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-dimethyl-aminopyridinium phenacyl halides as starting materials. Recently, we reported on a direct and highly selective synthesis of decahydropyrrolo[2,1,5 cd]indolizin-6-one derivatives 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 competitive reaction pathway that leads to Pechman bislactones. Following the classical experimental procedure, dimethyl maleate was added to in situ generated pyridinium ylid, in turn obtained from the corresponding N-phenacyl-4-dimethylaminopyridinium bromide (1) and 1,8-diazabicycloundec-7-ene (DBU). The pyridinium bromide is easily available from w-bromoacetophenone 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[2,1,5 cd]indolizin-6-one derivative (4; Table 1, entries 1–3). By optimizing the reaction conditions we found that the ratio of bislactone 2 to tricyclic compound 4 increases with increasing amounts of DBU. When the reaction was performed at 70–80 8C 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 dichloromethane 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 isolated 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[2,1,5 cd]indolizin-6-one (4) is probably formed by a double addition process via the corresponding tri-
Abstract: A facile synthesis of Pechmann dyes has been accomplished by the reaction of substituted N-phenacyl4-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 a-haloaroyl or heteroaroyl derivatives. DBU = 1,8-diazabicycloundec-7-ene, DMAP = 4-dimethylaminopyridine.
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] Thiophene-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 1950 s.[4, 5] Several synthetic routes to the Pechmann dye family are known. One of the most representative routes consists of the dehydrative dimerization of b-aroylacrylic acids in acetic anhydride, in the presence of cuprous chloride as a catalyst.[6] Recently, the acid catalyzed double lactonization of triarylamine-conjugated dimethyl diethynylfumarate has opened up a new synthetic route to Pechmann dyes.[7]
[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: [email protected] [email protected] [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. Chem. Eur. J. 2014, 20, 1 – 5
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Communication known bislactones 2 and 6 a–c are in agreement with those reported. Under basic conditions and/or elevated temperatures several Pechmann dyes undergo isomerization to the corresponding endo-6,6’-dilactones.[5c] Although our synthetic procedure requires basic conditions, no 6,6’-dilactones were identified. Moreover, by reacting bislactone 2 with DBU no isomerization was recorded. The lack of alkaline isomerization to the 6,6’-dilactones was also reported for thiophene containing Pechmann dyes.[6b] From the reaction of N-(4-methoxyphenacyl)-4-dimethylaminopyridinium bromide (5 b) 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);
Table 1. Reaction of 4-dimethylaminopyridinium phenacyl bromide (1) with DBU and dimethyl maleate.
Solvent 1 2 3 4 5
CH2Cl2 CH2Cl2 CH2Cl2 EtOH dioxane
DBU [equiv]
T [8C]
Ratio 2
3
4
Yield [%]
0.6 1 2 2 2
20 20 20 70 80
1.7 2 2.3 1 1
1.7 2 2.3 1 1
1 1 1 – –
65 68 69 70 80
Figure 1. Isolated monolactones.
cyclic enamine, as previously described by us.[8] Its structure was determined by 2D NMR spectroscopy and mass spectrometry. 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. 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 4dimethylaminopyridinium salts 5 a–d (Table 2).[9] On heating
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 5 b with dimethyl maleate in dioxane was stopped 30 min after the addition of the latter compound 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 reaction of N-phenacyl-4-dimethylaminopyridinium bromide (1) with 3-phenacylideneoxindoles in the presence of triethylamine has been reported recently.[10] The carbonyl group in 1 has also been replaced by ester and amide functionalities (Table 2). No Pechmann dyes were obtained when compounds 5 e–i were heated in dioxane with dimethyl maleate and DBU. However, when pyridinium bromide 5 i was treated with DBU and dimethyl maleate in dichloromethane at room temperature, we were able to isolate product 11. This is probably formed via intermediate 10 by Michael addition of pyridinium ylid to dimethyl maleate followed by 4-dimethylaminopyridine elimination (Scheme 1).
Table 2. Investigated pyridinium bromides.
