Amines 2a Research Articles

Synthesis, Characterizationand Antibacterial Activity of Quaternary Ammonium Compounds Bearing Mixed N-Substituted Groups

Sixteen quaternary ammonium bromides [QAB]4(a-d)-7(a-d)bearing mixed N-branches were synthesized by treating n-butyl 2a, cyclohexyl 2b, 2,3,4,6-tetra-O-acetyl – Dglucosyl 2c and cholesteryl 2d bromides, separately with n-butyl amine 3a, benzyl amine 3b, N,N-dimethyl amino ethyl-2methyl acrylate 3c and N,N-diethyl amino ethyl-2methyl acrylate 3d. N,N-Diphenyl amine 3e failed to react with any bromides within the scope of this work. The synthesized bromides and QAB were characterized by FT-IR, H-NMR and C-NMR. All compounds were tested for their activity against some gram-positive and gram-negative bacteria and some of them exhibited significant antibacterial activities.

Cyclometalation of (2R,5R)-2,5-Diphenylpyrrolidine and 2-Phenyl-2-imidazoline Ligands with Half-Sandwich Iridium(III) and Rhodium(III) Complexes

Cyclometalation of (2R,5R)-2,5-diphenylpyrrolidine (1) with [(η5-Cp*)MCl2]2 using NaOAc in CH2Cl2 at room temperature, followed by cationization with KPF6 in CH3CN, cleanly yielded the cationic cyclometalated amines 2a,b (a, M = Ir; b, M = Rh). This constituted an improvement with regard to another cyclometalation pathway, which had led to unwanted oxidation of the ligand to an imine. Compounds 2a,b were characterized by elemental analysis and X-ray diffraction of single crystals; the latter gave evidence of an R configuration of the metal center, and a λ envelope conformation of the five-membered metallacycle. Successful application of the NaOAc/CH2Cl2 methodology to the cycloiridation and cyclorhodation of the imidazolines 3–5 led to the neutral half-sandwich chloro complexes 6–8, which were completely characterized, with yields ranging from 44% to 82%. In these complexes, the labile NH proton was localized in a γ position with regard to the metal. From the enantiopure chiral ligands 4 and 5, both diastereoisomers of the four compounds 7a,b and 8a,b were identified in solution by NMR; they were in equilibrium in solution. Complexes 6b, (SM)-7a,b, and (RM)-8a,b were characterized by radiocrystallography, which showed that the metallacycles were planar. Complexes 6–8 were tested as catalysts for the reduction of acetophenone and imines by hydrogen transfer.

Synthons for supramolecular assemblies: Synthesis of new triazine-core polyhydroxylated and multi-N-donor compounds

The synthesis of new triazine-core polyhydroxylated and multi- N -donor compounds are being reported. The reaction of 2,4,6- tris (4- n -butylaminophenyl)triazine (1) with cyanuric chloride provided star-shaped fragment (2) with six reactive chloro-substituents. Upon treatment of this fragment with bis (2-hydroxyethyl)amine (3a) and bis (2-pyridylmethyl)amine (3b), functionalized polyhydroxylated (4a) and multi- N -donor compounds (4b) were obtained in high yields through nucleophilic aromatic substitution. These functionalized compounds are expected to have unique applications in supramolecular self-assembly and material chemistry.

Synthesis of β-amino carbonyl derivatives of coumarin and benzofuran and evaluation of their biological activity

A series of β-amino carbonyl compounds containing coumarin (4a–h) and benzofuran (6a–i) moieties was synthesized by a three component Mannich reaction of 3-acetyl-2H-chromen-2-one (1) or 1-(1-benzofuran-2-yl) ethanone (5) with p-substituted aromatic aldehydes (2a–g) and aromatic amines (3a–b) in the presence of cerric ammonium nitrate as a catalyst. The newly synthesized compounds were screened for antimicrobial and antioxidant activities. Compounds 4b, 4e, 4f, 6f, 6g, and 6i showed microbial inhibition with minimal inhibition concentration ranging between 0.040 and 0.500 mg/mL, compounds 4b, 4c, 6c, 6e, and 6i showed promising free radical scavenging activity and compounds 4b, 4f, 6c, 6d, and 6h showed good chelating ability with Fe2+ ions. The synthesized compounds were studied for docking on the enzyme, glucosamine-6-phosphate synthase to predict the binding affinity and orientation at the active site of the receptor.

