Abstract
Ullmann type reactions are one of the most effective methods to carry out
the N-arylation of the pyrazole using copper catalyst. The Ullmann reaction
carried out by conventional methods occur under hard reaction conditions using
copper reagents at stoichiometric ratio and at high temperatures. With the
development of more efficient copper catalysts, studies in this field have been
continued and very efficient copper/ligand systems have been developed under
mild conditions. Although it is known that many of copper / ligand system
reactions are carried out under relatively mild conditions to increase the
efficiency of Ullmann type reactions, in recent years, studies have been made
on simpler catalyst systems which are
ligand free and "green" solvents or solvent free.
In this study, in order to contribute to N-arylation of pyrazoles in mild
conditions, 4-Iodo-1-phenyl -1H-pyrazole (Ph-IPz) and
4-iodo-3,5-dimethyl-1-phenyl-1H-pyrazole
(Ph-IDMPz) compounds were synthesized according to the methods adapted from
literature with N-arylation reaction of 4-Iodo-1H-pyrazole (4-IP) or 4-iodo-3,5-dimethyl-1H-pyrazole (4-IDMPz) with phenyl boronic acid in the prences of Cu2O
catalyst. N-Arylation reactions of
4-iodopyrazols with phenyl boronic acit were carried out the presence of Cu2O
catalyst, at atmospheric conditions, at room temperature, in methyl alcohol and
without the use of any base and ligand. In
this way , the synthesis of Ph-IPz and Ph-IDMPz was carried out for the first
time with Ullmann reaction under the milder conditions.
Synthesized ligands Ph-IPz and Ph-IDMPz were characterized by FT-IR, NMR and GC-MS mass spectra. The
NMR and FT-IR spectra of the compounds showed characteristic peaks of both the
pyrazole and the phenyl group. The absence of N-H proton peaks in the 1 H-NMR
spectra of the obtained Ph-IP 2 and Ph-IDMP 2 compounds indicates that the
phenyl group is attached from the pyrazole NH. The shifts in the C4 carbon
peaks which are determinant for 4-substituted pyrazoles in the 13C-NMR spectra
also confirm the structure of the compounds.
Keywords
References
- [1] Eicher, T.; Hauptmann, S.; Speicher, The chemistry of heterocycles: structure, reactions, synthesis and applications-3rd edition (Wiley‐VCH Verlag GmbH & Co. KGaA, Weinheim, Germany, 2003)
- [2] Wang X.Y., Liu S.Q., Zhang C.Y., Song G., Bai F.Y., Xing Y.H. ve Shi Z., Synthesis, structural, and biological evaluation of the arene-linked pyrazolyl methane ligands and their d9/d10 metal complexes. Polyhedron, 47 (2012) 151-164.
- [3] Potapov, A.S., Khlebnikov, A.I., Synthesis of mixed-ligand copper(II) complexes containing bis(pyrazole-1-yl) methane ligands. Polyhedron, 25 (2006) 2683-2690.
- [4] Fustero S., Sanchez-Rosello M., Barrio P. ve Simon-Fuentes A., From 2000 to Mid-2010: A fruitful decade for the synthesis of pyrazoles. American Chemical Society, 111 (2011) 6984-7034.
- [5] Bouabdallah I., Touzani R., Zidane I., Ramdani A., ve Radi S., Synthesis of some 1-aryl-3,5-disubstituted-pyrazoles by N-arylation of 3,5-disubstituted-pyrazoles with 4-fluoro and 2-fluoronitrobenzene under microwave irradiation and classical heating. Arkivoc, 12 (2006) 138-144.
- [6] Xu Z.L., Li H.X., Ren Z-G. , Du W.Y., Xu W.C. ve Lang J.P., Cu(OAc)2.H2O-catalyzed N-arylation of nitrogen-containing heterocycles. Tetrahedron, 67 (2011) 5282-5288.
- [7] Kaplars A., Antilla J.C., Huang X. ve Buchwald S.L.J., A general and efficient copper catalyst for the amidation of aryl halides and the N-arylation of nitrogen heterocycles. Journal of American Chemical Society, 123 (31) (2001) 7727-7729.
