Erbium(III) triflate: A valuable catalyst for the synthesis of aldimines, ketimines, and enaminones

Article abstract of DOI:10.1055/s-2006-926378

Aldimines, ketimines, and enaminones can be obtained under erbium(III) inflate catalysis. The reaction mechanism is that typical of imine synthesis. The role of the catalyst is demonstrated for the synthesis of aromatic imines. In contrast to CeCl₃/NaI addition to unsaturated aldehydes, which results in Michael addition, no Michael adduct was observed under erbium(III) triflate catalysis. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-2006-926378

PAPER
1127
Erbium(III) Triflate: A Valuable Catalyst for the Synthesis of Aldimines,
Ketimines, and Enaminones
Erbium(III)
Trifl
e
te:
A
C
ata
n
S
a
ynthesisof
t
A
ldim
o
ines,
K
etimines, an
D
d
E
naminones alpozzo,*a Antonio De Nino,a Monica Nardi,a Beatrice Russo,b Antonio Procopiob
a
Dipartimento di Chimica, Univesità della Calabria, Ponte Bucci, cubo 12C, 87030 Arcavacata di Rende (Cs), Italy
Fax +39(0984)493077; E-mail: dalpozzo@unical.it
b
Dipartimento di Scienze Farmaco-Biologiche, Università della Magna Graecia, Complesso Ninì Barbieri, 88021 Roccelletta di Borgia
(Cz), Italy
Received 17 October 2005; revised 7 November 2005
nucleophilic attack on the carbonyl compound.4,5 Most of
these methodologies suffer from drawbacks, such as high
reaction temperatures, prolonged reaction times, high cost
or moisture sensitive reagents or catalysts, requirement of
Abstract: Aldimines, ketimines, and enaminones can be obtained
under erbium(III) triflate catalysis. The reaction mechanism is that
typical of imine synthesis. The role of the catalyst is demonstrated
for the synthesis of aromatic imines. In contrast to CeCl3/NaI addi-
tion to unsaturated aldehydes, which results in Michael addition, no special apparatus for hazardous solvents, production of
Michael adduct was observed under erbium(III) triflate catalysis.
side products, or involvement of cumbersome product iso-
lation procedures.
Key words: imines, enaminones, erbium triflate, Lewis acids, ca-
talysis
In recent years metal triflates were introduced as mild and
efficient Lewis acid catalysts.6 Their Lewis acidity was
related to their hydrolysis constant (Kh) and water ex-
change rate constants (WERC). The metals, which exhib-
ited good catalytic activity in screening experiments, had
pKh values in the range 4–10 and WERC values grater
than 3.2 × 106 M–1s–1. More recently, the relative Lewis
acidity of rare earth metal triflates was evaluated based on
their competitive ligand dissociation from complexes us-
ing tandem mass spectrometry.7 However, metal triflates
have only been applied to three-component reactions, in-
volving carbonyl compounds and amines, where imines
were not the final product.8
Azomethines are useful and versatile intermediates in
many organic transformations. More than one hundred
years ago Schiff1 reported their preparation by the con-
densation of amines with carbonyl compounds and since
then azomethines have found broad application in organic
chemistry. The condensation of carbonyl compounds with
primary amines proceeds through an addition–elimination
mechanism (Scheme 1), initially the basic nitrogen of the
amine adds to the carbonyl moiety to furnish a tetrahedral
intermediate, which undergoes elimination of a water
molecule to generate an imine.2
In the last few years we were interested in the Lewis acid
behavior of erbium(III) triflate as a useful and environ-
mentally friendly catalyst for many acid-catalyzed reac-
tions.9 It should be noted that, among lanthanide triflates
the erbium salt has been neglected, although it is theoret-
ically in good agreement with Kobayashi’s criteria and
should exhibit high catalytic activity with its pKh of 7.9
and WERC = 1.4 × 108.6 These observations prompted us
to test erbium(III) triflate as a catalyst for the synthesis of
azomethine derivatives such as imines and enaminones.
Initially we investigated the optimum conditions, adopt-
ing the reaction between 4-methoxybenzaldehyde and
hexylamine (Table 1) as the model reaction.
