Straightforward synthesis of aromatic imines from alcohols and amines or nitroarenes using an impregnated copper catalyst

Article abstract of DOI:10.1002/ejoc.201200319

The impregnated copper on magnetite catalyst is a versatile system for the synthesis of imines starting from alcohols and amines. This catalyst does not require any type of expensive and difficult to handle organic ligand or typical transition metals, and provides excellent yields achievable under mild reaction conditions. Moreover, the catalyst is very easy to remove from the reaction medium by simply using a magnet. The one-pot process of dehydrogenation of alcohols in the presence of aniline followed by aqueous hydrolysis gave pure alcohols in excellent yields. In addition to amines, nitroarenes could be used as the nitrogen-containing reagent. In the case of primary amines the expected imines were successfully prepared under similar reaction conditions. The impregnated copper on magnetite catalyst is a versatile system for the synthesis of imines starting from alcohols and amines or nitroarenes. A similar synthesis of imines was accomplished using only primary amines. This catalyst avoids the use of expensive organic ligands and other transition metals while enabling excellent yields under mild reaction conditions. Copyright

Full text of DOI:10.1002/ejoc.201200319

Job/Unit: O20319
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FULL PAPER
DOI: 10.1002/ejoc.201200319
Straightforward Synthesis of Aromatic Imines from Alcohols and Amines or
Nitroarenes Using an Impregnated Copper Catalyst
Juana M. Pérez,[a] Rafael Cano,[a] Miguel Yus,[a] and Diego J. Ramón*[a]
Dedicated to Professor Miguel A. Miranda on the occasion of his 60th birthday
Keywords: Copper / Heterogeneous catalysis / Hydrogen transfer / Imines / Oxidation
The impregnated copper on magnetite catalyst is a versatile
system for the synthesis of imines starting from alcohols and
amines. This catalyst does not require any type of expensive
and difficult to handle organic ligand or typical transition
metals, and provides excellent yields achievable under mild
reaction conditions. Moreover, the catalyst is very easy to re-
move from the reaction medium by simply using a magnet.
The one-pot process of dehydrogenation of alcohols in the
presence of aniline followed by aqueous hydrolysis gave
pure alcohols in excellent yields. In addition to amines, ni-
troarenes could be used as the nitrogen-containing reagent.
In the case of primary amines the expected imines were suc-
cessfully prepared under similar reaction conditions.
to the use of catalysts to effectively carry out this transfor-
mation. In fact, some complexes and compounds derived
from transition metals of the second and third row, such as
ruthenium,[8] palladium,[9] osmium,[10] iridium,[11] plati-
num,[12] and gold[13] have shown promise for this imine syn-
thesis strategy. However, the toxicities, pricing, and stability
of these metals prohibits their general use for industrial
purposes.
Consequently, we have recently developed a new, simple
and robust method to immobilize different metal oxides[14]
onto magnetite.[15] Along this research line, we report herein
the first catalyst derived from the cheaper and safer first-
row copper transition metal impregnated on magnetite and
its use in the preparation of imines by reaction of alcohols
and different nitrogen-atom sources such as amines[16] or
nitroarenes.[17]
Introduction
Imines are crucial intermediates and their reactions are
fundamental and ubiquitous in the synthesis of biologically
active nitrogen compounds, such as β-lactams, dyes, fra-
grances, pharmaceuticals, fungicides, and agricultural
chemicals.[1] Generally, imines, including Schiff bases, are
produced from the condensation of primary amines with
carbonyl compounds. However, several new synthetic stra-
tegies have been developed in recent years, including the
metal-catalyzed oxidation (or dehydrogenation) of primary
amines to give the corresponding imines.[2] Imines have also
been prepared from symmetrical secondary amines.[3] How-
ever, the variety of compounds obtained in this manner was
very limited; the use of secondary arylamine derivatives cir-
cumvented this restriction enabling access to a much wider
range of products.[4]
The in situ oxidative imine formation process starting
from alcohols and amines by manganese oxides and molec-
ular sieves formally permitted access to several types of
imines.[5] It should be pointed out that the same intermedi-
ates have been detected in the alkylation[6] of amines by
alcohols through the hydrogen autotransfer reaction.[7] The
use of stoichiometric amounts of manganese oxidants is
highly undesirable from both economical and environmen-
tal points of view. Therefore, much attention has been paid
Results and Discussion
Preparation of Imines from Alcohols and Amines
The first process evaluated was the reaction between
benzyl alcohol (1a) and aniline (2a) under an Ar atmo-
sphere to give corresponding imine (3a) as depicted in
Table 1, using the impregnated copper on magnetite as cata-
lyst. It should be pointed out that simple copper(II) acetate
gave, in a similar process,[18] the typical monoalkylated
amine, rendering, in this case, N-benzylaniline. However,
using the new copper catalyst, imine could be isolated after
a few days of reaction in the absence of oxygen. Thus, the
reaction using NaOH as base gave expected imine (3a) with
[a] Departamento Química Orgánica and Instituto de Síntesis
Orgánica, Universidad de Alicante,
Apdo. 99, 03080 Alicante, Spain
Fax: +34-965903549
E-mail: djramon@ua.es
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201200319.