- [8] Taillefer M., Cristau H.J., Cellier P.P. ve Spindler J.F., Patents FR 2833947-WO0353225 (Pr. Nb. Fr 2001 16547) (2001).
- [9] Evano G., Blanchard N. ve Toumi M., Copper-mediated coupling reactions and their applications in natural products and designed biomolecules synthesis. Chemical Reviews, 108 (8) (2008) 3054-3131.
- [10] Ley S.V. ve Thomas A.W., Modern synthetic methods for copper-mediated C(aryl)[bond]O, C(aryl)[bond]N, and C(aryl)[bond]S bond formation. Angewandte Chemie International Edition, 42 (44) (2003) 5400-5449.
- [11] Kim M. M., Ruck R.T., Zhao D. ve Huffman M.A., Green iodination of pyrazoles with iodine/hydrogen peroxide in water. Tetrahedron Letters, 49 (2008) 4026-4028.
- [12] Kantam M.L., Venkanna G.T., Sridhar C., Sreedhar B. ve Choudary B.M., An efficient base-free n-arylation of imidazoles and amines with arylboronic acids using copper-exchanged fluorapatite. Jornal of Organic Chemistry, 71 (2006) 9522-9524.
- [13] Joubert N., Baslé E., Vaultier M. ve Pucheault M., Mild, base-free copper-catalyzed N-arylations of heterocycles using potassium aryltrifluoroborates in water under air. Tetrahedron Letters, 51 (2010) 2994–2997.
- [14] Rao H., Fu H., Jiang Y.ve Zhao Y., Easy copper-catalyzed synthesis of primary aromatic amines by coupling aromatic boronic acids with aqueous ammonia at room temperature. Angewandte Chemie International Edition, 48 (2009) 1114-1116.
- [15] Roy S., Roy S. ve Gribble G.W., Metalation of pyrazoles and indazoles, Topics in Heterocycle Chemistry, 29 (2012) 155-260.
- [16] Coates J., Interpretation of Infrared Spectra, A Practical Approach, 10815-10837, R.A. Meyers (Ed.). Encyclopedia of Analytical Chemistry (John Wiley & Sons Ltd., Coates Consulting, Newtown, USA, 2000)
- [17] Skoog D.A., Holler F.J. ve Nieman T.A., Principles of Instrumental Analysis, Fifth Edition (Harcourt Brace &Company, Florida, USA, 1998)
- [18] Stuart B.H., Infrared Spectroscopy: Fundamentals and Applications (John Wiley & Sons Ltd., İngiltere, 2004).
- [19] Sharma S., Barooah N., ve Baruah J.B., Tris (3,5-dimethylpyrazole) copper(II) nitrate: as an oxidation catalyst. Journal of Molecular Catalysis A: Chemical, 229 (2005) 171-176.
- [20] Ovejero P. , Mayoral M. J., Cano M., Campo J.A., Heras J.V., Pinilla E., Torres M. R., The 3,5-dimethyl-4-nitropyrazole ligand in the construction of supramolecular networks of silver(I) complexes, Journal of Organometallic Chemistry, 692 (2007) 4093–4105.
- [21] Mezei G., Raptis R.G., Effect of pyrazole-substitution on the structure and nuclearity of Cu(II)-pyrazolato complexes, Inorganica Chimica Acta, 357 (2004) 3279–3288
Iyodo Pirazollerin Cu2O Katalizörlüğünde Fenil Boronik Asit ile Ullmann Tipi N-Arilasyon Reaksiyonları
Abstract
Ullmann tipi reaksiyonlar bakır katalizörü kullanılarak pirazollerin
N-arilasyonu gerçekleştirmek için en etkili yöntemlerden birisidir. Geleneksel
yöntemlerle gerçekleştirilen Ullmann reaksiyonu yüksek sıcaklıklarda ve
stokiyometrik oranda bakır reaktifleri kullanılarak sert reaksiyon koşulları
altında gerçekleşmektedir. Daha verimli bakır katalizörlerinin gelişmesi ile bu
alanda yapılan çalışmalar devam ederek hafif koşullar altında oldukça verimli
bakır/ligant sistemleri geliştirildi. Ullmann
tipi reaksiyonların verimliliğini arttırmak için birçok bakır/ligant
kombinasyon reaksiyonlarının nispeten yumuşak koşullar altında gerçekleştirdiği
bilinmesine rağmen, son yıllarda ligant içermeyen ve "yeşil"
çözücülerle ya da çözücüsünden arındırılmış daha basit katalizör sistemleri üzerine
çalışmalar yapılmaktadır.
