Syntheses and UV/Vis properties of amino-functionalized fulgimides

Article abstract of DOI:10.1002/ejoc.200200680

Functionalized fulgimides are regarded as a promising class of photochromic compounds for modulating the structure and function of biomolecules. A new synthetic route to fulgimides bearing amino-functionalized substituents at the imide nitrogen atom has been developed. The synthesis of the fulgimides has been achieved by base-catalyzed cyclization of phenacyl esters of the succinamic acids derived from fulgides and N-Boc-protected alkyl- and aryl-substituted diamines with triethylamine or tert-butyllithium. The UV/Vis spectroscopic data and the photochromic properties of these new compounds have been studied. Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003).

Full text of DOI:10.1002/ejoc.200200680

FULL PAPER
Syntheses and UV/Vis Properties of Amino-Functionalized Fulgimides
Bernhard Otto[a] and Karola Rück-Braun*[a]
Keywords: Fulgides / Fulgimides / Photochromism / UV/Vis spectroscopy
Functionalized fulgimides are regarded as a promising class
of photochromic compounds for modulating the structure and with triethylamine or tert-butyllithium. The UV/Vis spectro-
function of biomolecules. A new synthetic route to fulgimides scopic data and the photochromic properties of these new
and N-Boc-protected alkyl- and aryl-substituted diamines
bearing amino-functionalized substituents at the imide nitro- compounds have been studied.
gen atom has been developed. The synthesis of the fulgim-
ides has been achieved by base-catalyzed cyclization of ( Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
phenacyl esters of the succinamic acids derived from fulgides
Germany, 2003)
Introduction
(carboxymethyl)thienylfulgimides[7,8] have been prepared
and the latter, activated as N-hydroxysuccinimide active es-
ters, have been employed for the modification of α-chymo-
trypsin and concavalin A and have been attached to lysine
residues.
Photochromic molecules have become important targets
for optical data storage and as optical switches.[1,2] Fulgides
display excellent fatigue resistance and thermal stability of
their photochromic isomers.[3Ϫ6] In general, fulgides exist in
three isomeric states as (Z), (E) and (C) forms. The (Z) and
(E) forms can reversibly be converted into each other by
irradiation with UV light and both have similar optical
properties. Upon irradiation of the generally pale yellow (E)
isomers with UV light an electrocyclic ring-closure reaction
occurs and the thermally stable colored (C) forms of ful-
gides are formed. The (C) isomers are almost planar and
their extended π-electron system causes a strong and broad
absorption band in the Vis wavelength range. The reverse
reaction to (E)-fulgides is achieved, for example, by expo-
sure to white light (Scheme 1). The almost unique thermal
stability of the photoisomeric states of fulgides is essential
for their application in optical data storage as well as for
biological applications.[1,7Ϫ10] In the latter case the severe
structural change during photocyclization is of interest for
modulating the structure and function of biomolecules by
irradiation with light of different wavelengths.[7,8] For bio-
logical applications high solvolytic resistance is required.
Therefore, the studies presented here focus on the imide de-
rivatives of fulgides, which have been less intensively and
systematically studied in the past.[9] In addition, the imide
moiety allows the introduction of functional substituents at
the imide nitrogen atom to allow attachment to biomolec-
ules.[7,8] For instance, N-(4-carboxyphenyl)furyl-[9] and N-
Scheme 1
Herein, we describe the synthesis of fulgimides (Schemes
2 and 3) bearing amino-functionalized substituents at the
imide nitrogen atom, derived from thienylfulgides 1 with an
isopropyl or methyl group as the substituent R (Scheme 1).
A bulky isopropyl group instead of a methyl residue is
known to increase the steric hindrance and constraints of
the exocyclic double bond, thereby lowering the efficiencies
for (E)-to-(Z) isomerization and increasing the (E)-to-(C)
isomerization quantum yields.[10] In the past 3-furyl-, 3-
thienyl- and 3-indolylfulgimides were synthesized by cycli-
zation of succinamic acids and derivatives stemming from
the reaction of the parent fulgide with a primary amine or
ammonia.[11Ϫ16] Treatment with acetyl chloride or acetic
anhydride at high temperature usually furnished the fulgim-
ides in unsatisfactorily low yields. For example, Matsushima
reported the synthesis of N-aryl-substituted furylfulgimides
in 12Ϫ18% yield employing acetyl chloride.[9] Heller et
al.[11,12] described the synthesis of furyl- and arylfulgimides
by treatment of succinic hemi-esters with Grignard salts of
primary amines and subsequent cyclization to the imide
[a]
Institut für Chemie, Technische Universität Berlin, Fakultät II,
TC 2,
Straße des 17. Juni 135, 10623 Berlin, Germany
Fax: (internat.) ϩ 49-30/31479651
E-mail: krueck@chem.tu-berlin.de
Supporting information for this article is available on the
WWW under http://www.eurjoc.org or from the author.
Eur. J. Org. Chem. 2003, 2409Ϫ2417
DOI: 10.1002/ejoc.200200680
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B. Otto, K. Rück-Braun
FULL PAPER
with acetyl chloride in 35% yield. Recently, Rentzepis[17] re-
ported the synthesis of N-alkyl- and N-aryl-2-indolylfulgi-
mides by ZnCl2 or ZnBr2 in the presence of HMDS
(1,1,1,3,3,3-hexamethyldisilazane) in benzene at high tem-
perature in 80Ϫ90% yield. Cyclization strategies in the ab-
sence of acidic reagents or Lewis acids have been less inten-
sively studied. Ringsdorf et al.[15] reported on the treatment
of a furylfulgimide with ammonia followed by esterification
of the succinamic acid intermediate with diazomethane.
Subsequent base-catalyzed cyclization applying sodium me-
thoxide furnished the fulgimide in 15% yield. From the lat-
ter, N-substituted derivatives were prepared by the reaction
with bromo- or hydroxy-substituted compounds.[15] Re-
cently, Yokoyama et al. reported a similar route, which af-
forded a 3-indolylfulgimide in 95% yield by using sodium
hydride in the cyclization step.[16] In this paper, we describe
base-catalyzed cyclization strategies that were developed for
the synthesis of N-Boc-protected thienylfulgimides. We also
report on the deprotection of these fulgimides.
Scheme 2. a) H2NCH2CH2NHBoc (2a), CH2Cl2, reflux, 3 h, 3:
99%; b) H2NC6H4CH2NHBoc (2b), CH2Cl2, reflux, 3 d, 4: 87%; c)
phenacyl bromide, NEt3, ethyl acetate, room temp., 5: 86%; 6: 96%;
d) Method A: tBuLi (2.2 equiv.), THF, Ϫ78 °C, 7: 48%; e) Method
B: NEt3 (10%), CH2Cl2, room temp., 8: 51%
Results and Discussion
Synthesis
The fulgides (Z)-1a[18] (Scheme 2) and (E)-1b[19]
(Scheme 3) were synthesized by Stobbe condensation[20] of
diethyl or dimethyl isopropylidenesuccinate with (2,5-di-
methyl-3-thienyl) methyl ketone and (2,5-dimethyl-3-thi-
enyl) isopropyl ketone, respectively, followed by hydrolysis
and subsequent cyclization of the resulting diacids with
acetic anhydride or dicyclohexylcarbodiimide. Separation
of the major isomers was achieved by chromatography or
crystallization. Treatment of the fulgide (Z)-1a (Scheme 2)
and (E)-1b (Scheme 3) with tert-butyl (2-aminoethyl)-
carbamate (2a) in refluxing dichloromethane gave the re-
gioisomeric succinamic acids in Ͼ 99% yield as inseparable
mixtures. The reaction of the aniline compound 2b with
(Z)-1a (Scheme 2) similarly afforded a mixture of re-
gioisomeric compounds 4 in 87% yield.
Scheme 3. a) H2NCH2CH2NHBoc (2a), CH2Cl2, reflux, 3 h, quant;
b) phenacyl bromide, NEt3, ethyl acetate, room temp., 94%; c)
tBuLi (2.4 equiv.), THF, Ϫ78 °C, 40%
Various strategies and reaction conditions were examined chromatography on silica gel and isolated in Ͼ 86% yield.
to achieve cyclization to the corresponding imide. Starting Under these reaction conditions, subsequent cyclization to
from the succinamic acids 3 with dicyclohexylcarbodiimide the fulgimides was not observed (TLC monitoring). How-
in dichloromethane, fulgimide (Z)-7 was isolated after 2 d ever, separate treatment of the regioisomeric phenacyl ester
at room temperature in only 13% yield, owing to slow and arylamide 6 with triethylamine furnished the fulgimide (Z)-
incomplete turnover.[21] Reactions of the regioisomeric suc- 8 upon increasing the amount to 10% triethylamine in di-
cinamic acids 3 and 4 with either ZnCl2 and ZnBr2 (1 chloromethane. After 3 d at room temperature, ca. 70%
equiv.) in the presence of HMDS (1.5 equiv.) in refluxing turnover and the formation of by-products was determined
1
benzene according to Rentzepis[17] generally led to incon- by TLC monitoring and by H NMR spectroscopy of the
sistent results. The formation of substantial amounts of by- crude material isolated. Pure compound (Z)-8 was isolated
products was observed due to deprotection and (Z)/(E) iso- in 51% yield by flash chromatography. However, when ap-
merization. Traces of hydrogen chloride were obviously dif- plied to the phenacyl ester alkylamides 5 and 10, this reac-
ficult to avoid. However, compound (Z)-7 was isolated in tion protocol led to poor turnovers and unsatisfactory
11% yield from the isolated crude material by flash chroma- yields (Table 1). Whereas compound (Z)-7 was isolated in
tography on silica gel.
