A facile synthesis of pechmann dyes

Article abstract of DOI:10.1002/chem.201400329

A facile synthesis of Pechmann dyes has been accomplished by the reaction of substituted N-phenacyl-4-dimethylaminopyridinium halides with dimethyl maleate in the presence of DBU. Based on a related 4-DMAP elimination product and an isolated monolactone intermediate a reaction mechanism has been proposed. The scope of this synthetic method is determined by the availability of α-haloaroyl or heteroaroyl derivatives. DBU=1,8-diazabicycloundec-7-ene, DMAP=4-dimethylaminopyridine. A facile synthesis of Pechmann dyes has been accomplished by the reaction of substituted N-phenacyl-4-dimethylaminopyridinium halides with dimethyl maleate in the presence of DBU (see scheme). Based on a related 4-DMAP elimination product and an isolated monolactone intermediate a reaction mechanism has been proposed. The scope of this synthetic method is determined by the availability of α-haloaroyl or heteroaroyl derivatives. DBU=1,8-diazabicycloundec-7-ene, DMAP=4-dimethylaminopyridine.

Full text of DOI:10.1002/chem.201400329

DOI: 10.1002/chem.201400329
Communication
&
Synthetic Methods
A Facile Synthesis of Pechmann Dyes
Henning Hopf,[b] Peter G. Jones,[c] Alina Nicolescu,[d] Elena Bicu,[a] Lucian M. Birsa,*[a] and
Dalila Belei*[a]
In this communication we report on a new synthetic
method for Pechmann dyes using various substituted 4-di-
Abstract: A facile synthesis of Pechmann dyes has been
accomplished by the reaction of substituted N-phenacyl-
methyl-aminopyridinium phenacyl halides as starting materials.
Recently, we reported on a direct and highly selective synthesis
4-dimethylaminopyridinium halides with dimethyl maleate
of
decahydropyrrolo[2,1,5 cd]indolizin-6-one
derivatives
in the presence of DBU. Based on a related 4-DMAP elimi-
nation product and an isolated monolactone intermediate
a reaction mechanism has been proposed. The scope of
this synthetic method is determined by the availability of
a-haloaroyl or heteroaroyl derivatives. DBU=1,8-diazabi-
cycloundec-7-ene, DMAP=4-dimethylaminopyridine.
through a double dipolar cycloaddition of acrylonitrile and
ethyl acrylate to 4-dimethylaminopyridinium ylids.[8] Extension
of this study to the interaction of other olefinic dipolarophiles
with 4-dimethylaminopyridinium ylids has disclosed a competi-
tive reaction pathway that leads to Pechman bislactones. Fol-
lowing the classical experimental procedure, dimethyl maleate
was added to in situ generated pyridinium ylid, in turn ob-
tained from the corresponding N-phenacyl-4-dimethylamino-
pyridinium bromide (1) and 1,8-diazabicycloundec-7-ene
(DBU). The pyridinium bromide is easily available from w-bro-
moacetophenone and 4-dimethylaminopyridine (4-DMAP).[9] In
sharp contrast to previous experiments, the reaction mixture
developed a deep red color within several minutes, followed
by the separation of a yellow fluorescent solid. During the
work-up, dimethyl fumarate was always isolated, along with
a crude mixture of other reaction products; its isolation proved
to be very important for the mechanistic rationalization of the
process (see below). Using dichloromethane as solvent at
room temperature and a substrate/dipolarophile molar ratio of
1:2, we always identified as a major reaction product a highly
fluorescent yellow compound, 2, along with the expected
decahydropyrrolo[2,1,5cd]indolizin-6-one derivative (4; Table 1,
entries 1–3).
Pechmann dyes were discovered in 1882; 42 years later, their
structures were conclusively demonstrated to be derivatives of
a 4-phenyl-3-butenolide dimer joined by an exocylic double
bond at the a-carbon in an E configuration.[1] Because of their
highly cross-conjugated planar (“indigoid”) structures, these
compounds have a great potential for applications in organic
electronics and molecular fluorescence technologies.[2] Thio-
phene-substituted Pechmann dyes have been the subject of
special interest in materials chemistry; additional thiophene
rings assist the formation of polymers, which are preferred
from a processing standpoint.[3] However, few synthetic reports
have been published since the mid 1950s.[4,5] Several synthetic
routes to the Pechmann dye family are known. One of the
most representative routes consists of the dehydrative dimeri-
zation of b-aroylacrylic acids in acetic anhydride, in the pres-
ence of cuprous chloride as a catalyst.[6] Recently, the acid cata-
lyzed double lactonization of triarylamine-conjugated dimethyl
diethynylfumarate has opened up a new synthetic route to
Pechmann dyes.[7]
By optimizing the reaction conditions we found that the
ratio of bislactone 2 to tricyclic compound 4 increases with in-
creasing amounts of DBU. When the reaction was performed
at 70–808C in ethanol or dioxane (Table 1, entries 4 and 5),
only the bislactone 2 and dimethyl fumarate were formed in
equimolar quantities. Moreover, the reaction outcome was
found to be sensitive to the order of addition of the reaction
partners. By adding two equivalents of DBU to a mixture of
pyridinium bromide 1 and dimethyl maleate in dichlorome-
thane at room temperature, the ratio of 2:4 is changed from
2.3:1 to 1:5. Regardless of the order of reactant addition, only
the Pechmann dye was obtained on heating. Investigating the
role of the base on reaction progress, we generated and isolat-
ed the corresponding N-ylid from bromide 1. By reacting this
N-ylid with dimethyl maleate, only tricyclic compound 4 was
obtained. When DBU was replaced by Et3N, smaller amounts of
bislactone 2 were produced. These results clearly indicate the
crucial role of the base on the formation of the Pechmann dye.