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J. M. Pérez, R. Cano, M. Yus, D. J. Ramón
FULL PAPER
a small amount of the corresponding N-benzylaniline, Table 1. Optimization of reaction conditions.[a]
which came from the aforementioned hydrogen auto-
transfer process. The study of the influence of base, as well
as its absence, showed that NaOH rendered the best results
(Table 1, compare Entries 1–7). The effect of reaction tem-
perature was also investigated. Temperatures below 130 °C
were found to minimize formation of by-product N-benzyl-
Entry Base (mol-%) Solvent
T
[°C]
t
[d]
Yield
[%][b]
65[c]
2[d]
39
3
27
1
2
aniline and to enhance imine formation; ideal yields rou-
tinely resulted from reactions run at 100 °C (Table 1, En-
tries 1 and 8–10). Choice of solvent was also found to influ-
ence reaction yield (Table 1, Entries 10–12), with toluene
providing the best results. In addition, increased reaction
basicity was found to have a significantly negative effect
(Table 1, Entries 13 and 14); an increase in the amount of
benzyl alcohol (Table 1, Entry 15) also had a negative ef-
fect, whereas an increase in the amount of aniline had a
beneficial effect on the yield, being practically quantitative
(Table 1, Entry 16). The influence of catalyst concentration
was also studied. Decreased catalyst concentrations led to
lower reaction yields though increases in catalyst produced
only marginal increases in yield (Table 1, Entries 17 and
18). The reaction was repeated in the presence of air to see
if this might be the actual source of oxidant in these reac-
tions. However, we found no difference in yield or required
reaction time between the reactions performed with or
without air (Table 1, Entries 16 and 19). The reaction was
performed also using the commercial micro-magnetite sup-
1
2
3
4
5
6
7
8
NaOH (140)
KOH (140)
LiOH (140)
Na2CO3 (140)
K2CO3 (140)
NaOAc (140)
–
NaOH (140)
NaOH (140)
NaOH (140)
NaOH (140)
NaOH (140)
NaOH (300)
NaOH (500)
NaOH (140)
NaOH (140)
NaOH (140)
NaOH (140)
NaOH (140)
NaOH (140)
PhMe
PhMe
PhMe
PhMe
PhMe
PhMe
PhMe
PhMe
PhMe
PhMe
dioxane
MeCN
PhMe
PhMe
PhMe
PhMe
PhMe
PhMe
PhMe
PhMe
130
130
130
130
130
130
130
25
4
4
4
4
4
4
7
7
7
4
6
6
4
4
4
4
4
4
4
4
27
71
91
9
70
10
11
12
13
14
15
16
17[i]
18[j]
19[k]
20[l]
100
100
100
100
100
100
100
100
100
100
100
61
18[e]
59[f]
25
20[g]
98[h]
81[h]
98[h]
95[h]
57[h]
[a] Reaction carried out using compound 1a (1.3 mmol), 2a
(1.0 mmol) in solvent (3 mL) and under an Ar atmosphere, unless
port only. This gave expected imine 3a in moderate yield otherwise stated. [b] Isolated yield after column chromatography.
[c] N-Benzylaniline was isolated in 14% yield. [d] N-Benzylaniline
was isolated in 89% yield. [e] N-Benzylaniline was isolated in 51%
yield. [f] N-Benzylaniline was isolated in 19% yield. [g] Reaction
carried out using compound 1a (2.6 mmol), 2a (1.0 mmol). [h] Re-
(Table 1, Entry 20), whereas the use of the most active nan-
opowder magnetite[15b] afforded a comparable yield (63%).
The standard catalyst[14b] was prepared from copper di-
chloride. To know the possible effect of anion on catalyst
activity, similar catalysts were prepared from copper di-
bromide and copper dinitrate. The FXR analysis revealed
that the total incorporation of copper was 1.26 and 1.35%
for bromide- and nitrate-derived catalyst, respectively; both
incorporations were similar to the observed for the stan-
action carried out using compound 1a (1.0 mmol), 2a (2.0 mmol).
[i] Reaction carried out using 0.3 mol-% of catalyst. [j] Reaction
carried out using 2.3 mol-% of catalyst. [k] Reaction carried out
under an air atmosphere. [l] Reaction performed using only magne-
tite support (powder Ͻ 5 μm; 65 mol-%).
dard chloride-derived catalyst. When these catalysts were a magnetic was analyzed by ICP-MS which revealed the
used in reactions similar to that presented in Table 1, En- presence of only 9.8% of the initial amount of copper, lower
try 16, similar yields were obtained (95 and 99% using that that obtained under typical reaction conditions involv-
bromide- and nitrate-derived catalysts, respectively), indi- ing the presence of amine. In another trial, quinoline
cating only a marginal effect of the counterion on catalytic (100 mol-%) was heated at 100 °C in toluene with the cata-
activity.
lyst and subsequent ICP-MS analysis showed an incorpora-
Once the optimal reaction conditions were established, tion of 18% of copper to the final solution which is similar
the prospect of catalyst recycling was examined. The cata- to that obtained from typical reaction conditions and sub-
lyst was recovered using a magnet, from the reaction de- stantially higher than that obtained in the absence of
scribed in Table 1, Entry 16 then washed with toluene and amines. These data support our hypothesis of a leaching
re-used under the same reaction conditions, to render ex- process. Moreover, the TEM images of the recycled catalyst
pected product 3a but in only 72% yield. A third cycle of showed a drastic change in copper particle size from
recovered catalyst use provided a modest yield of 3a (44%). 7.0Ϯ6 nm (maximum at 3 nm) for freshly prepared catalyst
The phenomenon of leaching was studied by ICP-MS to 13.0Ϯ6 nm for the recycled catalyst (Figure 1). This
analysis of the resulting reaction solution mixture, and 17% change in particle size may affect the reactivity of the recy-
of the initial amount of copper was detected (0.002% for cled catalyst. However, the BET surface area did not suffer
iron), which could be due to the formation of different im- a great change, from 6.2 m2 g–1 for the initial catalyst to
ine-copper complexes. To validate this hypothesis the pro- 11.4 m2 g–1 for the used catalyst, which is practically the
cess was repeated in the absence of amine. After 4 d of same specific area. It should be pointed out that the recy-
reaction with benzyl alcohol and NaOH in toluene at cled catalyst from the aforementioned treatment without
100 °C the solution obtained after trapping the catalyst by amine showed
a
similar particle size distribution
2
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Aromatic Imines from Alcohols and Amines or Nitroarenes
(3.7Ϯ1.5 nm, see Supporting Information) to that of the dered slightly lower yields than those obtained for aromatic
initial catalyst. However, the results obtained from treat- ones (compare, for instance, Table 2, Entries 1 and 5–7).
ment with quinoline were slightly different (9.2Ϯ1.9 nm,
see Supporting Information), indicating that nitrogen-con-
taining compounds may not only favor the leaching process
but may also facilitate the generation of CuO-particles.