Spiro[[1]benzothiophen-4,4′-piperidines] – carba analogs of potent σ1 ligands

Spiro[[1]benzothiophene-4,4′-piperidines] 5 are structurally related to aminoethyl substituted 1-benzothiophenes 4 and spirocyclic thienopyrans 3. The spirocyclic ring system 13 was established in a four step synthesis starting from 1-benzothiophen-4-one 7. The conjugate addition of an acetonitrile anion to the electron deficient double bond of 10 activated by two electron withdrawing groups and the hydrolysis of dinitrile 12 with H2O2/NaOH represent the key steps of the synthesis of the spirocyclic scaffold 13. LiAlH4 reduction of the spirocyclic imide 13 and subsequent reductive alkylation of the secondary amine 5a provided a set of spirocyclic σ ligands. Receptor binding studies revealed that exchange of the O-atom of the lead compound 3b (Ki = 0.31 nM) by a CH2 moiety (5b: Ki = 10.5 nM) decreased the σ1 affinity, whereas conformational restriction of the aminoethyl side chain of 4b (Ki = 49 nM) resulted in increased σ1 affinity. Conformational restriction as well as the ring O-atom is important for high σ1 affinity.

Molecular iodine catalyzed synthesis of tetrazolo[1,5-a]-quinoline based imidazoles as a new class of antimicrobial and antituberculosis agents

Abstract A series of some new tetrazolo[1,5-a]quinoline based tetrasubstituted imidazole derivatives 6a–l have been synthesized by a reaction of tetrazolo[1,5-a]quinoline-4-carbaldehyde 3a–d, benzil 4, aromatic amine 5a–c and ammonium acetate in the presence of iodine through one-pot multi-component reaction (MCR) approach. All the derivatives were screened for antimicrobial and antituberculosis activities and results worth further investigations.

Synthesis of amidine and bis amidine derivatives and their evaluation for anti-inflammatory and anticancer activity

2-Cyanopyridine (1a), 4-cyanopyridine (1b), 2-cyanopyrazine (1c) on condensation with mono amines (2a–c) and diamines (4a–c) in the presence of sodium methoxide as catalyst gave amidine derivatives (3a–i) and bis amidine derivatives (5a–i) in good yields. All these compounds were fully characterized by spectroscopic means and elemental analysis. On screening for anti-inflammatory activity and for in vitro anticancer activity compounds 5c and 5d exhibited good anti-inflammatory activity whereas compounds 5d breast (T47D), 5h, 5i lung (NCI H-522), 5i colon (HCT-15), 3c, 3h, 5i ovary (PA-1) and 3c, 5b, 5h liver (HepG2) exhibited good anticancer activity.

Synthesis and Characterization of Monosaccharide Derivatives and Application of Sugar‐Based Prolinamides in Asymmetric Synthesis

AbstractFor the first time, the β‐anomer of N‐acetylglucosamine derivative methyl 2‐acetamido‐3,4,6‐tri‐O‐benzyl‐2‐deoxy‐β‐D‐glucopyranoside (9b) was synthesized, isolated, and used in the synthesis of sugar‐based primary amine 4b. Sugar‐based primary amine 5a, an anomeric pair of monosaccharide derivatives 6a and 6b, and precursors to all these compounds were also synthesized, isolated, and well studied by standard spectroscopic methods, including 2D NMR spectroscopy experiments such as 1H–1H COSY and HSQC. Then sugar‐based primary amines 4a, 5a, 6a, and 6b were converted into the corresponding prolinamide organocatalysts (i.e., 1a, 2a, 3a, and 3b) in high yields. The catalytic activity of these sugar‐based prolinamide organocatalysts was demonstrated in asymmetric aldol reactions in various solvents and at different temperatures. The oraganocatalyst 3a was shown to be an efficient and powerful organocatalyst for the enantioselective aldol reaction of various cyclic or acyclic ketones with aromatic aldehydes in a mild and facile reaction, which gave the corresponding aldol adducts with high levels of diastereoselectivity (up to 99:1) and enantioselectivity (up to >99 %) in almost all cases.