R1
R2
R1
R2
A+
OH
R3NH2
O
R1
NHR3
O
R2
A+
H
A
O
R1
R2
R1
NHR3
NR3
H2O +
R2
A+= H+ or Lewis Acid
All experiments were run at room temperature, in simple
flasks, with 1 mol% erbium(III) triflate, and the disap-
pearance of the reactants was monitored by GC-MS. The
reactions always went to completion, but the reaction time
varied (Table 1, entries 1–5). Poor yield were only ob-
served under anhydrous conditions (vide infra). The reac-
tion was faster in less polar solvents, particularly in
dichloromethane, which was our solvent of choice.
Scheme 1
For many years, azeotropic distillation was the most pop-
ular technique to remove the liberated water, thus shifting
the equilibrium towards the imine.3 Subsequently, molec-
ular sieves, dehydrating solvents, or Lewis acid catalysts
have all been shown to remove water as well as facilitate
Very good yields were obtained with both aromatic and
aliphatic aldehydes and amines (Table 2).10 Under the
same reaction conditions ketones were found to be less re-
active than aldehydes (Table 3). Yields are moderate and
SYNTHESIS 2006, No. 7, pp 1127–1132
Advanced online publication: 08.03.2006
DOI: 10.1055/s-2006-926378; Art ID: Z20105SS
© Georg Thieme Verlag Stuttgart · New York
x
x
.
x
x
.2
0
0
6

1128
R. Dalpozzo et al.
PAPER
1–5) also failed to impact on the yield. In the case of
ketimines isolation of the imine was impossible and a one-
pot reduction was carried out resulting in the more stable
amines.
Table 1 Determination of the Best Solvent
Entry
Solvent
Reaction time
(min)
Yield (%)a
1
Et2O
7
5
100
100
100
100
100
15
Finally, we extended the reaction to 1,3-dicarbonyl com-
pounds. It is well-known that azomethine derivatives form
on the most electrophilic carbonyl carbon and instanta-
neously tautomerize to enaminones. Interestingly, these
reactions can be carried out in both dichloromethane and
in THF–water (9:1) without affecting the yields (Table 4).
2
CH2Cl2
3
CHCl3
30
45
30
30
4
CH3CN
CH3NO2
anhyd CH2Cl2
5
A milestone in imine synthesis was the review published
by Layer in 1963,11 in which the following was reported:
(i) aromatic aldehydes react readily and nearly quantita-
tively with amines even without removal of water; (ii)
para-substituted electron-withdrawing groups decrease
the reaction rate, while the reverse is true for aniline with
para-substituted electron-donating groups; (iii) aliphatic
aldehydes generally give dimeric or polymeric materials
with aromatic amines, but this does not occur with aliphat-
6
a GC yields.
are affected neither by the addition of a classical water
scavenger such as anhydrous MgSO4 nor by molecular
sieves. Increasing the amount of catalyst (Table 3, entries
Table 2 Synthesis of Aldimines
H
R1
H
R1
R2
H
R1
Er(OTf)3 (1 mol%), r.t.
LiBH4, THF
+
R2NH2
O
N
HN
R2
1
2
3
4
Entry
1
R1
R2
Product
Reaction time (min) Yield (%)a
4-MeOC6H4
C6H13
3a
5
95
1a
2a
2
3
2-HOC6H4
1b
2a
2a
2a
2a
3b
4a
3c
3d
3e
3f
5
98
Ph
1c
30b
20
97
4
4-NO2C6H4
1d
98
5
PhCH=CH
1e
30
67
6
1c
1c
1c
Ph
2b
45
67
7
4-MeOC6H4
2c
30
95
8
4-NO2C6H4
2d
3g
4b
4a
3h
1440
30b
25b
120d
52c
92
9
C5H11
1f
2a
10
11
1f
PhCH2
2e
82
1f
2b
traces
a Isolated yields.
b Refers to time taken for starting materials to disappear as monitored by GC-MS; reduction with LiBH4 requires about 5 min.
c Longer reaction times do not modify the product/reactant ratio; 45% of starting materials were recovered.
d After 2 h the aldehyde had disappeared and a dimeric product was detected by GC-MS.
Synthesis 2006, No. 7, 1127–1132 © Thieme Stuttgart · New York

PAPER
Erbium(III) Triflate: A Catalyst for the Synthesis of Aldimines, Ketimines, and Enaminones
1129
Table 3 Synthesis of Ketimines
R3
R1
R3
R1
R2
R3
HN
R1
R2
Er(OTf)3 (1 mol%), r.t.
