Diaminoterephthalates: Scaffolds for combinatorial chemistry

Article abstract of DOI:10.1002/chem.200802151

2,5-Diaminoterephthalates that possess four points of diversification are introduced as new scaffolds for combinatorial chemistry. A straightforward synthesis of an orthogonally protected platform compound was developed. This platform was transformed by s

Full text of DOI:10.1002/chem.200802151

DOI: 10.1002/chem.200802151
Diaminoterephthalates: Scaffolds for Combinatorial Chemistry
Rebekka Pflantz and Jens Christoffers*[a]
In memory of Professor Peter Kçll
Abstract: 2,5-Diaminoterephthalates that possess four points of diversification are
introduced as new scaffolds for combinatorial chemistry. A straightforward synthe-
Keywords: amino acids · carbox-
amides · combinatorial chemistry ·
fluorescence · terephthalates
sis of an orthogonally protected platform compound was developed. This platform
was transformed by stepwise deprotection and amidation of the two amino and
two carboxylic acid moieties into tetra-amides with a central aromatic ring as a
fluorescence chromophore.
AHCTUNGTRENNUNG
Introduction
2,5-Diaminoterephthalates are intensively colored fluores-
cent materials that are easily prepared by the enamine for-
mation of succinyl succinates with primary amines followed
by oxidative aromatization.[1] When anilines are used as
amines, this reaction is a key step in the industrial synthesis
of quinacridone pigments.[2] We recently prepared symmetric
(D2h) diaminoterephthalates 1 with two biphenyl, terphenyl,
or quaterphenyl moieties as new fluorescent materials
(Scheme 1).[3] In an extension of this study, we report the de-
velopment of compounds 2 as colored and fluorescent scaf-
folds with four different effector groups R1–R4. Fluores-
cence is an interesting feature in high-throughput synthesis
and biological essays. In particular, we aim to access tetra-
amides 2 derived from two carboxylic acids R1CO2H and
R3CO2H and two amines R2NH2 and R4NH2. A precondi-
tion for this project would be the availability of an orthogo-
nally protected (PG1–PG3) platform, that is, compound 3,
which might be prepared from mixed succinyl succinate 4.
Scheme 1. Synthetic plan for 2,5-diaminoterephthalate derivatives 2.
PG=protecting group.
Results and Discussion
Succinyl succinates 4 are prepared by the Dieckmann con-
densation of succinates; however, only cases with two equal
ester groups have been reported so far.[4] Herein, benzyl and
methyl ester were chosen as carboxylate protective groups
PG1 and PG3. Mixed ester 6 was prepared in almost quanti-
tative yield by the methylation of mono-benzyl succinate 5
(Scheme 2). The preparation of compound 6 by a conjugate
addition reaction has been reported previously.[5] The inter-
and intramolecular Claisen condensation of mixed ester 6
gave a mixture of benzyl methyl succinyl succinates 4a–c,
which were separated by crystallization followed by column
chromatography. Acidification of the reaction mixture
[a] R. Pflantz, Prof. Dr. J. Christoffers
Institut fꢀr Reine und Angewandte Chemie
Carl von Ossietzky Universitꢁt Oldenburg
26111 Oldenburg (Germany)
Fax : (+49)441-798-3873
E-mail: jens.christoffers@uni-oldenburg.de
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/chem.200802151.
2200
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Chem. Eur. J. 2009, 15, 2200 – 2209

FULL PAPER
Scheme 2. Synthesis of succinyl succinates 4a–c. a) MeI, Na2CO3, DMF,
4 h, 238C; b) 1. NaH, DMSO, 0.5 h, 08C; 3 h, 238C; 2. HCl, H2O; 3. re-
crystallization; 4. isolation by column chromatography. DMSO=dimethyl
sulfoxide.
during the workup must be carried out with cooling and
careful control of the temperature. If the temperature raises
significantly over 238C, the esters oxidize with air to give
hydroquinone dicarboxylates. Symmetric esters 4b and 4c
are known compounds,[4] mixed ester 4a was obtained in
moderate yield (36%), though multigram amounts were ob-
tained.
Oxidative aminolysis of diester 4a was performed with an
ethanolic solution of NH3. Saponification or transesterifica-
tion was not observed. The transformation has to be per-
formed in the following manner: The bis-enamine was
formed readily within one hour at 608C. The mixture was
buffered by the addition of HCl, and oxidation proceeded
slowly at 608C. If the reaction is performed with a buffered
system from the beginning, enamine formation is slow rela-
tive to oxidation and hydroquinone dicarboxylates and ami-
nophenol dicarboxylates are formed as hardly separable by-
products. A solution of NH3 in EtOH (ca. 15 moldmÀ3 by ti-
tration) was prepared by storing a beaker of EtOH and a
large amount of a 25% aqueous NH3 in a desiccator for two
days. After chromatography, diamino terephthalate 7 was
obtained in good yield (Scheme 3). The conversion of dia-
mine 7 with one equivalent of Boc2O in dichloromethane
gave regioisomeric carbamates 3a and 3b, which were sepa-
rable by column chromatography. Only the major isomer 3a
was used in further studies. The other regioisomer 3b was
collected and deprotected with TFA to recycle diamine 7.
We planned to prove the constitution of major isomer 3a
(or by-product 3b) by using X-ray single-crystal studies. To
obtain crystalline materials, we prepared bromobenzene sul-
fonamides 8a and 8b, which did not, however, give suitable
crystals. Therefore, we deprotected carbamates 8a and 8b,
and, indeed, anilines 9a and 9b gave suitable single crystals.
An ORTEP representation of the molecular structure of 9a
in the solid state is given in Figure 1.[6]
Scheme 3. Synthesis of platform 3a from succinyl succinate 4a. a) 1. NH3,
EtOH, 1 h, 608C, then addition of HCl, air, 3 d, 608C; b) Boc2O
(1.0 equiv), dichloromethane, 16 h, 238C; c) TFA, dichloromethane, 16 h,
238C; d) 4-BrC6H4SO2Cl, pyridine, cat. DMAP, dichloromethane, 16 h,
238C. DMAP=4-dimethylaminopyridine, TFA=trifluoroacetic acid.
Figure 1. ORTEP view of 9a in the solid state.
tion was performed with N-Boc-b-Ala (product: 12a in 75%
yield). Catalytic hydrogenolysis gave free carboxylic acid
13a (94% yield), which was amidated with b-Ala tert-butyl
ester (b-Ala-OtBu; product 14a in 94% yield). The amida-
tion of aromatic carboxylic acids, such as 13 and 15, required
(as well as DCC/HOBt) the addition of catalytic amounts of
DMAP to give satisfactory yields. The second last transfor-
mation was saponification of the methyl ester in compound
14. The conversion with K2CO3 in EtOH/H2O proceeded
very well within 2–4 hours at 508C; however, the workup
As the first explorative example of a final tetracarbox-
ACHTUNGTRENNUNGamide 2, we prepared 2a with four b-alanine (b-Ala) moiet-
ies bound to the central aromatic fluorescent scaffold
(Scheme 4). The amidation of the aromatic NH2 groups with
N-protected amino acids proceeded with DCC/HOBt at ele-
vated temperature. The conversion of the platform com-
pound 3a with N-Fmoc-b-Ala gave amide 10a in 82% yield
(Scheme 5, Table 1, series a). After the deprotection of the
Boc group (product: 11a in 98% yield), the second amida-
Chem. Eur. J. 2009, 15, 2200 – 2209
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J. Christoffers and R. Pflantz
protocol turned out to be the
crucial part of this step because
acids 15 are already very solu-
ble in H2O. Finally, the fourth
amidation with b-Ala-OtBu
gave 2a in 93% yield. In sum-
mary, the final product 2a was
obtained from platform com-
pound 3a in seven steps and
35% overall yield.
Scheme 4. Final compounds 2a and 2b. Fmoc=9-fluorenylmethoxycarbonyl.
In the second series (Table 1,
series b), we changed the acids
and amines for the amidation, but kept the order of the de-
protecting transformations the same (Scheme 5). The cou-
pling partners in their synthetic order were: N-Fmoc-l-Pro
(Pro=proline), N-Boc-l-Val (Val=valine), benzylamine
(BnNH2), and l-neopentylglycine methyl ester (l-Npg-
OMe). The final compound 2b was obtained in lower over-
all yield (11%). Most products in this series (with optically
active amino acid derivatives) show a doubled signal set in
the NMR spectra in CDCl3 at 238C. A single signal set was
obtained (which was shown for 14b) at 808C in [D6]DMSO.
Therefore, we assume hindered rotation along the aniline
2
À
sp -C N bond that results in atropisomerism (axial chirali-
ty), thus leading to diastereoisomeric conformers and a dou-
bled signal set at 238C.
For the third series (Scheme 6), we changed the coupling
partners and the sequence of the deprotecting operations to
introduce the most challenging residue (biotin) as the last
step. Moreover, sulfur compounds might influence the cata-
lytic activity during hydrogenolytic debenzylation. First, the
amidation was carried out using N-Fmoc-l-Npg from the
platform compound 3a (product: 10c in 59% yield). After
catalytic hydrogenolytic debenzylation (product: 16 in 98%
yield), the acid was coupled with 4-MeOC6H4CH2NH2
(PMB-NH2) (product: 17 in 61% yield). Methyl aminoiso-
butyrate (Aib-OMe) was introduced (product: 19 in 53%
yield) after methyl ester saponification (product: 18 in 70%
yield). Finally, the Boc group was cleaved (product: 20 in
95% yield) and the scaffold was coupled with (+)-biotin to
give the final compound 2c (34%). The overall yield in this
series was 4%.
Scheme 5. Synthesis of final compounds 2a and 2b (see Table 1 for the
yields and residues R1–R4). a) R3CO2H or R1CO2H, DCC, HOBt, di-
chloromethane, 2 d, 808C; b) TFA, dichloromethane, 16 h, 238C; c) cat.
Pd/C, H2, ethyl acetate, 16 h, 238C; d) R4NH2 or R2NH2, DCC, HOBt,
cat. DMAP, dichloromethane, 2 d, 808C; e) K2CO3, H2O, EtOH, 2–4 h,
508C.
Boc=tert-butoxycarbonyl,
DCC=dicyclohexylcarbodiimide,
HOBt=hydroxybenzotriazole.
Finally, UV/vis and fluorescence spectra were recorded of
the three final compounds 2a–c. All the spectra showed, of
course, a strong absorption at l=230–250 nm caused by the
Fmoc groups. In addition, a weaker band was observed at
l=330–350 nm (Table 2). Upon irradiation of this band,
strong fluorescence was observed in the visible region at l=
410–450 nm.
Table 1. Yields for the preparation of 2a and 2b from 3a.