A practical one pot synthesis of novel 2-hydroxy-4-chromanone derivatives from 3-formylchromone

A one pot synthesis of 4-chromanone derivatives (5a–j) is described using Zn[(L)(Proline)]2 as catalyst in aqueous media. The compounds have been characterized on the basis of elemental and spectral data (IR, 1H NMR and mass). The advantages of this protocol include high yields, mild reaction conditions, environmentally benign and simple operational procedure. The use of water as solvent and Zn[(L)proline]2 as recyclable, non-toxic catalyst make such synthesis a truly green process. An ecofriendly synthetic route has been developed for the synthesis of 2-hydroxy-4-chromanone derivatives (5a–j) in excellent yields employing 3-formylchromone (1) and primary aromatic amines (2a–j) in the presence of non-toxic, green Zn[(L)proline]2 catalyst in water. The catalyst is recyclable and shows activity up to three cycles.

A Diversity‐Oriented Approach to Spiroindolines: Post‐Ugi Gold‐Catalyzed Diastereoselective Domino Cyclization

Gold-catalyzed carbocyclization and heteroannulation strategies have recently attracted much attention owing to the selective and efficient activation of the C C bond towards a wide range of nucleophiles that these methods provide. Domino approaches involving gold-catalysis lead to complex heterocyclic compounds under exceedingly mild reaction conditions. Although gold-catalyzed approaches are rising to prominence, they suffer in terms of diversity and procedural length. Multistep sequences are usually required for assembling the starting material for cyclization. We have recently reported a concise route to indoloazocines by a sequential Ugi/gold-catalyzed intramolecular hydroarylation approach. Inspired by these findings and as a result of our continued synthetic interest in the indole core, multicomponent reactions and transition metal-catalysis, we have developed a post-Ugi gold-catalyzed domino cyclization method to generate spiroindolines. The Ugi four-component reaction (4-CR) of indole-3carboxaldehyde (1a) with p-methoxybenzyl amine (2a), 2-butynoic acid (3a) and tert-butyl isonitrile (4a) in methanol at 50 8C gave Ugi-adduct 5a in 71% yield. When this was treated with 5 mol% of Au[PPh3]OTf (OTf= trifluoromethanesulfonate) in CDCl3 at RT, the expected outcome of the reaction was indoloazepinone 6a’ through an endo-dig cyclization followed by rearrangement (Scheme 1). Surprisingly, an exo-dig cyclization followed by intramolecular trapping of the spiro intermediate occurred instead, resulting in the diastereoselective formation of tetracyclic spiroindoline 6a in 61% yield (Scheme 1). This observation was remarkable, as the attack on the a-position of an alkyne conjugated with an amide is rare, and trapping of the spiro intermediate by a sterically hindered tert-butyl amide is rather unexpected, as was the diastereoselectivity observed. Spiroindolines are prominent molecular motifs that are frequently encountered among the large family of alkaloids; for example, it is present in communesines and perophoramidines (Figure 1), which display distinct pharmacological properties. These fused polycyclic systems, which feature quaternary stereocenters, present a nontrivial challenge for organic chemists to develop synthetic approaches.

Microwave-assisted synthesis of novel bis(2-thioxothiazolidin-4-one) derivatives as potential GSK-3 inhibitors

(5Z,5′Z)-3,3′-(1,4-Phenylenebis(methylene)-bis-(5-arylidene-2-thioxothiazolidin-4-one) derivatives (5a–r) have been synthesized by the condensation reaction of 3,3′-(1,4- or 1,3-phenylenebis(methylene))bis(2-thioxothiazolidin-4-ones) (3a,b) with suitably substituted aldehydes (4a–f) or 2-(1H-indol-3-yl)2-oxoacetaldehydes (8a–c) under microwave conditions. The bis(2-thioxothiazolidin-4-ones) were prepared from the corresponding primary alkyl amines (1a,b) and di-(carboxymethyl)-trithiocarbonyl (2). The 2-(1H-indol-3-yl)-2-oxoacetaldehydes (8a–c) were synthesized from the corresponding acid chlorides (7a–c) using HSnBu3.

