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Hetero Diels-Alder Reactionof o-Benzoquinones with2,5-Dimethylpyrrole:Synthesis of NovelBenzodioxinsVijay Nair a & Sasi Kumar aa Organic Chemistry Division, Regional ResearchLaboratory (CSIR), Trivandrum, 695019, INDIAVersion of record first published: 21 Aug 2006.

To cite this article: Vijay Nair & Sasi Kumar (1996): Hetero Diels-Alder Reactionof o-Benzoquinones with 2,5-Dimethylpyrrole: Synthesis of Novel Benzodioxins,Synthetic Communications: An International Journal for Rapid Communication ofSynthetic Organic Chemistry, 26:2, 217-224

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SYNTHETIC COMMUNICATIONS, 26(2), 217-224 (1996)

HETERO DIELS-ALDER REACTION OF

SYNTHESIS OF NOVEL BENZODIOXINS O-BENZOQUINONES WITH 2,s-DIMETHYLPYRROLE:

Vijay Nair" and Sasi Kumar

Organic Chemistry Division, Regonal Research Laboratory (CSIR) Trivandrum - 695 019, INDIA.

Abstract : An eficient one step procedure for the preparation of dihydro[l,4]benzodioxino[2,3-b]pyrrole using Diels-Alder reaction of o-benzoquinones with 2,5-dimethylpyrrole I S described.

The potent phannacologcal properties associated with

benzodioxins have drawn considerable attention to the synthesis of

compounds incorporating t h s heterocyclic system. 1-8

Of particular interest are the reports on

the potent and selective a2-antagonist acbvity of U O k N "

the tetrahydrobenzodioxino[2,3-c]pyrrole 1 and O H

the synthetic efforts towards congeners of this 1

compound. 9.10

* To whom correspondence should be addressed

217

Copyright 0 1996 by Marcel Dekker, Inc.

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218 NAIR AND KUMAR

FuransllJ and 3-methylindole13 have been reported to

undergo hetero Diels-Alder reaction with o-quinones to yield benzodioxins

albeit in very low yield. However no such work has been reported with

pyrroles.14 We have recently shown that o-benzoquinones undergo facile

hetero Diels-Alder reaction with electron rich acyclic dienes to afford

benzodioxins in very high yieldl5J6 and here we report a facile one step

synthesis of certain dihydro[ 1,4]benzodioxino[2,3-b]pyrrole derivatives

using the same protocol involving o-quinones and 2,5-dimethylpyrrole,

whch illustrates a novel cycloaddition process of pyrroles. Reaction of

3,5-di-teut-butyl-o-benzoquinone 2 with 2,5-&rnethylpyrrole 3 at room

temperature afforded the (3a-czs)-6,8-bis-( 1,l -dimethylethyl)-3a,9a-&hydro

2,9a-dimethyl- 3H [1,4]benzodioxino [2,3-b] pyrrole 5 in 32% yield.

Me +Me

5

IR Spectrum of 5 does not show any absorptions due to

carbonyl and -NH groups. In the 1H NMR spectrum of 5, the -CH2-

protons appeared at 6 2.83 (J=3.6 Hz) as a doublet whereas the -CH-

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NOVEL BENZODIOXINS 219

Table 1. Diels-Alder Reactions of t,!j-Dimethylpyrrole with o-Benzoquinones

Entry Quinone Conditions Produet(sf (Yield %)’

2

3

6

8

Benzene, RT, 3 h

OMe

10

9 (15)

1 All products gave satisfactory spectroscopic and analysis data 2 Isolated yield 3 2: 1 Mixture of isomers

proton adjacent to the -CH2- group in the benzodioxin ring appeared at

6 4.28 (J=3.6 Hz) as a tiplet. The corresponding carbon signals appeared

at 6 45.52 and 78.52 respectively. The carbon bearing the oxygen and

nitrogen in the benzodioxin ring resonates at 6 102.80. The imine carbon

atom appeared at 6 174.05. Similar results were obtained with 4-tert-buty1,

4-nitro- and 3-methoxy-o-benzoquinones and these are given in Table 1.

Since there is a possibility for charge transfer complex

formation between the quinone and the pyrrole prior to the cycloaddltion

we studied the UV profile of this reaction. In a series of UV spectra of the

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220 NAIR AND KUMAR

Table 2. HOMO-LUMO energies of the reactants

Reactant HOMOeV LUMOev

3,5-Di-tert-butyl-o-benzoquinone -9.800 -1.188

2,5-Dimethylpyrrole -8.357 0.945

4-tert-Butyl-o-benzoquinone -10.009 -1.435

4-Nitro-u-benzoquinone -10.412 -2.598

3-Methoxy-o-benzoquinone -9.109 -2.006

reaction mixture no charge transfer band was observed for the above

reaction. Therefore it is assumed that the reaction involves a direct addition

followed by isomerization.

