Quaternary ammonium salt-assisted synthesis of extended π-systems from methyldiazines and aromatic aldehydes

Article abstract of DOI:10.1081/SCC-100105893

4-Methyl- and 4,6-dimethylpyrimidines, methyl- and 2,5-dimethylpyrazines, as well as 3-methylpyridazine readily react with aromatic aldehydes in a hot solution of sodium hydroxide in the presence of a catalytic amount of a quaternary ammonium salt and in

Full text of DOI:10.1081/SCC-100105893

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QUATERNARY AMMONIUM SALT-ASSISTED SYNTHESIS
OF EXTENDED π-SYSTEMS FROM METHYLDIAZINES
1
AND AROMATIC ALDEHYDES
a
a
a
Jean Jacques Vanden Eynde , Laurent Pascal , Yves Van Haverbeke & Philippe Dubois
a
a
Département de Chimie Organique, Université de Mons-Hainaut, 20 Place du Parc,
Mons, B-7000, Belgium
Published online: 16 Aug 2006.
To cite this article: Jean Jacques Vanden Eynde , Laurent Pascal , Yves Van Haverbeke & Philippe Dubois (2001)
QUATERNARY AMMONIUM SALT-ASSISTED SYNTHESIS OF EXTENDED π-SYSTEMS FROM METHYLDIAZINES AND AROMATIC
1
ALDEHYDES , Synthetic Communications: An International Journal for Rapid Communication of Synthetic Organic
Chemistry, 31:20, 3167-3173, DOI: 10.1081/SCC-100105893
To link to this article: http://dx.doi.org/10.1081/SCC-100105893
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SYNTHETIC COMMUNICATIONS,31(20),3167–3173 (2001)
QUATERNARY AMMONIUM
SALT-ASSISTED SYNTHESIS OF
EXTENDED n-SYSTEMS FROM
METHYLDIAZINES AND
1
AROMATIC ALDEHYDES
1
,
1
Jean Jacques Vanden Eynde, * Laurent Pascal,
1
Yves Van Haverbeke, and Philippe Dubois
2
1
De
´
partement de Chimie Organique
riaux Polymeres et Composites,
Universite de Mons-Hainaut,
2
Service des Mate
´
`
´
20 Place du Parc,B-7000 Mons,Belgium
ABSTRACT
4-Methyl- and 4,6-dimethylpyrimidines, methyl- and 2,5-
dimethylpyrazines,as well as 3-methylpyridazine readily
react with aromatic aldehydes in a hot solution of sodium
hydroxide in the presence of a catalytic amount of a quater-
nary ammonium salt and in the absence of any organic solvent
to yield the corresponding condensation products.
*
Corresponding author. E-mail: jjvde@umh.ac.be
3
167
Copyright & 2001 by Marcel Dekker,Inc.
www.dekker.com

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3
168
VANDEN EYNDE ET AL.
INTRODUCTION
Nowadays there is an increasing awareness of the necessity to limit,as
far as possible,the use of organic solvents to transform chemicals.
That new challenge has led to an exploding development of two lead
methodologies which are i) the organic synthesis under solvent-free con-
2
3
ditions and microwave irradiation ii) the transfer of organic processes to
4
aqueous media, the latter concept having already been successfully extra-
5
polated at the industrial scale.
Condensation reactions benefit from both approaches and it remains
6
room for the disclosure of improved protocols enabling the fast and simple
preparation of conjugated systems under such environmentally friendly con-
ditions. The aim of this paper is to demonstrate that methyldiazines,despite
the poor activation of the aliphatic C-H bonds in such compounds,can
readily react with aromatic aldehydes in an aqueous solution of sodium
hydroxide in the presence of a quaternary ammonium salt and in the
absence of any organic solvent.
RESULTS
We observed that 4-methyl- (1,Figure 1) and 4 6, -dimethylpyrimidines
2),methyl- ( 3) and 2,5-dimethylpyrazines (4),as well as 3-methylpyridazine
5) readily react with aromatic aldehydes in a hot aqueous solution of
(
(
sodium hydroxide (5 M) and in the absence of any organic solvent.
Whereas the reactions do not occur in the absence of catalyst,the
addition of a quaternary ammonium salt (10% mol) substantially favors
the kinetics of the process (Table). Methyltrioctylammonium chloride
Õ
(aliquat 336) and tetrabutylammonium hydrogen sulfate appeared to be
the most effective catalysts among those we tested (see experimental),a
7
result that parallels the conclusions of Herriott for the reaction of thio-
phenoxide ion with 1-bromooctane in a two-phase system.
Our protocol enabled us to obtain compounds 6–15 (Figure 2) within
short reaction times (1 h–8 h) and,interestingly,the crude products can
Figure 1.