In vitro antiproliferative effect of β-phenylethylamine derivatives and doxorubicin combinations on MCF/ADR cell lines

A series of 3,4-dimethoxyphenylethylamine derivatives was prepared from Baylis–Hillman (BH) adducts. The effect of these compounds on the proliferation of breast cancer cell lines (MCF-7) and the corresponding Doxorubicin (Dox) resistant cell lines (MCF-7/ADR) was studied. Aminoalcohols 1a–d were obtained from the Michael addition reaction of 3,4-dimethoxyphenylethylamine and BH adducts. For the preparation of unsaturated amines 2a–d, BH adducts were converted into allylic bromides by treatment with HBr in acidic solution. N-nucleophile introduction could be controlled by the choice of solvent furnishing the corresponding amines 2a–d. A third class of amines (3a–c) was prepared by hydrogenation reaction of amines 2a–d. In respect of the biological evaluation, some of the synthesized compounds exhibited moderate inhibitory effect on the cell growth. In addition, in MCF-7/ADR cell lines, the antiproliferative effect of Dox shifted from 5 to 88 % when co-administrated with compound 2b.

Arylhydrazononitriles as precursors to 2-substituted 1,2,3-triazoles and 4-amino-5-cyano-pyrazole derivatives utilizing microwave and ultrasound irradiation

Cyanoacetamides 3a–d were prepared by reacting ethyl cyanoacetate with primary aliphatic amines 2a–d. The formed cyanoacetamides 3a–d were coupled with aromatic diazonium salts to give the corresponding arylhydrazones 4a–i which were used as precursors to title triazoles and pyrazoles by reacting with hydroxylamine and chloroacetonitrile. Yields of products formed by conventional heating are compared with those of microwave and ultrasound irradiation

Synthesis and characterization of novel substituted N-benzothiazole-2-yl-acetamides

Schiff base derivatives of benzothiazole 2a–e have been synthesized by reacting with substituted 2-aminobenzothiazole 1a–e and different substituted benzaldehydes 5a–e. The obtained Schiff bases reaction with NaBH4 has afforded the corresponding some novel amines 3a–e. The condensation of amines with chloroacetylchloride leads to novel amide derivatives 4a–e. The structures of the synthesized compounds are characterized by elemental analysis, IR, MS, 1H NMR and 13C NMR.

A facile synthesis of novel 3-(aryl/alkyl-2-ylmethyl)-2-thioxothiazolidin-4-ones using microwave heating

(Z)-5-(2-(1H-Indol-3-yl)-2-oxoethylidene)-3-(aryl/alkyl-2-ylmethyl)-2-thioxothiazolidin-4-ones (7a–w) have been synthesized by the Knoevenagel condensation reaction of 3-(aryl/alkyl-2-ylmethyl)-2-thioxothiazolidin-4-ones (3a–d) with suitably substituted 2-(1H-indol-3-yl)2-oxoacetaldehydes (6a–g) under microwave conditions. The thioxothiazolidin-4-ones were prepared from the corresponding aryl/alkyl amines (1a–d) and di-(carboxymethyl)-trithiocarbonyl (2). The aldehydes (6a–g) were synthesized from the corresponding acid chlorides (5a–g) using HsnBu3.

