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This article was downloaded by: [University of Arizona]On: 28 April 2013, At: 03:46Publisher: Taylor & FrancisInforma Ltd Registered in England and Wales Registered Number:1072954 Registered office: Mortimer House, 37-41 Mortimer Street,London W1T 3JH, UK
Synthetic Communications:An International Journalfor Rapid Communication ofSynthetic Organic ChemistryPublication details, including instructions forauthors and subscription information:http://www.tandfonline.com/loi/lsyc20
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
To link to this article: http://dx.doi.org/10.1080/00397919608003607
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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.
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Nair,V.; Kumar, S. J. Chem. SOC., Chem. Commun., 1994,1341.
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1995, 35,1605. ii, Nair, V.; Kumar, S.; Rath, N. P.; Morton, G. 0.
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