19th Iranian Chemistry Congress , 2017-02-21

Title : ( Novel bis-pyrimidine derivatives: Synthesis and characterization )

Authors: Toktam Afrough , Mehdi Bakavoli , Hossein Eshghi ,

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Introduction: Pyrimidine nucleus has played crucial role in the history of heterocyclic chemistry and has been used extensively as important pharmacophor and synthon in the field of organic chemistry and drug design. Bis-heterocyclic compounds are considered as bis-drugs, due to their double therapeutic behavior compared to their mono-heterocyclic analogues. For example, bispyrimidines show various biological properties such as anti-bacterial [1], anti-inflammatory [2] and anti-amobeic [3]. Here, we wish to report the synthesis of new series of bis-pyrimidine derivatives. Methods / Experimentals: Initially, bis-pyrimidine (2) was prepared from reaction of compound (1) [4] with methyl iodide in DMF. Consecutive reaction of compound (2) with 2- aminothiophenol and secondary amines gave compound (3) and the desired bis-pyrimidine derivatives (4a-g), respectively. Results and Discussion: The general route for the synthesis of 2-((5-bromo-6-(1-(5-bromo-6- methyl-2 (substituted)pyrimidin-4-yl)ethyl)-2-( substituted)pyrimidin-4-yl)thio)aniline (4a-g) is depicted in scheme 1. Scheme 1 Attempted heterocyclization of these compounds (3) and (4a-g) in the presence of NaNH2 and CH3CN as have been reported for the synthesis of pyrimido[4,5-b][1,4]benzothiazine derivatives [5] was not successful. This reaction did not even proceed when different base/solvent systems was employed and each time the starting material was recovered. The poor electrophilicity of C- 5 of these compounds can be accounted on the fact that the methine’s hydrogen is more acidic than NH2 hydrogens. For tentative confirmation of this idea, we exchanged acidic hydrogen of compound 3 in isopropanol-d8 and obtained deuterated product 3ʹ. In the 1H NMR spectrum of compound 3ʹ quartet peak at δ 4.91 ppm belonging to hydrogen of methine adjoined to methyl group disappeared. Antimicrobial activities of the new products were evaluated against a variety of Gram-positive and -negative bacteria. Conclusion: In summary, new bis-pyrimidine derivatives (4a-g) were prepared in a three-step procedure based on 5-bromo-2,4-dichloro-6-methylpyrimidine (1) as starting material. In spite of our expectation based on our previous studies, the heterocyclization of compounds (3) and (4a-g) was not performed. It is proved that the poor electrophilicity of C-5 of these compounds can be responsible for synthesis of new bis-pyrimidine derivatives (4a-g) despite pyrimido[4,5- b][1,4]benzothiazine derivatives. Refrences [1] N. O. Mahmoodi; S. Shoja; B. Sharifzadeh; M. Rassa. Med. Chem. Res, 2014, 23, 1207-1213. [2] Sh. M. Sondhi; Sh. Jain; M. Dinodia; R. Shukl; R. Raghubir. Bioorg. Med. Chem, 2007, 15, 3334–3344. [3] H. Parveen; F. Hayat; S. Mukhtar; A. Salahuddin; A. Khan; F. Islam; A. Azam. Eur. J. Med. Chem, 2011, 46, 4669-4675. [4] M. Bakavoli; M. Nikpour; M. Rahimizadeh. J. Heterocycl. Chem, 2006, 43, 1327-1329. [5] M. Bakavoli; M. Nikpour; M. Rahimizadeh; M. R. Saberi; H. Sadeghian. Bioorg. Med. Chem, 2007, 15, 2120–2126.


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author = {Afrough, Toktam and Bakavoli, Mehdi and Eshghi, Hossein},
title = {Novel bis-pyrimidine derivatives: Synthesis and characterization},
booktitle = {19th Iranian Chemistry Congress},
year = {2017},
location = {شیراز, IRAN},
keywords = {bis-pyrimidine derivativesو Synthesisو characterization},


%0 Conference Proceedings
%T Novel bis-pyrimidine derivatives: Synthesis and characterization
%A Afrough, Toktam
%A Bakavoli, Mehdi
%A Eshghi, Hossein
%J 19th Iranian Chemistry Congress
%D 2017