Series a Series b
Product Yield [%] Coupling Product Yield [%]
Coupling
partner
or deprotec-
tion reagent
partner
or deprotec-
tion reagent
N-Fmoc-b-
Ala
TFA
N-Boc-b-Ala 12a
H2/Pd
b-Ala-OtBu
K2CO3
b-Ala-OtBu
10a
11a
82
N-Fmoc-l-
Pro
TFA
N-Boc-l-Val
H2/Pd
BnNH2
K2CO3
10b
78
Conclusion
98
75
94
94
70
93
11b
12b
13b
14b
15b
2b
90
90
94
64
75
37
The fluorescence of single compounds is an interesting fea-
ture for high-throughput synthesis and screening. 2,5-Diami-
noterephthalates are intensively colored, fluorescent materi-
als. We have developed a combinatorial-like synthesis of tet-
13a
14a
15a
2a
l-Npg-OMe
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Chem. Eur. J. 2009, 15, 2200 – 2209

Diaminoterephthalates as Fluorescent Materials
FULL PAPER
Experimental Section
General methods: Preparative column chromatography was carried out
using Merck SiO2 (0.035–0.070 mm, type 60 A) with petroleum ether
(PE; b.p. 40–608C) and ethyl acetate (EA) as eluents. TLC was per-
formed on Merck SiO2 F254 plates on aluminum sheets. 1H and 13C NMR
spectra were recorded on Bruker Avance DRX 500 and Avance DPX
300 spectrometers in CDCl3 at 238C with trimethylsilane (TMS) as the
internal standard, if not otherwise stated. Multiplicities were determined
with DEPT experiments. EI-MS, CI-MS, and HRMS spectra were ob-
tained with a Finnigan MAT 95 spectrometer, ESI-MS (HRMS) spectra
with a Waters Q-TOF Premier. A Thermo system equipped with AS 3000
autosampler and Finnigan MAT ESI-MS was used for LC–MS. IR spec-
tra were recorded on a Bruker Tensor 27 spectrometer equipped with a
“GoldenGate” diamond-ATR unit. Elemental analyses were measured
with a Euro EA-CHNS from HEKAtech. UV and fluorescence spectra
were recorded with a Perkin Elmer LS 50 spectrometer. Monobenzyl suc-
cinate 5[7] and the following amino acid derivatives were prepared ac-
cording to reported protocols: N-Fmoc-b-Ala,[8] N-Fmoc-l-Pro,[9] N-
Fmoc-l-Npg,[10] N-Boc-b-Ala,[11] N-Boc-l-Val,[12] b-Ala-OtBu,[13] l-Npg-
OMe,[14] and Aib–OMe.[15] All other starting materials were commercially
available. Spectroscopic and analytical data of 4b and 4c have been re-
ported previously.[4b]
Benzyl methyl succinate (6): MeI (9.40 mL, 21.3 g, 150 mmol, 1.1 equiv)
and Na2CO3 (19.0 g, 136 mmol, 1.0 equiv) were added to a solution of
mono-ester 5 (28.29 g, 136.0 mmol) in DMF (200 mL). The resulting mix-
ture was stirred for 4 h at 238C, diluted with ethyl acetate (100 mL), and
washed with H2O (3ꢃ200 mL). The organic layer was dried (MgSO4) and
filtered, and the solvent evaporated to give di-ester
6 (30.48 g,
133.0 mmol, 97%; >98% purity by GC) as a yellow oil, which was used
without further purification. 1H NMR (CDCl3, 500 MHz): d=2.64–2.68
(m, 4H), 3.66 (s, 3H), 5.13 (s, 2H), 7.31–7.37 ppm (m, 5H);
13C{1H} NMR (CDCl3, 125 MHz): d=28.78 (CH2), 29.05 (CH2), 51.68
(CH3), 66.39 (CH2), 128.07 (2 CH), 128.13 (CH), 128.42 (2 CH), 135.69
(C), 171.94 (C), 172.52 ppm (C); IR (ATR): n˜ =3035 (w), 2954 (m), 1733
(vs), 1678 (s), 1439 (m), 1354 (m), 1213 (s), 1153 (vs), 997 (s), 847 (m),
700 cmÀ1 (vs); MS (EI, 70 eV): m/z (%): 222 (8) [M+], 194 (15), 115 (82),
107 (50), 91 (100); HRMS (EI, 70 eV): m/z: calcd for C12H14O4:
222.0892; found: 222.0891 [M+]; elemental analysis calcd for C12H14O4
(222.24): C 64.85, H 6.35; found: C 64.30, H 6.41.
Scheme 6. Synthesis and constitution of final compound 2c. a) N-Fmoc-l-
Npg, DCC, HOBt, dichloromethane, 2 d, 808C (59%); b) cat. Pd/C, H2,
ethyl acetate, 16 h, 238C (98%); c) PMB–NH2, DCC, HOBt, cat. DMAP,
dichloromethane, 2 d, 808C (61%); d) K2CO3, H2O, EtOH, 2–4 h, 508C,
70%; e) Aib–OMe, DCC, HOBt, cat. DMAP, dichloromethane, 2 d,
808C (53%); f) TFA, dichloromethane, 16 h, 238C (95%); g) (+)-biotin,
DCC, HOBt, dichloromethane, 2 d, 808C (35%).
Benzyl methyl 2,5-dihydroxycyclohexa-1,4-diene-1,4-dicarboxylate (4a):
Succinate 6 (60 g, 270 mmol) was added to a cooled (icebath) suspension
of NaH (21.6 g, 60% dispersion in mineral oil, 540 mmol, 2.0 equiv) in
DMSO (250 mL). After stirring for 30 min at 08C and 3 h at 238C, the
reaction mixture was neutralized by the dropwise addition (icebath) of
half-concentrated hydrochloric acid (50 mL). The precipitate was filtered
off, collected on a glass frit, and washed portionwise with H2O (300 mL)
until the red/brown color disappeared. The residue was stirred for 1 h at
508C with PE/dichloromethane (500 mL, 9:1) and the warm suspension
was filtered through a glass frit. The residue was dibenzyl ester 4b
(7.20 g, 18.9 mmol, 14%; Rf =0.55 (SiO2, toluene)). The filtrate was
evaporated and purified by column chromatography (SiO2, toluene) to
give benzyl methyl ester 4a (14.7 g, 48.3 mmol, 36%) as a colorless solid
(m.p. 1278C) in the first fraction (Rf =0.49). The second fraction (Rf =
0.42) was dimethyl ester 4c (6.16 g, 27.0 mmol, 20%) also a colorless
solid. 1H NMR (CDCl3, 500 MHz): d=3.18–3.24 (m, 4H), 3.79 (s, 3H),
5.23 (s, 2H), 7.33–7.41 (m, 5H), 12.11 ppm (s, 2H; OH); 13C{1H} NMR
(CDCl3, 125 MHz): d=28.48 (CH2), 28.58 (CH2), 51.76 (CH3), 66.28
(CH2), 93.08 (C), 93.12 (C), 127.97 (2 CH), 128.34 (CH), 128.61 (2 CH),
135.52 (C), 168.43 (C), 168.87 (C), 170.92 (C), 171.55 ppm (C); IR
(ATR): n˜ =3086 (m, br; OH), 3035 (w), 2951 (m), 2899 (m), 1661 (vs),
1626 (vs), 1424 (s), 1320 (s), 1203 (s), 1121 (s), 1057 (vs), 801 (s),
702 cmÀ1 (s); MS (EI, 70 eV): m/z (%): 304 (6) [M+], 228 (7), 165 (3), 91
(100); HRMS (EI, 70 eV): m/z: calcd for C16H16O6: 304.0947; found:
304.0945 [M+]; elemental analysis calcd for C16H16O6 (304.30): C 71.15,
H 5.30; found: C 71.06, H 5.14.
Table 2. Absorption and emission bands of 2a–c recorded in CH2Cl2 at
238C.
Compound
lmax [nm]
e [dm3 molÀ1 cmÀ1
]
lem [nm]
2a
2b
2c
352
329
327
1682
944
7247
423
440
447
racarboxamides that starts from an orthogonally protected
platform compound 3a. The two amino and two carboxylic
acid groups were transformed by stepwise deprotection and
amidation into three tetracarboxamides 2a–c with different
amino acids or amines as effector groups attached to the
central aromatic fluorescence chromophore.
1-Benzyl 4-methyl 2,5-diaminoterephthalate (7): Succinyl succinate 4a
(10.00 g, 32.87 mmol) was added to a solution of NH3 in EtOH (200 mL,
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2203

J. Christoffers and R. Pflantz
ca. 15 moldmÀ3) and the resulting mixture was heated for 1 h at 608C.
Concentrated hydrochloric acid (10 mL) was added and the mixture was
further stirred at 608C for 3 d. After cooling to ambient temperature, the
solvent was evaporated and the residue diluted with dichloromethane
(200 mL) and washed with H2O (200 mL). The aqueous layer was ex-
tracted with dichloromethane (3ꢃ200 mL), the combined organic layers
were dried (MgSO4) and filtered, and the solvent was evaporated. The
residue was purified by column chromatography (Al2O3, basic, activity 1;
PE/EA/acetone 5:5:1, Rf =0.56) to give 7 (8.31 g, 27.7 mmol, 84%) as a
red oil. 1H NMR (CDCl3, 500 MHz): d=3.86 (s, 3H), 5.07 (brs, 4H;
NH2), 5.30 (s, 2H), 7.27 (s, 1H), 7.30 (s, 1H), 7.33–7.37 (m, 2H), 7.38–
7.43 ppm (m, 3H); 13C{1H} NMR (CDCl3, 125 MHz): d=51.84 (CH3),
66.53 (CH2), 117.28 (C), 117.55 (C), 118.74 (CH), 118.67 (CH), 128.19 (2
CH), 128.29 (2 CH), 128.60 (CH), 135.70 (C), 140.46 (C), 140.69 (C),
166.89 (C), 167.53 ppm (C); IR (ATR): n˜ =3476 (s), 3473 (s), 3034 (w),
2952 (m), 1690 (vs), 1584 (vs), 1501 (vs), 1439 (vs), 1379 (m), 1286 (s),
1201 (vs), 1096 (vs), 961 (m), 890 (m), 791 (s), 735 (s), 698 cmÀ1 (s); MS
(EI, 70 eV): m/z (%): 300 (100) [M+], 209 (28), 165 (31), 133 (18), 91
(43), 86 (12); HRMS (EI, 70 eV): m/z: calcd for C16H16N2O4: 300.1110;
found: 300.1110 [M+]; 300.31 (C16H16N2O4).
(MgSO4) and filtered, and the solvent evaporated to give the deprotected
amines, which could be purified by chromatography.
Deprotection of 3b: Following general procedure A, 3b (1.02 g,
2.55 mmol) was deprotected and the residue purified by column chroma-
tography (Al2O3, basic, activity 1, PE/EA/acetone 5:5:1, Rf =0.56) to give
7 (730 mg, 2.42 mmol, 95%) as a red oil.
1-Benzyl 4-methyl 2-(4-bromobenzenesulfonylamino)-5-(tert-butyloxycar-
bonylamino)terephthalate (8a): Pyridine (35 mg, 0.44 mmol), a solution
of DMAP in dichloromethane (4 mL, c=1 mmoldmÀ3, 4 mmol), and a so-
lution of 4-BrC6H4SO2Cl (112 mg, 0.44 mmol) in dichloromethane (2 mL)
were subsequently added to a solution of amine 3a (160 mg, 0.40 mmol)
in dichloromethane (2 mL). The reaction mixture was stirred for 16 h at
238C and washed with H2O (10 mL). The organic layer was separated
and dried (MgSO4). After filtration, the solvent was evaporated, and the
residue purified by column chromatography on SiO2 (PE/EA 2:1, Rf =
0.49) to give 8a (213 mg, 0.34 mmol, 85%) as a yellow solid. M.p. 1758C;
1H NMR (CDCl3, 500 MHz): d=1.43 (s, 9H), 3.90 (s, 3H), 5.23 (s, 2H),
7.29–7.34 (m, 7H), 7.41–7.47 (m, 2H), 8.28 (s, 1H), 8.95 (s, 1H), 9.86 (s,
1H; NH), 9.93 ppm (s, 1H; NH); 13C{1H} NMR (CDCl3, 125 MHz): d=
28.26 (3 CH3), 52.98 (CH3), 67.66 (CH2), 81.12 (C), 119.00 (C), 121.47
(CH), 122.90 (C), 124.23 (CH), 128.11 (C), 128.40 (2 CH), 128.64 (CH),
128.67 (2 CH), 128.72 (2 CH), 132.06 (C), 132.20 (2 CH), 134.93 (C),
137.80 (C), 138.30 (C), 152.57 (C), 166.73 (C), 167.17 ppm (C); IR
(ATR): n˜ =3295 (w), 3174 (m), 2983 (w), 1722 (vs), 1685 (vs), 1583 (m),
1528 (vs), 1400 (s), 1226 (vs), 1107 (s), 1071 (s), 935 (m), 790 (s),
691 cmÀ1 (s); MS (EI, 70 eV): m/z (%): 618 (34) [M+], 576 (35), 562 (79),
518 (100), 500 (3); HRMS (CI, isobutane): m/z: calcd for
C27H28BrN2O8S: 619.750; found: 619.0756 [M+H+]; elemental analysis
calcd for C27H27BrN2O8S (619.48): C 52.35, H 4.39, N 4.52; found: C
51.74, H 4.45, N 4.45.
Introduction of the Boc protecting group (3a,b): A solution of Boc2O
(1.88 g, 8.63 mmol) in dichloromethane (6 mL) was added dropwise to a
solution of diamine 7 (2.59 g, 8.63 mmol) in dichloromethane (6 mL) and
the resulting mixture was stirred for 16 h at 238C. The solution was dilut-
ed with dichloromethane (20 mL) and washed with H2O (20 mL). The
aqueous layer was extracted with dichloromethane (3ꢃ20 mL), the com-
bined organic layers were dried (MgSO4) and filtered, and the solvent
was evaporated. The residue was purified by column chromatography
(Al2O3, basic, activity 1; PE/EA 3:1) to give 3b (0.83 g, 2.07 mmol, 24%)
in the first fraction (Rf =0.48) and 3a (2.11 g, 5.27 mmol, 61%) in the
second fraction (Rf =0.43) as yellow solids.