Preparation of Aldehydes from Alcohols and Aniline
The success obtained in preparing imines using our cop-
per impregnated magnetite catalyst inspired us to formulate
a
process for synthesizing aldehydes from alcohols
(Table 3).
Table 3. Preparation of arenecarbaldehydes.[a]
Figure 1. Size of CuO-Fe3O4 catalyst.
Entry
Ar
Product
Yield [%][b]
The optimized protocol was then applied to other sub-
strates in order to study the scope of the reaction (Table 2).
The protocol gave excellent results in the case of aromatic
alcohols independent of the presence of electron-with-
drawing or electron-donating groups; even the relative posi-
tion of this substituent had no influence on reaction effi-
ciency. However, the reaction failed when the aliphatic 3-
methyl-1-butanol was used as a substrate (Table 2, En-
try 19). The methodology could be applied to aromatic
amines, with different functional groups as well as to ali-
phatic amines. However, the use of aliphatic amines ren-
1
2
3
4
5
6
7
8
Ph
4-ClC6H4
4-MeC6H4
4-MeOC6H4
3-MeC6H4
4a
4b
4c
4d
4e
4f
4g
4h
4i
99
93
88
96
85
95
32
88
98
94
81
3-MeOC6H4
2,6-Cl2C6H3
3,4-Cl2C6H3
3,5-Me2C6H3
3,5-(MeO)2C6H3
3,4,5-(MeO)3C6H2
9
10
11
4j
4k
[a] Reaction carried out using compound
(2.0 mmol) in toluene (3 mL) for the first step; and HCl (2 mL) and
ether (2 mL) for the second step. [b] Isolated yield after extraction.
1
(1.0 mmol), 2a
Table 2. Preparation of imine derivatives.[a]
Thus, the above standard reaction of arylmethanol deriv-
atives 1 with aniline catalyzed by impregnated copper on
magnetite was followed by treatment with aqueous HCl,
following catalyst removal with a magnet. The whole pro-
cess provided an organic layer in which the aldehyde could
be isolated in good yields and with excellent purity simply
by solvent removal under low pressure. Addition of
Na2CO3 to the aqueous solution and extraction of the re-
sulting mixture rendered the pure aniline (2a) in good yields
(79–96%), showing the possible recyclability of the inte-
grated process. The reaction was found to proceed with ex-
cellent yields regardless of the presence of electron-donating
or -withdrawing groups on the aromatic ring. Only in the
case of the 2,6-dichlorophenyl derivative was the yield of
the corresponding arenecarbaldehyde 4g significantly lower
(Table 3, Entry 7). This is perhaps best explained by steric
hindrance of the starting reagent, since the related 3,4-
dichlorophenyl derivative gave corresponding aldehyde 4h
in good yield (Table 3, Entry 8).
Entry
Ar
R
Product
Yield
[%][b]
1
2
3
4
Ph
Ph
Ph
Ph
Ph
Ph
3-ClC6H4
4-MeOC6H4
2,5-Me2C6H3
nBu
3a
3b
3c
3d
3e
3f
3g
3h
3i
3j
3k
3l
3m
3n
3o
3p
3q
3r
3s
98
71
73
41
75
45
77
80
98
69
97
30
99
62
74
86
93
89
0
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
Ph
Ph
tBuCH2
Me(CH2)11
Ph
3-ClC6H4
Ph
Ph
3-ClC6H4
Ph
Ph
Ph
3-ClC6H4
Ph
3-ClC6H4
Ph
4-ClC6H4
4-ClC6H4
4-MeC6H4
4-MeOC6H4
4-MeOC6H4
3-MeC6H4
3-MeOC6H4
3,5-Me2C6H3
3,5-Me2C6H3
3,5-(MeO)2C6H3
3,5-(MeO)2C6H3
iPrCH2
Preparation of Imines from Alcohols and Nitrobenzene
A new entry to the synthesis of imines has been ac-
complished very recently using nitroarenes as the nitrogen-
containing moiety[8c,17] and an excess of alcohol as the
source of both aldehyde and reducing agent.
[a] Reaction carried out using compound
(2.0 mmol) in toluene (3 mL). [b] Isolated yield after bulb-to-bulb
distillation.
1
(1.0 mmol), 2a
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The reaction of nitrobenzene (5) with four equivalents of a one-pot process to yield pure aldehydes, simply by aque-
alcohol (1) catalyzed by the impregnated copper catalyst ous acidic treatment and subsequent catalyst removal with
gave expected imines 3 with reasonable yields independent a magnet. This catalyst does not require the use of any type
of the alcohols used and substitution on the aromatic ring of expensive and difficult to handle organic ligands, leads
(Table 4). Although the process using simple amines is more to excellent yields of product, and requires mild conditions.
effective than the one using nitroarenes, it is interesting to
note that the same copper catalyst could be used for both
processes and demonstrated similar activities in both sce-
Experimental Section
General Remarks: Melting points were obtained with a Reichert
narios.
