Synthesis of imines, diimines and macrocyclic diimines as possible ligands, in aqueous solution

Article abstract of DOI:10.1039/b102749m

Although it is recognized that the presence of water is disadvantageous for imine synthesis, we demonstrate that such synthesis can be effective in completely aqueous media, without any catalyst and under mild conditions. Thus, arylaryl, aryl-alkyl, alkyl-aryl and alkyl-alkyl monoimines as well as a large variety of diimines are obtained by direct condensation of the corresponding carbonyl compounds and amines, in water. The same process is used to synthesize macrocyclic diimines starting from methylene, ethylene, trimethylene and tetramethylene glycol bis(2-formylphenyl ether) and ethylene-, trimethylene- and tetramethylene-diamine, some of these macrocycles being known for their chelating properties.

Full text of DOI:10.1039/b102749m

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Synthesis of imines, diimines and macrocyclic diimines as possible
ligands, in aqueous solution
Alina Simion,a Cristian Simion,a Tadeshige Kanda,a Satoko Nagashima,a Yoshiharu Mitoma,a
Tomoko Yamada,a Keisuke Mimuraa and Masashi Tashiro*b
1
a Tohwa Institute for Science, Tohwa University, 1-1-1 Chikushigaoka, Minami-ku, Fukuoka,
815-8510, Japan
b University of Southern California, Loker Hydrocarbon Research Institute,
Department of Chemistry, Los Angeles, California, 90089-1661, USA
Received (in Cambridge, UK) 26th March 2001, Accepted 28th June 2001
First published as an Advance Article on the web 13th August 2001
Although it is recognized that the presence of water is disadvantageous for imine synthesis, we demonstrate that such
synthesis can be effective in completely aqueous media, without any catalyst and under mild conditions. Thus, aryl-
aryl, aryl-alkyl, alkyl-aryl and alkyl-alkyl monoimines as well as a large variety of diimines are obtained by direct
condensation of the corresponding carbonyl compounds and amines, in water. The same process is used to synthesize
macrocyclic diimines starting from methylene, ethylene, trimethylene and tetramethylene glycol bis(2-formylphenyl
ether) and ethylene-, trimethylene- and tetramethylene-diamine, some of these macrocycles being known for their
chelating properties.
heating the reagents alone or in an anhydrous organic solvent,
the presence of water usually being regarded as disadvan-
Introduction
Nowadays, regarding the new concept of Green Chemistry,1
tageous. However, on scrutinizing the chemical literature, we
water tends to replace more and more organic solvents (e.g.,
found out that in the mid-50s, based on earlier works,6–9 the idea
in chemical processes such as Diels–Alder2 or aldol addition
of ‘cell-possible’ reactions, which are those organic reactions
reactions3) taking into account environmental concerns and
that could proceed under physiological conditions, including
the aspects of cost, safety or simple operations. Following this
aqueous media, had appeared. The earliest ideas regarding
direction, the research program of our laboratory has been
such non-enzymatic reactions were connected with alkaloid
devoted for some time to the study of organic reactions in
syntheses.10–12 Later, Haley and Maitland13 reported the form-
water. Thus, we have been dealing for a while with reduction,
ation of a few aromatic Schiff bases in saturated aqueous solu-
tions and in the presence of various catalysts, performing
reductive coupling or condensation reactions in aqueous
media.4 While studying the reductive coupling of benzaldehyde
the reactions at different pH values, from 2.5 up to 13.0. In
azine 1 and related compounds, instead of the desired product 2
we obtained mainly benzylidenebenzylamine 3a. This surpris-
ing result could be explained following the pathway presented
in Scheme 1.
addition, in the early 60s, Jencks and Cordes14 studied the
formation of semicarbazones,15 oximes15b and the kinetics of
formation of N-(p-chlorobenzylidene)aniline14a and hydrolysis
of N-benzylidenebutylamine14b in aqueous solutions.
Our aim was to determine the scope and the limitations of
the imine synthesis in aqueous media, under mild conditions,
without using any buffered system or catalyst. At the same time,
our purpose was to find out if these unusual, but simple and
economically practical, reaction conditions are of wide appli-
cation and of preparative value in the field of imine synthesis. A
recent report, in which a condensation reaction between benz-
aldehyde and aniline occurred as a side-reaction in a Mannich-
type reaction catalyzed by In,16 in water, prompted us to report
our results in this field. Our final target was to apply the same
process to the synthesis of diimines (open-chain or macrocyclic)
that could be used as possible chelating agents for metallic
cations.
Scheme 1
The reactions were carried out in the simplest manner, by
Benzaldehyde azine suffered both hydrolysis and reduction
and the resulting benzaldehyde and benzylamine condensed
yielding benzylidenebenzylamine. This pathway was confirmed
by mixing directly in water stoichiometric amounts of benz-
aldehyde and benzylamine, which yielded almost quanti-
tatively benzylidenebenzylamine. Thus, it appeared to us that
imine synthesis could take place in aqueous conditions. Since its
discovery in 1864 by H. Schiff,5 the condensation reaction
between aldehydes and amines was normally carried out by
mixing directly the amines and the carbonyl compounds in
water, without adding any other solvent or catalyst, at room
temperature. When the imines did not separate directly from the
aqueous solution, extraction was used.
This work is described below in two sections: first, the general
experiments which show the scope and limitations of the imine
synthesis in aqueous media and, second, the synthesis of open-
chain and macrocyclic diimines that are possible chelating
agents for metallic cations.
DOI: 10.1039/b102749m
J. Chem. Soc., Perkin Trans. 1, 2001, 2071–2078
This journal is © The Royal Society of Chemistry 2001
2071

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Table 2 Reaction of aromatic aldehydes with aromatic amines
Table 1 Reaction of aromatic aldehydes with aliphatic amines
Run
4
5
3 (Yield, %)
Run
4
6
7 (Yield, %)
1
2
3
4
5
6
7
8
9
10
11
12
13
14
a
a
a
a
a
b
c
b
d
d
e
e
f
a
b
c
d
e
b
a
e
e
b
c
e
f
a (85)
b (90)
c (74)
d (65)
e (76)
f (76)
g (85)
h (67)
i (86)
j (81)
k (78)
l (97)
m (79)
n (93)
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
a
a
a
a
a
a
a
a
a
a
b
c
d
f
a
b
c
d
e
f
a (97)
b (21)
c (48)
d (58)
e (32)
f (80)
g (63)
h (16)
i (80)
j (94)
k (72)
l (87)
m (78)
n (80)
o (58)
p (69)
q (94)
r (95)
g
h
i
j
a
a
a
a
k
a
a
a
g
a
g
h
i
Results and discussions
j
A. Synthesis of monoimines
Table 3 Reaction of aliphatic aldehydes with aromatic amines
Schiff bases of benzaldehyde and its derivatives are usually easy
to obtain, under mild conditions and at relatively low temper-
atures, by a condensation reaction with amines.17 General
chemistry of this process showed a two-step reaction, with
intermediate formation of an amino alcohol and final elimin-
ation of water.18 Thus, in order to obtain the desired anil, excess
of a suitable anhydrous organic solvent is generally used
for azeotropic elimination of water from the system,17 usually
through a Dean–Stark device. In a completely different
approach, we attempted the synthesis of a wide range of imine
derivatives, in water and in the absence of any catalyst or buffer-
ing mixture. As starting materials we used aromatic, hetero-
aromatic and aliphatic aldehydes together with aliphatic and
aromatic amines (the ketone series and other pseudo-keto
compounds will undergo further investigations in the following
step of our research).