1-Benzyl 4-methyl 5-(4-bromobenzenesulfonylamino)-2-(tert-butyloxycar-
bonylamino)terephthalate (8b): Following the procedure reported for
sulfonamide 8a, a solution of amine 3b (0.2 g, 0.5 mmol) in dichlorome-
thane (2.5 mL) was treated with pyridine (44 mg, 0.55 mmol), a solution
of DMAP in dichloromethane (5 mL, c=1 mmoldmÀ3, 5 mmol), and a so-
lution of 4-BrC6H4SO2Cl (124 mg, 0.55 mmol) in dichloromethane
(2.5 mL) to give amide 8b as a yellow solid (280 mg, 0.45 mmol, 90%)
1-Benzyl 4-methyl 2-amino-5-(tert-butyloxycarbonylamino)terephthalate
(3a): M.p. 1468C; 1H NMR (CDCl3, 500 MHz): d=1.51 (s, 9H), 3.91 (s,
3H), 5.38 (s, 2H), 5.46 (s, 2H; NH2), 7.32 (s, 1H), 7.32–7.33 (m, 1H),
7.36–7.39 (m, 2H), 7.46–7.47 (m, 2H), 8.87 (s, 1H), 9.43 ppm (s, 1H;
NH); 13C{1H} NMR (CDCl3, 125 MHz): d=28.41 (3 CH3), 52.51 (CH3),
66.39 (CH2), 80.16 (C), 115.68 (C), 118.54 (CH), 120.91 (C), 122.25 (CH),
127.87 (2 CH), 128.07 (CH), 128.54 (2 CH), 130.75 (C), 136.12 (C),
144.28 (C), 153.05 (C), 167.16 (C), 167.49 ppm (C); IR (ATR): n˜ =3479
(s), 3369 (s), 3337 (m), 2978 (w), 2952 (w), 1695 (vs), 1625 (m), 1566 (s),
1528 (vs), 1452 (m), 1419 (s), 1316 (s), 1213 (vs), 1156 (vs), 1107 (vs),
1022 (m), 905 (m), 788 (vs), 731 (vs), 685 cmÀ1 (s); MS (EI, 70 eV): m/z
(%): 400 (17) [M+], 344 (42), 300 (100), 252 (10), 238 (19), 209 (25), 165
(14), 133 (10), 91 (67); HRMS (CI, isobutane): m/z: calcd for
C21H25N2O6: 401.1713; found: 401.1714 [M+H+]; elemental analysis
calcd for C21H24N2O6 (400.43): C 62.99, H 6.04, N 7.00; found: C 62.42, H
6.23, N 6.80.
1
after chromatography (SiO2, PE/EA 2:1, Rf =0.58). M.p. 1748C; H NMR
(CDCl3, 500 MHz): d=1.51 (s, 9H), 3.86 (s, 3H), 5.38 (s, 2H), 7.37 (d,
J=8.7 Hz, 2H), 7.46–7.47 (m, 5H), 7.54 (d, J=8.7 Hz, 2H), 8.30 (s, 1H),
8.97 (s, 1H), 9.95 (s, 1H; NH), 10.06 ppm (s, 1H; NH); 13C{1H} NMR
(CDCl3, 125 MHz): d=28.28 (3 CH3), 53.01 (CH3), 67.20 (CH2), 81.13
(C), 118.96 (C), 121.31 (CH), 121.81 (C), 122.58 (CH), 128.13 (C), 128.33
(2 CH), 128.81 (CH), 128.88 (2 CH), 128.90 (2 CH), 132.35 (2 CH),
132.40 (C), 134.97 (C), 137.75 (C), 137.89 (C), 152.65 (C), 166.35 (C),
167.43 ppm (C); IR (ATR): n˜ =3332 (w), 2982 (w), 1730 (s), 1694 (vs),
1574 (s), 1526 (vs), 1393 (vs), 1320 (m), 1228 (vs), 1152 (vs), 1111 (s),
1070 (s), 910 (s), 824 (m), 734 cmÀ1 (vs); MS (EI, 70 eV): m/z (%): 618
(37) [M+], 562 (73), 518 (100); HRMS (EI, 70 eV): m/z: calcd for
C27H27BrN2O8S: 618.0671; found: 618.0668 [M+]; elemental analysis
calcd for C27H27BrN2O8S (619.48): C 52.35, H 4.39, N 4.52; found: C
52.30, H 4.67, N 4.42.
1-Benzyl 4-methyl 5-amino-2-(tert-butyloxycarbonylamino)terephthalate
(3b): M.p. 1448C; 1H NMR (CDCl3, 500 MHz): d=1.52 (s, 9H), 3.89 (s,
3H), 5.33 (s, 2H), 5.47 (s, 2H; NH2), 7.36 (s, 1H), 7.38–7.39 (m, 2H),
7.41–7.42 (m, 3H), 8.83 (s, 1H), 9.52 ppm (s, 1H); 13C{1H} NMR (CDCl3,
125 MHz): d=28.42 (3 CH3), 52.09 (CH3), 67.30 (CH2), 80.20 (C), 115.81
(C), 118.70 (CH), 120.57 (C), 121.84 (CH), 128.36 (2 CH), 128.63 (CH),
128.77 (2 CH), 130.92 (C), 135.24 (C), 144.18 (C), 153.09 (C), 166.87 (C),
167.89 ppm (C); IR (ATR): n˜ =3476 (m), 3358 (m), 2976 (w), 1690 (vs),
1620 (s), 1565 (m), 1526 (s), 1449 (m), 1415 (vs), 1311 (s), 1212 (s), 1152
(s), 1102 (s), 1019 (m), 898 (m), 780 (vs), 728 cmÀ1 (s); MS (EI, 70 eV):
m/z (%): 400 (12) [M+], 344 (35), 300 (89), 209 (26), 165 (20), 133 (12),
91 (100); HRMS (EI, 70 eV): m/z: calcd for C21H24N2O6: 400.1634;
found: 400.1634 [M+]; 400.43 (C21H24N2O6).
1-Benzyl 4-methyl 5-amino-2-(4-bromobenzenesulfonylamino)terephtha-
late (9a): Following general procedure A, 8a (56 mg, 86 mmol) was de-
protected and the residue purified by column chromatography (SiO2, PE/
EA 2:1, Rf =0.31) to give 9a (40 mg, 77 mmol, 90%) as a yellow solid.
M.p. 1038C; 1H NMR (CDCl3, 500 MHz): d=3.77 (s, 3H), 5.36 (s, 2H),
5.65 (s, 2H; NH2), 7.16 (s, 1H), 7.34–7.37 (m, 2H), 7.40–7.44 (m, 2H),
7.45–7.48 (m, 3H), 7.52–7.53 (m, 2H), 8.19 (s, 1H), 9.29 ppm (s, 1H);
13C{1H} NMR (CDCl3, 125 MHz): d=52.66 (CH3), 66.78 (CH2), 114.91
(C), 118.84 (CH), 124.17 (C), 125.66 (CH), 126.92 (C), 127.77 (C), 128.19
(2 CH), 128.48 (CH), 128.76 (2 CH), 129.04 (2 CH), 132.01 (2 CH),
135.68 (C), 138.14 (C), 146.35 (C), 166.51 (C), 167.31 ppm (C); IR
(ATR): n˜ =3482 (m), 3373 (m), 2955 (w), 1696 (vs), 1593 (s), 1507 (s),
1404 (s), 1316 (m), 1235 (vs), 1167 (vs), 1108 (vs), 926 (m), 743 cmÀ1 (s);
MS (EI, 70 eV): m/z (%): 518 (8) [M+], 299 (33), 91 (100), 57 (51);
HRMS (EI, 70 eV): m/z: calcd for C22H19BrN2O6S: 518.0147; found:
General procedure A: deprotection of the Boc group: TFA (10 equiv)
was added to a cooled (icebath) solution of the carbamate (1 equiv) in di-
chloromethane (c=0.1 moldmÀ3) and the mixture was stirred for 16 h at
238C. The solvent was evaporated and H2O (20 dm3 molÀ1) and KOH
(10% in H2O) were added dropwise to the residue until pH>10
(ca. 2 dm3 molÀ1) was reached. The aqueous layer was extracted with di-
chloromethane (4ꢃ50 dm3 molÀ1), the combined organic layers dried
2204
www.chemeurj.org
ꢂ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2009, 15, 2200 – 2209

Diaminoterephthalates as Fluorescent Materials
FULL PAPER
518.0148 [M+]; elemental analysis calcd for C22H19BrN2O6S (519.37): C
50.88, H 3.69, N 5.39; found: C 50.51, H 3.71, N 5.81.
13.1 Hz, 1H), 5.17 (B part of an AB system, J=12.7 Hz, 1H), 5.31 (s,
2H), 7.01–7.05 (m, 2H), 7.15–7.17 (m, 2H), 7.23–7.27 (m, 2ꢃ2H), 7.30–
7.34 (m, 2ꢃ2H), 7.36–7.40 (m, 2ꢃ4H), 7.55 (d, J=7.1 Hz, 1H), 7.61 (d,
J=7.7 Hz, 1H), 7.64 (d, J=7.1 Hz, 1H), 7.73–7.74 (m, 1H), 7.75–7.76 (m,
2H), 9.15 (s, 2ꢃ1H), 9.34 (s, 1H), 9.39 (s, 1H), 10.00 (s, 1H; NH), 10.04
(s, 1H; NH), 11.18 (s, 1H; NH), 11.34 ppm (s, 1H; NH); 13C{1H} NMR
(CDCl3, 125 MHz), two isomers: d=23.46 (CH2), 24.40 (CH2), 28.28 (2ꢃ
3 CH3), 30.24 (CH2), 31.46 (CH2), 47.05 (CH2), 47.08 (CH2), 47.33 (CH),
47.42 (CH), 52.69 (CH3), 52.73 (CH3), 62.06 (CH), 62.40 (CH), 66.92
(CH2), 67.30 (CH2), 67.57 (CH2), 67.76 (CH2), 80.70 (C), 80.80 (C),
118.95 (2ꢃC), 119.81 (CH), 119.91 (CH), 120.45 (C), 120.62 (C), 121.13
(2ꢃ2 CH), 122.54 (2ꢃ2 CH), 124.59 (CH), 124.74 (CH), 125.24 (CH),
125.37 (CH), 126.88 (2 CH), 126.96 (2 CH), 127.49 (2 CH), 127.67 (2
CH), 128.09 (2ꢃCH), 128.16 (2ꢃCH), 128.45 (2ꢃ2 CH), 133.73 (C),
133.92 (C), 135.19 (2ꢃC), 136.78 (C), 136.85 (C), 141.11 (2 C), 141.25 (2
C), 143.66 (C), 143.73 (C), 144.28 (C), 144.33 (C), 152.62 (2ꢃC), 154.97
(C), 155.61 (C), 166.93 (C), 167.10 (C), 167.70 (2ꢃC), 170.96 (C),
171.10 ppm (C); IR (ATR): n˜ =3318 (w), 2953 (m), 1689 (vs), 1538 (vs),
1407 (s), 1320 (m), 1222 (vs), 1152 (vs), 1107 (s), 908 (s), 727 cmÀ1 (vs);
MS (ESI): m/z (%): 742 (67) [M+Na+], 593 (100), 422 (42); HRMS
(ESI): m/z: calcd for C41H42N3O9: 720.2921; found: 720.2928 [M+H+]; el-
emental analysis calcd for C41H41N3O9 (719.78): C 68.42, H 5.74, N 5.84;
found: C 68.07, H 5.88, N 5.82.
1-Benzyl 4-methyl 2-amino-5-(4-bromobenzenesulfonylamino)terephtha-
late (9b): Following general procedure A, 8b (280 mg, 0.45 mmol) was
deprotected and the residue purified by column chromatography (SiO2,
PE/EA 2:1, Rf =0.27) to give 9b (210 mg, 0.404 mmol, 90%) as a yellow
solid. M.p. 1068C; 1H NMR (CDCl3, 500 MHz): d=3.76 (s, 3H), 5.35 (s,
2H), 5.67 (s, 2H; NH2), 7.16 (s, 1H), 7.38–7.40 (m, 2H), 7.42–7.43 (m,
2H), 7.45–7.48 (m, 3H), 7.50–7.52 (m, 2H), 8.18 (s, 1H), 9.29 ppm (s,
1H); 13C{1H} NMR (CDCl3, 125 MHz): d=52.62 (CH3), 66.73 (CH2),
114.84 (C), 118.85 (CH), 124.14 (C), 125.59 (CH), 126.90 (C), 127.77 (C),
128.16 (2 CH), 128.45 (CH), 128.73 (2 CH), 129.01 (2 CH), 131.99 (2
CH), 135.66 (C), 137.94 (C), 146.82 (C), 166.53 (C), 166.90 ppm (C); IR
(ATR): n˜ =3482 (m), 3372 (m), 2953 (w), 1691 (vs), 1591 (s), 1504 (vs),
1399 (s), 1314 (m), 1229 (vs), 1163 (vs), 1104 (vs), 923 (m), 740 cmÀ1 (s);
MS (EI, 70 eV): m/z (%): 518 (11) [M+], 299 (42), 91 (100); HRMS (EI,
70 eV): m/z: calcd for C22H19BrN2O6S: 518.0147; found: 518.0147 [M+];
elemental analysis calcd for C22H19BrN2O6S (519.37): C 50.88, H 3.69, N
5.39; found: C 50.53, H 3.68, N 5.61.
