Synthetic Protocols towards Selenacalix[3]triazines

Article abstract of DOI:10.1055/s-0032-1318265

Selenium-bridged heteracalixarenes were synthesized by convenient one-pot S_NAr reactions starting from variously 2-substituted 4,6-dichloro-1,3,5-triazine building blocks. Reactions of these precursors with sodium hydroselenide afforded the sel

Full text of DOI:10.1055/s-0032-1318265

734▌
PAPER
paper
Synthetic Protocols towards Selenacalix[3]triazines
Synthesis of Selenacalix[3]triazines
Joice Thomas,a Wim Van Rossom,a Kristof Van Hecke,b,c Luc Van Meervelt,b Mario Smet,a Wim Dehaen*a
Wouter Maes*a,d
a
Molecular Design and Synthesis, Department of Chemistry, KU Leuven, Celestijnenlaan 200F, 3001 Leuven, Belgium
Fax +32(16)327990; E-mail: wim.dehaen@chem.kuleuven.be
b
Biomolecular Architecture, Department of Chemistry, KU Leuven, Celestijnenlaan 200F, 3001 Leuven, Belgium
c
Department of Inorganic and Physical Chemistry, Ghent University, Krijgslaan 281, Building S3, 9000 Ghent, Belgium
d
Design & Synthesis of Organic Semiconductors (DSOS), Institute for Materials Research (IMO-IMOMEC), Hasselt University,
Universitaire Campus, Agoralaan 1 – Building D, 3590 Diepenbeek, Belgium
E-mail: wouter.maes@uhasselt.be
Received: 25.10.2012; Accepted after revision: 30.01.2013
years clearly indicates a renewed interest in the synthesis
and applications of aza- and oxacalixarenes.3e–i Several
azacalixarene cyclooligomers have been explored as pow-
erful hosts towards the binding of fullerenes (C60 and C70)
Abstract: Selenium-bridged heteracalixarenes were synthesized by
convenient one-pot SNAr reactions starting from variously 2-substi-
tuted 4,6-dichloro-1,3,5-triazine building blocks. Reactions of these
precursors with sodium hydroselenide afforded the selenaca-
lix[3]triazines as the only macrocyclic products. Yields of the cy- and some derivatives were also studied for their selective
adsorption of CO2 in the solid state.5 The field of oxaca-
lix[n]arenes has recently witnessed a fast growth as an in-
clotrimers were significantly increased by optimization of the
macrocyclization conditions, the optimum parameters being depen-
dent on the triazine functionalization pattern. X-ray diffraction stud-
creasing amount of work was devoted to their synthesis
ies allowed unambiguous identification of the structures and
comparison with the solid-state features of analogous heteracalix-
and conformational studies.6 There have also been a few
reports on silicon- and germanium-linked calixarenes, as
well as related structures bridging heteroaromatic sub-
units.3a
arenes.
Key words: (hetera)calixarenes, macrocycles, selenium, 1,3,5-tri-
azines, substituent effects
Following the discovery of selenoenzymes, organoseleni-
um chemistry has received considerable interest, aiming
at potential applications in biochemistry, organic synthe-
sis (as reagents or intermediates), heavy atom versions of
oligonucleotides and proteins for crystallographic studies,
the synthesis of semiconducting materials, and ligand
chemistry.7,8 Many organo-Se compounds have been ana-
lyzed as biological mimics capable to stimulate the anti-
oxidant function of glutathione peroxidase (GPx).8 The
chemistry of macrocyclic ligands containing Se atoms is
of great interest because they are generally better σ-donor
ligands than their corresponding O and S counterparts.9
The large size of Se leads to an increased cavity size and
imposes significant differences on the electronic and con-
formational features of the selenamacrocycles, resulting
in an interesting coordination behavior that is quite differ-
ent from its lighter congeners. One of the additional ad-
vantages of Se-based macrocycles is the possibility to
monitor host–guest interactions by the shift in the 77Se
NMR resonance.
Calixarenes have extensively been studied as efficient
(scaffolds towards) artificial receptors in molecular recog-
nition chemistry.1 A possible structural modification of
the calixarene skeleton involves replacement of the meth-
ylene bridges between the aromatic units by heteroatoms.
Such substitutions have resulted in the emergence of a
novel subclass within the calixarene family, known as
‘heteracalixarenes’ (mostly S, NR, and O).2–6 The pres-
ence of heteroatoms instead of the usual CH2 bridges
makes heteracalixarenes appealing macrocycles with
many features that are not present in the chemistry of clas-
sical calixarenes. The heteroatom bridges provide an ad-
ditional opportunity to tune the ring size, conformation,
and binding properties, with the possibility of a wider
range of noncovalent interactions and recognition events
(via the lone pairs with donor ability on the heteroatoms).
Among these heteracalixarenes, the sulfur analogues have
been studied most due to their straightforward synthetic
accessibility through condensation of phenols with ele-
mental sulfur.3a–d,4 They are widely recognized as receptor
molecules for small organic compounds and heavy met-
als, and their coordination complexes with transition met-
als have been explored as catalytically active surfaces. On
the other hand, the analysis of published data in recent
The peculiar features of Se and the projected difference in
physical properties of the heteracalixarene subclass com-
pared to classical calixarenes encouraged us to design and
synthesize calixarenoid macrocycles containing bridging
Se atoms as attractive target molecules. We have previ-
ously reported on the synthesis of a series of homoselena-
calix[n]arenes (with CH2SeCH2 linkages) of varying ring
size (n = 3–8) by two different approaches, either via a
[2+2] reductive coupling protocol or by applying sodium
hydroselenide (NaSeH) to generate (in situ) a Se bisnu-
cleophile.10 The first method provided a high yield and se-
SYNTHESIS 2013, 45, 0734–0742
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DOI: 10.1055/s-0032-1318265; Art ID: SS-2012-N0838-OP
© Georg Thieme Verlag Stuttgart · New York

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Synthesis of Selenacalix[3]triazines
735
lectivity for the tetrameric cyclic oligomers, whereas the yellow colored crude product mixture. Analysis of a sam-
second approach resulted in a mixture of macrocycles of ple by ESI-MS revealed the formation of calix[3]arene 2a
different ring size (with somewhat higher selectivity for (m/z = 643.2). No ESI-MS traces of other linear or cyclic
the homoselenacalix[3]arenes). On the other hand, our oligomers could be observed. Purification by column
group has wide experience in the preparation of oxygen- chromatography (silica gel) yielded selenacalix[3]triazine
bridged calix[n]arenes through nucleophilic aromatic sub- 2a in a very poor yield (4%). A thorough search for the op-
stitution (SNAr) reactions on halogenated pyrimidine timum conditions to obtain a maximum amount of macro-
building blocks.11 With this background in organoseleni- cycle 2a was hence conducted (Table 1).
um and heteracalixarene chemistry, we envisaged the syn-
Table 1 Optimization of the Yield of Selenacalix[3]triazine 2a
thesis and supramolecular studies of unknown
selenacalix[n]arenes (with direct Ar–Se–Ar bonds) –
Entry
Solvent
NaSeHa
Temp (°C)
2a (%)b
missing links within the heteracalixarene series – by SNAr
reactions on activated hetarenes.12
1
2
THFc
THFd
THFd
THFd
THFd
EtOH
EtOH
EtOH
H2O
0 to r.t.
0 to r.t.
