Tandem Aldol-Michael reactions in aqueous diethylamine medium: a greener and efficient approach to dimedone-barbituric acid derivatives

Chemistry Central Journal

Assem Barakat¹  Abdullah Mohammed Al-Majid²  Abdulaziz Moshabab Al-Ghamdi²  Yahia Nasser Mabkhot²  Mohammed Rafiq Hussain Siddiqui²  Hazem A Ghabbour³  Hoong-Kun Fun³ 

[1] Department of Chemistry, Faculty of Science, Alexandria University, P.O. Box 426, Ibrahimia, Alexandria 21321, Egypt

[2] Department of Chemistry, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia

[3] Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia

关键词: Zwitterions;    Dimedone;    Green chemistry;    Aqueous media;    Barbituric acid;    MCRs;    Tandem Aldol-Michael reactions;   

Others  :  787802
DOI  :  10.1186/1752-153X-8-9

 received in 2013-10-27, accepted in 2014-01-28,  发布年份 2014

【 摘 要 】

Background

Green chemistry is a rapidly developing new field that provides us with a proactive avenue for the sustainable development of future science and technologies. Green chemistry uses highly efficient and environmentally benign synthetic protocols to deliver lifesaving medicines, accelerating lead optimization processes in drug discovery, with reduced unnecessary environmental impact. From this view point, it is desirable to use water instead of organic solvents as a reaction medium, since water is safe, abundant and an environmentally benign solvent.

Results

A convenient one-pot method for the efficient synthesis of the novel Zwitterion derivatives 4a-pvia a three-component condensation reaction of barbituric acid derivatives 1a,b, dimedone 2, and various aldehydes 3 in the presence of aqueous diethylamine media is described. This new approach is environmentally benign, with clean synthetic procedure, short reaction times and easy work-up procedure which proceeded smoothly to provide excellent yield (88-98%). The synthesized products were characterized by elemental analysis, IR, MS, NMR and CHN analysis. The structure of 4a was further confirmed by single crystal X-ray diffraction. The compound crystallizes in the orthorhombic space group Pbca with α = 14.6669 (5) Å, b = 18.3084 (6) Å, c = 19.0294 (6) Å, α = 90°, β = 90°, = 90°, V = 5109.9 (3) ų, and Z = 8. The molecules are packed in crystal structure by weak intermolecular C–H⋅ ⋅ ⋅O hydrogen bonding interactions.

Conclusions

An environmentally benign Aldol-Michael protocol for the synthesis of dimedone-barbituric derivatives using aqueous diethylamine medium is achieved.

【 授权许可】

   
2014 Barakat et al.; licensee Chemistry Central Ltd.

【 图 表 】

Figure 1.

Scheme 1

Figure 2.

Figure 3.

Figure 4.

Scheme 2

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