Facile synthesis of substituted mono-, di-, tri- And tetra-2-aryl-2,3- dihydro1H-perimidines

Article abstract of DOI:10.1002/ejoc.201000670

The efficient synthesis of a variety of substituted 2-aryl-2, 3dihydro-1H-perimidines using Zn-catalysis is reported. A series of 2,3-dihydroperimidines with various functional groups have been isolated in high yield by simple filtration from the reaction

Full text of DOI:10.1002/ejoc.201000670

FULL PAPER
DOI: 10.1002/ejoc.201000670
Facile Synthesis of Substituted Mono-, Di-, Tri- and Tetra-2-aryl-2,3-dihydro-
1H-perimidines
Marta Martínez Belmonte,[a] Eduardo C. Escudero-Adán,[a] Jordi Benet-Buchholz,[a]
Robert M. Haak,[a] and Arjan W. Kleij*[a,b]
Keywords: Nitrogen heterocycles / Perimidines / Zinc catalysis
The efficient synthesis of a variety of substituted 2-aryl-2,3-
dihydro-1H-perimidines using Zn-catalysis is reported. A
series of 2,3-dihydroperimidines with various functional
groups have been isolated in high yield by simple filtration
from the reaction mixture. The new compounds have been
fully characterized by spectroscopic and spectrometric analy-
ses and in some cases also by X-ray diffraction. The synthetic
approach was subsequently also tested for di-, tri-, and tetra-
(salicyl)aldehyde reagents and afforded the corresponding
multi-perimidines in good yields. In the present studies also
an unexpected bis(2,3-dihydro-1H-perimidine) decomposi-
tion product has been identified. The current approach
underlines the simplicity of creating a series of perimidines
which may be post-altered by using the functional group di-
versity introduced through the aldehyde reagents.
tems that find use as ligand scaffolds for catalytically active
complexes,[6] as convenient “stoppers” of supramolecular
systems such as [2]- and [4]rotaxanes,[7] and as fragments of
N-salicylideneaniline structures.[8]
We here report a versatile Zn-mediated approach towards
a small library of functionalized 2-aryl-2,3-dihydro-1H-per-
imidines with ample scope that is among the mildest and
most efficient methods reported to date. Additionally, we
report on various multi-2,3-dihydro-1H-perimidinal sys-
tems that can also easily be obtained from di-, tri- and
tetra-aldehyde precursors.
Introduction
Perimidines[1] are tricyclic heterocycles consisting of a di-
hydropyrimidine ring ortho- and peri-fused to a naphtha-
lene fragment. These structures have been shown to be
interesting candidates for biological activity studies and
find widespread application in industry, agriculture and
medicine.[2] A generally applied synthetic route towards per-
imidines comprises the reaction of 1,8-diaminonaphthalene
with a carbonyl compound such as carboxylic acids, anhy-
drides, acid halides, ketones or aldehyde reagents.[3] In the
latter case 2,3-dihydro-1H-perimidines are produced which
can be easily converted to perimidines by dehydrogenation.
The preparation of (2,3-dihydro-1H-)perimidines has been
subject of many investigations using Lewis acid promoted
reactions[4] or other methods.[5] Although aryl-function-
alized 2,3-dihydro-1H-perimidines have been known for
quite some time, their corresponding derivatives con-
structed from salicylaldehyde reagents remain remarkably
unexplored. Properly functionalized salicylaldehydes would
allow post-functionalization of the perimidine structure
and/or combination with other scaffolds by coupling pro-
cedures to give rise to new (multi-)perimidines with poten-
tially interesting properties relevant for pharmaceutical ap-
plications. On the other hand, recent literature has wit-
nessed the communication of various multi-perimidinal sys-
Results and Discussion
Our interest in using 1,8-diaminonaphthalene as a scaf-
fold originates from the studies we have undertaken to ex-
plore various salen structures as versatile building blocks
for new materials[9] and supramolecular structures.[10] We
are particularly attracted to diamino-aryl scaffolds that are
able to induce a planar geometry around the ligated metal
ion, and have reported on the unusual properties of Zn-
centred salphen complexes [salphen = N,NЈ-salicylidene-
1,2-diaminophenyl].[11] We envisioned that 1,8-diaminona-
phthalene would be a useful starting point for the creation
of other types of geometrically planar ligands that, upon
ligation of Zn ions, should be able to amplify the arsenal of
intriguing structures potent as a molecular building block.
Molecular modelling studies[12] revealed that indeed a
rather planar geometry may be obtained and therefore we
set out to prepare the corresponding salen complex derived
from 1,8-diaminonaphthalene using conditions that have
previously been proven to be successful for salphen deriva-
View this journal online at
[a] Institute of Chemical Research of Catalonia (ICIQ),
Av. Països Catalans 16, 43007 Tarragona, Spain
Fax: +34-977920224
E-mail: akleij@iciq.es
[b] Catalan Institute for Research and Advanced Studies (ICREA),
Passeig Lluís Companys 23, 08010 Barcelona, Spain
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201000670.
wileyonlinelibrary.com
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A. W. Kleij et al.
FULL PAPER
tives.[13] Combination of 2 equiv. of 3,5-di-tert-butylsalicyl- studies is shown in Figure 2. The 1,5-substitution of the two
aldehyde with 1,8-diaminonaphthalene 1 and an excess of salicylidene groups in 2b probably originates from an impu-
Zn(OAc)2·2H2O in MeOH (see Exp. Sect. and Scheme 1) rity (i.e., 1,5-diaminonaphthalene) in the starting material
gave a fast precipitation of a white solid. This solid was first 1,8-diaminonaphthalene.[15]
1
analyzed by H NMR spectroscopy ([D6]acetone solution)
and showed a single, pure compound with a resonance
pattern that could not be associated with a Zn(salen) com-
plex. Typical peaks at δ = 6.20 and 5.75 ppm (2:1 integral
ratio) were observed that indicated the formation of a dis-
tinct species. Closer inspection of the NMR spectrum and
mass spectroscopic data confirmed the isolation of 2-(2-hy-
droxy-3,5-di-tert-butylphenyl)-2,3-dihydro-1H-perimidine
(2, Scheme 1) in 48% yield. The selective formation and iso-
lation of 2 was further supported by X-ray diffraction
(XRD) analysis (Figure 1).
Figure 2. Molecular structure for 2b (minor product) determined
by XRD with the adopted numbering scheme; co-crystallized sol-
vent molecules and H-atoms are omitted for clarity.[14]
The synthesis of 2 was then probed with and without
the presence of a catalytic amount of Zn(OAc)2·2H2O (8–
10 mol-%) and with a slight excess of salicylaldehyde rea-
gent. The isolated yield in the presence of Zn catalyst
proved to be significantly higher at different stages of the
reaction (Scheme 2, scale: 4 mmol of 1,8-diaminonaphth-
alene using 1.2 mol equiv. of salicylaldehyde). The simple
isolation of compound 2 prompted us to investigate the
scope of this reaction in more detail. We therefore screened
a number of salicylaldehyde reagents for the preparation
of a series of substituted 2-aryl-2,3-dihydro-1H-perimidines
(Scheme 1, 2–14) with the use of Zn(OAc)2·2H2O as cata-
lyst. In particular, salicylaldehydes with functional groups
that allow for post-modification were utilized and the re-
sults of this screening are summarized in Table 1.
Scheme 1. Synthesis of 2,3-dihydro-1H-perimidines 2–14 via a Zn-
mediated procedure.
Figure 1. Molecular structure for 2 determined by XRD with the
adopted numbering scheme; co-crystallized solvent molecules and
H-atoms are omitted for clarity.[14]
Scheme 2. Time-dependent isolated yield in the presence (lane 1)
and absence (lane 2) of Zn(OAc)2·2H2O.