Run
8
6
9 (Yield, %)
1
2
3
4
5
6
a
a
a
b
c
c
a
c
k
l
e
j
a (45)
b (38)
c (33)
d (61)
e (36)
f (44)
In the first series of experiments, we studied the occurrence
of aryl-aryl-and aryl-alkyl-imines (Tables 1 and 2). The crude
reaction products were submitted to GC-MS and NMR anal-
yses. Both analysis methods showed a high purity (with few
exceptions) for the reaction product. Therefore, we used the
same experimental procedure for all the experiments yielding
monoimines. The yields are quite acceptable for a condensation
process that occurs in aqueous conditions, exception being
made for some halogeno-substituted anilines, especially in
the ortho-position. On the other hand, the formation of the
imines precipitated directly from the aqueous solution. Thus,
the extraction step used for the separation of the imine from
the aqueous media can be avoided and the synthesis can be
regarded as one ‘completely performed in aqueous media’ (see
also part B). The second step of our investigation was the study
of alkyl-alkyl- and alkyl-aryl imines (Tables 3 and 4). In this
case, although the corresponding imines are formed in reason-
able proportions, the yields are lower, even if reaction times are
longer. This is probably because of the volatility of the starting
materials and the formation of side-products such as dimers or
polymers, as a result of an aldol-type condensation or of a
polycondensation reaction.19
-CH᎐N- double bond decreased when using aliphatic amine-
᎐
s > aromatic amines > substituted aromatic amines (especially
ortho—see entries 2, 7 and 8 in Table 2). Good yields of imine
formation, even at shorter reaction times, were observed in the
case of heteroaryl carbaldehydes, either with aromatic or
aliphatic amines.
In order to study the influence of a modified emulsion
system, some binary systems water—organic solvent (1 : 1)
were used. As solvents we chose ethanol, dichloromethane or
benzene (mixed in different proportions with water) and for the
When solid imines formed in some of the reactions men-
tioned in Table 2 (for example entries 3, 10, 11, 13, 17, 18) the
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Table 4 Reaction of aliphatic aldehydes with aliphatic amines
Scheme 2
filtration and drying permitted the isolation of the pure
diimine, in very good yields. For example, on comparing the
yield of the benzaldehyde azine synthesis by the classical
method as described in Organic Synthesis26 and the yield of the
same azine formation by direct condensation, in water, the
difference is quite small (91–94%26 compared with 89% – see
Experimental section).
Recently, we focused our research on the intramolecular
reductive coupling reaction of some aromatic dialdehydes 13.27
Such dialdehydes seemed to be suitable starting materials for
the synthesis of open-chain or macrocyclic diimines (Scheme 3).
Run
8
5
10 (Yield, %)
1
2
3
4
5
6
a
a
b
b
c
c
e
g
g
f
b
a
a (72)
b (45)
c (71)
d (65)
e (53)
f (51)
sake of comparison we also performed the same reactions
in pure benzene. In all these experiments, the stoichiometry was
10 mmol aldehyde : 10 mmol amine : 7.5 mL water : 7.5 mL
organic solvent. Reactions in pure water or in pure benzene
were carried out in 15 mL of solvent. All reactions were
performed at room temperature. Solvent-modified emulsions
didn’t seem to be more effective than simple water. On the other
hand, except for the cases when yields are comparatively the
same, the addition of an organic solvent to the starting reaction
mixture lowered the yields. Marvel and co-workers revealed a
similar result for a polycondensation reaction involving the
formation of a poly-Schiff base from o-phenylenediamine or
hydrazine and 5,5Ј-methylenedisalicylaldehyde or disalicyl-
aldehyde-5,5Ј-sulfone.20 The compounds synthesized by Marvel
and co-workers were used as chelating agents for nickel and
cadmium salts. Thus, our attention was very soon attracted
toward synthesis of such diimines that could function as
possible chelating reagents for metallic cations.
Scheme 3
Scrutinizing the chemical literature, we found out that a small
number of such cyclic diimines had already been obtained by
the usual method of boiling stoichiometric amounts of diamine
and dialdehyde in methanol.28,29 Thus, compounds with m,
n = 2, 3 were directly submitted to reduction with NaBH4, gen-
erally without isolation or characterization of the diimines, and
the diamine was used as a nitrogen–oxygen donor macrocyclic
ligand.28,29 There are many more examples of diamines than
diimines that are used as macrocyclic donor ligands. Neverthe-
less, macrocyclic diimines of type 15, with m = 2 and instead of
(CH2)n having the moiety -(CH2)2N(CH3)(CH2)2- proved to be
effective in complexation of the Mo cation.30 The complex was
formed directly by mixing the dialdehyde, the diamine and a
Mo salt in refluxing toluene. Beside the macrocyclic diimines
obtained by Lindoy and co-workers,28,29 only one other diimine
macrocylic ligand, 17, with similar structure, was previously
reported31 (see Scheme 4).
B. Open-chain and macrocyclic diimines
Most of the examples of diimines encountered in the literature
were considered as chelating compounds. For example,
Horrocks and co-workers prepared ethylene and trimethylene
diimines of tolualdehydes and the corresponding Ni complexes
in a boiling n-butyl alcohol solution.21 Salicylaldehyde diimines
with ethylene-, hexamethylene- or o-phenylene-diamine were
used for complexation of Ir or Rh salts.22 In this case, the
diimines were obtained by boiling stoichiometric amounts of
aldehydes and diamines in methanol. Ethylene and trimethylene
diimines of salicylaldehyde, obtained by condensation in boil-
ing absolute benzene or absolute methanol, were used in the
formation of some Ge derivatives.23 A report from 1975 pre-
sented the synthesis of some Zn complexes of salicylaldehyde
and ethylenenediamine or 1,3-diaminopropane in an aqueous
solution.24
Surprisingly, all the papers dealing with the formation of
such diimines treated them especially as complexing reagents,
with no physical description of the diimine molecule itself (mp,
NMR or MS data). Moreover, even if these diimines were used
as chelating reagents, only one attempt24 has been made to
obtain the complex diimine–metal cation directly in aqueous
solution. In this case, the Zn ion in the buffered reaction
mixture is considered to function by effectively reducing the
condensation reaction from a second-order to a first-order
process. The term promnastic (matchmaker) was applied to this
effect.25
In our work, we performed the condensation reaction of
benzaldehyde 4a, anisaldehyde 4b and salicylaldehyde 4c
with hydrazine, ethylene-, trimethylene- and tetramethylene-
diamine, in water, at room temperature and without any
catalyst (Scheme 2).
Scheme 4
Starting from bridged dialdehydes 13a–d, in a series of pre-
liminary experiments, we attempted the synthesis of some
open-chain diimines, in aqueous solution. We selected aniline
and benzylamine as amine partners in the condensation pro-
cess. The reactions were carried out under the same protocol:
mixing both reagents in water and stirring for 4 h at room tem-
perature. After filtration and drying, the crude material was
submitted to NMR analysis.
The diimines were very soon formed and readily precipitated
in the reaction flask, after a few minutes of stirring. Direct
The NMR spectra of crude reaction products showed, with
few exceptions, a high purity of the target molecule, confirming
J. Chem. Soc., Perkin Trans. 1, 2001, 2071–2078
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Table 5 Abbreviations used
that the 1 : 2 dialdehyde : amine stoichiometry and the simple
reaction conditions are very effective for diimines synthesis. The
exceptions mentioned presented small supplementary signals in
the CH = N region (δ 8.70–8.90), generally at lower values of
δ, which we presumed to belong to the monoimine compounds.
In order to clear the affiliation of the small supplementary
signals, we tried the same reactions with a 1 : 1 stoichiometry of
dialdehyde : amines. For example, in the case of o,oЈ-tetra-
methylenebis(salicylideneaniline) 14g, there are in the crude
m
n
Abbreviation
Cmpd
1
1
1
2
2
2
3
3
3
4
4
4
2
3
4
2
3
4
2
3
4
2
3
4
O-mn-N-en
O-mn-N-tn
O-mn-N-bn
O-en-N-en28,29
O-en-N-tn28,29
O-en-N-bn
15a
15b
15c
15d
15e
15f
15g
15h
15i
O-tn-N-en28,29
O-tn-N-tn28,29
O-tn-N-bn
reaction product NMR spectrum two signals in the CH᎐N
᎐
area, one at δ 8.90 and the second at δ 8.88, in the ratio
1.00 : 0.04; when performing the same reaction with 1 : 1
stoichiometry, the signal at δ 8.88 is highly increased. Neverthe-
less, the ratio between the main CH = N signal (of the diimine)
and the secondary signal (for monoimine) never exceeded
1.00 : 0.05. Incidentally, we also found that the reaction time
can be shortened to 2 h if the reaction is carried out in boiling
water.