Thermovar apparatus. NMR spectra were recorded with a Bruker
Table 4. Preparation of N-phenyl imine derivatives.[a]
1
AC-300 (300 MHz for H and 75 MHz for 13C) using CDCl3 as a
solvent and TMS as internal standard for 1H and 13C; chemical
shifts are given in δ (ppm) and coupling constants (J) in Hertz. FT-
IR spectra were obtained with a JASCO 4100LE (Pike Miracle
ATR) spectrophotometer. Mass spectra (EI) were obtained at
70 eV using a Himazdu QP-5000 spectrometer, giving fragment
ions in m/z with relative intensities (%) in parentheses. Thin layer
chromatography (TLC) was carried out on Schleicher & Schuell
F1400/LS 254 plates coated with a 0.2 mm layer of silica gel; detec-
tion by UV254 light, staining with phosphomolybdic acid [25 g of
phosphomolybdic acid, 10 g of Ce(SO4)2·4H2O, 60 mL of concen-
trated H2SO4 and 940 mL of H2O]. The chromatographic analyses
were carried out with a Younglin 6100GC instrument equipped
with a flame ionization detector and a 30 m capillary column
(0.25 mm diameter, 0.25 mm film thickness, HP-5 stationary
phase), using nitrogen (2 mL/min) as carrier gas, P = 10 psi, Tinjector
= 270 °C and Tdetector = 270 °C; 60 °C for 3 min then at 15 °C/min
to 270 °C for 15 min; tr values are given in min under these condi-
tions. Column chromatography was performed using silica gel 60
of 35–70 mesh. All reagents were commercially available (Acros,
Aldrich, Fluorochem) and were used as received. The ICP-MS
analyses were carried out with a Thermo Elemental VGPQ-ExCell
spectrometer. The X-ray Fluorescence analyses were carried out
using a PHILIPS MAGIX PRO (PW2400) X-ray spectrometer
equipped with a rhodium X-ray tube and a beryllium window. The
reactions were performed in a 12-vessel carousel reaction station
(Radleys). The CuO-Fe3O4 catalyst was prepared according to the
literature procedure.[14e]
Entry
Ar
No.
Yield [%][b]
1
2
3
4
Ph
3a
3k
3l
70
61
84
58
4-MeC6H4
4-MeOC6H4
3-MeC6H4
3n
[a] Reaction carried out using compound
(1.0 mmol) in toluene (3 mL). [b] Isolated yield after bulb-to-bulb
distillation.
1
(4.0 mmol), 5
Preparation of Imines from Primary Amines
Finally, we studied the possible catalytic activity of the
impregnated copper on magnetite for the preparation of
imines starting from primary amines (6).[2] Thus, the treat-
ment of arylmethylamines with a base and substoichi-
ometric amounts of the copper catalyst under Ar gave ex-
pected imines 7 in good yields (Table 5); the apparent dis-
crepancy with formation of 7b was more a matter of isola-
tion difficulties rather than of the product formation.
General Procedure for the Synthesis of Aryl Imines Derivatives from
Alcohols and Amines: To a stirred solution of the corresponding
alcohol (1 1 mmol) in toluene (3 mL) under an Ar atmosphere was
added CuO-Fe3O4 (50 mg), NaOH (56 mg, 1.4 mmol) and the cor-
responding amine (2, 2 mmol). The resulting mixture was stirred at
100 °C for 4 D. The catalyst was removed by a magnet and washed
with EtOAc (2ϫ 5 mL). The collected organic phases were dried
with MgSO4, and the solvents were removed under reduced pres-
sure. The product was purified either by bulb-to-bulb distillation or
crystallization to give corresponding pure products 3. Imine 3a[19] is
commercially available and was characterized by comparison of its
physical and spectroscopic data with those of authentic material.
Yields are included in Table 2. Physical and spectroscopic data, as
well as literature data for known compounds, follow:
Table 5. Preparation of aryl imine derivatives.[a]
Entry
Ar
Product
Yield [%][b]
1
2
4
Ph
4-MeC6H4
3-MeC6H4
7a
7b
7c
95
49
71
[a] Reaction carried out using compound 6 (2.0 mmol) in toluene
(3 mL). [b] Isolated yield after bulb-to-bulb distillation.
(E)-N-Benzylidene-3-chloroaniline (3b):[20] Pale yellow oil; tr = 14.8.
1
R = 0.87 (hexane/EtOAc, 4:1). IR: ν = 1622, 1582, 1067 cm–1. H
˜
f
NMR (300 MHz, CDCl3): δ = 7.05–7.1, 7.15–7.2, 7.3–7.35, 7.4–
7.5, 7.85–7.9 (5m, 1, 2, 1, 3 and 2 H, respectively, ArH), 8.4 (s, 1
H, NCH) ppm. 13C NMR (75 MHz, CDCl3): δ = 119.4, 120.9,
125.8, 128.8 (2 C), 128.9 (2 C), 130.0, 131.7, 134.7, 135.8, 153.3,
Conclusions
In conclusion, impregnated copper on magnetite has
been shown to be an active, highly selective and broadly
applicable catalyst for the preparation of imines starting 161.3 ppm. EI-MS: m/z (%) = 217 (31) [M + 1]+, 216 (45) [M]+,
215 (93), 214 (100), 111 (26), 89 (10), 75 (15).
(E)-N-Benzylidene-4-methoxyaniline (3c):[4c] White solid; M.p. 66–
from different feed-stocks such as alcohols and amines or
nitroarenes, or primary amines. The copper-catalyzed dehy-
drogenation-condensation process could be integrated into 68 °C; t = 15.4. R = 0.53 (hexane/EtOAc, 4:1). IR: ν = 1609, 1581,
˜
r
f
4
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Aromatic Imines from Alcohols and Amines or Nitroarenes
1
1247 cm–1. H NMR (300 MHz, CDCl3): δ = 3.85 (s, 3 H, CH3), 248 (99), 138 (19), 113 (20), 112 (13), 111 (63), 89 (26), 77 (10), 76
6.95–7.0 (m, 2 H, ArH), 7.25–7.3 (m, 2 H, ArH), 7.45–7.5 (m, 3
H, ArH), 7.9–7.95 (m, 2 H, ArH), 8.51 (s, 1 H, NCH) ppm. 13C
NMR (75 MHz, CDCl3): δ = 55.4, 114.3 (2 C), 122.1 (2 C), 128.5
(2 C), 128.7 (2 C), 131.0, 136.4, 144.8, 158.2, 158.3 ppm. EI-MS:
m/z (%) = 212 (14) [M + 1]+, 211 (88) [M+], 210 (15), 197 (15), 196
(100), 167 (22).
