Condensation Of 2-aminopyridines Research Articles

A “neat” synthesis of substituted 2-hydroxy-pyrido[1,2-a]pyrimidin-4-ones

We report the synthesis of a series of substituted 2-hydroxy-pyrido[1,2-a]pyrimidin-4-ones through a condensation of 2-aminopyridines and diethyl malonate. This method is contrasted with three reported general procedures for the preparation of these compounds, revealing that simple, “neat” synthesis conditions are suitable for a number of derivatives, including halogenated compounds suitable for further functionalization. Environmental, safety, and economic factors were considered in exploring this effective and robust synthetic method.

A Facile Three-Steps, One-Pot Synthesis of Novel 2-Alkylamino and 2-Dialkylamino-4H-Pyrido[1,2-A][1,3,5] Triazin-4-Ones from 2-Aminopyridine and 2-Aminopicolines

A straightforward approach to novel 2-dialkylamino-4H-pyrido[1,2-a][1,3,5]triazin-4-ones synthesis is presented. The construction of these compounds was achieved by one-pot synthesis involving condensation of 2-aminopyridine or 2-aminopicolines with ethoxycarbonylisothiocianate, followed by amination of the thioureas, and finally thermal ring closure of resulting guanidines. This allowed access to the unreported title heterocycles. We described an efficient, facile, one-pot synthesis of a novel 2-dialkylamino-4H-pyrido[1,2-a][1,3,5]triazin-4-ones in order to obtain a library of pyridotriazines which will be used as building blocks in medicinal chemistry.

Fused chromeno and quinolino[1,8]naphthyridines: Synthesis and biological evaluation as topoisomerase I inhibitors and antiproliferative agents

The synthesis of 1,8-naphthyridine derivatives fused with other heterocycles, such as chromenes and quinolines, as well as their behaviour as topoisomerase I inhibitors is studied. The preparation is carried out through a direct and simple process as an intramolecular [4 + 2] cycloaddition reaction between functionalized aldimines, obtained by the condensation of 2-aminopyridine and unsaturated aldehydes, and olefins. In particular, while no clear inhibitory activity is observed for chromeno[4,3-b][1,8]naphthyridine fused heterocycles, a very different result is observed for quinolino[4,3-b][1,8]naphthyridine derivatives. Experimental assays indicated that quinolino[4,3-b][1,8]naphthyridines inhibited the topoisomerase I enzymatic reaction behaving like a poison, as occurs with the natural TopI inhibitor, camptothecin. Furthermore, the cytotoxic effect on cell lines derived from human lung adenocarcinoma (A549), human ovarian carcinoma (SKOV3), and on non-cancerous lung fibroblasts cell line (MRC5) was also screened.

Synthesis, characterization and antimicrobial studies on Schiff base derived from 2-aminopyridine and 2-methoxybenzaldehyde and its cobalt (ii) and nickel (ii) complexes

A Schiff base ligand has been synthesized by the condensation of 2-aminopyridine and 2- methoxybenzaldehyde. Metal complexes of the Schiff base were prepared by the reaction of the Schiff base and metal (II) chlorides of cobalt and nickel in ethanol. The complexes were isolated, washed and dried. The Schiff base is pale yellow, while cobalt and nickel complexes are blue and light green respectively. The Schiff base and its metal (II) complexes were characterized by solubility test, melting and decomposition temperature determination, FTIR, magnetic susceptibility, molar conductance gravimetric analysis and UV spectroscopy. Solubility test carried on the Schiff base and the complexes showed that they are all soluble in DMSO and DMF, but insoluble in water. From the FTIR result, a peak at 1577cm-1 is assigned to the azomethine of the Schiff base which shifted to 1637 and 1622 cm-1 in cobalt (II) and nickel (II) complexes respectively. The complexes are high spin, non electrolytic in nature and have high thermal stability. Job’s method of continuous variation suggests 1:2 metal to ligand ratio. The Schiff base is inactive against Staphylococcus aureus at all concentrations while the complexes were found to be active and the activity increases with increase in concentration. The Schiff base and its complexes are found to be active against E. coli at all concentrations. The anifungal study revealed that the Schiff base and its complexes are active against Candida albican at all concentrations, but inactive againstMucor specie at all concentrations.KEY WORDS: 2-aminopyridine, 2-methoxybenzaldehyde, Ligand, Characterization, Antimicrobial activity