Decahydropyrrolo[2,1,5cd]indolizin-6-one (4) is probably
formed by a double addition process via the corresponding tri-
[a] Prof. E. Bicu, Dr. L. M. Birsa, Dr. D. Belei
Department of Chemistry, ‘Al. I. Cuza’ University of Iasi
11 Carol I, 700506 Iasi (Romania)
E-mail: lbirsa@uaic.ro
dalila@uaic.ro
[b] Prof. H. Hopf
Institute of Organic Chemistry, Technical University of Braunschweig
Hagenring 30, D-38106 Braunschweig (Germany)
[c] Prof. P. G. Jones
Institute of Inorganic and Analytical Chemistry
Technical University of Braunschweig, Hagenring 30
D-38106 Braunschweig (Germany)
[d] Dr. A. Nicolescu
“Petru Poni” Institute of Macromolecular Chemistry
Aleea Grigore Ghica 41A, 6600, Iasi (Romania)
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/chem.201400329.
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known bislactones 2 and 6a–c are in agreement with those re-
ported. Under basic conditions and/or elevated temperatures
several Pechmann dyes undergo isomerization to the corre-
sponding endo-6,6’-dilactones.[5c] Although our synthetic proce-
dure requires basic conditions, no 6,6’-dilactones were identi-
fied. Moreover, by reacting bislactone 2 with DBU no isomeri-
zation was recorded. The lack of alkaline isomerization to the
6,6’-dilactones was also reported for thiophene containing
Pechmann dyes.[6b]
Table 1. Reaction of 4-dimethylaminopyridinium phenacyl bromide (1)
with DBU and dimethyl maleate.
From the reaction of N-(4-methoxyphenacyl)-4-dimethylami-
nopyridinium bromide (5b) with dimethyl maleate we isolated
a small amount (8%) of the monolactone 8 with an exocyclic
double bond, bearing an ethyl ester functionality (Figure 1);
Solvent
DBU
[equiv]
T
[8C]
Ratio
2
Yield
[%]
3
4
1
2
3
4
5
CH2Cl2
CH2Cl2
CH2Cl2
EtOH
0.6
1
2
2
2
20
20
20
70
80
1.7
2
2.3
1
1.7
2
2.3
1
1
1
1
–
–
65
68
69
70
80
Figure 1. Isolated monolactones.
dioxane
1
1
cyclic enamine, as previously described by us.[8] Its structure
was determined by 2D NMR spectroscopy and mass spectrom-
etry. The relative stereochemistry was also proved by X-ray
analysis; however, there is a disordered ester group and the
structure could not be completely refined.
the ethyl group probably resulted from the ethanol used
during work-up by transesterification. The formation of the
monolactone prompted us to study whether this structure is
an intermediate in the bislactone-forming sequence. Thus the
DBU-catalyzed reaction of 5b with dimethyl maleate in diox-
ane was stopped 30 min after the addition of the latter com-
pound and the reaction mixture worked up without ethanol.
The corresponding monolactone 9 was isolated in 28% yield
(Figure 1). The formation of a related structure from the reac-
tion of N-phenacyl-4-dimethylaminopyridinium bromide (1)
with 3-phenacylideneoxindoles in the presence of triethyl-
amine has been reported recently.[10]
In order to test the limitations of this new synthetic method,
various substituted pyridinium halides have been synthesized
and subjected to the above reaction conditions. Differently
substituted w-bromoacetophenones were used to prepare 4-
dimethylaminopyridinium salts 5a–d (Table 2).[9] On heating
Table 2. Investigated pyridinium bromides.
The carbonyl group in 1 has also been replaced by ester
and amide functionalities (Table 2). No Pechmann dyes were
obtained when compounds 5e–i were heated in dioxane with
dimethyl maleate and DBU. However, when pyridinium bro-
mide 5i was treated with DBU and dimethyl maleate in di-
chloromethane at room temperature, we were able to isolate
product 11. This is probably formed via intermediate 10 by Mi-
chael addition of pyridinium ylid to dimethyl maleate followed
by 4-dimethylaminopyridine elimination (Scheme 1).
