Extended mesoionic systems: Synthesis and characterization of monocyclic, polycyclic and macrocyclic pyrimidinium-olate derivatives and their photochemical behavior

Article abstract of DOI:10.1016/j.tet.2004.08.003

Mesoionic pyrimidinium-olate derivatives have been known to undergo photoreactions upon irradiation with UV light to form bis(beta-lactame) structures for about two decades. Here, new mono-, poly- and macrocyclic mesoions were prepared and their photochem

Full text of DOI:10.1016/j.tet.2004.08.003

Tetrahedron 60 (2004) 10011–10018
Extended mesoionic systems: synthesis and characterization of
monocyclic, polycyclic and macrocyclic pyrimidinium-olate
derivatives and their photochemical behavior
b
a
Achim Koch,a Ulrich Jonas,a, Helmut Ritter and Hans-Wolfgang Spiess
*
aMax Planck Institute for Polymer Research, Ackermannweg 10, 55128 Mainz, Germany
b
¨
¨
Institute of Organic Chemistry and Macromolecular Chemistry, Universitatsstraße 1, 40225 Dusseldorf, Germany
Received 23 October 2003; revised 29 July 2004; accepted 3 August 2004
Available online 11 September 2004
Abstract—Mesoionic pyrimidinium-olate derivatives have been known to undergo photoreactions upon irradiation with UV light to form
bis(beta-lactame) structures for about two decades. Here, new mono-, poly- and macrocyclic mesoions were prepared and their
photochemical rearrangement behavior was investigated. The synthesized compounds were characterized by NMR, IR, UV/Vis
spectroscopy, elemental analysis and mass spectrometry. The extension of the aromatic core leads to a significant red-shift of the absorption
maximum from w380 to w430 nm, indicating a strong electronic coupling of the mesoionic base chromophore with the annellated aromatic
subunit. The rigidity of the extended aromatic system prevents polycyclic mesoions from shifting to their bis(beta-lactame) isomers, while
the alkyl bridge of the 16-membered macrocycle in an ansa-mesoion does not inhibit photochemical rearrangement.
q 2004 Elsevier Ltd. All rights reserved.
1. Introduction
Unfortunately, reversible photoswitching has not yet been
reported with this class of compounds, and little is known
about the photoreactivity of polycyclic and macrocyclic
mesoionic compounds. In this paper, we present the
synthesis and photochemical behavior of mesoionic struc-
tures with an extended conjugated p-system and carbon
framework.
Since the discovery of the five-membered Sydnone system1
there has been growing interest in mesoions as heterocyclic
compounds and in their reactions. Six-membered mesoionic
ring systems are known that undergo various 1,4-dipolar
cycloaddition reactions, for example, with alkenes, ketones
and singulet oxygen.2–6 Mesoionic 6-oxo-1,6-dihydropyr-
imidin-3-ium-4-olates (1) are cross-conjugated mesomeric
betaines whose positive and negative charges are exclu-
sively restricted to separate parts of the molecules’ p-
electron system. Their irradiation with UV light irreversibly
results in the formation of the much less polar bis(beta-
lactames) (2), as shown in Scheme 1. The bis(beta-lactame)
structure of the photo products was first reported by
Gotthardt et al.3 in 1986 and is consistent with the 13C
NMR spectroscopic data (particularly for the C–C bridge
across the 3.6-positions).
2. Results and discussion
Monocyclic mesoions 5a and 5b were synthesized starting
from 1,3-diphenylthiourea (3) and pentyl bromide, using a
modified literature procedure.9 The resulting N,N0-disub-
stituted amidine S-pentyl-1,3-diphenylisothiourea 4 was
reacted with substituted malonic acid (RZmethyl, butyl)
and dicyclohexylcarbodiimide (DCC) as a condensing agent
at room temperature (Scheme 2) to yield the mesoionic
structures 5. As 5b resembles the cleaved macrocyclic
Since such mesoions are photoactive compounds with
interesting physical properties, such as photoinduced
change of polarity, refractive index, and density, new
polymeric materials have been synthesized that contain
mesoions either in the side chains or in the backbone.7,8
Keywords: Polycyclic mesoions; Pyrimidinium-olates; Photocyclization
reaction.
* Corresponding author. Tel.: C49-6131-379-124; fax: C49-6131-379-
100; e-mail: jonas@mpip-mainz.mpg.de
Scheme 1. Photochemical conversion of mesoionic 6-oxo-1,6-dihydropyr-
imidin-3-ium-4-olates 1 to bis(beta-lactames) 2.
0040–4020/$ - see front matter q 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2004.08.003

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A. Koch et al. / Tetrahedron 60 (2004) 10011–10018
Scheme 2. Synthesis of monocyclic mesoions 5.
structure 21 with a symmetrically broken ansa ring, it can be
regarded as a model structure for the synthetic incorporation
of the photoactive substance into a macrocyclic system at
the 3- and 6-position, which is discussed further below.