LiBH4, THF
+
2
O
N
5
6
7
Entry
Ketone
Amine
Solvent
Catalyst
(mol%)
Drying agent Product
Reaction time Yield (%)b
(h)a
1
2
3
4
5
6
R1 = R3 = Et 5a
2a
2a
2a
2a
2a
2a
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
–
1
3
1
1
1
1
–
7a
7a
7a
7a
7a
7b
2
51
58
46
48
50
68
5a
5a
5a
5a
–
2
MgSO4
2
4 Å MS
2
–
–
2
R1 = Ph R3 = Me
CH2Cl2
4.5
5b
7
8
R1 = R3 = -(CH2)5-
5c
2a
2e
CH2Cl2
CH2Cl2
1
1
–
–
7c
2.5
3
60
55
5c
7d
a Time taken to reach equilibrium; reduction with LiBH4 requires about 5 min.
b Isolated yields, remaining is reduced ketone and amine, longer reaction times do not modify the product/reactant ratio.
ic amines; (iv) ketones react more slowly with amines
than aldehydes and water must be removed from the reac-
tion mixture; and (v) aldol condensation products form
more readily from methyl ketones than from methylene
ketones.
Table 4 Synthesis of Enaminones
H
R2
O
O
O
N
Er(OTf)3 (1 mol%), r.t.
+ 2
R1
R1
8
9
More recently an extensive evaluation of the best catalyst
for aldimine preparation was reported by Chakraborti et
al. The efficiency of twenty-two catalysts in different sol-
vents for the reaction of 4-methoxybenzaldehyde and 4-
nitroaniline was analyzed.4k He suggested magnesium
perchlorate in DCE at room temperature as the best cata-
lyst for this reaction.
Entry
1
1,3-Dicar- Amine Product Time
Yield (%)a
bonyl
(h)
R1
R2
CH2Cl2 THFb
Me
2a
9a
3
97
95
8a
As described by Layer,11 aromatic aldehydes react rapidly
and almost quantitatively with amines; however, some in-
teresting features are observed. Electron-donating groups
should reduce the electrophilicity of the carbonyl com-
pound through resonance, and ortho-substituents through
steric hindrance. Nevertheless, the reactions of 4-meth-
oxybenzaldehyde (1a) and 2-hydroxybenzaldehyde (1b)
with hexylamine were the fastest (Table 2, entries 1 and
2). This is clear evidence for the coordination of erbi-
um(III) to the carbonyl oxygen of the aldehyde. In fact,
the same resonance effect, which decreases electrophilic-
ity of the carbonyl carbon, enhances the Lewis basicity of
the carbonyl oxygen, thus, erbium cannot coordinate to
oxygen. This compensates for the lack of electrophilicity
and provides for an increase in the reaction rate.
2
3
4
8a
8a
8a
2b
2e
9b
9c
9d
2.5
95
98
87
93
98
78
23
30
i-Pr
2f
5
6
8a
allyl
2g
9e
9f
26
96
93
100
92
Ph
8b
2b
2.5
7
8
8b
2e
2a
9g
9h
2
2
97
96
OEt
8c
100
100
9
8c
2b
9i
6c
71
70
a Isolated yields.
Coordination seems to become less important in the ab-
sence of electron-donating groups (Table 2, entries 3 and
4). The reaction rate is, in fact, lowered, but the trend is
not linear: a four-fold decrease in the reaction rate was ob-
served when 4-nitrobenzaldehyde was used in place of 4-
b THF–water (9:1).
c After 24 h the yield was almost quantitative.
Synthesis 2006, No. 7, 1127–1132 © Thieme Stuttgart · New York

1130
R. Dalpozzo et al.
PAPER
3+
methoxybenzaldehyde, while benzaldehyde resulted in an
even slower reaction rate. Chakraborti reported that 4-ni-
trobenzaldehyde (1d) reacts with aniline without catalyst
in 75% yield in one hour and this fact was explained
through an enhanced electrophilicity of the carbonyl car-
bon by resonance.4k However, here we have improved the
yield further by the addition of erbium(III) triflate (98%
vs 75% isolated yield) and also had a positive impact on
the reaction time (20 min vs 1 h).
nH2O
Er⋅nH2O + 3 (OTf)–
Er(OTf)3
Er3+⋅(n-1)H2O
H
O
3+
+ 1
R2
R1
2
R1
NHR3
Er⋅nH2O
R2
O
Er3+⋅(n-1)H2O
H2O
Er3+⋅(n-1)H2O
Amine nucleophilicity is not influenced by erbium coor-
dination to nitrogen; however, increasing the nucleophi-
licity of the amine accelerates the reaction (Table 2,
entries 3, 6–8).