From the reaction described above a second fraction of
Both apolar, aliphatic as well as distinct polar groups can
product was also isolated but proved to be impure and con- be readily introduced in the perimidine structure
tained, besides 2, another compound (2b) with an NMR (Table 1).[16] With the exception of 11, all isolated yields are
pattern having characteristic peaks a 13.94 and 9.08 ppm beyond 70%. It should be noted that for the majority of
(Supporting Information). These chemical shifts pointed to the cases simple filtration of the reaction mixture afforded
the formation of an imine species and fortunately this com- the pure product in high yield. In some cases the isolation
ponent selectively crystallized from the NMR solvent mix- of the product was carried out by concentration and/or
ture ([D6]acetone/[D6]DMSO). The result of these XRD cooling of the reaction mixture. The products 6 and 9 (the
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Mono-, Di-, Tri- and Tetra-2-aryl-2,3-dihydro-1H-perimidines
Table 1. Synthesis of various substituted 2-aryl-2,3-dihydro-1H- was used. Therefore, the synthesis of 9 was finally carried
perimidines 2–14 and 1H and 13C{1H} NMR spectroscopic data
for the aryl-CH fragment.
out with equimolar amounts of 1,8-diaminonaphthalene
and 5-bromosalicylaldehdye and the product was isolated
through precipitation of the product by addition of water
to the reaction mixture.
Although the reactions of Table 1 were not followed in
time, there are strong indications that the products are
formed much faster than the experimental conditions indi-
cate. For instance, the syntheses of 5 (30 min reaction time,
85% yield) and 6 (5 min reaction time, 99% yield) suggest
that 2,3-dihydro-1H-perimidine formation might indeed be
a fast process and the use of stoichiometric amounts of sali-
cylaldehyde (see 9) should be sufficient to reach full conver-
1
sion of the starting materials. All compounds showed H
and 13C{1H} consistent with their structures: the data of
the characteristic aryl-CH fragment is listed in Table 1. The
structure for 12 was also determined by XRD (Figure 3).
Figure 3. Molecular structure for 12 determined by XRD with the
adopted numbering scheme; co-crystallized solvent molecules and
H-atoms are omitted for clarity. Note that only one of the indepen-
dent molecules in the unit cell is shown.[14]
As the 2,3-dihydro-1H-perimidine compounds 2–14
(Table 1, Scheme 1) are easily obtained, we then focused on
more challenging substrates such as 2-hydroxyisophthal-
aldehyde 15 and previously reported di-salicylaldehyde 16
(Scheme 3).[17] Using the same synthetic methodology, the
bis(2,3-dihydro-1H-perimidine) compounds 17 and 18 were
isolated in 94% and 85% yield, respectively. The identity of
17 and 18 could be simply deduced from the NMR spectro-
scopic data through the diagnostic integral ratio (1:4:2 for
17 and 2:4:2 for 18) between the OH, the NH and aryl-CH
groups, and the ESI(–)-MS data. The proposed structure
for 17 was also supported by XRD (Figure 4).[18]
The synthesis of 20 from known trialdehyde 17[19] proved
to be more cumbersome (Scheme 4). Our initial intent
failed due to precipitation of partially substituted 17 as
identified by both NMR and MS analysis. We then used a
more dilute reaction mixture and short heating time to re-
flux temperature in order to prevent precipitation of both
the tri-aldehyde reagent as well as incompletely substituted
17 at an early stage of the process. Much to our surprise we
discovered the formation of bis(2,3-dihydro-1H-perimidine)
[a] Isolated yield. [b] NMR spectroscopic data recorded in [D6]-
acetone unless stated otherwise. [c] Recorded in [D6]DMSO. [d] Re-
corded in 90:10 v/v [D6]acetone/[D6]DMSO. [e] Recorded in 70:30
v/v [D6]acetone/[D6]DMSO.
brominated derivatives) behaved completely different. While 21 as the major isolated product under these conditions.
compound 6 was isolated in nearly quantitative yield after Compound 21 has two 2,3-dihydro-1H-perimidine frag-
one single filtration, the isolation of its isomeric 9 proved ments but surprisingly comprises a protonated central aryl
to be complicated when an excess of salicylaldehyde reagent unit instead of the expected, unreacted aryl-CHO group.
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A. W. Kleij et al.
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Scheme 3. Synthesis of bis(2,3-dihydro-1H-perimidines) 17 and 18 using dialdehydes 15 and 16.
Figure 4. Molecular structure for 17 determined by XRD with the
adopted numbering scheme; co-crystallized solvent molecules and
H-atoms are omitted for clarity.[14]
The isolation of 21 was fully supported by NMR and mass
spectrometric analyses.[20] For instance, the 13C{1H} NMR
spectrum recorded for 21 did not show the characteristic
aldehyde carbon around 190 ppm and displayed one carbon
peak less than would be expected for the bis(2,3-dihydro-
1H-perimidine) product having the aldehyde function still
intact. An alternative synthesis of 20 was then probed by
using DMSO as co-solvent (see Exp. Sect.). Under these
latter conditions a homogeneous mixture results at the be-
ginning of the reaction, after which rapidly a solid starts to
precipitate. The identity of this precipitate was established
with NMR and MS and the product turned out to be the
mono-2,3-dihydro-1H-perimidine 20a (61% isolated yield,
Scheme 3). From the mother liquor a second fraction was
Scheme 4. Use of trialdehyde 19 for the synthesis of 20a, 20b and
21.
We then also investigated the possibility to create multi-
isolated and this was analyzed as the tris(2,3-dihydro-1H- perimidine structures supported by calixarenes by treatment
perimidine) 20b (14% isolated yield, Scheme 3). These find- of known tetraformylcalix[4]arene 22[22] with an excess of
ings emphasize the low solubility of the intermediate struc- 1,8-diaminonaphthalene in THF (Scheme 5). This pro-
tures in the conversion 19Ǟ20b. Crystals of 20b could be cedure afforded calix[4]-perimidine 23 in 55% isolated yield.
obtained from DMSO/Et2O, and the structure (Figure 5) The structure of 23 was fully supported by NMR analysis
comprises the three perimidine units in a non-planar ar- showing only one pattern for the calixarene scaffold and
rangement around the aromatic core.[21] To the best of our perimidine fragments, with a correct integral ratio. The pro-
knowledge, solid-state structures of tri-perimidines have not posed structure of 23 was further supported by MALDI-
been reported to date.
TOF mass spectrometry.
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Mono-, Di-, Tri- and Tetra-2-aryl-2,3-dihydro-1H-perimidines
Zn(OAc)2·2H2O as catalyst. The procedure involves the use
of salicylaldehydes equipped with various functionalities
that may be useful in further synthesis. The developed pro-
tocol has also been proven to be successful for the synthesis
of various bis(2,3-dihydro-1H-perimidines) such as 17 and
18. In the case of tri-aldehyde 19 as reagent we have en-
countered an unusual product, viz. bis(2,3-dihydro-1H-per-
imidine) 21 that is believed to result from a cleavage of one
aryl–C(perimidine) bond within 20b. An alternative syn-
thetic approach afforded both the mono- as well as tris-
(2,3-dihydro-1H-perimidine) compounds 20a and 20b, and
the isolation of the mono-, di- and tris(2,3-hydro-1H-per-
imidines) derived from 19 shows the synthetic versatility of
this interesting scaffold. The preparation of tetrakis-per-
imidine 23 having a calix[4]arene support shows that multi-
perimidines are easily accessed. This latter compound has
an array of NH donors potentially useful to create a molec-
ular receptor. Studies towards the use of this (23) and other
multi-perimidinal compounds as hydrogen-bond donors in
recognition events are in progress.
Figure 5. Molecular structure for 20b determined by XRD with the
adopted numbering scheme; co-crystallized solvent molecules, H-
atoms and disorders are omitted for clarity.
Experimental Section
General Information: All manipulations were done in air without
any necessary precautions. All reagents [1,8-diaminonaphthalene,
all salicylaldehydes, 2-hydroxyisophthalaldehyde, Zn(OAc)2·2H2O
and solvents] were commercially purchased and used as received.
The NMR spectra were recorded on a Bruker 400 MHz spectrome-
ter, the mass spectral measurements and X-ray analyses were per-
formed by the Research Support Unit from ICIQ, and the elemen-
tal analyses were obtained from the University of Santiago de
Compostela (Spain), Unidad de Análisis Elemental.