The reactions leading to the macrocyclic diimines occurred
under almost the same conditions, although in this case better
yields were obtained if working in boiling water. As previously
mentioned, some of these diimines were prepared in situ and
submitted directly to further reduction, by Lindoy and co-
workers, to the diamine structures as macrocyclic ligands
(m, n = 2, 3).28,29 Therefore we used the abbreviations proposed
by Lindoy, which seemed very clear and convenient, and can be
adapted to the other compounds that we synthesized.
O-bn-N-en
O-bn-N-tn
O-bn-N-bn
15j
15k
15l
hydrolysis of imine compound occurred). Even small amounts
of oligomer accompanying the diimine prevented it from
crystallizing. Nevertheless, in these cases, the NMR spectra of
the crude reaction products and GC-MS or MS analyses were a
thorough confirmation of the diimine structure. For a complete
proof of the cyclic structure, we performed the reduction of
some cyclic diimines with NaBH4,28,29 the cyclic diamines that
were formed presenting spectral and physical data identical
with those collected from the literature.28
Conclusions
Synthesis of imines in completely aqueous media is effective
without using any catalyst or buffered solution for a wide range
of aromatic, aliphatic or heteroaromatic aldehydes in reaction
with aromatic or aliphatic amines. The best results were
obtained in the case of monoimines coming from aromatic –
including also heteroaromatic – aldehydes and aliphatic and
aromatic amines (when unsubstituted in the ortho-position).
Room temperature proved to be convenient enough for the
condensation process to take place. This condensation process
can be applied to the synthesis of diimines, both open-chain
and macrocyclic. Both diamines (in reaction with monoalde-
hydes) and dialdehydes (reacting with monoamines) afforded
good yields in the condensation reactions, even at room tem-
perature. Only in the last case, and occasionally, were small
amounts of monoimines recorded as side products. Macro-
cyclic diimines, compounds that can be used as ligands as pre-
viously mentioned in the chemical literature, were obtained in
good yields, in some cases the presence of dimers (but no
monoimine) being detected. So, in our view, when imine
compounds (especially common ones) are desired, before using
classical methods (such as azeotropic distillation, molecular
sieves, etc.) the convenient method that requires only water and
room temperature is worth trying.
Along with the main reaction products, the diimines, one or
two secondary reaction products were sometimes formed in this
process, as a result of a polycondensation reaction. Thus, the
NMR spectra of some crude reaction products presented in the
region δ 8.60–8.80 two or three signals, which we assumed to
come either from the monoimine (since there still is a carb-
aldehyde signal around δ 10.50) or from an oligomeric structure
(in spite of the fact that we worked at high dilution, we couldn’t
eliminate the possibility of a polycondensation reaction).
Indeed, according to Krassig and Greber32 the para-isomer of
13a in reaction with 11b, 11c or 11d in anhydrous diethyl ether,
for at least two days, yielded several open-chain oligomers with
a degree of polymerization up to 10.
Although for the single imine that is described by NMR28a
(O-tn-N-tn, 15h) there were two distinct signals reported for the
two CH᎐N groups (Lindoy and co-workers28a reported for 15h
᎐
two singlets: δ 8.66 and 8.70), our recrystallized 15h showed
only one singlet, at δ 8.66. In fact, samples taken from the
crude reaction mixtures and purified by recrystallization or by
Kugelrohr distillation, presented in their NMR spectra only
one signal for the CH᎐N protons, in the diimine compounds.
᎐
GC-MS and MS analyses eliminated the possibility of mono-
imine formation. Thus, secondary products were oligomers.
There are two possibilities for the structure of oligomeric prod-
ucts: open-chain or macrocyclic. Analysis by mass spectra of
the mixtures presenting at least two NMR signals in the area
δ 8.60–8.80 showed mostly cyclic dimers as secondary reaction
products (the third NMR signal, according also to MS, could
be attributed to an open-chain dimer). It is interesting to note
that almost all dimeric structures (open-chain or cyclic) showed
Experimental
Distilled water was used in all experiments. Aldehydes (with the
exception of dialdehydes 13a–d) and amines used as starting
materials were purchased from chemical companies and were
purified before use (when needed). Mps were determined on a
Yanaco Micro Melting-Point Apparatus and are uncorrected.
All NMR spectra were recorded on a JEOL JNM-LA 300, 300
MHz, for samples in CDCl3 with Me4Si as internal standard.
Coupling constants (J-values) are given in Hz. Identification of
monoimines was made by GC (Shimadzu GC-17A GC instru-
ment, carrier gas N2, pressure 135 kgf cmϪ2,† flow 55 mL minϪ1
on a J&W Scientific DB-1 fused silica capillary column, length
30 m, I.D. 0.32 mm with film thickness of 0.25 mm) and GC-
MS (Hewlett-Packard HP6890 GC, carrier gas He, flow 1.5 mL
minϪ1, velocity 48 cm sϪ1 and pressure 10.3 psi, J&W Scientific
DB-1 fused silica capillary column and JEOL – Automass
higher chemical shifts for CH᎐N protons and for some aliphatic
᎐
protons (especially protons from the C directly connected to the
hetero-atom – O or N); similarly, aromatic signals for the
proton in ortho-positions from the CH᎐N bond are deshielded.
᎐
For example, if the signal for the CH᎐N protons of the cyclic
᎐
diimine usually appear around δ 8.66 (see Experimental
section), the dimers present a δ-value >8.70 ppm (δ 8.82 for
O-tn-N-en 15g, δ 8.74 for O-tn-N-bn 15i, δ 8.70 for O-tn-N-tn
15h, δ 8.84 for O-en-N-bn 15f, δ 8.68 for O-en-N-en 15d or 8.73
for O-bn-N-bn 15l).5
Unfortunately, in some cases, the macrocyclic diimines
couldn’t be completely separated from oligomeric compounds,
either by recrystallization or by column chromatography (when
† 1kgf = 9.806 N.
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system II MS). Mass spectra and high-resolution mass spectra
were recorded on a JEOL JMS-700T, with 45 eV ionization
energy and 600 µA current.
ArH), 7.62–7.70 (4H, m, ArH), 8.26 (2H, s, 2 × CH᎐N); δ 61.6
᎐
C
(N-C-C-N), 128.1, 128.5, 130.5, 136.1 (Car-CH᎐), 162.6
᎐
(CH᎐N); m/z 236 (1, Mϩ), 132 (63, Mϩ Ϫ PhCH᎐N), 118
᎐
᎐
(28, Mϩ Ϫ PhCH᎐NCH ), 104 [70, Mϩ Ϫ Ph-CH᎐N (CH ) ],
᎐
᎐
2
2 2
91 (100).
General procedure for the synthesis of monoimines 3, 7, 9, 10
In a standard procedure, in a three-necked round-bottom flask
equipped with a mechanical stirrer and, optionally, with a
reflux condenser, were introduced 10 mmol of carbonyl com-
pound and 15 mL of water. The amine (10.0 mmol) was added
in one portion and the flask was kept at room temperature
under vigorous mechanical stirring for 2 h for aryl-aryl and
aryl-alkyl imines, and for 3 h for alkyl-aryl and alkyl-alkyl
imines. If no precipitation occurred, the aqueous mixture was
extracted twice with dichloromethane. The crude precipitate
(when formed) was analyzed by GC-MS and NMR. In case of
extraction, combined organic layers were dried over MgSO4.
The organic solvent was evaporated off and the residue was
analyzed by GC-MS and NMR. All synthesized imines pre-
sented the same retention times, corresponding mps or bps,
and identical NMR spectra as authentic samples (Aldrich or
Sigma – when available – or obtained by the classic method of
Dean–Stark azeotropic distillation).
