PAPER
Photoinduced Decarboxylation of N-Phthaloylanthranilic Acid Amides
1165
Hz. Mass spectroscopy (EI or CI): Finnigan Incos 500; m/z (rel. %).
UV/VIS: Perkin-Elmer Lambda 7, UV/VIS spectrophotometer; in
nm ( ). HR-Mass spectroscopy (FAB): Finnigan MAT H-SQ 30.
Combustion analyses: Elementar Vario EL. Optical rotations were
determined on a Perkin-Elmer polarimeter 241, CD spectra on a Jas-
co J-715 spectrometer. All solvents were freshly distilled before
use. Starting materials were purchased from Aldrich.
2-(1,3-Dihydro-1-hydroxy-3-oxoisoindol-2-yl)-benzoic Acid
(13)
A solution of the bis-postassium salt of 7b (830 mg, 2.09 mmol) in
H2O (200 mL) was photolyzed following procedure D. After col-
umn chromatography of the crude product mixture (630 mg), 97 mg
(13%) of 7c was isolated beside 123 mg (22%) of the photoreduc-
tion product 13.
1H NMR (CDCl3): = 6.63 (s, 1 H), 7.31 (dt, J = 1.1, 7.8 Hz, 1 H),
7.68 (m, 4 H), 7.93 (d, J = 7.4 Hz, 1 H), 8.13 (dt, J = 1.3, 7.7 Hz, 2
H).
Coupling of N-Phthaloylanthranilic Acid with Amino Acid
Benzyl Esters; General Procedure
N-Phthaloylanthranilic acid was synthesized from anthranilic acid
and phthalic anhydride via solvent-free condensation at 140°C. A
solution of equimolar amounts of N-phthaloylanthranilic acid, 1-hy-
droxybenzotriazol (HOBt), Et3N and the p-toluenesulfonate of the
-amino acid benzyl ester in DMF (200 mL of DMF/40 mmol of
amino acid component) was cooled to –20°C and treated with
equimolar amounts of dicyclohexyl carbodiimide (DCC). After stir-
ring for 3 h at –30°C and 4–6 d at r.t., the solution was filtered and
the filtrate was washed with 5% aq NaHCO3 (3 50 mL), 10% HCl
(2 50 mL) and brine (2 100 mL). After drying (MgSO4) and
evaporation of the organic solvents, the residue was directly used
for the debenzylation step.
13C NMR (CDCl3): = 84.7 (CH), 115.1 (Cq), 119.6 (CH), 124.1
(CH), 124.7 (CH), 125.4 (CH), 131.0 (CH), 131.3 (CH), 131.7 (Cq),
133.7 (CH), 135.9 (CH), 138.0 (Cq), 138.8 (Cq), 162.6 (Cq), 164.5
(Cq).
2-[2-(Azetidino-1-carbonyl)phenyl]isoindole-1,3-dione (14)
A solution of the potassium salt of 9b (700 mg, 2.00 mmol) in H2O–
acetone (200 mL, 1:1) was photolyzed following procedure A. After
column chromatography of the crude product mixture (270 mg), 80
mg (13%) of 9c was isolated beside 60 mg (10%) of the decarbox-
ylation product 14.
1H NMR (CDCl3): = 2.31 (quin, J = 7.7, 7.8 Hz, 2 H), 4.02 (t,
J = 7.8 Hz, 2 H), 4.22 (t, J = 7.7 Hz, 2 H), 7.13–7.56 (m, 4 H), 7.73
(dd, J = 3.1, 5.5 Hz, 2 H), 7.90 (dd, J = 3.1, 5.5 Hz, 2 H).
Hydrogenolytic Debenzylation of Benzyl Esters 1a–12a, 1d–
12d; General Procedure
A suspension of 10% Pd/C (500 mg) in MeOH (10 mL) was added
to a solution of benzyl ester (30 mmol) in MeOH (100 mL) under
N2. Vigorous stirring was continued under positive hydrogen gas
pressure for 14–18 h at r.t. The MeOH solution was filtrated over
Celite and the Celite was subsequently washed with EtOAc (100
mL) and 10% HCl (50 mL). The organic layer was separated and
treated with 5% aq NaHCO3 (3 50 mL). After phase separation,
the pH of the aqueous layer was adjusted to pH 3 and extracted with
EtOAc (3 75 mL). After drying (MgSO4) the combined organic
phases and evaporation of the solvents, the residue was crystallized
from Et2O–acetone or purified by flash chromatography.