Compound
R
Compound
R
5 a, 6 a 5 b, 6 b 5 c, 6 c 5 d, 6 d 5e 5f 5g
4-MeC6H4 4-MeOC6H4 4-BrC6H4 4-CNC6H4 OEt 4-MeC6H4NH 1H-indazolyl
5h 5i
10H-phenothiazinyl 2-Cl-10H-phenothiazinyl
7a 7b 7c 7d
H CN Me OMe
5 a–d in dioxane for 6 h the corresponding Pechmann bislactones were obtained in moderate to good yields (6 a 42 %, 6 b 45 %, 6 c 38 %, 6 d 34 %), along with one equivalent of dimethyl fumarate. The structure of bislactones 2 and 6 a–d was proved by 2D NMR analysis and mass spectrometry. The analytical data of &
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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 Xray analysis (Figure 2).[11] Although this reaction does not provide Pechmann derivatives, it yields important results; 4-DMAP is eliminated and the mechanism of a Michael addition supports the formation of a dimethyl fumarate substructure. Furthermore, when dimethylamino group of the pyridine ring was replaced by other substituents (Table 2, 7 a–d), no formation 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 reactions of 4-dimethylaminopyridinium halides often lead to intractable colored reaction products.[12] 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 elimination); 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 important intermediates in the synthesis of monolactones such as 8 and 9 (while the amide functionality of 11 cannot undergo keto-enolic tautomerism, this is possible for phenacyl derivatives, for which the intramolecular cyclization of their O-enolates leads to monolactones of type 8 and 9); 4) when reactions 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. 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-dimethylaminopyridinium ylids (from 1 and 5 a–d with excess DBU) to dimethyl maleate provides intermediate A after 4-DMAP elimination. This intermediate forms the O-enolate B that provides monoChem. Eur. J. 2014, 20, 1 – 5
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Scheme 2. Proposed mechanism for the formation of Pechmann dyes.
lactones C (e.g., 9) by intramolecular cyclization. The elimination of dimethyl fumarate indicates an intermolecular interaction between C-enolate B’ and monolactone C leading to intermediate 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-dimethylaminopyridinium halides with dimethyl maleate in the presence of DBU. The scope of this synthetic method is determined by the availability of a-haloaroyl or heteroaroyl derivatives. Oligo- and polythiophene-substituted Pechmann dyes can easily be produced by this method. The formation of pyrrolo[2,1,5 cd]indolizin-6-one derivatives, their stereochemistry and the interaction of pyridinium halides 5 e–i and 7 a–d with olefinic dipolarophiles are under investigation.
Acknowledgements L.M.B. is indebted to the Alexander von Humboldt Foundation for a short stay in Braunschweig. Part of this work was supported 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 [1] a) H. von Pechmann, Ber. Dtsch. Chem. Ges. 1882, 15, 881; b) M. T. Bogert, J. J. Ritter, J. Am. Chem. Soc. 1924, 46, 2871 – 2878. [2] a) W. Wu, Y. Liu, D. Zhu, Chem. Soc. Rev. 2010, 39, 1489 – 1502; b) Z. Cai, Y. Guo, S. Yang, Q. Peng, H. Luo, Z. Liu, G. Zhang, Y. Liu, D. Zhang, Chem. Mater. 2013, 25, 471 – 478; c) R. Sakamoto, S. Kusaka, M. Hayashi, M. Nishikawa, H. Nishihara, Molecules 2013, 18, 4091 – 4119; d) T. Aysha,
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[3] [4] [5]
[6] [7]
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S. Lunak, Jr., A. Lycka, J. Vynuchal, Z. Elias, A. Ruzicka, Z. Padelkova, R. Hrdina, Dyes Pigm. 2013, 98, 530 – 539. E. A. B. Kantchev, T. B. Norsten, M. L. Y. Tan, J. J. Y. Ng, M. B. Sullivan, Chem. Eur. J. 2012, 18, 695 – 708. E. Klingsberg, Chem. Rev. 1954, 54, 59 – 77. a) J. Silver, M. T. Afmet, K. Bowden, J. R. A. Reynolds, A. Bashall, M. McPartlin, J. Trottee, J. Mater. Chem. 1994, 4, 1201 – 1204; b) K. Bowden, W. M. F. Fabian, G. Kollenz, J. Chem. Soc. Perkin Trans. 2 1997, 547 – 552; c) H. Irikawa, N. Adachi, Heterocycles 2000, 53, 135 – 142; d) H. Hashimoto, K. Shiratori, K. Kawakita, T. Tanaka, R. Senike, H. Irikawa, Heterocycles 2005, 65, 1385 – 1392. a) C. S. Fang, W. Bergmann, J. Org. Chem. 1951, 16, 1231 – 1237; b) T. B. Norsten, E. A. B. Kantchev, M. B. Sullivan, Org. Lett. 2010, 12, 4816 – 4819. M. Hayashi, F. Toshimitsu, R. Sakamoto, H. Nishihara, J. Am. Chem. Soc. 2011, 133, 14518 – 14521.