General procedure B: amidation of aliphatic carboxylic acids: N,N-Dicy-
clohexylcarbodiimide (DCC; 1.2 equiv) was added to a solution of car-
boxylic acid (1.1 equiv) in dichloromethane (0.30 moldmÀ3). After the re-
action mixture was stirred at ambient temperature for 1 min, a colorless
precipitate was formed and HOBt (88% purity, 1.2 equiv) was added.
After further stirring for 1 min, the amine (1.0 equiv) was added. The re-
action mixture was stirred in a tightly closed reaction flask for 2 d at
808C. After cooling to 238C, the mixture was diluted with dichlorome-
1-Benzyl 4-methyl 5-(tert-butyloxycarbonylamino)-2-[(S)-4,4-dimethyl-2-
(fluoren-9-ylmethyloxycarbonylamino)pentanoylamino]terephthalate
(10c): Following general procedure B, 3a (880 mg, 2.20 mmol) was cou-
pled with N-Fmoc-l-Npg (888 mg, 2.42 mmol) by using DCC (499 mg,
2.42 mmol) and HOBt (371 mg, 2.42 mmol) to give 10c (966 mg,
1.29 mmol, 59%) after chromatography (SiO2, PE/EA 2:1, Rf =0.09) as a
yellow solid. M.p. 1298C; 1H NMR (CDCl3, 500 MHz): d=1.00 (s, 9H),
1.46–1.49 (m, 2H), 1.51 (s, 9H), 3.93 (s, 3H), 4.25 (t, J=6.8 Hz, 1H),
4.37–4.49 (m, 3H), 5.11 (d, J=7.9 Hz, 1H; NH), 5.22 (A part of an AB
system, J=12.7 Hz, 1H), 5.26 (B part of an AB system, J=12.6 Hz, 1H),
7.27–7.29 (m, 6H), 7.36–7.40 (m, 3H), 7.61 (d, J=7.3 Hz, 1H), 7.66 (d,
J=7.3 Hz, 1H), 7.75 (d, J=7.4 Hz, 2H), 9.16 (s, 1H), 9.35 (s, 1H), 10.00
(s, 1H; NH), 11.27 ppm (s, 1H; NH); 13C{1H} NMR (CDCl3, 125 MHz):
d=28.30 (3 CH3), 29.65 (3 CH3), 30.66 (C), 46.35 (CH2), 47.31 (CH),
52.70 (CH3), 54.34 (CH), 67.14 (CH2), 67.19 (CH2), 80.76 (C), 118.97 (C),
119.94 (2 CH), 120.52 (C), 121.53 (CH), 122.59 (CH), 125.14 (CH),
125.22 (CH), 127.00 (2 CH), 127.03 (CH), 127.69 (2 CH), 127.77 (CH),
128.25 (CH), 128.54 (2 CH), 133.84 (C), 135.06 (C), 135.19 (C), 136.19
(C), 141.27 (C), 143.65 (C), 144.06 (C), 152.65 (C), 155.86 (C), 167.04
(C), 167.67 (C), 171.63 ppm (C); IR (ATR): n˜ =3303 (w), 2951 (m), 1731
(s), 1695 (s), 1548 (s), 1450 (w), 1409 (m), 1322 (w), 1227 (vs), 1154 (s),
1107 (s), 1073 (m), 789 (m), 738 (s), 696 cmÀ1 (m); MS (ESI): m/z (%):
772 (100) [M+Na+], 716 (14); HRMS (ESI): m/z: calcd for
C43H47N3NaO9: 772.3210; found: 772.3227 [M+Na+]; elemental analysis
calcd for C43H47N3O9 (749.85): C 68.88, H 6.32, N 5.60; found: C 68.35, H
6.38, N 5.42.
thane (20 dm3 molÀ1
) and washed with saturated NH4Cl solution
(20 dm3 molÀ1), saturated NaHCO3 solution (20 dm3 molÀ1), and H2O
(20 dm3 molÀ1). After drying over MgSO4 and filtration, the organic layer
was evaporated and the residue purified by chromatography on SiO2.
1-Benzyl 4-methyl 5-(tert-butyloxycarbonylamino)-2-[3-(fluoren-9-ylme-
thyloxycarbonylamino)propanoylamino]terephthalate (10a): Following
general procedure B, 3a (470 mg, 1.17 mmol) was coupled with N-Fmoc-
b-Ala (402 mg, 1.29 mmol) by using DCC (291 mg, 1.41 mmol) and
HOBt (216 mg, 1.41 mmol) to give 10a (670 mg, 0.97 mmol, 82%) after
chromatography (SiO2, PE/EA 2:1, Rf =0.20) as a yellow solid. M.p.
968C; 1H NMR (CDCl3, 500 MHz): d=1.53 (s, 9H), 2.66 (t, J=5.4 Hz,
2H), 3.56 (q, J=5.6 Hz, 2H), 3.95 (s, 3H), 4.20 (t, J=6.9 Hz, 1H), 4.35
(d, J=7.0 Hz, 2H), 5.37 (s, 2H), 5.53 (s, 1H; NH), 7.25–7.28 (m, 2H),
7.33–7.40 (m, 5H), 7.46 (d, J=7.4 Hz, 2H), 7.57 (d, J=7.4 Hz, 2H), 7.73
(d, J=7.5 Hz, 2H), 9.17 (s, 1H), 9.27 (s, 1H), 10.01 (s, 1H; NH),
10.71 ppm (s, 1H; NH); 13C{1H} NMR (CDCl3, 125 MHz): d=28.29 (3
CH3), 36.73 (CH2), 37.49 (CH2), 47.23 (CH), 52.78 (CH3), 66.71 (CH2),
67.40 (CH2), 80.82 (C), 118.99 (C), 119.90 (2 CH), 120.13 (C), 121.25 (C),
122.59 (C), 125.05 (2 CH), 126.97 (2 CH), 127.61 (2 CH), 128.01 (2 CH),
128.46 (2 CH), 128.64 (3 CH), 133.95 (C), 135.19 (C), 136.77 (C), 141.24
(C), 143.92 (C), 152.67 (C), 156.58 (C), 167.17 (C), 167.59 (C),
170.22 ppm (C); IR (ATR): n˜ =3318 (m), 2952 (w), 1723 (s), 1692 (s),
1543 (vs), 1407 (s), 1321 (m), 1224 (vs), 1152 (vs), 1107 (s), 1070 (m),
1017 (m), 907 (s), 727 cmÀ1 (vs) ; MS (EI, 70 eV): m/z (%): 693 (2) [M+],
593 (12), 441 (7), 415 (14), 397 (70), 371 (12), 300 (71), 209 (11), 196 (25),
178 (91), 165 (61), 91 (100), 57 (15); HRMS (ESI): m/z: calcd for
C39H40N3O9: 694.2765; found: 694.2758 [M+H+]; elemental analysis
calcd for C39H39N3O9 (693.74): C 67.52, H 5.67, N 6.06; found: C 67.61, H
5.93, N 5.86.
1-Benzyl 4-methyl 5-amino-2-[3-(fluoren-9-ylmethyloxycarbonylamino)-
propanoylamino]terephthalate (11a): Following general procedure A,
10a (1.21 g, 1.75 mmol) was deprotected and the crude product purified
by column chromatography (SiO2, PE/EA 1:1, Rf =0.44) to give 11a
(1.02 g, 1.72 mmol, 98%) as
a
yellow solid. M.p. 1758C; 1H NMR
(CDCl3, 500 MHz): d=2.63 (t, J=5.0 Hz, 2H), 3.58 (q, J=5.2 Hz, 2H),
3.89 (s, 3H), 4.20 (t, J=6.8 Hz, 1H), 4.36 (d, J=7.0 Hz, 2H), 4.50 (brs,
1H; NH), 5.26 (s, 2H), 5.60 (brs, 2H; NH2), 7.25–7.27 (m, 2H), 7.33–7.34
(m, 2H), 7.36–7.37 (m, 2H), 7.38–7.39 (m, 4H), 7.57 (d, J=7.3 Hz, 2H),
7.72 (d, J=7.4 Hz, 2H), 9.08 (s, 1H), 10.36 ppm (s, 1H; NH);
13C{1H} NMR (CDCl3, 125 MHz): d=36.87 (CH2), 37.36 (CH2), 47.20
(CH), 52.08 (CH3), 66.70 (CH2), 67.48 (CH2), 115.00 (C), 118.61 (C),
119.87 (2 CH), 121.11 (C), 123.37 (CH), 125.08 (2 CH), 126.96 (2 CH),
127.57 (2 CH), 128.40 (2 CH), 128.69 (2 CH), 128.73 (2 CH), 129.49 (C),
134.92 (C), 141.21 (C), 143.92 (2 C), 145.35 (C), 156.40 (C), 166.89 (C),
167.63 (C), 169.67 ppm (C); IR (ATR): n˜ =3475 (m), 3364 (m), 3310 (m),
2948 (w), 1713 (s), 1692 (vs), 1645 (s), 1532 (vs), 1438 (s), 1233 (vs), 1109
(s), 1050 (m), 962 (m), 909 (m), 731 (vs), 695 cmÀ1 (s); MS (EI, 70 eV):
m/z (%): 593 (14) [M+], 397 (39), 300 (20), 246 (4), 178 (29), 165 (100),
1-Benzyl 4-methyl 5-(tert-butyloxycarbonylamino)-2-{[(S)-1-(fluoren-9-yl-
methyloxycarbonyl)pyrrolidin-2-yl]carbonylamino}terephthalate
(10b):
Following general procedure B, 3a (220 mg, 0.55 mmol) was coupled with
N-Fmoc-l-Pro (202 mg, 0.60 mmol) by using DCC (124 mg, 0.60 mmol)
and HOBt (92 mg, 0.60 mmol) to give 10b (310 mg, 0.43 mmol, 78%)
after chromatography (SiO2, PE/EA 2:1, Rf =0.08) as a yellow solid. M.p.
718C; a partly doubled signal set (ratio 1:1) was observed in the NMR
spectra: 1H NMR (CDCl3, 500 MHz), two isomers: d=1.51 (s, 9H), 1.53
(s, 9H), 1.90–1.93 (m, 2H), 2.00–2.03 (m, 2H), 2.21–2.23 (m, 2H), 2.27–
2.31 (m, 2H), 3.62 (t, J=8.1 Hz, 2ꢃ1H), 3.71–3.74 (m, 1H), 3.82–3.84
(m, 1H), 3.93 (s, 3H), 3.97 (s, 3H), 4.09 (t, J=6.7 Hz, 2ꢃ1H), 4.29–4.32
(m, 2ꢃ2H), 4.54–4.55 (m, 2ꢃ1H), 5.14 (A part of an AB system, J=
Chem. Eur. J. 2009, 15, 2200 – 2209
ꢂ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
2205

J. Christoffers and R. Pflantz
139 (5), 91 (45), 57 (3); HRMS (EI, 70 eV): m/z: calcd for C34H31N3O7:
593.2162; found: 593.2163 [M+]; C34H31N3O7 (593.63).