4
9
The envisaged protocol towards the synthesis of selenaca-
lixarenes involved the SNAr reaction of in situ generated
NaSeH with electrophilic halogenated heterocycles. In the
initial attempts, 4,6-dichloropyrimidine or 2,6-dichloro-
pyrazine were combined with NaSeH under different con-
ditions (temperature, solvent, concentration, NaSeH
preparation; see below). This approach did, however, not
yield any desired macrocyclic compounds. A somewhat
more encouraging result was obtained for the reaction of
2,6-dichloropyridine and NaSeH at an elevated tempera-
ture (130 °C for 24 h in DMSO). The formation of a sele-
nacalix[3]pyridine cyclooligomer was observed by
electrospray ionization-mass spectrometry (ESI-MS). The
low reactivity of the electrophilic pyridine species, the
rather harsh reaction conditions, and major difficulties in
isolating and purifying the desired selenacalix[3]pyridine
were, however, crucial drawbacks. Hence the focus was
directed towards 2-substituted 4,6-dichloro-1,3,5-triazine
building blocks, whose highly electron-deficient nature
imposes excellent reactivity in SNAr reactions.3g,6a,b,d–h,13
For this purpose, several 4,6-dichlorotriazine building
blocks 1a–e, easily available by the possibility of con-
trolled sequential substitution on cyanuric chloride, were
synthesized (Scheme 1).
3
–78 to r.t.
–78 to r.t.
–78 to r.t.
0 to r.t.
16
32
23
35
22
60
75
20
48
4
5
H2Oe
H2O
d
6
CH2Cl2
CH2Cl2
d
7
EtOH
H2O
0 to r.t.
8
acetoned
acetonef
acetoned
acetoned
–78 to r.t.
–78 to r.t.
–78 to r.t.
–78 to r.t.
9
H2O
10
11
EtOH
H2Oe
a NaSeH: 1 equiv in 4 mL of solvent.
b Yields for the isolated analytically pure compounds.
c Concentration of triazine precursor 1a (before NaSeH addition): 24
mM.
d Concentration of triazine precursor 1a (before NaSeH addition): 6.9
mM.
e NaSeH: 1.2 equiv in 4 mL of H2O.
f Concentration of triazine precursor 1a (before NaSeH addition): 3.4
mM.
Performing the reaction under high dilution conditions re-
sulted in an increase in the yield of 2a to 9% (Table 1, en-
try 2). In an attempt to limit the formation of colored
noneluting side products, NaSeH was added at –78 °C
(entry 3), decreasing the amount of side products and in-
creasing the yield to 16%. An encouraging result was then
obtained by changing the solvent for the preparation of
NaSeH from ethanol to water (entry 4). The amount of
colored side products was further reduced and the yield
was doubled (32%) as compared to the NaSeH/EtOH
combination. Increasing the ratio of NaSeH to 1.2 equiv-
alents slightly decreased the yield of 2a (entry 5). The cy-
clooligomerization reaction was also performed in
CH2Cl2 (entries 6,7). Although decomposition of the tri-
azine precursor was limited under these two-phase condi-
tions, the reactivity was also strongly reduced. Even after
4 days the conversion was still not complete and the max-
imum isolated yield of calix[3]arene 2a was 35%. An in-
crease in the ratio of NaSeH or an elevated temperature
(35 °C) did not considerably affect the obtained yield. A
breakthrough was finally achieved by using acetone as the
R
R
N
N
N
N
NaSeH
acetone
N
N
N
Se
N
Se
N
–78 °C to r.t., 12 h
or
0 to 40 °C, 48 h
Cl
N
Cl
N
N
1a–e
Se
R
R
2a R = n-Bu (75%), 2b R = t-Bu (72%),
2c R = OPh (70%), 2d R = NEt2 (55%),
2e R = NHEt (52%)
Scheme 1 One-pot synthetic pathway towards selenacalix[3]tri-
azines 2a–e
In the first trial towards the synthesis of selenaca-
lix[n]arenes employing triazine building blocks, NaSeH
(freshly prepared by reaction of a 1:2 molar ratio of Se
powder and NaBH4 suspended in ethanol) was added to a
solution of 2-butyl-4,6-dichloro-1,3,5-triazine (1a) in
THF at 0 °C (and the reaction was continued at r.t. over-
night), resulting in the formation of a moderately soluble
© Georg Thieme Verlag Stuttgart · New York
Synthesis 2013, 45, 734–742

736
J. Thomas et al.
PAPER
reaction solvent with an increase in the overall yield of 2a the degree of polymer formation was considerably re-
to 60% (entry 8). Only a slight yellow coloration was ob- duced. The pure product 2d was obtained in 55% yield by
served when NaSeH in water was added to triazine pre- precipitation in water followed by crystallization of the
cursor 1a at –78 °C. The decomposition was almost precipitate in MeCN–CH2Cl2 (3:2) (to purify the macro-
absent when the amount of acetone was doubled (resulting cycle from oligomeric open chain structures). Similar ob-
in a concentration decrease from 6.9 to 3.4 mM), afford- servations were made for the synthesis of
ing cyclotrimer 2a in 75% yield (entry 9). A significant re- selenacalix[3]arene 2e (isolated yield of 52% by precipi-
duction in the yield was observed upon repeating the tation from acetone–water). Attempts to synthesize sele-
reaction as reported above but using NaSeH in ethanol nacalix[n]arenes starting from 2-aryltriazine precursors
(entry 10). Changing the ratio of the reagents (1.2 equiv of were hampered by the poor solubility of the desired mac-
NaSeH in H2O) again caused a drop in the obtained yield rocycles. Several aromatic substituents such as 2-thienyl,
of 2a (entry 11). Hence, by carefully optimizing the SNAr p-methoxyphenyl and p-tolyl groups were introduced on
conditions the yield for selenacalix[3]triazine 2a was in- the triazine heterocycle and the resulting 4,6-dichlorotri-
creased spectacularly from 4% to 75%. It is important to azine derivatives were reacted with NaSeH. The forma-
note that in this case the cyclic trimer14 is essentially the tion of the corresponding selenacalix[3]triazines was
only (major) product formed and it can easily and effi- confirmed by ESI-MS. However, the rather insoluble na-
ciently be isolated in pure form by simple precipitation of ture of the products severely hampered efficient purifica-
the macrocycle directly from the reaction mixture in wa- tion and characterization.
ter.
All selenacalix[3]triazines 2a–e showed good solubility
To vary the substitution pattern of the selenacalix[3]tri- in a variety of organic solvents (e.g., CH2Cl2) and the
azine macrocycle, a few (proof-of-principle) functional macrocycles were completely characterized by NMR
groups were introduced at the stage of the triazine build- spectroscopy (1H, 13C, and 77Se) and (high resolution)
1
ing blocks (prior to macrocyclization). The substituted mass spectrometry. The H NMR spectra of dichlorotri-
4,6-dichlorotriazines 1b–e were then reacted with NaSeH azines 1a–e and the corresponding selenacalixarenes 2a–
under the conditions as optimized for 2a (Scheme 1). The e showed only marginal differences, which complicated
SNAr reaction of 2-tert-butyl-4,6-dichloro-1,3,5-triazine 1H NMR analysis. On the other hand, the 13C NMR spec-
(1b) and NaSeH resulted in the analogous selenaca- tra gave a clear shift for the carbon atoms linked to Se (as
lix[3]triazine 2b in an overall yield of 72%. Once again, compared to the C–Cl bonds in the acyclic precursors).
purification could simply be achieved by precipitation The 77Se NMR spectra for 2a–e contained only one signal
from the reaction mixture (acetone) in water. Through in- arising from the bridging Se atoms, confirming the unifor-
troduction of a phenoxy group on the dichlorotriazine pre- mity of all selenium bridges (see Supporting Information).
