s-Indacene-1,3,5,7(2H,6H)-tetraone ('Janus dione') and 1-3-dioxo-5,6- indane-dicarboxylic acid: Old and new 1,3-indandione derivatives

Article abstract of DOI:10.1055/s-2004-831184

Efficient syntheses, X-ray structures and spectroscopic properties of s-indacene-1,3,5,7(2H,6H)-tetraone (1) and 1,3-dioxo-5,6-indanedicarboxylic acid (2), their precursors and derivatives, are described for the first time.

Full text of DOI:10.1055/s-2004-831184

PAPER
2509
s-Indacene-1,3,5,7(2H,6H)-tetraone (‘Janus dione’) and 1,3-Dioxo-5,6-indane-
dicarboxylic Acid: Old and New 1,3-Indandione Derivatives
s-
Indacene-1,3
n
,5,7(2
H
,6
H
)
i
n
e
and 1,3-D
i
oxo-5, 6-indanedi
K
c
arboxylic
A
cid rief,a James Y. Becker,*a Arkady Ellern,a Vladimir Khodorkovsky,*a,b Ojars Neilands (the late),c
Lev Shapiroa
a
Department of Chemistry, Ben Gurion University of the Negev, Beer Sheva 84105, Israel
Fax +972(8)6472188; E-mail: hodor@bgumail.bgu.ac.il
b
Université de la Méditerranée, UMR CNRS 6114, 13288 Marseille 09, France
c
Department of Organic Chemistry, Riga Technical University, Riga 1048, Latvia
Received 14 May 2004
densation product 4, which can easily be determined by
Abstract: Efficient syntheses, X-ray structures and spectroscopic
properties of s-indacene-1,3,5,7(2H,6H)-tetraone (1) and 1,3-di-
oxo-5,6-indanedicarboxylic acid (2), their precursors and deriva-
tives, are described for the first time.
1H NMR spectrum of the crude reaction mixture. All pre-
vious syntheses of 5 (or the dimethoxycarbonyl deriva-
tive) employed condensation of pyromellitic acid
tetraester with ethyl (or methyl) acetate in the presence of
sodium alcoholates.2,3 The purity of poorly soluble disodi-
um salt of 5 cannot be effectively controlled. Neutral di-
ester 5 also possesses a very low solubility, is unstable at
elevated temperatures and cannot be purified either by
crystallization or chromatography. When this compound,
prepared by the acidification of 3, was contaminated with
6, it afforded only or mostly the polymer even in HOAc.
Therefore, the purity of 3 is crucial.
Key words: arenes, s-indacene, ketones, indandiones, hydrolyses
Recently we demonstrated that the condensation products
of s-indacene-1,3,5,7(2H,6H)-tetraone (1) with p-dialkyl-
amino derivatives of benzaldehyde and cinnamaldehyde
possess large two-photon absorption (TPA) cross-section
coefficient and high quantum yields of fluorescence,
which makes them attractive chromophores for two-pho-
ton fluorescent imaging.1 The TPA behaviour of these
chromophores was attributed, in particular, to the unusual
orbital structure of 2,6-diylidene substituted derivatives.
The above finding and high potential of 1 as a precursor
for other s-indacene derivatives was the driving force for
studying its chemistry in more detail. However, the litera-
ture search showed that the synthesis of 1, which we pro-
pose to name as ‘Janus dione’, is still a challenge.
The optimized procedures for synthesis of 3 and 4, afford-
ed the clean compounds in 60% and 50% yields, respec-
tively. The structure of both compounds was determined
by X-ray diffraction analyses (Figures 1 and 2).
O
O
O
O
O
O
Thus, the first attempts to synthesize 1 by mineral acid
catalyzed hydrolysis of the 2,6-diethoxycarbonyl deriva-
tive and subsequent decarboxylation in analogy to the
well known procedure for 1,3-indandione, afforded only a
black insoluble polymer as a result of self-condensation.2
Back in 1963, one of us found that 1 formed grey leaflets
in low yields, when the hydrolysis was performed in
HOAc.3 Unfortunately, to the best of our knowledge, this
is the only method known to date. The practical yields of
1 never exceeded 10% of the theoretical values. More-
over, the reaction often fails completely giving a polymer
as the only product.