(12), 75 (45), 51 (10).
(E)-N-(4-Methylbenzylidene)aniline (3j):[19] Yellow oil; tr = 14.3. Rf
= 0.67 (hexane/EtOAc, 4:1). IR: ν = 3027, 1602, 1498 cm–1. 1H
˜
NMR (300 MHz, CDCl3): δ = 2.4 (s, 3 H, CH3), 7.1–7.25 (m, 7 H,
ArH), 7.77–7.8 (d, J = 8.0 Hz, 2 H, ArH), 8.40 (s, 1 H, NCH) ppm.
13C NMR (75 MHz, CDCl3): δ = 21.6, 115.0 (2 C), 118.4 (2 C),
120.8, 128.7 (2 C), 129.5 (2 C), 133.5, 141.8, 145.3, 160.4 ppm. EI-
MS: m/z (%) = 196 (20) [M + 1]+, 195 (100) [M]+, 194 (100), 91
(19), 77 (58), 51 (16).
(E)-N-Bencylidene-2,5-dimethylaniline (3d):[21] Orange solid; M.p.
86–90 °C (hexane); t = 14.5. R = 1.5 (hexane/EtOAc, 4:1). IR: ν
˜
r
f
= 3019, 1629, 1573 cm–1. 1H NMR (300 MHz, CDCl3): δ = 2.31
(s, 3 H, CH3), 2.34 (s, 3 H, CH3), 6.75 (s, 1 H, ArH), 6.9–6.95 (d,
J = 7.6 Hz, 1 H, ArH), 7.1–7.12 (d, J = 7.6 Hz, 1 H, ArH), 7.45–
7.5 (m, 3 H, ArH), 7.9–7.93 (m, 2 H, ArH) 8.36 (s, 1 H,
NCH) ppm. 13C NMR (75 MHz, CDCl3): δ = 17.5, 21.2, 118.5,
126.4, 128.8 (4 C), 130.2, 131.3, 136.4, 136.7, 151.1 (2 C),
159.4 ppm. EI-MS: m/z (%) = 210 (19) [M + 1]+ 209 (100) [M]+,
208 (96), 194 (13), 193 (33), 132 (100), 131 (12), 130 (13), 117 (16),
105 (12), 103 (16), 79 (14), 77 (27).
(E)-N-(4-Methoxybenzylidene)aniline (3k):[4c] Yellow solid; M.p.
45–48 °C; t = 15.4. R = 0.2 (hexane/EtOAc, 4:1). IR: ν = 1679,
˜
r
f
1600, 1245 cm–1. 1H NMR (300 MHz, CDCl3): δ = 3.78 (s, 3 H,
CH3), 6.9–6.95, 7.15–7.2, 7.3–7.35, 7.75–7.85 (4m, 2,3,2 and 2 H,
respectively, ArH), 8.32 (s, 1 H, NCH) ppm. 13C NMR (75 MHz,
CDCl3): δ = 54.8, 113.6 (2 C), 120.4 (2 C), 125.0, 128.6 (2 C), 128.7
(2 C), 130.0, 151.8, 159.1, 161.7 ppm. EI-MS: m/z (%) = 213 (1)
[M]+, 212 (13), 211 (88), 210 (100), 167 (12), 77 (20).
(E)-N-Bencylidenebutan-1-amine (3e):[9c] Brown oil; tr = 10.1. Rf =
(E)-3-Chloro-N-(4-methoxybenzylidene)aniline (3l):[24] Brown oil; tr
0.56 (hexane/EtOAc, 4:1). IR: ν = 3026, 1645, 1451 cm–1. 1H NMR
˜
= 16.7. R = 0.57 (hexane/EtOAc, 4:1). IR: ν = 1621, 1597, 1243,
˜
f
(300 MHz, CDCl3): δ = 0.95 (t, J = 6.6 Hz, 3 H, CH3), 1.35–1.7
(2m, 4 H, 2 CH2), 3.6 (t, J = 6.4 Hz, 2 H, NCH2), 7.4–7.7 (m, 5
H, ArH), 8.3 (s, 1 H, NCH) ppm. 13C NMR (75 MHz, CDCl3): δ
= 14.0, 20.6, 33.1, 61.6, 128.1 (2 C), 128.7 (2 C), 130.6, 136.4,
160.9 ppm. EI-MS: m/z (%) = 161.1 (8) [M]+ 160.1 (21), 132 (31),
119 (29), 118 (100), 117 (10), 105 (10), 104 (30), 91 (93), 90 (9), 89
(13), 84 (19), 83 (14), 77 (15).
1
1027 cm–1. H NMR (300 MHz, CDCl3): δ = 3.86 (s, 3 H, CH3),
7.15–7.3 (m, 6 H, ArH), 7.82–7.85 (d, J = 8.5 Hz, 2 H, ArH), 8.33
(s, 1 H, NCH) ppm. 13C NMR (75 MHz, CDCl3): δ = 55.2, 113.1,
113.8 (2 C), 114.2, 118.3, 130.1 (2 C), 130.2, 134.7, 153.5, 159.5,
160.6, 162.4 ppm. EI-MS: m/z (%) = 247 (32) [M + 2]+, 246 (45)
[M + 1]+, 245 (96) [M]+, 244 (100), 111 (23), 77 (10), 75 (17).