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New series of 3-substituted heterocyclic compounds containing bridge head nitrogen were synthesized through multi-step reactions. In order to prepare the starting 2-substituted heterocyclic compounds of pyridine, a known procedure was used by condensation of 2-amino pyridine with (4-bromo phenacyl bromide). Carbaldehyde group was introduced at position-3 of prepared 2-substituted imidazo / pyridine rings by Vilsmeier-Haack reaction. 3-Carbaldehyde derivatives underwent Claisen condensation with different aryl ketons to give unsaturated ketones of these derivatives, which on cyclization with urea and thiourea afforded 3-cyclic oxopyrimidines and thiopyrimidines derivatives of imidazo / pyridine rings. In addition, 3-carbaldehyde derivatives was reacted with hydrazine, semicarbazide and hydroxyl amine hydrochloride to yield new hydrazone, semicarbazone and oxime derivatives of imidazo / pyridine rings. All prepared compounds were characterised via FT-IR spectroscopy, some of them were characterised by 1H-NMR spectroscopy. These new 3-subistituted derivatives of imidazo /pyridine rings were tested in different species bacterial and fungi. Some of tested compounds showed strong activity while the other showed moderate against. Interestingly, All these new prepared compounds showed high activity against fungi.

Synthesis and Characterization with Antimicrobial Activity Studies on some Transition Metal Complexes of N, O Donor Novel Schiff Base Ligand

Metal complexes of Mn(II), Fe(II), Co(II) and Cd(II) ions with Schiff base ligand 4-{(pyridin-2-ylimino)methyl}phenol derived from condensation of 2-amino pyridine with 4-hydroxybenzaldehyde was prepared. The ligand and complexes were isolated from the reaction in the solid form and characterized by conductivity, magnetic moment, TLC, IR, UV-Visible, thermal analysis and some physical measurements. During complexation reaction with transition metal ions Schiff base act as a deprotonated tridentate ligand and IR spectra showed that N and O atoms are coordinated to the central metal atom. The observed values confirmed that the complexes have octahedral geometry. The Schiff base and its metal complexes have been found to have moderate to strong antibacterial activity.

Facile synthesis of novel 3-substituted pyrido[1,2-a]pyrimidinium salts using vinamidinium salts

ABSTRACTPyrido[1,2-a]pyrimidinium salt derivatives 2a–f were prepared in good yields by condensation of 2-aminopyridine with 2-substituted vinamidinium salt derivatives 1a–f. The purity and the structure of the synthetized compounds were ascertained by elemental analysis, mass spectrometry, infrared, and NMR (¹H and ¹³C 400 MHz) spectroscopy.

Solvent- and catalyst-free synthesis of imidazo[1,2-a]pyridines under microwave irradiation

A facile solvent- and catalyst-free method for the synthesis of a series of imidazo[1,2-a]pyridines in good to excellent yields by the condensation of 2-aminopyridines with α-bromoketones under microwave irradiation has been developed. The important features of this method are that it is reasonably fast, very clean, high yielding, simple workup and environmentally benign.

ChemInform Abstract: Microwave Assisted Synthesis of Disubstituted Imidazo[1,2‐a]pyridine‐3‐carboxylic Acid Esters

Abstractby condensation of 2‐aminopyridines and ethyl 2‐halogenated acetoacetates

Sodium ion assisted molecular self-assembly in a class of Schiff-base copper(II) complexes

Syntheses, characterization and crystal structures of three new sodium based heterotrinuclear ionic clusters [(CuL1)2Na(ClO4-O,O′)(OH2)]·C8H8O2 (1), [(CuL2)2Na(ClO4-O,O′)] (2) and [{Cu(L3)2}2Na]+·ClO4− (3) derived from three different Schiff bases (L1=1:2 condensation of 1,2-propane diamine and o-hydroxy acetophenone, L2=1:2 condensation of 1,2-propane diamine and 2-hydroxy-5-methoxy acetophenone and L3=1:1 condensation of 2-amino pyridine and 3-ethoxy salicylaldehyde) are reported herein. The crystal structure analysis reveals that the square-planar Cu–ligand complexes act as building block for the trinuclear complex in which Na+ ion guides the orientation of Cu(II) Schiff-base complexes into a scissor like architecture in 1 and 2. The unique assembling feature of Na+ ion is also evident in complex 3 where even in the presence of a widely different Schiff-base ligand, Na+ guides two Cu(II)(L3)2 complexes to assemble around it in a crown ether like environment. In complexes 1 and 2 the square planar metal coordination provide suitable sites for chelate ring π···π interaction and Cu···π interaction which ensures columnar assembly of trinuclear units at the supramolecular level. The present study reveals the unique nature of the self-assembly of square-planar Cu(II) Schiff-base complexes around Na+.

