Generation and cycloaddition of o-quinodimethane in aqueous medium

Article abstract of DOI:10.3390/60500472

o-Quinodimethane can be generated from α,α′-dihalo-o- xylenes using zinc in aqueous solution. In the presence of activated dienophiles cycloadducts can be obtained directly. Catalysis with tris-triphenylphosphine ruthenium(II) dichloride reduces side reac

Full text of DOI:10.3390/60500472

Molecules 2001, 6, 472-476
molecules
ISSN 1420-3049
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Generation and Cycloaddition of o-Quinodimethane in
Aqueous Medium
Lothar W. Bieber* and Margarete F. da Silva
Departamento de Química Fundamental, Universidade Federal de Pernambuco, Cidade Universitária,
50670-901 Recife - PE, Brazil
*Author to whom correspondence should be addressed; e-mail: lothar@dqfex.ufpe.br
Received: 9 March 2001; in revised form 24 April 2001 / Accepted: 24 April 2001 / Published: 30
April 2001
Abstract: o-Quinodimethane can be generated from =α,α'-dihalo-o-xylenes using zinc
in aqueous solution. In the presence of activated dienophiles cycloadducts can be
obtained directly. Catalysis with tris-triphenylphosphine ruthenium(II) dichloride
reduces side reactions such as reduction and polymerisation and improves the yield.
This is the first example of an organometallic cyclisation in aqueous medium using
dihalo compounds.
Keywords: Dehalogenation, zinc, Diels-Alder reaction, Ru catalysis, aqueous solvent
Introduction
o-Quinodimethanes (o-xylylenes) are reactive intermediates widely used for the synthesis of
polycyclic compounds via inter- or intramolecular Diels-Alder reactions [1]. Because of their high
reactivity and thermal instability they must be generated in situ by various methods: dehalogenation
of =α,α'-dihalo-o-xylenes, thermal or photochemical extrusion of stable molecules or ring opening of
benzocyclobutenes. The unsubstituted parent compound, generated at low temperature, has been
proven to exist in a singlet ground state [2]. To our knowledge, all synthetic or mechanistic work in

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Molecules 2001, 6
this field has been performed in organic solvents under anhydrous conditions. Recent progress in
aqueous Diels-Alder cycloadditions and organometallic reactions [3], especially the successful Wurtz
coupling of benzylic halides [4] and their Barbier addition to carbonyl compounds [5], prompted us to
study the behaviour of α,α'-dihalo-o-xylenes (1) under similar conditions in the hope to obtain
benzocyclobutene (2) or, in the presence of dienophiles, cycloadducts of o-quinodimethane.
Results and Discussion
The reaction of the dibromo compound 1a with zinc dust in saturated aqueous ammonium
chloride was complete in a few minutes at r.t. and produced a polymeric material 3 containing 67 %
of C-C coupled methylene groups and 28 % of methyl groups as a result of reduction; only trace
amounts of o-xylene and dimeric or trimeric coupling products, but no 2 at all could be detected by
GC/MS (Table 1, entry 1). These results agree rather well with those obtained by Alder under
anhydrous conditions in DMF [6]. The reaction of the dichloride 1b was much slower (1 h), but gave
a very similar product composition (entry 2). Use of metal catalysts such as CuCl2, CuI, AgNO3 and
Pb(OAc)2, which had an important influence on the reactivity of benzylic monohalides [4], brought no
significant change.
X
X
H
H
Zn
NH4Cl/H 2O
n
2
1a (X = Br)
b (X = Cl)
3
More promising results were obtained in the presence of dimethyl fumarate (solubilized with
CH3CN): 22 % of the trans-cycloadduct 6 was produced with the dibromide and 53 % with the
dichloride. In both cases, polymerisation to 3 and reduction of the dienophile to dimethyl succinate
were important side reactions (entries 3 and 4). In an attempt to obtain a cleaner reaction and better
yield, different temperatures, acidic, neutral and basic salt solutions and several water soluble or
unsoluble cosolvents were tried without positive results. Other metals were also tested in different
solvent systems: Mg, Al, Mn and Ti gave no cycloadduct at all and In, Sn, Fe and Bi produced only
modest yields (15 -30 %). Similarly, 15 different transition metal ions and the triphenylphosphine
complexes of Ni, Pd and Ru were examined as catalysts in the Zn-promoted reaction. Cu and Fe were
found to increase the amount of the polymer 3 and Co, Ni, Pd and Au catalyzed the reduction of 1b.
The only improvement of the cycloaddition reaction was observed with tris-triphenylphosphine
ruthenium(II) dichloride; using 5 mg of this catalyst, the yield of 6 raised to 40 % for the dibromide
and 84 % for the dichloride (entries 5 and 6); in the latter case, all side reactions were reduced to a

