Indian Journal of Chemistry Vol. 49B, February 2010, pp. 253-255 Note Potassium triiodide catalyzed Friedlander synthesis of 1,8-naphthyridines in aqueous media K Mogilaiah*, K Shiva Kumar & N Vasudeva Reddy Department of Chemistry, Kakatiya University, Warangal 506 009, India E-mail: mogilaiah_k@yahoo.co.in Received 29 January 2009; accepted (revised) 9 July 2009 Potassium triiodide catalyses the Friedlander condensation of 2-aminonicotinaldehyde 1 with carbonyl compounds containing α-methylene group 2 in aqueous media to afford 1,8- naphthyridines 3 in high yields. Keywords: Friedlander synthesis, 2-aminonicotinaldehyde, carbonyl compounds containing α-methylene group, potassium triiodide, aqueous media There has been growing interest in the use of metallic elements 1 in aqueous media, as they offer significant advantages over conventional reactions using organic solvents. The development of such reactions is of interest because they also offer the possibility of obtaining environmentally benign reaction conditions by reducing the burden of organic solvent disposal 2 . In recent years there has been increasingly emphasis on the use of environment friendly conditions to reduce the amount of toxic waste and by-products arising from the chemical processes. The study and application of Friedlander condensation in water is still in its infancy. Friedlander synthesis is an acid or base catalyzed condensation followed by a cyclo- dehydration between an aromatic 2-aminoaldehyde or ketone with the carbonyl compound containing a reaction α-methylene group. 2-Aminonicotinaldehyde condense readily with active methylene compounds in the presence of base (piperdine) 3 and acid (CH 3 COOH/H 2 SO 4 ), (Ref 4) catalysts to give 1,8- naphthyridines. But these methods suffer from drawbacks such as long reaction times, high temperature and low yields. In view of this and in continuation of the interest on environmentally benign protocols 5-8 , herein is reported the KI 3 catalyzed Friedlander condensation in aqueous media. The Friedlander condensation of 2-amino- nicotinaldehyde 1 with various carbonyl compounds containing α-methylene group 2 in the presence of KI 3 in aqueous media afforded the corresponding 1,8- naphthyridines 3 (Scheme I). The reaction is clean, rapid and efficient and is devoid of any by-products. The products are obtained in very good yields and in a state of high purity. Here the role of KI 3 is that of a mild base and the reaction is probably similar to the reactions promoted by bases. The process is environmentally benign. The experimental procedure is also very simple. In a typical case, an equimolar mixture of 1, ethyl acetoacetate 2a (R 1 = CH 3 ; R 2 = COOC 2 H 5 ) and KI 3 in water was heated at 70ºC for 12 min. After usual work-up ethyl-2-methyl-1,8-naphthyridine-3-carbo- xylate 3a (R 1 = CH 3 ; R 2 = COOC 2 H 5 ) was obtained in 92% yield. The reaction is of general applicability and the various 1,8-naphthyridines 3b-n synthesized are given in Table I. The compounds obtained were characterized by spectroscopic (IR and 1 H NMR) methods and finally by comparison with authentic samples 3, 9-12 . To the best of the knowledge, this is the first report on rapid Friedlander synthesis of 1,8-naphthyridines using KI 3 as catalyst in aqueous media. In conclusion, the present investigation under aqueous conditions offers a convenient and alternative method for the Friedlander synthesis of 1,8-naphthy- ridines where the reaction is rapid, the yields are very good, the procedure is simple and employs only nontoxic and inexpensive catalysts. Experimental Section Melting points were determined on a Cintex melting point apparatus and are uncorrected. The homogeneity of the compounds was checked using precoated TLC plates (Merck, 60F-254). IR spectra (KBr, cm -1 ) were recorded on a Perkin Elmer spectrum BX series FT-IR spectrophotometer and 1 H NMR spectra on a Varian Gemini 200 MHz spectrometer (chemical shifts in δ, ppm) using TMS as internal standard. General procedure for the synthesis of 1,8- naphthyridines 3. To a solution of potassium triiodide (0.01 mole), 2-aminonicotinaldehyde 1 (0.01 mole) and active methylene compound 2 were added at RT. After stirring for 2 min, the resulting mixture