Synthesis, spectroscopic (IR, electronic, FAB-mass, and PXRD), magnetic, and antimicrobial studies of new iron(III) complexes containing Schiff bases and substituted benzoxazole ligands

Mixed ligand complexes of iron(III), [Fe(sb)2(py)Cl] · 2H2O (1–9) [where sbH = Schiff bases (derived from condensation of 2-aminopyridine (sapH), 2-aminophenol (saphH), o-toluidine (o-smabH), aminobenzene (sabH), p-toluidine (p-smabH), 3-nitroaniline (snabH), and anthranilic acid (saaH) with salicylaldehyde and substituted (mercapto-)benzimidazole (mbzH), {2-(o-hydroxyphenyl)}benzoxazole, (pboxH)], have been synthesized by the interactions of iron(III) chloride with corresponding ligands in 1 : 2 molar ratio in refluxing pyridine. These complexes have been characterized by elemental analyses, melting points, spectral, and magnetic studies. Powder X-ray diffraction studies of some representative complexes are also reported herein. The antibacterial and antifungal activities of the free ligands and their iron(III) complexes were found in vitro. The complexes showed good antibacterial and antifungal effect to some bacteria and fungi. Two standard antibiotics (chloromphenicol and terbinafine) were used for comparison with these complexes.

Catalyst- and Solvent-Free Synthesis of Substituted Imidazo[1,2-a]pyridines

Reported is the rapid and convenient synthesis of imidazo[1,2-a]pyridines 3 via the condensation of 2-aminopyridines 1 with β-keto esters 2 under solvent-free conditions. Under thermal conditions, the products were obtained in 80-89% yield in under 35 minutes, except for one case (R¹ = 4-Me-5-Br, R² = Me, R³ = Et) where a moderate 58% yield was obtained. Higher yields (85-95%) were obtained in under two minutes by performing the reaction under microwave irradiation on alumina support. Diversely substituted 2-aminopyridines and several β-keto esters were equally well tolerated in this process. A reasonable mechanism involving sequential condensation ­reactions is proposed without evidence.

Living Radical Polymerization of Acrylates Mediated by 1,3‐Bis(2‐pyridylimino)isoindolatocobalt(II) Complexes: Monitoring the Chain Growth at the Metal

A new type of mediator for cobalt(II)-mediated radical polymerization is reported which is based on 1,3-bis(2-pyridylimino)isoindolate (bpi) as ancillary ligand. The modular synthesis of the bis(pyridylimino)isoindoles (bpiH) employed in this work is based on the condensation of 2-aminopyridines with phthalodinitriles. Reaction of the bpiH protio-ligands with a twofold excess of cobalt(II) acetate or cobalt(II) acetylacetonate in methanol gave [Co(bpi)(OAc)], which crystallize as coordination polymers, and a series of [Co(acac)(bpi)(MeOH)], which are mononuclear octahedral complexes. Upon heating the [Co(acac)(bpi)(MeOH)] compounds to 100 degrees C under high vacuum, the coordinated methanol was removed to give the five-coordinate complexes [Co(acac)(bpi)]. The polymerization of methyl acrylate at 60 degrees C was investigated by using one molar equivalent of the relatively short-lived radical source 2,2'-azobis(4-methoxy-2,4-dimethylvaleronitrile) (V-70) as initiator (monomer/catalyst/V-70: 600:1:1). The low solubility of the acetato complexes inhibits their significant activity as mediators in this reaction, whereas the acetylacetonate complexes control the radical polymerization of methyl acrylate more effectively. The radical polymerizations of the hexacoordinate complexes did not show a linear increase in number-average molecular weight (M(n)) with conversion; however, the polydispersities were relatively low (PDI=1.12-1.40). By using the pentacoordinate complexes [Co(acac)(bpi)] as mediators, a linear increase in M(n) values with conversion, which were very close to the theoretical values for living systems, and very low polydispersities (PDI<1.13) were obtained. This was also achieved in the block copolymerization of methyl acrylate and n-butyl acrylate. The intermediates with the growing acrylate polymer radical ((.)PA) were identified by liquid injection field desorption/ionization mass spectrometry as following the general formula [Co(acac)(4-methoxy-bpi)-(MA)(n)-R] (MA: methyl acrylate; R: C(CH(3))(CH(2)C(CH(3))(2)OCH(3))CN), a notion also confirmed by NMR end-group analysis.

New Approach for the Synthesis of Pyrido[1,2-a]pyrimidines

A novel method was successfully demonstrated towards the synthesis of pyrido[1,2-a]pyrimidines having chloroethyl as an intractable side chain, through dihydrofuranone intermediates. The dihydrofuranone intermediates were synthesized by condensation of 2-aminopyridines with α-acetyl-γ-butyrolactone, which upon cyclization using phosphorus oxychloride or ethanol in sodium ethoxide furnished the pyrido[1,2-a]pyrimidines in good yield.

Reactions of 3-Chloropropeniminium Salts with Aminopyridines. Synthesis of N-Pyridylpyridinium and Pyrido[1,2-a]pyrimidinium Salts

Abstract N-(Pyridyl)pyridinium salts 7 and 8 as well as 4-phenylpyrido[1,2-a]pyrimidinium salts 4 and 12 have been prepared by reactions of 3-aryl-3-chloropropeniminium salts 5 with aminopyridines (6) using glacial acetic acid as solvent. 2-Phenylpyrido[1,2-a]pyrimidinium salts 2 are formed when ethanol is used as the solvent. The condensation of 2-aminopyridine (6a) with 3-chloro-2,3- dehydromorpholino-2-carbiminium salt 13 is described. The HSAB principle of Pearson is discussed to explain the different regioselective ring closure reactions.