CH3COCH2COOEt
Ac2O, Et3N
O
O
O
O
O
O
O
O
EtO
O
O
+
O
OEt
Et3NH
OEt
O
4
3
2Et3NH
H+
We investigated the condensation reaction of pyromellitic
anhydride with ethyl acetoacetate in the presence of Et3N
in acetic anhydride and report here on efficient high yield
synthesis of 1 and previously unknown 1,3-dioxo-5,6-in-
danedicarboxylic acid (2) (Scheme 1). We found that
whereas the above modification afforded good yields of
the salt 3, it was always contaminated with the mono-con-
O
O
O H
O
O H
O
EtO
O
O
HO
HO
OEt
OEt
O
H O
O
6
5
- CH2=CH2, -CO2
O
O
O
O
O
O
O
HO
HO
SYNTHESIS 2004, No. 15, pp 2509–2512
x
x.
x
x
.
2
0
0
4
Advanced online publication: 19.08.2004
O
1
2
DOI: 10.1055/s-2004-831184; Art ID: P04804SS
© Georg Thieme Verlag Stuttgart · New York
Scheme 1

2510
P. Krief et al.
PAPER
Figure 1 ORTEP of 3 at 50% probability level for non-hydrogen
atoms. The triethylammonium cations and hydrogen atoms are omit-
ted for clarity. Selected distances: C1-O1, 1.231 (2); C1-C2, 1.505
(2); C5-O2, 1.240 (2); C5-C6, 1.432 (2); C1-C6 (–x + 1, –y, –z), 1.437
(2).
Figure 3 ORTEP of 1 at 50% probability level. Selected distances:
C2-C3, 1.496 (2); C3-O1, 1.203 (2); C3-C4, 1.512 (2).
Figure 2 ORTEP of one of two crystallographically independent
molecules of 4 at 50% probability level. The triethylammonium cati-
on and hydrogen atoms are omitted for clarity. Selected distances:
C4-O1, 1.177 (5); C4-O2, 1.403 (5); C3-C4, 1.472 (5); C5-O3, 1.210
(5); C5-O2, 1.369 (5); C5-C6, 1.471 (5).
Figure 4 Absorption spectrum of a mixture of 1 and two equiva-
lents of DBU in DMSO.
Neutral ester derivatives 5 and 6 decomposed on crystal-
lization attempts. However, we found that refluxing both
derivatives in anhydrous polar solvents afforded pure 1 or
2 in almost quantitative yields. The purity and the yields
of the products depended on the presence of water; using
thoroughly dried 5 and 6 in absolute MeCN gave the best
results. This surprising finding led us to believe that both
°C. The X-ray quality crystals were obtained from MeCN
(Figure 5). Even clean samples of 2 are unstable and de-
compose slowly within a few weeks, forming a complicat-
ed mixture of self-condensation products.
5 and 6, being very strong O-H acids, are capable of self- Heating of 2 in a mixture of toluene and acetic anhydride
protonation and decarboxylation occurs after elimination afforded 1,3,7-trioxo-3,7-dihydro-1H-indeno[5,6-c]fu-
of ethylene. The reaction indeed did not occur with the ran-5-yl acetate (7), which is stable in the absence of
corresponding methyl esters.
moisture. In the presence of basic or acidic catalysts, this
derivative can be used as a relatively stable synthetic
equivalent of 2. The reactivity of 2 is similar to that of 1,3-
indandione. In particular, it reacts smoothly with p-dieth-
ylamino derivatives of benzaldehyde and cinnamaldehyde
in the presence of mineral acids affording the correspond-
ing donor/acceptor substituted alkene derivatives 8 and 9
(Figure 6). The long wave absorption band of derivative 8
is red-shifted by about 30 nm compared to its 5,6-unsub-
‘Janus dione’ forms colourless leaflets when it precipi-
tates from the MeCN reaction mixtures and sublimes
above 277 °C, forming colourless plates poorly soluble in
most common organic solvents. Crystals suitable for X-
ray analysis were obtained from an MeCN solution of a
freshly sublimed sample (Figure 3). ‘Janus dione’ under-
goes fast polymerization in the presence of acids, but
forms stable dianion in the presence of bases. The UV–
Vis spectrum of the dianion solution features a broad
structured band around 500 nm (e = 2,600) (Figure 4).
