2-aminobenzyl Alcohol Research Articles

Rhodium-Catalyzed One-pot Chemoselective Insertion-Rearrangement-Cyclization of Azavinyl Carbenes with 2-Aminobenzyl Alcohols.

Chemoselective insertion of in situ generated α-imino rhodium carbene onto the O-H bond of 2-aminobenzyl alcohols over the N-H bond followed by [1,3]-alky shift has been successfully accomplished for the synthesis of amine tethered ketone derivatives. The resultant product was further cyclized under acidic conditions to afford biologically important 3-aminoquinolines. Successful integration of chemoselective insertion-cum-rearrangement and cyclization in one pot offered access to various 3-aminoquinolines in a good yield. Conversion of 3-aminoquinolines into biological important motifs has also been demonstrated.

Syntheses of Novel Spirobenzazepinoindole Derivatives via Lewis-Acid Catalyzed Pictet-Spengler Cyclization.

The syntheses of novel spirobenzazepinoindole derivatives has been achieved through a highly efficient and synthetic route. The approach involves a two-step reaction, utilizing indole derivatives, 2-amino benzyl alcohol, and ninhydrin as key starting materials under mild reaction conditions. The reaction proceeds via a sequential cascade process involving cyclization, condensation and spiro-annulation, leading to the formation of the spirobenzazepinoindole core structure in good to excellent yields. The method offers broad substrate scope, high atom economy, and operational simplicity. The synthesized spirobenzazepinoindoles were fully characterized by spectroscopic techniques, including NMR (1H & 13C), IR and mass spectrometry. The methodology provides a valuable tool for the rapid generation of structurally complex spirobenzazepinoindoles, which could serve as scaffolds for the development of new therapeutic agents.

Synthesis of Quinolines Catalyzed by Bidentate Terpyridine Mn(I) Complex

ABSTRACTA method for efficient synthesis of quinolines via acceptorless dehydrogenative condensation is presented. A series of quinolines are obtained by the coupling reaction of 2‐aminobenzyl alcohols with secondary alcohols in the presence of bidentate terpyridine Mn(I) complex in good to excellent yields. Pleasantly, various substituted secondary alcohols and substituted aminobenzyl alcohols all provide quinolines with good functional group tolerance. Importantly, this investigation also provides a green and environmentally friendly protocol for constructing heterocyclic compounds.

I2 and aqueous TBHP induced aerial oxidative coupling of 2-aminobenzyl alcohols and nitriles: A novel metal-free route towards quinazolines synthesis

A series of 2-phenylquinazolines were synthesized by using I2/tert-butyl hydroperoxide via oxidative coupling of 2-aminobenzyl alcohols and nitriles. Metal free approach, shorter reaction time, high atom efficiency and scale up synthesis are the salient features of the protocol. Experimental evidence followed by DFT calculations indicate that the reaction pathway of quinazoline formation proceed through radical intermediate.

Synthesis of 2-substituted quinoline derivatives using [RuCl2(p-cymene)]2-ferrocene thioamide catalytic system via acceptorless dehydrogenative coupling

The substituted quinolines were synthesized via acceptorless dehydrogenative coupling (ADC) of 2-aminobenzyl alcohol with ketones/secondary alcohols, which was accomplished using the in situ catalytic activity of [RuCl2(p-cymene)]2 and ferrocene thioamide (Fc-TA) ligands. The catalysis was extended to aromatic and heterocyclic ketones and secondary alcohols, with unsubstituted and chloro‑substituted 2-aminobenzyl alcohols. The Fc-TA ligands (L1-L3) were synthesized, and characterized using spectroscopic techniques such as FT-IR, UV–Vis, NMR and HRMS. The influence of ligands on the catalysis was studied. Overall, the synthesis of quinolines was accomplished with good to moderate yields, via both mono and double dehydrogenation reactions along with hydrogen and water as only by-products.

Schiff-base Polymer Immobilized Ruthenium for Efficient Catalytic Cross-coupling of Secondary Alcohols with 2-amino- and γ-aminobenzyl Alcohols to Give Quinolines and Pyridines.

A Schiff-base porous polymer has been impregnated with ruthenium trichloride for acceptor-free dehydrogenation coupling (ADC) of secondary alcohols with γ-amino- and 2-aminobenzyl alcohols to give pyridines and quinolines. This heterogenous catalyst exhibited high catalytic efficiency over repeated cycles with wide functional group tolerance.

Lewis acid-mediated modular route to the synthesis of 3-substituted quinolines from 2-aminobenzyl alcohols and enamine(one)s

A Lewis acid-mediated modular synthesis of 3-substituted quinolines bearing electron-withdrawing groups from readily available 2-aminobenzyl alcohols and N,N′-dimethylenamine(one)s is described.