doubled signal set (ratio 1:1) is observed in the NMR spectra: 1H NMR
(CDCl3, 500 MHz), two isomers: d=0.89–1.04 (m, 2ꢃ6H), 1.44 (s, 9H),
1.45 (s, 9H), 1.85–1.92 (m, 2ꢃ2H), 2.21–2.32 (m, 2ꢃ3H), 3.60–3.66 (m,
2ꢃ1H), 3.74–3.76 (m, 2ꢃ1H), 3.87 (s, 3H), 3.92 (s, 3H), 4.13–4.16 (m,
2ꢃ1H), 4.29–4.33 (m, 2ꢃ2H), 4.36–4.39 (m, 2ꢃ1H), 4.53–4.54 (m, 2ꢃ
1H), 5.00–5.07 (m, 2H), 5.12–5.20 (m, 2H), 5.58 (brs, 1H, NH), 5.64
(brs, 1H, NH), 7.02 (t, J=7.0 Hz, 1H), 7.06 (t, J=7.2 Hz, 1H), 7.20–7.22
(m, 2ꢃ2H), 7.28–7.34 (m, 2ꢃ5H), 7.38–7.39 (m, 2ꢃ1H), 7.42–7.47 (m,
2ꢃ1H), 7.59–7.66 (m, 2ꢃ1H), 7.70–7.75 (m, 2ꢃ2H), 9.19 (s, 1H), 9.21 (s,
1H), 9.42 (s, 1H), 9.47 (s, 1H), 10.95 (s, 1H; NH), 11.06 (s, 1H; NH),
11.27 (s, 1H; NH), 11.34 ppm (s, 1H; NH); 13C{1H} NMR (CDCl3,
125 MHz), two isomers: d=19.42 (2 CH3), 19.44 (2 CH3), 23.47 (2ꢃCH2),
28.28 (3 CH3), 28.31 (3 CH3), 30.19 (CH2), 30.21 (CH2), 31.47 (CH), 31.49
(CH), 47.07 (CH), 47.09 (CH), 47.36 (CH2), 47.39 (CH2), 52.00 (CH3),
52.06 (CH3), 60.36 (2ꢃCH), 62.08 (CH), 62.36 (CH), 67.10 (2ꢃCH2),
67.76 (CH2), 67.85 (CH2), 78.61 (2ꢃC), 113.35 (2ꢃCH), 115.05 (C),
115.07 (C), 118.52 (CH), 118.53 (CH), 119.01 (2ꢃCH), 119.76 (CH),
119.92 (CH), 123.17 (C), 123.26 (C), 124.80 (CH), 124.97 (CH), 125.26
(CH), 125.41 (CH), 126.93 (2 CH), 126.96 (2 CH), 127.48 (CH), 127.66
(CH), 128.00 (2ꢃ2 CH), 128.44 (2 CH), 128.50 (2 CH), 128.58 (2ꢃ2 CH),
129.40 (C), 129.42 (C), 134.98 (2ꢃC), 139.40 (2ꢃC), 141.09 (C), 141.14
(C), 143.73 (C), 143.75 (C), 144.28 (C), 144.31 (C), 145.32 (C), 145.45
(C), 155.61 (C), 155.63 (C), 157.85 (C), 157.86 (C), 166.84 (C), 166.89
(C), 167.77 (2ꢃC), 170.14 (C), 170.16 (C), 170.78 (C), 170.81 ppm (C);
IR (ATR): n˜ =3299 (w), 2953 (w), 1686 (vs), 1528 (s), 1404 (s), 1316 (m),
1225 (vs), 1104 (vs), 984 (w), 913 (m), 737 cmÀ1 (vs); MS (ESI): m/z (%):
841 (67) [M+Na+], 774 (60), 643 (48), 619 (100); HRMS (ESI): m/z:
1-Benzyl 4-methyl 5-amino-2-{[(S)-1-(fluoren-9-ylmethyloxycarbonylami-
no)pyrrolidin-2-yl]carbonylamino}terephthalate (11b): Following general
procedure A, 10b (580 mg, 0.81 mmol) was deprotected and the crude
product purified by column chromatography (SiO2, PE/EA 1:2, Rf =0.19)
to give 11b (450 mg, 0.73 mmol, 90%) as a yellow solid. M.p. 558C; a
partly doubled signal set (ratio 1:1) was observed in the NMR spectra:
1H NMR (CDCl3, 500 MHz), two isomers: d=1.92–1.99 (m, 2ꢃ2H),
2.17–2.30 (m, 2ꢃ2H), 3.61 (t, J=8.7 Hz, 1H), 3.63 (t, J=8.6 Hz, 1H),
3.72–3.74 (m, 2ꢃ1H), 3.86 (s, 3H), 3.90 (s, 3H), 4.14 (t, J=6.3 Hz, 2ꢃ
1H), 4.29–4.39 (m, 2ꢃ2H), 4.53–4.57 (m, 2ꢃ1H), 4.67 (s, 2ꢃ2H; NH2),
4.99 (A part of an AB system, J=12.2 Hz, 1H), 5.05 (B part of an AB
system, J=12.3 Hz, 1H), 5.13 (A part of an AB system, J=12.1 Hz, 1H),
5.19 (B part of an AB system, J=12.1 Hz, 1H), 7.02 (t, J=6.8 Hz, 1H),
7.06 (t, J=7.0 Hz, 1H), 7.19–7.22 (m, 2ꢃ1H), 7.27–7.28 (m, 2ꢃ2H),
7.30–7.31 (m, 2ꢃ3H), 7.33–7.34 (m, 2ꢃ2H), 7.42 (d, J=7.8 Hz, 2H), 7.46
(d, J=7.8 Hz, 2H), 7.59–7.60 (m, 2ꢃ1H), 7.63–7.66 (m, 2ꢃ1H), 7.75 (s,
2ꢃ1H), 9.19 (s, 1H), 9.20 (s, 1H), 10.95 (s, 1H; NH), 11.06 ppm (s, 1H;
NH); 13C{1H} NMR (CDCl3, 125 MHz), two isomers: d=23.43 (CH2),
24.36 (CH2), 30.16 (CH2), 31.42 (CH2), 47.03 (2ꢃCH2), 47.31 (CH), 47.45
(CH), 51.96 (CH3), 52.02 (CH3), 62.06 (CH), 62.32 (CH), 67.07 (CH2),
67.35 (CH2), 67.73 (CH2), 67.81 (CH2), 114.98 (C), 115.08 (C), 118.53 (2ꢃ
CH), 119.75 (CH), 119.87 (CH), 121.16 (C), 121.42 (C), 123.12 (2 CH),
123.24 (2 CH), 124.76 (CH), 124.94 (CH), 125.24 (2 CH), 125.37 (2 CH),
126.88 (2ꢃ2 CH), 126.93 (2 CH), 127.48 (2 CH), 127.63 (CH), 127.97
(CH), 128.44 (2ꢃCH), 128.55 (2ꢃ2 CH), 129.32 (C), 129.61 (C), 134.95
(2ꢃC), 140.95 (2ꢃC), 141.07 (C), 141.22 (C), 143.70 (C), 143.82 (C),
144.37 (C), 144.40 (C), 145.31 (C), 145.46 (C), 155.13 (C), 155.62 (C),
166.69 (C), 166.88 (C), 167.73 (2ꢃC), 170.26 (C), 170.52 ppm (C); IR
(ATR): n˜ =3353 (w), 2951 (w), 1687 (vs), 1567 (m), 1525 (s), 1417 (s),
1314 (m), 1223 (vs), 1102 (vs), 910 (m), 736 cmÀ1 (s). MS (ESI): m/z (%):
642 (35) [M+Na+], 420 (100), 360 (40); HRMS (ESI): m/z: calcd for
C36H33N3NaO7: 642.2216; found: 642.2243 [M+Na+]; elemental analysis
calcd for C36H33N3O7 (619.66): C 69.78, H 5.37, N 6.78; found: C 69.52, H
5.58, N 6.60.
calcd for C46H50N4NaO10
C46H50N4O10 (818.91).
:
841.3425; found: 841.3440 [M+Na+];
General procedure C: hydrogenolysis of benzyl ester: A catalytic amount
of Pd (5 w/w% on C, 5 gmolÀ1 substrate) was added to a solution of
benzyl ester in ethyl acetate (c=30 mmoldmÀ3) and the mixture stirred
for 16 h at 238C in a H2 atmosphere (1 atm, balloon). Subsequently, the
catalyst was removed by filtration, the residue washed with ethyl acetate
(100 dm3 molÀ1), and the filtrate evaporated to give the crude hydrogena-
tion product.
1-Benzyl 4-methyl 5-[3-(tert-butyloxycarbonylamino)propanoyl]amino-2-
[3-(fluoren-9-ylmethyloxycarbonylamino)propanoyl]aminoterephthalate
(12a): Following general procedure B, 11a (400 mg, 0.674 mmol) was
coupled with N-Boc-b-Ala (383 mg, 2.02 mmol) by using DCC (417 mg,
2.02 mmol) and HOBt (310 mg, 2.02 mmol) to give 12a (390 mg,
0.508 mmol, 75%) as a yellow solid after chromatography (SiO2, PE/EA
5-[3-(tert-Butyloxycarbonylamino)propanoyl]amino-2-[3-(fluoren-9-ylme-
thyloxycarbonylamino)propanoyl]aminoterephthalic acid 4-methyl ester
(13a): Following general procedure C, 12a (420 mg, 0.547 mmol) was de-
protected to give 13a (350 mg, 0.516 mmol, 94%) as a yellow solid.
M.p. 1518C; 1H NMR (CDCl3, 500 MHz): d=1.43 (s, 9H), 2.67–2.70 (m,
4H), 3.51–3.53 (m, 2H), 3.59–3.61 (m, 2H), 3.95 (s, 3H), 4.17 (t, J=
6.6 Hz, 1H), 4.37 (q, J=7.0 Hz, 2H), 5.29 (brs, 1H), 5.45 (brs, 1H), 5.88
(brs, 1H), 7.23–7.25 (m, 1H), 7.31–7.38 (m, 3H), 7.56 (d, J=7.4 Hz, 2H),
7.69 (d, J=7.2 Hz, 2H), 9.27 (s, 1H), 9.33 (s, 1H), 10.82 (s, 1H),
11.16 ppm (s, 1H); 13C{1H} NMR (CDCl3, 125 MHz): d=24.74 (CH2),
25.49 (CH2), 28.38 (3 CH3), 32.98 (CH2), 33.59 (CH2), 47.14 (CH), 52.89
(CH3), 66.84 (CH2), 79.35 (C), 119.31 (C), 119.85 (2 CH), 120.47 (C),
123.19 (CH), 123.95 (CH), 125.04 (2 CH), 126.95 (2 CH), 127.58 (2 CH),
135.25 (C), 135.62 (C), 140.46 (C), 141.20 (C), 143.84 (C), 148.94 (C),
156.78 (C), 157.76 (C), 167.79 (C), 169.94 (C), 170.34 (C), 170.48 ppm
(C); IR (ATR): n˜ =3341 (s), 2934 (m), 1678 (vs), 1529 (vs), 1437 (w),
1404 (s), 1320 (w), 1228 (vs), 1169 (s), 1104 (s), 955 (m), 910 (s), 790 (m),
729 cmÀ1 (s); MS (ESI, neg. mode): m/z (%): 673 (100) [MÀH+], 573
(40), 533 (22), 506 (74), 391 (34), 293 (25), 206 (33); HRMS (ESI): m/z:
calcd for C35H38N4NaO10: 697.2486; found: 697.2485 [M+Na+]; elemental
analysis calcd for C35H38N4O10 (674.70): C 62.31, H 5.68, N 8.30; found: C
62.72, H 5.75, N 8.02.
1
1:1, Rf =0.17). M.p. 1558C; H NMR (CDCl3, 500 MHz): d=1.42 (s, 9H),
2.63–2.66 (m, 4H), 3.49 (q, J=5.6 Hz, 2H), 3.57 (q, J=5.5 Hz, 2H), 3.91
(s, 3H), 4.17 (t, J=6.9 Hz, 1H), 4.36 (d, J=7.0 Hz, 2H), 5.28 (s, 1H;
NH), 5.34 (s, 2H), 5.69 (t, J=6.0 Hz, 1H; NH), 7.21–7.24 (m, 2H), 7.31–
7.34 (m, 3H), 7.37–7.40 (m, 2H), 7.46 (d, J=7.4 Hz, 2H), 7.55 (d, J=
7.4 Hz, 2H), 7.69 (d, J=7.5 Hz, 2H), 9.27 (s, 1H), 9.37 (s, 1H),
10.78 ppm (s, 2H; NH); 13C{1H} NMR (CDCl3, 125 MHz): d=28.34 (3
CH3), 36.28 (CH2), 36.66 (CH2), 37.58 (CH2), 37.86 (CH2), 47.15 (CH),
52.88 (CH3), 66.62 (CH2), 67.53 (CH2), 79.19 (C), 119.47 (C), 119.58 (C),
119.82 (2 CH), 122.31 (C), 122.45 (C), 124.98 (2 CH), 126.89 (2 CH),
127.54 (2 CH), 128.08 (2 CH), 128.49 (2 CH), 128.66 (3 CH), 134.96 (C),
135.26 (C), 135.46 (C), 141.16 (C), 143.85 (C), 155.82 (C), 156.38 (C),
166.96 (C), 167.58 (C), 170.21 (C), 170.38 ppm (C); IR (ATR): n˜ =3321
(m), 2932 (w), 1684 (vs), 1531 (s), 1404 (m), 1322 (m), 1224 (vs), 1176 (s),
1103 (s), 918 (m), 792 (s), 728 cmÀ1 (m); MS (ESI): m/z (%): 787 (45)
[M+Na+], 694 (8), 563 (60), 517 (80), 471 (35), 293 cmÀ1 (100); HRMS
(ESI): m/z: calcd for C42H45N4O10: 765.3163; found: 765.3143 [M+H+];
elemental analysis calcd for C42H44N4O10 (764.82): C 65.96, H 5.80, N
7.33; found: C 65.64, H 5.36, N 6.90.