3 + H2O
Scheme 2 A tentative mechanism for the reaction
In conclusion we can state that the rate of the reaction is
governed by balancing the opposite forces exerted by the
carbonyl moiety: the electrophilicity of the carbon and the
coordination of the erbium cation to oxygen.
when there is enough water present to dissociate erbium
triflate, so that under anhydrous conditions, where the wa-
ter is generated during the reaction, a sluggish reaction re-
sults.
There was a significant difference in the stability of ald-
imines formed from aromatic amines and aliphatic
amines. Aromatic amines resulted in aldol condensation
aldimine products, while their aliphatic derivatives were
found to be unstable and reduction of the imines formed
was required, which is in agreement with the results re-
ported by Layer (Table 2, entries 9–11).11
It should be noted in the reaction with ketones erbium(III)
triflate was confirmed to be a weak acidic catalyst, since
aldol condensation products were never observed in the
reaction of a methyl ketone such as acetophenone
(Table 3, entry 6).11,13
Finally steric hindrance seems to influence the enaminone
synthesis; in fact, the reaction with isopropylamine is the
slowest. The was confirmed by the reaction with diethyl-
amine; 4-(N,N-diethylamino)pent-3-en-2-one was isolat-
ed in only 11% yield after a day in dichloromethane and
no significant amounts were detected in THF–water, not-
withstanding the higher electrophilicity of a secondary
with respect to a primary amine.
Finally, it should be noted that a,b-unsaturated aldehydes
resulted exclusively in imine formation, which is an ad-
vantage over the CeCl3/NaI system, which was reported to
give exclusively Michael addition products.12
Layer reported that ketones react slower than aldehydes
and an equilibrium is reached. Moreover, none of the
ketimines tested were stable under our conditions and a
subsequent reduction step was necessary to fully charac-
terize the products.
In this paper we have reported a good method for the syn-
thesis of imines and enaminones. The yields are compara-
ble to those previously reported, but this protocol shows
some tangible advantages: use of non-anhydrous condi-
tions, non-sophisticated equipment, non-toxic14 and non-
explosive catalyst, an easy and consistent recovery of the
catalyst, therefore a negligible release into the environ-
ment,15 and last but not least low costs. In fact, although
Er(OTf)3 is the most expensive (€/mmol) catalyst among
those employed in imine synthesis,4,5 it is recoverable and
used in much lower amounts.
It is noteworthy that attempts to remove water by classical
scavengers were unsuccessful (Table 3, entries 1–5).
Moreover, imine synthesis was much slower in anhydrous
conditions (Table 3, entry 6), which appears to be a con-
tradiction. A tentative explanation of this behavior may be
attributed to the role of erbium in sequestering the water
formed during the reaction. According to Kobayashi’s
theory,6 only hydrated cations are able to act as Lewis ac-
ids. During the fast water exchange of hydrated cations,
carbonyl compounds can be activated by coordinating to
the metal cation (Scheme 2).
All reactants, catalyst, and solvents are commercially available and
were used without purification, except aldehydes, which were dis-
tilled immediately before use. PE used had a bp range 40–60 °C. 1H
NMR and 13C NMR spectra were recorded with a Brucker WM 300
instrument at 300 MHz and 75 MHz, respectively, in CDCl3. Chem-
If water is scavenged cations cannot be dissociated from
the counter ion and catalysis does not occur, so the reac-
tion rate is lowered. Therefore, a very subtle equilibrium
between these two opposite needs must occur: there must
be enough water present to partially hydrate the cation to
exploit catalysis, but not too much to reverse the equilib-
rium back towards the reagents.