Potent pincer-zinc catalyzed homogeneous α-alkylation and Friedländer quinoline synthesis reaction of secondary alcohols/ketones with primary alcohols.

Herein, we describe an air- and moisture-stable, homogeneous zinc catalyst stabilised using an electron deficient N^N^N pincer-type ligand. This ternary, penta-coordinated neutral molecular catalyst [Zn(N^N^N)Cl2] selectively produces α-alkylated ketone derivatives (14 examples) through a one-pot acceptorless dehydrogenative coupling (ADC) reaction between secondary and primary alcohols using the borrowing hydrogen (BH) approach in good to excellent isolated yields (up to 93%). It is worth noting that this catalyst also provides an eco-friendly route for the synthesis of quinoline derivatives (30 examples) using 2-aminobenzyl alcohols as alkylating agents via successive dehydrogenative coupling and N-annulation reactions. This cost effective, easy to synthesize and environmentally benign catalyst shows excellent stability in catalytic cycles under open-air conditions, as evident from its high turnover number (∼104), and is activated by using a catalytic amount of base under milder conditions.

Molecular oxygen-promoted sustainable synthesis of functionalized quinolines using catalytic glucose-derived ionic liquids and copper.

An expedient one-pot sustainable synthesis of quinoline analogues was developed via protection-free chemo-selective oxidation of 2-aminobenzyl alcohols to form aldehydes, followed by annulation with various 1,3-dicarbonyl compounds or nitriles under mild reaction conditions in an acetonitrile-water medium using a copper catalyst and new hydrogen bond-rich glucose-based ionic liquids (GSILs). Overall, 40 functionalized quinolines were synthesized with up to 93% yields following significant green chemistry parameters. The developed GSILs were recyclable with not much decrease in the yields of the products and the reaction rate.

Reaction of 2-Aminobenzyl Alcohols with β-Dicarbonyl Compounds to Synthesize Quinoline Derivatives in Water Promoted by Active Manganese Dioxide

Reaction of 2-Aminobenzyl Alcohols with <i>β</i>-Dicarbonyl Compounds to Synthesize Quinoline Derivatives in Water Promoted by Active Manganese Dioxide

Catalytic utility of PNN-based MnI pincer complexes in the synthesis of quinolines and transfer hydrogenation of carbonyl derivatives.

This manuscript describes the synthesis of a triazolyl-pyridine-based phosphine, N-((diphenylphosphaneyl)methyl)-N-methyl-6-(1-phenyl-1H-1,2,3-triazol-4-yl)pyridin-2-amine, [2,6-{(PPh2)CH2N(Me)(C5H3N)(C2HN3C6H5)}] (1) (here onwards referred to as PNN) and its cationic and neutral MnI complexes and catalytic applications. The reaction of 1 with Mn(CO)5Br afforded a cationic complex [Mn(CO)3(PNN)]Br (2), which is highly stable in solid state, but in solution it gradually loses one of the CO groups to form a neutral complex [Mn(CO)2(PNN)Br] (3). Complex 2 on treatment with AgBF4 also yielded a cationic complex [Mn(CO)3(PNN)]BF4 (4). These complexes efficiently promoted the synthesis of quinoline derivatives via acceptor-less dehydrogenative coupling of 2-aminobenzyl alcohol and ketones, with complex 3 showing the highest activity with a very low catalyst loading (0.03 mol%) at 110 °C. Complex 3 (0.5 mol%) also showed excellent catalytic activity in the transfer hydrogenation of ketones and aldehydes to form respective secondary and primary alcohols.

New synthetic method for ring-fused quinazoline by palladium-catalyzed oxidative cyclization of 2-aminobenzyl alcohol: Chiral separation and structural analysis

We demonstrate the borrowing hydrogen reaction of readily available 2-aminobenzyl alcohol 1, which is a new synthetic strategy for the construction of ring-fused quinazoline systems. The cascade reaction involves the dehydrogenative oxidation of alcohol 1 to the corresponding aldehyde 3 followed by self-condensation and reduction utilizing the benzyl Pd(II) system. The racemate 2 was successfully separated by chiral HPLC, affording a pair of enantiomers with high purity (>99 % ee) in a 1:1 ratio. The absolute configuration of one enantiomer was established via X-ray crystallography of its heavy atom analog. The structures of the racemate 2 and the pure enantiomer 2a were characterized by single-crystal X-ray analysis.

Mucosal damage and γ-H2AX formation in the rat urinary bladder induced by aromatic amines with structures similar to o-toluidine and o-anisidine.