2-(3,5-Di-tert-butyl-2-hydroxyphenyl)-2,3-dihydro-1H-perimidine
(2): To a solution of 1,8-diaminonaphthalene (0.59 g, 3.73 mmol)
in MeOH (20 mL) was added a solution of 3,5-di-tert-butylsalicyl-
aldehyde (1.08 g, 4.61 mmol) dissolved in MeOH (10 mL). Then
solid Zn(OAc)2·2H2O (71.6 mg, 0.326 mmol, 8.7 mol-%) was added
and the mixture stirred at room temperature for 18 h. In due
course, a precipitate was noted which was collected by filtration
after 18 h and dried. Off-white solid, yield 1.15 g (3.07 mmol,
82%). Crystals were obtained from hot CH3CN and also from
MeOH. Only in the latter case the crystals proved to be suitable
Scheme 5. Use of calixarene 22 in the synthesis of tetrakis-perimid-
ine 23.
1
for X-ray diffraction. H NMR (400 MHz, [D6]acetone): δ = 9.09
4
(s, 1 H, OH), 7.36 (d, J = 2.4 Hz, 1 H, ArH), 7.22–7.29 (m, 4 H,
ArH), 7.18 (d, 4J = 2.4 Hz, 1 H, ArH), 6.78 (d, 3J = 7.0, 4J =
1.2 Hz, 2 H, ArH), 6.20 (br. s, 2 H, NH), 5.75 (s, 1 H, Ar-CH),
1.42 [s, 9 H, C(CH3)3], 1.30 [s, 9 H, C(CH3)3] ppm. 13C{1H} NMR
(100 MHz, [D6]acetone): δ = 155.03, 143.56, 141.48, 137.00, 135.90,
127.72, 125.58, 125.28, 124.02, 118.70, 114.99, 107.57, 71.01, 35.78,
34.84, 32.05, 30.17 ppm. ESI(+)-MS (MeOH): m/z = 771.4 (2M +
Na)+ (calcd. 771.5), 397.2 [M + Na]+ (calcd. 397.2), 375.2
[M + H]+ (calcd. 375.2). C25H30N2O·CH3CN (415.57): calcd. C
78.03, H 8.00, N 10.11; found C 77.91, H 8.20, N 9.61.
The calixarene structure 23 comprises a set of eight NH
fragments that might be of use as hydrogen bond partners.
Recently, deep cavity calix[4]arenes appended on the upper
rime with four 1H-phenanthro[9,10-d]imidazol-2-yl groups
were reported by de Mendoza and co-workers,[23] and they
showed that the cavity of these systems can be stabilized
by hydrogen bonding to suitable H-acceptors. Since these
calixarene structures are potentially useful in molecular re-
cognition processes and catalysis, compound 23 may form
a good starting point for achieving these objectives.
Synthesis of 2 without Zn Catalyst: To a solution of 1,8-diamino-
naphthalene (0.51 g, 3.22 mmol) in MeOH (20 mL) was added a
solution of 3,5-di-tert-butylsalicylaldehyde (0.90 g, 3.84 mmol) dis-
solved in MeOH (10 mL). The mixture was stirred at room tem-
perature for 18 h. In due course, a precipitate was noted which was
collected by filtration after 18 h and dried; yield 0.78 g (2.08 mmol,
Conclusions
Here we present
a general synthetic method for
2-aryl-substituted 2,3-dihydro-1H-perimidines employing 65%). Spectroscopic features are as reported above.
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A. W. Kleij et al.
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2-(3-tert-Butyl-2-hydroxyphenyl)-2,3-dihydro-1H-perimidine (3): To
1.74 mmol) dissolved in MeOH (5 mL). Then solid Zn(OAc)2·
2H2O (33.5 mg, 0.153 mmol, 9.7 mol-%) was added and the mix-
ture stirred at room temperature for 5 min. The precipitate that had
formed was collected by filtration and dried. Off-white solid, yield
535.0 mg (1.57 mmol, 99%). 1H NMR (400 MHz, [D6]acetone +
a
solution of 1,8-diaminonaphthalene (0.61 g, 3.86 mmol) in
MeOH (20 mL) was added a solution of 3-tert-butylsalicylaldehyde
(0.77 g, 4.32 mmol) dissolved in MeOH (10 mL). Then solid
Zn(OAc)2·2H2O (72.7 mg, 0.331 mmol, 8.6 mol-%) was added and
the mixture stirred at room temperature. The off-white solid that
precipitated in due course was collected by filtration after 18 h and
dried (fraction 1: 352.8 mg). A second fraction of product was ob-
tained by concentration of the mother liquor to 15 mL (fraction 2:
588.3 mg); total yield 941.1 mg (2.96 mmol, 77%). 1H NMR
(400 MHz, [D6]acetone): δ = 9.32 (s, 1 H, OH), 7.22–7.30 (m, 5 H,
ArH), 7.13 (d, 3J = 7.4, 4J = 1.5 Hz, 1 H, ArH), 6.79 (t, 3J =
3
4
10% [D6]DMSO): δ = 7.54 (d, J = 8.0, J = 1.6 Hz, 1 H, ArH),
3
4
3
7.43 (d, J = 7.6, J = 1.5 Hz, 1 H, ArH), 7.22 (t, J = 7.8 Hz, 2
3
4
3
H, ArH), 7.14 (d, J = 8.3, J = 0.9 Hz, 2 H, ArH), 6.85 (t, J =
3
4
7.7 Hz, 1 H, ArH), 6.67 (d, J = 7.3, J = 0.9 Hz, 2 H, ArH), 5.58
(s, 1 H, Ar-CH) ppm. Both the NH as well as the OH protons are
not observed. 13C{1H} NMR (100 MHz, [D6]DMSO): δ = 152.70,
142.47, 134.31, 132.88, 128.68, 128.47, 126.90, 120.85, 116.46,
112.91, 110.79, 105.62, 64.02 ppm. ESI(–)-MS (MeOH): m/z =
3
4
7.7 Hz, 1 H, ArH), 6.77 (d, J = 7.0, J = 1.2 Hz, 2 H, ArH), 6.21
(br. s, 2 H, NH), 5.48 (s, 1 H, Ar-CH), 1.41 [s, 9 H, C(CH3)3] 339.0 (M – H)– (calcd. 339.0). C17H13BrN2O (341.20): calcd. C
ppm. 13C{1H} NMR (100 MHz, [D6]acetone): δ = 157.50, 143.37,
137.76, 135.86, 128.91, 128.39, 127.72, 124.77, 119.42, 118.80,
114.98, 107.68, 70.62, 35.52, 30.06 ppm. ESI(–)-MS (MeOH): m/z
= 317.2 (M – H)– (calcd. 317.2). C21H22N2O (318.41): calcd. C
79.21, H 6.96, N 8.80; found C 79.03, H 6.96, N 8.77.
59.84, H 3.84, N 8.21; found C 59.82, H 3.84, N 8.05.
2-(3-Allyl-2-hydroxyphenyl)-2,3-dihydro-1H-perimidine (7): To
a
solution of 1,8-diaminonaphthalene (0.24 g, 1.52 mmol) in MeOH
(15 mL) was added a solution of 3-allylsalicylaldehyde (0.34 g,
2.10 mmol) dissolved in MeOH (5 mL). Then solid Zn(OAc)2·
2H2O (30.0 mg, 0.137 mmol, 9.0 mol-%) was added and the mix-
ture stirred at room temperature for 18 h. Then the reaction mix-
ture was concentrated to 10 mL upon which a white precipitate
was formed. Filtration afforded 205.5 mg of product (fraction 1).
