[1 + 4]cycloaddition of isocyanides with 2-acetyl-1,4-benzoquinone; a convenient synthesis of isobenzofuran-4,7-quinones

Article abstract of DOI:10.1039/a903897c

Isocyanides undergo formal [1 +4]cycloaddition with 2-acetyl-1,4- benzoquinone to afford isobenzofuran-4,7-quinone derivatives.

Full text of DOI:10.1039/a903897c

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582 J. CHEM. RESEARCH (S), 1999
J. Chem. Research (S),
1999, 582^583y
[1 + 4]Cycloaddition of Isocyanides with
2-Acetyl-1,4-benzoquinone; a Convenient
Synthesis of Isobenzofuran-4,7-quinones
Ahmad Shaabani,* Shahram Ajabi, Farhad Farrokhzad and
Hamid Reza Bijanzadeh
aChemistry Department, Shahid Beheshti University, P.O. Box 19395-4716, Tehran, Iran
bChemistry Department, Tarbiat Modarres University, P.O. Box 14155-4838, Tehran, Iran
Isocyanides undergo formal
quinone derivatives.
1
4 cycloaddition with 2-acetyl-1,4-benzoquinone to afford isobenzofuran-4,7-
1
The ‰1 ‡ 4Šcycloaddition reactions of isocyanides with
electrophilic heterodienes are of interest for the synthesis
of heterocyclic compounds. Cycloaddition of isocyanides
with
a b-unsaturated esters,4 a b-unsaturated ketones,5 particu-
Structure 4 was further con¢rmed by H NMR spectra that
revealed, in each case, a fairly broad singlet in the region
of d 3.7^4.8 which readily disappeared upon addition of
D2O. The mass spectra of the cycloadducts 4 are similar,
as expected, and con¢rm their molecular weights. The
1H NMR spectrum of 4a exhibited three singlet signals
arising from tert-butyl (d 1.49), methyl (d 2.58) and
N^H ‰d 3.71 (br)] along with two doublets ‰d 6.62,
(J ˆ 10 3 Hz) and d 6.77, (J ˆ 10 3 Hz)], for the two vicinal
CH groups. The proton decoupled 13C NMR spectrum of
4a displayed eleven singlet signals. The 1H and 13C NMR
spectra of 4b and 4c are similar to that of 4a. The structure
assignments made on the basis of the NMR spectra of com-
pounds 4a^c were supported by their IR spectra; of special
interest being N^H absorptions at 3285, 3270 and
N-acylimines,1
azadienes,2
diazadienes,3
catalyst,6
larly with diethylaluminium chloride as
a
nitroalkanes,7 vinyl isocyanates,8 1,1,1,5,5,5-hexa£uoro-
pentane-2,4-dione9 and 3-(1-hydroxyethylidene)pentane-
2,4-dione,10 have been described. The work reported here
was undertaken in order to synthesise substituted
17
isobenzofuran-4,7-quinones11
by the ‰1 ‡ 4Šcycloaddition
of alkyl isocyanides, such as tert-butyl isocyanide,
cyclohexyl isocyanide and benzyl isocyanide with
2-acetyl-1,4-benzoquinone 1, as an electron-de¢cient
hetero-1,3-diene. The ‰1 ‡ 4Šcycloaddition of isocyanides 2
with heterodiene 1 would a¡ord compounds 3, which
isomerize to produce the stable N-substituted 1-alkylamino-
3-methylisobenzofuran-4,7-quinones in high yields (Scheme
1).
1
3275 cm for 4a, 4b and 4c, respectively.
In summary, the reaction of alkyl isocyanides with an
electron de¢cient heterodiene, 2-acetyl-1,4-benzoquinone,
provides a simple one-pot entry into the synthesis of stable
N-substituted
1-alkylamino-3-methylisobenzofuran-4,7-