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QUATERNARY AMMONIUM SALT
3169
Table
Catalyst
Yield in 7 (%)
None
Not Detected
Benzyltrimethylammonium
Cetyltrimethylammonium bromide
Methyltrioctylammonium chloride
Tetrabutylammonium hydrogen sulfate
30
45
85
95
Figure 2.
be isolated by a mere filtration thus limiting the use of an organic solvent
to the purification by recrystallization. Benzene-1,4-dicarboxaldehyde
mono(diethyl acetal) has also been successfully involved in such reactions
(
to yield 11,Figure 2) so that the controlled stepwise preparation of oligo-
mers and/or polymers (by a series of deprotection/condensation reactions)
can hopefully be foreseen.
In addition,when the reactions are carried out at room temperature
aldol products can be isolated,at least from methylpyrimidines,and further
dehydrated in a subsequent step by a simple increase of the temperature
(
Figure 3). Therefore,it is anticipated that hydroxylated oligomers and/or
polymers could readily be available and processed before dehydration.
The key step of the reactions we studied is the formation of carbanions
from the (di)methyldiazines,a mechanism that is favored by a profitable
delocalisation of the negative charge on both nitrogen atoms of the
8
pyrimidine ring. In pyrazines and pyridazines,the delocalisation involves
one nitrogen atom only,what is responsible for the lower reactivity of
those systems when compared to the pyrimidine analogs. Under identical
experimental conditions (reflux for 1 h) final products are obtained in yields

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3
170
VANDEN EYNDE ET AL.
Figure 3.
ranging from 90% in the pyrimidine series to 20% in the pyrazine and
pyridazine series. Consequently when starting from 3, 4,and 5 reaction
times were extended to eight hours and by-products arising from a
9
Cannizzaro reaction were detected. That side-reaction could be minimized
(
but actually not suppressed) by adding the aldehydes by small portions
in the hot medium. Anyway,inspection of the literature reveals that the
title compounds,which are poorly described,can be prepared under sophis-
1
ticated or drastic experimental conditions only. Derivative 12,for
0
11
ꢀ
example,had been prepared by heating at 150–200 C a mixture of 3
and an excess of benzaldehyde and zinc chloride in a sealed tube for
1
1c
several hours.
CONCLUSION
In this paper we demonstrate that methyldiazines readily react with
aromatic aldehydes,in a hot basic aqueous solution containing a quaternary
ammonium salt,to afford the expected condensation compounds. Therefore
we disclose here a very simple environmentally friendly method yielding
diazine(s)-containing ꢀ-conjugated systems which are hardly accessible
through other methods. Quantum-chemical calculations and investigation
of the optical and nonlinear optical properties of the above model systems
and related derivatives are under progress as phenyl and pyridine analogs
are known to exhibit interesting properties for the design of light-emitting
1
2
devices.
EXPERIMENTAL
Solvents and reagents (including 1–5) are commercially available
Acros Organics,Aldrich Co) and were used without further purification.
(

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QUATERNARY AMMONIUM SALT
3171
Melting points (uncorrected) were determined on a Electrothermal 9100
apparatus. NMR spectra (CDCl ) were recorded on a Jeol JNP-PMX 60
3
1
spectrometer (60 MHz for H at 1.4 T) or a Bruker AMX spectrometer
1
300 MHz for H and 75 MHz for C at 7.0 T). Chemical shifts are given
13
(
in ppm using TMS as internal reference. IR spectra were recorded on a
Perkin-Elmer FTIR 1760 K spectrophotometer. UV spectra were recorded
on a Varian Cary 50 spectrophotometer. The elemental analyses were car-
ried out at the Station de Haute Belgique (Libramont-Chevigny,Belgium).
1
1a,13
14
15
11c
Compounds (Yield) 6 (90%),
7 (90%), 9 (90%), 12 (30%),
1
4
16
11c
11c
1
3 (70%), 14 (20%), 15 (65%), and 16 (65%) have been described in
the literature.
General procedure for the preparation of the pyrimidine derivatives
–11. A stoechiometric mixture of the (di)methylpyrimidine and the
6
aromatic aldehyde in an aqueous solution (25 mL for 5 mmol of the hetero-
cycles) of sodium hydroxide (5 M) containing methyltrioctylammonium
chloride or tetrabutylammonium hydrogen sulfate (10% mol vs. the hetero-
cycle) was heated under reflux for 1 h. After cooling the crude product was
filtered off and recrystallized.
General procedure for the preparation of the pyrazine and pyridazine
derivatives 12–15. A stoechiometric amount of the aromatic aldehyde
was slowly added over a period of 5 h to a mixture of the (di)methylpyrazine
(
butylammonium hydrogen sulfate (0.17 g; 0.5 mmol) in hot
5 mmol) and methyltrioctylammonium chloride (0.20 g; 0.5 mmol) or tetra-
a
aqueous solution (25 mL) of sodium hydroxide (5 M). The reflux was main-
tained for 3 h. After cooling the crude product was filtered off and recrys-
tallized.
Preparation of 16. A mixture of 4-methylpyrimidine 1 (0.91 mL;
1
(
0 mmol) and benzaldehyde (1.02 mL; 10 mmol) in an aqueous solution
20 mL) of sodium hydroxide (5 M) containing methyltrioctylammonium
chloride (0.40 g; 1 mmol) or tetrabutylammonium hydrogen sulfate (0.34 g;
mmol) was stirred at rt for 6 h. The crude product was filtered off and
recrystallized.
Conversion of 16 into 6: A mixture of compound 16 (1 g; 5 mmol) in an
1
aqueous solution (25 mL) of sodium hydroxide (5 M) containing methyl-
trioctylammonium chloride (0.20 g; 0.5 mmol) or tetrabutylammonium
hydrogen sulfate (0.17 g; 0.5 mmol) was heated under reflux for 1 h. After
cooling the crude product was filtered off and recrystallized. Yield 90%.
General procedure for the kinetic study. A mixture of 4-methylpyrimi-
dine (0.47 g; 0.46 mL; 5 mmol),the catalyst (0.5 mmol),and an aqueous
ꢀ
solution (25 mL) of sodium hydroxide (5 M) was thermostatized at 50 C.
Para-anisaldehyde (0.61 mL; 5 mmol) was rapidly added under stirring
(
1000 rpm) and heating was maintained for 1 h. After rapid cooling,the