5-[(S)-2-(tert-Butyloxycarbonylamino)-3-methylbutanoyl]amino-2-{[(S)-1-
(fluoren-9-ylmethyloxycarbonylamino)pyrrolidin-2-yl]carbonylamino}ter-
ephthalic acid 4-methyl ester (13b): Following general procedure C, 12b
(500 mg, 0.611 mmol) was deprotected to give 13b (418 mg, 0.574 mmol,
94%) as a yellow solid. M.p. 1128C; a partly doubled signal set (ratio
1:1) is observed in the NMR spectra: 1H NMR (CDCl3, 500 MHz), two
isomers: d=0.78–0.95 (m, 2ꢃ6H), 1.34 (s, 9H), 1.39 (s, 9H), 1.77–1.87
(m, 2ꢃ2H), 2.11–2.13 (m, 2ꢃ3H), 3.41–3.48 (m, 2ꢃ1H), 3.64–3.66 (m,
2ꢃ1H), 3.76 (s, 3H), 3.82 (s, 3H), 4.01–4.05 (m, 2ꢃ1H), 4.19–4.22 (m,
2ꢃ2H), 4.30–4.32 (m, 2ꢃ1H), 4.46–4.48 (m, 2ꢃ1H), 5.20 (brs, 2ꢃ1H),
1-Benzyl 4-methyl 5-[(S)-2-(tert-butyloxycarbonylamino)-3-methylbuta-
noyl]amino-2-{[(S)-1-(fluoren-9-ylmethyloxycarbonylamino)pyrrolidin-2-
yl]carbonylamino}terephthalate (12b): Following general procedure B,
11b (420 mg, 0.678 mmol) was coupled with N-Boc-l-Val (295 mg,
1.36 mmol) by using DCC (280 mg, 1.36 mmol) and HOBt (208 mg,
1.36 mmol) to give 12b (500 mg, 0.611 mmol, 90%) as a yellow solid
after chromatography (SiO2, PE/EA 1:2, Rf =0.44). M.p. 748C; a partly
2206
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ꢂ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2009, 15, 2200 – 2209

Diaminoterephthalates as Fluorescent Materials
FULL PAPER
5.50 (brs, 2ꢃ1H), 6.93 (t, J=7.3 Hz, 1H), 6.96 (t, J=7.3 Hz, 1H), 7.23–
7.30 (m, 2ꢃ3H), 7.32–7.36 (m, 2ꢃ1H), 7.49 (t, J=7.2 Hz, 2ꢃ1H), 7.53
(t, J=7.0 Hz, 2ꢃ1H), 7.63 (t, J=6.8 Hz, 2ꢃ1H), 9.02 (s, 1H), 9.08 (s,
1H), 9.20 (s, 1H), 9.30 (s, 1H), 10.97 (s, 1H; NH), 11.01 (s, 1H; NH),
11.44 (s, 1H; NH), 11.46 ppm (s, 1H; NH); 13C{1H} NMR (CDCl3,
125 MHz), two isomers: d=19.41 (2 CH3), 19.53 (2 CH3), 23.29 (2ꢃCH2),
28.23 (3 CH3), 28.29 (3 CH3), 30.44 (2ꢃCH2), 31.38 (2ꢃCH), 47.09 (2ꢃ
CH), 47.38 (2ꢃCH2), 51.92 (CH3), 52.01 (CH3), 60.39 (2ꢃCH), 62.09 (2ꢃ
CH), 68.03 (CH2), 68.11 (CH2), 80.09 (2ꢃC), 114.76 (2ꢃC), 117.96 (2ꢃ
CH), 119.39 (C), 119.50 (C), 119.77 (CH), 119.88 (CH), 124.73 (CH),
124.87 (CH), 125.04 (CH), 125.20 (CH), 125.87 (2ꢃ2 CH), 126.92 (2ꢃ2
CH), 127.49 (2 CH), 127.64 (2 CH), 129.24 (2ꢃC), 141.04 (C), 141.17
(C), 143.56 (C), 143.61 (C), 143.76 (2ꢃC), 145.24 (C), 145.29 (C), 145.57
(2ꢃC), 155.23 (C), 155.45 (C), 155.69 (C), 155.89 (C), 167.71 (C), 167.76
(C), 169.26 (C), 169.36 (C), 169.99 (C), 170.35 (C), 170.87 (C),
171.21 ppm (C); IR (ATR): n˜ =3457 (m), 2970 (m), 1738 (vs), 1525 (s),
1437 (m), 1365 (s), 1228 (vs), 1205 (s), 1109 (m), 896 (m), 794 (m),
738 cmÀ1 (m); MS (ESI, neg. mode): m/z (%): 727 (88) [MÀH+], 527
(50), 306 (100); 728.79 (C39H44N4O10): elemental analysis calcd for
C39H44N4O10: C 64.27, H 6.09, N 7.69; found: C 63.97, H 6.08, N 7.81.
then stirred in a tightly closed reaction flask for 2 d at 808C. After cool-
ing to 238C, the mixture was diluted with dichloromethane
(20 dm3 molÀ1), and washed with saturated NH4Cl solution
(20 dm3 molÀ1), saturated NaHCO3 solution (20 dm3 molÀ1), and H2O
(20 dm3 molÀ1). After drying over MgSO4 and filtration, the organic layer
was evaporated and the residue purified by chromatography on SiO2.
5-[(S)-2-(tert-Butyloxycarbonylamino)-3-methylbutanoyl]amino-2-{[(S)-1-
(fluoren-9-ylmethyloxycarbonylamino)pyrrolidin-2-yl]carbonylamino}ter-
ephthalic acid 1-benzylamide 4-methyl ester (14b): Following general
procedure E, 13b (150 mg, 0.206 mmol) was coupled with BnNH2 (26 mg,
0.25 mmol) by using DMAP (4 mmol, 2 mL solution), DCC (52 mg,
0.25 mmol), and HOBt (38 mg, 0.25 mmol) to give 14b (160 mg,
0.131 mmol, 64%) as a yellow solid after chromatography (SiO2, PE/EA/
MeOH 2:2:1, Rf =0.35). M.p. 1388C; 1H NMR ([D6]DMSO, 500 MHz,
808C, TMS): d=0.83–0.93 (m, 3H), 0.95–0.98 (m, 3H), 1.40 (s, 4.5H),
1.42 (s, 4.5H), 1.83–1.88 (m, 2H), 1.96–1.99 (m, 3H), 3.57–3.59 (m, 1H),
3.62–3.64 (m, 1H), 3.83 (s, 3H), 3.90–3.92 (m, 1H), 4.32 (A part of an
AB system, J=7.6 Hz, 1H), 4.36–4.42 (m, 4H), 4.66 (B part of an AB
system, J=7.6 Hz, 1H), 4.74 (s, 1H; NH), 5.28 (s, 1H; NH), 6.66–6.68
(m, 2H), 6.92–6.94 (m, 2H), 7.24–7.25 (m, 3H), 7.30–7.33 (m, 4H), 7.76–
7.78 (m, 1H), 7.84–7.86 (m, 1H), 8.56 (s, 2H), 10.63 (s, 1H; NH),
10.88 ppm (s, 1H; NH); 13C{1H} NMR ([D6]DMSO, 125 MHz, 808C,
TMS): d=19.21 (CH3), 19.24 (CH3), 24.37 (CH2), 28.30 (3 CH3), 30.74
(CH2), 32.86 (CH), 43.89 (CH2), 44.10 (CH), 51.82 (CH3), 55.65 (CH2),
65.23 (CH), 65.35 (CH), 73.20 (CH2), 73.74 (CH2), 80.10 (C), 111.63 (2
CH), 116.34 (C), 116.86 (2 CH), 120.01 (C), 121.03 (C), 127.17 (CH),
127.54 (CH), 127.76 (CH), 127.94 (2 CH), 128.23 (CH), 128.70 (2 CH),
129.12 (CH), 130.01 (C), 130.94 (2 CH), 137.84 (C), 140.30 (C), 140.46
(C), 141.17 (2 C), 150.12 (2 C), 166.75 (C), 167.11 (C), 176.82 ppm (C);
IR (ATR): n˜ =3424 (m), 2923 (w), 2852 (w), 1694 (vs), 1539 (w), 1440 (s),
1244 (s), 1162 (m), 1024 (vs), 1004 (vs), 822 (s), 759 cmÀ1 (s); MS (ESI):
m/z (%): 839 (18) [MÀH+Na+], 729 (89), 630 (39), 431 (23), 314 (100);
HRMS (ESI): m/z: calcd for C46H50N5NaO9: 839.3506; found: 839.3505
[MÀH+Na+]; 817.93 (C46H51N5O9).
General procedure D: amidation of aromatic carboxylic acids with amino
acid hydrochlorides:
A solution of DMAP in dichloromethane (c=
1 mmoldmÀ3, 0.01 equiv) and DCC (2.0 equiv) were added to a solution
of carboxylic acid (1.0 equiv) in dichloromethane (0.30 moldmÀ3). After
the reaction mixture was stirred for 1 min at ambient temperature, a col-
orless precipitate was formed and HOBt (88% purity, 2.0 equiv) was
added. In a separate flask, NEt3 (1.2 equiv) was added to a suspension of
the amino acid hydrochloride (1.1 equiv) in dichloromethane
(0.30 moldmÀ3). This suspension was added to the first one and the re-
sulting mixture was stirred in a tightly closed reaction flask for 2 d at
808C. After cooling to 238C, the mixture was diluted with dichlorome-
thane (20 dm3 molÀ1
) and washed with saturated NH4Cl solution
(20 dm3 molÀ1), saturated NaHCO3 solution (20 dm3 molÀ1), and H2O
(20 dm3 molÀ1). After drying over MgSO4 and filtration, the organic layer
was evaporated and the residue purified by chromatography on SiO2.
General procedure F: saponification of methyl ester: K2CO3 (10% aque-
ous solution, 1.1 equiv) was added to a solution of the respective methyl
ester (1.0 equiv) in EtOH (c=0.1 moldmÀ3) and the mixture was stirred
at 508C for 2 h. Subsequently, the reaction mixture was diluted with H2O
(30 dm3 molÀ1), acidified with concentrated hydrochloric acid (ca. 5–
10 dm3 molÀ1), and brine (30 dm3 molÀ1) was added. The aqueous layer
was extracted with dichloromethane (3ꢃ60 dm3 molÀ1) and the combined
organic layers were dried (MgSO4) and filtered. The solvent was evapo-
rated to give the crude carboxylic acids.
5-[3-(tert-Butyloxycarbonylamino)propanoyl]amino-2-[3-(fluoren-9-ylme-
thyloxycarbonylamino)propanoyl]aminoterephthalic acid 1-[2-(tert-buty-
loxycarbonyl)ethyl]amide 4-methylester (14a): Following general proced-
ure D, 13a (114 mg, 0.168 mmol) was coupled with b-Ala-OtBu·HCl
(34 mg, 0.19 mmol) by using NEt3 (19 mg, 0.19 mmol), DMAP
(1.68 mmol, 1.68 mL), DCC (76 mg, 0.37 mmol), and HOBt (56 mg,
0.37 mmol) to give 14a (120 mg, 0.149 mmol, 94%) as a yellow solid
after chromatography (SiO2, PE/EA/MeOH 2:2:1, Rf =0.46). M.p. 1428C;
1H NMR (CDCl3, 500 MHz): d=1.43 (s, 9H), 1.46 (s, 9H), 2.57 (t, J=
5.8 Hz, 2H), 2.60–2.68 (m, 4H), 3.36 (q, J=6.0 Hz, 2H), 3.58 (q, J=
5.0 Hz, 2H), 3.64 (q, J=5.5 Hz, 2H), 3.91 (s, 3H), 4.17 (t, J=6.6 Hz,
1H), 4.36 (d, J=7.0 Hz, 2H), 5.20 (s, 1H; NH), 5.27 (s, 1H; NH), 5.73 (s,
1H; NH), 7.23–7.25 (m, 2H), 7.32–7.35 (m, 2H), 7.56 (d, J=7.3 Hz, 2H),
7.69 (d, J=7.3 Hz, 2H), 8.84 (s, 1H), 9.10 (s, 1H), 10.85 (s, 1H; NH),
10.95 ppm (s, 1H; NH); 13C{1H} NMR (CDCl3, 125 MHz): d=24.81
(CH2), 24.90 (CH2), 25.46 (CH2), 25.58 (CH2), 28.06 (3 CH3), 28.37 (3
CH3), 33.07 (CH2), 33.89 (CH2), 47.21 (CH), 52.87 (CH3), 66.50 (CH2),
77.22 (C), 81.42 (C), 117.51 (C), 119.85 (2 CH), 120.25 (C), 123.28 (CH),
125.03 (2 CH), 126.93 (2 CH), 127.56 (2 CH), 128.97 (CH), 133.44 (C),
135.96 (C), 141.14 (C), 141.21 (C), 143.86 (C), 143.93 (C), 155.82 (C),
156.41 (C), 167.52 (C), 167.75 (C), 170.19 (C), 170.28 (C), 171.31 ppm
(C); IR (ATR): n˜ =3326 (m), 2932 (m), 2855 (w), 1697 (s), 1605 (s), 1541
(s), 1439 (m), 1401 (s), 1366 (m), 1323 (w), 1243 (vs), 1154 (vs), 912 (m),
729 cmÀ1 (vs); MS (ESI): m/z (%): 824 (17) [M+Na+], 727 (9), 563 (25),
477 (86), 431 (100), 352 (39), 293 (19); HRMS (ESI): m/z: calcd for
C42H52N5O11: 802.3663; found: 802.3658 [M+H+]; 801.88 (C42H51N5O11).