N,NЈ-Trimethylenebis[benzylidenealdimine] 12c. (2.22 g, 89%)
white prisms (from hexane), mp 82–83 ЊC; δH 2.15 (2H, quintet,
J 6.9, ᎐NCH CH CH N᎐), 3.72 (4H, t, J 6.9, ᎐NCH CH -
᎐
᎐
᎐
2
2
2
2
2
CH N᎐), 7.39–7.42 (6H, m, ArH), 7.71–7.74 (4H, m, ArH),
᎐
2
8.30 (2H, s, 2 × CH᎐N); δ 31.9 (N-C-C-C-N), 59.2 (N-C-C-
᎐
C
C-N), 127.8, 128.5, 129.4, 130.5, 136.2 (Car-CH᎐), 161.3
᎐
(CH᎐N); m/z 250 (1, Mϩ), 146 (35, Mϩ Ϫ PhCH᎐N), 132 (56,
᎐
᎐
Mϩ Ϫ PhCH᎐NCH ), 118 [100, Mϩ Ϫ PhCH᎐N(CH ) ], 91
᎐
᎐
2
2 2
(42).
N,NЈ-Tetramethylenebis[benzylidenealdimine] 12d. (2.11 g,
80%) white prisms (from hexane), mp 41 ЊC (lit.,33 41–42 ЊC);
δH 1.76–1.80 (4H, m, ᎐NCH CH CH CH N᎐), 3.61–3.65 (4H,
᎐
᎐
2
2
2
2
m, ᎐NCH CH CH CH N᎐), 7.34–7.37 (6H, m, ArH), 7.68–
᎐
᎐
2
2
2
2
7.71 (4H, m, ArH), 8.23 (2H, s, 2 × CH᎐N); δ 28.5 (N-C-C-C-
᎐
C
C-N), 61.3 (N-C-C-C-C-N), 127.8, 128.1, 128.6, 129.0, 130.3,
136.0 (Car-CH᎐), 160.7 (CH᎐N); m/z 264 (1, Mϩ), 159 (100,
᎐
᎐
Mϩ Ϫ PhCH᎐N), 132 [13, Mϩ Ϫ PhCH᎐N(CH ) ], 91 (93).
᎐
᎐
2
2
N-Salicylideneaniline 7. (1.72 g, 87%): yellow needles (from
hexane), mp 50–51 ЊC (lit.,33 51 ЊC); δH 6.92–7.09 (2H, m, ArH),
N,NЈ-Ethylenebis[p-methoxybenzylidenealdimine] 12f. (2.54
g, 86%) light yellow pellets (from hexane–EtOH), mp 112–
7.25–7.45 (m, 7H, ArH), 8.62 (1H, s, CH᎐N), 13.27 (1H, s,
᎐
OH); δC 117.2, 119.0, 119.2, 121.1, 126.9, 129.4, 132.3, 133.1,
113 ЊC; δH 3.81 (6H, s, 2 × OCH ), 3.91 [4H, s, ᎐N(CH ) N᎐],
᎐
᎐
3
2 2
148.5 (Car-N), 161.1 (Car-OH), 162.7 (CH᎐N); m/z 197 (100,
᎐
7.26 (8H, dd, JAB 23.0 and 8.7, 2 × ArH), 8.16 (2H, s, 2 × CH᎐
᎐
Mϩ), 180 (17, Mϩ Ϫ HO), 120 (22, Mϩ Ϫ Ph), 77 (66).
N); δC 55.3 (N-C-C-N), 61.7 (2 × OCH3), 113.8, 129.1, 129.6,
161.5 (Car-O), 161.9 (CH᎐N); m/z 296 (1, Mϩ), 163 (95,
᎐
Mϩ Ϫ CH OC H CH᎐N), 135 [76, Mϩ Ϫ CH OC H CH᎐N-
N-Salicylidenebenzylamine 3g. (1.79 g, 85%) lemon yellow
plates (from hexane), mp 29–30 ЊC; δH 4.77 (2H, s, CH2),
6.83–6.97 (2H, m, ArH), 7.21–7.36 (7H, m, ArH), 8.39 (1H, s,
᎐
᎐
3
6
4
3
6
4
(CH ) ], 121 [100, Mϩ Ϫ CH OC H CH᎐N (CH ) N᎐].
᎐
᎐
2
2
3
6
4
2 2
CH᎐N), 13.41 (1H, s, OH); δ 63.2 (CH ), 117.0, 118.6, 118.8,
᎐
C
2
N,NЈ-Trimethylenebis[p-methoxybenzylidenealdimine] 12g.
(2.57 g, 83%) colorless pellets (from hexane–EtOH), mp
127.3, 127.8, 127.9, 128.7, 131.4, 132.4, 138.2 (Car-CH2-N),
161.1 (Car-OH), 165.6 (CH᎐N); m/z 211 (29, Mϩ), 194
᎐
74–76 ЊC; δH 2.09 (2H, quintet, J 6.8, ᎐NCH CH CH N᎐),
᎐
᎐
2
2
2
(4, Mϩ Ϫ HO), 120 (7, Mϩ Ϫ PhCH2), 91 (100).
3.69 (4H, t, J 6.8, ᎐NCH -CH CH N᎐), 3.83 (6H, s, 2 ×
᎐
᎐
2
2
2
OCH3), 7.26 (8H, dd, JAB 24.6 and 8.7, 2 × ArH), 8.21 (2H, s,
General procedure for the synthesis of dialdehydes 13
2 × CH᎐N); δ 32.0 (N-C-C-C-N), 55.3 (N-C-C-C-N), 59.1
᎐
C
(OCH ), 113.8, 129.2, 129.5, 160.5 (Car-O), 161.4 (CH᎐N);
᎐
3
In a 500 mL 3-necked round-bottom flask provided with reflux
condenser were introduced 12.2 g (0.1 mol) salicylaldehyde in
10 mL of EtOH and 200 mL of 2% aq. NaOH (0.1 mol
NaOH). After 15 min of stirring, a solution of 0.05 mol of the
corresponding dibrominated compound dissolved in 150 mL of
EtOH was added in one portion. The mixture was magnetically
stirred, under reflux, for 72 h. The reaction mixture was cooled
and kept for 24 h on ice. The dialdehyde slowly precipitated.
After filtration and drying in vacuo the crude dialdehydes were
recrystallized from EtOH or PirOH. All these compounds have
been described elsewhere.27
m/z 310 (2, Mϩ), 176 (48, Mϩ Ϫ CH OC H CH᎐N), 162 (61,
᎐
3
6
4
Mϩ Ϫ CH OC H CH᎐NCH ), 148 [100, Mϩ Ϫ CH OC H -
᎐
3
6
4
2
3
6
4
CH᎐N(CH ) ], 134 [23, Mϩ Ϫ CH OC H CH᎐N(CH ) ], 120
᎐
᎐
2
2
3
6
4
2 3
[26, Mϩ Ϫ CH OC H CH᎐N(CH ) N᎐].
᎐
᎐
3
6
4
2 3
N,NЈ-Tetramethylenebis[p-methoxybenzylidenaldimine] 12h.
(2.43 g, 75%): white prisms (hexane–EtOH), mp 116–117 ЊC;
δH 1.73–1.78 (4H, m, ᎐NCH CH CH CH N᎐), 3.71–3.75 (4H,
᎐
᎐
2
2
2
2
m, ᎐NCH CH CH CH N᎐), 3.83 (6H, s, 2 × OCH ), 7.26 (8H,
᎐
᎐
2
2
2
2
3
dd, JAB 8.7 and 23.2, ArH), 8.15 (2H, s, 2 × CH᎐N); δ 28.8
᎐
C
(N-C-C-C-C-N), 55.3 (N-C-C-C-C-N), 61.4 (OCH3), 113.9,
114.2, 129.2, 129.5, 131.9, 160.2 (CH᎐N), 161.4 (Car-O); m/z
᎐
General procedure for the synthesis of open-chain diimines 12, 14
324 (1, Mϩ), 189 (100, Mϩ Ϫ CH OC H CH᎐N), 162 [15,
᎐
3
6
4
Mϩ Ϫ CH OC H CH᎐N(CH ) ], 134 [36, Mϩ Ϫ CH OC H -
In a standard procedure, in a 100 mL round-bottom flask
equipped with a reflux condenser were introduced 20 mmol of
dialdehyde or 0.1 mol of aldehyde and 30 mL of water. The
amine (40 mmol) or diamine (0.05 mol) was added in one por-
tion and the flask was kept at room temperature under vigorous
magnetic stirring for 2 h in the case of diimines 12 and at room
temperature for 4 h or under reflux for 2 h for diimines 14.