cursor, the corresponding trimeric cyclooligomer 2c was
In an attempt to synthesize a selenacalix[4]triazine macro-
also prepared in a similarly high yield (70%). Since the
cycle, a [2+2] reductive fragment coupling protocol was
electrophilicity of the triazine moiety is reduced by the in-
performed starting from 2-butyl-4,6-dichlorotriazine (1a)
and diselenocyanate 3a (Scheme 2). The latter was syn-
thesized by the reaction of 1a and KSeCN. Remarkably,
troduction of the phenoxy group, the above reaction was
carried out at a higher concentration of precursor 1c (11.7
mM). When the reaction was repeated with larger reagent
this approach induced significant scrambling and selena-
quantities and at a higher concentration (1.0 g 1c, 20.7
calix[3]triazine 2a was still the major product (67% isolat-
ed yield). Surprisingly, no trace of the targeted
selenacalix[4]triazine (or other cyclic homologues) could
mM), the analytically pure macrocycle 2c was precipitat-
ed from acetone–water in 56% yield. Once more none of
the larger cyclooligomers was observed in the crude mix-
be observed. In general, the lack of evidence for the for-
ture (as evidenced by ESI-MS). Under the same reaction
mation of cyclic tetramers or other (larger) cyclic struc-
tures in any of the procedures points to a reversible
macrocyclization reaction. A dynamic process of ring
opening and (re)cyclization favors selective formation of
conditions as described above for cyclotrimer 2c, the re-
action of 4,6-dichloro-N,N-diethyl-1,3,5-triazin-2-amine
(1d) with NaSeH resulted in an unsatisfactory yield of 4%
of selenacalix[3]arene 2d (after chromatographic purifi-
the thermodynamically most stable products, in this case
cation). An appreciable amount of unreacted starting ma-
apparently the selenacalix[3]triazines.15 Heteraca-
terial remained in the reaction mixture, even after 48
lix[3]arenes, the smallest possible cyclooligomers within
hours of reaction, which may be attributed to the further
the series, have previously been obtained for the S- and N-
increase in electron density in the triazine precursor. A
bridged macrocycles, but have never been observed for
larger amount of 2d was obtained (39%) by using a small
excess of NaSeH (1.2 equiv) in ethanol and avoiding too
high dilution (20.5 mM in acetone). However, the reaction
oxacalixarenes, for which the cyclotetramers are the ther-
modynamically favored species.3,6,14
Using two different triazine building blocks, we also suc-
mixture still contained quite some remaining precursor 1d
ceeded in synthesizing an asymmetrically substituted
and some polymeric material was observed as well. When
selenacalix[3]triazine. Combination of thienyl-substituted
the reaction was performed using NaSeH (1.05 equiv in
diselenocyanate 3f with triazine building block 1a in a 1:1
water) in acetone (18.1 mM 1d) at 40 °C over a period of
ratio under reductive coupling conditions afforded asym-
two days, most of the starting material was consumed and
metrical selenacalix[3]triazine 2f in 73% yield. Addition-
Synthesis 2013, 45, 734–742
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Synthesis of Selenacalix[3]triazines
737
R1
N
R1
N
R2
N
N
Se
NaBH4
acetone
N
N
N
N
N
N
N
R2
+
Se
N
–78 °C to r.t.
12 h
Cl
Cl
NCSe
SeCN
N
N
N
Se
1a R1 = n-Bu
3a R2 = n-Bu
3f R2 = thien-2-yl
R2
2a R1, R2 = n-Bu (67%)
2f R1 = n-Bu, R2 = thien-2-yl (73%)
Scheme 2 One-pot synthetic pathway towards selenacalix[3]triazines 2a,f
ally, the selenacalix[3]triazine analogue with two n-butyl framework, since the remaining alkyl group guarantees
and one 2-thienyl substituent was formed in a small reasonable solubility. The 77Se NMR spectrum of 2f con-
amount. The [2+2] approach thus allowed the introduc- tains two signals with a 1:2 intensity arising from the two
tion of aromatic substituents on the selenacalixarene types of Se atoms bridging the different aromatic constit-
uents.
To confirm the structures and to elucidate the conforma-
tions of the synthesized macrocycles in the solid state, sin-
gle crystals of some of the selenacalix[3]triazines were
grown.16 The solid-state conformations determined for
these cyclotrimers are similar to the approximately disk-
shaped structure reported for the analogous thiaca-
lix[3]triazine derivative (R = t-Bu).14c,17 Selenaca-
lix[3]triazine 2c (R = OPh) adopts an almost planar
conformation (Figure 1), that is, the triazine rings are tilt-
ed 1.8(2)°, 2.2(2)°, and 2.3(2)° to the plane through the
bridging Se atoms (compared to 3.4°, 16.3°, and 32.1° for
the thiacalix[3]triazine14c). Two phenoxy groups are
found disordered on the macrocyclic framework. The
Figure 1 ORTEP representation (with atom labeling scheme) of sele-
three triazine units are not related by any crystallographic
nacalix[3]triazine 2c as determined by X-ray crystallography. Ther-
symmetry and the C–Se bond lengths vary within the
range of 1.899(5) to 1.936(4) Å. Short intramolecular con-
mal ellipsoids are shown at the 50% probability level. For clarity, the
disordered phenoxy groups are not shown.
Figure 2 Packing of the crystal structure of selenacalix[3]triazine 2c, indicating the stacking of two Se atoms and one O atom on the triazine
rings of a second symmetry-equivalent molecule
© Georg Thieme Verlag Stuttgart · New York
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J. Thomas et al.
PAPER
evaporated to dryness to afford the crude product. Purification by
column chromatography (silica gel, eluent CH2Cl2–heptane, 4:1) af-
forded triazine derivative 1a (9.0 g, 80%) as a colorless oil.
1H NMR (300 MHz, CDCl3): δ = 2.91 (t, J = 7.7 Hz, 2 H), 1.81 (q,
J = 7.7 Hz, 2 H), 1.42 (s, J = 7.4 Hz, 2 H), 0.96 (t, J = 7.4 Hz, 3 H).
13C NMR (75 MHz, CDCl3): δ = 184.4, 171.8, 38.5 (CH2), 29.6
(CH2), 22.5 (CH2), 13.8 (CH3).
tacts (within their van der Waals radius) are observed be-
tween the interior nitrogen atoms, with distances of
2.881(6), 2.938(6), and 2.879(6) Å, respectively (2.73–
2.79 Å for the thiacalix[3]triazine congener14c). In the
packing, the macrocycles are stacked on top of each other,
that is, two selenium atoms and one phenoxy oxygen atom
are stacked on the triazine rings of a second symmetry-
equivalent molecule [distances between Se and O atoms
and ring centroids are 3.441(2), 3.455(2) and 3.456(5) Å,
respectively; Figure 2].8e,18 CH–π and π–π ring-ring inter-
actions are observed between the triazine rings of symme-
try-equivalent molecules, as also described for the
thiacalix[3]triazine,14c as well as between the phenoxy
substituents [distances between the centroids in the range
of 4.303(3)–5.974(4) Å].
MS (ESI+): m/z = 206 [MH+].
HRMS (EI): m/z [M+] calcd for C7H9Cl2N3: 205.0174; found:
205.0159.
2-tert-Butyl-4,6-dichloro-1,3,5-triazine (1b)
This compound was prepared according to the procedure reported
by Hintermann et al.21 Material identity and purity were confirmed
by MS, 1H, and 13C NMR analyses.
2,4-Dichloro-6-phenoxy-1,3,5-triazine (1c)
This compound was prepared according to the procedure reported
by Götz et al.22 Material identity and purity were confirmed by MS,
1H, and 13C NMR analyses.