DESIGN, SYNTHESIS AND ANTIDIABETIC ACTIVITY OF SOME NEW 4-AMINO (OR 6-OXO)-2-METHYL/BENZYLTHIO (OR SUBSTITUTED AMINO) PYRIMIDINE DERIVATIVES

A new series of 4-amino-5-cyano-2-methyl/benzylthio (or substituted amino) 6-substituted phenyl pyrimidines 5a-l, and 2-methyl/benzylthio (or substituted amino)-5-cyano-1,6-dihydro-6oxo-4-(substitutedphenyl) pyrimidines 6a-l was prepared. The reaction of S-methyl (or benzyl) isothiourea salts 1a,b with benzylidenemalononitriles 2a-c afforded compounds 5a-f. Reaction of compounds 5a-c (R= methylthio) with the appropriate amines 4a,b (cyclohexylamine or 2phenylethylamine) afforded 4-amino-2-substituted amino-5-cyano-6- (substituted phenyl) pyrimidines 5g-l. On the other hand, reaction of S-methyl (or benzyl) isothiourea salts 1a,b with ethyl α-cyanocinnamates 3a-c afforded compounds 6a-f. Reaction of compounds 6a-c (R= methylthio) with the appropriate amines 4a,b afforded 2-substituted amino-5-cyano-4-oxo-6(substituted phenyl) pyrimidines 6g-l. The purity of the new compounds was checked by TLC and elucidation of their structures was confirmed by IR, 1H-NMR, and mass spectrometry along with elemental microanalyses. All the target compounds were evaluated for their in-vivo antidiabetic effects in rates in comparison with metformin as a reference drug.

Transformations of enaminones. A simple one-pot synthesis of imidazolone derivatives

Ethyl (5-benzoyl-2-oxo-3-substituted-2,3-dihydro-1 H-imidazol-1-yl)carbamates 7 were prepared by the Michael addition of diethyl azodicarboxylate ( 3) to ( E)-3-(dimethylamino)-1-phenylprop-2-en-1-one ( 2) followed by substitution of the dimethylamino group with primary amines 5a– n to afford a mixture of ( E) and ( Z) diethyl 1-(1-(substituted)amino)-3-oxo-3-phenylprop-1-en-2-yl)hydrazine-1,2-dicarboxylates ( 6a– n), followed by cyclization to give final products 7a– n. The intermediate 6i was isolated and characterized and transformed into 7i. All imidazolones 7a– n were synthesized in one pot reaction sequences with individual reactions being very clean.

Atropisomerism at C–N Bonds of Acyclic Amines: Synthesis and Application to Palladium‐Catalyzed Asymmetric Allylic Alkylations

AbstractAcyclic amines 1 were obtained by a nucleophilic aromatic substitution (SNAr) reaction and N‐methylation followed by silane reduction. The optical resolution of C(aryl)–N(amine) bond atropisomers of amines 1 is described. We found that chiral acyclic amine 1a can be resolved by crystallization without any outside chiral source. Finally, we demonstrate the ability of chiral amines 1 as a ligand in a palladium‐catalyzed asymmetric allylic alkylation (up to 93 % ee).

Synthesis, characterization and anticancer activity of new chiral Pd(II)-complexes derived from unsymmetrical α-diimine ligands

A set of new diastereopure unsymmetrical α-diimine ligands 2a– d derived from methylglyoxal and optically pure primary amines 1a– d afforded the new chiral Pd(II)-complexes ( S, S)- 3a, ( S, S)- 3b, ( S, S)- 3c, and (1 S, 2 S, 3 S, 5 R)- 3d. All compounds have been characterized by IR, 1H, and 13C NMR spectroscopies along with MS-FAB + spectrometry. The crystal and molecular structure for the complexes 3a, 3b and 3d have been fully confirmed by single-crystal X-ray studies. Likewise, complexes 3a– d have also been screened for their in vitro cytotoxicity against different classes of cancer: leukemia (K-562 CML), colon cancer (HCT-15), human breast adenocarcinoma (MCF-7), central nervous system (U-251 Glio) and prostate cancer (PC-3) cell lines.

Synthesis, antifungal activity and semi-empirical AM1-MO calculations of some new 4-oxo-4H-chromene derivatives

Some new antifungal agents have been prepared through reaction of 4-oxo-4 H -chromene-3-carbaldehydes ( 1a , b ) with some active primary amines ( 2a - e ) and amides/thioamides ( 6a - d ) in different conditions. Structures of the products were established on the basis of elemental analysis, IR, 1 H NMR, mass spectra and semi-empirical AM1-MO calculations.