Irradiation of 5a in dichloromethane at 365 nm gave the
colorless photoproduct 6a as an oil, although the substituent
lengths at the 3- and 6-position should give rise to
crystalline bis(beta-lactame) derivatives after the
photoreaction.3
activation energy barrier in acetonitrile compared to
dichloromethane also accounts for the longer photoreaction
times required in acetonitrile.
Alcohols are not appropriate as solvents for the photo-
cyclization reaction, since product decomposition is
observed by thin layer chromatography.10 With different
substitution patterns of the mesoionic systems, it can be
shown that the long wavelength absorption maximum
strongly depends on the number of rings in the aromatic
core and weakly on the alkyl chain length at positions 3 and
6. The corresponding UV/Vis spectra from 10K4 mol lK1
dichloromethane solutions and compound colors are shown
in Figure 1.
The routes to polycyclic mesoions are based on the same
strategy via N,N0-disubstituted amidines 7 and 10 (Scheme
3). The latter was synthesized from 2-chloroquinone and
aniline by nucleophilic aromatic substitution according to a
literature procedure.11
Due to the fact that the desired photochemical back reaction
from the bis(beta-lactame) 2 to the pyrimidinium-olate 1 is
not observed in conventional monocyclic mesoions, poly-
cyclic compounds with extended aromatic systems were
synthesized and their switching behavior was investigated.
These investigations should address the question whether
the extension of the aromatic system can lead to a reversible
photoreaction. The long wavelength UV/Vis absorption
maximum of the mesoions shows a significant red-shift with
increasing ring number of the aromatic core, which
indicates an enlarged delocalization of the mesoionic
aromatic system. The reason for the bathochromic shift
from w380 to w430 nm of 11 compared to the simple
mesoions 5 can be found in the electronic coupling of the
mesoionic base chromophore with the formal styrene
subunit leading to a new extended orbital structure. The
coupling of the aromatic cores is substantially higher than in
the mesoion 5 with a principally isoelectronic pi-electron
system including the phenyl substituent and free sulfur
electron pair. Additionally, alkyl chain extension at the 3-
and 6-position of the mesoionic core also leads to a weak
bathochromic shift due to changes of the polarity in the
vicinity of the mesoionic core similar to a solvent effect
(compare in Fig. 1 compounds 5a: 3-methyl, 5b: 3-butyl,
and 21: 3,6-undecamethylene bridge; or 11a: 3-methyl, and
11b: 3-ethyl).
Less polar solvents are better suited for the photocyclization
reaction of mesoions 5 (solubility provided), due to their
ability to stabilize the transition states to the much less polar
bis(beta-lactames).10 In fact, the absorption maxima in
acetonitrile solution are shifted to shorter wavelengths as
compared to those in dichloromethane. This indicates
negative solvatochromism because the energy difference
between ground state and excited state (HOMO–LUMO),
which is correlated to the activation energy, is inversely
proportional to the absorption wavelength. The larger
The UV spectra of the polycyclic mesoions show specific
new features that can be attributed to the N,N0-disubstituted
amidine substructure: a strong absorption band at 290–
300 nm, and a double band at 320–330 nm for the two-ring
Scheme 3. Synthesis of polycyclic mesoions 8 and 11.

A. Koch et al. / Tetrahedron 60 (2004) 10011–10018
10013
Figure 1. UV/Vis-spectra with the long wavelength absorption maxima of all synthesized mesoionic systems (10K4 mol lK1 in dichloromethane solution).
system 8 and even more distinct at 340–360 nm for the
three-ring system 11, respectively.
the longest energy absorption in 13. The excited p-system
could then directly interact with the almost parallely
oriented antibonding orbital of the transannular s-bond to
break this bond and again form the polycyclic mesoion.
It was speculated that a photochemical ring opening of the
hypothetical bis(beta-lactame) 13 might take place based on
the fact, that the ortho-amino styrene fragment in 13 can be
in hyperconjugation with the highly strained transannular s-
bond of the bis(beta-lactame) substructure. This hypothesis
is supported by the structure of the LUMO of 11 (calculated
by semiempirical PM3) which shows high orbital coeffi-
cients in the styrene subunit and a lobe at the carbon in
position 3 (Scheme 4). This LUMO orbital should primarily
control the course of the reaction upon photoexcitation.
Thus, the styrene fragment, which is the largest chromo-
phore in 13, should be selectively excited by irradiation at
Surprisingly, none of the three annulated compounds
formed the bis(beta-lactame) isomer upon irradiation in
degassed dichloromethane solution (Scheme 5). Laser
irradiation of 8 at 364 nm and of 11 at 457 nm led to very
slow decomposition, whereas the starting compound 10
could be re-isolated after irradiation and fragmentation of
11 at the shorter wavelength absorption of 364 nm (double
band feature in Fig. 1).