Cooling of the mother liquor to –25 °C afforded a second fraction
of microcrystalline product (142.5 mg). Total yield 348.0 mg
2-(5-tert-Butyl-2-hydroxyphenyl)-2,3-dihydro-1H-perimidine (4): To
a
solution of 1,8-diaminonaphthalene (0.47 g, 2.97 mmol) in
MeOH (20 mL) was added a solution of 5-tert-butylsalicylaldehyde
(0.62 g, 3.48 mmol) dissolved in MeOH (10 mL). Then solid
Zn(OAc)2·2H2O (55.5 mg, 0.253 mmol, 8.5 mol-%) was added and
the mixture stirred at room temperature. The off-white solid that
precipitated in due course was collected by filtration after 18 h and
dried (fraction 1: 527.3 mg). A second fraction of product was ob-
tained by cooling the concentrated mother liquor (15 mL) to
–25 °C (fraction 2: 207.9 mg); total yield 735.2 mg (2.31 mmol,
1
(1.15 mmol, 76%). H NMR (400 MHz, [D6]acetone): δ = 8.97 (s,
1 H, OH), 7.22–7.29 (m, 4 H, ArH), 7.15–7.17 (m, 2 H, ArH), 6.81
(t, 3J = 7.5 Hz, 1 H, ArH), 6.75 (d, 3J = 7.0, 4J = 1.1 Hz, 2 H,
ArH), 6.16 (br. s, 2 H, NH), 5.97–6.07 (m, 1 H, -CH2-C(H)=CH2),
78%). 1H NMR (400 MHz, [D6]acetone): δ = 8.54 (s, 1 H, OH), 5.49 (s, 1 H, Ar-CH), 5.09 [d, JAB = 17.1, J = 1.9 Hz, 1 H, one
2
4
4
3
4
2
7.44 (d, J = 2.5 Hz, 1 H, ArH), 7.29 (d, J = 8.5, J = 2.6 Hz, 1
of -CH2-C(H)=CH2], 5.01 [d, JAB = 10.0 Hz, 1 H, one of -CH2-
H, ArH), 7.22–7.26 (m, 2 H, ArH), 7.17 (d, J = 8.3, J = 0.9 Hz, C(H)=CH2], 3.39 [d, 3J = 6.7 Hz, 2 H, -CH2-C(H)=CH2] ppm.
3
4
2 H, ArH), 6.79 (d, J = 8.5 Hz, 1 H, ArH), 6.71 (d, J = 7.3, J 13C{1H} NMR (10 MHz, 70% [D6]acetone + 30% [D6]DMSO): δ
3
3
4
= 1.0 Hz, 2 H, ArH), 6.05 (br. s, 2 H, NH), 5.59 (s, 1 H, Ar-CH),
1.28 [s, 9 H, C(CH3)3] ppm. 13C{1H} NMR (100 MHz, [D6]-
acetone): δ = 155.50, 143.80, 142.59, 135.92, 127.71, 127.69, 127.04,
124.95, 118.20, 116.86, 114.78, 107.04, 68.09, 34.66, 31.95 ppm.
ESI(–)-MS (MeOH): m/z = 317.2 (M – H)– (calcd. 317.2).
C21H22N2O (318.41): calcd. C 79.21, H 6.96, N 8.80; found C
78.94, H 6.96, N 8.78.
= 155.13, 143.40, 137.58, 135.16, 130.71, 128.31, 127.97, 127.25,
125.50, 119.50, 117.35, 115.68, 114.08, 106.58, 67.39, 34.28 ppm.
ESI(–)-MS (MeOH): m/z = 301.1 (M – H)– (calcd. 301.1).
C20H18N2O (302.37): calcd. C 79.44, H 6.00, N 9.26; found C
79.13, H 5.89, N 9.07.
2-(2-Hydroxy-3,5-dinitrophenyl)-2,3-dihydro-1H-perimidine (8): To
a
solution of 1,8-diaminonaphthalene (0.24 g, 1.52 mmol) in
2-(3,5-Dichloro-2-hydroxyphenyl)-2,3-dihydro-1H-perimidine (5): To
MeOH (20 mL) was added a solution of 3,5-di-nitro-salicylalde-
hyde (0.34 g, 1.60 mmol) dissolved in MeOH (10 mL). Then solid
Zn(OAc)2·2H2O (28.8 mg, 0.131 mmol, 8.6 mol-%) was added and
the mixture stirred at room temperature. Instantaneously an
orange-brown precipitate was formed which was collected after
a
solution of 1,8-diaminonaphthalene (0.49 g, 3.10 mmol) in
MeOH (35 mL) was added a solution of 3,5-dichlorosalicylalde-
hyde (0.75 g, 3.93 mmol) dissolved in MeOH (15 mL). Then solid
Zn(OAc)2·2H2O (57.3 mg, 0.261 mmol, 8.4 mol-%) was added and
the mixture stirred at room temperature. Instantaneously an off-
white precipitate was formed which was collected after 30 min by
filtration (fraction 1: 584.9 mg). A second fraction of the product
was obtained by concentration of the mother liquor to 15 mL (frac-
tion 2: 286.4 mg); total yield 871.3 mg (2.63 mmol, 85%). 1H NMR
1
18 h by filtration and dried; yield 441.8 mg (1.25 mmol, 83%). H
NMR (400 MHz, [D6]acetone): δ = 8.87 (d, 4J = 2.8 Hz, 1 H, ArH),
4
3
8.67 (d, J = 2.5 Hz, 1 H, ArH), 7.26 (t, J = 7.8 Hz, 2 H, ArH),
3
3
7.19 (d, J = 8.2 Hz, 2 H, ArH), 6.71 (d, J = 7.2 Hz, 2 H, ArH),
6.04 (s, 1 H, Ar-CH), 2.93 (br., 2 H, NH) ppm. The OH was not
observed. 13C{1H} NMR (100 MHz, [D6]DMSO): δ = 157.85,
(400 MHz, [D6]acetone): δ = 9.64 (br. s, 1 H, OH), 7.45 (d, 4J =
4
2.4 Hz, 1 H, ArH), 7.40 (d, J = 2.4 Hz, 1 H, ArH), 7.24–7.31 (m, 141.24, 136.86, 136.16, 134.23, 133.34, 127.56, 126.97, 121.72,
3
4
4 H, ArH), 6.75 (d, J = 7.0, J = 0.9 Hz, 2 H, ArH), 6.27 (br. s, 116.66, 112.52, 105.79, 60.57 ppm. ESI(–)-MS (MeOH): m/z =
2 H, NH), 5.67 (s, 1 H, Ar-CH) ppm. 13C{1H} NMR (100 MHz, 351.1 (M – H)– (calcd. 351.1). C17H12N4O5·1/3H2O (358.31): calcd.
[D6]DMSO): δ = 150.62, 142.25, 134.30, 130.89, 128.71, 127.40,
126.93, 123.11, 121.86, 116.25, 112.62, 105.33, 61.98 ppm. ESI(–)-
MS (MeOH): m/z = 329.0 (M – H)– (calcd. 329.0). C17H12Cl2N2O
(331.20): calcd. C 61.65, H 3.65, N 8.46; found C 61.52, H 3.62, N
8.19.
C 56.99, H 3.56, N 15.64; found C 57.10, H 3.33, N 15.44.
2-(5-Bromo-2-hydroxyphenyl)-2,3-dihydro-1H-perimidine (9): To a
solution of 1,8-diaminonaphthalene (0.41 g, 2.59 mmol) in MeOH
(20 mL) was added a solution of 5-bromo-salicylaldehyde (0.53 g,
2.64 mmol) dissolved in MeOH (10 mL). Then solid Zn(OAc)2·
2H2O (51.3 mg, 0.234 mmol, 9.0 mol-%) was added and the mix-
ture stirred at room temperature. After 18 h, the mixture was con-
centrated to dryness and the residue triturated with MeOH (10 mL)
2-(3-Bromo-2-hydroxyphenyl)-2,3-dihydro-1H-perimidine (6): To a
solution of 1,8-diaminonaphthalene (0.25 g, 1.58 mmol) in MeOH
(15 mL) was added a solution of 3-bromo-salicylaldehyde (0.35 g,
4828
www.eurjoc.org
© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2010, 4823–4831

Mono-, Di-, Tri- and Tetra-2-aryl-2,3-dihydro-1H-perimidines
and filtered to yield 330.7 mg of a beige solid. To the mother liquor
was added distilled water (10 mL) which caused the precipitation
of a beige solid, which was collected by filtration and dried in vacuo
tion (96.9 mg) of product; total yield 622.8 mg (2.25 mmol, 79%).
Crystals suitable for X-ray diffraction were obtained from MeOH.