13C NMR (CDCl3): = 15.7 (CH2), 48.7 (CH2), 52.6 (CH2), 123.7
(CH), 127.9 (CH), 128.2 (CH), 129.4 (Cq, 129.8 (CH), 130.5 (CH),
131.6 (Cq, 132.0 (CH), 134.2 (CH), 167.3 (Cq, 169.7 (Cq).
X-Ray Structure Analyses of Compounds 3c, 4c, and 9c
Data Collection: Nonius-Kappa-CCD diffractometer, room temper-
ature, Mo-K -radiation ( = 0.71073 Å), graphite monochromator,
–
– scans, 2 limits [°]: 2–54.
Structure Analysis and Refinement: solved by direct methods; full
matrix least-squares refinement with anisotropic thermal parame-
ters for C, N and O and isotropic parameters for H.
Photocyclization of 1b–12b, 1e–12e
Programs Used: for structure determination SHELXS-97 and for
General Procedure A: A solution of the starting material (3 mmol)
in acetone (10 mL) was combined with a solution of K2CO3 (207
mg, 1.5 mmol) in H2O (10 mL) and heated to 50°C for 1 min. The
resulting clear solution was diluted with equal volumes of H2O and
acetone (total solvent volume: 150–200 mL) and irradiated in a pyr-
ex tube in a Rayonet® chamber photoreactor RPR-208 (8 3000Å
lamps, ca 800 W, = 300 10 nm) with constant N2 purging at r.t.
for 12–20 h. The slightly yellow solution was treated with of sat. aq
NaHCO3 (2 mL) and brine (40 mL). After extraction with EtOAc (3
100 mL), drying (MgSO4) and evaporation of the organic sol-
vents, the residue was purified by flash chromatography.
refinement SHELXL-97.
Crystal Data of 3c: C19H18N2O3 (from acetone): M = 322.3, orthor-
hombic, a = 10.501(1), b = 18.600(1), c = 20.024(1) Å; space group
P212121, Z = 8, 29362 reflections measured, 8237 unique reflec-
tions, 4966 reflections with I>2 (I), R1 = 0.054, wR2 = 0.106; 4c
C20H20N2O3C6H12O2 (from acetone): M = 452.5, triclinic
a = 13.552(1), b = 13.572(1), c = 15.567(1) Å, = 104.73(1)°,
= 108.57(1)°, = 103.82(1)°, space group P–1, Z = 4, 9464 re-
flections measured, 9464 unique reflections, 5366 reflections with
I>2 (I), R1 = 0.060, wR2 = 0.122; 9c C18H14N2O3H2O (from
EtOAc). M = 324.3, monoclinic, a = 11.228(1), b = 10.794(1), c =
13.201(1) Å, = 104.65(1)°, space group P21/n, Z = 4, 6435 reflec-
tions measured, 3374 unique reflections, 2615 reflections with
I>2 (I), R1 = 0.041, wR2 = 0.101. Crystallographic data (excluding
structure factors) for the structures reported in this paper have been
deposited with the Cambridge Crystallographic Data Centre as sup-
plementary publications no. CCDC-157753 (3c), CCDC-157754
(4c), CCDC-157755 (9c). Copies of the data can be obtained free of
charge from CCDC, 12 Union Road, Cambridge CB2 1EZ, UK
(fax: +44–1223–336–033, e-mail: deposit@ccdc.cam.ac.uk).
General Procedure B: A solution of the starting material (30
mmol) in acetone (50 mL) was combined with a solution of K2CO3
(2.07 g, 15 mmol) in H2O (200 mL) and heated to 50°C for 1 min.
The resulting clear solution was diluted with H2O (1750 mL) and ir-
radiated in a falling-film photoreactor with a 3.5 kW XeCl excimer
lamp with constant argon purging at r.t. for 4–5 h. The yellow prod-
uct solution was treated with sat. aq NaHCO3 (40 mL) and brine
(200 mL). After extraction with EtOAc (3 400 mL), drying
(MgSO4) and evaporation of the organic solvents, the residue was
purified by fractional crystallization from acetone.
General Procedure C: Analogous to B; MeCN instead of acetone
as organic co-solvent.
Acknowledgement
General Procedure D: Analogous to B; suspension or solution in
H2O without organic co-solvent.
We acknowledge the financial support by the Deutsche Forschungs-
gemeinschaft (GR 881/7–3), the Fonds der Chemischen Industrie,
Aventis AG and Degussa-Hüls AG.
Synthesis 2001, No. 8, 1159–1166 ISSN 0039-7881 © Thieme Stuttgart · New York