Chem. Eur. J. 2014, 20, 1 – 5
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[8] D. Belei, C. Abuhaie, E. Bicu, P. G. Jones, H. Hopf, M. L. Birsa, Synlett 2012, 23, 545 – 548. [9] K. Sarkunam, M. Nallu, J. Heterocycl. Chem. 2005, 42, 5 – 11. [10] Q. Fu, C.-G. Yan, Tetrahedron 2013, 69, 5841 – 5849. [11] CCDC-956496 (11) contains the supplementary crystallographic data for this paper. These data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_request/cif.. [12] a) O. Tsuge, S. Kanemasa, S. Takenaka, Chem. Lett. 1985, 355 – 358; b) O. Tsuge, S. Kanemasa, S. Takenaka, Bull. Chem. Soc. Jpn. 1985, 58, 3137 – 3157.
Received: January 26, 2014 Published online on && &&, 0000
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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-dimethylaminopyridinium halides with dimethyl maleate in the presence of DBU (see scheme). Based on a related 4-DMAP elimination product and an isolated
Chem. Eur. J. 2014, 20, 1 – 5
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-diazabicycloundec-7-ene, DMAP = 4-dimethylaminopyridine.
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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-dimethyl-aminopyridinium phenacyl halides as starting materials. Recently, we reported on a direct and highly selective synthesis of decahydropyrrolo[2,1,5 cd]indolizin-6-one derivatives 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 competitive reaction pathway that leads to Pechman bislactones. Following the classical experimental procedure, dimethyl maleate was added to in situ generated pyridinium ylid, in turn obtained from the corresponding N-phenacyl-4-dimethylaminopyridinium bromide (1) and 1,8-diazabicycloundec-7-ene (DBU). The pyridinium bromide is easily available from w-bromoacetophenone 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[2,1,5 cd]indolizin-6-one derivative (4; Table 1, entries 1–3). By optimizing the reaction conditions we found that the ratio of bislactone 2 to tricyclic compound 4 increases with increasing amounts of DBU. When the reaction was performed at 70–80 8C 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 dichloromethane 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 isolated 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[2,1,5 cd]indolizin-6-one (4) is probably formed by a double addition process via the corresponding tri-
Abstract: A facile synthesis of Pechmann dyes has been accomplished by the reaction of substituted N-phenacyl4-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 a-haloaroyl or heteroaroyl derivatives. DBU = 1,8-diazabicycloundec-7-ene, DMAP = 4-dimethylaminopyridine.
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] Thiophene-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 1950 s.[4, 5] Several synthetic routes to the Pechmann dye family are known. One of the most representative routes consists of the dehydrative dimerization of b-aroylacrylic acids in acetic anhydride, in the presence of cuprous chloride as a catalyst.[6] Recently, the acid catalyzed double lactonization of triarylamine-conjugated dimethyl diethynylfumarate has opened up a new synthetic route to Pechmann dyes.[7]
[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: [email protected] [email protected] [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. Chem. Eur. J. 2014, 20, 1 – 5
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Communication known bislactones 2 and 6 a–c are in agreement with those reported. Under basic conditions and/or elevated temperatures several Pechmann dyes undergo isomerization to the corresponding endo-6,6’-dilactones.[5c] Although our synthetic procedure requires basic conditions, no 6,6’-dilactones were identified. Moreover, by reacting bislactone 2 with DBU no isomerization was recorded. The lack of alkaline isomerization to the 6,6’-dilactones was also reported for thiophene containing Pechmann dyes.[6b] From the reaction of N-(4-methoxyphenacyl)-4-dimethylaminopyridinium bromide (5 b) 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);
Table 1. Reaction of 4-dimethylaminopyridinium phenacyl bromide (1) with DBU and dimethyl maleate.
Solvent 1 2 3 4 5
CH2Cl2 CH2Cl2 CH2Cl2 EtOH dioxane
DBU [equiv]
T [8C]
Ratio 2
3
4
Yield [%]
0.6 1 2 2 2
20 20 20 70 80
1.7 2 2.3 1 1
1.7 2 2.3 1 1
1 1 1 – –
65 68 69 70 80
Figure 1. Isolated monolactones.
cyclic enamine, as previously described by us.[8] Its structure was determined by 2D NMR spectroscopy and mass spectrometry. 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. 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 4dimethylaminopyridinium salts 5 a–d (Table 2).[9] On heating
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 5 b with dimethyl maleate in dioxane was stopped 30 min after the addition of the latter compound 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 reaction of N-phenacyl-4-dimethylaminopyridinium bromide (1) with 3-phenacylideneoxindoles in the presence of triethylamine has been reported recently.[10] The carbonyl group in 1 has also been replaced by ester and amide functionalities (Table 2). No Pechmann dyes were obtained when compounds 5 e–i were heated in dioxane with dimethyl maleate and DBU. However, when pyridinium bromide 5 i was treated with DBU and dimethyl maleate in dichloromethane at room temperature, we were able to isolate product 11. This is probably formed via intermediate 10 by Michael addition of pyridinium ylid to dimethyl maleate followed by 4-dimethylaminopyridine elimination (Scheme 1).