Although aromatic amines are widely used as raw materials for dyes, some, such as o-toluidine and o-anisidine, have shown concerning results regarding carcinogenicity in the urinary bladder. We have recently developed a short-term detection method for bladder carcinogens using immunohistochemistry for γ-H2AX, a DNA damage marker. Here, using this method, we evaluated aromatic amines with structures similar to o-toluidine and o-anisidine for bladder mucosal damage and potential carcinogenicity. In total, 17 aromatic amines were orally administered to male F344 rats for 28days, and histopathological examination and γ-H2AX immunostaining of the urinary bladder were performed. Histopathological analysis revealed that seven aromatic amines, including 4-chloro-o-toluidine (4-CT), o-aminoazotoluene, 2-aminobenzyl alcohol (ABA), o-acetotoluidine (o-AT), 3,3'-dimethoxybenzidine, 4-aminoazobenzene (AAB), and 4,4'-methylenedianiline (MDA), induced various bladder lesions, such as hemorrhage, necrosis, and urothelial hyperplasia. The morphological characteristics of mucosal damage induced by these substances were divided into two major types: those resembling o-toluidine and those resembling o-anisidine. Six of these aromatic amines, excluding MDA, also caused significant increases in γ-H2AX formation in the bladder urothelium. Interestingly, 4-CT did not cause mucosal damage or γ-H2AX formation at the lower dose applied in previous carcinogenicity studies. These results showed for the first time that o-AT and ABA, metabolites of o-toluidine, as well as AAB caused damage to the bladder mucosa and suggested that they may be bladder carcinogens. In addition, 4-CT, which was thought to be a noncarcinogen, was found to exhibit bladder toxicity upon exposure to high doses, indicating that this compound may contribute to bladder carcinogenesis.

Diversity-Oriented Synthesis of Benzo[f][1,4]oxazepine-, 2H-Chromene-, and 1,2-Dihydroquinoline-Fused Polycyclic Nitrogen Heterocycles under Microwave-Assisted Conditions.

An efficient, diversity-oriented synthesis of oxazepino[5,4-b]quinazolin-9-ones, 6H-chromeno[4,3-b]quinolines, and dibenzo[b,h][1,6]naphthyridines was established involving a substrate-based approach under microwave-assisted and conventional heating conditions in high yields (up to 88%). The CuBr2-catalyzed, chemoselective cascade annulation of O-propargylated 2-hydroxybenzaldehydes and 2-aminobenzamides delivered oxazepino[5,4-b]quinazolin-9-ones involving a 6-exo-trig cyclization-air oxidation-1,3-proton shift-7-exo-dig cyclization sequence. This one-pot process showed excellent atom economy (-H2O) and constructed two new heterocyclic rings (six- and seven-membered) and three new C-N bonds in a single synthetic operation. On the other side of diversification, the reaction between O/N-propargylated 2-hydroxy/aminobenzaldehydes and 2-aminobenzyl alcohols delivered 6H-chromeno[4,3-b]quinolines and dibenzo[b,h][1,6]naphthyridines involving sequential imine formation-[4 + 2] hetero-Diels-Alder reaction-aromatization steps. The influence of microwave assistance was superior to conventional heating, where the reactions were clean, rapid, and completed in 15 min, and the conventional heating required a longer reaction time at a relatively elevated temperature.

Borrowing hydrogen and dehydrogenative/oxidative cyclization reactions catalyzed by a CCC-NHC pincer Re complex: An air stable catalyst for the synthesis of α-alkylated ketones and quinolines

Successful catalytic activity of the CCC-NHC pincer Re(I) complex was achieved for the borrowing hydrogen coupling reaction between primary and secondary benzylic alcohols. An expansive scope of 17 aromatic and 2 aliphatic substrates were investigated and isolated yields from 40% to 91% were collected. The aliphatic substrates yielded complex aldol self-condensation by-products. The catalytic activity of the CCC-NHC pincer Re(I) complex was also evaluated for the formation of quinolines via the dehydrogenative/oxidative cyclization of 2-aminobenzyl alcohols with benzylic ketones or secondary benzylic alcohols. Isolated yields from 68% to 87% were obtained for 12 examples. All products and by-products were fully characterized by 1H &13C NMR and mass spectroscopies. Control studies such as dehydrogenative and hydrogen transfer reaction were carried out, and the results from these experiments supported a proposed mechanism of a borrowing hydrogen coupling reaction catalyzed by the CCC-NHC pincer Re(I) complex.

Transition metal-free synthesis of 2-aryl quinazolines via alcohol dehydrogenation

We report here a transition metal-free synthesis of quinazoline derivatives starting from 2-aminobenzyl alcohols and aryl amides via an alcohol dehydrogenation strategy promoted by potassium tertiary butoxide. The control experiments are carried out to identify the reaction intermediates and the role of the K+ ion in the reaction. The DFT calculations unveil the reaction mechanism, with special focus on the rate determining state. The present method tolerates a variety of functional groups providing easy access to diversely substituted quinazolines.

Synthesis of 3-Oxo Quinolines by Cyclization Using Lignin Models and 2-Aminobenzyl Alcohols.