Synthesis and crystal structure of Schiff bases obtained by condensation of 2-aminopyridines with acrylic aldehydes

We synthesized a series of novel imines by reactions of 2-amino-4-methylpyridine with (hetero)aromatic derivatives of acrolein in the presence of molecular sieves (as a dehydrating and acid-catalyzing agent). We determined the molecular and crystal structure of two 2-pyridylazomethines containing the CH=CH−CH=N group by X-ray diffraction analysis.

Novel reaction of aminopyridines with glyoxal and formaldehyde; synthesis of 4,8-di (N-aminopyridyl) 2,6-dioxa 4,8-diazabicyclo[3.3.0]octane, 6,8-di(N-aminopyridyl) 2,4-dioxa 6,8-diazabicyclo[3.3.0]octane and X-ray structural study of related 1,3-di(N-aminopyridyl) 4,5-dihydroxy imidazolidine

Condensation of 2-aminopyridine with glyoxal proceeds with high selectivity to a mixture of meso and dl diol 7 to be easily transformed into the corresponding bicyclooctane 2a and 3a with formaldehyde and acetonitrile as solvent. In water, however, the reaction selectively produces imidazolidine 4a. Based on NMR analysis, the major diastereomers were assigned as syn derivatives. X-ray crystal structure of 4a shows a planar configuration for imidazolidine ring, in line with two anomeric effects, first a strong n N → σ C-O ∗ interaction and second a weak n O → σ C-N ∗ one. A network of hydrogen bonding between pyridyl nitrogens and hydroxy hydrogens forms a pattern of twelve atom in a chair-like conformation.

2‐Aminopyridiniomethylphosphonite: A hydrogen‐bonded polymer from the hydrolysis of 1,3,4‐diazaphospholo[1,2‐a]pyridine

AbstractCondensation of 2‐aminopyridine and chloromethyldichlorophosphane yields 1,3,4‐diazaphospholo[1,2‐a]pyridine 2. Methanol adds to 2 while diethylamine does not; with additional elemental sulfur, in both cases the sulfides 4, 6 of the respective adducts are formed. Hydrolysis of 2 specifically opens the PN‐bond and gives the zwitterionic 2‐aminopyridinio‐methylphosphonite 7. The compound crystallizes with one molecule water in the monoclinic space group P21/c with a = 25.490(7)Å, b = 7.365(4)Å, c = 9.088(3)Å, β = 100.06(3)°, and Z = 8 with two independent molecules of 7 and of water. In the crystal hydrogen bonds connect the molecules of 7 to form double‐chain structured polymers. The individual double‐chains are linked to each other by hydrogen‐bonded water molecules.

Electro-organic reactions part 35. Efficient carbon—oxygen bond formation in the anodic coupling of pyridopyrimidine derivatives.

4-H-Pyrido[1,2-a]pyrimidine-2,4-diones (Chichibabin) derivatives, formed by condensation of 2-aminopyridines with substituted dialkylmalonates, are electroactive. In solution in CH 2Cl 2/CF 3CO 2H mixtures they are smoothly and selectively anodically coupled in high yield. The products are novel and unexpected; radical coupling at the C-3 and O-4 positions is involved and the proposed mechanism is analogous to that of oxidative phenolic coupling.

Synthesis of cypridina luciferin and related compounds. VI. Synthesis of 3-hydroxyimidazo[1,2-a]pyridines

Condensation of 2-aminopyridine with benzaldehyde sodium bisulfite adduct and NaCN by the method of Ohta, et al. gave, instead of the nitrile as previously suggested, 3-amino-2-phenylimidazo[1, 2-α]pyridine (VI), which in turn was converted by treatment with conc. hydrochloric acid into 3-hydroxy-2-phenyl derivative (X). 3-Amino (IV) and 3-amino-2-methyl derivative (V) by the same treatment, however, gave the corresponding carboxylic acids (XI and XII). Instead of the unsuccessful cyclization of XI and XII, the ethyl ester of XII (XIV) was smoothly converted, on being heated in vacuo, to pure 3-hydroxy-2-methyl derivative (IX). It is interesting to note that the chemiluminescence activity is observed with 3-hydroxy compounds (VIII, IX and X), but not with 2-hydroxy-3-methyl derivative (III), which is synthesized from I and α-chloropropionyl chloride and exists in a tautomeric mixture of 2-hydroxy type (IIIb) and 2-keto type (IIIc) in a DMSO solution.