In conclusion, selenacalix[3]triazine macrocycles were
synthesized selectively in high yields by carefully opti-
mized one-pot SNAr reactions on m-dichlorinated triazine
heterocycles. Different functionalities on the triazine
building blocks were proven to be compatible with the ap-
plied SNAr conditions, allowing the preparation of a num-
ber of substituted selenacalix[3]triazines, including an
asymmetrically substituted derivative. The optimum (di-
lution) conditions were dependent on the electronic nature
of the appended groups. The choice of substituents is
somewhat limited to moieties engendering sufficient sol-
ubility to the macrocycles. A major advantage of the re-
ported synthetic method is the easiness of purification
simply by precipitating the selenacalix[3]arene cyclo-
oligomer from the reaction mixture (acetone) in water. All
macrocycles were completely characterized, including
solid-state structures for two derivatives.
4,6-Dichloro-N,N-diethyl-1,3,5-triazin-2-amine (1d)
This compound was prepared according to the procedure reported
by Hermon et al.23 Material identity and purity were confirmed by
MS, 1H, and 13C NMR analyses.
4,6-Dichloro-N-ethyl-1,3,5-triazin-2-amine (1e)
This compound was prepared according to the procedure reported
by Bruun et al.24 Material identity and purity were confirmed by
MS, 1H, and 13C NMR analyses.
2,4-Dichloro-6-(thien-2-yl)-1,3,5-triazine (1f)
To a solution of cyanuric chloride (1.00 g, 5.42 mmol) in anhyd
THF (20 mL) at 0 °C was added a solution of 2-thienylmagnesium
bromide (6.52 mL, 1 M in THF) dropwise over 5 min. The temper-
ature was gradually increased to r.t. and stirring was continued for
another 5 h. The reaction was quenched by careful addition of aq
NH4Cl (20 mL), and CH2Cl2 (50 mL) was subsequently added. The
organic solution was washed with distilled H2O (20 mL), dried
(MgSO4), filtered, and evaporated to dryness to afford the crude
product mixture. Purification by column chromatography (silica
gel, eluent CH2Cl2–heptane, 80:20) afforded the product as a slight-
ly yellow solid (1.02 g, 81%); mp 105–106 °C.
NMR spectra were acquired on commercial instruments (Bruker
Avance 300 MHz or Bruker AMX 400 MHz) and chemical shifts
(δ) are reported in parts per million (ppm) referenced to TMS (1H)
or the internal (NMR) solvent signals (13C).19 J values are given in
Hz. The 77Se NMR spectra were recorded using Ph2Se2 in CDCl3 as
an external reference (δSe = 463).20 Mass spectra were run using a
HP5989A apparatus (CI, 70 eV ionization energy) with Apollo 300
data system or a Thermo Finnigan LCQ Advantage apparatus (ESI).
Exact mass measurements were acquired on a Kratos MS50TC in-
strument (performed in the EI mode at a resolution of 10 000) or a
Bruker Daltonics Apex2 FT-ICR instrument (performed in the ESI
mode at a resolution of 60 000). Both the calculated and experimen-
tal masses reported refer to the 100% intensity peak of the isotopic
distribution. Melting points (not corrected) were determined using
a Reichert Thermovar apparatus. For column chromatography 70–
230 mesh silica gel 60 (E. Merck) was used as the stationary phase.
Chemicals received from commercial sources were used without
further purification. Reaction solvents (THF, EtOH, and acetone)
were used as received from commercial sources.
1H NMR (300 MHz, CDCl3): δ = 8.26 (d, J = 2.8 Hz, 1 H), 7.87 (d,
J = 4.0 Hz, 1 H), 7.26–7.22 (m, 1 H).
13C NMR (75 MHz, CDCl3): δ = 171.7 (CCl), 170.3, 138.1, 136.3
(CH), 135.2 (CH), 129.4 (CH).
MS (CI): m/z = 231 [MH+].
HRMS (EI): m/z [M+] calcd for C7H3Cl2N3S: 230.9425; found:
230.9431.
Selenacalix[3]triazines
NaSeH; Safety Precautions
The most convenient procedure to prepare NaSeH involves reduc-
tion of Se with NaBH4. It allows a rapid and easy preparation of
NaSeH without the necessity of generating dangerously toxic H2Se.
NaSeH is an unstable compound and decomposes in moist air with
the formation of polyselenides and precipitation of Se. It should be
used directly as prepared (in a fume hood) in solution or suspension
without isolation.25
Triazine Building Blocks
2-Butyl-4,6-dichloro-1,3,5-triazine (1a)
n-BuMgBr (56 mL, 1 M in THF) was added dropwise to a cold
(0 °C) solution of cyanuric chloride (10.0 g, 54.3 mmol) in anhyd
THF (100 mL) over a period of 5 min. The temperature was gradu-
ally increased to r.t. and stirring was continued for another 5 h. The
reaction was quenched by careful addition of aq NH4Cl (100 mL).
CH2Cl2 (200 mL) was added, the organic layer was separated and
washed with distilled H2O (100 mL), dried (MgSO4), filtered, and
4,6,10,12,16,18,19,20,21-Nonaaza-5,11,17-tributyl-2,8,14-
triselenacalix[3]arene (2a)
Dichlorotriazine precursor 1a (0.100 g, 0.48 mmol) was dissolved
in acetone (140 mL) and the solution was degassed by purging with
argon for 10 min. A solution of NaSeH (0.48 mmol, 1 equiv) in dis-
tilled H2O (4 mL) was freshly prepared according to a reported
Synthesis 2013, 45, 734–742
© Georg Thieme Verlag Stuttgart · New York

PAPER
Synthesis of Selenacalix[3]triazines
739
procedure26 and added dropwise by syringe into the flask containing
1a at –78 °C. The temperature was gradually increased to r.t. over 1
h. After stirring the resulting mixture for another 12 h, the reaction
mixture was added to H2O (40 mL), and the precipitate formed was
collected by filtration and dried under vacuum to afford the analyt-
ically pure product 2a (0.078 g, 75%) as an off-white solid; mp 73–
74 °C.
1H NMR (300 MHz, CDCl3): δ = 2.77 (t, J = 7.7 Hz, 6 H), 1.77 (q,
J = 7.6 Hz, 6 H), 1.40 (s, J = 7.4 Hz, 6 H), 0.95 (t, J = 7.3 Hz, 9 H).
13C NMR (75 MHz, CDCl3): δ = 179.2, 178.0, 38.1 (CH2), 29.8
1d at 0 °C. The temperature was gradually increased to 40 °C and
stirring was continued for 2 days. The reaction mixture was cooled
to r.t., H2O (50 mL) was added, and the resulting precipitate was
collected by filtration and dried under vacuum to afford crude prod-
uct 2d (0.150 g, 72%) as an off-white solid; mp 175–176 °C.
1H NMR (300 MHz, CDCl3): δ = 3.60–3.48 (m, 12 H), 1.15 (t,
J = 6.8 Hz, 18 H).
13C NMR (75 MHz, CDCl3): δ = 177.4, 160.2, 41.7 (CH2), 12.8
(CH3).
77Se NMR (76.3 MHz, CDCl3): δ = 549.
MS (ESI+): m/z = 688.2 [M + H]+.
FTMS (ESI+): m/z [M + H]+ calcd for C21H30N12Se3: 688.0228;
(CH2), 22.5 (CH2), 13.9 (CH3).
77Se NMR (76.3 MHz, CDCl3): δ = 559.
MS (ESI+): m/z = 643.2 [M + H]+.
FTMS (ESI+): m/z [M + Na]+ calcd for C21H27N9Se3 + Na:
found: 688.0330.