1
ical shifts are given in ppm from TMS as internal standard for H
NMR spectra. For 13C NMR spectra the central line of CDCl3 (77
ppm) has been used as the internal reference. Assignment of the sig-
nals in the 13C NMR spectra was made by DEPT experiments. Imine
synthesis has been monitored by a GC-MS Shimadzu workstation
fitted with a GC 2010 (30 m QUADREX 007-5MS capillary col-
umn, operating in splitless mode, 1 mL/min flow of He as carrier
gas) and a 2010 quadrupole mass-detector.
This hypothesis is also supported by the results observed
in enaminone synthesis. In fact, in both anhydrous dichlo-
romethane and THF, reaction times are much longer. This
evidence confirms that the hydrated erbium cation is re-
sponsible for the catalytic cycle. The reaction starts only
Spectroscopic data for benzylhexylamine (4a),16 benzylidene-
aniline (3e),17 benzylidene-4-methoxyaniline (3f),17 benzylidene-4-
Synthesis 2006, No. 7, 1127–1132 © Thieme Stuttgart · New York

PAPER
Erbium(III) Triflate: A Catalyst for the Synthesis of Aldimines, Ketimines, and Enaminones
1131
nitroaniline (3g),18 dihexylamine (4b),19 hexyl-(1-phenylethyl-
amine (7b),20 cyclohexylhexylamine (7c),21 cyclohexylbenzyl-
amine (7d),22 4-(N-phenylamino)pent-3-en-2-one (9b),23 4-(N-
benzylamino)pent-3-en-2-one (9c),24 4-(N-isopropylamino)pent-3-
en-2-one (9d),25 4-(N-allylamino)pent-3-en-2-one (9e),5e 4-(N,N-
diethylamino)pent-3-en-2-one,26 3-(N-phenylamino)-1-phenylbut-
2-en-1-one (9f),27 3-(N-benzylamino)-1-phenylbut-2-en-1-one
(9g),5c and ethyl 3-(N-phenylamino)but-2-enoate (9i)28 were com-
parable with literature data.
13C NMR: d = 13.98 (CH3), 22.53 (CH2), 26.97 (CH2), 30.65 (CH2),
31.56 (CH2), 61.94 (CH2), 123.79 (2 × CH), 128.62 (2 × CH),
141.83 (C), 148.86 (C), 158.30 (C=N).
MS: m/z (%) = 233 (M+ – 1, 1), 205 (100), 177 (20), 163 (25), 117
(65), 90 (40), 88 (25).
Anal. Calcd for C13H18N2O2: C, 66.62; H, 7.76; N, 5.98. Found: C,
66.60; H, 7.75; N, 6.00.
1-Hexyl-4-phenyl-1-aza-1,3-butadiene (3d)
Oil.
General Procedure
1H NMR: d = 0.89 (t, J = 6.9 Hz, 3 H, Me), 1.20–1.73 (m, 8 H, 4 ×
CH2), 3.50 (dt, J = 1.2, 6.9 Hz, 2 H, CH2N), 6.88–6.95 (m, 2 H,
CH=CH), 7.23–7.50 (m, 5 H, ArH), 7.99–8.04 (m, 1 H, CH=N).
13C NMR: d = 14.00 (CH3), 22.56 (CH2), 26.99 (CH2), 30.88 (CH2),
31.62 (CH2), 61.59 (CH2), 127.13 (2 × CH), 128.30 (CH), 128.74
(2 × CH), 128.97 (CH), 130.36 (C), 135.83 (CH), 141.14 (CH=N).
To a solution of carbonyl compound 1a–f, 5a–c, or 8a–c (2 mmol)
in CH2Cl2 (4 mL), Er(OTf)3 (20 mmol, 1%) and appropriate amine
2a–g (2.2 mmol) were added and the resulting solution was stirred
at r.t. When the starting material had disappeared or there was not
change in the starting material/product ratio (GC-MS), the crude
imine were poured into a sat. solution of Na2CO3 (5 mL), and ex-
tracted with CH2Cl2 (2 × 5 mL). The organic layer was dried over
anhydrous Na2SO4 and concentrated under reduced pressure. Any
unreacted starting materials were reused.
MS: m/z (%) = 215 (M+, 14), 200 (11), 186 (47), 158 (29), 144 (81),
130 (53), 115 (100), 91 (36), 41 (75).
Anal. Calcd for C15H21N: C, 83.64; H, 9.86; N, 6.50. Found: C,
83.65; H, 9.85; N, 6.50.