The major structural differences of polycyclic mesoions
compared to simple mesoions are provided by the forced
planarity of the molecular framework in contrast to the
possible phenyl ring rotation in 5. In addition, the
conjugation pathways between the phenyl ring and the 6-
positionofthemesoioncore(fornumberingrefertoScheme1)
are different. As discussed before, the conjugation pathway in
the annulated derivatives leads to a new orbital structure with
longer wavelength absorption, but photoexcitation of the
mesoionic core is still possible. What is to be held responsible
for the lacking photorearrangement of the annulated systems 8
and 11 is the rigidity of the aromatic scaffold, which sterically
hinders the photocyclization reaction in contrast to mono-
cyclic systems, thus preventing the excited planar mesoionic
core to convert to the roof-shaped photoproduct.
Ansa-bridged macrocyclic mesoions are not known from
literature, so there is no data available addressing a possible
hindrance of photocyclization due to the attachment of an
alkyl bridge between the 3- and 6-position (designated R1
and R3 in Scheme 1). Synthesis of the macrocycle 21
was performed in 7 steps, as shown in Scheme 6.12
u-Bromoundecanol 14, whose alcohol functionality was
protected by 3,4-dihydro-2H-pyran (15),13 was coupled
with malonic acid di-tert-butyl ester using basic conditions.
Scheme 4. Top: hypothetical photoreaction of 11 to 13 (with styrene
subunit in light grey and transannular s-bond in dark green). Bottom: left:
LUMO of bis(beta-lactame) 13b with the transannular s-bond marked with
an arrow; right: LUMO of 13b with skeched p-orbitals of aromatic subunit
and s*-orbitals of transannular s-bond.

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A. Koch et al. / Tetrahedron 60 (2004) 10011–10018
Scheme 5. Results of the laser irradiation experiments with 8 and 11 in solution.
After acidic deprotection of the alcohol group13 the
resulting alcohol 17 was tosylated using 4-methyl-benze-
nesulfonyl chloride and pyridine in dichloromethane.
Alkylation of 1,3-diphenylthiourea by the tosylate 18
leads to the formation of the corresponding isothiourea 19.
The soft nucleophilic sulphur makes 1,3-diphenylthiourea a
good candidate for the reaction with soft electrophiles such
as alkyl halogenides and sulphonates. The rather polar
solvent tert-butyl alcohol stabilizes the intermediate S-
alkyl-thiouronium salt. Basic workup yielded the desired
diester 19.
Irradiation of 21 in degassed dichloromethane gave the
bis(beta-lactame) macrocycle 22. The uniformity of the
photocyclization process is proven by the isosbestic points
in the UV/Vis spectra of Figure 2 and the detection of only
one new spot by TLC.
3. Conclusion
Mesoions with an extended aromatic core show a shifted
absorption maximum to longer wavelength compared to the
6-membered parent derivatives, but the stiffness of the
molecular framework in such annulated systems prevents
photochemical rearrangement to the roof-shaped bis(beta-
lactames). This leaves the question if bis(beta-lactames)
with extended aromatic systems in principle show a
photochemical back reaction to their corresponding
mesoions. This has to be investigated further, for example,
by modifying the aromatic backbone.
Basic saponification reactions for transforming 19 to 20 are
not applicable here since the isothiourea functionality would
decompose to 1,3-diphenylurea and the corresponding
thiol.14 Acidic deprotection of 19 with trifluoroacetic acid
in dichloromethane was successful and led to complete
conversion of the tert-butyl diester to the free carboxylic
diacid after a few hours. Cyclization of 20 to the mesoionic
macrocycle 21 was achieved using pseudo-dilution con-
ditions with DCC in dichloromethane.
In contrast, the long alkyl bridge of a macrocyclic ansa-
Figure 2. UV/Vis-spectra for the irradiation experiment of 21 (irradion with a UVP UV crosslinker consisting of 5 Sylvania lamps F8W/BL350 8 W each at
350 nm maximum, 10K4 mol lK1 in dichloromethane solution, Argon atmosphere).

A. Koch et al. / Tetrahedron 60 (2004) 10011–10018
10015
Scheme 6. Synthetic route to the macrocyclic mesoion 21.
mesoion does not markedly change intramolecular strain
nor the electronic system, hence the photochemical
rearrangement process is unhindered. This provides the
possibility to incorporate the mesoionic function into
flexible macrocyclic systems as a photosensitive unit,
which may lead to interesting new material properties for
macrocyclic systems, such as catenanes and cyclic ligands
for biomolecular binding studies.