UV/Vis (MeCN): λmax (log ε) = 259 nm (4.50).
665.9793; found: 665.9784.
4,6,10,12,16,18,19,20,21-Nonaaza-5,11,17-tris(N-ethylamino)-
2,8,14-triselenacalix[3]arene (2e)
4,6,10,12,16,18,19,20,21-Nonaaza-5,11,17-tri-tert-butyl-2,8,14-
triselenacalix[3]arene (2b)
The dichlorotriazine precursor 1e (0.200 g, 1.03 mmol) was dis-
solved in acetone (50 mL) and the solution was degassed by purging
with argon for 10 min. A solution of NaSeH (1.08 mmol, 1.05
equiv) in distilled H2O (3 mL) was freshly prepared according to a
reported procedure26 and added dropwise by syringe into the flask
containing 1e at 0 °C. The temperature was gradually increased to
40 °C and stirring was continued for 2 days. The reaction mixture
was cooled to r.t., H2O (50 mL) was added, and the resulting precip-
itate was collected by filtration and dried under vacuum to afford
analytically pure product 2e (0.110 g, 52%) as an off-white solid;
mp 197–198 °C.
The dichlorotriazine precursor 1b (0.100 g, 0.48 mmol) was dis-
solved in acetone (140 mL) and the solution was degassed by purg-
ing with argon for 10 min. A solution of NaSeH (0.48 mmol, 1
equiv) in distilled H2O (4 mL) was freshly prepared according to a
reported procedure26 and added dropwise by syringe into the flask
containing 1b at –78 °C. The temperature was gradually increased
to r.t. over 1 h. After stirring the resulting mixture for another 12 h,
the reaction mixture was added to H2O (40 mL), and the precipitate
formed was collected by filtration and dried under vacuum to afford
the analytically pure product 2b as an off-white solid (0.075 g,
72%); mp 176–177 °C.
1H NMR (300 MHz, CDCl3): δ = 5.59 (br t, J = 4.1 Hz, 3 H), 3.45
(t, J = 4.9 Hz, 6 H), 1.21 (t, J = 5.3 Hz, 9 H).
13C NMR (75 MHz, CDCl3): δ = 178.8, 161.8, 36.1 (CH2), 14.7
1H NMR (300 MHz, CDCl3): δ = 1.34 (s, 27 H).
13C NMR (75 MHz, CDCl3): δ = 184.0, 179.0, 39.6, 28.7 (CH3).
77Se NMR (76.3 MHz, CDCl3): δ = 562.
(CH3).
MS (ESI+): m/z = 643.5 [M + H]+.
FTMS (ESI+): m/z [M + Na]+ calcd for C21H27N9Se3 + Na:
77Se NMR (76.3 MHz, CDCl3): δ = 549.
MS (ESI+): m/z = 603.6 [MH+].
665.9793; found: 665.9790.
FTMS (ESI+): m/z [M + Na]+ calcd for C15H18N12Se3 + Na:
626.9179; found: 626.9174.
4,6,10,12,16,18,19,20,21-Nonaaza-5,11,17-triphenoxy-2,8,14-
triselenacalix[3]arene (2c)
Diselenocyanates
Dichlorotriazine precursor 1c (0.200 g, 0.82 mmol) was dissolved
in acetone (70 mL) and the solution was degassed by purging with
argon for 10 min. A solution of NaSeH (0.82 mmol, 1 equiv) in dis-
tilled water (4 mL) was freshly prepared according to a reported
procedure26 and added dropwise by syringe into the flask containing
1c at –78 °C. The temperature was gradually increased to r.t. over 1
h. After stirring the resulting mixture for another 12 h, H2O (70 mL)
was added, and the precipitate formed was collected by filtration
and dried under vacuum to afford the analytically pure product 2c
(0.145 g, 70%) as an off-white solid; mp 222–223 °C.
2-Butyl-4,6-diselenocyanato-1,3,5-triazine (3a)
To a solution of 1a (0.100 g, 0.48 mmol) in degassed THF (6 mL)
at 0 °C was added a solution of KSeCN (0.244 g, 1.7 mmol) in THF
(10 mL) dropwise over 5 min. The temperature was gradually in-
creased to 40 °C and stirring was continued for 2 days. EtOAc (20
mL) was subsequently added and the organic solution was washed
with distilled H2O (20 mL), dried (MgSO4), filtered, and evaporated
to dryness to afford the crude product. Purification by column chro-
matography (silica gel, eluent: CH2Cl2) afforded 3a as a slightly
yellow oil (0.056 g, 12%).
1H NMR (300 MHz, CDCl3): δ = 7.43 (t, J = 7.8 Hz, 6 H), 7.33–
7.26 (m, 3 H), 7.15 (d, J = 8.5 Hz, 6 H).
13C NMR (75 MHz, CDCl3): δ = 180.9, 166.8, 151.3, 129.9 (CH),
1H NMR (300 MHz, CDCl3): δ = 2.88 (t, J = 7.6 Hz, 2 H), 1.87–
1.73 (m, 2 H), 1.50–1.33 (m, 2 H), 0.96 (t, J = 7.3 Hz, 3 H).
13C NMR (75 MHz, CDCl3): δ = 181.3, 176.4, 97.6 (CN), 38.3
126.7 (CH), 121.3 (CH).
77Se NMR (76.3 MHz, CDCl3): δ = 577.
MS (ESI+): m/z = 751.5 [M + H]+.
FTMS (ESI+): m/z [M + Na]+ calcd for C27H15N9O3Se3 + Na:
(CH2), 29.2 (CH2), 22.4 (CH2), 13.8 (CH3).
77Se NMR (76.3 MHz, CDCl3): δ = 436.
MS (CI): m/z = 346 [MH+].
FTMS (ESI+): m/z [M + Na]+ calcd for C9H9N5Se2 + Na: 369.9083;
773.8703; found: 773.8704.
found: 369.9078.
4,6,10,12,16,18,19,20,21-Nonaaza-5,11,17-tris(N,N-diethylami-
no)-2,8,14-triselenacalix[3]arene (2d)
2,4-Diselenocyanato-6-(thien-2-yl)-1,3,5-triazine (3f)
Dichlorotriazine precursor 1d (0.200 g, 0.90 mmol) was dissolved
in acetone (50 mL) and the solution was degassed by purging with
argon for 10 min. A solution of NaSeH (0.98 mmol, 1.05 equiv) in
distilled H2O (3 mL) was freshly prepared according to a reported
procedure26 and added dropwise by syringe into the flask containing
To a solution of 1f (0.400 g, 1.72 mmol) in degassed THF (6 mL) at
0 °C was added a solution of KSeCN (0.868 g, 6.02 mmol) in THF
(10 mL) dropwise over 5 min and the resulting mixture was stirred
at r.t. for 2 days. EtOAc (20 mL) was subsequently added and the
organic solution was washed with distilled H2O (20 mL), dried
© Georg Thieme Verlag Stuttgart · New York
Synthesis 2013, 45, 734–742

740
J. Thomas et al.
PAPER
(MgSO4), filtered, and evaporated to dryness to afford the crude
product mixture. Purification by column chromatography (silica
gel, eluent CH2Cl2–heptane 90:10) afforded 3f as a slightly yellow
solid (0.270 g, 42%); mp 142–143 °C.