5-[3-(tert-Butyloxycarbonylamino)propanoyl]amino-2-[3-(fluoren-9-ylme-
thyloxycarbonylamino)propanoyl]aminoterephthalic acid 1-[2-(tert-butyl-
AHCTUNGTRENNUNG
a
1H NMR (CDCl3, 500 MHz): d=1.43 (s, 9H), 1.45 (s, 9H), 2.38 (t, J=
4.8 Hz, 1H), 2.45 (t, J=4.7 Hz, 1H), 2.62–2.64 (m, 1H), 2.67–2.69 (m,
2H), 2.83–2.85 (m, 1H), 3.39–3.43 (m, 2H), 3.55–3.56 (m, 4H), 4.09–4.16
(m, 1H), 4.29–4.33 (m, 2H), 5.19 (brs, 1H), 5.30 (brs, 1H), 5.73 (brs,
1H), 6.77 (brs, 1H), 7.27–7.29 (m, 4H), 7.36–7.38 (m, 4H), 8.16 (s, 1H),
8.62 (s, 1H), 10.89 (s, 1H), 11.3 ppm (s, 1H); IR (ATR): n˜ =3285 (w),
2985 (m), 1684 (vs), 1532 (vs), 1500 (s), 1452 (m), 1360 (w), 1231 (vs),
1150 (s), 1084 (m), 1021 (m), 967 (m), 722 cmÀ1 (s); MS (ESI, neg.
mode): m/z (%): 786 (70) [MÀH+], 697 (100); HRMS (ESI, neg. mode):
m/z: calcd for C41H48N5O11: 786.3350; found: 786.3358 [MÀH+]; 787.85
(C41H49N5O11).
5-[(S)-2-(tert-Butyloxycarbonylamino)-3-methylbutanoyl]amino-2-{[(S)-1-
(fluoren-9-ylmethyloxycarbonylamino)pyrrolidin-2-yl]carbonylamino}ter-
ephthalic acid 1-benzylamide (15b): Following general procedure F, 14b
(40 mg, 50 mmol) was deprotected to give 15b (31 mg, 38 mmol, 75%,
purity >95% by LC–MS) as a yellow oil. 1H NMR (CDCl3, 500 MHz):
d=0.76–0.94 (m, 6H), 1.35 (s, 4.5H), 1.37 (s, 4.5H), 1.79–1.85 (m, 2H),
2.18–2.21 (m, 3H), 3.39–3.42 (m, 1H), 3.76–3.82 (m, 1H), 4.36–4.38 (m,
1H), 4.46–4.48 (m, 2H), 4.51–4.57 (m, 2H), 4.75 (A part of an AB
system, J=7.2 Hz, 1H), 5.08 (s, 1H, br), 5.23 (B part of an AB system,
General procedure E: amidation of aromatic carboxylic acids with
amines: A solution of DMAP in dichloromethane (c=1 mmoldmÀ3
,
0.01 equiv) and DCC (1.2 equiv) was added to a solution of carboxylic
acid (1.0 equiv) in dichloromethane (0.30 moldmÀ3). After the reaction
mixture was stirred for 1 min at ambient temperature, a colorless precipi-
tate was formed and HOBt (88% purity, 1.2 equiv) was added. After fur-
ther stirring for 1 min, the amine (1.2 equiv) was added. The mixture was
Chem. Eur. J. 2009, 15, 2200 – 2209
ꢂ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
2207

J. Christoffers and R. Pflantz
J=7.0 Hz, 1H), 6.08 (brs, 1H), 6.81–6.86 (m, 2H), 7.24–7.28 (m, 6H),
7.31–7.34 (m, 5H), 7.71 (s, 2H), 7.94 (brs, 1H), 8.98 (brs, 1H), 9.04 ppm
(brs, 1H); IR (ATR): n˜ =3294 (m), 2950 (w), 1703 (s), 1526 (s), 1510
(vs), 1385 (m), 1224 (vs), 1152 (vs), 1077 (s), 1010 (m), 963 (m), 817 (m),
745 cmÀ1 (m); MS (ESI, neg. mode): m/z (%): 803 (100) [M+], 651 (70),
445 (77), 391 (50); 803.91 (C45H49N5O9).
(vs), 1111 (m), 1017 (m), 908 (s), 860 (w), 729 cmÀ1 (vs); MS (ESI): m/z
(%): 682 (100) [M+Na+], 634 (35), 485 (40), 437 (22), 271 (21); MS
(ESI, neg. mode): m/z (%): 658 (100) [MÀH+], 436 (54); HRMS (ESI):
m/z: calcd for C36H41N3NaO9: 682.2740; found: 682.2740 [M+Na+]; ele-
mental analysis calcd for C36H41N3O9 (659.73): C 65.54, H 6.26, N 6.37;
found: C 65.97, H 6.18, N 6.26.
5-[3-(tert-Butyloxycarbonylamino)propanoyl]amino-2-[3-(fluoren-9-ylme-
thyloxycarbonylamino)propanoyl]aminoterephthalic acid 1,4-bis[2-(tert-
butyloxycarbonyl)ethyl]amide (2a): Following general procedure D, 15a
(10 mg, 13 mmol) was coupled with b-Ala-OtBu·HCl (3 mg, 15 mmol),
which was first treated with NEt3 (2 mg, 15 mmol), by using DMAP
(0.1 mmol, 0.1 mL), DCC (3 mg, 15 mmol), and HOBt (3 mg, 15 mmol) to
give 2a (11 mg, 12 mmol, 93%, 90% purity by LCMS) as a yellow oil.
1H NMR (CDCl3, 500 MHz): d=1.36 (s, 9H), 1.38 (s, 18H), 2.29 (t, J=
6.2 Hz, 1H), 2.37 (t, J=5.8 Hz, 1H), 2.50–2.54 (m, 2H), 2.60–2.64 (m,
4H), 3.29–3.35 (m, 2H), 3.43–3.47 (m, 6H), 4.21–4.23 (m, 1H), 4.30–4.34
(m, 2H), 5.08 (brs, 1H), 5.22 (brs, 1H), 5.50 (brs, 1H), 6.52 (brs, 1H),
7.33–7.39 (m, 2H), 7.47–7.52 (m, 2H), 7.59–7.62 (m, 2H), 7.95–7.98 (m,
2H), 8.84 (s, 2H), 10.94 ppm (brs, 2H); IR (ATR): n˜ =3250 (w), 2930 (s),
2855 (m), 1706 (s), 1618 (vs), 1548 (m), 1450 (m), 1366 (s), 1247 (s), 1153
(vs), 845 (w), 742 cmÀ1 (m); MS (ESI): m/z (%): 937 [M+Na+]; 915.04
(C48H62N6O12).
5-(tert-Butyloxycarbonylamino)-2-[(S)-4,4-dimethyl-2-(fluoren-9-ylmeth-
AHCTUNGTERGyNNUN loxycarbonylamino)pentanoylamino]terephthalic acid 1-(4-methoxyben-
zyl)amide 4-methyl ester (17): Following general procedure E, 16
(530 mg, 0.80 mmol) was coupled with PMB–NH2 (132 mg, 0.96 mmol)
by using DMAP (4 mmol, 4 mL solution), DCC (199 mg, 0.96 mmol), and
HOBt (148 mg, 0.96 mmol) to give 17 (385 mg, 0.49 mmol, 61%) as a
yellow oil after chromatography (SiO2, PE/EA 1:1, Rf =0.50). 1H NMR
(CDCl3, 500 MHz): d=1.03 (s, 9H), 1.46 (s, 9H), 1.55–1.63 (m, 2H), 3.67
(s, 3H), 3.91 (s, 3H), 4.23 (t, J=7.1 Hz, 1H), 4.31–4.37 (m, 2H), 4.42–
4.78 (m, 3H), 5.66 (brs, 1H; NH), 6.72–6.73 (m, 2H), 7.03 (brs, 1H;
NH), 7.11–7.13 (m, 2H), 7.23–7.26 (m, 2H), 7.34–7.35 (m, 2H), 7.54 (d,
J=7.4 Hz, 1H), 7.62 (d, J=7.5 Hz, 1H), 7.68 (d, J=7.5 Hz, 2H), 8.53 (s,
1H), 9.17 (s, 1H), 10.10 (s, 1H; NH), 11.49 ppm (s, 1H; NH);
13C{1H} NMR (CDCl3, 125 MHz): d=28.16 (3 CH3), 29.62 (3 CH3), 30.59
(C), 43.16 (CH2), 46.27 (CH2), 47.17 (CH), 52.51 (CH3), 54.11 (CH),
55.04 (CH3), 67.06 (CH2), 80.79 (C), 113.86 (2 CH), 113.95 (C), 116.50
(CH), 116.80 (C), 119.76 (2 CH), 123.25 (CH), 124.90 (C), 125.09 (CH),
125.15 (CH), 125.66 (C), 126.89 (2 CH), 127.49 (2 CH), 128.96 (2 CH),
132.18 (C), 136.80 (C), 141.10 (C), 143.65 (C), 144.02 (C), 152.81 (C),
155.88 (C), 158.83 (C), 167.36 (C), 167.62 (C), 171.72 ppm (C); IR
(ATR): n˜ =3318 (m), 2953 (m), 1699 (s), 1656 (m), 1541 (s), 1512 (s),
1438 (m), 1406 (m), 1367 (w), 1322 (w), 1238 (vs), 1154 (vs), 1047 (m),
973 (s), 921 (s), 733 cmÀ1 (vs); MS (ESI): m/z (%): 801 (100) [M+Na+],
557 (22), 471 (19), 389 (5), 304 (2), 238 (8); HRMS (ESI): m/z: calcd for
5-[(S)-2-(tert-Butyloxycarbonylamino)-3-methylbutanoyl]amino-2-{[(S)-1-
(fluoren-9-ylmethyloxycarbonylamino)pyrrolidin-2-yl]carbonylamino}ter-
ephthalic acid 1-benzylamide 4-[(S)-1-(methoxycarbonyl)-3,3-dimethylbu-
tyl]amide (2b): Following general procedure D, 15b (25 mg, 0.031 mmol)
was coupled with l-Npg-OMe·HCl (7 mg, 34 mmol), which was first treat-
ed with NEt3 (3 mg, 34 mmol), by using DMAP (0.3 mmol, 0.3 mL), DCC
(13 mg, 62 mmol), and HOBt (10 mg, 62 mmol) to give 2b (10 mg,
11 mmol, 37%, purity >90% by HPLC) as a colorless solid. M.p. 1248C;
1H NMR (CDCl3, 500 MHz): d=0.88–0.96 (m, 6H), 1.13 (s, 9H), 1.47 (s,
4.5H), 1.49 (s, 4.5H), 1.66–1.84 (m, 5H), 1.90–1.96 (m, 2H), 3.16–3.31
(m, 1H), 3.60–3.67 (m, 1H), 3.75 (s, 3H), 4.19–4.20 (m, 1H), 4.30–4.38
(m, 2H), 4.22–4.45 (m, 1H), 4.56–4.67 (m, 2H), 4.80–4.89 (m, 1H), 5.30
(s, 1H; NH), 5.38–5.41 (m, 1H), 5.92 (s, 1H; NH), 6.37 (s, 1H; NH),
7.33–7.34 (m, 1H), 7.40–7.49 (m, 2H), 7.57–7.61 (m, 2H), 7.68 (d, J=
8.4 Hz, 2H), 7.86 (d, J=8.3 Hz, 2H), 8.06 (d, J=8.4 Hz, 2H), 8.08 (d, J=
8.4 Hz, 2H), 8.17 (s, 1H), 8.41 (s, 1H), 9.68 (s, 1H; NH), 9.76 ppm (s,
1H; NH); IR (ATR): n˜ =3420 (m), 2896 (w), 1691 (vs), 1567 (s), 1440
(s), 1301 (m), 1162 (m), 1012 (s), 986 (m), 822 (s), 759 cmÀ1 (s); MS
(ESI): m/z (%): 967 [M+Na+] (10), 821 (42), 739 (79), 470 (100); 945.11
(C53H64N6O10).
C44H50N4NaO9:
(C44H50N4O9).