4. Experimental
4.1. General
All NMR spectra were acquired on Bruker Spectrospin 250
and AMX 500 spectrometers with the corresponding
deuterated solvents as internal standard, IR spectra were
measured on a Perkin Elmer Paragon 1000, EI- and FD-MS

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A. Koch et al. / Tetrahedron 60 (2004) 10011–10018
spectra on a TRIO-2000 and ZAB 2-SE-FPD by VG-
Instruments, UV/Vis spectra on a Perkin–Elmer Lambda 2
using 1!10K4 mol dichloromethane solutions of the
respective substances. Melting points were measured on a
Bu¨chi B-545 apparatus and are uncorrected. 5a was
irradiated with a 600 W medium pressure mercury lamp
with pyrex glass filter. 8, 11a and 11b were irradiated using
an Ar-Laser at 364 nm (0.25 W) and 457 nm (1.00 W), 21
using a UV crosslinker by UVP with 5 lamps (Sylvania
F8W/BL350, 8 W each). Irradiation experiments were
performed at 10K3 mol/l in degassed and argon-flushed
dichloromethane.
119, 91, 83, 77, 71, 69, 59, 56, 55. C22H24N2O2S (380.50):
calcd C 69.44 H 6.36 N 7.36; found C 69.31 H 6.51 N 7.46.
The other compounds were prepared in a similar manner. If
necessary, purification was performed with chromato-
graphic standard methods, using the TLC solvents.
4.1.1. 5-Butyl-6-oxo-1,3-diphenyl-2-pentylthio-pyrimidi-
nium-4-olate 5b. Yellow solid, mp 108–109 8C. TLC RF
0.89 (dichloromethane/methanol 20:1). IR (KBr) 3063,
3050, 2955, 2928, 2857, 1648, 1594 cmK1 1H NMR
.
(250 MHz, CDCl3) dZ0.74 (t, JZ7.1 Hz, 3H), 0.85 (t,
JZ7.3 Hz, 3H), 0.87–1.00 (m, 2H), 1.01–1.12 (m, 2H),
1.14–1.26 (m, 2H), 1.26–1.40 (m, 2H), 1.41–1.58 (m, 2H),
1.95 (t, JZ7.4 Hz, 2H), 2.44 (t, JZ7.7 Hz, 2H), 7.31–7.34
(m, 4H), 7.44–7.49 (m, 6H). 13C NMR (63 MHz, CDCl3) d
13.6, 13.9, 21.6, 22.9, 24.5, 28.8, 30.0, 30.1, 36.0, 97.2,
128.3, 129.2, 129.5, 137.3, 159.5, 159.7. UV (CH2Cl2) 234
(1.38), 383 (0.15) nm (log e). MS (FD) m/z 422 [M]C.
C25H30N2O2S (422.58): calcd C 71.06 H 7.16 N 6.63; found
C 70.70 H 7.02 N 7.03.
Chemicals were purchased from ABCR, Merck and Sigma-
Aldrich and were used without further purification. Solvents
were dried with standard methods and stored over molecular
˚
sieve (4 A).
S-Pentyl-1,3-diphenyl-isothiourea 4. Pentyl bromide
(15.10 g, 100 mmol, 1.4 equiv) was slowly added to a
stirred suspension of 3 (16.34 g, 71.6 mmol) in ethanol
(60 ml). The mixture was heated to reflux while the thiourea
dissolved completely. After 25 h the reaction mixture was
cooled and poured into aqueous ammonium hydroxide
solution (220 ml, 2%) at 0 8C with rigorous stirring. The
aqueous phase was decanted from the oil and extracted with
diethyl ether, the combined organic phases were dried and
concentrated. The crude product was purified by MPLC
over silica (petrol ether/acetone 5:1) yielding a pale yellow
waxy solid (12.76 g, 60%). TLC RF 0.64 (petrol ether/
acetone 5:1). IR (neat) 3383, 3057, 3028, 2956, 2929, 2858,
4.1.2. 3-Methyl-2-oxo-1-phenyl-1,2-dihydropyrido[1,2-
a]pyrimidin-5-ium-4-olate 8. Yellow solid, mp ca.
290 8C (dec.). TLC RF 0.12 (petrol ether/acetone 5:1). IR
(KBr) 3110, 3070, 2926, 2854, 1638, 1627, 1586 cmK1. 1H
NMR (250 MHz, d6-DMSO) d 1.92 (s, 3H), 6.73 (d, JZ
8.85 Hz, 1H), 7.39–7.49 (m, 3H), 7.53–7.66 (m, 3H), 8.04
(ddd, JZ1.58, 1.90, 8.85 Hz, 1H), 9.22 (dd, JZ1.26,
6.95 Hz, 1H). 13C NMR (63 MHz, d6-DMSO) d 10.3, 87.8,
114.6, 116.2, 129.2, 129.3, 130.0, 130.1, 136.3, 142.2,
146.5, 153.8, 159.7. UV (CH2Cl2) 234 (1.74), 282 (0.40),
332 (0.17), 388 (0.20) nm (log e). MS (FD) m/z 253 [MC
H]C. C15H12N2O2 (252.27): calcd C 71.42 H 4.79 N 11.10;
found C 71.16 H 5.25 N 11.00.