Phenoxy acetophenones were usually employed as β-O-4' lignin models for chemical conversion. Herein, an iridium-catalyzed dehydrogenative annulation between 2-aminobenzylalcohols and phenoxy acetophenones was demonstrated to prepare valuable 3-oxo quinoline derivatives, which are hard to prepare using previous methods. This operationally simple reaction tolerated a wide scope of substrates and enabled successful gram-scale preparation.

Ru(II)‐p‐cymene complexes containing hydrazone ligands catalyzed α‐alkylation of ketones and one‐pot synthesis of bioactive quinolines and 3‐(quinolin-2-yl)‐2H‐chromen‐2‐one

Ru(II)-arene complexes (1-4) containing salicylaldehyde based hydrazone ligands (L1-L4) have been synthesized and characterized. Molecular structure of complex 1 has been solved by single crystal X-ray crystallography. The ligands coordinated to Ru center through O and N atoms. Catalytic activity of all the complexes was tested in the α-alkylation of acetophenone with benzyl alcohol. Complex 1 showed better activity with the conversion of 97% under the optimized conditions. Then, using complex 1, scope of the reaction was extended to different aromatic ketones and primary alcohols. One pot synthesis of several bioactive quinolines was achieved using aromatic ketones and amino alcohols as coupling partners in the presence of complex 1 as a catalyst. Further, complex 1 catalyzed the one pot synthesis of 3-(quinolin-2-yl)-2H-chromen-2-one from 2-aminobenzyl alcohol and 3-acetyl coumarin, which led to a new synthetic approach for making this compound.

Understanding the Visible-Light-Initiated Manganese-Catalyzed Synthesis of Quinolines and Naphthyridines under Ambient and Aerobic Conditions

Polyaromatic N-heterocycles are some of the most common building blocks in natural products and active pharmaceutical ingredients. Significant efforts have been devoted to developing catalytic protocols, including those which use an acceptorless dehydrogenation strategy at elevated temperatures, to produce polyaromatic N-heterocycles like quinolines and naphthyridines. However, photoinitiated catalysis driven by visible light offers a milder and often more selective protocol as an alternative to thermal reactions. Here, we present the catalytic syntheses of quinolines and naphthyridines from ortho-aminobenzyl alcohols and ketones using the photocatalyst [Mn(L1H)(CO)3Br] (L1H = 7-hydroxy-2-methyl-1,8-naphthyridine-N-oxide), bearing a phenolic unit on a 1,8-naphthyridine-N-oxide scaffold, under ambient and aerobic conditions with visible light illumination. We describe a broad, functional group-tolerant substrate scope of >30 examples under modest reaction conditions. A variety of 2-aminobenzyl alcohols containing electron-donating and electron-deficient groups and (2-aminopyridin-3-yl)methanol are converted to the corresponding quinolines and naphthyridines using ambient air as an oxidant in the presence of KOH. We synthesized a wide range of derivatives, including some of the bioactive antimalarial drug chloroquine and the steroids progesterone and pregnenolone to highlight the value-added applications of this catalytic protocol for pharmaceutical ingredient and natural product syntheses. We performed substrate viability, ultraviolet–visible, electron paramagnetic resonance, and X-ray photoelectron spectroscopy studies, as well as density functional theory calculations to gain mechanistic insights to the reaction pathway. The catalytic cycle involves condensation of the amino group in the ortho-aminobenzyl alcohol with the ketone initially, which is followed by aerobic oxidation of the benzyl alcohol to the corresponding benzaldehyde catalyzed by the photoinitiator [Mn(L1H)(CO)3Br] in the presence of visible light, and finally, a KOH-promoted condensation and cyclization to afford quinolines as the final products.

Cyclometalated iridium complexes-catalyzed acceptorless dehydrogenative coupling reaction: construction of quinoline derivatives and evaluation of their antimicrobial activities.

The acceptorless dehydrogenative coupling (ADC) reaction is an efficient method for synthesizing quinoline and its derivatives. In this paper, various substituted quinolines were synthesized from 2-aminobenzyl alcohols and aryl/heteroaryl/alkyl secondary alcohols in one pot via a cyclometalated iridium-catalyzed ADC reaction. This method has some advantages, such as easy availability of raw materials, mild reaction conditions, wide range of substrates, and environmental friendliness which conforms to the principles of green chemistry. Furthermore, a gram-scale experiment with low catalyst loading offers the potential to access the aryl/heteroaryl quinolones in suitable amounts. In addition, the antibacterial and antifungal activities of the synthesized quinolines were evaluated in vitro, and the experimental results showed that the antibacterial activities of compounds 3ab, 3ad, and 3ah against Gram-positive bacteria and compound 3ck against C. albicans were better than the reference drug norfloxacin.