1H NMR (400 MHz, [D6]acetone): δ = 8.86 (s, 1 H, OH), 7.21–
3
3
(486.6 mg); total yield 817.3 mg (2.40 mmol, 92%). 1H NMR 7.28 (m, 4 H, ArH), 7.14 (t, J = 7.4 Hz, 2 H, ArH), 6.76 (t, J =
(400 MHz, [D6]DMSO): δ = 10.13 (br., 1 H, OH), 7.53 (d, 4J =
7.5 Hz, 1 H, ArH), 6.74 (d, J = 7.1, J = 1.2 Hz, 2 H, ArH), 6.11
3
4
3
4
2.5 Hz, 1 H, ArH), 7.33 (d, J = 8.6, J = 2.5 Hz, 1 H, ArH), 7.16
(br., 2 H, NH), 5.48 (s, 1 H, Ar-CH), 2.20 (s, 3 H, Me) ppm.
(t, J = 7.8 Hz, 2 H, ArH), 7.00 (d, J = 8.0 Hz, 2 H, ArH), 6.86 13C{1H} NMR (10 MHz, [D6]acetone + 10% [D6]DMSO): δ =
3
3
(d, 3J = 8.6 Hz, 1 H, ArH), 6.60 (br., 2 H, NH), 6.52 (d, 3J =
7.3 Hz, 2 H, ArH), 5.63 (s, 1 H, Ar-CH) ppm. 13C{1H} NMR
(100 MHz, [D6]DMSO): δ = 154.82, 142.87, 134.38, 131.59, 130.86,
129.88, 126.89, 117.71, 115.56, 112.36, 110.06, 104.65, 60.09 ppm.
ESI(–)-MS (MeOH): m/z = 339.0 (M – H)– (calcd. 339.0), 681.1
(2M – H)– (calcd. 681.0). C17H13BrN2O·1/3H2O (347.21): calcd. C
58.81, H 3.97, N 8.07; found C 58.80, H 3.65, N 7.78.
155.31, 143.02, 134.90, 131.19, 127.42, 126.84, 125.33, 124.56,
118.85, 117.11, 113.84, 106.26, 67.52, 15.49 ppm. ESI(–)-MS
(MeOH): m/z = 275.1 (M – H)– (calcd. 275.1). C18H16N2O (276.33):
calcd. C 78.24, H 5.84, N 10.14; found C 77.63, H 5.78, N 10.02.
2-(2-Hydroxyphenyl)-2,3-dihydro-1H-perimidine (13): To a solution
of 1,8-diaminonaphthalene (0.66 g, 4.17 mmol) in MeOH (30 mL)
was added a solution of salicylaldehyde (0.62 g, 5.08 mmol) dis-
solved in MeOH (15 mL). Then solid Zn(OAc)2·2H2O (80.6 mg,
0.367 mmol, 8.8 mol-%) was added and the mixture stirred at room
temperature. After 18 h the reaction mixture was concentrated to
15 mL and filtered to yield 488.1 mg of product. A second fraction
(299.8 mg) was obtained from the mother liquor at room temp.
in due course; total yield 787.9 mg (3.00 mmol, 72%). 1H NMR
2-(5-Carboxy-2-hydroxyphenyl)-2,3-dihydro-1H-perimidine (10): To
a
solution of 1,8-diaminonaphthalene (0.21 g, 1.33 mmol) in
MeOH (15 mL) was added a solution of 2-formyl-3-hydroxyben-
zoic acid (0.27 g, 1.60 mmol) dissolved in MeOH (5 mL). Then so-
lid Zn(OAc)2·2H2O (24.5 mg, 0.112 mmol, 8.4 mol-%) was added
and the mixture stirred at room temperature. After 18 h the reac-
tion mixture was concentrated to 10 mL and filtered to afford a
3
(400 MHz, [D6]DMSO): δ = 9.67 (s, 1 H, OH), 7.46 (d, J = 7.6,
beige solid; yield 349.3 mg (1.13 mmol, 85%). 1H NMR (400 MHz, 4J = 1.6 Hz, 1 H, ArH), 7.17 (t, J = 7.7, J = 1.6 Hz, 1 H, ArH),
[D6]DMSO): δ = 12.46 (br., 1 H, COOH), 10.60 (br., 1 H, OH), 7.14 (t, J = 7.8 Hz, 2 H, ArH), 6.98 (d, J = 7.6 Hz, 2 H, ArH),
3
4
3
3
4
3
4
3
4
3
8.14 (d, J = 2.1 Hz, 1 H, ArH), 7.79 (d, J = 8.5, J = 2.2 Hz, 1
6.88 (d, J = 8.1, J = 0.7 Hz, 1 H, ArH), 6.83 (t, J = 7.4 Hz, 1
3
3
3
4
H, ArH), 7.15 (t, J = 7.8 Hz, 2 H, ArH), 6.99 (d, J = 7.7 Hz, 2 H, ArH), 6.54 (br., 2 H, NH), 6.52 (d, J = 7.4, J = 0.5 Hz, 2 H,
H, ArH), 6.95 (d, J = 8.5 Hz, 1 H, ArH), 6.58 (br. s, 2 H, NH), ArH), 5.65 (s, 1 H, Ar-CH) ppm. 13C{1H} NMR (100 MHz, [D6]-
3
6.52 (d, 3J = 7.1 Hz, 2 H, ArH), 5.66 (s, 1 H, Ar-CH) ppm. 13C{1H} DMSO): δ = 155.45, 143.27, 134.41, 129.11, 128.41, 127.09, 126.83,
NMR (100 MHz, [D6]DMSO): δ = 167.76, 159.49, 143.23, 134.47,
131.05, 130.77, 127.10, 126.92, 121.91, 115.54, 115.33, 112.44,
118.90, 115.44, 115.38, 112.50, 104.59, 60.89 ppm. ESI(+)-MS
(MeOH): m/z = 263.1 [M + H]+ (calcd. 263.1), 285.1 [M + Na]+
104.65, 60.28 ppm. ESI(–)-MS (MeOH): m/z = 305.1 (M – H)– (calcd. 285.1). C17H14N2O·1/3H2O (268.32): calcd. C 76.10, H 5.51,
(calcd. 305.1). C18H14N2O3·3/4H2O (319.83): calcd. C 67.60, H N 10.44; found C 76.44, H 5.20, N 10.22.
4.88, N 8.76; found C 68.01, H 4.38, N 8.67.
2-(2-Hydroxynaphthyl)-2,3-dihydro-1H-perimidine (14): To a solu-
2-(5-Allyl-2-hydroxy-3-methoxyphenyl)-2,3-dihydro-1H-perimidine
(11): To a solution of 1,8-diaminonaphthalene (0.13 g, 0.822 mmol)
in MeOH (5 mL) was added a solution of 3-methoxy-5-allylsalicyl-
aldehyde (0.16 g, 0.832 mmol) dissolved in MeOH (5 mL). Then
tion of 1,8-diaminonaphthalene (0.43 g, 2.72 mmol) in MeOH
(30 mL) was added a solution of 2-hydroxy-1-naphthaldehyde
(0.49 g, 2.85 mmol) dissolved in warm MeOH (10 mL). Then solid
Zn(OAc)2·2H2O (49.5 mg, 0.226 mmol, 8.3 mol-%) was added and
solid Zn(OAc)2·2H2O (14.7 mg, 0.0670 mmol, 8.1 mol-%) was the mixture stirred at room temperature. After 18 h the reaction
added and the mixture stirred at room temperature. After 18 h the
reaction mixture was concentrated to 5 mL and cooled to –25 °C.