Diimines 12 were separated by direct filtration while most of
the diimines 14 needed extraction. The crude reaction products
were analyzed by NMR and GC-MS, MS and high-resolution
MS. When needed, further purification by recrystallization was
performed.
᎐
3
6
4
2
2
3
6
4
CH᎐N(CH ) ], 91 (21).
᎐
2
4
N,NЈ-Ethylenebis[salicyldinealdimine] 12j. (2.17 g, 81%):
lemon yellow plates (from hexane–MeOH), mp 130–131 ЊC
(lit.,22 139 ЊC); δH 3.92 [4H, s, ᎐N(CH ) N᎐], 6.82–6.94 (4H, m,
᎐
᎐
2
2
ArH), 7.20–7.29 (4H, m, ArH), 8.34 (2H, s, 2 × CH᎐N), 13.21
᎐
(2H, s, 2 × OH); δC 59.8 (CH2), 117.0, 118.6, 118.7, 131.5, 132.4,
161.0 (Car-OH), 166.6 (CH᎐N); m/z 268 (35, Mϩ), 147 (52,
᎐
Mϩ Ϫ HOC H CH᎐N), 107 (100).
᎐
6
4
N,NЈ-1,3-Trimethylenebis[salicylidenealdimine] 12k. (2.37 g,
84%): lemon yellow plates (from hexane), mp 52–53 ЊC (lit.,23
N,NЈ-Ethylenebis[benzylidenealdimine] 12b. (1.93 g, 82%):
very light yellow prisms (from hexane), mp 52–53 ЊC (lit.,34
52 ЊC); δH 2.11 (2H, quintet, J 6.6, ᎐NCH CH CH N᎐), 3.71
᎐ ᎐
2 2 2
(4H, t, ᎐NCH CH CH N᎐), 6.85–6.97 (4H, m, ArH), 7.22–
᎐
᎐
2
2
2
52–53 ЊC); δH 3.96 [4H, s, ᎐N(CH ) N᎐], 7.33–7.39 (6H, m,
7.34 (4H, m, ArH), 8.37 (2H, s, 2 × CH᎐N), 13.44 (2H, s, OH);
᎐
᎐
᎐
2
2
J. Chem. Soc., Perkin Trans. 1, 2001, 2071–2078
2075

View Article Online
δC 31.6 (C-C-C), 56.8 (C-C-C), 116.9, 118.6, 118.7, 131.2,
(O-C-C-C-O), 65.2 (ArCN᎐), 11.8, 112.2, 120.9, 124.6, 126.7,
᎐
132.2, 161.0 (Car-OH), 165.4 (CH᎐N); m/z 282 (16, Mϩ), 148
127.4, 127.8, 127.9, 128.1, 128.2, 128.4, 130.6, 131.8, 139.4,
᎐
(100, Mϩ Ϫ HOC H CH᎐NCH ), 134 [86, Mϩ Ϫ HOC H CH᎐
157.5 (CH᎐N), 157.8 (Car-O); m/z 462 (7, Mϩ), 371 (100,
᎐
᎐
᎐
6
4
2
6
4
N(CH2)2)].
Mϩ Ϫ PhCH ), 266 (10, Mϩ Ϫ PhCH N᎐CHC H O), 91 (36).
᎐
2
2
6
4
O,OЈ-Tetramethylenebis(salicylideaniline) 14g. (0.77 g, 86%):
white prisms (from MeOH–CHCl3), mp 102–104 ЊC (lit.,35 103–
104.5 ЊC); δH 2.05 (4H, quintet, J 5.3, OCH2CH2CH2CH2O),
4.13 (4H, t, J 5.3, OCH2CH2CH2CH2O), 6.90–7.05 (4H, m,
ArH), 7.16–7.41 (12H, m, ArH), 8.12–8.15 (2H, dd, J 7.7 and
1.7, ArH), 8.90 (2H, s, 2 × CH᎐N); δ 26.1 (O-C-C-C-C-O),
N,NЈ-1,4-Tetramethylenebis[salicylidenealdimine] 12l. (2.37 g,
80%): lemon yellow plates (from hexane), mp 89–90 ЊC; δH 1.79
(4H, s, ᎐NCH CH CH CH N᎐), 3.64 (4H, s, ᎐NCH CH CH -
᎐
᎐
᎐
2
2
2
2
2
2
2
CH N᎐), 6.84–6.96 (4H, m, ArH), 7.22–7.32 (4H, m, ArH),
᎐
2
8.35 (2H, s, 2 × CH᎐N), 13.52 (2H, s, OH); δ 28.5 (C-C-C-C),
᎐
C
59.2 (C-C-C-C), 116.9, 118.5, 118.7, 131.1, 132.1, 161.1
᎐
C
(Car-OH), 164.8 (CH᎐N); m/z 296 (34, Mϩ), 175 (100, Mϩ Ϫ
67.9 (O-C-C-C-C-O), 111.9, 121.0, 121.1, 125.1, 125.7, 127.7,
᎐
129.1, 132.7, 152.9 (Car-N᎐), 156.3 (CH᎐N), 158.8 (Car-O); m/z
HOC H CH᎐N).
᎐
᎐
᎐
6
4
448 (52, Mϩ), 371 (100, Mϩ Ϫ Ph), 252 (12, Mϩ Ϫ PhN᎐
᎐
CHC H O), 196 [28, Mϩ Ϫ PhN᎐CHC H O(CH ) ].
O,OЈ-Methylenebis(salicylideneaniline) 14a. (0.7 g, 87%):
white prisms (from hexane), mp 89–91 ЊC (lit.,35 88.5–90 ЊC);
δH 5.91 (2H, s, OCH2O), 7.10–7.48 (16H, m, ArH), 8.15–8.18
᎐
6
4
6
4
2 4
O,OЈ-Tetramethylenebis(salicylidenebenzylamine) 14h. (0.85
g, 89%): white prisms (from hexane–CHCl3), mp 94–96 ЊC;
δH 2.02 (4H, quintet, J 5.3, OCH2CH2CH2CH2O), 4.10 (4H, t,
(2H, dd, J 7.8 and 1.6, ArH), 8.81 (2H, s, 2 × CH᎐N); δ 91.7
᎐
C
(O-C-O), 115.1, 120.9, 123.1, 125.8, 126.0, 127.9, 129.1, 132.7,
152.4 (Car-N᎐), 155.8 (CH᎐N), 156.8 (Car-O); m/z 406 (5,
2
2
2
2
2
J 5.3, OCH CH CH CH O), 4.79 (4H, s, 2 × ArCH N᎐), 6.88–
᎐
᎐
᎐
Mϩ), 376 (57), 210 (100, Mϩ Ϫ PhN᎐CHC H O), 196 (89,
6.99 (4H, m, ArH), 7.21–7.37 (12H, m, ArH), 8.01–8.04 (2H,
dd, J 7.7 and 1.7, ArH), 8.83 (2H, s, 2 × CH᎐N); δ 26.1 (O-C-
᎐
6
4
Mϩ Ϫ PhN᎐CHC H OCH ).
C
᎐
᎐
6
4
2
C-C-C-O), 65.3 (ArCN᎐), 67.7 (O-C-C-C-C-O), 11.8, 120.8,
᎐
124.7, 126.8, 127.5, 127.9, 128.4, 131.9, 139.5, 157.7 (CH᎐N),
᎐
O,OЈ-Methylenebis(salicylidenebenzylamine) 14b. (0.77 g,
89%): white needles (from hexane), mp 55–57 ЊC; δH 4.74 (4H, s,
158.1 (Car-O); m/z 476 (16, Mϩ), 385 (100, Mϩ Ϫ PhCH2), 280
(9, Mϩ Ϫ PhCH N᎐CHC H O), 91 (32).