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Molecules 2001, 6
few percent. The use of the preformed catalyst was essential, because addition of ruthenium(III)
chloride and triphenylphosphine had no effect (entry 7).
Table 1. Reactions of α,α'-dihalo-o-xylenes (1) and zinc in aqueous mediuma
Yields (%)b
Entry
X
Br
Cl
Br
Cl
Br
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Salt
Dienophile
-
Cosolvent
-
Catalyst
Coupling Reduction
6
7
-
1
2
NH4Cl
NH4Cl
NH4Cl
NH4Cl
NH4Cl
NH4Cl
NH4Cl
K3PO4
K3PO4
K3PO4
NH4Cl
NH4F
-
65
62
70
10
52
5
28
25
4
-
-
-
-
-
-
3
Dimethyl fumarate
Dimethyl fumarate
Dimethyl fumarate
Dimethyl fumarate
Dimethyl fumarate
Methyl acrylate
Acrylonitrile
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
-
-
22
53
40
84
48
85
86
92
37
33
22
15
8
4
-
36
8
5
Ru(PPh3)3Cl2
Ru(PPh3)3Cl2
6
10
12
12
13
5
7
c
7
RuCl3 + PPh3
Ru(PPh3)3Cl2
Ru(PPh3)3Cl2
Ru(PPh3)3Cl2
Ru(PPh3)3Cl2
Ru(PPh3)3Cl2
15
3
10
-
8
9
4
-
10
11
12
Methyl vinyl ketone
Dimethyl maleate
Methyl crotonate
3
1
46
60
16
5
5
-
a General procedure: see Experimental.
b Determined by 1 H-NMR.
c 2 mg of each were employed.
In the following experiments, the dichloride was reacted under standard conditions with other
types of dienophiles. Electron deficient terminal olefins such as methyl acrylate, acrylonitrile and
methyl vinyl ketone gave even higher yields of cycloaddition when basic conditions were employed
to prevent polymerisation (entries 8-10). Somewhat surprisingly, dimethyl maleate produced only 37
% of pure cis-substituted cycloadduct (entry 11), probably due to a less favorable overlap in the endo
transition state; in a competion experiment using a mixture of dimethyl fumarate and maleate (1 eq. of
each), only the former reacted and produced trans-cycloadduct 6. Methyl crotonate was also less
reactive, giving the same 33 % yield in the presence or absence of catalyst, and unactivated olefins
like 1-heptene, styrene and cyclohexene did not react at all. The observed differences in the reactivity
agree with those found in previously reported demetalating reactions [6-8]. However, the aqueous
procedure gives much better yields than the electrochemical generation [7], uses unexpensive starting
materials, is experimentally simple and avoids the use of DMF, a solvent which is toxic and difficult
to dry.
From the mechanistic point of view, the effect of the ruthenium complex is remarkable but not
surprising. Indeed, stable o-xylylene complexes of type 5 bearing aryldialkylphosphine ligands have

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Molecules 2001, 6
been synthesized and characterized by x-ray analysis [9]. Furthermore, oxidative decomposition of the
exo-complex in the presence of dimethyl acetylenedicarboxylate has produced a cycloadduct in very
low yield [10]. This cycloaddition under oxidative conditions and the inexistence of a stable, isolated
complex with triphenylphosphine ligands suggest a similar, but less stable intermediate in our
reaction, probably in equilibrium with the free o-quinodimethane 4 (scheme 1). The complexation
may prevent the polymerisation of 4, increasing thus its lifetime. Highly reactive dienophiles probably
react rapidly with the complex 5 or with free 4. Less reactive olefins need free 4 and have to compete
with the polymerisation reaction; for this reason no improvement is observed in the presence of the
catalyst. Benzocyclobutene (2) can be excluded as a possible intermediate because it was recovered
unchanged in control experiments in the presence or absence of catalyst.
Scheme 1
Ru(PPh 3)3Cl2 / Zn
Zn
1a,b
RuL3
H2O
4
5
polymerisation
cycloaddition
+
RCH=CHR'
R
3
+
RCH2CH2R'
R'
6
7
Conclusions
In conclusion, the generation of o-quinodimethane (4) in aqueous medium is a very simple and
high yielding alternative for intermolecular cycloadditions to activated dienophiles, especially when
catalized by the ruthenium complex. The reaction represents the first example of a one-step
cyclisation using dihalo compounds and zinc in aqueous medium.
Acknowledgements
This work was supported by CNPq (Brasilia). We thank Ms. Érida M.A. Pequeno for GC/MS
analyses.

476
Molecules 2001, 6
Experimental
General
In all experiments commercially available reagents and solvents were used without further
purification or activation. The cycloadducts obtained in preparative yields (entries 6, 8-10) showed
physical and spectroscopic properties in perfect agreement with previously reported data [6-8, 11].
Reaction of α,α'-dihalo-o-xylenes (1) with zinc in the presence or absence of dienophiles
To 2 mL of saturated aqueous salt solution (see Table 1) a mixture of 1 (0.5 mmol), dienophile
(0.6 mmol), catalyst (5 mg) and 0.5 mL of CH3CN was added at r.t. Under vigorous stirring zinc dust
(1.0 mmol) was added portionwise over a period of 10 min. After 1h, the mixture was hydrolysed
with 2 N HCl, extracted with 1 mL of CCl4 containing 0.05 mmol of cyclohexane as internal
1
quantitative reference. The crude extracts were analysed by H-NMR and GC/MS. In preparative
runs, the products were purified by CC and crystallisation.
References and Notes
1. Reviews: (a) W.Oppolzer, Synthesis 1978, 793-802. (b) R.L. Funk and K.P.C. Vollhardt, Chem.
Soc. Rev. 1980, 9, 41-61.
2. C.R.Flynn and J. Michl, J. Am. Chem. Soc. 1974, 96, 3280-3288.
3. (a) C.-J. Li and T.H. Chan, Organic Reactions in Aqueous Media, John Wiley & Sons, New York,
1997. (b) C.-J.Li, Tetrahedron 1996, 52, 5643-5668. (c) A. Lubineau, J. Augé, Y. Queneau,
Synthesis 1994, 741-760.
4. L.W. Bieber and I. Malvestiti, unpublished results.
5. L.W. Bieber, E.C. Storch, I. Malvestiti and M.F. Silva, Tetrahedron Lett. 1998, 39, 9393-9396.
6. K. Alder and M. Fremery, Tetrahedron 1961, 14, 190-200.
7. E. Eru, G.E. Hawker, J.H.P. Utley and P.B. Wyatt, Tetrahedron 1995, 51, 3033-44.
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1035-1036.
11. R.D. Haworth and F.H. Slinger, J. Chem. Soc. 1940, 1321-27.
Samples Availability: Not available.
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