If the imine formed was unstable instead of the work-up described
above the mixture was treated with a solution of LiBH4 (2 M, THF;
1.2 mL) for about 5 min. Subsequently the mixture was cautiously
poured into a solution of dilute HCl (4:1), then neutralized with a
sat. solution of Na2CO3, and extracted with CH2Cl2 (2 × 5 mL). The
organic layer was dried over anhyd Na2SO4 and concentrated under
reduced pressure. Products 3a,b, 4a,b, 7a–d, 9a–i were then puri-
fied on a short silica gel column (PE–Et2O, 9:1).
(1-Ethylpropyl)hexylamine (7a)
Oil.
1H NMR: d = 0.88 (t, J = 6.3 Hz, 3 H, Me), 1.02 (t, J = 7.3 Hz, 6 H,
2 × Me), 1.24–1.39 (m, 6 H), 1.70–195 (m, 6 H), 2.83–3.02 (m, 3
H), 7.18 (br s, 1 H).
13C NMR: d = 9.28 (2 × CH3), 13.86 (CH3), 22.25 (2 × CH2), 25.84
(CH2), 26.18 (CH2), 26.53 (CH2), 31.17 (CH2), 45.19 (CH2N),
60.31 (CH=N).
MS: m/z (%) = 170 (M+ – 1, 0.5). 142 (100), 100 (7), 84 (3), 72 (8),
58 (23), 43 (12).
Hexyl(4-methoxybenzylidene)amine (3a)
Oil.
1H NMR: d = 0.87 (t, J = 6.3 Hz, 3 H, Me), 1.20–1.45 (m, 6 H, 3 ×
CH2), 1.68 (quint, J = 6.7 Hz, 2 H, CH2), 3.56 (t, J = 7.0 Hz, 2 H,
CH2N), 3.83 (s, 3 H, OMe), 6.80–7.70 (A2B2, 4 H, ArH), 8.19 (s, 1
H, CH=N).
13C NMR: d = 14.01 (CH3), 22.58 (CH2), 27.07 (CH2), 30.99 (CH2),
31.66 (CH2), 55.29 (OCH3), 61.68 (CH2), 113.94 (2 × CH), 129.49
(2 × CH), 131.94 (C), 159.95 (CH=N), 161.45 (CO).
Anal. Calcd for C11H25N: C, 77.08; H, 14.74; N, 8.18. Found: C,
77.10; H, 14.75; N, 8.15.
4-(N-Hexylamino)pent-3-en-2-one (9a)
Oil.
MS: m/z (%) = 219 (M+, 5), 204 (10), 190 (57), 162 (50), 148 (65),
135 (40), 121 (100), 91 (30), 77 (29).
1H NMR: d = 0.89 (t, J = 5.4 Hz, 3 H, Me), 1.10–1.80 (m, 8 H, 4 ×
CH2), 1.91 (s, 3 H, MeC=C), 1.99 (s, 3 H, MeC=O), 3.22 (q, J = 6.6
Hz, 2 H, CH2N), 4.95 (s, 1 H, CH=C), 10.85 (br s, 1 H, NH).
13C NMR: d = 13.89 (CH3), 18.68 (CH3), 22.41 (CH2), 26.42 (CH2),
28.60 (CH3), 29.98 (CH2), 31.36 (CH2), 42.94 (CH2), 94.88 (CH),
163.03 (C), 194.46 (C).
Anal. Calcd for C14H21NO: C, 76.64; H, 9.68; N, 6.39. Found: C,
76.65; H, 9.65; N, 6.40.
(2-Hexyliminomethyl)phenol (3b)
Oil.
1H NMR: d = 0.89 (t, J = 7.0 Hz, 3 H, Me), 1.26–1.44 (m, 6 H, 3 ×
CH2), 1.68 (quint, J = 7.0 Hz, 2 H, CH2), 3.56 (dt, J = 7.0, 1.2 Hz, 2
H, CH2N), 6.8–7.2 (m, 4 H, ArH), 8.31 (t, J = 1.2 Hz, 1 H, CH=N),
13.68 (s, 1 H, OH).
MS: m/z (%) = 183 (M+, 85), 168 (93), 126 (84), 112 (100), 98 (44),
84 (63), 70 (61), 43 (76).