Bu çalışmada pirazollerin ılıman şartlarda N-arilasyonuna katkı sağlaması
amacıyla fenil boronik asit ile 4-iyodo-1H-pirazol
(I-Pz) veya 4-iyodo-3,5-dimetil-1H-pirazolün (I-DMPz) Cu2O
katalizörlüğünde N-arilasyonu ile 4-Iyodo-1-fenil-1H-pirazol (Ph-IPz) ve 4-Iyodo-3,5-dimetil-1-fenil-1H-pirazol (Ph-IDMPz) bileşikleri
literatürdeki yönteme göre uyarlanarak sentezlenmiştir. 4-İyodo pirazollerin fenil boronik
asit ile N-arilleme reaksiyonları Cu2O katalizörlüğünde, atmosferik
koşullarda, oda sıcaklığında ve metil alkol içerisinde herhangi bir baz ve
ligant kullanılmadan gerçekleştirilmiştir. Böylece daha ılıman koşullarda
Ullmann reaksiyonu ile ilk defa Ph-IPz ve Ph-IDMPz’ın sentezi
gerçekleştirilmiştir.
Sentezi
gerçekleşen Ph-IPz ve Ph-IDMPz’in yapıları FT-IR, NMR ve GC-MS kütle
spektrumları alınarak karakterize edilmiştir. Bileşiklerin
NMR ve FT-IR spektrumunda hem pirazole hem de fenil grubuna ait karakteristik
pikler gözlenmiştir.Elde edilen Ph-IPz ve Ph-IDMPz bileşiklerinin 1H-NMR
spektrumlarında N-H proton piklerinin görülmemesi fenil grubunun pirazole
NH’dan bağlandığının bir göstergesidir. 13C-NMR spektrumlarında
4-sübstitüe pirazoller için belirleyici olan
C4 karbon piklerindeki kaymalar da bileşiklerin yapılarını
doğrulamaktadır.
Keywords
References
- [1] Eicher, T.; Hauptmann, S.; Speicher, The chemistry of heterocycles: structure, reactions, synthesis and applications-3rd edition (Wiley‐VCH Verlag GmbH & Co. KGaA, Weinheim, Germany, 2003)
- [2] Wang X.Y., Liu S.Q., Zhang C.Y., Song G., Bai F.Y., Xing Y.H. ve Shi Z., Synthesis, structural, and biological evaluation of the arene-linked pyrazolyl methane ligands and their d9/d10 metal complexes. Polyhedron, 47 (2012) 151-164.
- [3] Potapov, A.S., Khlebnikov, A.I., Synthesis of mixed-ligand copper(II) complexes containing bis(pyrazole-1-yl) methane ligands. Polyhedron, 25 (2006) 2683-2690.
- [4] Fustero S., Sanchez-Rosello M., Barrio P. ve Simon-Fuentes A., From 2000 to Mid-2010: A fruitful decade for the synthesis of pyrazoles. American Chemical Society, 111 (2011) 6984-7034.
- [5] Bouabdallah I., Touzani R., Zidane I., Ramdani A., ve Radi S., Synthesis of some 1-aryl-3,5-disubstituted-pyrazoles by N-arylation of 3,5-disubstituted-pyrazoles with 4-fluoro and 2-fluoronitrobenzene under microwave irradiation and classical heating. Arkivoc, 12 (2006) 138-144.
- [6] Xu Z.L., Li H.X., Ren Z-G. , Du W.Y., Xu W.C. ve Lang J.P., Cu(OAc)2.H2O-catalyzed N-arylation of nitrogen-containing heterocycles. Tetrahedron, 67 (2011) 5282-5288.