stituted
analog
2-p-diethylaminobenzylidene-1,3-
indandione4 [lmax (CH2Cl2) = 488 nm, e = 77,000).
The chemical properties of 1 resemble that of 1,3-indan- Upon heating derivatives 8 and 9 in acetic anhydride the
dione in many aspects and will be reported elsewhere.
corresponding cyclic anhydrides are formed easily. Albeit
poorly soluble, both anhydrides are highly reactive and
rapidly form mono-esters and cyclic imides in reactions
with alcohols and primary amines, respectively. Since the
2-ylidene-1,3-indandione-5,6-dicarboxylic acid moiety is
1,3-Dioxo-5,6-indanedicarboxylic acid (1,3-indandione-
5,6-dicarboxylic acid) (2) is hitherto unknown. It precipi-
tates from the MeCN reaction mixture as colourless nee-
dles and sublimes under elimination of water above 224
Synthesis 2004, No. 15, 2509–2512 © Thieme Stuttgart · New York

PAPER
s-Indacene-1,3,5,7(2H,6H)-tetraone and 1,3-Dioxo-5,6-indanedicarboxylic acid
2511
HRMS: m/z [M – 2 Et3N] calcd for C18H15O8: 359.0767; found:
359.0700.
7-Oxy-1,3,5-trioxo-3,5-dihydro-1H-2-oxa-s-indacene-6-carbox-
ylic Acid Ethyl Ester Triethylammonium Salt (4); Typical Pro-
cedure
A mixture of pyromellitic anhydride and ethyl acetoacetate (1:1
equiv) with Et3N (6 equiv) in acetic anhydride (16 mL per 1 g of py-
romellitic anhydride) was heated at 70 °C for 15 min following
overnight cooling at 0–5 °C afforded a precipitate of clean 4 in 54%
yield, which was washed with acetic anhydride and Et2O. Yellow-
orange large crystals become green at 120 °C and decomposed at
140 °C.
1H NMR (CDCl3): d = 1.33 (t, 9 H, CH3), 1.35 (t, 3 H, CH3), 1.68
(br s, 1 H, NH), 3.30 (m, 6 H, CH2N), 4.23 (q, 2 H, CH2O), 8.01 (s,
2 H, CH).
Figure 5 ORTEP of 2 at 50% probability level. Selected distances
C2-O1: 1.204 (2); C1-C2: 1.499(2); C2-C3: 1.518 (2); C4-O2: 1.219
(2); C4-C5: 1.482 (2); C3-C4: 1.503 (2).
HRMS: m/z [M – Et3N] calcd for C14H9O7: 289.0348; found:
289.0344.
a stronger acceptor than 2-ylidene-1,3-indandione moiety,
these derivatives are expected to be more effective second
harmonic generation (SHG) chromophores than the corre-
sponding derivatives of 1,3-indandione.5 In addition, the
presence of two o-carboxylic groups offers wide opportu-
nities for further structural modifications and, owing to
their hydrophilic properties, allows studies of such chro-
mophores using the Langmuir technique and fabrication
of SHG capable LB films. These studies are currently un-
der way in our research labs.
s-Indacene-1,3,5,7(2H,6H)-tetraone (1); Typical Procedure
Concentrated H2SO4 acid (1 mL) was added to a solution of 3 (1 g,
1.78 mmol) in water (100 mL) at 0 °C. The orange precipitate was
filtered off, washed with EtOH (25 mL) and thoroughly dried at r.t.
to give 5 (0.6 g, 94%). A suspension of 5 (1 g, 2.79 mmol) and an-
hyd MeCN (100 mL) was heated under reflux for 2 h. After cooling
to r.t. the colourless precipitate was filtered off and dried to give 1
(0.54 g, 90%). The compound was crystallized from MeCN as co-
lourless leaflets. It sublimes above 277 °C.