1H NMR (300 MHz, CDCl3): δ = 8.29 (dd, J = 4.0, 1.1 Hz, 1 H),
7.81 (dd, J = 4.9, 1.1 Hz, 1 H), 7.26–7.20 (m, 1 H).
bic, P212121 (No. 19), a = 4.7517(3), b = 19.3543(13),
c = 28.3517(16) Å, V = 2607.4(3) Å3, T = 100(2) K, Z = 4,
ρ
size 0.3 × 0.15 × 0.1 mm, 4793 independent reflections
(Rint = 0.0699). Final R = 0.0491 for 4453 reflections with I > 2σ(I)
and wR2 = 0.1293 for all data.
calc = 1.911 g cm–3, μ(CuKα) = 5.585 mm–1, F(000) = 1464, crystal
CH–π ring interactions were found between C(8A)–H(8A),
C(15B)–H(15B), C(17B)–H(17B) and aromatic rings C4B–C9B
(2.97 Å between the H atom and the ring centroid), C22–C27 (2.87
Å), and C4A–C9A (2.67 Å), respectively. Phenoxy rings O1/C4–
C9 and O2/C13–C18 were found disordered and could be modeled
in two positions with occupancies of 0.51 and 0.49, respectively.
Therefore, 1,2- and 1,3-distances were restrained to be equal with
those of phenoxy ring O3/C22–C27.29
13C NMR (75 MHz, CDCl3): δ = 176.0, 166.9, 137.6, 137.4 (CH),
136.2 (CH), 129.7 (CH), 97.8 (CN).
77Se NMR (76.3 MHz, CDCl3): δ = 439.
MS (CI): m/z = 373 [MH+].
FTMS (ESI+): m/z [M + Na]+ calcd for C9H3N5SSe2 + Na:
395.8332; found: 395.8330.
[2+2] Cyclooligomerization
Acknowledgment
4,6,10,12,16,18,19,20,21-Nonaaza-5,11,17-tributyl-2,8,14-
triselenacalix[3]arene (2a)
We thank the FWO (Fund for Scientific Research – Flanders), the
KU Leuven, and the Ministerie voor Wetenschapsbeleid for conti-
nuing financial support.
A solution of NaBH4 (8 mg, 0.202 mmol) in distilled H2O (3 mL)
was added dropwise to a stirred mixture of diselenocyanate 3a (35
mg, 0.101 mmol) and triazine 1a (21 mg, 0.101 mmol) in degassed
acetone (30 mL) at –78 °C. The temperature was gradually in-
creased to r.t. over 1 h and stirring was continued for another 6 h.
CH2Cl2 (20 mL) was subsequently added and the organic solution
was washed with distilled H2O (20 mL), dried (MgSO4), filtered,
and evaporated to dryness to afford the crude product mixture. Pu-
rification by column chromatography (silica gel, eluent: CH2Cl2–
heptane–EtOAc, 45.5:45.5:9) afforded 2a as a slightly yellow solid
(22 mg, 67%).
Supporting Information for this article is available online at
http://www.thieme-connect.com/ejournals/toc/synthesis. Included
1
are H, 13C and 77Se NMR spectra for the triazine precursors and
selenacalix[3]triazines, and FTMS (ESI+) isotopic patterns for
selenacalix[3]triazines 2a and 2f.SnugIoipfn
m
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iot
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References
4,6,10,12,16,18,19,20,21-Nonaaza-5,11-dibutyl-2,8,14-triselena-
17-(thien-2-yl)calix[3]arene (2f)
(1) (a) Calixarenes 2001; Asfari, Z.; Böhmer, V.; Harrowfield,
J.; Vicens, J., Eds.; Kluwer Academic Publishers: Dordrecht
(The Netherlands), 2001. (b) Gutsche, C. D. Calixarenes:
An Introduction, 2nd ed., Stoddart, J. F., Ed.; Royal Society
of Chemistry: Cambridge, 2008.
(2) We prefer the term heteracalixarenes to distinguish this class
of heteroatom-bridged macrocycles from heterocalixarenes,
the heterocyclic analogues of classical C-bridged
A solution of NaBH4 (10 mg, 0.268 mmol) in distilled H2O (3 mL)
was added dropwise to a stirred mixture of triazine 1a (27 mg, 0.134
mmol) and diselenocyanate 3f (50 mg, 0.134 mmol) in degassed ace-
tone (30 mL) at –78 °C. The temperature was gradually increased to
r.t. over 1 h and stirring was continued for another 6 h. CH2Cl2 (20
mL) was subsequently added and the organic solution was washed
with distilled H2O (20 mL), dried (MgSO4), filtered, and evaporated
to dryness to afford the crude product mixture. Purification by col-
umn chromatography (silica gel, eluent: CH2Cl2–heptane–EtOAc,
45.5:45.5:9) afforded 2f as a slightly yellow solid (34 mg, 73%),
which could not perfectly be purified by standard column chroma-
tography; mp 204–205 °C.
1H NMR (300 MHz, CDCl3): δ = 8.18 (d, J = 3.8 Hz, 2 H), 7.70 (d,
J = 4.9 Hz, 2 H), 7.20 (t, J = 4.4 Hz, 2 H), 2.78 (t, J = 7.7 Hz, 2 H),
1.80–1.73 (m, 2 H), 1.45–1.34 (m, 2 H), 0.96 (t, J = 7.2 Hz, 3 H).
13C NMR (75 MHz, CDCl3): δ = 179.4, 177.9, 164.8, 138.9, 134.7
(CH), 134.0 (CH), 129.0 (CH), 38.2 (CH2), 29.8 (CH2), 22.5 (CH2),
13.9 (CH3).
calixarenes, e.g., calixpyrroles.
(3) Heteracalixarene review articles: (a) König, B.; Fonseca, M.
H. Eur. J. Inorg. Chem. 2000, 2303. (b) Lhotak, P. Eur. J.
Org. Chem. 2004, 1675. (c) Morohashi, N.; Narumi, F.; Iki,
N.; Hattori, T.; Miyano, S. Chem. Rev. 2006, 106, 5291.
(d) Kajiwara, T.; Iki, N.; Yamashita, M. Coord. Chem. Rev.
2007, 251, 1734. (e) Tsue, H.; Ishibashi, K.; Tamura, R. In
Heterocyclic Supramolecules I; Vol. 17; Matsumoto, K.,
Ed.; Topics in Heterocyclic Chemistry; Springer:
Heidelberg, 2008, 73–96. (f) Maes, W.; Dehaen, W. Chem.
Soc. Rev. 2008, 37, 2393. (g) Wang, M.-X. Chem. Commun.
2008, 4541. (h) Zuo, C.-S.; Wiest, O.; Wu, Y.-D. J. Phys.
Org. Chem. 2011, 24, 1157. (i) Wang, M.-X. Acc. Chem.
Res. 2012, 45, 182.
77Se NMR (76.3 MHz, CDCl3): δ = 564, 561.
MS (ESI+): m/z = 695.9 [MH+].
FTMS (ESI+): m/z [M + Na]+ calcd for C21H15N9S2Se3 + Na:
(4) Thiacalixarenes: (a) Kajiwara, T.; Iki, N.; Yamashita, M.
Coord. Chem. Rev. 2007, 251, 1734. (b) Buccella, D.;
Parkin, G. J. Am. Chem. Soc. 2008, 130, 8617. (c) Kozlova,
M. N.; Ferlay, S.; Kyritsakas, N.; Hosseini, M. W.;
Solovieva, S. E.; Antipin, I. S.; Konovalov, A. I. Chem.
Commun. 2009, 2514. (d) Yamada, M.; Shimakawa, Y.;
Kondo, Y.; Hamada, F. CrystEngComm 2010, 12, 1311.