Anal. Calcd for C11H21NO: C, 72.05; H, 11.55; N, 7.64. Found: C,
72.00; H, 11.55; N, 7.65.
13C NMR: d = 14.00 (CH3), 22.52 (CH2), 26.79 (CH2), 30.77 (CH2),
31.49 (CH2), 59.46 (CH2), 117.00 (2 × CH), 118.29 (2 × CH),
118.75 (C), 130.99 (CH), 131.93 (CH), 161.36 (CO), 164.35
(CH=N).
MS: m/z (%) = 205 (M+, 82), 190 (15), 176 (80), 148 (98), 134 (92),
107 (100).
Ethyl 4-(N-Hexylamino)but-2-enoate (9h)
Oil.
1H NMR: d = 0.89 (t, J = 5.4 Hz, 3 H, Me), 1.20–1.65 (m, 11 H,
OCH2CH3, 4 × CH2), 1.91 (s, 3 H, MeC=C), 3.19 (q, J = 6.5 Hz, 2
H, CH2N), 4.08 (q, J = 6.9 Hz, 2 H, CH2O), 4.43 (s, 1 H, CH=C),
8.55 (br s, 1 H, NH).
13C NMR: d = 13.93 (CH3), 14.59 (CH3), 19.31 (CH3), 22.45 (CH2),
26.47 (CH2), 30.36 (CH2), 31.45 (CH2), 43.00 (CH2), 58.14 (CH2),
81.66 (CH), 161.88 (C), 170.60 (C).
Anal. Calcd for C13H19NO: C, 76.03; H, 9.35; N, 6.83. Found: C,
76.00; H, 9.35; N, 6.80.
Hexyl(4-nitrobenzylidene)amine (3c)
Oil.
MS: m/z (%) = 213 (M+, 29), 198 (14), 184 (20), 168 (40), 126 (40),
1H NMR: d = 0.87 (t, J = 7.0 Hz, 3 H, Me), 1.5–1.8 (m, 8 H, 4 ×
CH2), 3.65 (t, J = 6.7 Hz, 2 H, CH2N), 7.75–8.30 (A2B2, 4 H, ArH),
8.34 (s, 1 H, CH=N).
96 (100), 71 (31), 55 (31).
Anal. Calcd for C12H23NO2: C, 67.57; H, 9.19; N, 6.57. Found: C,
67.60; H, 9.20; N, 6.55.
Synthesis 2006, No. 7, 1127–1132 © Thieme Stuttgart · New York

1132
R. Dalpozzo et al.
PAPER
(7) (a) Tsuruta, H.; Yamaguchi, K.; Imamoto, T. Tetrahedron
2003, 59, 10419. (b) Tsuruta, H.; Yamaguchi, K.; Imamoto,
T. Chem. Commun. 1999, 1703.
(8) (a) Firouzabadi, H.; Iranpoor, N.; Sobhani, S. Synthesis
2004, 2692. (b) Aspinall, H. C.; Bissett, J. S.; Greeves, N.;
Levin, D. Tetrahedron Lett. 2002, 43, 323.
(9) (a) Procopio, A.; Dalpozzo, R.; De Nino, A.; Maiuolo, L.;
Russo, B.; Sindona, G. Adv. Synth. Catal. 2004, 346, 1465.
(b) Dalpozzo, R.; De Nino, A.; Maiuolo, L.; Nardi, M.;
Procopio, A.; Tagarelli, A. Synthesis 2004, 496.
(c) Procopio, A.; Dalpozzo, R.; De Nino, A.; Nardi, M.;
Sindona, G.; Tagarelli, A. Synlett 2004, 2633. (d) Procopio,
A.; Dalpozzo, R.; De Nino, A.; Maiuolo, L.; Nardi, M.;
Russo, B. Adv. Synth. Catal. 2005, 347, 1447. (e) Procopio,
A.; Dalpozzo, R.; De Nino, A.; Maiuolo, L.; Nardi, M.;
Romeo, G. Org. Biomol. Chem. 2005, 4129. (f) Procopio,
A.; Dalpozzo, R.; De Nino, A.; Nardi, M.; Russo, B.;
Tagarelli, A. Synthesis 2006, 332.
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Synthesis 2006, No. 7, 1127–1132 © Thieme Stuttgart · New York