1
1624, 1586 cmK1. H NMR (250 MHz, CDCl3) d 0.93 (t,
JZ7 Hz, 3H), 1.31–1.36 (m, 4H), 1.63 (quint., JZ7.2 Hz,
2H), 2.73 (t, JZ6.9 Hz, 2H), 6.41 (s, br, 1H), 7.12 (t, JZ
7.2 Hz, 2H), 7.28 (d, JZ7.2 Hz, 4H), 7.36 (t, JZ7.2 Hz,
4H). 13C NMR (63 MHz, CDCl3) d 13.9, 22.1, 29.2, 30.8,
31.7, 121.5, 123.6, 129.0, 143.8. MS (FD) m/z 298 [M]C.
4.1.3.
2-Methyl-3-oxo-4-phenyl-3,4-dihydropyri-
mido[1,2-a]chinolin-11-ium-1-olate 11a. Orange solid,
mp 232 8C (dec.). TLC RF 0.27 (ethyl acetate). IR (KBr)
3323, 3150, 3047, 2921, 2854, 1685, 1636, 1610, 1561,
1518 cmK1. 1H NMR (250 MHz, d6-DMSO) d 1.94 (s, 3H),
6.70 (d, JZ9.5 Hz, 1H), 7.44–7.48 (m, 2H), 7.58–7.70 (m,
4H), 7.82 (ddd, JZ1.58, 1.90, 8.85 Hz, 1H,), 8.00 (dd, JZ
1.58, 7.9 Hz, 1H); 8.30 (d, JZ9.48 Hz, 1H), 9.64 (d, JZ
8.85 Hz, 1H). 13C NMR (63 MHz, d6-DMSO) d 10.6, 90.1,
114.0, 122.3, 124.1, 126.8, 129.0, 129.4, 130.0, 130.9,
134.4, 136.8, 141.5, 148.2, 158.5, 159.4. UV (CH2Cl2) 240
(2.45), 288 (1.12), 342 (0.25), 358 (0.25), 430 (0.20) nm
(log e). MS (EI) m/z 302 [M]C, 274, 273, 245, 219, 218,
128, 83, 77. C19H14N2O2 (302.33): calcd C 75.48 H 4.67 N
9.27; found C 75.22 H 4.77 N 9.15.
Preparation of mesoions 5, 8, and 11. A typical procedure is
exemplified for 5-methyl-6-oxo-1,3-diphenyl-2-pentylthio-
pyrimidinium-4-olate 5a as follows. To a stirred suspension
of 4 (770 mg, 2.6 mmol) and methylmalonic acid (305 mg,
2.6 mmol) in dichloromethane (3 ml), DCC (1065 mg,
5.2 mmol) in dichloromethane (3 ml) was added with a
syringe while the temperature was maintained at about
20 8C by water cooling. The mixture turned yellow and 1,3-
dicyclohexylurea precipitated, showing the reaction pro-
gress. After stirring for another 3.5 h at ambient temperature
the urea was filtered off and washed with dichloromethane.