(5) Azacalixarenes: (a) Wang, M.-X.; Zhang, X.-H.; Zheng, Q.-
Y. Angew. Chem. Int. Ed. 2004, 43, 838. (b) Zhang, E.-X.;
Wang, D.-X.; Zheng, Q.-Y.; Wang, M.-X. Org. Lett. 2008,
10, 2565. (c) Tsue, H.; Ishibashi, K.; Tokita, S.; Takahashi,
H.; Matsui, K.; Tamura, R. Chem. Eur. J. 2008, 14, 6125.
(d) Lawson, K. V.; Barton, A. C.; Spence, J. D. Org. Lett.
2009, 11, 895. (e) Katz, J. L.; Tschaen, B. A. Org. Lett.
2010, 12, 4300. (f) Wang, L.-X.; Wang, D.-X.; Huang, Z.-
719.8280; found: 719.8283.
Crystal Structure Determination
For the structure of compound 2c, X-ray intensity data were collect-
ed on a SMART 6000 diffractometer equipped with a CCD detector
using CuKα radiation (λ = 1.54178 Å), and using φ and ω scans.
The images were interpreted and integrated with the program
SAINT from Bruker.27 The structure was solved by direct methods
and refined by full-matrix least-squares on F2 using the SHELXTL
program package.28 Non-hydrogen atoms were anisotropically re-
fined and the hydrogen atoms in the riding mode and isotropic tem-
perature factors fixed at 1.2 times U(eq) of the parent atoms.
Crystal data for 2c: C27H15N9O3Se3, M = 750.36, crystallization by
vapor diffusion of pentane into a CHCl3 solution of 2c, orthorhom-
Synthesis 2013, 45, 734–742
© Georg Thieme Verlag Stuttgart · New York

PAPER
T.; Wang, M.-X. J. Org. Chem. 2010, 75, 741. (g) Xue, M.;
Synthesis of Selenacalix[3]triazines
741
K.; Van Meervelt, L.; Wozniak, K.; Smet, M.; Maes, W.;
Dehaen, W. Org. Biomol. Chem. 2012, 10, 6526.
Chen, C.-F. Chem. Commun. 2011, 47, 2318. (h) Touil, M.;
Elhabiri, M.; Lachkar, M.; Siri, O. Eur. J. Org. Chem. 2011,
1914. (i) Vicente, A. I.; Caio, J. M.; Sardinha, J.; Moiteiro,
C.; Delgado, R.; Félix, V. Tetrahedron 2012, 68, 670.
(j) Tsue, H.; Takahashi, H.; Ishibashi, K.; Inoue, R.;
Shimizu, S.; Takahashi, D.; Tamura, R. CrystEngComm
2012, 14, 1021. (k) Yi, Y.; Fa, S.; Cao, W.; Zeng, L.; Wang,
M.; Xu, H.; Zhang, X. Chem. Commun. 2012, 48, 7495.
(l) Wu, J.-C.; Zhao, L.; Wang, D.-X.; Wang, M.-X. Inorg.
Chem. 2012, 51, 3860.
(11) (a) Maes, W.; Van Rossom, W.; Van Hecke, K.; Van
Meervelt, L.; Dehaen, W. Org. Lett. 2006, 8, 4161. (b) Van
Rossom, W.; Maes, W.; Kishore, L.; Ovaere, M.; Van
Meervelt, L.; Dehaen, W. Org. Lett. 2008, 10, 585. (c) Maes,
W.; Dehaen, W. Pol. J. Chem. 2008, 82, 1145. (d) Van
Rossom, W.; Ovaere, M.; Van Meervelt, L.; Dehaen, W.;
Maes, W. Org. Lett. 2009, 11, 1681. (e) Van Rossom, W.;
Kishore, L.; Robeyns, K.; Van Meervelt, L.; Dehaen, W.;
Maes, W. Eur. J. Org. Chem. 2010, 4122. (f) Van Rossom,
W.; Kundrat, O.; Ngo, T. H.; Lhotak, P.; Dehaen, W.; Maes,
W. Tetrahedron Lett. 2010, 51, 2423. (g) Van Rossom, W.;
Robeyns, K.; Ovaere, M.; Van Meervelt, L.; Dehaen, W.;
Maes, W. Org. Lett. 2011, 13, 126. (h) Van Rossom, W.;
Caers, J.; Robeyns, K.; Van Meervelt, L.; Maes, W.;
Dehaen, W. J. Org. Chem. 2012, 77, 2791.
(12) A short communication on the synthesis and host-guest
chemistry of these materials has very recently been
published: Thomas, J.; Van Rossom, W.; Van Hecke, K.;
Van Meervelt, L.; Smet, M.; Maes, W.; Dehaen, W. Chem.
Commun. 2012, 48, 43.
(13) (a) Verheyde, B.; Maes, W.; Dehaen, W. Mater. Sci. Eng. C
2001, 18, 243. (b) Steffensen, M. B.; Simanek, E. E. Angew.
Chem. Int. Ed. 2004, 43, 5178. (c) Blotny, G. Tetrahedron
2006, 62, 9507. (d) Rothmann, M. M.; Haneder, S.; Da
Como, E.; Lennartz, C.; Schildknecht, C.; Stroghriegl, P.
Chem. Mater. 2010, 22, 2403.
(6) Oxacalixarenes: (a) Wang, M.-X.; Yang, H.-B. J. Am.
Chem. Soc. 2004, 126, 15412. (b) Wang, D.-X.; Zheng, Q.-
Y.; Wang, Q.-Q.; Wang, M.-X. Angew. Chem. Int. Ed. 2008,
47, 7485. (c) Ma, M.-L.; Li, X.-Y.; Wen, K. J. Am. Chem.
Soc. 2009, 131, 8338. (d) Wang, Q.-Q.; Wang, D.-X.; Yang,
H.-B.; Huang, Z.-T.; Wang, M.-X. Chem. Eur. J. 2010, 16,
7265. (e) Wang, D.-X.; Wang, Q.-Q.; Han, Y.; Wang, Y.;
Huang, Z.-T.; Wang, M.-X. Chem. Eur. J. 2010, 16, 13053.
(f) Hu, S.-Z.; Chen, C.-F. Chem. Commun. 2010, 46, 4199.
(g) Alberto, M. E.; Mazzone, G.; Russo, N.; Sicilia, E.
Chem. Commun. 2010, 46, 5894. (h) Chen, Y.; Wang, D.-X.;
Huang, Z.-T.; Wang, M.-X. Chem. Commun. 2011, 47,
8112. (i) Gargiulli, C.; Gattuso, G.; Notti, A.; Pappalardo,
S.; Parisi, M. F.; Puntoriero, F. Tetrahedron Lett. 2012, 53,
616.
(7) (a) Mugesh, G.; du Mont, W.-W.; Sies, H. Chem. Rev. 2001,
101, 2125. (b) Björkhem-Bergman, L.; Torndal, U.-B.;
Eken, S.; Nystrom, C.; Capitanio, A.; Larsen, E. H.;
Björnstedt, M.; Eriksson, L. C. Carcinogenesis 2005, 26,
125. (c) Nogueira, C. W.; Zeni, G.; Rocha, J. B. T. Chem.
Rev. 2004, 104, 6255. (d) Roy, G.; Mugesh, G. J. Am. Chem.
Soc. 2005, 127, 15207. (e) Mukherjee, J. A.; Zade, S. S.;
Singh, H. B.; Sunoj, R. B. Chem. Rev. 2010, 110, 4357.
(8) GPx mimics: (a) Back, T. G.; Moussa, Z.; Parvez, M.
Angew. Chem. Int. Ed. 2004, 43, 1268. (b) Dong, Z.; Liu, J.;
Mao, S.; Huang, X.; Yang, B.; Ren, X.; Luo, G.; Shen, J.