31% yield (ca. 35% turnover), for (E)-11 less than 10% turn-
1
We then prepared the regioisomeric phenacyl ester am- over was observed within 7 d according to H NMR spec-
ides 5, 6 (Scheme 2) and 10 (Scheme 3) from the succinamic troscopy of the crude material isolated. Fortunately, treat-
acids, phenacyl bromide (1.1 equiv.) and triethylamine (2.1 ment of 5 with tert-butyllithium (2.2 equiv.) in THF at Ϫ78
equiv.) in ethyl acetate.[21] The products were purified by °C resulted in 80% turnover and gave product (Z)-7 in 48%
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Syntheses and UV/Vis Properties of Amino-Functionalized Fulgimides
FULL PAPER
yield after flash chromatography on silica gel. Increasing obtained upon treatment of (Z)-7 with 50% TFA in di-
the excess of tert-butyllithium and prolonged reaction times chloromethane. However, (E)/(Z) isomerization could be
led only to formation of substantial amounts of by-prod- avoided employing 5% TFA followed by subsequent
ucts. The reaction of the sterically demanding phenacyl es- workup with diluted aqueous ammonia solution prior to
ter alkylamide 10 with tert-butyllithium (2.4 equiv.) gave concentration. Thus, fulgimide (Z)-13 was isolated in 87%
50% turnover in 6 h and fulgimide (E)-11 was isolated in yield and 90Ϫ95% purity according to 1H NMR spec-
40% yield (flash chromatography) in pure form. However, troscopy and HPLC analysis of the crude product isolated.
treatment of the phenacyl ester arylamide 6 with tert-butyl- All attempts to increase the purity applying flash chroma-
lithium resulted in the formation of substantial amounts of tography failed. Preparative reversed-phase HPLC with
by-products and incomplete turnover. Fulgimide (Z)-8 was acetonitrile/water containing 1% TFA led to (E)/(Z) iso-
isolated in 14% yield.
merization.
Table 1. Synthesis of fulgimides according to Schemes 2 and 3
Entry
Starting
material
Method
Reaction
time
[h]
Product
Yield[a]
[%]
1
2
3
4
5
6
5
5
A
B
A
B
A
B
2[b]
144
6[c]
7
7
48
31
14
51
6
8
6
10
10
72
8
11
11
6[d]
40
Scheme 5. a) (Z)-8: HCl in dioxane, 89%, ratio (Z)/(E) ϭ 88:12; b)
(Z)-7: 5% TFA in CH2Cl2, then aqueous NH3 solution, 87%
188
10[e]
[a] Isolated yield. [b] 2.2 equiv. of tBuLi. [c] 3.0 equiv. of tBuLi. [d] 2.4
equiv. of tBuLi. [e] Turnover according to 1H NMR spectroscopy of
the crude material isolated.
X-ray Analysis
The structure of fulgimide (Z)-7 was determined by X-
ray structure analysis (Figure 1). The triene system of (Z)-
7 is twisted, owing to the steric hindrance caused by the
atoms C(8) and C(15) and the atoms O(1) and C(6). The
torsion angle C(7)ϪC(9)ϪC(10)ϪC(13) is Ϫ51.0°, which is
slightly larger than for other (Z)-fulgides. For example, a
phenyl-substituted (Z)-thienylfulgide[23] was reported to
contain a corresponding torsion angle of Ϫ48° and for a
(Z)-furylfulgide[24] a torsion angle of Ϫ47° was determined.
In contrast to this, (E)-thienylfulgides[23] and (E)-furylful-
gides[24] have a smaller torsion angle of 39 and Ϫ39.6°,
The (E) isomers (E)-7 and (E)-8 (Scheme 4) were pre-
pared by irradiation of a solution of the (Z) isomers at
365 nm (200 W mercury lamp) until the photostationary
state was reached (14 h). The deep red solutions obtained,
enriched in the (C) forms, were converted into the (E) iso-
mers with 514-nm light (1000-W xenon lamp). The resulting
crude product mixtures were then separated by column
chromatography to yield 57% of (E)-7 and 73% of (E)-8.
Scheme 4. a) (E)-7: toluene, room temp., 365 nm, 13.5 h; then day-
light, 4 h, 57%; b) (E)-8: toluene, room temp., 365 nm, 12 h; then
daylight, 4 h, 73%
HCl in dioxane was applied successfully for the deprotec-
tion of (Z)-8 (Scheme 5).[22] However, (E)/(Z) isomerization
was observed, yielding (Z)-12 in a ratio (Z)/(E) ϭ 91:9 (1H
NMR spectroscopy). Upon purification by reversed-phase
HPLC, 12 was isolated in 89% yield [(Z)/(E) ϭ 88:12]. De-
protection of the Boc-protected fulgimide (Z)-7 with TFA
in dichloromethane proved to be a challenge.[22] Reactions
employing 5% TFA in dichloromethane at room tempera-
ture looked very promising but during concentration of the
reaction mixture (E)/(Z) isomerization and the formation
Figure 1. ORTEP plot of (Z)-7; selected bond lengths [pm], angles
[°] and torsion angles [°]: N(1)ϪC(11) 139.4(6), N(1)ϪC(12)
139.0(6), C(1)ϪC(4) 136.7(7), C(1)ϪC(7) 149.6(6), C(7)ϪC(9)
133.6(8),
C(9)ϪC(10)
147.0(6),
C(10)ϪC(13)
135.7(7);
127.6(5);
C(7)ϪC(9)ϪC(10)
128.9(5),
C(9)ϪC(10)ϪC(13)
C(7)ϪC(9)ϪC(10)ϪC(13) Ϫ51.0(9), C(12)ϪC(9)ϪC(10)ϪC(11)
Ϫ17.4(5), C(1)ϪC(7)ϪC(9)ϪC(10) Ϫ179.0(5); for further details
of by-products were again observed. Similar results were see Exp. Sect. and ref.[25]
Eur. J. Org. Chem. 2003, 2409Ϫ2417
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B. Otto, K. Rück-Braun
FULL PAPER
respectively. The inner torsion angle of the imide ring sys-
tem of (Z)-7 [C(12)ϪC(9)ϪC(10)ϪC(11)] is Ϫ17.4°. This
value is in good accord with those of other (Z)-fulgides
(Ϫ18, Ϫ15.7°) as well as (E)-fulgides (15, Ϫ16.5°).[23,24] Be-
tween
the
two
isomers
the
torsion
angle
C(1)ϪC(7)ϪC(9)ϪC(10) does differ significantly and this
angle indicates whether the double bond is (Z)- or (E)-con-
figured. For (Z)-furylfulgides this torsion angle is 173.2° in
contrast to Ϫ8.5° for (E)-furylfulgides.[24] The torsion angle
for (Z)-7 is consistently Ϫ179.0°. Steric repulsion between
the atoms C(8) and C(15) also widens the bond angles of
(Z)-7. The bond angles C(7)ϪC(9)ϪC(10) and
C(9)ϪC(10)ϪC(13) are 128.9 and 127.6°. These values are
close to those of other (Z)-thienylfulgides[23] (130.3, 128.7°)
and (Z)-furylfulgides[24] (128.4, 130.7°) whereas the bond
angles for (E)-thienylfulgides[23] (132.1, 131.5°) and (E)-fur-
ylfulgides[24] (132.1, 131.2°) are slightly higher.
Photochromism and UV/Vis Spectroscopy
Figure 2 displays the photochromism of compound 8 in
toluene solution at room temperature. Irradiation of the (Z)
and the (E) form at 366 nm is shown, indicating ring closure
to the (C) form by the increasing absorption around
526 nm. Because of the (Z)/(E) isomerization prior to cycli-
zation isosbestic points for this electrocyclic ring-closure
process are not observed. Ring opening of the (C) isomer
was accomplished by irradiation at 514 or 520 nm of the
solutions enriched in the (C) form obtained from either the
(Z) or (E) isomer. For this reaction process the isosbestic
points are listed in Table 2 as well as the absorption maxima
of the fulgides and fulgimides measured in toluene.