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3
172
VANDEN EYNDE ET AL.
mixture was diluted with ethanol in order to adjust the final volume to
00 mL. A sample of that stock solution was then diluted 500 X with etha-
nol,and the UV spectrum was recorded (under similar conditions,we
1
recorded e ¼ 25000 at ꢁ
¼ 342 nm for a pure sample of 7).
max
4
-[2-(4-fluorophenyl)ethenyl]pyrimidine 8: Yield: 75%. M.p. (C H )
6
12
ꢀ
1
1
7
1
1
25–7 C. H NMR d 9.1 (1H,s),8.6 (1H,d,5 Hz),7.8 (1H,d,16 Hz),
1
3
.6–6.8 (6H,m) ppm;
C NMR d 165.1,162.0,161.7,158.9,157.4,136.1,
31.8,131.7,129.5,129.4,125.2,118.7,116.1,115.8 ppm. IR (KBr) 1640,
ꢁ
1
578,1510,1212,1164 cm
. Anal. Calcd. for C H FN C,71.99; H,4.53;
12 9 2
N,13.99. Found C,71.84; H,4.51; N,14.24.
,6-bis[2-(4-methoxyphenyl)ethenyl]pyrimidine 10: Yield: 90%. M.p.
4
ꢀ
1
(
C H ) 184–5 C. H NMR d 9.0 (1H,s),7.8 (2H,d,16 Hz),7.5 (4H,d,
6
12
9
Hz),7.1 (1H,s),6.8 (4H,d,9 Hz),6.8 (2H,d,16 Hz),3.9 (6H,s) ppm;
C NMR d 162.9,160.7,158.6,136.5,129.1,128.5,123.5,115.9,114.3,
1
3
ꢁ
1
55.3 ppm. IR (KBr) 1636,1605,1576,1514,1250 cm
C H N O C,76.72; H,5.85; N,8.13. Found C,76.91; H,5.52; N,8.04.
. Anal. Calcd. for
2
2
20
2
2
4,6-bis{2-[4-(diethoxymethyl)phenyl]ethenyl}pyrimidine 11: The general
procedure for the preparation of the pyrimidine derivatives was applied
from benzene-1,4-dicarboxaldehyde mono(diethyl acetal) (20 mmol).
Yield: 80%. A pure sample has been obtained after chromatography
ꢀ
(
C H /ether,1/1) and recrystallization. M.p. (petroleum ether) 81–3 C.
6
H NMR d 9.1 (1H,s),7.9 (2H,d,16 Hz),7.7–7.4 (8H,m),7.3 (1H,s),
6
1
7
.0 (2H,d,16 H),5.5 (s,2H),3.6 (8H,m),1.2 (12H,t,7 Hz) ppm;
C NMR d 162.7,158.7,140.4,136.7,135.7,127.5,127.2,125.9,116.5,
01.1,61.1,15.2 ppm. IR (KBr) 1637,1579,1514,1328,1056 cm
1
3
ꢁ
1
1
Calcd. for C H N O C,73.74; H,7.43; N,5.73. Found C,74.21; H,7.18;
. Anal.
3
0
36
2
4
N,5.58.
ACKNOWLEDGMENTS
L.P. thanks the ‘‘fonds pour la formation a
`
trie et dans l’agriculture (FRIA)’’ for a grant. P.D. is grateful to the ‘‘Re
´
la recherche dans l’indus-
gion
Wallonne’’ and the European Community for general support in the frame
of ‘‘Objectif 1: Materia Nova’’.
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Received in the Netherlands January 2,2001

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