In order to understand the reactivity parameters of the above

systems, we have carried out some theoretical calculations using MNDO

program. The results are given in Table 2. From the HOMO-LUMO

energy differences it is evident that the above reactions proceed by inverse

electron demand.

In conclusion, the present work describes the first example of

the cycloaddition of an o-quinone to a pyrrole and it appears that the

reaction is useful for the synthesis of benzod1oxino[2,3-b]pyrroles. It is

noteworthy that pyrrole generally functions as a diene in Diels-Alder

reaction and the reactivity as a dienophile observed here is unprecedented.

Experimental

IR spectra were recorded on a Perkin-Elmer model 882 spectrometer.

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NOVEL BENZODIOXINS 22 1

1H and 13C NMR spectra were recorded on a Nicolet GE 300 or Jeol EX-

90 spectrometers. Petroleum ether refers to the fraction boiling between

60-80 OC. Column chromatography was done using 100-200 mesh silica

gel and appropriate mixture of petroleum ether and ethyl acetate for elution.

(3a-cis)-6,8-bis(l, l-Dimeihylethyl)-3a, 9a- dihydro-2, 9a-dimethyi-3H[l,4/

benzodioxino[2,3-b]pyrrole (5). 3,5-Di-fert-butyl-o-benzoquinone (0.22g,

l.Olmmo1) and 2,5-dimethylpyrrole (0.20 g, 2.1 mmol) were dissolved in

dry toluene (1 0 mL) and stirred under nitrogen for 2 h. The solvent was

removed in vacuo and the residue on column chromatography using

petroleum ether-ethyl acetate as eluent afforded 5 (0.11 g, 32%) as pale

yellow crystalline solid. mp. 136-138 OC. IR : 2967, 1645, 1590, 1486, 1421cm-l; lH NMR (CDC13): 6 6.82 (s, 2H), 4.28 (t, J=3.6 Hz, lH), 2.83

(d, J=3.6, 2H), 2.25 (s, 3H), 1.45 (s, 3H), 1.26 (s, 9H), 1.22 (s, 9H); 13C

NMR(CDC13): 6 174.05, 143.92, 143.41, 139.50, 137.60, 115.90, 112.92,

102.80, 78.52, 45.52, 34.72, 34.36, 31.41, 29.83, 23.98, 20.25;

HRMS: C20H2902N : 315.4411; found : 315.4397.

(3a-cis)- 7-(1,l -Dimthylethyl)-3a, 9a-dihydro-2,9a-dimethyl-3H[l, 4/benzo

dioxino/2,3-bfpyrroie (7). A sample of 4-tert-butyl-o-bemoquinone (0.2g,

1.2 mmol.) and 2,5-dimethylpyrrole (0.5 mL, excess) was Qssolved in

Qchloromethane (5 mL) and stirred under nitrogen at 0 OC. It was then

warmed to room temperature and stirred for 2 h. The solvent was removed

and the residue on column chromatography furnished 7 (0.187, 60%) as

pale yellow viscous oil. R : 2980, 1640, 1595, 1420 cm-1; 1H NMR (CDC13) : 6 6.60 (m, 3H), 4.15 (t, J=3.7 Hz,lH), 2.60 (d, J=3.6 Hz, 2H),

1.9 (s, 3H), 1.35 (s, 3H), 1.20 (s, 9H); 13C NMR: (CDC13) 6 174.0, 144.0,

143.5, 138.0, 117.0, 113.5, 109.5, 101.0, 79.0, 46.0, 34.5, 30.0, 24.0, 21.0;

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222 NAIR A N D KCMAR

MS m/e : 260 (M++l), 220, 178, 164, 140, 72. CHN analysis : C=74.09,

H=8.17, N=5.4; found : C=73.89, H=8.01, N=5.29.

(3a-cis)-7-Nitr0-3~, 9a-dihydro-2,9a-dimethyl-3H/ 1,4/benzodioxino /2,3-b/

pyrrole (9). To an ice cooled solution of 4-nitrocatechol (0.155 g, 1.0

mmol.) in dry ether (10 mL), silver oxide (1 .O g) was added and stirred for

5 minutes. To this solution, 2,5-dImethylpyrrole (0.2mL, excess) was

added dropwise by a synnge and stirred for 10 h. The inorganic material

was removed by filtration and the filtrate was concentrated in vucuo. The

residue on column chromatography furnished 9 (0.037 g, 15%) as yellow viscous oil. IR: 2939, 1600, 1517, 1096 cm-1; 1H NMR (CDC13): 6 7.5

(m, 2H), 6.6 (m, lH), 4.4 (t. lH), 2.8 (br d, 2H), 2.0 (s, 3H), 1.5 (s, 3H).