The UV/Vis spectra of (Z)-1a and (E)-1b as well as of
(Z)-7, (E)-7 and (Z)-8, (E)-8 show a typical maximum at
ca. 311Ϫ339 nm, whereas for (E)-11 (315 nm) and (Z)-13
Figure 2. Change of UV/Vis spectra of fulgimide 8: c ϭ 1.0 ϫ 10Ϫ4
mol/L in toluene, XBO 1000 W; top: (Z)-8, 365-nm filter, Tmax
:
(321 nm) only absorption shoulders are detected in the cor- 50%, HW: 10 nm, ∆t ϭ 60 s, pss reached after 600 s; center: (E)-8,
365-nm filter, Tmax: 50%, HW: 10 nm, ∆t ϭ 60 s, pss reached after
responding wavelength range. The data are consistent with
540 s; bottom: solution enriched in (C)-8 (Entry 4, Table 2, pss365
)
previously published work.[9] The spectral features reveal
that selective excitation of the (E) forms at 365 nm is less
effective because of significant absorption of the light by
the (C) forms formed. The (E) configuration was found to
obtained by irradiation of (Z)-8, 514-nm filter, Tmax: 50%, HW:
10 nm, ∆t ϭ 10 s, pss reached after 80 s
shift the absorption maximum to shorter wavelengths com- atom is found to be negligible. According to Rentzepis[17]
,
pared to the (Z) configuration. For the (C) isomers a broad substituents at the N-position of 2-indolylfulgimides were
maximum at about 514Ϫ526 nm is observed. In the case of also found to have little effect on the photochromism and
N-arylfulgimide 8 the absorption maxima of the (Z), (E) the absorption maxima. For compound (Z)-7 a ratio of (Z)/
and (C) form are red-shifted by about 6Ϫ15 nm compared (E)/(C) ϭ 9:31:60 (Entry 3, Table 2) was determined and
to the isomers of the N-alkylfulgimide 7.
similar results were obtained for (Z)-8 (Entry 4, Table 2).
We have also determined the ratio of the isomers in the For compound (Z)-13, bearing the more polar amino
photostationary states at 365 and 514 nm by 1H NMR group, the absorption maxima are lower in intensity and
1
spectroscopy in [D8]toluene. The data published previously only 51% of (C)-13 was determined in the pss by H NMR
for (E)-1b by Effenberger et al.[19] were confirmed, whereas spectroscopy. However, irradiation of (E)-11 containing the
for (Z)-1a the data were found to deviate from the litera- bulky isopropyl group led to a photostationary equilibrium
ture.[18] For adamantylidene-substituted N-methyl- and N- containing 67% of the (C) form. Similarly, in the literature
phenylfurylfulgimides Heller et al.[11] determined a 55:45 for a 3-indolylfulgimide[16] possessing an isopropyl group, a
and a 30:70 mixture of the (C) and the (E) form in the 68% (C)-form content has been reported at the photo-
photostationary state (pss) measured by 1H NMR spec- stationary state of UV irradiation (405 nm) although the
troscopy upon irradiation in CDCl3 (366 nm). In contrast (Z) isomers of 3-indolylfulgides and -fulgimides are not in-
to these examples for fulgimides 7 and 8 in [D8]toluene the volved in the photochromic reaction. However, Matsush-
influence of aryl or alkyl substituents on the imide nitrogen ima[9] reported not less than 80% conversion into the (C)
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Eur. J. Org. Chem. 2003, 2409Ϫ2417

Syntheses and UV/Vis Properties of Amino-Functionalized Fulgimides
Table 2. UV/Vis data of fulgides and fulgimides in toluene
FULL PAPER
pss365 (Z)/(E)/(C)[c]
pss514 (Z)/(E)/C[c]
Isosbestic point514
[a]
[b]
[a]
[b]
[a]
Entry
Compound
λZ
εZ
λE
εE
λC
1
2
3
4
5
6
(Z)-1
339
Ϫ
328
334
Ϫ
7980
Ϫ
5460
6250
Ϫ
Ϫ
Ϫ
524
524
516
526
518
514
8:11:81
0:8:92
9:31:60
9:34:57
5:28:67
16:33:51
12:88:0
0:100:0
10:90:0
9:91:0
5:95:0
19:81:0
393
382
368
362
357
370
(E)-2
327
311
326
315
Ϫ
3920
7410
6850
5150
Ϫ
(E)-7/(Z)-7
(E)-8/(Z)-8
(E)-11
(Z)-13
321
4440
[a]
[b]
[c]
1
[nm].
[dm3·molϪ1·cmϪ1]. Ratios determined by H NMR spectroscopy in [D8]toluene in the pss upon illumination with 365 nm
and 514 nm, respectively.
˚
inert gas on silica gel (ICN silica, 63Ϫ200 µm, 60 A, ICN Biomed-
forms during measurements focusing on the photochemical
reversibility and recyclizability of fulgimides in toluene
solutions and solid PMMA films. Likewise, Rentzepis[17]
observed more than 80% transformation of the (E) form to
the (C) form for 2-indolylfulgimides in either CH3CN or
hexane. However, the data of these authors do not refer to
NMR measurements and thus a comparison of the data
seems to be inappropriate since the ratios determined in the
photostationary states depend upon the concentration of
the photochromic compounds.
icals GmbH). All reactions were performed under argon. Solvents
were dried before use according to standard procedures.[27] The am-
ines H2NCH2CH2NHBoc (2a)[28] and H2NC6H4CH2NHBoc
(2b)[29] and the fulgides 1a[18] and 1b[19] were prepared according
to literature procedures. tert-Butyllithium (1.6  in pentane) was
purchased from Aldrich. Changes in the absorption spectra of ful-
gides and fulgimides in toluene (c ϭ 1 ϫ 10Ϫ4 mol/L) were investi-
gated by light irradiation starting from the (Z) isomers at 365 nm
(365-nm interference filter, Amko, Tornesch) and by light ir-
radiation starting from the (C) isomers in the pss at 514 nm (514-
nm interference filter, Amko, Tornesch) and were determined with
an MCS 320/340 Diodenarray spectrometer from Zeiss with an ir-
radiation beam of a xenon lamp 1000 XBO (Osram, München) ver-
tical to the measuring cell. These measurements were carried out
at the University of Mainz in the research group of Prof. Dr. H.
Meier, Institut für Organische Chemie. The irradiation was carried
out in 10- or 30-s intervals for 365 and 520 nm, respectively, in
order to bring about the pss. Otherwise, photoirradiation was per-
formed at the TU Berlin using a high-pressure mercury lamp 200
HBO (Osram, München) with a 365-nm interference filter (Amko,
Conclusion
Boc-protected amino-functionalized thienylfulgimides
have been synthesized from phenacyl ester amides by a
base-catalyzed cyclization strategy employing triethylamine
for arylamides and tert-butyllithium for alkylamides. De-
protection of (Z)-7, furnishing (Z)-13 and avoiding (E)/(Z)
isomerization, was carried out with 5% TFA in dichloro- Tornesch) and a xenon lamp 1000 XBO (Osram, München) with a
514-nm interference filter (Amko, Tornesch) or by exposure to day-
light. Samples were placed at the focus of the irradiation beam
(suprasil lens, focus 10 cm) and 2 cm behind the corresponding fil-
ter. The isomeric ratio in the pss was determined by irradiation
of the compounds in [D8]toluene in a quartz NMR tube and by
integration of the corresponding signals of the hydrogen atoms in
the 4-position of the thiophene moiety (δ ϭ 5.8Ϫ6.6 ppm). The
NMR spectroscopic data of the fulgimides in [D8]toluene are listed
in Table 3. Large-scale photoisomerization using the high-pressure
mercury lamp 200 HBO at 365 nm were carried out in a round-
bottom flask placed 4 cm behind the filter and about 12 cm behind
the suprasil lens (focus 10 cm). All experiments were conducted
with a 5-cm water filter between the lamp and the lens to cut off
the IR irradiation of the lamp. All solutions were degassed and
stirred during irradiation.
methane and subsequent workup with aqueous ammonia
solution. The UV/Vis data and photochromic properties of
the synthesized fulgimides have been determined and the
results obtained have been discussed in relation to their
structure and in comparison to literature data. We are eval-
uating applications of the amino-functionalized fulgimides.
