A new synthesis of methanoisoindoles

Full text of DOI:10.1134/S1070428012040264

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2012, Vol. 48, No. 4, pp. 605–606. © Pleiades Publishing, Ltd., 2012.
Original Russian Text © A.M. Magerramov, I.A. Aliev, U.F. Askerova, I.M. Akhmedov, S.F. Farzaliev, 2012, published in Zhurnal Organicheskoi Khimii,
2012, Vol. 48, No. 4, pp. 607–608.
SHORT
COMMUNICATIONS
A New Synthesis of Methanoisoindoles
A. M. Magerramov, I. A. Aliev, U. F. Askerova, I. M. Akhmedov, and S. F. Farzaliev
Baku State University, ul. Z. Khalilova 23, Baku, AZ-1148 Azerbaijan
e-mail: idrismecid@yahoo.com, rayten507@mail.ru
Received April 25, 2011
DOI: 10.1134/S1070428012040264
Isoindoles occupy a particular place in the chem-
istry of heterocyclic compounds [1, 2]. Some isoindole
derivatives were found to exhibit antihypertensive,
antidiabetic, and antibacterial activity [3, 4]. Polymeric
composite materials based on isoindoles and methano-
isoindoles are used in optoelectronics as fluorescent
sensors and laser dyes [5, 6]. Aromatic character and
high reactivity of isoindoles make them convenient
model substrates for theoretical studies [7].
We succeeded in obtaining compound ΙΙa in 55–
60% yield by treatment of adduct Ι with 2 N aqueous
HCl at 75°C over a period of 0.5 h (as described in [8])
and subsequent addition of a mixture of 5 equiv of
aniline and AcONa·7 H2O in CHCl3. Presumably,
initial hydrolysis of compound Ι gives intermediate
dialdehyde A which then reacts with amine according
to Paal–Knorr to afford compounds ΙΙ (Scheme 2).
Scheme 2.
Among isoindole derivative, methanoisoindoles
have been studied relatively poorly, and available data
on these compounds are contradictory [7]. Lebedev
et al. [4] described a procedure for the synthesis of
4-aryl-4-azatricyclo[5.2.1.02,6]deca-2,5,8-trienes ΙΙ in
62–65% yield by reaction of amines with cyclopenta-
diene adduct Ι with cis/trans-isomeric 2,5-dimethoxy-
2,5-dihydrofurans in glacial acetic acid at 70–100°C
(Scheme 1). However, we failed to reproduce this
procedure. Kobayashi et al. [7] also failed to obtain
compound ΙΙ under the conditions described in [4].
The authors [7] developed a four-step procedure for
the synthesis of ΙΙ via reaction of aromatic amine with
3-(diethoxymethyl)bicyclo[2.2.1]hepta-2,5-diene-2-
carbaldehyde (adduct of cyclopentadiene with 4,4-di-
ethoxybut-2-ynal), followed by reduction of the prod-
ucts to amines and cyclization of the latter to the cor-
responding methanoisoindoles. However, the yields
were relatively poor (18–22%).
CHO
CHO
RNH2
2 N HCl
I
IIa, IIb
A
The properties of compound ΙΙa were fully con-
sistent with those reported in [7]. The structure of ΙΙa
and IIb was confirmed by their H and 13C NMR
1
spectra and elemental analysis. The 1H NMR spectrum
of 4-phenyl-4-azatricyclo[5.2.1.02,6]deca-2,5,8-triene
(ΙΙa) contained two doublets at δ 2.29 (J = 6.85 Hz)
and 2.44 ppm (J = 6.85 Hz) from protons in the meth-
ylene bridge with an intensity ratio of 1:1. Magneti-
cally equivalent (in pairs) 3-H/5-H protons in the pyr-
role ring and 1-H/7-H and 8-H/9-H in the norbornene
fragment resonated as singlets at δ 6.72, 3.80, and
6.78 ppm, respectively. Signals from protons in the
benzene ring appeared as three triplets at δ 7.10 (J =
7.20 Hz), 7.26 (J = 7.55 Hz), and 7.32 ppm (J =
7.26 Hz) with an intensity ratio of 1:2:2.
Scheme 1.
10
OMe
RNH2, AcOH
5
Initial compound Ι was synthesized according to
the procedure described in [9].
7
70–100°C
6
8
O
N4
R
1
9
3
2
Compounds ΙΙa and IIb (general procedure).
A mixture of 1 mmol of adduct Ι and 3.5 ml of 0.2 N
hydrochloric acid was stirred for 0.5 h at 75°C and
cooled to room temperature, 7.1 mmol of AcONa·
OMe
I
IIa, IIb
R = Ph (a), PhCH2 (b).
605

MAGERRAMOV et al.
606
7H2O, 5 mmol of aniline or benzylamine, and 15 ml of
chloroform were added, and the mixture was heated
for 24 h under reflux. The progress of the reaction was
monitored by TLC (Silufol UV-254, hexane–ethyl
acetate, 8:2). The mixture was washed with a saturated
solution of sodium hydrogen carbonate, the organic
phase was separated and dried over MgSO4, the
solvent was distilled off, and the residue was subjected
to column chromatography on KSK silica gel
(O-70MK) using hexane–ethyl acetate (8:2) as eluent.
124.00, 129.34, 138.55, 141.58, 142.52. Found, %:
C 86.94; H 6.70; N 6.41. Calculated, %: C 86.88;
H 6.78; N 6.33.
1
The H and 13C NMR spectra were recorded on
a Bruker 400FT spectrometer at 400 and 100 MHz,
respectively, using CDCl3 as solvent and tetramethyl-
silane as internal reference.
REFERENCES
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4-Phenyl-4-azatricyclo[5.2.1.02,6]deca-2,5,8-tri-
ene (ΙΙa). Yield 0.10 g (50%), mp 91–95°C (from hex-
1
ane); published data [7]: mp 91–92°C. H NMR spec-
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3-H, 5-H), 6.78 s (2H, 8-H, 9-H), 7.10 t (1H, Harom, J =
7.20 Hz), 7.26 t (2H, Harom, J = 7.55 Hz), 7.32 t (2H,
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141.52, 142.50. Found, %: C 87.12; H 6.51; N 6.85.
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6.84 m (2H, Harom), 7.22 m (3H, Harom). 13C NMR spec-
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