Azido Alcohols Research Articles

Oxone-Mediated Regioselective Oxy-iodination of 1-Aryl/Alkyl Butadienes Using TBAI.

A simple, mild, and environmentally benign regioselective oxy-iodination of 1-aryl/alkyl butadienes has been developed. While styrenes have been explored previously, this work on dienes has been highly regioselective and metal-free in oxy-iodination following Markovnikov's rule. The oxy-iodination products were obtained in good to excellent yields using various co-solvents (H2O, MeOH, EtOH, AcOH, etc.). In addition, the halohydrins have been useful building blocks in the synthesis of various functionalized keto iodides and azido alcohols.

Resolution of trans-2-azidocycloalkanols by separation of their mandelic acid esters

It is presented that resolution of (±)-trans-2-azidocylohexanol and (±)-trans-2-azidocyclooctanol can be effected with (R)-mandelic acid. (R)-Mandelate esters of these azido alcohols can be separated by column chromatography on silica gel in an efficient manner. Upon methanolysis (transesterification) of the diastereomerically pure (R)-mandelate esters by K2CO3, enantiomerically pure trans-2-azidocylohexanols and trans-2-azidocyclooctanols are obtained. Their synthetic relevance has been also demonstrated by subjecting them to some enantiospecific transformations, such as the Mitsunobu reaction and hydrogenolysis of the azide functionality. Notably, this is the first study reporting the preparation of enantiopure trans-2-azidocyclooctanols.

Experimental and theoretical investigations of two quinolin-8-ol derivatives as inhibitors for carbon steel in 1 M HCl solution

Two quinolin-8-ol derivatives, 5-(((1-azido-3-chloropropan-2-yl)oxy)methyl)quinolin-8-ol (ACQ) and 5-(((1,3-diazidopropan-2-yl)oxy)methyl)-quinolin-8-ol (DAQ), were prepared via the O-alkylation of 5-chloromethylquinolin-8-ol salts by azido alcohols under simple and mild conditions with good yields. The structures of ACQ and DAQ were characterized by spectroscopic methods: Fourier transform infrared, elemental analysis, and nuclear magnetic resonance. The ACQ and DAQ were screened as organic inhibitors of carbon steel (CS) corrosion in 1 M HCl using experimental and simulation methods. The experimental findings revealed that ACQ and DAQ greatly improved the corrosion resistance of CS, and DAQ performed better than ACQ. Tafel polarization results showed that quinolin-8-ol derivatives were mixed-type inhibitors with different corrosion rates. The impedance trials data showed that the inhibition performance of ACQ and DAQ reached 93.8% and 96.7% at 10−3 M, respectively. The adsorption process of quinolin-8-ol derivatives followed a Langmuir adsorption isotherm and the estimated thermodynamic values suggested physisorption for both ACQ and DAQ. The morphology of the CS surface was analyzed utilizing scanning electron microscopy. The UV–visible spectra showed a strong interaction between ACQ and DAQ with Fe ions between specific atoms. Computational correlations (density functional theory and molecular dynamic simulations) supported the experimental observations.

Total stereocontrolled synthesis of a novel pyrrolizidine iminosugar

Herein we describe a versatile approach to the pyrrolizidine alkaloids skeleton by tailoring our original strategy already used for the pyrrolidine iminosugars synthesis. The key steps are the regio- and stereoselective azidolysis of the suitable chiral vinyl epoxide and then asymmetric dihydroxylation of the corresponding azido alcohol by using (DHQ)2AQN as the ligand. Further optimized elaborations addressed to the closure of the two rings allowed us to achieve the target iminosugar with complete stereocontrol. The wide range of pyrrolizidine iminosugars’ biological properties make them a key focus of new drug research and therefore the development of synthetic strategies for obtaining them is of decisive importance.

Novel preparation of substituted oxazolines condensed to d-ring of estrane skeleton and characterization of their antiproliferative properties

A simple and efficient synthesis of novel estrone 16α,17α-oxazoline derivatives substituted at the D ring (compounds 6a-g) is described. The reduction of 16α-azido-3-methoxyestra-1,3,5-trien-17-one (1) in methanol in the presence of CeCl3 under the condition of the Luche reaction produced two epimeric azido alcohol (16α-azido-17α-hydroxy and 16α-azido-17β-hydroxy) derivatives of estra-1,3,5(10)-triene-3-methyl ether (compounds 2 and 3) in a yield of 90% and 7.6%. The reaction of the sterically unhindered 16α-azido-17α-hydroxy-estra-1,3,5(10)-triene-3-methyl ether (2) with a range of benzaldehydes under the condition of the Schmidt rearrangement yielded d-ring substituted estrone 16α,17α-oxazoline derivatives 6a-g. The in vitro antiproliferative activities of compounds 1, 2, 3, 6a-g were also determined by means of MTT assays on a panel of human cancer cell lines HeLa, SiHa, C-33 A, A2780, MCF-7, MDA-MB-231 and T47D.

Asymmetric azidohydroxylation of styrene derivatives mediated by a biomimetic styrene monooxygenase enzymatic cascade.