quinones under mild reaction conditions using a simple
experimental procedure.
O
O
O
CH2Cl2
0 ˚C
O
+ RNC
Experimental
2
H
N
All melting points are uncorrected. Elemental analyses were
performed using a Heraeus CHN-O rapid analyzer. Mass spectra
were recorded on a Finnigan-Matt 8430 mass spectrometer operating
at an ionization potential of 70 eV. IR spectra were measured on a
Shimadzu IR-470 spectrometer. 1H and 13C NMR spectra were
recorded on a Bruker DRX-500 Avance spectrometer at 500 and
125.77 MHz, respectively. The synthesis of 2-acetyl-1,4-benzoquinone
1 was carried out as described in the literature.18
O
O
O
R
1
3
[1,3]-H Shift
R
2,4a But
O
b c-C6H11
c CH2Ph
General Procedure for the Preparation of N-Substituted
1-Alkylamino-3-methylisobenzofuran-4,7-quinones
4.öTo
a
N
R
O
magnetically stirred solution of
1 (150 mg, 1 mmol) in di-
H
chloromethane (10 ml) was added dropwise a mixture of tert-butyl
isocyanide (0.113 ml, 1 mmol) in dichloromethane (10 ml) at 20 8C
over 10 min. The reaction mixture was allowed to warm to 0 8C,
stirred for 24 h and the solvent removed under reduced pressure to
afford the red product. For further puri®cation, the product was
recrystallized from 5% ethyl acetate±petroleum ether.
4
Scheme 1
Structure 4 was assigned to isolated cycloadducts on the
basis of their elemental analyses as well as their IR, 1H,
13C NMR and mass spectral data. IR spectroscopy was
1-(N-tert-Butylamino)-3-methylisobenzofuran-4,7-quinone
4a:
1
yield 85%; mp 87^90 8C (decomp.). nmax(KBr)/cm
3285 (N±H),
1650 (CˆO†, 1622 (CˆC). dH(CDCl3, Me4Si) 1.49 (9H, s, But), 2.58
(3H, s, Me), 3.71 (1H, br s, NH), 6.62 (1H, d, J ˆ 10 3 Hz), 6.77 (1H,
d, J ˆ 10 3 Hz). dC(CDCl3, Me4Si) 13.42 (CH3), 29.79 (CMe3), 53.75
(CMe3), 96.07 (CˆC N), 116.29 (CˆC O†, 139.61 and 142.66
(2CH), 150.45 (CˆC N), 158.88 (CˆC O†, 177.19 and 182.41
applied to distinguish structure
4
from the initial
cycloadducts 3, which apparently isomerize to produce
N-substituted isobenzofurane derivatives under the present
reaction conditions. Thus, the IR spectra of the isolated
products showed strong NH stretching bands at ca. 3280
‡
(2CˆO). MS m/z(%) 233(M , 21), 177(100), 162(55), 57(67) (Found:
C, 66.81; H, 6.63; N, 5.90. C13H15O3N requires: C, 66.93; H, 6.80; N,
cm 1. Further evidence was obtained from H NMR spectra
1
6.00%).
1-(N-Cyclohexylamino)-3-methylisobenzofuran-4,7-quinone
4b:
which showed the absence of a methine hydrogen resonance.
1
yield 90%; mp 106^108 8C (decomp.). nmax(KBr)/cm 3270 (N±H),
1671 (CˆO†, 1635 (CˆC). dH(CDCl3, Me4Si) 1.26±2.05 (11H, m,
C6H11, 2.61 (3H, s, CH3) 3.71 (1H, br s, NH), 6.62 (1H, d,
J ˆ 10 3 Hz), 6.77 (1H, d, J ˆ 10 3 Hz). dC(CDCl3, Me4Si) 13.37
(CH3), 24.66, 25.18 and 33.51 (3CH2), 52.16 (CH), 95.16 (CˆC N),
116.71 (CˆC O†, 139.53 (CH), 142.74 (CH), 150.22 (CˆC N),
* To receive any correspondence.
This is a Short Paper as de¢ned in the Instructions for Authors,
Section 5.0 [see J. Chem. Research (S), 1999, Issue 1]; there is
therefore no corresponding material in J. Chem. Research (M).