The beige solid that precipitated was collected by filtration and
mixture was filtered to yield a first fraction (531.4 mg). Concen-
trated of the mother liquor to 10 mL and cooling to –25 °C af-
forded
a second fraction (116.8 mg); total yield 648.2 mg
1
dried; yield 181.1 mg (0.545 mmol, 66%). 1H NMR (400 MHz,
(2.08 mmol, 76%). H NMR (400 MHz, [D6]acetone): δ = 9.88 (s,
3
3
3
[D6]DMSO): δ = 7.96 (br. s, 1 H, OH), 7.21 (t, J = 7.8 Hz, 2 H, 1 H, OH), 8.26 (d, J = 8.3 Hz, 1 H, ArH), 7.86 (t, J = 7.6 Hz, 2
3
4
3
4
ArH), 7.11 (d, J = 8.0 Hz, 2 H, ArH), 7.00 (d, J = 1.6 Hz, 1 H,
H, ArH), 7.47 (t, J = 7.7, J = 1.1 Hz, 1 H, ArH), 7.27–7.36 (m,
4
3
3
3
4
ArH), 6.83 (d, J = 1.8 Hz, 1 H, ArH), 6.65 (d, J = 7.4 Hz, 2 H,
ArH), 5.90–6.00 [m, 1 H, -CH2-C(H)=CH2], 5.86 (br. s, 2 H, NH),
6 H, ArH), 7.16 (d, J = 8.9 Hz, 1 H, ArH), 6.80 (d, J = 6.8, J
= 1.2 Hz, 2 H, ArH), 6.46 (s, 1 H, Ar-CH), 6.24 (br., 2 H, NH)
ppm. 13C{1H} NMR (10 MHz, [D6]acetone + 20% [D6]DMSO): δ
2
4
5.78 (s, 1 H, Ar-CH), 5.09 [d, JAB = 17.0, J = 1.6 Hz, 1 H, one
2
4
of -CH2-C(H)=CH2], 5.00 [d, JAB = 10.2, J = 1.0 Hz, 1 H, one = 156.16, 144.56, 135.64, 133.94, 131.22, 129.46, 128.89, 127.34,
of -CH2-C(H)=CH2], 3.86 (s, 3 H, OMe), 3.31 [d, 3J = 6.7 Hz, 2
H, -CH2-C(H)=CH2] ppm. 13C{1H} NMR (100 MHz, [D6]-
DMSO): δ = 147.46, 143.44, 142.92, 137.91, 134.40, 129.96, 126.86,
126.58, 123.30, 119.49, 117.17, 117.10, 115.81, 114.24, 106.35,
62.53 ppm. ESI(–)-MS (MeOH): m/z = 311.1 (M – H)– (calcd.
311.1). C21H16N2O (312.36): calcd. C 80.75, H 5.16, N 8.97; found
126.75, 119.93, 115.55, 115.36, 112.49, 111.91, 104.53, 60.91, 55.99, C 80.30, H 5.17, N 9.09.
39.38 ppm. ESI(–)-MS (MeOH): m/z = 331.2 (M – H)– (calcd.
331.1). C21H20N2O2·1/3H2O (338.41): calcd. C 74.53, H 6.16, N
8.28; found C 74.71, H 5.86, N 8.08.
1,3-Bis[2,3-dihydro-1H-perimidin-2-yl]phenol (17): To a solution of
1,8-diaminonaphthalene (269.3 mg, 1.70 mmol) in MeOH (15 mL)
was added a solution of 2-hydroxyisophthalaldehyde (121.5 mg,
0.809 mmol) dissolved in MeOH (5 mL). Then solid Zn(OAc)2·
2H2O (18.4 mg, 0.0838 mmol, 10.4 mol-%) was added and the mix-
ture stirred at room temperature. After 18 h the reaction mixture
2-(2-Hydroxy-3-methylphenyl)-2,3-dihydro-1H-perimidine (12): To a
solution of 1,8-diaminonaphthalene (0.45 g, 2.84 mmol) in MeOH
(30 mL) was added a solution of 3-methylsalicylaldehyde (0.43 g,
3.16 mmol) dissolved in MeOH (10 mL). Then solid Zn(OAc)2·
2H2O (60.1 mg, 0.274 mmol, 9.6 mol-%) was added and the mix-
ture stirred at room temperature. After 18 h the reaction mixture
was filtered to furnish 525.9 mg of a microcrystalline solid. Con-
centration of the mother liquor to 10 mL afforded a second frac-
1
was filtered to yield a beige solid (327.2 mg, 0.76 mmol, 94%). H
NMR (400 MHz, [D6]DMSO): δ = 9.62 (s, 1 H, OH), 7.41 (d, 3J
3
3
= 7.6 Hz, 2 H, ArH), 7.19 (t, J = 7.8 Hz, 4 H, ArH), 7.05 (d, J
3
= 7.8 Hz, 4 H, ArH), 6.88 (t, J = 7.6 Hz, 1 H, ArH), 6.71 (br., 4
H, NH), 6.60 (d, 3J = 7.3 Hz, 4 H, ArH), 5.65 (s, 2 H, Ar-CH)
Eur. J. Org. Chem. 2010, 4823–4831
© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
4829

A. W. Kleij et al.
FULL PAPER
ppm. 13C{1H} NMR (10 MHz, [D6]acetone + 20% [D6]DMSO): δ
= 156.02, 143.41, 135.55, 129.61, 127.97, 127.55, 119.53, 117.30,
114.10, 106.46, 65.01 ppm. ESI(–)-MS (MeOH): m/z = 429.2 (M –
H)– (calcd. 429.2), 859.4 (2M – H)– (calcd. 859.4). C28H22N4O·
2/3H2O (442.51): calcd. C 76.00, H 5.31, N 12.66; found C 75.81,
H 5.30, N 12.45.
1 H, Ar-H), 5.76 (s, 2 H, Ar-CH) ppm. 13C{1H} NMR (100 MHz,
[D6]DMSO): δ = 158.28, 157.50, 142.94, 134.26, 126.72, 116.98,
113.37, 106.54, 102.86, 94.95, 60.46 ppm. ESI(–)-MS (MeOH): m/z
= 461.2 (M – H)– (calcd. 461.2). HRMS (ESI-, MeOH): calcd. for
C28H21N4O3: 461.1614; found 461.1626.
Tetrakis(2,3-dihydro-1H-perimidine) Compound 23: To a solution of
tetraformylcalix[4]arene 22[22] (95.7 mg, 0.136 mmol) and 1,8-di-
aminonaphthalene (180.6 mg, 1.14 mmol) was added solid
Zn(OAc)2·2H2O (20.0 mg, 0.0911 mmol). The reaction mixture was
stirred for 18 h after which 1H NMR (CDCl3) confirmed a full
conversion. Concentration in vacuo and trituration with MeOH
followed by filtration afforded an off-white solid (95.3 mg,
0.0753 mmol, 55%). 1H NMR (400 MHz, CDCl3): δ = 7.13 (s, 8
Bis(2,3-dihydro-1H-perimidine) Compound 18: To a solution of 1,8-
diaminonaphthalene (59.7 mg, 0.377 mmol) in MeOH (10 mL) was
added a solution of dialdehyde 16[14] (56.3 mg, 0.158 mmol) dis-
solved in THF (20 mL). Then solid Zn(OAc)2·2H2O (8.9 mg,
0.0405 mmol, 8.9 mol-%) was added and the mixture stirred at
room temperature for 1 h. The reaction mixture was concentrated
to dryness and triturated with MeOH (10 mL) to afford, after fil-
tration, a beige solid (85.0 mg, 0.133 mmol, 85%). 1H NMR H, ArH), 7.08 (d, J = 6.3 Hz, 8 H, ArH), 6.98 (t, J = 6.2 Hz, 8
3
3
3
(400 MHz, [D6]acetone + 30% [D6]DMSO): δ = 8.74 (br. s, 2 H,
H, ArH), 6.17 (d, J = 5.8 Hz, 8 H, ArH), 5.22 (s, 4 H, Ar-CH),
OH), 7.17 (t, 3J = 7.8 Hz, 4 H, ArH), 7.04 (d, 3J = 8.2 Hz, 4 H, 4.59 (d, J = 10.5 Hz, 4 H, CHAHX), 4.24 (br. s, 8 H, NH2), 3.98
2
3
3
2
ArH), 7.02 (s, 2 H, ArH), 6.82 (s, 2 H, ArH), 6.60 (d, J = 7.3 Hz,
(t, J = 6.0 Hz, 8 H, OCH2CH2CH3), 3.34 (d, J = 10.5 Hz, 4 H,
4 H, ArH), 6.25 (br., 4 H, NH), 5.74 (s, 2 H, Ar-CH), 5.65 (m, 2 CHAHX), 2.07 (m, 8 H, OCH2CH2CH3), 1.10 (t, 3J = 6.0 Hz, 12
H, -CH=CH-), 3.77 (br. s, 6 H, OMe), 3.29 (m, 4 H, Ar-CH2) ppm.
