A new photochemical synthesis of benzoxazolo[3,2-b]isoquinolin-11-one and isoquinolino[3,2-b][1,3]benzoxazin-11-one

Article abstract of DOI:10.1016/S0040-4039(02)01955-X

Photocyclization of substituted tetrahydroisoquinoline-1,3-diones, under base-mediated conditions, afforded benzoxazolo[3,2-b]isoquinolin-11-ones and an isoquinolino[3,2-b]benzoxazin-11-one.

Full text of DOI:10.1016/S0040-4039(02)01955-X

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 43 (2002) 8379–8381
A new photochemical synthesis of
benzoxazolo[3,2-b]isoquinolin-11-one and
isoquinolino[3,2-b][1,3]benzoxazin-11-one
Annamalai Senthilvelan and Vayalakkavoor T. Ramakrishnan*
Department of Organic Chemistry, School of Chemical Sciences, University of Madras, Guindy Campus, Chennai 600 025, India
Received 29 June 2002; revised 30 August 2002; accepted 9 September 2002
Abstract—Photocyclization of substituted tetrahydroisoquinoline-1,3-diones, under base-mediated conditions, afforded benzoxa-
zolo[3,2-b]isoquinolin-11-ones and an isoquinolino[3,2-b]benzoxazin-11-one. © 2002 Elsevier Science Ltd. All rights reserved.
Tetrahydroisoquinolines constitute a class of com-
pounds attracting increasing interest due to their bio-
logical activities. They are important key intermediates
for the synthesis of isoquinoline alkaloids.1,2 Isoquino-
line fused heterocyclic compounds are also highly
important showing significant biological activity.3
reported10 the photocyclization of triazole-3-thiones to
triazolo[3,4-b]-1,3-(4H)-benzothiazines, under basic
conditions. To the best of our knowledge there is no
report on the photochemical synthesis of isoquinoline-
fused benzoxazole and benzoxazine systems. We report
here our preliminary results on the photocyclization of
substituted tetrahydroisoquinoline-1,3-diones to ben-
zoxazolo[3,2-b]isoquinolin-11-ones and an isoquino-
A few methods have been reported for the synthesis of
oxazoloisoquinoline analogues.4,5 Xu et al,6 reported
the synthesis of benzoxazolo[3,2-b]isoquinolin-11-ones
lino[3,2-b][1,3]benzoxazin-11-one,
under
basic
conditions.
and
isoquinolino[2,3-a][3,1]benzoxazine-5,12-dione
from homophthalic anhydride. Recently, photocycliza-
tion of N-(2-halophenyl)-pyridine carboxamides to 2-
pyridyl benzoxazoles has been reported.7
The required starting materials, tetrahydroisoquinoline-
1,3-diones 1a–h, were prepared by using the recently
emerging solvent free microwave technique. Microwave
irradiation of homophthalic acid and substituted anili-
nes/benzylamine in acidic silica gel afforded the iso-
quinoline-1,3-diones 1a–h in good yields (Scheme 1).
In continuation of our interest in the photochemical
synthesis of benzothiazoles,8,9 we have recently
Scheme 1.
Keywords: photocyclization; basic conditions; photohydrolysis.
* Corresponding author. Tel.: 91-44-2351269, ext. 214; fax: 91-44-2352494; e-mail: vtrk28@yahoo.com
0040-4039/02/$ - see front matter © 2002 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(02)01955-X

8380
A. Senthil6elan, V. T. Ramakrishnan / Tetrahedron Letters 43 (2002) 8379–8381
The structures of compounds 1a–h were confirmed by
spectral data. Further, the structure of compounds 1b,
1f and 1h were confirmed by single-crystal X-ray
diffraction.11
The formation of product 3 is probably due to ineffec-
tive deprotonation of the benzyl derivative 1h in 1 M
NaOH. Obviously, an increase in the concentration
of base (3 M NaOH) facilitates the deprotona-
tion considerably, which leads to intramolecular substi-
tution of the o-chlorine of the N-benzyl isoquinoline
1h.
Irradiation of the quinoline 1a under aqueous basic
conditions (CH3CN/1 M NaOH, two-phase) in a multi-
lamp reactor (MLR) (254 nm) under nitrogen furnished
the benzoxazolo[3,2-b]isoquinolin-11-one 2a in good
yield (Scheme 1). Similarly, photolysis of compounds
1b–f also gave the corresponding benzoxazolo[3,2-
b]isoquinolin-11-ones 2b–f as the sole products (Table
1). Irradiation of the bromo analogue 1g also afforded
the oxazole 2a. A model reaction of 1a under dark
conditions gave no product; starting material 1a was
isolated.
The structures of the photoproducts 2a–f, 3 and 4 were
consistent with the spectral data.12 Furthermore, the
structure of the compound 2c13 was confirmed by sin-
gle-crystal X-ray diffraction.
In conclusion, it has been observed that irradiation of
tetrahydroisoquinolines 1a–g under base-mediated con-
ditions afforded the respective benzoxazolo isoquinoli-
nes. Photolysis of isoquinoline 1h gave the
decarboxylated or cyclized product depending on the
concentration of the base employed.
The photosubstitution reaction described here involves
intramolecular replacement of the halogen atom present
in the N-phenyl moiety of the isoquinoline-1,3-diones
1a–g by the carbonyl oxygen (C3ꢀCO) under the basic
conditions.
A mechanistic study and experimental details will be
published elsewhere.
Next, the irradiation of the N-benzyl derivative 1h was
carried out using CH3CN/1 M NaOH in a MLR under
nitrogen to afford the N-(2-chlorobenzyl)-2-methyl ben-
zamide 3 involving hydrolysis followed by decarboxyla-
tion (Scheme 2), instead of the expected isoquino-
linobenzoxazine 4. Whereas, irradiation of 1h using the
CH3CN/3 M NaOH (two-phase) conditions afforded
the expected isoquinolino[3,2-b][1,3]benzoxazin-11-one
4 (Table 1) as the only product.
Acknowledgements
We wish to thank the UGC, New Delhi, for the Special
Assistance Programme to the Department of Organic
Chemistry and CSIR-New Delhi for providing the
research fellowship (A.S.V.).
Table 1. Photolysis of tetrahydroisoquinolines 1a–h
1
a
X
R1
H
R2
H
R3
H
R4
H
n
Irradiation time (h)
12
Product
Product yield (%)
41
Mp (°C)
Cl
0
2a
200–202
(204–206)6
188–190
205–207
213–215
(211–212)6
183–185
200–202
198–200
210–212
b
c
d
Cl
Cl
Cl
Cl
H
H
H
Cl
H
H
H
Cl
H
H
H
0
0
0
7
8
9
2b
2c
2d
43
48
46
e
f
g
h
Cl
Br
Br
Cl
H
H
H
H
H
CH3
H
H
H
H
H
Cl
H
H
H
0
0
0
1
10
7
8
2e
2f
2a
4
40
52
50
47
H
12
Scheme 2.

A. Senthil6elan, V. T. Ramakrishnan / Tetrahedron Letters 43 (2002) 8379–8381
8381
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