Experimental Section
General Remarks: Melting points were measured with a Büchi ap-
paratus and are uncorrected. 1H and 13C NMR spectra were re-
corded with a Bruker AC 200, AM 400 or DRX 500 spectrometer,
residual solvent protons were used as internal standard. All chemi-
cal shifts are given in ppm relative to TMS and coupling constants
in Hz. FT IR spectra were recorded with a Nicolet Avatar 360 FT
IR or a PerkinϪElmer FT IR spectrometer 1760X. Low- and high-
resolution electron-impact mass spectra (EIMS, 70 eV) were re-
corded with a Finnigan MAT 95 SQ or a Varian MAT 711 spec-
3: A solution of tert-butyl (2-aminoethyl)carbamate (2a) (0.96 g,
5.79 mmol) in CH2Cl2 (5 mL) was added to a solution of fulgide
1a (1.50 g, 5.43 mmol) in CH2Cl2 (50 mL). The mixture was re-
fluxed for 3 h and the solvent was evaporated under reduced press-
trometer. Elemental analyses were carried out by the Microana- ure. The crude product was then purified by chromatography on
lytical Division of the Institute of Organic Chemistry at the Univer-
sity of Mainz (Germany) or were measured with an Elementar Va-
rio EI from Analytik Jena at the Institute of Chemistry, TU Berlin.
silica gel using ethyl acetate/methanol (67:33, v/v) as eluent to give
3 as a yellow solid. Yield: 2.34 g (99%), mixture of isomers, ratio
I/II ϭ 55:45 (1H NMR); m.p. 68Ϫ70 °C; Rf ϭ 0.59 [ethyl acetate/
For TLC, Merck silica-gel 60-F254 plates were used. Flash chroma- methanol, 67:33, v/v). 1H NMR (200 MHz, CDCl3; 25 °C): isomer
˚
tography was performed on silica gel (ICN silica, 32Ϫ63 µm, 60 A,
ICN Biomedicals GmbH). Column chromatography was carried
out using the technique developed by Helquist et al.[26] but without
I: δ ϭ 7.59 (br. s, 1 H, NH), 6.41 (s, 1 H, 4-H thienyl), 5.20 (br. s,
1 H, NH), 3.35Ϫ3.48 (m, 2 H, CH2), 3.25Ϫ3.35 (m, 2 H, CH2),
2.32 (s, 3 H, CH3), 2.20 (s, 3 H, CH3), 1.93 (s, 3 H, CH3), 1.85 (s,
Eur. J. Org. Chem. 2003, 2409Ϫ2417
www.eurjoc.org
 2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
2413

B. Otto, K. Rück-Braun
FULL PAPER
1
ppm. IR (KBr): ν˜ ϭ 3369, 3055, 2980, 2922, 2864, 1703, 1655,
1599, 1582, 1511, 1451, 1392 cmϪ1. MS (70 eV, EI): m/z (%) ϭ 554
(18) [Mϩ], 394 (42), 258 (100). HR MS (70 eV, EI): calcd. 554.2451,
found 554.2451 (for C30H36N2O6S).
Table 3. H NMR spectroscopic data of fulgimides in [D8]toluene
Compound
4-H
Me[a]
Me
Me
Me
Me
tBu
(Z)-7
(E)-7
(C)-7
(Z)-8
(E)-8
(C)-8
(E)-11
(C)-11
(Z)-12
(E)-12
(C)-12
6.56
6.42
5.81
6.54
6.44
5.83
6.62
6.12
6.53
6.40
5.80
2.51
2.82
2.33
2.55
2.89
2.39
2.39
1.99
2.53
2.84
2.34
2.51
2.43
1.96
2.52
2.47
1.97
2.11
1.87
2.49
2.44
1.94
2.36
2.25
1.84
2.36
2.28
1.85
1.33
1.72
2.35
2.24
1.83
1.89
2.14
1.70
1.93
2.18
1.66
1.58
1.59
1.59
1.65
1.68
1.67
1.60
1.61
Ϫ
(Z)-7: A solution of tert-butyllithium (1.5  in pentane, 1.87 mL,
3.17 mmol) was added to a solution of 5 (800 mg, 1.44 mmol) in
THF (50 mL) at Ϫ78 °C. The mixture was stirred for 2.5 h and
brine (100 mL) was added. The aqueous layer was extracted with
diethyl ether (2 ϫ 100 mL) and the combined organic layers were
dried (MgSO4) and concentrated in vacuo. The crude product was
purified by flash chromatography on silica gel with light petroleum
ether/ethyl acetate (80:20 Ǟ 67:33 Ǟ 50:50, v/v) as eluent to give 7
as a yellow solid. Yield: 290 mg (48%) [besides 177 mg (22%) 5];
m.p. 49Ϫ50 °C; Rf ϭ 0.51 (light petroleum ether/ethyl acetate,
1.27
[b]
1.75
1.33
[b]
1.60
[b] [c]
Ϫ
Ϫ
1.65
1.26
1.57
[b]
1.88
2.17
1.66
Ϫ
Ϫ
1
67:33, v/v). H NMR (200 MHz, CDCl3, 25 °C): δ ϭ 6.50 (s, 1 H,
[a]
The signals of the methyl groups are listed according to their
3
[b]
4-H thienyl), 4.85 (br. s, 1 H, NH), 3.55 (t, JH,H ϭ 5 Hz, 2 H,
chemical shifts.
the other isomers.
The signal is overlapped by adjacent signals of
3
[c]
CH2), 3.35 (m, JH,H ϭ 5 Hz, 2 H, CH2), 2.38 (s, 3 H, CH3), 2.37
The signal is overlapped by the signals of
residual solvent protons of [D8]toluene.
(s, 3 H, CH3), 2.27 (s, 3 H, CH3), 2.04 (s, 3 H, CH3), 1.89 (s, 3 H,
CH3), 1.42 (s, 9 H, tBu) ppm. 13C NMR (50.3 MHz, CDCl3, 25
°C): δ ϭ 168.4, 166.0, 155.8, 148.0, 141.5, 137.3, 136.3, 135.4,
125.3, 124.8, 123.9, 79.1, 39.8, 37.2, 28.3, 26.9, 26.1, 21.7, 15.2, 14.1
ppm. IR (KBr): ν˜ ϭ 3355, 2977, 2921, 1776, 1699, 1587, 1515,
1439, 1392, 1367 cmϪ1. MS (70 eV, EI): m/z (%) ϭ 418 (28) [Mϩ],
347 (100). HR MS (70 eV, EI): calcd: 418.1926; found 418.1926
(for C22H30N2O4S).
3 H, CH3), 1.74 (s, 3 H, CH3), 1.37 (s, 9 H, tBu); isomer II: δ ϭ
6.46 (s, 1 H, 4-H thienyl), 6.19 (br. s, 1 H, NH), 4.58 (br. s, 1 H,
NH), 3.00Ϫ3.25 (m, 2 H, CH2), 2.80Ϫ3.00 (m, 2 H, CH2), 2.38 (s,
3 H, CH3), 2.22 (s, 3 H, CH3), 2.08 (s, 3 H, CH3), 1.88 (s, 3 H,
CH3), 1.75 (s, 3 H, CH3), 1.39 (s, 9 H, tBu) ppm. 13C NMR
(50.3 MHz, CDCl3, 25 °C, mixture of isomers, * minor compo-
nent): δ ϭ 171.8, 157.1, 156.3, 146.2*, 142.0, 141.0, 137.6, 137.2*,
135.7, 133.0, 132.0, 131.0*, 127.3, 125.3, 79.8, 41.1*, 40.8, 40.3,
28.3, 22.2, 21.8, 21.4, 21.0*, 15.1, 13.6, 13.5* ppm. IR (KBr): ν˜ ϭ
3358, 3063, 2978, 2921, 2864, 2734, 1696, 1646, 1577, 1523, 1448,
1393, 1367, 1273, 1250, 1171 cmϪ1. MS (70 eV, EI): m/z (%) ϭ 436
(14) [Mϩ], 261 (45). HR MS (70 eV, EI): calcd. 436.2032, found
436.2031 (for C22H32N2O5S).