᎐
2 × ArCH from N᎐), 5.87 (2H, s, OCH O), 7.07–7.44 (16H, m,
2
6
4
᎐
2
2
ArH), 8.02–8.06 (2H, dd, J 7.7 and 1.4, ArH), 8.74 (2H, s,
2 × CH᎐N); δ 65.4 (Ar-C-N᎐), 65.8 (Ar-C-N᎐), 91.8 (O-C-O),
General procedure for the synthesis of macrocyclic diimines 15
᎐
᎐
᎐
C
115.1, 122.9, 126.0, 126.8, 127.8, 127.9, 128.4, 131.9, 139.4,
In a standard procedure, into a 100 mL round-bottom flask
equipped with a reflux condenser were introduced 10 mmol of
dialdehyde in 30 mL of water. The diamine (10.0 mmol) was
added in one portion and the flask was kept at reflux under
vigorous magnetic stirring for 2 h. The aqueous solution was
extracted twice with dichloromethane. Combined organic
layers were dried on MgSO4 and the organic solvent was evap-
orated off. The crude reaction products obtained after evapor-
ation was analyzed by NMR, MS and high-resolution MS.
When possible, further purification by recrystallization was
performed.
156.5 (Car-O), 157.4 (CH᎐N); m/z 434 (1, Mϩ), 404 (1), 343 (65,
᎐
Mϩ Ϫ PhCH ), 211 (63, Mϩ Ϫ PhCH N᎐CHC H OCH ), 91
᎐
2
2
6
4
2
(100).
O,OЈ-Ethylenebis(salicylideaniline) 14c. (0.6 g, 72%): white
prisms (from hexane–EtOH), mp 143–145 ЊC (lit.,35,36 128–
150 ЊC); δH from 4.46 (4H, s, OCH2CH2O), 6.99–7.45 (16H, m,
ArH), 8.12–8.15 (2H, dd, J 7.7 and 1.7, ArH), 8.84 (2H, s,
2 × CH᎐N); δ 67.4 (O-C-C-O), 112.6, 115.2, 121.1, 121.7,
᎐
C
125.3, 125.8, 127.9, 129.1, 129.4, 132.8, 152.7 (Car-N᎐), 156.2
᎐
(CH᎐N), 158.6 (Car-O); m/z 420 (16, Mϩ), 390 (18), 343 (87,
᎐
Mϩ Ϫ Ph), 224 (31, Mϩ Ϫ PhN᎐CHC H O), 197 (100,
᎐
6
4
14,15-Dihydrodibenzo[d,l][1,3,7,10]dioxadiazacyclotridecine
(O-mn-N-en) 15a. (0.42 g, 76%): light yellow prisms (hexane–
Mϩ Ϫ PhN᎐CHC H OCH ).
᎐
6
4
2
CHCl3), mp 61–63 ЊC; δH 3.88 (4H, s, ᎐NCH CH N᎐), 5.63
(2H, s, OCH2O), 6.98–7.32 (6H, m, ArH), 7.89–7.92 (2H, dd,
᎐
᎐
2
2
O,OЈ-Ethylenebis(salicylidenebenzylamine) 14d. (0.54 g,
65%): white plates (from hexane–CHCl3 99 : 1), mp 107–108 ЊC;
J 1.7 and 7.7, ArH), 8.59 (2H, s, 2 × CH᎐N); δ 59.2 (N-C-C-
᎐
C
δH 4.44 (4H, s, OCH CH O), 4.74 (4H, s, 2 × ArCH N᎐), 6.97–
᎐
2
2
2
N), 98.6 (O-C-O), 114.8, 115.7, 117.9, 123.6, 128.5, 131.5, 159.0
(Car-O), 161.4 (CH᎐N); m/z 280 (8, Mϩ), 279 (4), 162 (7), 148
7.04 (4H, m, ArH), 7.20–7.29 (10H, m, ArH), 7.37–7.42 (2H,
ddd, J 8.8, 1.7 and 0.9, ArH), 8.03–8.06 (2H, dd, J 7.7 and 1.7,
᎐
(6), 135 (100), 121 (3), 91 (5).
ArH), 8.79 (2H, s, 2 × CH᎐N); δ 65.3 (Ar-C-N᎐), 67.2 (O-C-
᎐
᎐
C
C-O), 112.4, 121.5, 125.1, 126.8, 127.7, 127.9, 128.3, 131.9,
15,16-Dihydro-6H,14H-dibenzo[d,m][1,3,7,11]dioxadiaza-
cyclotetradecine (O-mn-N-tn) 15b. (0.51 g, 87%): light yellow
plates (from MeOH), mp 63–66 ЊC; δH 2.01 (2H, t, J 5.8,
139.5, 157.6 (CH᎐N), 157.9 (Car-O-); m/z 448 (10, Mϩ), 357
᎐
(100, Mϩ Ϫ PhCH ), 211 [40, Mϩ Ϫ PhCH N᎐CHC H O-
᎐
2
2
6
4
(CH2)2], 91 (54).
᎐NCH CH CH N᎐), 3.60 (4H, t, J 5.8, ᎐NCH CH CH N᎐),
᎐
᎐
᎐
᎐
2
2
2
2
2
2
5.77 (2H, s, OCH2O), 7.02–7.39 (6H, m, ArH), 7.92–7.95 (2H,
O,OЈ-Trimethylenebis(salicylideaniline) 14e. (0.77 g, 89%):
very light yellow prisms (from Et2O), mp 85–87 ЊC (lit.,35 86–
87 ЊC); δH 2.36 (2H, t, J 6.0, CH2CH2CH2), 4.27 (4H, t, J 6.0,
CH2CH2CH2), 6.94–7.24 (16H, m, ArH), 8.12–8.15 (2H, dd,
J 7.7 and 1.7, ArH), 8.88 (2H, s, 2 × CH᎐N); δ 29.1 (C-C-C),
dd, J 1.6 and 7.7, ArH), 8.60 (2H, s, 2 × CH᎐N); δ 27.0 (N-C-
᎐
C
C-C-N), 58.6 (N-C-C-C-N), 97.8 (O-C-O), 118.3, 123.1, 123.9,
127.1, 127.5, 127.8, 131.8, 157.5 (Car-O), 158.6 (CH᎐N); m/z
᎐
294 (78, Mϩ), 293 (62), 266 (60), 162 (42), 148 (46), 134 (100), 91
(47).
᎐
C
64.8 (C-C-C), 112.1, 120.9, 121.1, 124.8, 125.6, 127.7, 129.1,
132.7, 152.8 (Car-N᎐), 156.2 (CH᎐N), 158.6 (Car-O); m/z 434
14,15,16,17-Tetrahydro-6H-dibenzo[d,n][1,3,7,12]dioxadiaza-
cyclopentadecine (O-mn-N-bn) 15c. (0.48 g, 79%); white prisms
(from MeOH), mp 64–68 ЊC; δH 1.71 (4H, br s, ᎐NCH -
᎐
᎐
(38, Mϩ), 357 (100, Mϩ Ϫ Ph), 237 (26, Mϩ Ϫ PhN᎐CHC -
᎐
6
H O), 197 [24, Mϩ Ϫ PhN᎐CHC H O(CH ) ), 77 (17).