Table 2. Investigated pyridinium bromides.
Compound
R
Compound
R
5 a, 6 a 5 b, 6 b 5 c, 6 c 5 d, 6 d 5e 5f 5g
4-MeC6H4 4-MeOC6H4 4-BrC6H4 4-CNC6H4 OEt 4-MeC6H4NH 1H-indazolyl
5h 5i
10H-phenothiazinyl 2-Cl-10H-phenothiazinyl
7a 7b 7c 7d
H CN Me OMe
5 a–d in dioxane for 6 h the corresponding Pechmann bislactones were obtained in moderate to good yields (6 a 42 %, 6 b 45 %, 6 c 38 %, 6 d 34 %), along with one equivalent of dimethyl fumarate. The structure of bislactones 2 and 6 a–d was proved by 2D NMR analysis and mass spectrometry. The analytical data of &
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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 Xray analysis (Figure 2).[11] Although this reaction does not provide Pechmann derivatives, it yields important results; 4-DMAP is eliminated and the mechanism of a Michael addition supports the formation of a dimethyl fumarate substructure. Furthermore, when dimethylamino group of the pyridine ring was replaced by other substituents (Table 2, 7 a–d), no formation 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 reactions of 4-dimethylaminopyridinium halides often lead to intractable colored reaction products.[12] 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 elimination); 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 important intermediates in the synthesis of monolactones such as 8 and 9 (while the amide functionality of 11 cannot undergo keto-enolic tautomerism, this is possible for phenacyl derivatives, for which the intramolecular cyclization of their O-enolates leads to monolactones of type 8 and 9); 4) when reactions 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. 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-dimethylaminopyridinium ylids (from 1 and 5 a–d with excess DBU) to dimethyl maleate provides intermediate A after 4-DMAP elimination. This intermediate forms the O-enolate B that provides monoChem. Eur. J. 2014, 20, 1 – 5
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Scheme 2. Proposed mechanism for the formation of Pechmann dyes.
lactones C (e.g., 9) by intramolecular cyclization. The elimination of dimethyl fumarate indicates an intermolecular interaction between C-enolate B’ and monolactone C leading to intermediate 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-dimethylaminopyridinium halides with dimethyl maleate in the presence of DBU. The scope of this synthetic method is determined by the availability of a-haloaroyl or heteroaroyl derivatives. Oligo- and polythiophene-substituted Pechmann dyes can easily be produced by this method. The formation of pyrrolo[2,1,5 cd]indolizin-6-one derivatives, their stereochemistry and the interaction of pyridinium halides 5 e–i and 7 a–d with olefinic dipolarophiles are under investigation.
Acknowledgements L.M.B. is indebted to the Alexander von Humboldt Foundation for a short stay in Braunschweig. Part of this work was supported 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 [1] a) H. von Pechmann, Ber. Dtsch. Chem. Ges. 1882, 15, 881; b) M. T. Bogert, J. J. Ritter, J. Am. Chem. Soc. 1924, 46, 2871 – 2878. [2] a) W. Wu, Y. Liu, D. Zhu, Chem. Soc. Rev. 2010, 39, 1489 – 1502; b) Z. Cai, Y. Guo, S. Yang, Q. Peng, H. Luo, Z. Liu, G. Zhang, Y. Liu, D. Zhang, Chem. Mater. 2013, 25, 471 – 478; c) R. Sakamoto, S. Kusaka, M. Hayashi, M. Nishikawa, H. Nishihara, Molecules 2013, 18, 4091 – 4119; d) T. Aysha,
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Received: January 26, 2014 Published online on && &&, 0000
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Communication
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-dimethylaminopyridinium halides with dimethyl maleate in the presence of DBU (see scheme). Based on a related 4-DMAP elimination product and an isolated
Chem. Eur. J. 2014, 20, 1 – 5
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-diazabicycloundec-7-ene, DMAP = 4-dimethylaminopyridine.
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