J. Am. Chem. Soc. 2004, 126, 16395. (c) Xu, H.; Gao, J.;
Wang, Y.; Wang, Z.; Smet, M.; Dehaen, W.; Zhang, X.
Chem. Commun. 2006, 796. (d) Bhabak, K. P.; Mugesh, G.
Acc. Chem. Res. 2010, 43, 1408. (e) Fu, Y.; Chen, J.; Van
Oosterwijck, C.; Zhang, X.; Dehaen, W.; Smet, M.
Macromol. Rapid Commun. 2012, 33, 798. (f) Soares, L. C.;
Alberto, E. E.; Schwab, R. S.; Taube, P. S.; Nascimento, V.;
Rodrigues, O. E. D.; Braga, A. L. Org. Biomol. Chem. 2012,
10, 6595.
(9) (a) Levason, W.; Orchard, S. D.; Reid, G. Coord. Chem.
Rev. 2002, 225, 159. (b) Shimizu, T.; Kawaguchi, M.;
Tsuchiya, T.; Hirabayashi, K.; Kamigata, N. Org. Lett. 2003,
5, 1443. (c) Shimizu, T.; Kawaguchi, M.; Tsuchiya, T.;
Hirabayashi, K.; Kamigata, N. J. Org. Chem. 2005, 70,
5036. (d) Levason, W.; Manning, J. M.; Pawelzyk, P.; Reid,
G. Eur. J. Inorg. Chem. 2006, 4380. (e) Panda, S.; Zade, S.
S.; Panda, A.; Singh, H. B.; Butcher, R. J. J. Organomet.
Chem. 2006, 691, 2793. (f) Hua, G.; Li, Y.; Slawin, A. M.
Z.; Woollins, J. D. Angew. Chem. Int. Ed. 2008, 47, 2857.
(g) Levason, W.; Manning, J. M.; Reid, G.; Tuggey, M.;
Webster, M. Dalton Trans. 2009, 4569. (h) Panda, A.
Coord. Chem. Rev. 2009, 253, 1056. (i) Jing, S.; Morley, C.
P.; Gu, C.-Y.; Di Vaira, M. Dalton Trans. 2010, 39, 8812.
(j) Panda, A.; Panda, S.; Srivastava, K.; Singh, H. B. Inorg.
Chim. Acta 2011, 372, 17.
(14) Heteracalix[3]arenes: (a) Reistad, K. R.; Groth, P.; Lie, R.;
Undheim, K. J. Chem. Soc., Chem. Commun. 1972, 1059.
(b) Sergeev, V. A.; Ovchinnikov, Y. E.; Nedelkin, V. I.;
Astankov, A. V.; Andrianova, O. B.; Shklover, V. E.;
Zamaev, I. A.; Struchkov, Y. T. Izv. Akad. Nauk SSSR, Ser.
Khim., Engl. Transl. 1989, 1440. (c) Mascal, M.;
Richardson, J. L.; Blake, J. A.; Li, W. Tetrahedron Lett.
1997, 38, 7639. (d) Ito, A.; Ono, Y.; Tanaka, K. J. Org.
Chem. 1999, 64, 8236. (e) Tanaka, R.; Yano, T.; Nishioka,
T.; Nakajo, K.; Breedlove, B. K.; Kimura, K.; Kinoshita, I.;
Isobe, K. Chem. Commun. 2002, 1686. (f) Kinoshita, I.;
Hamazawa, A.; Nishioka, T.; Adachi, H.; Suzuki, H.;
Miyazaki, Y.; Tsuboyama, A.; Okada, S.; Hoshino, M.
Chem. Phys. Lett. 2003, 371, 451. (g) Nishioka, T.; Onishi,
Y.; Nakajo, K.; Guo-Xin, J.; Tanaka, R.; Kinoshita, I. Dalton
Trans. 2005, 2130. (h) Suzuki, Y.; Yanagi, T.; Kanbara, T.;
Yamamoto, T. Synlett 2005, 263. (i) Hamazawa, R. T.;
Nishioka, T.; Kinoshita, I.; Takui, T.; Santo, R.; Ichimura, A.
Dalton Trans. 2006, 1374. (j) Kanbara, T.; Suzuki, Y.;
Yamamoto, T. Eur. J. Org. Chem. 2006, 3314.
(k) Tsukahara, Y.; Hirotsu, M.; Hattori, S.; Usuki, Y.;
Kinoshita, I. Chem. Lett. 2008, 37, 452. (l) Uchida, N.;
Taketoshi, A.; Kuwabara, J.; Yamamoto, T.; Inoue, Y.;
Watanabe, Y.; Kanbara, T. Org. Lett. 2010, 12, 5242.
(15) Rowan, S. J.; Cantrill, S. J.; Cousins, G. R. L.; Sanders, J. K.
M.; Stoddart, J. F. Angew. Chem. Int. Ed. 2002, 41, 898.
(16) The crystallographic features of selenacalix[3]triazine 2d
(R = NEt2) are reported in our previous communication (ref.
12).
(17) The related azacalix[3]pyridine (R = p-tolyl) macrocycle
reported by Yamamoto and co-workers adopts a triangular
shape (approximate CS symmetry) with one pyridine ring
facing an opposite direction to minimize electrostatic
repulsion between the pyridine lone pairs inside the cavity
(ref. 14h).
(10) Homoselenacalixarenes: (a) Thomas, J.; Maes, W.;
Robeyns, K.; Ovaere, M.; Van Meervelt, L.; Smet, M.;
Dehaen, W. Org. Lett. 2009, 11, 3040. (b) Thomas, J.;
Dobrzanska, L.; Van Hecke, K.; Sonawane, M. P.; Robeyns,
(18) For an overview of nonbonding interactions involving Se
atoms: Coles, M. P. Curr. Org. Chem. 2006, 10, 1993.
(19) Gottlieb, H. E.; Kotlyar, V.; Nudelman, A. J. Org. Chem.
1997, 62, 7512.
© Georg Thieme Verlag Stuttgart · New York
Synthesis 2013, 45, 734–742

742
J. Thomas et al.
PAPER
(25) Mochowski, J.; Syper, L. Sodium Hydrogen Selenide, In
Encyclopedia of Reagents for Organic Synthesis; Paquette,
L. A., Ed.; Wiley: New York, 2001, rs079.
(26) Klayman, D. L.; Griffin, T. S. J. Am. Chem. Soc. 1973, 95,
197.
(27) SAINT, Manual Version 5/6.0; Bruker Analytical X-ray
Systems Inc: Madison, 1997.
(28) SHELXTL-NT, Manual Version 5.1; Bruker Analytical X-
ray Systems Inc: Madison, 1997.
(29) CCDC 808716 contains the supplementary crystallographic
data for this paper (compound 2c) and can be obtained free
of charge via www.ccdc.cam.ac.uk/data_request/cif.
(20) Duddeck, H. Prog. Nucl. Magn. Reson. Spectrosc. 1995, 27,
1.
(21) Hintermann, L.; Xiao, L.; Labonne, A. Angew. Chem. Int.
Ed. 2008, 47, 8246.
(22) Götz, R. J.; Robertazzi, A.; Mutikainen, I.; Turpeinen, U.;
Gamez, P.; Reedijk, J. Chem. Commun. 2008, 3384.
(23) Hermon, T.; Tshuva, E. Y. J. Org. Chem. 2008, 73, 5953.
(24) Bruun, L.; Koch, C.; Jakobsen, M. H.; Pedersen, B.;
Christiansen, M.; Aamand, J. Anal. Chim. Acta 2001, 436,
87.
Synthesis 2013, 45, 734–742
© Georg Thieme Verlag Stuttgart · New York