IR (KBr): 2962, 2925, 1757, 1724, 1714, 1693, 1385, 1362, 1350,
1225, 874, 733 cm–1.
1H NMR (CD2Cl2): d = 3.39 (s, 4 H, CH2), 8.44 (s, 2 H, CH).
O
O
OAc
O
HO
HO
1,3-Indandione-5,6-dicarboxylic Acid (2); Typical Procedure
Concentrated H2SO4 acid (4 mL) was added to a solution of 4 (1 g,
2.57 mmol) in water (50 mL) at 0 °C. The yellow precipitate was
filtered, washed with EtOH (5 mL) and thoroughly dried at r.t. to
give 6 (0.75 g, 95%). A suspension of 6 (1 g, 3.26 mmol) and anhyd
MeCN (100 mL) was heated under reflux for 30 min. The solvent
was removed under reduced pressure to give 2 (0.8 g, 95%). Pure
product (0.75 g, 90%) was obtained by crystallization from MeCN
as colourless needles. It sublimes above 224 °C under elimination
of water.
O
n
O
O
O
O
7
8, n = 0
9, n = 1
N Et
Et
Figure 6
In summary, we elaborated reproducible synthetic proce-
dures and for the first time characterized two simple 1,3-
IR (KBr): 3356 (br), 3099, 3050, 2918, 1736, 1693, 1252, 1232,
indandione derivatives: s-indacene-1,3,5,7(2H,6H)-tetra- 1196, 1128, 895, 783, 768 cm–1.
1H NMR (acetone-d6): d = 8.20 (s, 2 H, CH), 3.41 (s, 2 H, CH2).
one (1) and 1,3-dioxo-5,6-indanedicarboxylic acid (2).
Both compounds can serve as valuable precursors for mo-
lecular and polymeric advanced materials.
1,3,7-Trioxo-3,7-dihydro-1H-indeno[5,6-c]furan-5-yl Acetate
(7); Typical Procedure
A mixture of 2 (0.2 g, 0.85 mmol), freshly distilled acetic anhydride
(5 mL) and toluene (5 mL) was heated at 90 °C for 1 h. The orange
precipitate was filtered off, washed with toluene (20 mL) to give 7
(0.14 g, 63%). Crystallization of pure 7 from toluene afforded yel-
low needles; mp 174 °C. Yellow crystals; mp 174 °C. X-Ray struc-
ture of 7 was determined and will be reported elsewhere.
IR spectra were recorded by Nicolet 5ZDX instrument and UV–Vis
spectra by Jasco 2500 spectrophotometer. NMR spectra were re-
corded on a Bruker DMX 500 MHz instrument.
3,7-Dioxy-1,5-dioxo-1,5-dihydro-s-indacene-2,6-dicarboxylic
Acid Diethyl Ester Bis(triethylammonium) Salt (3); Typical
Procedure
Heating a mixture of pyromellitic anhydride (1 equiv), ethyl ace-
toacetate (3 equiv), Et3N in (12 equiv) acetic anhydride (16 mL per
1 g of pyromellitic anhydride) at 100 °C for 1.5 h and leaving the
mixture overnight at 0–5 °C afforded a precipitate of clean 3 in 60%
yield, which was washed with acetic anhydride and Et2O. Orange
large crystals become brown at 120 °C and decomposed at 140 °C.
IR (KBr): 2930, 1849, 1797, 1771, 1709, 1565, 1454, 1376, 1273,
1153, 904, 833, 781, 742 cm–1.
1H NMR (CDCl3): d = 2.48 (s, 3 H, CH3CO), 6.45 (s, 1 H, CH), 7.84
(s, 1 H, CH), 8.03 (s, 1 H, CH).