4: Fulgide 1a (478 mg, 1.73 mmol) and tert-butyl (4-aminobenzyl)-
carbamate (2b) (500 mg, 2.25 mmol) were dissolved in CH2Cl2
(30 mL). The mixture was refluxed for 72 h and the solvent was
evaporated in vacuo. The crude product was then purified by flash
chromatography on silica gel with light petroleum ether/ethyl acet-
ate (83:17 Ǟ 67:33 Ǟ 0:100, v/v) as eluent to give 4 as a yellow
solid. Yield: 748 mg (87%), mixture of isomers, ratio I/II ϭ 46:54
(1H NMR); m.p. 167 °C; Rf ϭ 0.13 (light petroleum ether/ethyl
5: A solution of phenacyl bromide (1.25 g, 6.30 mmol) in ethyl acet-
ate (10 mL) was added dropwise to a solution of 3 (2.50 g,
5.73 mmol) in ethyl acetate (50 mL), followed by dropwise addition
of triethylamine (0.89 mL, 12.0 mmol). After a few minutes, a col-
orless precipitate was formed and the solution turned orange. The
mixture was stirred for 4 d (TLC monitoring). Then water (50 mL)
was added and the aqueous layer was separated and extracted with
ethyl acetate (2 ϫ 50 mL). The combined organic layers were
washed with water (50 mL), 0.5  KHCO3 solution (50 mL), and
water (50 mL), dried (MgSO4), and concentrated in vacuo. The
crude product was purified by chromatography on silica gel using
light petroleum ether/ethyl acetate (80:20 Ǟ 67:33 Ǟ 50:50, v/v) as
eluent to give 5 as a colorless solid. Yield: 2.73 g (86%), mixture of
isomers, ratio I/II ϭ 60:40 (1H NMR); m.p. 47Ϫ48 °C; Rf ϭ 0.18
(light petroleum ether/ethyl acetate, 67:33, v/v). 1H NMR
(200 MHz, CDCl3, 25 °C): isomer I: δ ϭ 7.41Ϫ7.95 (m, 5 H, Ar-
H), 6.42 (s, 1 H, 4-H thienyl), 5.28 (br. s, 2 H, CH2), 3.46Ϫ3.55 (m,
2 H, CH2), 3.28Ϫ3.34 (m, 2 H, CH2), 3.23 (s, 3 H, CH3), 2.20 (s,
3 H, CH3), 2.05 (s, 3 H, CH3), 1.99 (s, 3 H, CH3), 1.77 (s, 3 H,
1
acetate, 67:33, v/v). H NMR (200 MHz, CDCl3, 25 °C): isomer I:
3
δ ϭ 7.18 (d, JH,H ϭ 7.9 Hz, 2 H, Ar-H), 7.17 (br. s, 1 H, NH),
7.04 (d, 3JH,H ϭ 7.9 Hz, 2 H, Ar-H), 6.57 (s, 1 H, 4-H thienyl), 4.83
(br. s, 1 H, NH), 4.24 (s, 2 H, CH2-Ar), 2.44 (s, 3 H, CH3), 2.22 (s,
3 H, CH3), 2.12 (s, 3 H, CH3), 2.03 (s, 3 H, CH3), 1.83 (s, 3 H,
CH3), 1.45 (s, 9 H, tBu) ppm; isomer II: δ ϭ 8.77 (br. s, 1 H, NH),
3
3
7.53 (d, JH,H ϭ 7.9 Hz, 2 H, Ar-H), 7.25 (d, JH,H ϭ 7.9 Hz, 2 H,
Ar-H), 6.45 (s, 1 H, 4-H thienyl), 4.88 (br. s, 1 H, NH), 4.26 (s, 2 H,
CH2-Ar), 2.37 (s, 3 H, CH3), 2.20 (s, 3 H, CH3), 2.05 (s, 3 H, CH3),
2.01 (s, 3 H, CH3), 1.82 (s, 3 H, CH3), 1.45 (s, 9 H, tBu) ppm. 13C
NMR (50.3 MHz, CDCl3, 25 °C): isomer I: δ ϭ 169.0, 168.5, 155.7,
146.5, 142.4, 138.5, 136.3, 135.9, 135.5, 133.6, 130.8, 127.9, 125.8,
124.3, 120.6, 79.5, 44.0, 28.2, 22.1, 22.0, 21.8, 15.0, 13.3 ppm. IR
(KBr): ν˜ ϭ 3338, 2977, 2920, 2862, 1696, 1594, 1516, 1447, 1413,
1367, 1249, 1169 cmϪ1. MS (70 eV, EI): m/z (%) ϭ 498 (64) [Mϩ],
277 (70), 165 (100). HR MS (70 eV, EI): calcd. 498.2188, found
498.2191 (for C27H34N2O5S).
6: A solution of phenacyl bromide (439 mg, 2.21 mmol) in ethyl
CH3), 1.36 (s, 9 H, tBu); isomer II: δ ϭ 7.41Ϫ7.95 (m, 5 H, Ar-H), acetate (5 mL) was added to a solution of 4 (1.00 g, 2.01 mmol) in
6.75Ϫ6.82 (br. s, 1 H, NH), 6.51 (s, 1 H, 4-H thienyl), 5.28 (br. s, ethyl acetate (30 mL). Triethylamine (0.58 mL, 4.21 mmol) was ad-
2 H, CH2), 3.14Ϫ3.22 (m, 2 H, CH2), 2.95Ϫ3.01 (m, 2 H, CH2), ded dropwise and the mixture was stirred at room temp. for 16 h.
2.39 (s, 3 H, CH3), 2.29 (s, 3 H, CH3), 2.27 (s, 3 H, CH3), 2.09 (s, Water (30 mL) was added and the aqueous layer was separated and
3 H, CH3), 1.83 (s, 3 H, CH3), 1.40 (s, 9 H, tBu) ppm. 13C NMR extracted with ethyl acetate (2 ϫ 30 mL). The organic layers were
(100.6 MHz, CDCl3, 25 °C, mixture of isomers, * minor compo-
washed with water (30 mL), saturated NaHCO3 solution (30 mL),
nent): δ ϭ 193.3, 193.1*, 169.8, 169.5*, 166.0, 165.8*, 156.1, 156.0*, and water (30 mL), dried (MgSO4), and concentrated in vacuo. The
155.4, 149.2, 141.1, 138.5, 138.3*, 137.2*, 136.4, 135.9*, 134.2, crude product was purified by flash chromatography on silica gel
134.1*, 134.0, 133.7*, 132.2, 131.0*, 129.0, 128.9*, 128.5, 127.9,
127.6*, 126.0, 125.2*, 79.0, 66.0, 65.8*, 41.4, 41.0*, 39.4, 28.4,
28.4*, 24.7*, 23.1, 22.5, 21.6, 21.6*, 21.0*, 15.1, 15.1*, 13.5, 13.4*
with light petroleum ether/ethyl acetate (83:17 Ǟ 67:33 Ǟ 50:50 Ǟ
0:100, v/v) as eluent to give a colorless solid. Yield: 1.19 g (96%),
mixture of isomers, ratio I/II ϭ 90:10 (1H NMR); m.p. 61Ϫ63 °C;
2414
 2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
Eur. J. Org. Chem. 2003, 2409Ϫ2417

Syntheses and UV/Vis Properties of Amino-Functionalized Fulgimides
FULL PAPER
Rf ϭ 0.40 (light petroleum ether/ethyl acetate, 67:33, v/v). 1H NMR HR MS (70 eV, EI): calcd. 418.1926, found 418.1927 (for
(500 MHz, CDCl3, 25 °C): isomer I: δ ϭ 8.09 (br. s, 1 H, NH), C22H32NO5S).
7.91Ϫ7.95 (m, 2 H, Ar-H), 7.57Ϫ7.63 (m, 1 H, Ar-H), 7.45Ϫ7.50
(E)-8: A solution of fulgimide (Z)-8 (920 mg, 1.91 mmol) in de-
gassed toluene (80 mL) was irradiated with 365-nm light [high-
pressure mercury lamp 200 HBO (Osram, München), 365-nm inter-
ference filter (Amko, Tornesch)] for 12 h (TLC monitoring). The
resulting red solution was exposed to daylight. After 4 h, the solu-
tion was light yellow. The solvent was evaporated in vacuo and the
3
(m, 2 H, Ar-H), 7.30 (d, JH,H ϭ 8.3 Hz, 2 H, Ar-H), 7.10 (d,
3JH,H ϭ 8.1 Hz, 2 H, Ar-H), 6.56 (s, 1 H, 4-H thienyl), 5.43 (s, 2 H,
CH2), 4.72 (br. s, 1 H, NH), 4.18 (s, 2 H, CH2-Ar), 2.37 (s, 3 H,
CH3), 2.30 (s, 3 H, CH3), 2.29 (s, 3 H, CH3), 2.07 (s, 3 H, CH3),
1.93 (s, 3 H, CH3), 1.42 (s, 9 H, tBu) ppm; isomer II (signals are
3
overlapped by adjacent signals of isomer I): δ ϭ 7.86 (d, JH,H
ϭ
resulting mixture of isomers was separated by flash chromatogra-
phy on silica gel with light petroleum ether/ethyl acetate (83:17, v/
v) as eluent to give (E)-8. Yield: 668 mg (73%) [besides 212 mg
(23%) of (Z)-8]; m.p. 68 °C; Rf ϭ 0.70 (light petroleum ether/ethyl
acetate, 67:33, v/v). 1H NMR (200 MHz, CDCl3, 25 °C): δ ϭ
7.31Ϫ7.43 (m, 4 H, Ar-H), 6.53 (s, 1 H, 4-H thienyl), 4.84 (br. s,
3
7.7 Hz, 2 H, Ar-H), 7.68 (d, JH,H ϭ 8.3 Hz, 2 H, Ar-H), 6.42 (s,
1 H, 4-H thienyl), 4.24 (s, 2 H, CH2-Ar), 2.35 (s, 3 H, CH3), 2.20
(s, 3 H, CH3), 2.06 (s, 3 H, CH3), 1.83 (s, 3 H, CH3), 1.43 (s, 9 H,
tBu) ppm. 13C NMR (125.8 MHz, CDCl3, 25 °C): isomer I: δ ϭ
193.9, 166.8, 165.8, 155.9, 155.5, 139.0, 137.9, 137.8, 137.0, 134.2,
134.1, 133.6, 132.6, 129.0, 128.0, 127.9, 125.5, 123.6, 120.2, 120.0,
79.5, 66.0, 44.4, 28.5, 24.8, 22.7, 21.9, 15.3, 13.7 ppm. IR (ATR):
ν˜ ϭ 3345, 3060, 2976, 2919, 2861, 1246, 1205, 1170 cmϪ1. MS
(70 eV, EI): m/z (%) ϭ 616 (25) [Mϩ], 259 (93), 231 (100). HR MS
(70 eV, EI): calcd. 616.2607, found 616.2605. C35H40N2O6S (616.8):
calcd. C 68.16, H 6.54, N 4.54; found C 67.78, H 6.83, N 4.77.
