New type of 2-alkyl-substituted 1,8-naphthyridine systems containing a phosphoryl group in the side chain

Abstract

First organophosphorus derivatives of 2 alkyl and 2,3 alkylene substituted 1,8 naphthyridi nes were synthesized by the Friedländer reaction starting from 2 aminonicotinaldehyde and diphenylphosphoryl(cyclo)alkanones, respectively.The chemistry of 1,8 naphthyridines has attracted increasing interest due to the structural features of these compounds. As opposed to five other isomeric naphthyridines, the arrangement of the nitrogen atoms in the heterocyclic system of 1,8 naphthyridines is optimal from the point of view of chelation to metal cations. 1 It should be noted that many functionalized representatives of this class of compounds have a broad range of biologi cal activities. 2 However, organophosphorus derivatives of 1,8 naphthyridine have attracted attention only in the recent past. A few compounds containing the diphenyl phosphine groups at positions 2 and 7 of the naphthyridine moiety were characterized. 3-5 It should also be empha sized that the functionalization of this class of compounds is often complicated by side reactions with the involve ment, in particular, of the heterocyclic moiety. 6 Our research interests in the synthesis of organophos phorus ligands and investigation of their coordination chemistry have generated a need for the development of a convenient procedure for the synthesis of functionalized 2 alkyl substituted 1,8 naphthyridines containing phos phoryl groups as additional donor centers in the side chain. Earlier, we have synthesized 7 first representatives of this class of compounds, which are potential tridentate hetero difunctional ligands, by the Friedländer reaction starting from phosphorylated derivatives of acetone and cyclo pentanone. The main drawback of the Friedländer reac tion is that unsymmetrical ketones give both possible regioisomeric naphthyridines in comparable amounts un der alkaline catalysis (Scheme 1). Scheme 1 R = Alk, CH 2 Ar, Ar, P(O)Ph 2In the present study, we developed an approach to the solution of the problem of the regioselectivity based on the modification of ketones by replacing one or both hydrogen atoms of the methylene unit, which links the carbonyl group of ketone and the substituent R, with an alkyl group. This approach provides the involvement of only two hydrogen atoms of the methyl group of functionalized unsymmetrical ketones in the reaction, re sulting in the formation of the only Friedländer reaction product, viz., the target 2 substituted 1,8 naphthyridine. Results and DiscussionIn the present study, we synthesized various represen tatives of phosphorylated ketones, which were then intro duced into the Friedländer reaction with 2 amino nicotinaldehyde (1). The phosphorylation of the starting cycloalkanones with chlorodiphenylphosphine and the synthesis of aldehyde 1 were carried out according to known procedures. 8,9 The Friedländer reaction was cata lyzed by either aqueous NaOH or pyrrolidine. In some * Dedicated to Academician G. A. Abakumov on the occasion of his 70th birthday.

Coordination of 2-phosphorylalkyl-substituted 1,8-naphthyridines in complexes with lanthanide nitrates

“…11,12 Synthesis of lanthanide complexes 1-12 (general procedure). To a solution of a ligand (L 1 or L 2 ) (0.3 mmol) in chloroform (1-2 mL), a solution of stoichiometric amount (0.3 or 0.15 mmol) of Ln(NO 3 ) 3 •nH 2 O in acetonitrile (2 mL) was slowly added dropwise at room temperature, and the mixture was concentrat ed in vacuo (~5 Torr) to ~1 mL.…”

“…2. Raman spectra of the free ligand L 2 and its complexes with lutetium nitrate with a metal to ligand ratio of 1 : 1 (9) and 1 : 2 (12) and of a solution of complex 12 in nitromethane (12s). The crossed lines refer to the solvent.…”

“…Taking into ac count that tertiary phosphine oxides can form a strong coordination bond with many metals (including lan thanides) through the lone electron pair of the phosphoryl oxygen atom, we synthesized new phosphorus containing ligands, viz., monosubstituted phosphorylalkyl 1,8 naph thyridines. 11, 12 The coordination properties of this type of ligands were investigated using the example of the complex ation of 2 [2 (diphenylphosphoryl)propan 2 yl] 1,8 naphthyridine (L 1 ) and 2 [2 (diphenylphosphoryl)ethyl] 1,8 naphthyridine (L 2 ) containing linkers of differ ent length with lanthanide nitrates Ln(NO 3 ) 3 (Ln = Nd, Eu, or Lu).…”

Effect of the nature of substituents at the phosphorus atom on extraction properties of phosphorylketones toward f-elements

“…4 (Diphenylphosphoryl)butan 2 one(3),30 4 (diisopropyl phosphoryl) 4 phenylbutan 2 one (5), 31 and 4 (diphenylphos phoryl) 4 phenylbutan 2 one (6) 32 were synthesized and puri fied according to the known procedures.Model compounds tributyl phosphate (BuO) 3 P(O) (7) (99%, Acros Organics) and trioctylphosphine oxide (C 8 H 17 )P(O) (8) (99%, Acros Organics) were used without additional purifica tion. (N,N Dibutylcarbamoylmethyl)diphenylphosphine oxide Ph 2 P(O)CH 2 C(O)NBu 2 (9) 40 was synthesized and purified ac cording to the known procedures.4 (Diisopropylphosphoryl)butan 2 one (1).A solution of di isopropylchlorophosphine (5.50 g, 36 mmol) in anhydrous aceto nitrile (18 mL) and a solution of acetic acid (2.40 g, 40 mmol) in anhydrous acetonitrile (7 mL) were added sequentially and drop wise to a solution of methyl vinyl ketone (2.65 g, 37.8 mmol) in anhydrous acetonitrile (15 mL) with stirring with a magnetic stirrer.…”

2-(N-Phosphorylamino)-substituted 1,8-naphthyridines. synthesis and structure

“…The presence of P III containing fragments in the side chains of these ligands gives rise to an additional coordination center and, correspondingly, to new coordination proper ties of 1,8 naphthyridine derivatives. 1 Previously, 5, 6 we have synthesized a series of phospho alkyl derivatives of 1,8 naphthyridine, in which the phos phoryl fragment is bound to the heterocyclic moiety by structurally different alkylene linkers of different lengths. The coordination properties of these systems have been studied, and these systems have shown to act as tridentate ligands in complexes with lanthanides, both the nitro gen atoms of the heterocyclic moiety and the oxygen atom of the phosphoryl group being involved in coordina tion bonds.…”