s, 3 H, OCH3), 3.55 (s, 3 H,
OCH3), 6.47 [d, J = 8.2 Hz, 1 H, Ph(H-5)], 6.78 [dd, J = 8.2, 1.4 Hz,
1 H, Ph(H-6)], 7.13 [d, J = 1.7 Hz, 1 H, Ph(H-2)], 7.78 (s, 1 H,
N=CH).
13C NMR (75 MHz, CDCl3): d = 24.1 [q, J = 121.1 Hz, CH2(CH3)2],
56.2 (q, J = 144.4 Hz, OCH3), 61.5 [d, J = 144.5 Hz, CH(CH3)2],
105.0 [d, J = 160.4 Hz, Ph(C-2), Ph(C-6)], 161.6 [d, J = 163.1 Hz,
Ph(C-3), Ph(C-5)], 139.9 [s, Ph(C-4)], 143.5 [s, Ph(C-1)], 157.8 (d,
J = 156.1 Hz, C=N).
13C NMR (75 MHz, CDCl3): d = 11.5 (NCH2CH2CH3), 23.9
(NCH2CH2CH3), 55.4 (q, J = 144.4 Hz, OCH3), 55.4 (q, J = 144.4
Hz, OCH3), 62.9 (NCH2CH2CH3), 108.6 [d, J = 163.1 Hz, Ph(C-5)],
110.2 [d, J = 160.4 Hz, Ph(C-2)], 122.6 [d, J = 160.4 Hz, Ph(C-6)],
129.25 [s, Ph(C-1)], 149.0 [d, J = 163.1, Hz, Ph(C-3)], 149.9 [d,
J = 163.4 Hz, Ph(C-4)], 160.0 (N=CH).
HMRS: m/z calcd for C13H19NO3: 237.13649; found: 237.1378.
N-(2-Propyl)piperonylideneamine (2f)
Yellow liquid; bp 43 °C (8 × 10–2 Torr).
1H NMR (300 MHz, CDCl3): d = 1.12 [d, 3J = 6.3 Hz, 6 H,
3
(CH3)2CH], 3.42 (hept, J = 6.3 Hz, 1 H, CHN=C), 5.94 (s, 2 H,
OCH2O), 7.34 [s, 1 H, Ar(H-6)], 6.76 [dd, J = 47.8, 7.9 Hz, 1 H,
Ar(H-2)], 7.00 [dd, J = 47.8, 7.9 Hz, 1 H, Ar(H-5)], 8.14 (s, 1 H,
N=CH).
HMRS: m/z calcd for C12H17NO2: 207.1259; found: 207.1256.
N-Propyl-3,5-dimethoxybenzylideneamine (2j)
Brown solid; mp 49 °C.
13C NMR (75 MHz, CDCl3): d = 24.2 [q, J = 126.1 Hz, CH2(CH3)2],
61.3 [d, J = 130.2 Hz, CH(CH3)2], 101.3 [d, J = 175 Hz, OCH2O],
124.1 [d, J = 155.2 Hz, Ar(C-2)], 128.6 [d, J = 161.8 Hz, Ar(C-6)],
131.2 [d, J = 163 Hz, Ar(C-5)], 148.6 [s, Ar(C-4)], 149.6 [s, Ar(C-
3)], 153.1 [s, Ar(C-1)], 157.5 (d, J = 151.8 Hz, C=N).
1H NMR (300 MHz, CDCl3): d = 0.90 (t, J = 7.4 Hz, 3 H,
NCH2CH2CH3), 1.67 (sext, J = 7.2 Hz, 2 H, NCH2CH2CH3), 3.50
(td, J = 6.9, 1.1 Hz, 2 H, NCH2CH2CH3), 3.73 (s, 3 H, OCH3), 3.85
(s, 3 H, OCH3), 6.45 [d, J = 8.2 Hz, 1 H, Ph(H-4)], 6.84 [d, J = 1.4
Hz, 2 H, Ph(H-6), Ph(H-2)], 8.09 (s, 1 H, N=CH).
HMRS: m/z calcd for C11H13NO2: 191.09463; found: 191.0951.
13C NMR (75 MHz, CDCl3): d = 11.8 (NCH2CH2CH3), 24.0
(NCH2CH2CH3), 55.2 (q, J = 144.4 Hz, OCH3), 63.3
(NCH2CH2CH3), 103.1 [(m, Ph(C-4)], 105.6 [d, J = 160.4 Hz,
Ph(C-2), Ph(C-6)], 138.4 [s, Ph(C-1)], 160.8 [d, J = 163.1 Hz,
Ph(C-3), Ph(C-5)], 160.9 (d, J = 155.5 Hz, C=N).