- [7] Kaplars A., Antilla J.C., Huang X. ve Buchwald S.L.J., A general and efficient copper catalyst for the amidation of aryl halides and the N-arylation of nitrogen heterocycles. Journal of American Chemical Society, 123 (31) (2001) 7727-7729.
- [8] Taillefer M., Cristau H.J., Cellier P.P. ve Spindler J.F., Patents FR 2833947-WO0353225 (Pr. Nb. Fr 2001 16547) (2001).
- [9] Evano G., Blanchard N. ve Toumi M., Copper-mediated coupling reactions and their applications in natural products and designed biomolecules synthesis. Chemical Reviews, 108 (8) (2008) 3054-3131.
- [10] Ley S.V. ve Thomas A.W., Modern synthetic methods for copper-mediated C(aryl)[bond]O, C(aryl)[bond]N, and C(aryl)[bond]S bond formation. Angewandte Chemie International Edition, 42 (44) (2003) 5400-5449.
- [11] Kim M. M., Ruck R.T., Zhao D. ve Huffman M.A., Green iodination of pyrazoles with iodine/hydrogen peroxide in water. Tetrahedron Letters, 49 (2008) 4026-4028.
- [12] Kantam M.L., Venkanna G.T., Sridhar C., Sreedhar B. ve Choudary B.M., An efficient base-free n-arylation of imidazoles and amines with arylboronic acids using copper-exchanged fluorapatite. Jornal of Organic Chemistry, 71 (2006) 9522-9524.
- [13] Joubert N., Baslé E., Vaultier M. ve Pucheault M., Mild, base-free copper-catalyzed N-arylations of heterocycles using potassium aryltrifluoroborates in water under air. Tetrahedron Letters, 51 (2010) 2994–2997.
- [14] Rao H., Fu H., Jiang Y.ve Zhao Y., Easy copper-catalyzed synthesis of primary aromatic amines by coupling aromatic boronic acids with aqueous ammonia at room temperature. Angewandte Chemie International Edition, 48 (2009) 1114-1116.
- [15] Roy S., Roy S. ve Gribble G.W., Metalation of pyrazoles and indazoles, Topics in Heterocycle Chemistry, 29 (2012) 155-260.
- [16] Coates J., Interpretation of Infrared Spectra, A Practical Approach, 10815-10837, R.A. Meyers (Ed.). Encyclopedia of Analytical Chemistry (John Wiley & Sons Ltd., Coates Consulting, Newtown, USA, 2000)
- [17] Skoog D.A., Holler F.J. ve Nieman T.A., Principles of Instrumental Analysis, Fifth Edition (Harcourt Brace &Company, Florida, USA, 1998)
- [18] Stuart B.H., Infrared Spectroscopy: Fundamentals and Applications (John Wiley & Sons Ltd., İngiltere, 2004).
- [19] Sharma S., Barooah N., ve Baruah J.B., Tris (3,5-dimethylpyrazole) copper(II) nitrate: as an oxidation catalyst. Journal of Molecular Catalysis A: Chemical, 229 (2005) 171-176.
- [20] Ovejero P. , Mayoral M. J., Cano M., Campo J.A., Heras J.V., Pinilla E., Torres M. R., The 3,5-dimethyl-4-nitropyrazole ligand in the construction of supramolecular networks of silver(I) complexes, Journal of Organometallic Chemistry, 692 (2007) 4093–4105.
- [21] Mezei G., Raptis R.G., Effect of pyrazole-substitution on the structure and nuclearity of Cu(II)-pyrazolato complexes, Inorganica Chimica Acta, 357 (2004) 3279–3288
Details
| Primary Language | Turkish |
|---|---|
| Journal Section | Research Article |
| Authors | |
| Publication Date | June 30, 2019 |
| Submission Date | October 29, 2018 |
| Acceptance Date | April 3, 2019 |
| Published in Issue | Year 2019Volume: 3 Issue: 1 |
Aksaray J. Sci. Eng. | e-ISSN: 2587-1277 | Period: Biannually | Founded: 2017 | Publisher: Aksaray University | https://asujse.aksaray.edu.tr
ASUJSE is indexing&Archiving in