3
1 H, NH), 4.33 (d, JH,H ϭ 6.3 Hz, 2 H, CH2-Ar), 2.61 (s, 3 H,
CH3), 2.40 (s, 3 H, CH3), 2.29 (s, 3 H, CH3), 2.18 (s, 3 H, CH3),
2.04 (s, 3 H, CH3), 1.46 (s, 9 H, tBu) ppm. 13C NMR (50.3 MHz,
CDCl3, 25 °C): δ ϭ 167.8, 167.3, 155.8, 150.1, 144.5, 140.4, 138.9,
137.0, 133.7, 131.2, 128.0, 127.1, 125.7, 124.0, 122.9, 79.5, 44.3,
28.4, 25.6, 22.2 (2 C), 15.1, 14.7 ppm. IR (ATR): ν˜ ϭ 3384, 2977,
2921, 1751, 1700, 1514, 1367, 1167, 1147 cmϪ1. MS (70 eV, EI):
m/z (%) ϭ 480 (17) [Mϩ], 424 (25), 409 (100). HR MS (70 eV, EI):
calcd. 480.2083, found 480.2087. C27H32N2O4S (480.2): calcd. C
67.47, H 6.71, N 5.83; found C 67.40, H 6.79, N 5.67.
(Z)-8: Triethylamine (2 mL) was added dropwise to a solution of 6
(300 mg, 0.49 mmol) in CH2Cl2 (20 mL). The mixture was stirred
at room temp. for 72 h. Then water (15 mL) was added and the
aqueous layer was separated and extracted with CH2Cl2 (2 ϫ
20 mL). The organic layers were dried (MgSO4) and concentrated
in vacuo. The crude product was purified by flash chromatography
on silica gel with light petroleum ether/ethyl acetate (83:17 Ǟ
67:33, v/v) as eluent to give 8 as a slightly yellow solid. Yield:
120 mg (51%) [by chromatography 71 mg of starting material 6
(24%) was isolated; yield of 8 based on isolated 6: 68%]; m.p. 73
°C; Rf ϭ 0.62 (light petroleum ether/ethyl acetate, 67:33, v/v). 1H
9: A mixture of fulgide 2 (300 mg, 0.99 mmol) and tert-butyl (2-
aminoethyl)carbamate 2a (205 mg, 1.28 mmol) was dissolved in
CH2Cl2 (30 mL) and refluxed for 3 h. Then CH2Cl2 (20 mL) was
added and the organic layer was extracted with aqueous HCl
(0.1 , 2 ϫ 20 mL), dried (MgSO4), and the solvent was concen-
trated under reduced pressure. The resulting yellow product 9 was
used without further purification. Yield: 456 mg (quant.), m.p.
76Ϫ77 °C; Rf ϭ 0.67 (ethyl acetate/methanol, 67:33, v/v). 1H NMR
(200 MHz, CDCl3; 25 °C): δ ϭ 7.30 (br. s, 1 H, NH), 6.16 (s, 1 H,
4-H thienyl), 5.02 (br. s, 1 H, NH), 3.42Ϫ3.54 (m, 2 H, CH2),
NMR (400 MHz, CDCl3, 25 °C): δ ϭ 7.25Ϫ7.33 (m, 4 H, Ar-H),
3
6.54 (s, 1 H, 4-H thienyl), 4.79 (br. s, 1 H, NH), 4.28 (d, JH,H
ϭ
5.5 Hz, 2 H, CH2-Ar), 2.46 (s, 3 H, CH3), 2.39 (s, 3 H, CH3), 2.32
(s, 3 H, CH3), 2.10 (s, 3 H, CH3), 2.01 (s, 3 H, CH3), 1.44 (s, 9 H,
tBu) ppm. 13C NMR (50.3 MHz, CDCl3, 25 °C): δ ϭ 167.3, 164.6,
155.6, 148.7, 142.2, 138.5, 137.5, 135.1, 135.3, 131.0, 128.8, 127.7,
127.5, 127.0, 125.0, 124.7, 123.7, 79.4, 44.2, 28.2, 26.9, 15.2, 14.1
ppm. IR (ATR): ν˜ ϭ 3376, 2977, 2918, 1755, 1707, 1632, 1599,
1514, 1437, 1366, 1251, 1165 cmϪ1. MS (70 eV, EI): m/z (%) ϭ 480
(18) [Mϩ], 424 (30), 409 (100). HR MS (70 eV, EI): calcd. 480.2083,
found 480.2088. C27H32N2O4S (480.2): calcd. C 67.47, H 6.71, N
5.83; found C 67.18, H 6.87, N 5.55.
3
3.30Ϫ3.42 (m, 2 H, CH2), 3.15 (sept, JH,H ϭ 6.4 Hz, 1 H,
CHMe2), 2.33 (s, 3 H, CH3), 2.16 (s, 3 H, CH3), 1.89 (s, 3 H, CH3),
1.84 (s, 3 H, CH3), 1.44 (s, 9 H, tBu), 1.00 (br. s, 6 H, CH(CH3)2]
ppm. 13C NMR (50.3 MHz, CDCl3, 25 °C): δ ϭ 170.9, 170.0,
156.8, 149.8, 148.8, 135.0, 133.3, 132.6, 131.2, 125.8, 124.7, 79.6,
40.5, 32.6, 28.2, 24.1, 22.8, 22.1, 21.4, 14.9, 14.1 ppm. IR (ATR):
ν˜ ϭ 3344, 2972, 2931, 2871, 1697, 1640, 1586, 1521, 1449, 1365,
1251, 1172 cmϪ1. MS (70 eV, EI): m/z (%) ϭ 464 (50) [Mϩ]. HR MS
(70 eV, EI): calcd. 464.2345, found 464.2345 (for C24H36N2O5S).
(E)-7: A solution of (Z)-7 (858 mg, 1.79 mmol) in degassed toluene
10: A mixture of 9 (425 mg, 0.92 mmol) and phenacyl bromide
(50 mL) was irradiated with 365-nm light [high-pressure mercury
(230 mg, 1.16 mmol) was dissolved in ethyl acetate (30 mL) and
lamp 200 HBO (Osram, München), 365-nm interference filter triethylamine (0.28 mL, 2.04 mmol) was added dropwise. After a
(Amko, Tornesch)] for 13.5 h (TLC monitoring). The resulting red
solution was exposed to daylight. After 4 h, the solution was light
orange. The solvent was evaporated in vacuo and the resulting mix-
ture of isomers was separated by flash chromatography on silica
gel with light petroleum ether/ethyl acetate (80:20, v/v) as eluent to
give (E)-7. Yield: 485 mg (57%), besides 243 mg (28%) of an (E)/
few minutes, a colorless precipitate was formed and the solution
turned orange. The mixture was stirred for 24 h and water (20 mL)
was added. The aqueous layer was extracted with ethyl acetate (2
ϫ 15 mL). The combined organic layers were washed with water
(20 mL), 0.5  KHCO3 solution (20 mL), and water (20 mL), dried
(MgSO4), and concentrated in vacuo. The product 10 was used
(Z) mixture, ratio (E)/(Z) ϭ 30:70; Rf ϭ 0.60 (light petroleum ether/ without further purification. Yield: 550 mg (94%); m.p. 54 °C; Rf ϭ
1
ethyl acetate, 67:33, v/v). H NMR (200 MHz, CDCl3, 25 °C): δ ϭ
6.49 (s, 1 H, 4-H thienyl), 4.93 (br. s, 1 H, NH), 3.71Ϫ3.77 (m, 2 H, (200 MHz, CDCl3, 25 °C): δ ϭ 7.92Ϫ8.02 (m, 2 H, Ar-H),
CH2), 3.35Ϫ3.38 (m, 2 H, CH2), 2.58 (s, 3 H, CH3), 2.38 (s, 3 H, 7.45Ϫ7.75 (m, 4 H, Ar-H, NH), 6.10 (s, 1 H, 4-H thienyl), 5.32 (br.