13C NMR (CDC13): 6 174.5, 149.5, 143.5, 142.0, 139.0, 130.5, 130.0,

101.5, 45.5, 24.0, 20.5; CHN analysis:C=58.05, H=4.88, N=ll.29; found:

C=58.11, H=4.78, N=l1.20.

(3a-cis)-d-Methoxy- 3a, 9a-dihydro-2, 9a- dimethyl-3H / I , 41 benzodioxino

[2,3-b]pyrrole (IZ). 3-Methoxycatechol (0.53 g, 3.78 mmol.) was dissolved

in benzene (10mL) and silver carbonate (1.2 g) was added to it and stirred.

To the above solution, 2,5-dimethylpyrrole (0.5 mL, excess) was added and

stirred for 5 h at room temperature. The inorganic material was removed

by passing through a short column of celite and the filtrate was

concentrated in vucuo. The residue obtained on column chromatography

furnished the adduct 11 (0.53 g, 60%) as pale yellow viscous oil. IR: 2940,

1608, 1501, 1479, 1295, 1098 cm-l; l H NMR (CDC13) : 6 6.8 (m, IH), 6.6

(m, 2H), 4.46 (t, J = 3Hz, 1H) 3.83 (s, 3H), 2.85 (m, 2H), 2.0 (s, 3H), 1.57

(s, 3H); 13C NMR (CDC13): 6 174.94, 120.64. 120.52, 110.41, 109.13.

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NOVEL BENZODIOXINS 223

105.19, 104.62, 101.10, 78.37, 56.17, 45.64, 23.83, 20.31. MS mlz : 233

(M'), 140, 95, 94, 69, 54; HRMS:C13H1503N: 233.1051; found: 233.1011

Acknowledgement

SK thanks Regional Research Laboratory and Department of

Science and Technology, Government of India, for research followships.

References and Notes

1.

2.

3.

4.

5 .

6.

7.

8.

9.

10.

11.

12.

Lee, T. V.; Leigh, A. J.; Chapleo, C. B.

Coudert, G.; Guillaumet, G.; Loubinoux, B. Tetrahedron Lett.,

1978, 1059,

Guillaumet, G.; Coudert, G. Loubinoux, B. Tetrahedron Lett.,

1979,4379.

Farina, G. Zecchi, G. Synthesis 1977,755.

Guillaumet, G.; Trumtel, M.; Coudert, G.; Zeggaf, C.

Angew. Chem., 1983,95,50.

Guillaumet, G.; Trumtel, M.; Coudert, G.; Zeggaf, C. Synthesis

1986,337.

Adam, W.; Schmidt, E.; Thakayama, K. Synthesis 1982, 322.

Lee, T.V.; Leigh, A. J.; Chapleo, C.B. Synthesis 1989,208.

Halliday, C. A.; Jones, B. J.; Skingle, M.; Walsh, D. M.;

Tyers, M. B. Br. J. Pharmacol., 1991, 102, 887.

Procopiou, P. A.; Cherry, P.C.; Deal, M. J.; Lamont, R. B.

J. Chem. Soc., Perkin Trans. 1 , 1994, 1773.

Horspool, W. M.; Tedder, J. M.; Din, Z. U. J. Chem. SOC., C,

1969, 1694.

Horspool, W. M.; Anderson, D. T. J. Chem. SOC., Perkin

Trans. I, 1971, 532.

Synlett 1989, 30.

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224

13.

14.

15.

16.

NAIR AND KUMAR

Komatsu, T.; Nishio, T.; Omote, Y. Chem. and Id., (London),

1978, 95.

For the reaction of enamines with o-benzoquinones, see Omote, Y.;

Tomatake, A.; Kashima, C.

1988,15 1.

Nair,V.; Kumar, S. J. Chem. SOC., Chem. Commun., 1994,1341.

For related work on the cycload&tion of o-quinones to fulvenes,

see, i, Nair, V.; Kumar, S.; Williard, P. G. Tetrahedron Lett.,

1995, 35,1605. ii, Nair, V.; Kumar, S.; Rath, N. P.; Morton, G. 0.

Chemistry Lett., 1995, 0000.

J. Chem. SOC., Chem. Commun.,

(Received in t h e UK 15 May 1995)

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