The filtrate was evaporated to dryness, dissolved in the
minimum amount of toluene to which a 20-fold excess of
hexane was slowly added. The product precipitated, was
filtered and washed with hexane to yield yellow plates
(770 mg, 78%), mp 174–175 8C. TLC RF 0.63 (dichlor-
omethane/methanol 20:1). IR (KBr) 3059, 3036, 2961,
2922, 2857, 1648, 1590 cmK1. 1H NMR (250 MHz, CDCl3)
d 0.75 (t, JZ7 Hz, 3H), 0.87–1.00 (m, 2H), 1.01–1.12 (m,
2H), 1.14–1.26 (m, 2H),1.95 (t, JZ7.9 Hz, 2H), 1.96 (s,
3H), 7.30–7.34 (m, 4H), 7.46–7.49 (m, 6H). 13C NMR
(63 MHz, CDCl3) d 9.6, 13.6, 21.7, 28.9, 30.1, 36.0, 92.5,
128.3, 129.3, 129.6, 137.3, 159.5, 159.6. UV (CH2Cl2) 226
(3.22), 376 (0.22) nm (log e). MS (EI) m/z 380 [M]C, 294,
4.1.4. 2-Ethyl-3-oxo-4-phenyl-3,4-dihydropyrimido[1,2-
a]chinolin-11-ium-1-olate 11b. Orange solid, mp 217–
218 8C (dec.). TLC RF 0.49 (ethyl acetate). IR (KBr) 3321,
3144, 3020, 2950, 2923, 2859, 1682, 1633, 1617, 1560,
1518 cmK1. 1H NMR (250 MHz, CDCl3) d 1.21 (t, JZ7.27,
7.58 Hz, 3H), 2.68 (q, JZ7.27, 7.58 Hz, 2H), 6.75 (d, JZ
9.5 Hz, 1H), 7.29–7.33 (m, 2H), 7.55–7.65 (m, 4H), 7.74–
7.82 (m, 2H), 7.93 (d, JZ9.5 Hz, 1H), 9.77 (d, JZ8.9 Hz,
1H). 13C NMR (63 MHz, CDCl3) d 12.8, 18.8, 99.5, 113.1,
123.5, 124.3, 127.3, 128.67, 128.73, 129.9, 130.6, 131.7,
135.2, 136.5, 141.2, 147.9, 158.9, 159.9. UV (CH2Cl2) 240

A. Koch et al. / Tetrahedron 60 (2004) 10011–10018
10017
(2.85), 290 (1.12), 344 (0.28), 358 (0.28), 432 (0.23) nm
(log e). MS (FD) m/z 317 [MCH]C. C20H16N2O2 (316.35):
calcd C 75.93 H 5.10 N 8.86; found C 75.77 H 5.12 N 8.90.
no longer be traced by TLC. The residue was filtered off and
the solvent removed in vacuo to yield 8.34 g (96%) of the
crude product as colorless oil. TLC RF 0.18 (petrol ether/
acetone 5:1). IR (neat) 3414, 2978, 2921, 2855, 1742,
1
1725 cmK1. H NMR (250 MHz, CDCl3) d 1.13–1.35 (m,
4.1.5. 4-Methyl-1-pentylsulfanyl-2,6-diphenyl-2,6-diaza-
bicyclo[2.2.0]hexane-3,5-dione 6a. 76 mg (0.2 mmol) 5a
were dissolved in degassed dichloromethane (200 ml) and
irradiated for 3.5 h with a medium pressure mercury lamp
(600 W) through a pyrex glass filter. The solvent was
removed in vacuo and the crude product purified by
preparative TLC (petrol ether/acetone 5:1) to yield a
colorless oil. TLC RF 0.38 (petrol ether/acetone 5:1). IR
(neat): 3065, 2958, 2930, 2859, 1782, 1750, 1599, 753,
691 cmK1. 1H NMR (250 MHz, CDCl3) d 0.85 (t, JZ7 Hz,
3 H), 1.20–1.36 (m, 4H), 1.53–1.65 (m, 2H), 1.73 (s, 3H),
2.68 (t, JZ7.2 Hz, 2H), 7.12–7.18 (m, 2H), 7.26–7.33 (m,
4H), 7.56 (d, JZ7.9 Hz, 4H). 13C NMR (63 MHz, CDCl3) d
7.0, 13.8, 22.0, 28.4, 30.4, 30.8, 79.5, 85.5, 119.7, 125.9,
129.2, 136.2, 162.7. UV (CH2Cl2) 232 (2.06) nm (log e).
MS (FD) m/z 398 [MCH2O]C, 133.
16H), 1.39 (s, 18H), 1.45–1.57 (m, 2H), 1.65–1.78 (m, 2H),
2.49 (s, 1H), 3.04 (t, JZ7.6 Hz, 1H), 3.56 (t, JZ6.6 Hz,
2H). 13C NMR (63 MHz, CDCl3) d 25.6, 27.1, 27.8, 28.5,
29.1, 29.2, 29.3, 29.4, 29.4, 29.5, 32.6, 53.9, 62.8, 81.1,
169.0. MS (FD) m/z 387 [M]C.
4.1.9. 2-[11-(Toluene-4-sulfonyloxy)-undecyl]-malonic
acid di-tert-butyl ester 18. 17 (8.16 g, 21.1 mmol) and
pyridine (3.34 g, 42.2 mmol) were dissolved in dichlor-
omethane (90 ml) and cooled to 0 8C in an ice-bath.