(E)-N-(3-Methylbenzylidene)aniline (3m):[19] Brown oil; tr = 14.3. Rf
(E)-N-Benzylidene-2,2-dimethylpropan-1-amine (3f):[22] Yellow oil; tr
= 0.7 (hexane/EtOAc, 4:1). IR: ν = 3030, 1627, 1584 cm–1. 1H
˜
= 9.9. Rf = 0.63 (hexane/EtOAc, 4:1). IR: ν = 3027, 1742,
˜
NMR (300 MHz, CDCl3): δ = 2.41 (s, 3 H, CH3), 7.2–7.4 (m, 7 H,
ArH), 7.64–7.66 (d, J = 7.4 Hz, 1 H, ArH), 7.75 (s, 1 H, ArH),
8.41 (s, 1 H, NCH) ppm. 13C NMR (75 MHz, CDCl3): δ = 21.3,
120.8 (2 C), 125.8, 126.4, 128.6, 128.9, 129.1 (2 C), 132.2, 136.1,
138.5, 152.1, 160.6 ppm. EI-MS: m/z (%) = 196 (15) [M + 1]+, 195
(100) [M]+, 194 (100), 104 (11), 91 (14), 77 (52), 51 (15).
1
1645 cm–1. H NMR (300 MHz, CDCl3): δ = 0.98 (s, 9 H, 3 CH3),
3.37 (s, 2 H, CH2), 7.35–7.45 (m, 3 H, ArH), 7.75–7.8 (m, 2 H,
ArH), 8.23 (s, 1 H, NCH) ppm. 13C NMR (75 MHz, CDCl3): δ =
28.1 (3 C), 32.8, 74.1, 128.2 (2 C), 128.7 (2 C), 130.5, 136.6,
160.9 ppm. EI-MS: m/z (%) = 175 (9) [M]+ 174 (21), 160 (16), 119
(37), 118 (100), 117 (10), 91 (100), 90 (9), 89 (10).
(E)-N-(3-Methoxybenzylidene)aniline (3n):[19] Yellow oil; tr = 15.2.
(E)-N-Benzylidenedodecan-1-amine (3g):[10] Yellow oil; tr = 16.4. Rf
R = 0.6 (hexane/EtOAc, 4:1). IR: ν = 3005, 1601, 1584, 1265,
˜
f
= 0.6 (hexane/EtOAc, 4:1). IR: ν = 3021, 1647, 1466 cm–1. 1H
1037 cm–1. H NMR (300 MHz, CDCl3): δ = 3.83 (s, 3 H, CH3),
1
˜
NMR (300 MHz, CDCl3): δ = 0.88 (t, J = 5.4 Hz, 3 H, CH3), 1.2–
1.5 (m, 18 H, 9 CH2), 1.65–1.75 (m, 2 H, CH2), 3.58–3.62 (t, J =
6.7 Hz, 2 H, NCH2), 7.25–7.4, 7.7–7.75 (2m, 3 and 2 H, respec-
tively, ArH), 8.26 (s, 1 H, NCH) ppm. 13C NMR (75 MHz, CDCl3):
δ = 14.0, 22.6, 27.3, 29.3, 29.4, 29.5, 29.6 (3 C), 30.9, 31.9, 61.8,
128.0 (2 C), 128.5 (2 C), 130.3, 136.3, 160.6 ppm. EI-MS: m/z (%)
= 273 (2) [M]+, 174 (16), 161 (12), 160 (100), 132 (25), 119 (16),
118 (35), 104 (11), 91 (29).
7.2–7.35 (m, 8 H, ArH), 7.4 (s, 1 H, ArH), 7.8 (s, 1 H, NCH) ppm.
13C NMR (75 MHz, CDCl3): δ = 55.1, 111.6, 118.3, 120.8 (2 C),
122.3, 125.9, 129.1 (2 C), 129.5, 137.4, 151.8, 159.8, 160.3 ppm. EI-
MS: m/z (%) = 212 (24) [M + 1]+, 211 (100) [M]+, 210 (100), 182
(11), 181 (26), 180 (13), 168 (10), 167 (24), 104 (18), 77 (63), 51
(16).
(E)-N-(3,5-Dimethylbenzylidene)aniline (3o):[25] Brown oil; tr = 14.9.
1
R = 0.67 (hexane/EtOAc, 4:1). IR: ν = 3014, 1625, 1588 cm–1. H
˜
f
(E)-N-(4-Chlorobenzylidene)aniline (3h):[13a] Yellow solid; M.p. 51–
NMR (300 MHz, CDCl3): δ = 2.40 (s, 6 H, 2 CH3), 7.15–7.25 (m,
4 H, ArH), 7.35–7.4 (m, 2 H, ArH), 7.5 (m, 2 H, ArH), 8.36 (s, 1
H, NCH) ppm. 13C NMR (75 MHz, CDCl3): δ = 21.3 (2 C), 124.9
(2 C), 125.9, 126.7 (2 C), 129.2 (2 C), 133.3, 136.2, 138.1 (2 C),
152.3, 161.0 ppm. EI-MS: m/z (%) = 210 (44) [M + 1]+, 209 (100)
[M]+, 208 (100), 194 (14), 193 (13), 165 (12), 105 (11), 104 (25), 103
(13), 91 (26), 78 (13), 77 (100), 51 (25).
54 °C; t = 14.8. R = 0.7 (hexane/EtOAc, 4:1). IR: ν = 1621, 1578,
˜
r
f
1092 cm–1. 1H NMR (300 MHz, CDCl3): δ = 7.15–7.2, 7.35–7.4,
7.75–7.85 (3m, 3, 4 and 2 H, respectively, ArH), 8.37 (s, 1 H,
NCH) ppm. 13C NMR (75 MHz, CDCl3): δ = 120.8 (2 C), 128.9
(2 C), 129.1 (2 C), 129.3, 129.8 (2 C), 134.6, 137.2, 151.5,
158.6 ppm. EI-MS: m/z (%) = 217 (32) [M + 1]+, 216 (46) [M]+,
215 (95), 214 (100), 104 (10), 77 (43), 51 (13).