801.3475; found: 801.3470
[M+Na+];
778.89
5-(tert-Butyloxycarbonylamino)-2-[(S)-4,4-dimethyl-2-(fluoren-9-ylmeth-
AHCTUNGTERGyNNUN loxycarbonylamino)pentanoylamino]terephthalic acid 1-(4-methoxyben-
zyl)amide (18): Following general procedure F, 17 (220 mg, 0.282 mmol)
was deprotected to give 18 (150 mg, 0.196 mmol, 70%) as a colorless
1
solid. M.p. 728C; H NMR (CDCl3, 500 MHz): d=1.01 (s, 9H), 1.37–1.40
(m, 2H), 1.49 (s, 9H), 3.74 (s, 3H), 4.04–4.06 (m, 1H), 4.34–4.42 (m, 3H),
4.49–4.53 (m, 2H), 5.21 (brs, 1H), 6.81–6.85 (m, 2H), 7.01 (brs, 1H),
7.25–7.33 (m, 4H), 7.41–7.44 (m, 2H), 7.56–7.58 (m, 2H), 7.67 (d, J=
8.4 Hz, 2H), 8.03 (d, J=8.5 Hz, 2H), 9.88 (brs, 1H), 10.10 (brs, 1H),
11.41 ppm (brs, 1H); 13C{1H} NMR (CDCl3, 125 MHz): d=28.28 (3
CH3), 29.50 (3 CH3), 30.65 (C), 42.81 (CH2), 46.10 (CH2), 47.31 (CH),
53.42 (CH3), 55.26 (CH), 67.21 (CH2), 85.07 (C), 109.41 (2 CH), 114.09
(CH), 114.32 (C), 118.84 (C), 120.07 (C), 120.21 (2 CH), 120.35 (C),
124.70 (CH), 125.05 (2 CH), 125.26 (CH), 127.08 (CH), 127.59 (CH),
128.71 (CH), 128.77 (2 CH), 128.96 (C), 129.42 (C), 136.70 (C), 141.53
(C), 143.49 (C), 144.32 (C), 152.32 (C), 157.82 (C), 159.03 (C), 166.91
(C), 168.23 ppm (C); IR (ATR): n˜ =3297 (m), 2956 (m), 1691 (s), 1537
(vs), 1511 (vs), 1410 (w), 1367 (m), 1239 (vs), 1152 (vs), 1084 (m), 1021
(m), 968 (m), 826 (w), 737 cmÀ1 (s); MS (ESI, neg. mode): m/z (%): 763
[MÀH+]; HRMS calcd for C43H47N4NaO9: 786.3241; found: 786.3242
[M+Na+]; 764.86 (C43H48N4O9).
5-(tert-Butyloxycarbonylamino)-2-[(S)-4,4-dimethyl-2-(fluoren-9-ylmethy-
loxycarbonylamino)pentanoylamino]terephthalic acid 4-methyl ester
(16): Following general procedure C, 10c (320 mg, 0.427 mmol) was de-
protected to give 16 (275 mg, 0.417 mmol, 98%) as a yellow solid. M.p.
1388C; a partly doubled signal set (ratio 1:1) was observed in the NMR
spectra: 1H NMR (CDCl3, 500 MHz), two isomers: d=0.90 (s, 9H), 0.99
(s, 9H), 1.54 (s, 9H), 1.56 (s, 9H), 1.94 (d, J=6.4 Hz, 2H), 1.97 (d, J=
6.4 Hz, 2H), 3.94 (s, 3H), 3.98 (s, 3H), 4.08 (t, J=6.9 Hz, 2ꢃ1H), 4.42–
4.44 (m, 2ꢃ2H), 4.49–4.55 (m, 2ꢃ1H), 5.77 (d, J=6.2 Hz, 2ꢃ1H; NH),
7.10 (t, J=6.8 Hz, 2H), 7.22 (t, J=6.7 Hz, 2H), 7.28–7.33 (m, 2ꢃ2H),
7.47 (t, J=7.9 Hz, 2H), 7.54 (d, J=7.4 Hz, 1H), 7.59 (t, J=7.7 Hz, 2H),
7.63 (d, J=7.5 Hz, 1H), 7.68 (d, J=7.5 Hz, 2ꢃ1H), 8.85 (s, 1H), 9.09 (s,
1H), 9.19 (s, 1H), 9.28 (s, 1H), 9.42 (s, 1H; NH), 9.50 (s, 1H; NH), 10.03
(s, 1H; NH), 10.06 (s, 1H; NH), 11.26 (brs, 1H OH), 11.34 ppm (brs,
1H; OH); 13C{1H} NMR (CDCl3, 125 MHz), two isomers: d=28.31 (3
CH3), 28.35 (3 CH3), 29.52 (3 CH3), 29.68 (3 CH3), 30.67 (2ꢃC), 45.87
(CH2), 46.33 (CH2), 47.17 (CH), 46.96 (CH), 52.72 (CH3), 52.77 (CH3),
54.32 (CH), 54.38 (CH), 67.22 (CH2), 67.75 (CH2), 80.48 (C), 80.99 (C),
118.89 (C), 118.94 (C), 119.86 (2 CH), 119.89 (2 CH), 120.66 (C), 120.68
(C), 121.18 (CH), 121.68 (CH), 122.21 (CH), 122.66 (CH), 124.56 (CH),
124.67 (CH), 125.04 (CH), 125.12 (CH), 126.89 (2 CH), 126.97 (2 CH),
127.63 (2 CH), 127.68 (2 CH), 133.95 (C), 134.00 (C), 136.63 (C), 136.78
(C), 141.20 (2ꢃ2 C), 143.25 (C), 143.30 (C), 143.56 (C), 143.78 (C),
152.62 (C), 152.80 (C), 156.25 (C), 156.84 (C), 167.40 (C), 167.67 (C),
169.68 (C), 170.70 (C), 171.97 ppm (2ꢃC); IR (ATR): n˜ =3319 (w), 2954
(m), 1692 (s), 1539 (vs), 1437 (m), 1410 (m), 1322 (w), 1239 (vs), 1152
5-(tert-Butyloxycarbonylamino)-2-[(S)-4,4-dimethyl-2-(fluoren-9-ylmeth-
AHCTUNGTERGyNNUN loxycarbonylamino)pentanoylamino]terephthalic acid 1-(4-methoxyben-
zyl)amide 4-[1-(methoxycarbonyl)-1-methylethyl]amide (19): Following
general procedure D, 18 (40 mg, 53 mmol) was coupled with Aib–
OMe·HCl (9 mg, 58 mmol), which was first treated with NEt3 (6 mg,
58 mmol), by using DMAP (0.5 mmol, 0.5 mL), DCC (21 mg, 0.105 mmol),
and HOBt (16 mg, 0.105 mmol) to give 19 (32 mg, 28 mmol, 53%, purity
>98% by HPLC) as a yellow oil after chromatography (SiO2, PE/EA/
MeOH 2:2:1, Rf =0.29). 1H NMR (CDCl3, 500 MHz): d=0.92–1.04 (m,
2H), 0.97 (s, 9H), 1.51 (s, 6H), 1.55 (s, 9H), 3.76 (s, 3H), 3.80 (s, 3H),
3.86–3.88 (m, 1H), 4.37–4.42 (m, 3H), 4.53–4.56 (m, 2H), 5.01 (brs, 1H),
5.15 (brs, 1H), 6.78–6.91 (m, 2H), 7.15–7.23 (m, 4H), 7.45–7.47 (m, 2H),
7.57–7.59 (m, 2H), 7.86 (d, J=8.4 Hz, 2H), 8.10 (d, J=8.5 Hz, 2H), 9.16
(brs, 1H), 10.13 (brs, 1H), 10.20 ppm (brs, 1H); IR (ATR): n˜ =3278 (m),
2945 (m), 1702 (vs), 1498 (s), 1356 (w), 1202 (s), 1098 (s), 1013 (m), 972
2208
www.chemeurj.org
ꢂ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2009, 15, 2200 – 2209

Diaminoterephthalates as Fluorescent Materials
FULL PAPER
(m), 911 (m), 866 (w), 723 cmÀ1 (s); MS (ESI): m/z (%): 886 (22)
[M+Na+], 786 (16), 690 (18), 586 (100), 410 (44), 305 (37); HRMS (ESI):
m/z: calcd for C48H57N5NaO10: 886.4003; found: 886.3995 [M+Na+];
863.99 (C48H57N5O10).
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[6] CCDC 705358 (9a) contains the supplementary crystallographic
data for this paper; these data can be obtained free of charge from
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ac.uk/data_request/cif
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5-Amino-2-[(S)-4,4-dimethyl-2-(fluoren-9-ylmethyloxycarbonylamino)-
pentanoylamino]terephthalic acid 1-(4-methoxybenzyl)amide 4-[1-(me-
thoxycarbonyl)-1-methylethyl]amide (20): Following general procedur-
e A, 19 (30 mg, 35 mmol) was deprotected and the residue purified by
column chromatography (PE/EA/MeOH 2:2:1, Rf =0.27) to give 20
1
(25 mg, 33 mmol, 95%, purity >95% by HPLC) as a yellow oil. H NMR
(CDCl3, 500 MHz): d=0.90–0.97 (m, 2H), 0.94 (s, 9H), 1.43 (s, 6H), 3.68
(s, 3H), 3.72 (s, 3H), 3.91–3.93 (m, 1H), 4.30–4.51 (m, 5H), 5.21 (brs,
1H), 5.93 (brs, 2H), 6.80–6.85 (m, 2H), 7.21–7.36 (m, 6H), 7.49–7.52 (m,
2H), 7.82–7.91 (m, 4H), 8.32 (brs, 1H), 9.56 (brs, 1H), 9.67 ppm (brs,
1H); IR (ATR): n˜ =3287 (w), 2953 (w), 1691 (vs), 1510 (s), 1404 (s), 1326
(m), 1225 (vs), 1088 (vs), 984 (w), 913 (m), 720 cmÀ1 (s); MS (ESI): m/z
(%): 764 (100) [M+H+]; HRMS (ESI): m/z: calcd for C43H49N5NaO8:
786.3479; found: 786.3485 [M+Na+]: 763.88 (C43H49N5O8).
2-[(S)-4,4-Dimethyl-2-(fluoren-9-ylmethyloxycarbonylamino)pentanoyl-
ACHTUNGTRENNUNGamino]-5-[(3aS,4R,6aR)-5-(hexahydro-2-oxothienoACHTUNGTRENN[UGN 3.4-d]imidazol-4-yl)-
pentanoylamino]terephthalic acid 1-(4-methoxybenzyl)amide 4-[1-(me-
thoxycarbonyl)-1-methylethyl]amide (2c): Following general procedur-
e B, 20 (20 mg, 26 mmol) was coupled with (+)-biotine (7 mg, 29 mmol)
by using DCC (6 mg, 31 mmol) and HOBt (5 mg, 31 mmol) to give 2c
(9 mg, 9.2 mmol, 35%) as a colorless solid after chromatography (SiO2,
PE/EA/MeOH 2:2:1, Rf =0.17, purity >90% by HPLC). M.p. 898C;
1H NMR (CDCl3, 500 MHz): d=1.08–1.09 (m, 6H), 1.11 (s, 9H), 1.25–
1.35 (m, 8H), 2.41–2.43 (m, 2H), 2.72–2.74 (m, 2H), 3.44–3.47 (m, 6H),
3.93–3.95 (m, 1H), 4.30–4.35 (m, 2H), 4.50–4.53 (m, 2H), 4.61–4.64 (m,
1H), 4.70–4.73 (m, 2H), 5.17 (brs, 1H), 5.24 (brs, 1H), 5.29 (brs, 1H),
5.66 (brs, 1H), 5.79 (brs, 2H), 6.10 (brs, 1H), 7.34–7.37 (m, 1H), 7.41–
7.43 (m, 2H), 7.53–7.56 (m, 2H), 7.67–7.68 (m, 2H), 7.76–7.79 (m, 1H),
7.86–7.87 (m, 1H), 7.98–8.00 (m, 2H), 8.05–8.06 (m, 2H), 8.37–8.40 ppm
(m, 2H); IR (ATR): n˜ =3288 (m), 2927 (s), 2854 (m), 1696 (vs), 1640 (s),
1542 (s), 1450 (s), 1285 (m), 1094 (m), 1028 (m), 737 cmÀ1 (s); MS (ESI):
m/z (%): 1013 [M+Na+]; 990.17 (C53H63N7O10S).
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Acknowledgements
This study was generously supported by the Fonds der Chemischen In-
dustrie. We are grateful to Wolfgang Saak and Detlev Haase for the
single-crystal X-ray analysis and Dr. Herbert Frey for his assistance in
preparing this manuscript.
Received: October 17, 2008
Published online: January 13, 2009
Chem. Eur. J. 2009, 15, 2200 – 2209
ꢂ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
2209