p-Toluenesulfonic acid chloride (4.02 g, 21.1 mmol) was
slowly added and the mixture stirred for 3 days at ambient
temperature. After washing with water the organic phase
was concentrated and the crude product purified by column
chromatography on silica (petrol ether/acetone 5:1), yield-
ing a colorless oil (7.59 g, 67%). TLC RF 0.32 (petrol ether/
acetone 5:1). IR (neat) 3072, 2977, 2928, 2855, 1742, 1727,
1598, 1367, 1177, 816 cmK1. 1H NMR (250 MHz, CDCl3)
d 1.16–1.24 (m, 16H), 1.41 (s, 18H), 1.53–1.64 (m, 2H),
1.67–1.80 (m, 2H), 2.41 (s, 3H), 3.06 (t, JZ7.6 Hz, 1H),
3.97 (t, JZ6.5 Hz, 2H), 7.30 (d, JZ8.2 Hz, 2H), 7.75 (d,
JZ8.2 Hz, 2H). 13C NMR (63 MHz, CDCl3) d 21.6, 25.2,
27.1, 27.9, 28.5, 28.7, 28.8, 29.2, 29.2, 29.3, 29.3, 29.4,
53.9, 70.6, 81.1, 127.8, 129.7, 133.2, 144.5, 169.0. MS (FD)
m/z 541 [M]C, 206, 172 [tosyl-OH]C.
4.1.6. 2-(11-Bromo-undecyloxy)-tetrahydro-pyran 15.
To a stirred suspension of 11-bromo-1-undecanol
(15.07 g, 60 mmol) and 3,4-dihydro-2H-pyrane (6.06 g,
72 mmol) in cyclohexane (30 ml) amberlyst H-15 (1.50 g,
10 mequiv) was added. After stirring for 4.5 h at ambient
temperature the residue was filtered off and the solvent
removed in vacuo. The crude product was purified by
distillation (a small piece of potassium hydroxide was added
to the flask), yielding 15 as a colorless oil (18.92 g, 94%), bp
145–150 8C, 0.15 mbar. TLC RF 0.66 (petrol ether/acetone
1
50:1). IR (neat) 2930, 2854 cmK1. H NMR (250 MHz,
4.1.10. 2-[11-(N,N0-Diphenyl-carbamimidoylsulfanyl)-
undecyl]-malonic acid di-tert-butyl ester 19. A solution
of 18 (7.30 g, 13.5 mmol) and 3 (3.08 g, 13.5 mmol) in tert-
butanol (20 ml) was refluxed while the thiourea completely
dissolved. After 16 h most of the solvent was removed in
vacuo and ethanol (20 ml) was added to the brownish
reaction mixture. Then the mixture was poured into an
aqueous ammonium hydroxide solution (41 ml, 2%) at 0 8C
with rigorous stirring. The aqueous phase was decanted
from the oil and the remaining water was distilled off as an
azeotrope with chloroform. The crude product was purified
by MPLC over silica (petrol ether/acetone 5:1) yielding a
waxy solid that was recrystallized from hexane to give a
pale yellow solid (3.49 g, 43%), mp 80–81 8C. TLC RF 0.40
(petrol ether/acetone 5:1). IR (KBr) 3362, 3057, 3030, 2977,
CDCl3) d 1.25–1.87 (series of m, 24H), 3.37 (t, JZ6.9 Hz,
2H), 3.30–3.88 (series of m, 4H), 4.54 (m, 1H). 13C NMR
(63 MHz, CDCl3) d 19.7, 25.5, 26.2, 28.1, 28.7, 29.4, 29.5,
29.7, 30.8, 32.8, 33.9, 62.3, 67.6, 98.8. MS (EI) m/z 337/335
[M]C, 85 [THP]C.
4.1.7. 2-[11-(Tetrahydro-pyran-2-yloxy)-undecyl]-malo-
nic acid di-tert-butyl ester 16. 0.57 g sodium metal was
dissolved in 20 ml tert-butanol at elevated temperature.
Malonic acid di-tert-butyl ester (5.36 g, 24.8 mmol) and 15
(7.51 g, 23.6 mmol) were added successively with a syringe.
The reaction mixture was refluxed overnight, until 15 was
no longer detected by TLC. After removing most of the
solvent in vacuo water was added to the cold reaction
mixture to dissolve the sodium bromide precipitate. The
aqueous phase was decanted and extracted twice with
diethyl ether, dried and concentrated to yield 10.56 g (95%)
of the product as a colorless viscous oil. TLC RF 0.72 (petrol
ether/acetone 5:1). IR (neat) 2977, 2928, 2855, 1748,
2927, 2854, 1737, 1727, 1626, 1588, 1368, 755, 694 cmK1
.
1H NMR (250 MHz, CDCl3) d 1.13–1.32 (m, 16H), 1.40 (s,
18H), 1.47–1.52 (m, 2H), 1.62–1.76 (m, 2H), 2.61 (t, br, JZ
7.1 Hz, 2H), 3.06 (t, JZ7.6 Hz, 1H), 5.90 (s, br, 1H), 7.02 (t,
JZ7.2 Hz, 2H), 7.18 (d, JZ7.2 Hz, 4H), 7.25 (t, JZ7.2 Hz,
4H). 13C NMR (63 MHz, CDCl3) d 27.1, 27.9, 28.5, 28.6,
29.0, 29.2, 29.2, 29.3, 29.4, 29.5, 31.7, 53.9, 81.1, 121.6,
123.7, 129.0, 169.0. MS (FD) m/z 596 [M]C.