(E)-3-Chloro-N-(3,5-dimethylbenzylidene)aniline (3p): Brown oil; tr
(E)-3-Chloro-N-(4-chlorobenzylidene)aniline (3i):[23] Brown oil; tr =
= 16.1. Rf = 0.7 (hexane/EtOAc, 4:1). IR: ν = 3019, 1597,
˜
16.1. R = 0.67 (hexane/EtOAc, 4:1). IR: ν = 3060, 1596, 1485 cm–1.
1485 cm–1. H NMR (300 MHz, CDCl3): δ = 3.80 (s, 6 H, 2 CH3),
1
˜
f
1H NMR (300 MHz, CDCl3): δ = 7.2–7.35 (m, 4 H, ArH), 7.45– 6.95–7.1 (m, 5 H, ArH), 7.82–7.85 (d, J = 8.6 Hz, 2 H, ArH), 8.33
7.5 (d, J = 8.5 Hz, 2 H, ArH), 7.8–7.85 (d, J = 8.5 Hz, 2 H, ArH),
(s, 1 H, NCH) ppm. 13C NMR (75 MHz, CDCl3): δ = 21.1 (2 C),
113.0, 114.8, 118.2, 126.0 (2 C), 129.8, 130.2, 134.7, 135.6, 138.1,
8.39 (s, 1 H, NCH) ppm. 13C NMR (75 MHz, CDCl3): δ = 119.4,
120.9, 126.1, 129.2 (2 C), 130.1 (2 C), 130.2, 134.3, 134.8, 137.8, 147.6, 161.9 ppm. EI-MS: m/z (%) = 245 (31) [M + 2]+, 244 (48)
152.9, 159.9 ppm. EI-MS: m/z (%) = 253 (10) [M + 4]+, 252 (18)
[M + 1]+, 243 (96) [M]+, 242 (100), 109 (23), 91 (12), 76 (11), 75
[M + 3]+, 251 (64) [M + 2]+, 250 (74) [M + 1]+, 249 (100) [M]+, (13). HRMS calcd. (%) for C15H14ClN: 243.0815, found 243.0800.
Eur. J. Org. Chem. 0000, 0–0
© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
5

Job/Unit: O20319
/KAP1
Date: 04-07-12 16:15:44
Pages: 8
J. M. Pérez, R. Cano, M. Yus, D. J. Ramón
FULL PAPER
(E)-N-(3,5-Dimethoxybenzylidene)aniline (3q): –[26] Brown oil. tr =
16.7. Rf = 0.5 (hexane/EtOAc, 4:1). IR: ν = 3004, 1627, 1587,
(E)-N-(3-Methylbenzylidene)-1-(m-tolyl)methanamine (7c):[33] Yel-
low oil; t = 15.2. R = 0.5 (hexane/EtOAc, 4:1). IR: ν = 1652,
˜
˜
r
f
1151 cm–1. H NMR (300 MHz, CDCl3): δ = 3.84 (s, 6 H, 2 CH3), 1568 cm–1. H NMR (300 MHz, CDCl3): δ = 2.33 (s, 3 H, CH3),
1
1
6.57–6.59 (t, J = 2.3 Hz, 1 H, ArH), 7.05–7.06 (d, J = 2.3 Hz, 2 H,
ArH), 7.2–7.25 (m, 3 H, ArH), 7.35–7.4 (m, 2 H, ArH), 8.4 (s, 1
H, NCH) ppm. 13C NMR (75 MHz, CDCl3): δ = 55.6 (2 C), 104.3,
106.5 (2 C), 121.0 (2 C), 126.1, 129.2 (2 C), 138.3, 152.0, 160.4,
2.37 (s, 3 H, CH3), 4.77 (s, 2 H, CH2), 7.25–7.6 (m, 6 H, ArH),
7.64 (s, 2 H, ArH), 8.35 (s, 1 H, NCH) ppm. 13C NMR (75 MHz,
CDCl3): δ = 21.2, 21.3, 65.1, 124.2, 125.0, 125.8, 127.7, 128.1,
128.7, 131.5, 132.6, 138.0, 138.3, 138.4, 139.1, 162.1 ppm. EI-MS:
161.1 (2 C) ppm. EI-MS: m/z (%) = 242 (37) [M + 1]+, 241 (100) m/z (%) = 223 (35) [M]+, 222 (22), 208 (15), 106 (54), 105 (100),
[M]+, 240 (100), 226 (10), 212 (23), 211 (56), 210 (19), 196 (12), 183 103 (15), 91 (14), 79 (13), 77 (19).
(10), 182 (18), 167 (12), 154 (12), 104 (24), 78 (10), 77 (78), 51 (18).
Supporting Information (see footnote on the first page of this arti-
1
cle): Particle size distribution and copies of the H NMR and 13C
(E)-3-Chloro-N-(3,5-dimethoxybenzylidene)aniline (3r): Red oil; tr =
NMR spectra.
17.9. R = 0.5 (hexane/EtOAc, 4:1). IR: ν = 3004, 1593, 1484, 1204,
˜
f
1064 cm–1. H NMR (300 MHz, CDCl3): δ = 3.84 (s, 6 H, 2 CH3),
1
7.05–7.1 (m, 4 H, ArH), 7.2–7.3 (m, 3 H, ArH), 8.31 (s, 1 H,
NCH) ppm. 13C NMR (75 MHz, CDCl3): δ = 55.6 (2 C), 104.4,
119.3, 120.8, 125.8, 130.1, 130.2 (2 C), 137.7, 147.6, 153.0, 160.9 (2
C), 161.2 ppm. EI-MS: m/z (%) = 277 (32) [M + 2]+, 276 (47) [M
+ 1]+, 275 (100) [M]+, 274 (99), 246 (12), 245 (21), 138 (11), 111
(20). HRMS: calcd. for C15H14ClNO2 275.0713; found 275.0730.