᎐
᎐
4
6
4
2
3
2
CH CH CH N᎐), 3.58 (4H, br s, ᎐NCH CH CH CH N᎐), 5.80
᎐
᎐
᎐
2
2
2
2
2
2
2
O,OЈ-Trimethylenebis(salicylidenebenzylamine) 14f. (0.76 g,
82%): white needles (from Et2O), mp 53–55 ЊC; δH 2.18 (2H,
quintet, J 6.0, OCH2CH2CH2O), 4.05 (4H, t, J 6.0, OCH2-
(2H, s, OCH2O), 6.92–7.38 (6H, m, ArH), 7.94–7.97 (2H, dd,
J 1.0 and 7.6, ArH), 8.61 (2H, s, 2 × CH᎐N); δ 28.6 (N-C-C-C-
᎐
C
C-N), 61.7 (N-C-C-C-C-N), 91.6 (O-C-O), 114.7, 122.5, 122.8,
CH CH O), 4.66 (4H, s, 2 × ArCH N᎐), 6.75–6.87 (4H, m,
123.6, 126.9, 127.5, 128.5, 131.6, 156.1 (Car-O), 156.4 (CH᎐N);
᎐
᎐
2
2
2
ArH), 7.08–7.24 (12H, m, ArH), 7.90–7.93 (2H, dd, J 1.7 and
7.7, ArH), 8.69 (2H, s, 2 × CH᎐N); δ 29.0 (O-C-C-C-O), 64.8
m/z 308 (9, Mϩ), 307 (13), 279 (15), 162 (16), 148 (11), 135 (100),
91 (19).
᎐
C
2076
J. Chem. Soc., Perkin Trans. 1, 2001, 2071–2078

View Article Online
6,7,15,16-Tetrahydrodibenzo[e,m][1,4,8,11]dioxadiazacyclo-
tetradecine (O-en-N-en) 15d. (0.38 g, 65%); white amorphous,
128.6, 131.8, 156.7 (Car-O), 157.7 (CH᎐N); m/z 336 (8, Mϩ), 335
(14), 307 (23), 267 (100), 162 (26), 148 (28), 121 (60), 91 (26).
᎐
mp 174–176 ЊC; δH 3.98 (4H, s, ᎐NCH CH N᎐), 4.38 (2H, s,
᎐
᎐
2
2
6,7,8,9,17,18-Hexahydrodibenzo[g,o][1,6,10,13]dioxadiaza-
cyclohexadecine (O-bn-N-en) 15j. (0.54 g, 84%): δH 1.82–1.90
(4H, m, OCH CH CH CH O), 3.94 (4H, s, ᎐NCH CH N᎐),
OCH2CH2O), 6.95–7.06 (4H, m, ArH), 7.33–7.39 (2H, ddd,
J 1.7, 7.7 and 8.3, ArH), 7.65–7.68 (2H, dd, J 1.7 and 7.7, ArH),
8.58 (2H, s, 2 × CH᎐N); δ 59.1 (N-C-C-N), 66.6 (O-C-C-O),
᎐
᎐
2
2
2
2
2
2
᎐
C
114.2 122.0, 122.7, 128.8, 131.2, 157.3 (Car-O), 161.2 (CH᎐N);
3.95–4.12 (4H, m, OCH2CH2CH2CH2O), 6.83–6.98 (4H, m,
ArH), 7.25–7.33 (2H, m, ArH), 7.90–7.93 (2H, dd, J 1.2 and 7.5
ArH), 8.69 (2H, s, 2 × CH᎐N); δ 26.2 (O-C-C-C-C-O), 62.1
᎐
m/z 294 (24, Mϩ), 293 (17), 265 (9), 176 (100), 148 (77), 121 (67),
91 (45).
᎐
C
(N-C-C-N), 68.1 (O-C-C-C-C-O), 112.3, 115.5, 120.7, 121.6,
124.7, 127.3, 128.8, 131.4, 158.0 (Car-O), 159.3 (CH᎐N); m/z
Tetrahydro-15H-dibenzo[e,n][1,4,8,12]dioxadiazacyclopenta-
decine (O-en-N-tn) 15e. (0.44 g, 71%): white prisms (dist. Kugel
rohr 250 ЊC/0.1 Torr), mp 149–151 ЊC (lit.,28a 164 ЊC); δH 2.29
᎐
322 (35, Mϩ), 321 (29), 293 (59), 204 (49), 162 (62), 148 (55), 121
(48), 91 (100).
(2H, quintet, J 5.3, ᎐NCH CH CH N᎐), 3.60 (4H, t, J 5.3,
᎐
᎐
2
2
2
᎐NCH CH CH N᎐), 4.39 (4H, s, OCH CH O), 6.95–6.98 (2H,
6,7,8,9,1B,19-Hexahydro-17H-dibenzo[g,p][1,6,10,14]dioxa-
diazacyclohexadecine (O-bn-N-tn) 15k. (0.57 g, 85%): white
needles (from MeOH–CHCl3), mp 194–196 ЊC; δH 2.08–2.11
᎐
᎐
2
2
2
2
2
dd, J 8.3 and 0.6, ArH), 7.02–7.07 (2H, ddd, J 0.6, 7.4 and 8.3,
ArH), 7.37–7.43 (2H, ddd, J 1.7, 7.4 and 8.3, ArH), 7.94–7.97
(2H, dd, J 1.7 and 7.4, ArH), 8.72 (2H, s, 2 × CH᎐N); δ 28.5
(4H,m,OCH CH CH CH O),2.20–2.27(2H,m,᎐NCH CH CH -
᎐
C
᎐
2
2
2
2
2
2
2
(N-C-C-C-N), 57.9 (N-C-C-C-N), 68.0 (O-C-C-O), 113.5,
N᎐), 3.55–3.59 (4H, m, ᎐NCH CH CH N᎐), 4.08–4.09 (4H, m,
OCH2CH2CH2CH2O), 6.88–7.01 (4H, m, ArH), 7.34–7.40 (2H,
ddd, J 1.8, 7.4 and 8.2, ArH), 7.89–7.92 (2H, dd, J 1.8 and 7.7,
᎐
᎐
᎐
2
2
2
121.7, 125.6, 127.0, 128.7, 131.7, 135.9, 158.6 (Car-O), 158.8
(CH᎐N); m/z 308 (19, Mϩ), 307 (33), 279 (24), 190 (43), 162
᎐
(100), 148 (16), 134 (73), 107 (99), 91 (63).
ArH), 8.78 (2H, s, 2 × CH᎐N); δ 26.2 (O-C-C-C-C-O), 29.0
᎐
C
(N-C-C-C-N), 56.8 (N-C-C-C-N), 67.2 (O-C-C-C-C-O), 113.6,
120.7, 124.9, 127.2, 131.7, 158.3 (Car-O), 158.7 (CH᎐N); m/z
6,7,15,16,17,18-Hexahydrodibenzo[e,o][1,4,8,13]dioxadiaza-
cyclohexadecine (O-en-N-bn) 15f. (0.42 g, 66%); light yellow
prisms (from MeOH–CHCl3), mp 59–61 ЊC; δH 1.69–1.75 (4H,
᎐
336 (8, Mϩ), 335 (12), 307 (4), 190 (26), 162 (38), 148 (32), 134
(45), 107 (100), 91 (62).
t, J 5.2, ᎐NCH CH CH CH N᎐), 3.70–3.73 (4H, t, J 5.2,
᎐
᎐
2
2
2
2
᎐NCH CH CH CH N᎐), 4.43 (4H, s, OCH CH O), 6.90–7.03
(4H, m, ArH), 7.31–7.39 (2H, m, ArH), 7.88–7.92 (2H, dd, J 1.8
᎐
᎐
6,7,8,9,17,18,19,20-Octahydrodibenzo[g,q][1,6,10,15]dioxa-
diazacyclooctadecine (O-bn-N-bn) 15l. (0.49 g, 70%): white
prisms (from hexane–CHCl3), mp 53–56 ЊC; δH 1.66–1.68 (4H,
2
2
2
2
2
2
and 7.7, ArH), 8.63 (2H, s, 2 × CH᎐N); δ 26.4 (N-C-C-C-C-
᎐
C
N), 58.9 (N-C-C-C-C-N), 66.1 (O-C-CO), 113.0, 121.8, 126.0,
m, OCH CH CH CH O), 1.87–1.92 (4H, m, ᎐NCH CH -
᎐
2
2
2
2
2
2
127.5, 127.6, 131.6, 157.0 (Car-O), 158.1 (CH᎐N); m/z 322 (21),
᎐
CH CH N᎐), 3.55–3.62 (4H, m, ᎐NCH CH CH CH N᎐),
᎐ ᎐ ᎐
2 2 2 2 2 2
3.98–4.05 (4H, m, OCH2CH2CH2CH2O), 6.76–6.89 (4H, m,
ArH), 7.21–7.27 (2H, m, ArH), 7.74–7.77 (2H, dd, J 1.8 and
321 (32), 293 (50), 253 (100), 204 (67), 176 (21), 148 (46), 121
(87), 91 (25).