13C{1H} NMR (100 MHz, [D6]DMSO): δ = 147.42, 143.51, 142.82,
134.40, 130.72, 130.21, 126.80, 126.76, 119.75, 115.35, 112.51,
111.80, 104.52, 60.86, 55.88, 38.12 ppm. ESI(–)-MS (MeOH): m/z
= 635.3 (M – H)– (calcd. 635.3). C40H36N4O4·H2O (654.75): calcd.
C 73.38, H 5.85, N 8.56; found C 73.08, H 5.53, N 8.32.
H, OCH2CH2CH3) ppm. 13C{1H} NMR (100 MHz, CDCl3): δ =
157.41, 141.98, 135.57, 134.91, 134.37, 127.77, 126.79, 177.99,
113.59, 106.21, 77.45, 68.02, 31.20, 23.51, 10.54 ppm. MALBIS(+)-
MS (dctb): m/z = 1264.7 (M)+ (calcd. 1264.6). HRMS (MALDI+,
dctb): calcd. for [M]+ (C84H80N8O4): 1264.6297; found 1264.6297.
CCDC-765488 (for 2), -765489 (for 2b), -765882 (for 12), -765883
(for 17) and -776256 (for 20b) contain the supplementary crystallo-
graphic data for this paper. These data can be obtained free of
charge from The Cambridge Crystallographic Data Centre via
www.ccdc.cam.ac.uk/data_request/cif.
2,3-Dihydro-1H-perimidine Derivative 20a and Tris(2,3-dihydro-1H-
perimidine) Compound 20b: To a solution of 1,8-diaminonaphth-
alene (223.5 mg, 1.41 mmol) in MeOH (30 mL) was added a hot
solution of trialdehyde 19[15] (90.4 mg, 0.430 mmol) in DMSO
(5 mL). Shortly hereafter a suspension was obtained which was fil-
tered to yield 20a (92.1 mg, 0.262 mmol, 61% based on 19). The
mother liquor was further stirred at room temp. and in due course
a second precipitate was obtained. This was collected by filtration
and analyzed as 20b (38.5 mg, 0.0610 mmol, 14% based on 19).
Supporting Information (see also the footnote on the first page of
this article): Selected copies of NMR and MS spectra.
Acknowledgments
1
Data for 20a: H NMR (400 MHz, [D6]DMSO): δ = 9.88 (s, 2 H,
We thank the Institute of Chemical Research of Catalonia
(ICIQ), the Catalan Institute for Research and Advanced Studies
(ICREA) and the Ministereo de Ciencia e Innovación (MICINN)
(project CTQ-2008–02050/BQU), and Consolider Ingenio 2010
(project CSD2006-0003) for support. Dr. Noemí Cabello and Alba
González Arandilla are thanked for the MS measurements.
3
CHO), 7.57 (s, 1 H, OH), 7.14 (t, J = 7.8 Hz, 2 H, ArH), 7.07 (d,
3
3J = 8.2 Hz, 2 H, ArH), 6.46 (d, J = 7.2 Hz, 2 H, ArH), 5.61 (br.
s, 1 H, Ar-CH) ppm. The other two OH and NH protons were
not observed. 13C{1H} NMR (100 MHz, [D6]DMSO): δ = 190.75,
170.85, 147.32, 138.34, 135.04, 128.45, 122.49, 119.66, 107.73,
104.81, 92.44, 40.42 ppm. ESI(–)-MS (MeOH): m/z = 349.1 (M –
H)– (calcd. 349.1). HRMS (ESI-, MeOH): calcd. for C19H13N2O5:
349.0824; found 349.0822.
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Pergamon, Oxford, 1996; b) A. F. Pozharskii, V. V. Dalnikov-
skaya, Russ. Chem. Rev. 1981, 50, 816–835.
[2] a) J. M. Herbert, P. D. Woodgate, W. A. Denny, J. Med. Chem.
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D. R. Luthin, A. K. Rabinovich, D. R. Bhumralkar, K. L.
Youngblood, R. A. Bychowski, D. S. Dhanoa, J. M. May, Bi-
oorg. Med. Chem. Lett. 1999, 9, 765–770.
[3] For some examples see: a) V. Paragamian, M. B. Baker, B. M.
Puma, J. Reale Jr., J. Heterocycl. Chem. 1968, 5, 591–597; b)
A. Shaabani, A. Maleki, Chem. Pharm. Bull. 2008, 56, 79–81;
c) J. B. Hendrickson, M. S. Hussoin, J. Org. Chem. 1987, 52,
4137–4139; d) J. J. Vanden Eynde, F. Delfosse, A. Mayence,
Y. V. Haverbeke, Tetrahedron 1995, 51, 5813–5818; e) V. A. Oz-
eryanskii, E. A. Filatova, V. I. Sorokin, A. F. Pozharskii, Russ.
Chem. Bull. 2001, 50, 846–853.
[4] a) A. Maquestiau, L. Berte, A. Mayence, L. Vanden Eynd,
Synth. Commun. 1991, 21, 2171–2180; b) A. Mobinikhaledi,
P. J. Steel, Synthesis and Reactivity in Inorganic, Metal-Organic,
and Nano-Metal Chemistry 2009, 39, 133–135; c) S.-L. Zhang,
J.-M. Zhang, Chin. J. Chem. 2008, 26, 185–189; d) J. Zhang, S.
Zhang, Synth. Commun. 2007, 37, 2615–2614.
1
Data for 20b: H NMR (400 MHz, [D6]DMSO): δ = 10.15 (s, 3 H,
OH), 7.25 (t, 3J = 7.8 Hz, 6 H, ArH), 7.18 (d, 3J = 7.6 Hz, 6 H,
3
ArH), 6.76 (d, J = 6.9 Hz, 6 H, ArH), 6.66 (s, 6 H, NH), 5.86 (s,
3 H, Ar-CH) ppm. 13C{1H} NMR (100 MHz, [D6]DMSO): δ =
157.63, 142.53, 134.22, 126.81, 117.36, 113.35, 106.99, 103.15,
60.52 ppm. ESI(–)-MS (MeOH): m/z = 629.3 (M – H)– (calcd.
629.3). HRMS (ESI-, MeOH): calcd. for C39H29N6O3: 629.2301;
found 629.2297. C39H30N6O3·H2O (648.71): calcd. C 72.21, H 4.97,
N 12.95; found C 72.28, H 4.77, N 12.83.
Bis(2,3-dihydro-1H-perimidine) Compound 21: To a solution of
1,8-diaminonaphthalene (211.6 mg, 1.34 mmol) in MeOH (20 mL)
was added a suspension of trialdehyde 19[14] (88.8 mg, 0.423 mmol)
in MeOH (20 mL). Then solid Zn(OAc)2·2H2O (28.0 mg,
0.128 mmol) was added and the mixture shortly brought to reflux.
After cooling to room temp., the mixture was stirred for 18 h and
filtered to yield a beige solid (64.2 mg, 0.139 mmol, 33% based on
19). Subsequent fractions contained mixtures of products. 1H
NMR (400 MHz, [D6]DMSO): δ = 9.84 (s, 1 H, OH), 9.57 (s, 2 H,
OH), 7.22 (t, 3J = 7.8 Hz, 4 H, ArH), 7.13 (d, 3J = 7.7 Hz, 4 H,
3
ArH), 6.70 (d, J = 7.0 Hz, 4 H, ArH), 6.65 (s, 4 H, NH), 5.98 (s,
4830
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© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2010, 4823–4831

Mono-, Di-, Tri- and Tetra-2-aryl-2,3-dihydro-1H-perimidines
[5] a) L. W. Deady, T. Rodemann, J. Heterocycl. Chem. 1998, 35,
1417–1419; b) N. Morita, J. I. Dickstein, S. I. Miller, J. Chem.