Anal. Calcd for C11H13NO2: C, 69.09; H, 6.85; N, 7.32. Found: C,
69.23; H, 6.84; N, 7.32.
N-Propylpiperonylideneamine (2g)
Yellow liquid; bp 68 °C (8 × 10–2 Torr).
HMRS: m/z calcd for C12H17NO2: 207.1259; found: 207.1258.
1H NMR (300 MHz, CDCl3): d = 0.95 (t, J = 7.4 Hz, 3 H, CH2CH3),
1.72 (sext, J = 7.2 Hz, 2 H, CH2CH3), 3.57 (td, J = 7.0, 1.2 Hz, 2 H,
CH2CH2), 6.03 (s, 2 H, OCH2O), 6.85 (d, J = 8.0 Hz, 1 H, Ar), 7.12
(dd, J = 8.0, 1.5 Hz, 1 H, Ar), 7.35 (d, J = 1.5 Hz, 1 H, Ar), 8.17 (s,
1 H).
N-Propyl-4-hydroxybenzylideneamine (2k)
Brown solid; mp 120 °C.
1H NMR (300 MHz, DMSO-d6): d = 0.88 (t, J = 7.4 Hz, 3 H,
NCH2CH2CH3), 1.59 (sext, J = 7.1 Hz, 2 H, NCH2CH2CH3),
3.45 (td, J = 6.8, 1.0 Hz, 2 H, NCH2CH2CH3), 6.80 (dt, J = 8.6, 1.8
Hz, 2 H, Ph), 7.55 (dt, J = 8.6, 1.9 Hz, 2 H, Ph), 8.17 (s, 1 H,
N=CH), 9.86 (s, 1 H, OH).
13C NMR (75 MHz, CDCl3): d = 11.8 (NCH2CH2CH3), 24.0
(NCH2CH2CH3), 63.3 (NCH2CH2CH3), 102.8 (d, J = 174.5 Hz,
OCH2O), 123.8 [d, J = 154.5 Hz, Ar(C-2)], 127.9 [d, J = 162.1 Hz,
Ar(C-6)], 132.8 [d, J = 163.3 Hz, Ar(C-5)], 148.4 [s, Ar(C-4)],
149.3 [s, Ar(C-3)], 152.8 [s, Ar(C-1)], 156.6 (d, J = 152.2 Hz,
C=N).
13C NMR (75 MHz, DMSO-d6): d = 12.2 (NCH2CH2CH3), 24.3
(NCH2CH2CH3), 62.7 (NCH2CH2CH3), 115.8 [d, J = 164.7 Hz,
Ph(C-3), Ph(C-5)], 128.0 [s, Ph(C-1)], 130.0 [d, J = 148.7 Hz,
Ph(C-2), Ph(C-6)], 160.1 [s, Ph(C-4)], 160.3 (d, J = 156.6 Hz,
C=N).
HMRS: m/z calcd for C11H13NO2: 191.09463; found: 191.0944.
Anal. Calcd for C11H13NO2: C, 69.09; H, 6.85; N, 7.32. Found: C,
69.23; H, 6.84; N, 7.32.
HMRS: m/z calcd for C10H13NO: 163.0997; found: 163.0993.
Anal. Calcd for C10H13NO: C, 73.59; H, 8.03; N, 8.58. Found: C,
73.89; H, 8.13; N, 8.55.
Synthesis 2006, No. 10, 1652–1656 © Thieme Stuttgart · New York

1656
L. Paquin et al.
PAPER
N-Methylbenzylideneamine (2l)25
Yellow liquid; bp 72 °C (0.024 Torr).
(5) Bose, A. K.; Manhas, M. S.; Ganguly, S. N.; Sharma, A. H.;
Banik, B. K. Synthesis 2002, 1578.
(6) Microwaves in Organic Synthesis; Loupy, A., Ed.; Wiley-
VCH: Weinheim, 2002.
4
1H NMR (300 MHz, CDCl3): d = 3.35 (d, J = 2 Hz, 3 H, NCH3),
7.15–7.80 (m, 5 H, Ph), 8.05 (q, 4J = 2 Hz, 1 H, CH=).
(7) (a) Loupy, A. Top. Curr. Chem. 1999, 206, 199.
(b) Tanaka, K.; Toda, F. Chem. Rev. 2000, 100, 2025.
(c) Sridharan, V.; Perumal, S.; Avendano, C.; Menendez, J.
C. Synthesis 2006, 91.
(8) Jeselnik, M.; Varma, R. S.; Polanc, S.; Kocevar, M. Chem.
Commun. 2001, 1716.