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J. CHEM. RESEARCH (S), 1999 583
158.38, (CˆC O), 177.11 and 182.46 (2CˆO). MS m/z(%)
4
5
E. A. Avetisyan and N. P. Gambaryan, Izv. Akad. Nauk
SSSR, Ser. Khim,, 1973, 2559 (Chem. Abstr., 1974, 80, 59809).
I. Yavari, A. Shaabani and M. T. Maghsoodlou, Monatsh.
Chem., 1997, 128, 697; G. Kollenz, W. Ott, E. Ziegler, E.
M. Peters, K. Peters, H. G. vonSchnerir, V. Formacek and
H. Quast, Liebigs Ann. Chem., 1984, 1137.
Y. Ito, H. Kato and T. Saegusa, J. Org. Chem., 1982, 47, 741.
A. Foucaud, C. Razorilalana-Rabearivony, E. Loukakou and
H. Person, J. Org. Chem., 1983, 48, 363.
J. H. Rigby and M. Qabar, J. Am. Chem. Soc., 1991, 113,
8975.
I. Yavari, A. Shaabani, S. Asghari, M. M. Olmstead and N.
Safari, J. Fluorine Chem., 1997, 86, 77.
‡
259(M , 44), 178(100), 97(2) (Found: C, 69.30; H, 6.51; N, 5.46.
C15H17O3N requires: C, 69.48; H, 6.60; N, 5.40%).
1-(N-Benzylamino)-3-methylisobenzofuran-4,7-quinone 4c: yield
1
80%; mp 88^90 8C (decomp.). nmax(KBr)/cm
3275 (N±H), 1660
(CˆO†, 1638 (CˆC). dH(CDCl3, Me4Si) 2.57 (3H, s, CH3), 4.66
(2H, s, CH2), 4.86 (1H, br s, NH), 6.61 (1H, d, J ˆ 10 4 Hz), 6.71
(1H, d, J ˆ 10 4 Hz), 7.28±7.49 (5H, m, C6H5). dC(CDCl3, Me4Si)
13.35 (CH3), 46.51 (CH2), 95.49 (CˆC N), 116.73 (CˆC O),
127.95, 128.21, 128.99 and 136.49 (C6H5), 139.86 (CH), 142.45 (CH),
150.33 (CˆC N†, 158.51 (CˆC O), 117.62 and 182.36 (2CˆO).
6
7
8
9
‡
MS m/z(%) 267(M , 21), 91(100), 65(17) (Found: C, 71.01; H, 4.84;
N, 5.10. C16H13O3N requires: C, 71.9; H, 4.90; N, 5.23%).
10 A. Shaabani and F. Farrokhzad, J. Chem. Res., 1997, (S) 344.
11 M. Chakraborty, D. B. McConville, G. F. Koser, C. A.
Tessier, T. Saito, P. L. Rinaldi and W. J. Youngs, J. Org.
Chem., 1997, 62, 8193.
We gratefully acknowledge ¢nancial support from the
Research Council of Shahid Beheshti University.
12 D. W. Cameron, I. T. Crosby, G. I. Feutrill and G. A. Pietersz,
Aust. J. Chem., 1992, 45, 2003.
13 G. M. L. Cragg, R. G. F. Giles and G. H. P. Roos, J. Chem.
Soc., Perkin Trans. 1, 1975, 1339.
Received, 17th May 1999; Accepted, 15th June 1999
Paper E/9/03897C
14 R. G. F. Giles and G. H. P. Roos, J. Chem. Soc., Chem. Com-
mun., 1975, 260.
15 J. Hanbrecht, H. Straub and E. Muller, Tetrahedron Lett.,
1976, 1789.
16 A. A. Hofmann, I. Wyrsch-Walraf, P. X. Iten and C. H.
Eugster, Helv. Chim. Acta, 1979, 62, 2211.
17 D. Passerieux, M. Casteignau and L. Lepage, Bull. Soc. Chim.
Fr., 1989, 441.
References
1
J. A. Deyrup and K. K. Killion, J. Heterocycl. Chem., 1972, 9,
1045.
2
G. Morel, E. Marchand, A. Foucaud and L. Toupet, J. Org.
Chem., 1989, 54, 1185; G. Morel, E. Marchand and A.
Foucaud, J. Org. Chem., 1985, 50, 771; W. Ott and V.
Formacek, Angew. Chem., Int. Ed. Engl., 1981, 20, 982.
G. Morel, E. Marchand, A. Foucaud and L. Toupet, J. Org.
Chem., 1990, 55, 1721, P. Imming, R. Mohr, E. Muller, W.
Overhen and G. Seitz, Angew. Chem., Int. Ed. Engl., 1982,
21, 284.
3
18 N. N. Vorozhtsov and V. P. Mamaev, Sborniok Statei
Obshchei Khim., Akad. Nauk SSSR, 1953, 1, 533 (Chem.
Abstr., 1955, 49, 925f).