Anal. Calcd for C13H6O6: C, 60.48; H, 2.34. Found: C, 60.53; H,
2.29.
1H NMR (CDCl3): d = 1.26 (t, 18 H, CH3), 1.30 (t, 6 H, CH3), 3.22
(m, 12 H, CH2N), 4.18 (q, 4 H, CH2O), 7.61 (s, 2 H, CH).
X-ray Crystal Structure Determinations
Intensity data for X-ray structure determination were collected with
Bruker diffractometer, 6K CCD detector [l(MoKa) = 0.711069A,
Synthesis 2004, No. 15, 2509–2512 © Thieme Stuttgart · New York

2512
P. Krief et al.
PAPER
graphite monochromator, 1800 frames with a scan width of 0.3° in
w for full sphere coverage of reciprocal space and 50 frames for de-
cay correction, and exposure time of 10 s/frame, detector-crystal
distance 4.95 cm] and integrated with Bruker Saint software pack-
age using a wide-frame integration algorithm. All structures were
solved by direct methods and refined by least squares in full-matrix
anisotropic approximation for all non-hydrogen atoms. The hydro-
gen atoms were included with geometrically calculated positions
and refined using ‘riding model’. Bruker SHELX software package
was used for all calculations and drawings.
(Rint = 0.0243) and 2041 with Fo>4s(Fo).: 179 parameters. Structure
was refined to R1 = 0.0463, wR2 = 0.1298, GOF = 1.059.
The crystallographic data for structures 1–4 have been deposited
with the Cambridge Crystallographic data Centre: CCDC 172783–
172786.
Acknowledgment
The authors thank EC FP5 (Grant 81851) and the Ministry of Sci-
ence (Israel) for financial support.
A yellow block (0.5 × 0.4 × 0.4 mm) of 3 is monoclinic, C18H12O8
× 2 (Et3NH), space group P21/n, at 298 K, a = 10.687(1), b = 13.365
(2), c = 11.701 (2) Å, b = 112.202 (3)°, V = 1547.5 (3) Å3, Z = 2,
F(000) = 604. 12867 reflections were collected (2q < 56.58°), of
which 3850 reflections were independent (Rint = 0.0358 and 1806
with Fo>4s(Fo): 189 parameters. Structure was refined to R1 =
0.0463, wR2 = 0.1210, GOF = 0.974. An orange prism (0.7 × 0.4 ×
0.3 mm) of 4 is monoclinic, C14H7O7 × Et3NH, space group P1, at
298 K, a = 10.440 (1), b = 13.998 (2), c = 15.088 (2) Å, a = 69.824
(3)°, b = 73.989 (3)°, g = 88.154 (3)°, V = 1984.5 (4) Å3, Z = 4,
F(000) = 824. A total of 17816 reflections were collected (2q <
49.42°), of which 6761 reflections were independent (Rint = 0.0471)
and 4365 with Fo >4s (Fo): 521 parameters. Structure was refined to
R1 = 0.0831, wR2 = 0.256, GOF = 1.005. A colourless plate (0.2 ×
0.2 × 0.05 mm) of 1 is orthorhombic, C12H6O4, space group Cmca,
at 293 K, a = 18.962 (2), b = 5.782 (2), c = 8.353 (2) Å, V = 915.9
(1) Å3, Z = 4, F(000) = 440. 5149 reflections were collected (2q <
56.58°), of which 587 reflections were independent (Rint = 0.0291)
and 495 with Fo>4s(Fo): 47 parameters. Structure was refined to
R1 = 0.0405, wR2 = 0.1072, GOF = 1.06. A colourless prism (0.4 ×
0.4 × 0.2 mm) of 2 is monoclinic, C11H6O6, space group P21/c, at
293 K, a = 7.662 (1), b = 9.814 (1), c = 13.458 (1) Å, b = 106.128
(2)°, V = 972.2 (2) Å3, Z = 4, F(000) = 8201 reflections were col-
lected (2q < 56.56°), of which 2410 reflections were independent
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Synthesis 2004, No. 15, 2509–2512 © Thieme Stuttgart · New York