Soc. Perkin Trans. 1 1979, 1, 2103–2106; c) I. Yavari, F. Jahani-
moghaddam, F. Adib, H. R. Bijanzadeh, Tetrahedron 2002, 58,
6901–6906; d) I. A. S. Smellie, A. Fromm, R. M. Paton, Tetra-
hedron Lett. 2009, 50, 4104–4106; e) A. Mobinikhaledi, N. For-
oughifar, N. Basaki, Turk. J. Chem. 2009, 33, 555–560; f) M.
Tajbakhsh, M. M. Heravi, B. Mohajerani, A. Ahmadi, J. Mol.
Catal. A 2006, 247, 213–215.
[6] I. G. Jung, S. U. Son, K. H. Park, K.-C. Chung, J. W. Lee, Y. K.
Chung, Organometallics 2003, 22, 4715–4720.
[7] S.-Y. Hsueh, K.-W. Cheng, C.-C. Lai, S.-H. Chiu, Angew.
Chem. Int. Ed. 2008, 47, 4436–4439.
[8] M. Sauer, C. Yeung, J. H. Chong, B. O. Patrick, M. J. Ma-
cLachlan, J. Org. Chem. 2006, 71, 775–788.
[9] a) S. J. Wezenberg, A. W. Kleij, Angew. Chem. Int. Ed. 2008,
47, 2354–2364; b) A. W. Kleij, Chem. Eur. J. 2008, 14, 10520–
10529.
[10] a) A. W. Kleij, Dalton Trans. 2009, 4635–4639; b) S. J. Wezen-
berg, E. C. Escudero-Adán, J. Benet-Buchholz, A. W. Kleij, In-
org. Chem. 2008, 47, 2925–2927; c) S. J. Wezenberg, E. C. Escu-
dero-Adán, J. Benet-Buchholz, A. W. Kleij, Chem. Eur. J. 2009,
15, 5695–5700.
Data for 12: C18H16N2O, M = 276.33, orthorhombic, Pca21
(no. 29), 12.4883(12) Å, 12.0727(11) Å,
9.1089(9) Å, V = 1373.3(2) Å3, Z = 4, ρ(calcd.) = 1.337 g/cm3,
F(000) 584, crystal size
0.084 mm–1,
0.01ϫ0.20ϫ0.30 mm, T = 100(2) K, θmin–max = 3.2–36.5°,
total/unique data = 15140/5091, R(int) = 0.033, data/restraints/
parameters = 5091/1/198, GOF = 1.038, R1/wR2 = 0.0489/
0.1188 [I Ͼ 2σ(I)], R1/wR2 = 0.0633/0.1282 (all data), min./
max. residual density = –0.234/0.622 e/Å3. Crystallographic
data for 17: 4(C28H22N4O)·0.5(C2H6O2)·3(CH3O)·4.08(H), M
= 1850.23, monoclinic, P21/c (no. 14), a = 14.5809(4) Å, b =
a
=
b
=
c =
=
µ
=
7.4563(2) Å, c = 21.2371(7) Å, β = 104.455(1)°, V =
2235.80(11) Å3, Z = 1, ρ(calcd.) = 1.374 g/cm3, F(000) = 976,
µ = 0.088 mm–1, crystal size 0.20ϫ0.40ϫ0.40 mm, T =
100(2) K, θmin–max = 3.1–36.4°, total/unique data = 48152/
10917, R(int) = 0.031, data/restraints/parameters = 10917/15/
327, GOF = 1.064, R1/wR2 = 0.0565/0.1698 [I Ͼ 2σ(I)], R1/
wR2 = 0.0710/0.1840 (all data), min./max. residual density =
–1.115/0.687 e/Å3.
[15] We used the 1,8-diaminonaphthalene from Aldrich (99% pu-
rity).
[16] Note that compounds 13 and 14 have been reported previously.
Nonetheless the synthesis and analysis data for these com-
pounds have been included for completeness. See for more de-
tails: a) O. Maloshitskaya, J. Sinkkonen, V. Ovcharenko, K. N.
Zelenin, K. Pihlaja, Tetrahedron 2004, 60, 6913–6921; b) M.
Zendehdel, A. Mobinikhaledi, A. Asgari, J. Inclusion Phenom.
Macrocyclic Chem. 2008, 60, 353–357; see also ref.[4b]
[17] R. M. Haak, M. M. Belmonte, E. C. Escudero-Adán, J. Benet-
Buchholz, A. W. Kleij, Dalton Trans. 2010, 39, 593–602.
[18] The structure for 17 closely resembles the one reported by
Chung et al., which does not comprise the phenol function; see
ref.[6]
[11] a) E. Escudero-Adán, J. Benet-Buchholz, A. W. Kleij, Chem.
Eur. J. 2009, 15, 4233–4237; b) M. M. Belmonte, E. C. Escud-
ero-Adán, J. Benet-Buchholz, A. W. Kleij, Eur. J. Inorg. Chem.
2009, 5307–5318.
[12] Software used: CAChe 7.5 WS (MM2 level).
[13] a) A. W. Kleij, Eur. J. Inorg. Chem. 2009, 193–205; b) A. W.
Kleij, D. M. Tooke, M. Lutz, A. L. Spek, J. N. H. Reek, Eur.
J. Inorg. Chem. 2005, 4626–4634; c) A. W. Kleij, D. M. Tooke,
M. Kuil, M. Lutz, A. L. Spek, J. N. H. Reek, Chem. Eur. J.
2005, 11, 4743–4750.
[14] Crystallographic data for 2: C25H30N2O, M = 374.51, mono-
[19] J. H. Chong, M. Sauer, B. O. Patrick, M. J. MacLachlan, Org.
Lett. 2003, 5, 3823–3826.
clinic, P21/c,
a = 18.854(2) Å, b = 11.8258(12) Å, c =
9.5335(10) Å, β = 96.995(3)°, V = 2109.8(4) Å3, Z = 4, [20] This result proved to be reproducible and was checked in a
ρ(calcd.)= 1.179 g/cm3, F(000) = 808, µ = 0.072 mm–1, crystal
size 0.02ϫ0.03ϫ0.40 mm, T = 100(2) K, θmin–max = 2.8–
29.8°, total/unique data = 27695/5907, R(int) = 0.096, data/
separate synthesis. NMR and MS data were identical in this
latter preparation.
[21] The structure of 20b was determined by XRD but the crystal
data proved to be poor (R1 = 0.137) and the structure could
not be solved satisfactorily. Despite this quality, the proposed
connectivity pattern could be unequivocally established. The
crystallographic data has been deposited at the CCDC with
reference number CCDC-776256.
[22] See: A. Dondoni, A. Marra, M.-C. Scherrmann, A. Casnati,
F. Sansone, R. Ungaro, Chem. Eur. J. 1997, 3, 1774–1782.
[23] E. Botana, K. Nalttinen, P. Prados, K. Rissanen, J. de Men-
doza, Org. Lett. 2004, 6, 1091–1094.
Received: May 10, 2010
Published Online: July 15, 2010
After publication in Early View, the name of an additional co-
author has been included.
restraints/parameters = 5907/0/268, GOF = 1.029, R1/wR2
=
0.0581/0.1362 [I Ͼ 2σ(I)], R1/wR2 = 0.1036/0.1576 (all data),
min./max. residual density = –0.268/0.373 e/Å3. Crystallo-
graphic data for 2b: C45.80H62N2O4S0.20, M = 710.99, triclinic,
¯
P1 (no. 2), a = 6.3817(10) Å, b = 10.5794(17) Å, c
16.884(4) Å, 103.763(15)°, 96.927(16)°,
=
=
α
=
β
=
γ
107.213(11)°, V = 1034.9(4) Å3, Z = 1, ρ(calcd.) = 1.141 g/cm3,
F(000)
=
386,
µ
=
0.081 mm–1,
crystal
size
0.01ϫ0.05ϫ0.30 mm, T = 100(2) K, θmin–max = 1.3–28.7°,
total/unique data = 17513/5212, R(int) = 0.065, data/restraints/
parameters = 5212/22/252, GOF = 1.051, R1/wR2 = 0.0594/
0.1669 [I Ͼ 2σ(I)], R1/wR2 = 0.1130/0.2105 (all data), min./
max. residual density = –0.362/0.748 e/Å3. Crystallographic
Eur. J. Org. Chem. 2010, 4823–4831
© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
4831