0.21 (light petroleum ether/ethyl acetate, 67:33, v/v). 1H NMR
CH3), 2.26 (s, 3 H, CH3), 2.10 (s, 3 H, CH3), 1.40 (s, 9 H, tBu), s, 2 H, CH2), 3.45Ϫ3.58 (m, 2 H, CH2), 3.30Ϫ3.42 (m, 2 H, CH2),
1.21 (s, 3 H, CH3) ppm. 13C NMR (50.3 MHz, CDCl3, 25 °C): δ ϭ 3.22 (m, 3JH,H ϭ 6.8 Hz, 1 H, CHMe2), 2.34 (s, 3 H, CH3), 2.10 (s,
168.8, 168.2, 155.7, 149.0, 143.4, 140.2, 136.7, 133.5, 125.5, 123.9,
122.9, 79.0, 39.5, 37.3, 28.2, 25.2, 21.8 (2 C), 14.9, 14.5 ppm. IR 0.98 [br. s, 6 H, CH(CH3)2] ppm. 13C NMR (100.6 MHz, CDCl3,
(ATR): ν˜ ϭ 3388, 2978, 2936, 1745, 1693, 1516, 1433, 1391, 1366, 25 °C): δ ϭ 193.2, 170.2, 165.1, 155.9, 153.4, 147.1, 134.8, 134.3,
1174 cmϪ1. MS (70 eV, EI): m/z (%) ϭ 418 (22) [Mϩ], 347 (100). 133.7, 133.2, 132.4, 128.9, 127.7, 125.8, 123.4, 78.8, 65.4, 41.3, 39.0,
3 H, CH3), 2.05 (s, 3 H, CH3), 2.01 (s, 3 H, CH3), 1.39 (s, 9 H, tBu),
Eur. J. Org. Chem. 2003, 2409Ϫ2417
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B. Otto, K. Rück-Braun
FULL PAPER
32.5, 28.3, 24.9, 22.2, 21.2, 15.0, 14.0 (one quaternary carbon signal
3
CDCl3, 25 °C): δ ϭ 6.50 (s, 1 H, 4-H thienyl), 3.56 (t, JH,H
ϭ
in the aromatic region is overlapped by adjacent signals) ppm. IR 6.1 Hz, 2 H, CH2), 2.85 (t, 3JH,H ϭ 6.1 Hz, 2 H, CH2), 2.41 (s, 3 H,
(ATR): ν˜ ϭ 3359, 2967, 2933, 1695, 1650, 1518, 1451, 1367, 1246,
1202, 1174 cmϪ1. MS (70 eV, EI): m/z (%) ϭ 582 (10) [Mϩ], 463 1.94 (s, 3 H, CH3) 1.76 (br. s, 2 H, NH2) ppm. 13C NMR
(60), 329 (100). HR MS (70 eV, EI): calcd. 582.2764, found (50.3 MHz, CDCl3, 25 °C): δ ϭ 168.7, 166.1, 147.8, 141.3, 137.1,
CH3), 2.39 (s, 3 H, CH3), 2.32 (s, 3 H, CH3), 2.03 (s, 3 H, CH3),
582.2767. C32H42N2O6S (582.8): calcd. C 65.95, H 7.26, N 4.81; 136.4, 135.5, 125.5, 124.9, 124.0, 40.9, 40.6, 26.9, 26.2, 21.7, 15.2,
found C 65.66, H 7.25, N 4.43.
14.1 ppm. MS (70 eV, EI): m/z (%) ϭ 318 (100) [Mϩ], 303 (40)
[Mϩ Ϫ CH3]. HR MS (70 eV, EI): calcd. 318.1402, found 318.1410
(for C17H22N2O2S).
(E)-11: A solution of tert-butyllithium (1.7  in pentane, 0.32 mL,
0.548 mmol) was added to a solution of 10 (133 mg, 0.23 mmol) in
THF (10 mL) at Ϫ78 °C. The mixture was stirred for 6.5 h and
brine (15 mL) was added. The aqueous layer was extracted with
diethyl ether (2 ϫ 10 mL) and the combined organic layers were
dried (MgSO4) and concentrated in vacuo. The crude product was
then purified by flash chromatography on silica gel with light petro-
leum ether/ethyl acetate (83:17 Ǟ 75:25, v/v) as eluent to give 11
as an orange solid. Yield: 41 mg (40%); m.p. 41 °C; Rf ϭ 0.80 (light
petroleum ether/ethyl acetate, 67:33, v/v). 1H NMR (200 MHz,
CDCl3, 25 °C): δ ϭ 6.55 (s, 1 H, 4-H thienyl), 4.89 (br. s, 1 H, NH),
X-ray Crystallographic Analysis of (Z)-7:[25] Suitable single crystals
of (Z)-7 (yellow prisms) were obtained by careful addition of a
layer of pentane to a concentrated solution (Z)-7 of in dichloro-
methane. After the two-phase system had been allowed to stand
unperturbed for some days in the dark at room temperature, suit-
able crystals had formed at the boundary between the two solvent
layers. C22H30N2O4S with Mr ϭ 418.54 g/mol; crystal size: 0.60 ϫ
0.32 ϫ 0.18 mm; orthorhombic crystal system with space group
Pna21 and Z ϭ 4, a ϭ 2139.16(6), b ϭ 1185.47(4), c ϭ 899.04(2)
pm; V ϭ 2.27988(11) nm3, ρcalcd. ϭ 1.219 Mg·mϪ3; F(000) ϭ 896;
linear absorption coefficient µ ϭ 0.171 mmϪ1; type of dif-
fractometer: Siemens SMART CCD; T ϭ 293(2) K; Mo-Kα radi-
ation; scan type: ω-scans; θ range 1.90Ϫ24.99°; index ranges Ϫ25
Յ h Յ 20, Ϫ14 Յ k Յ 14, Ϫ10 Յ l Յ 10; reflections collected
13546; independent reflections 3964 (Rint ϭ 0.0946); observed re-
flections 2029 [I Ͼ 2σ(I)], reflection used for refinement 3964;
Flack parameter (absolute structure) ϭ 0.18(17); program system
used: SHELXS-97, SHELXL-97 and SHELXTL; empirical ab-
sorption correction, direct methods, full-matrix refinement at F2
with all independent reflection, weighting scheme SHELXL; good-
ness-of-fit parameter (based on F2) S ϭ 0.670; residual densities
∆ρmax and ∆ρmin. ϭ 134 and Ϫ172 e ϫ nmϪ3. Hydrogen atoms:
refined with riding model, refined with a temperature factor 1.5
times Ueq of the carbon atoms; non-hydrogen atoms: refined aniso-
tropically. Data/restraints/parameters: 3964/1/275; R index (all
data): wR2 (based on F2) ϭ 0.1646; R index (conventional)
[I Ͼ 2σ(I)]: R1 (based on F) ϭ 0.0518.
3
4.39 (sept, JH,H ϭ 6.8 Hz, 1 H, CHMe2), 3.60Ϫ3.85 (m, 2 H,
CH2), 3.33Ϫ3.45 (m, 2 H, CH2), 2.41 (s, 3 H, CH3), 2.34 (s, 3 H,
CH3), 1.96 (s, 3 H, CH3), 1.40 (s, 9 H, tBu), 1.33 [d, 3JH,H ϭ 6.8 Hz,
3
3 H, CH(CH3)2], 1.24 (s, 3 H, CH3), 0.76 [d, JH,H ϭ 6.8 Hz, 3 H,
CH(CH3)2] ppm. 13C NMR (50.3 MHz, CDCl3, 25 °C): δ ϭ 168.4,
155.8, 154.3, 148.8, 136.1, 135.6, 133.3, 125.3, 124.7, 123.1, 79.2,
37.3, 30.2, 29.7, 28.3, 26.0, 23.2, 21.7, 20.4, 15.2, 14.1 ppm (one
quaternary carbon signal in the aromatic region is overlapped by
adjacent signals). IR (ATR): ν˜ ϭ 3385, 2917, 1745, 1693, 1513,
1434, 1390, 1365, 1248, 1174 cmϪ1. MS (70 eV, EI): m/z (%) ϭ 446
(10) [Mϩ], 390 (20), 346 (70). HR MS (70 eV, EI): calcd. 446.2239,
found 446.2241 (for C24H34N2O4S).
(Z)-12: HCl in dioxane (4 , 5 mL) was added to fulgimide (Z)-8
(32 mg, 0.067 mmol) at 0 °C. The mixture was stirred for 40 min
and then the solution was allowed to warm to room temperature.
After additional 50 min, the crude product was isolated by lyo-
philization to give a yellow solid (40 mg); (E)/(Z) isomerization of
the crude product was observed by 1H NMR spectroscopy [ratio
(Z)/(E) ϭ 91:9]. The crude product was purified by preparative
HPLC (Luna C18, 50 cm ϫ 4.6 cm, acetonitrile/water, 50:50, v/v ϩ
0.1% TFA). The presence of TFA in the eluent proved to be neces-
sary for chromatography of the free amine, and because of (E)/(Z)
isomerization the product was isolated as a mixture of isomers.
Yield: 25 mg [89%, ratio (Z)/(E) ϭ 88:12]. 1H NMR (200 MHz,
CDCl3, 25 °C): (Z) isomer: δ ϭ 7.14Ϫ8.10 (m, 7 H, Ar-H, NH3),
6.54 (s, 1 H, 4-H thienyl), 3.82Ϫ4.00 (m, 2 H, CH2), 2.44 (s, 3 H,
CH3), 2.34 (s, 3 H, CH3), 2.30 (s, 3 H, CH3), 2.13 (s, 3 H, CH3),
2.05 (s, 3 H, CH3) ppm; (E) isomer: δ ϭ 7.14Ϫ8.10 (m, 7 H, Ar-H,
NH3), 6.54 (s, 1 H, 4-H thienyl), 3.82Ϫ4.00 (m, 2 H, CH2), 2.59 (s,
3 H, CH3), 2.41 (s, 3 H, CH3), 2.27 (s, 3 H, CH3), 2.18 (s, 3 H,
CH3), 2.02 (s, 3 H, CH3) ppm. 13C NMR (50.3 MHz, CDCl3, 25
°C): δ ϭ 167.5, 165.5, 151.4, 144.5, 137.9, 136.1, 135.7, 132.5,
132.0, 130.1, 127.8, 124.7, 124.2, 122.8, 43.5, 27.1, 26.3, 21.8, 14.8,
13.9 ppm. IR (ATR): ν˜ ϭ 3420, 2960, 2923, 1751, 1700, 1518, 1437,
1374, 1207, 1135 cmϪ1. MS (70 eV, EI): m/z (%) ϭ 380 (46) [Mϩ
Ϫ HCl], 365 (100) [Mϩ Ϫ HCl Ϫ CH3]. HR MS (70 eV, EI): calcd.