N-Methyl-4-methoxybenzylideneamine (2m)26
Yellow liquid; bp 65 °C (0.035 Torr).
4
1H NMR (200 MHz, CDCl3): d = 3.37 (d, J = 2 Hz, 3 H, NCH3),
3.73 (s, 3 H, 4-CH3OPh), 6.78 – 7.67 (m, 4 H, Ph), 7.86 (q, 4J = 2
Hz, 1 H, CH=).
(9) Abdallah-El Ayoubi, S.; Texier-Boullet, F.; Hamelin, J.
Synthesis 1994, 258.
N-Methyl-4-Chlorobenzylideneamine (2n)26
Pale yellow liquid; bp 50 °C (0.04 Torr).
(10) Spring, M. M. Chem. Rev. 1940, 26, 297.
(11) Wagner, E. C. J. Org. Chem. 1954, 19, 1862.
(12) Layer, R. W. Chem. Rev. 1963, 63, 489.
(13) Staudinger, H.; Liebigs, H. Liebigs Ann. Chem. 1907, 51,
356.
4
1H NMR (200 MHz, CDCl3): d = 3.48 (d, J = 2 Hz, 3 H, NCH3),
7.20–7.69 (m, 4 H, Ph), 8.20 (q, 4J = 2 Hz, 1 H, CH=).
N-Methyl-4-nitrobenzylideneamine (2o)27
Yellow/brown solid; mp 48 °C.
(14) Ojima, I.; Inaba, S.; Oshida, K. Tetrahedron Lett. 1977,
3643.
(15) Ojima, I.; Inaba, S. Tetrahedron Lett. 1980, 21, 2077.
(16) Taggi, A. E.; Hafez, A. M.; Wack, H.; Young, B.; Ferraris,
D.; Lectka, T. J. Am. Chem. Soc. 2002, 124, 6626.
(17) Mukaiyama, T.; Akamatsu, H.; Han, J. S. Chem. Lett. 1990,
889.
(18) Schunk, S.; Enders, D. Org. Lett. 2000, 2, 907.
(19) Texier-Boullet, F.; Latouche, R.; Hamelin, J. Tetrahedron
Lett. 1993, 34, 2123.
4
1H NMR (200 MHz, CDCl3): d = 3.55 (d, J = 2 Hz, 3 H, NCH3),
7.70–8.30 (m, 4 H, Ph), 8.33 (q, 4J = 2 Hz, 1 H, CH=).
N-Methyl-4-methylbenzylideneamine (2p)28
Yellow liquid; bp: 25 °C (0.034 Torr).
1H NMR (200 MHz, CDCl3): d = 2.32 (s, 3 H, 4-CH3Ph), 3.46 (d,
4J = 2 Hz, 3 H, NCH3), 7.10–7.69 (m, 4 H, Ph), 8.22 (q, 4J = 2 Hz,
1 H, CH=).
(20) Texier-Boullet, F. Synthesis 1985, 679.
(21) Leardini, R.; Nanni, D.; Tundo, A.; Zanardi, G.; Ruggieri, F.
J. Org. Chem. 1992, 57, 1842.
Acknowledgment
(22) Midland, M.; Koops, R. J. Org. Chem. 1992, 57, 1158.
(23) Commarmot, R.; Didenot, R.; Gardais, J. F. Prolabo Rhône-
Poulenc/Prolabo Patent number 84/03496, 1986; Chem.
Abstr. 1986, 105, 17442.
L.P. thanks E.C. for financial support (5th RTDP).
(24) Rault, P.; Pilard, J. F.; Touaux, B.; Texier-Boullet, F.;
Hamelin, J. Synlett 1994, 93.
References
(1) Loupy, A.; Petit, A.; Hamelin, J.; Texier-Boullet, F.;
Jacquault, P.; Mathé, D. Synthesis 1998, 1213; and
references cited therein.
(2) Lidström, P.; Tierney, J.; Wathey, B.; Westman, J.
Tetrahedron 2001, 9225; and references cited therein.
(3) Varma, R. S. Green Chem. 1999, 1, 43.
(25) Compare to a commercial product: CAS number 6852-56-8.
(26) Beilsteins Handbuch der Organischen Chemie; E IV, Vol. 7:
518; compare to a commercial product, CAS number 622-
29-7.
(27) Jang, J.; Sin, K. S.; Park, H. Arch. Pharm. Res. 2001, 24,
503.
(4) Varma, R. S. Clean Prod. Processes 1999, 1, 132.
(28) Kaupp, G.; Schmeyers, J.; Boy, J. Tetrahedron 2000, 56,
6899.
Synthesis 2006, No. 10, 1652–1656 © Thieme Stuttgart · New York