7.7, ArH), 8.70 (2H, s, 2 × CH᎐N); δ 26.1 (N-C-C-C-C-N),
28.8 (O-C-C-C-C-O), 61.8 (N-C-C-C-C-N), 67.8 (O-C-C-C-C-
᎐
C
7,8,16,17-Tetrahydro-6H-dibenzo[f,n][1,5,9,12]dioxadiaza-
cyclopentadecine (O-tn-N-en) 15g. (Literature data28,29 gave a
general experimental method for the in situ generation of the
ligand but no physical data for this compound; only the final Ni
complex is characterized.) (0.41 g, 66%): δH 2.16 (2H, t, J 6.0,
O), 112.3, 120.6, 120.7, 121.2, 124.7, 125.9, 127.3, 128.3, 131.5,
156.6 (Car-O), 157.9 (CH᎐N); m/z 350 (10, Mϩ), 349 (12), 321
᎐
(20), 281 (100), 174 (19), 162 (15), 148 (12), 134 (17), 91 (12).
OCH CH CH O), 3.93 (4H, s, ᎐NCH CH -N᎐), 4.10 (4H, t,
᎐
᎐
2
2
2
2
2
References and notes
J 6.0, OCH2CH2CH2O), 6.83–9.95 (4H, m, ArH), 7.26–7.32
(2H, m, ArH), 7.89–7.91 (2H, dd, J 1.1 and 7.2, ArH), 8.68 (2H,
s, 2 × CH᎐N); δ 29.3 (O-C-C-CO), 58.6 (N-C-C-N), 68.7
1 See for example: (a) Green Chemistry: Theory and Practice, ed. P. T.
Anastas and J. C. Warner, 1998, Oxford University Press, New York;
(b) Green Chemistry: Frontiers in Benign Chemical Syntheses and
Processes, ed. P. T. Anastas and T. C. Williamson, 1998, Oxford
University Press, New York.
᎐
C
(O-C-C-CO), 112.9, 120.9, 121.2, 125.6, 127.4, 128.1, 131.8,
136.0, 157.8 (Car-O), 158.9 (CH᎐N); m/z 308 (4, Mϩ), 307 (6),
᎐
284 (45), 162 (50), 148 (24), 135 (63), 121 (100), 91 (32).
2 (a) D. C. Rideout and R. Breslow, J. Am. Chem. Soc., 1980, 102,
7816; (b) R. Breslow and T. Guo, J. Am. Chem. Soc., 1988, 110, 5613.
3 (a) A. Lubineau and E. Meyer, Tetrahedron, 1988, 44, 6065;
(b) C. Petrier and J.-L. Luche, J. Org. Chem., 1985, 50, 910.
4 See for example: (a) T. Tsukinoki, Y. Mitoma, S. Nagashima,
T. Kawaji, I. Hashimoto and M. Tashiro, Tetrahedron Lett., 1998,
39, 8873; (b) Y. Mitoma, S. Nagashima, T. Tsukinoki, Z. Li and
M. Tashiro, Abstracts of 1999 IAMS, International Symposium on
New Reactions and Novel Structures, ed. I. Mochida, Kyushu
University, Fukuoka, 1999, pp. 69–72; (c) T. Tsukinoki, T. Kawaji,
I. Hashimoto, S. Mataka and M. Tashiro, Chem. Lett., 1997, 235;
(d ) T. Tsukinoki, S. Nagashima, Y. Mitoma and M. Tashiro, Green
Chem., 2000, 2.
7,8,17,18-Tetrahydro-6H,16H-dibenzo[f,o][1,5,9,13]dioxa-
diazacyclohexadecine (O-tn-N-tn) 15h. (0.53 g, 82%); white
28a
prisms (from hexane–CHCl3), mp 128–30 ЊC (lit.,
129 ЊC);
δH 2.24–2.29 (4H, 2 superimposed quintets, J 5.0 and 5.3,
respectively, OCH CH CH O and ᎐NCH CH CH N᎐, respect-
᎐
᎐
2
2
2
2
2
2
ively), 3.61 (4H, t, J 5.3, ᎐NCH CH CH -N᎐), 4.32 (4H, t,
᎐
᎐
2
2
2
J 5.0, OCH2CH2CH2O), 6.97–7.04, 4H, m, ArH), 7.26 (2H,
ddd, J 1.7, 7.3 and 8.2, ArH), 7.95–7.98 (2H, dd, J 1.7 and 7.6,
ArH), 8.66 (2H, s, 2 × CH᎐N); δ 28.7 (N-C-C-C-N), 29.6
᎐
C
(O-C-C-C-O), 57.1 (N-C-C-C-N), 68.3 (O-C-C-C-O), 112.7,
121.2, 125.5, 127.5, 131.7, 158.2 (Car-O), 158.8 (CH᎐N); m/z
5 H. Schiff, Justus Liebigs Ann. Chem., 1864, 131, 11.
6 G. Pyl, Ber. Dtsch. Chem. Ges., 1927, 60, 287.
᎐
322 (51, Mϩ), 321 (100), 293 (56), 176 (32), 162 (94), 148 (61),
134 (76), 107 (64), 91 (41).
7 A. H. Cook, I. Heilbron and A. L. Levy, J. Chem. Soc., 1947, 1598.
8 J. S. Morley and J. C. E. Simpson, J. Chem. Soc., 1948, 2024.
9 R. E. Lutz, J. C. E. Wilson III, A. J. Deinet, G. H. Harnest, T. A.
Martin and J. A. Freek, J. Org. Chem., 1947, 12, 96.
10 E. Winterstein and G. Trier, Die Alkaloide, Borntraeger, Berlin,
1910, pp. 263–317.
11 R. Robinson, J. Chem. Soc. Trans., 1917, 111, 762.
12 C. Schopf, Angew. Chem., 1937, 50, 779.
13 C. A. C. Haley and P. Maitland, J. Chem. Soc., 1951, 3155.
14 (a) E. H. Cordes and W. P. Jencks, J. Am. Chem. Soc., 1962, 84, 832;
(b) E. H. Cordes and W. P. Jencks, J. Am. Chem. Soc., 1963, 85, 2843.
15 (a) E. H. Cordes and W. P. Jencks, J. Am. Chem. Soc., 1962, 84, 4319;
(b) W. P. Jencks, J. Am. Chem. Soc., 1959, 81, 475.
Hexahydro-6H-dibenzo[f,p][1,5,9,14]dioxadiazacyclohepta-
decine (O-tn-N-bn) 15i. (0.49 g, 72%); white solid (from
MeOH), mp 99–102 ЊC; δH 1.75 (4H, br s, ᎐NCH CH -
᎐
2
2
CH CH N᎐), 2.32 (2H, t, J 6.0, OCH CH CH O), 3.62 (4H, br
᎐
2
2
2
2
2
s, ᎐NCH CH CH CH N᎐), 4.20 (4H, t, J 6.0, OCH CH -
᎐
᎐
2
2
2
2
2
2
CH2O), 6.88–7.00 (4H, m, ArH), 7.25–7.35 (2H, m, ArH),
7.91–7.93 (2H, dd, J 1.2 and 7.6, ArH), 8.68 (2H, s, 2 × CH᎐N);
᎐
δC 26.7 (N-C-C-C-C-N), 29.2 (O-C-C-C-O), 59.9 (N-C-C-C-C-
N), 68.8 (O-C-C-C-O), 112.4, 121.0, 12.8, 124.9, 125.7, 127.4,
J. Chem. Soc., Perkin Trans. 1, 2001, 2071–2078
2077

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2078
J. Chem. Soc., Perkin Trans. 1, 2001, 2071–2078