Acknowledgments
This work was supported by the current Spanish Ministerio de
Economía y Competitividad (Consolider Ingenio 2010 CSD2007-
00006, CTQ2007-65218/BQU and CTQ2011-24151) and the Gene-
ralitat Valenciana (G.V.; PROMETEO 2009/03, FEDER). R. C.
thanks the G.V. for a fellowship through the PROMETEO pro-
gram. J. M. P. thanks the Spanish Ministerio de Educación and the
Universidad de Alicante for undergraduate grants. We gratefully
acknowledge the refinement of our English by Mrs. Oriana C.
Townley.
General Procedure for the Synthesis of Arenecarbaldehydes 4: To a
stirred solution of corresponding alcohol (1 1 mmol) in toluene
(3 mL) under an Ar atmosphere was added CuO-Fe3O4 (50 mg),
NaOH (56 mg, 1.4 mmol) and corresponding aniline (2a, 0.18 mL,
2 mmol). The resulting mixture was stirred at 100 °C for 4 d. The
catalyst was removed by a magnet and then HCl (2 mL) and ether
(2 mL) were added. The resulting mixture was stirred for 2 h at
room temperature, and then it was quenched with water (2 mL)
and extracted with EtOAc (3ϫ 5 mL). The organic phases were
dried with MgSO4, followed by evaporation under reduced pressure
to remove the solvent. The product was purified by vacuum distil-
lation at 120 °C to give corresponding products 4. Alcohols 4a,[27]
4b,[28] 4c–f,[27] 4g,[29] 4h,[30] 4i,[31] 4j,[28] and 4k[32] are commercially
available and were characterized by comparison of their physical
and spectroscopic data with those of pure commercial samples.
Yields are included in Table 3.
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General Procedure for the Synthesis of Aryl Imines Derivatives from
Primary Amines: To a stirred solution of corresponding amine (6
2 mmol) in toluene (3 mL) under air was added CuO-Fe3O4
(50 mg) and NaOH (120 mg, 2 mmol). The resulting mixture was
stirred at 100 °C for 3 d. The catalyst was removed by a magnet
and washed with EtOAc (2ϫ 5 mL). The collected organic phases
were dried with MgSO4, and the solvents were removed under re-
duced pressure. The product was purified either by bulb to bulb
distillation or crystallization to give corresponding pure products
7. Yields are included in Table 5. Physical and spectroscopic data
as well as literature data for known compounds follow:
(E)-N-Benzylidene-1-phenylmethanamine (7a):[2g] Brown oil; tr
=
13.9. R = 0.56 (hexane/EtOAc, 4:1). IR: ν = 3061, 3027, 1643,
˜
f
1579 cm–1. H NMR (300 MHz, CDCl3): δ = 4.82 (s, 2 H, CH2),
1
7.2–7.5 (m, 8 H, ArH), 7.78–7.79 (d, J = 3.3 Hz, 2 H, ArH), 8.39
(s, 1 H, NCH) ppm. 13C NMR (75 MHz, CDCl3): δ = 65.0, 126.9,
127.9 (2 C), 128.2 (2 C), 128.5 (2 C), 128.6 (2 C), 130.7, 136.1,
139.2, 162.0 ppm. EI-MS: m/z (%) = 196 (7) [M + 1]+, 195 (45)
[M]+, 194 (44), 117 (12), 92 (33), 91 (100), 89 (15), 65 (14).
(E)-N-(4-Methylbenzylidene)-1-(p-tolyl)methanamine (7b):[2g] White
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Angew. Chem. Int. Ed. 2003, 42, 1480–1483; b) K. Yamaguchi,
N. Mizuno, Chem. Eur. J. 2003, 9, 4353–4361; c) J.-R. Wang,
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solid; M.p.: 51–53 °C; tr = 15.4. Rf = 0.6 (hexane/EtOAc, 4:1). IR:
1
ν = 3015, 1646, 1558 cm–1. H NMR (300 MHz, CDCl ): δ = 2.34
˜
3
(s, 6 H, 2 CH3), 4.77 (s, 2 H, CH2), 7.1–7.25 (m, 6 H, ArH), 7.65–
7.67 (d, J = 7.8 Hz, 2 H, ArH), 8.34 (s, 1 H, NCH) ppm. 13C NMR
(75 MHz, CDCl3): δ = 21.1, 21.5, 64.8, 127.9 (2 C), 128.2 (2 C),
129.1 (2 C), 129.3 (2 C), 133.6, 136.3, 136.5, 140.9, 161.7 ppm. EI-
MS: m/z (%) = 223 (27) [M]+, 222 (12), 106 (20), 105 (100), 77 (12).
6
www.eurjoc.org
© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 0000, 0–0

Job/Unit: O20319
/KAP1
Date: 04-07-12 16:15:44
Pages: 8
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Received: March 15, 2012
Published Online: ᭿
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7

Job/Unit: O20319
/KAP1
Date: 04-07-12 16:15:44
Pages: 8
J. M. Pérez, R. Cano, M. Yus, D. J. Ramón
FULL PAPER
Impregnated Copper Catalysts
J. M. Pérez, R. Cano, M. Yus,
D. J. Ramón* .................................... 1–8
Straightforward Synthesis of Aromatic
Imines from Alcohols and Amines or
Nitroarenes Using an Impregnated Copper
Catalyst
The impregnated copper on magnetite
catalyst is a versatile system for the syn-
thesis of imines starting from alcohols and
amines or nitroarenes. A similar synthesis
of imines was accomplished using only pri-
mary amines. This catalyst avoids the use
of expensive organic ligands and other
transition metals while enabling excellent
yields under mild reaction conditions.
Keywords: Copper / Heterogeneous cataly-
sis / Hydrogen transfer / Imines / Oxidation
8
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Eur. J. Org. Chem. 0000, 0–0