1
1729 cmK1. H NMR (250 MHz, CDCl3) d 1.16–1.32 (m,
16H), 1.41 (s, 18H), 1.42–1.53 (m, 6H), 1.65–1.82 (m, 4H),
3.05 (t, 1H), 3.28–3.37 (m, 1H), 3.42–3.46 (m, 1H), 3.63–
3.72 (m, 1H), 3.78–3.85 (m, 1H), 4.54 (s, 1H). 13C NMR
(63 MHz, CDCl3) d 19.6, 25.4, 26.2, 27.1, 27.9, 28.5, 29.2,
29.3, 29.4, 29.5, 29.5, 29.7, 30.7, 53.9, 62.2, 67.6, 81.0,
98.7, 169.0. MS (EI) m/z 472 [MC1]C.
4.1.11. 2-[11-(N,N0-Diphenyl-carbamimidoylsulfanyl)-
undecyl]-malonic acid 20. 19 (500 mg, 0.84 mmol) and
trifluoroacetic acid (1.91 g, 16.8 mmol, 20 equiv) were
dissolved in dichloromethane (10 ml) and stirred for 10 h
at ambient temperature. After the volatile part was removed
in vacuo, the product was used without further purification.
Colorless oil (320 mg, 79%). TLC RF 0.30 (dichloro-
methane/methanol/25%NH3 in water 13:6:1). IR (neat)
4.1.8. 2-(11-Hydroxy-undecyl)-malonic acid di-tert-butyl
ester 17. Amberlyst H-15 (674 mg, 10 mequiv) was added
to a solution of 16 (10.56 g, 22.4 mmol) in methanol (40 ml)
and the mixture was stirred at 45 8C for 10 h until 16 could

10018
A. Koch et al. / Tetrahedron 60 (2004) 10011–10018
3207, 2980, 2929, 2857, 1722, 1605, 1573, 1172, 759,
(through the ‘Center of Multifunctional Materials and
Miniaturized Devices’ in Mainz, BMBF No. 03N 6500),
the Fonds der Chemischen Industrie, and the Gesellschaft
Deutscher Chemiker/Dr. Hermann Schnell Stiftung is
highly appreciated.
1
693 cmK1. H NMR (250 MHz, CDCl3) d 1.10–1.40 (m,
16H), 1.46–1.60 (m, 2H), 1.85–1.95 (m, 2H), 3.02 (t, br,
2H), 3.40 (t, JZ7.2 Hz, 1H), 5.90 (s, br, 1H),7.29–7.44 (m,
10H), 9.74 (s, br, 2H). 13C NMR (63 MHz, CDCl3) d 26.9,
27.7, 28.3, 28.6, 28.9, 29.0, 30.9, 32.1, 51.2, 126.0, 129.7,
130.2, 133.7, 174.9. MS (FD) m/z 485 [M]C, 441 [MK
CO2]C.
References and notes
4.1.12. 16-Aza-17-azonia-16,17-diphenyl-18-oxido-15-
oxo-2-thia-bicyclo-[11.2.2]octadeca-1(17),14(18)-diene
21. DCC (87 mg, 0.42 mmol) in dichloromethane (50 ml)
was added to a stirred solution of 20 (100 mg, 0.21 mmol) in
dichloromethane (150 ml) with a syringe while the tem-
perature was maintained at about 20 8C by water cooling.
The mixture turned yellow and 1,3-dicyclohexylurea
precipitated, showing the progress of the reaction. After
stirring overnight at ambient temperature the urea was
filtered off and washed with dichloromethane. The filtrate
was concentrated and the crude product purified by
preparative TLC (petrol ether/acetone 5:1) yielding a yellow
solid (19 mg, 20%), mp 171 8C. IR (KBr) 2926, 2854, 1649,
1358, 1244 cmK1. 1H NMR (250 MHz, CDCl3) d 1.25–1.65
(m, 18H), 2.20 (t, JZ6 Hz, 2H), 2.58 (t, JZ6 Hz, 2H),
7.27–7.58 (m, 10H). 13C NMR (63 MHz, CDCl3) d 24.1,
25.9, 26.8, 26.9, 27.1, 27.8, 28.6, 30.6, 36.1, 97.8, 128.4,
128.9, 129.2, 129.8, 137.5, 159.6. UV (CH2Cl2) 392 (0.60)
nm (log e). MS (FD) m/z 531, 448 [M]C. HRMS found MC
448.2190. C27H32N2O2S requires 448.2185.
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Acknowledgements
The authors would like to thank Verona Maus for synthetic
help and Dr. Alexander Theis for helpful discussions.
Financial support by the Max Planck Society, the BMBF
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