380.1559 [Mϩ Ϫ HCl], found 380.1559.
Acknowledgments
Support of this work by the Volkswagen Stiftung and by the Fonds
der Chemischen Industrie is gratefully acknowledged. We thank
Prof. Dr.-Ing. J. Pickardt, TU Berlin, for the X-ray structural analy-
sis and Prof. Dr. H. Meier, University of Mainz, for the use of the
MCS 320/340 Diodenarray spectrometer from Zeiss. We also thank
Prof. Dr. A. G. Woolley, University of Toronto, and S. Dietrich,
TU Berlin, for useful discussions.
[1]
I. Willner, S. Rubin, Angew. Chem. 1996, 108, 419Ϫ439; Angew.
Chem. Int. Ed. Engl. 1996, 35, 367Ϫ385.
[2]
N. Tamai, H. Miyasaka, Chem. Rev. 2000, 100, 1875Ϫ1890.
[3]
Y. Yo koya m a , Chem. Rev. 2000, 100, 1717Ϫ1739.
[4]
M.-G Fan, L. Yu, W. Zhao, in Organic Photochromic and Ther-
mochromic Compounds, vol. 1 (Eds.: J. C. Crano, R. Gugliel-
metti), Plenum Press, New York, 1999, pp. 141Ϫ206.
[5] [5a]
H. G. Heller, in CRC Handbook of Organic Photochemistry
and Photobiology (Eds.: W. M. Horspool, P.-S. Song), CRC,
(Z)-13: Trifluoroacetic acid (3 mL) was added dropwise to a solu-
tion of (Z)-7 (307 mg, 0.73 mmol) in CH2Cl2 (57 mL). After 2 h,
the reaction mixture was washed with aqueous ammonia (5%,
45 mL). The aqueous layer was extracted with CH2Cl2 (2 ϫ 30 mL)
and the organic layers were dried (MgSO4) and concentrated in
vacuo to give (Z)-13 as a yellow solid. Yield: 204 mg (87%); Rf ϭ
0.11 (ethyl acetate/methanol, 67:33, v/v). 1H NMR (200 MHz,
[5b]
Boca Raton, FL, USA 1995, vol. 13, pp. 174Ϫ183.
H. G.
Heller, K. Koh, C. Elliot, J. Whittall, Mol. Cryst. Liq. Cryst.
1994, 246, 79Ϫ86.
[6] [6a]
C. J. Thomas, M. A. Wolak, R. R. Birge, W. J. Lees, J. Org.
Chem. 2001, 66, 1914Ϫ1918. [6b] M. A. Wolak, N. B. Gillespie,
C. J. Thomas, R. R. Birge, W. J. Lees, J. Photochem. Photobiol.
A: Chem. 2002, 147, 39Ϫ44 and references cited therein.
2416
 2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
Eur. J. Org. Chem. 2003, 2409Ϫ2417

Syntheses and UV/Vis Properties of Amino-Functionalized Fulgimides
FULL PAPER
P. M. Rentzepis, Tetrahedron Lett. 1999, 40, 8067Ϫ8069.
Y. Liang, A. S. Dvornikov, P. M. Rentzepis, J. Mater. Chem.
2000, 10, 2477Ϫ2482.
A. P. Glaze, S. A. Harris, H. G. Heller, W. Johncock, S. N.
Oliver, P. J. Strydom, J. Whittall, J. Chem. Soc., Perkin Trans.
1 1985, 957Ϫ961.
K. Ulrich, H. Port, H. C. Wolf, J. Wonner, F. Effenberger, H.-
D. Ilge, Chem. Phys. 1991, 154, 311Ϫ322.
H. Stobbe, Ber. Dtsch. Chem. Ges. 1893, 26, 2312Ϫ2319.
M. Bodanszky, Principles of Peptide Synthesis, 2nd. ed.,
Springer-Verlag, Berlin, 1993.
T. W. Greene, P. G. M. Wuts, Protective Groups in Organic Syn-
thesis, 3rd. ed., Wiley-Interscience, New York, 1999.
M. Kaftory, Acta Crystallogr., Sect. C 1984, 40, 1015Ϫ1019.
Y. Yoshioka, M. Irie, Electron. J. Theor. Chem. 1996, 1,
183Ϫ190.
CCDC-198518 [(Z)-7] contains the supplementary crystallo-
graphic data for this paper. These data can be obtained free of
charge at www.ccdc.cam.ac.uk/conts/retrieving.html [or from
the Cambridge Crystallographic Data Center, 12 Union Road,
Cambridge CB2 1EZ, UK; Fax: (internat.) ϩ 44-1223/336-033;
E-mail: deposit@ccdc.cam.ac.uk].
[7]
[17c]
I. Willner, S. Rubin, J. Wonner, F. Effenberger, P. Bäuerle, J.
Am. Chem. Soc. 1992, 114, 3150Ϫ3151.
I. Willner, M. Lion-Dagan, S. Rubin, J. Wonner, F. Effenberger,
[8]
[18]
P. B äuerle, Photochem. Photobiol. 1994, 59, 491Ϫ496.
[9]
[9a] R. Matsushima, H. Sakaguchi, J. Photochem. Photobiol. A:
[9b]
Chem. 1997, 108, 239Ϫ245 and references cited therein.
R.
[19]
Matsushima, M. Nishiyama, M. Doi, J. Photochem. Photobiol.
A: Chem. 2001, 139, 63Ϫ69.
[20]
[21]
[10] [10a] Y. Yokoyama, T. Goto, T. Inoue, M. Yokoyama, Y. Kurita,
Chem. Lett. 1988, 1049Ϫ1052. [10b] Y. Yokoyama, T. Inoue, M.
Yokoyama, T. Goto, T. Iwai, N. Kera, I. Hitomi, Y. Kurita,
[10c]
[22]
Bull. Chem. Soc. Jpn. 1994, 67, 3297Ϫ3303.
J. Kiji, T. Ok-
ano, H. Kitamura, Y. Yokoyama, S. Kubota, Y. Kurita, Bull.
Chem. Soc. Jpn. 1995, 68, 616Ϫ619. [10d] S. Uchida, S. Yamada,
Y. Yokoyama, Y. Kurita, Bull. Chem. Soc. Jpn. 1995, 68,
1677Ϫ1682.
[23]
[24]
[11]
[25]
A. P. Glaze, H. G. Heller, J. Whittall, J. Chem. Soc., Perkin
Trans. 2 1992, 591Ϫ594.
[12] [12a]
H. G. Heller, R. M. Megit, J. Chem. Soc., Perkin Trans. 1
[12b]
1974, 923Ϫ927.
P. J. Darcy, H. G. Heller, S. Patharakorn,
R. D. Piggott, J. Whittall, J. Chem. Soc., Perkin Trans. 1
1986, 315Ϫ319.
S. Goldschmidt, R. Riedle, A. Reichardt, Justus Liebigs Ann.
Chem. 1957, 604, 121Ϫ132.
V. Deblauwe, G. Smets, Makromol. Chem. 1988, 189,
2503Ϫ2512.
[13]
[14]
[15]
[16]
[26]
[27]
[28]
[29]
P. Helquist, K. A. M. Kremer, Organometallics 1984, 3,
1743Ϫ1745.
D. D. Perrin, W. L. F. Armarego, Purification of Laboratory
Chemicals, 3rd. ed., Pergamon Press, Oxford, 1988.
D. M. Kneeland, K. Ariga, V. M. Lynch, C. Y. Huang, E. V.
Anslyn, J. Am. Chem. Soc. 1993, 115, 10042Ϫ10055.
G. P. Moloney, G. R. Martin, N. Mathews, A. Milne, H.
Hobbs, S. Dodsworth, P. Y. Sang, C. Knight, M. Williams, M.
Maxwell, R. C. Glen, J. Med. Chem. 1999, 42, 2504Ϫ2526.
Received December 12, 2002
I. Cabrera, A. Dittrich, H. Ringsdorf, Angew. Chem. 1991, 103,
106Ϫ108; Angew. Chem. Int. Ed. Engl. 1991, 30, 76Ϫ78.
T. Okumyama, Y. Yokoyama, Y. Yokoyama, Bull. Chem. Soc.
Jpn. 2001, 74, 2181Ϫ2187.
[17] [17a]
Y. C. Liang, A. S. Dvornikov, P. M. Rentzepis, Res. Chem.
[17b]
Intermed. 1998, 25, 905Ϫ914.
Y. Liang, A. S. Dvornikov,
Eur. J. Org. Chem. 2003, 2409Ϫ2417
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 2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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