Compound
R
Compound
R
5a, 6a
5b, 6b
5c, 6c
5d, 6d
5e
4-MeC6H4
4-MeOC6H4
4-BrC6H4
4-CNC6H4
OEt
5h
5i
10H-phenothiazinyl
2-Cl-10H-phenothiazinyl
7a
7b
7c
7d
H
CN
Me
OMe
5 f
5g
4-MeC6H4NH
1H-indazolyl
5a–d in dioxane for 6 h the corresponding Pechmann bislac-
tones were obtained in moderate to good yields (6a 42%, 6b
45%, 6c 38%, 6d 34%), along with one equivalent of dimethyl
fumarate.
The structure of bislactones 2 and 6a–d was proved by 2D
NMR analysis and mass spectrometry. The analytical data of
Scheme 1. Reaction of pyridinium bromide 5 i with dimethyl maleate.
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Figure 2. Molecular structure of compound 11. Ellipsoids represent 50%
probability levels.
Because of the free rotation around the former double bond
of dimethyl maleate, elimination of 4-DMAP from intermediate
10 leads to the more stable trans-configuration at the double
bond of 11. The structure of compound 11 was proved by X-
ray analysis (Figure 2).[11] Although this reaction does not pro-
vide Pechmann derivatives, it yields important results; 4-DMAP
is eliminated and the mechanism of a Michael addition sup-
ports the formation of a dimethyl fumarate substructure.
Furthermore, when dimethylamino group of the pyridine
ring was replaced by other substituents (Table 2, 7a–d), no for-
mation of Pechmann bislactones was observed. This indicates
the important role of 4-DMAP in the formation of compounds
of type 2. In fact, Tsuge has reported that cycloaddition reac-
tions of 4-dimethylaminopyridinium halides often lead to in-
tractable colored reaction products.[12]
Scheme 2. Proposed mechanism for the formation of Pechmann dyes.
lactones C (e.g., 9) by intramolecular cyclization. The elimina-
tion of dimethyl fumarate indicates an intermolecular interac-
tion between C-enolate B’ and monolactone C leading to inter-
mediate D. An addition–elimination mechanism provides a 1:1
mixture of the Pechmann dye and dimethyl fumarate.
In conclusion, we present a facile synthesis of Pechmann
dyes from the reaction of various substituted N-phenacyl-4-di-
methylaminopyridinium halides with dimethyl maleate in the
presence of DBU. The scope of this synthetic method is deter-
mined by the availability of a-haloaroyl or heteroaroyl deriva-
tives. Oligo- and polythiophene-substituted Pechmann dyes
can easily be produced by this method. The formation of
pyrrolo[2,1,5cd]indolizin-6-one derivatives, their stereochemis-
try and the interaction of pyridinium halides 5e–i and 7a–d
with olefinic dipolarophiles are under investigation.
Summarizing the experimental evidence, we conclude that:
1) the presence of a strong base is essential for the formation
of bislactones (4-DMAP may also act as a base after its elimina-
tion); 2) the formation of equimolar quantities of bislactones
and dimethyl fumarate suggests a common intermediate for
both compounds; 3) compounds of type 11 appear to be im-
portant intermediates in the synthesis of monolactones such
as 8 and 9 (while the amide functionality of 11 cannot under-
go keto-enolic tautomerism, this is possible for phenacyl deriv-
atives, for which the intramolecular cyclization of their O-eno-
lates leads to monolactones of type 8 and 9); 4) when reac-
tions are performed in dichloromethane at room temperature
the formation of tricyclic compounds of type 4 by successive
intramolecular Michael additions competes with elimination of
4-DMAP.
Acknowledgements
L.M.B. is indebted to the Alexander von Humboldt Foundation
for a short stay in Braunschweig. Part of this work was support-
ed by a grant of the Romanian National Authority for Scientific
Research, CNDI-UEFISCDI, project number 51/2012.
Keywords: dimethylaminopyridine · dyes/pigments · Michael
addition · Pechmann lactones · ylids
A plausible mechanism for the synthesis of the Pechmann
dyes is proposed (Scheme 2) that accounts for the above facts.
Michael addition of various substituted 4-dimethylaminopyridi-
nium ylids (from 1 and 5a–d with excess DBU) to dimethyl
maleate provides intermediate A after 4-DMAP elimination.
This intermediate forms the O-enolate B that provides mono-
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Received: January 26, 2014
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COMMUNICATION
&
Synthetic Methods
H. Hopf, P. G. Jones, A. Nicolescu, E. Bicu,
L. M. Birsa,* D. Belei*
&& – &&
A Facile Synthesis of Pechmann Dyes
A facile synthesis of Pechmann dyes
has been accomplished by the reaction
of substituted N-phenacyl-4-dimethyla-
minopyridinium halides with dimethyl
maleate in the presence of DBU (see
scheme). Based on a related 4-DMAP
elimination product and an isolated
monolactone intermediate a reaction
mechanism has been proposed. The
scope of this synthetic method is deter-
mined by the availability of a-haloaroyl
or heteroaroyl derivatives. DBU=1,8-di-
azabicycloundec-7-ene, DMAP=4-dime-
thylaminopyridine.
Chem. Eur. J. 2014, 20, 1 – 5
www.chemeurj.org
5
ꢀ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
&
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These are not the final page numbers! ÞÞ