Enantioenriched azido alcohols are precursors for valuable chiral aziridines and 1,2-amino alcohols, however their chiral substituted analogues are difficult to access. We established a cascade for the asymmetric azidohydroxylation of styrene derivatives leading to chiral substituted 1,2-azido alcohols via enzymatic asymmetric epoxidation, followed by regioselective azidolysis, affording the azido alcohols with up to two contiguous stereogenic centers. A newly isolated two-component flavoprotein styrene monooxygenase StyA proved to be highly selective for epoxidation with a nicotinamide coenzyme biomimetic as a practical reductant. Coupled with azide as a nucleophile for regioselective ring opening, this chemo-enzymatic cascade produced highly enantioenriched aromatic α-azido alcohols with up to >99% conversion. A bi-enzymatic counterpart with halohydrin dehalogenase-catalyzed azidolysis afforded the alternative β-azido alcohol isomers with up to 94% diastereomeric excess. We anticipate our biocatalytic cascade to be a starting point for more practical production of these chiral compounds with two-component flavoprotein monooxygenases.

Palladium(II), silver(I), and gold(I) complexes of a new class of chiral bicyclic [1,2,3]-triazolooxazine derived N-heterocyclic carbenes (NHCs): Synthesis, structure and application studies

A new class of chiral bicyclic [1,2,3]-triazolooxazine derived N-heterocyclic carbene (NHC) ligands was synthesised in its enantiopure form from commercially available, cheap amino acid without undertaking any chiral resolution. In particular, the bicyclic N-heterocyclic carbene precursor, (S)-7-benzyl-6,6-(R1)2–2-R2-[1,2,3]-triazolooxazinium iodide [R1 = R2 = Me (1a); R1 = H, R2 = Me (2a); R1 = H, R2 = Et (3a)] salts were conveniently prepared by the N-alkylation reactions of the corresponding [1,2,3]- triazolooxazine derivatives with alkyl iodides in ca. 37–73% yields. The copper mediated [3 + 2] cycloaddition reaction of the PhCH2CH(N3)CR2OH (R = H, Me) azido alcohol compounds and propargyl bromide gave the desired [1,2,3]-triazolooxazines. These chiral bicyclic [1,2,3]- triazolooxazine derived N-heterocyclic carbene ligands were characterised in the form of its silver (NHC)AgCl (1–3)b, gold (NHC)AuCl (1–3)c, and the palladium (NHC)2PdCl2 (1–3)d and the PEPPSI type (NHC)PdI2(NC5H5) (1–3)e complexes (NHC = (S)-7-benzyl-6,6-(R1)2–2-R2-[1,2,3]-triazolooxazin-3-ylidene; R1 = H, Me and R2 = Me, Et; PEPPSI = Pyridine Enhanced Precatalyst Preparation Stabilisation and Initiation).

Photocatalytic Conversion of Benzyl Alcohols/Methyl Arenes to Aryl Nitriles via H-Abstraction by Azide Radical.

This report presents the visible-light-assisted synthesis of aryl nitriles from easily accessible alcohols or methyl arenes in the presence of O2 . Organic photoredox catalyst, 4CzIPN (1,2,3,5-tetrakis(carbazol-9-yl)-4,6-dicyanobenzene), induces single electron transfer (SET) from azide N3 - and generates azide radical N3 ⋅.The photogenerated N3 ⋅ abstracts H atom from α-C-H bond of benzylic system, which provides aldehyde and hydrazoic acid (HN3 ) in situ. This reaction subsequently forms azido alcohol intermediate that transforms into nitrile with the assistance of triflic acid (Brønsted acid). A range of alcohols and methyl arenes successfully underwent cyanation at room temperature with good to excellent yields and showed good functional group tolerance.

Stereocontrolled total synthesis of iminosugar 1,4-dideoxy-1,4-imino-D-iditol

The first stereocontrolled total synthesis of iminosugar 1,4-dideoxy-1,4-imino-D-iditol is described. The key step in our approach was the double diastereoselection in the asymmetric dihydroxylation (AD) of suitable optically active olefin, the chiral vinyl azido alcohol 9. Performing the AD using the most common Cinchona alkaloids as ligands enabled us to identify the ligand of choice for the stereodivergent synthesis of 1,4-dideoxy-1,4-imino-D-iditol and 1,4-dideoxy-1,4-imino-D-galactitol. These type of iminosugars, both natural and unnatural, are intensively studied for their promising chemotherapeutic properties against viral infections, diabetes, cancer, and tuberculosis.

Mn-catalyzed radical initiated domino transformation of alkynylated cyclohexadienones with TMSN3 and O2 to bicyclic azido alcohols.

An efficient Mn-catalyzed cascade azide radical addition/cyclization/oxygen insertion reaction of alkyne-tethered cyclohexadienones with TMSN3 under mild conditions is reported. This domino reaction presents good diastereoselectivity generating bicyclic azido alcohol scaffolds which can be transformed into useful building blocks in organic synthesis for medicinal chemistry.

Uniform copper nanoparticles as an inexpensive and efficient catalyst for synthesis of novel β-carbonyl-1, 2, 3-triazoles in water medium

Copper nanoparticles as an efficient, inexpensive catalyst were prepared via ball milling for synthesis of β-carbonyl 1, 2, 3-triazoles from azido alcohol by click reaction in water. An extensive range of raw materials such as sodium azide, phenacyl bromide, epichlorohydrin, and terminal alkynes were used. Complete reduction of CuO in presence of NaBH4 was done via ball milling with a ball-to-powder weight ratio of 50:1 under air atmosphere at room temperature. The final copper nanoparticles (Cu NPs) were characterized by SEM, EDX, XRD and FT-IR. The Cu NPs catalyzed one-pot three component synthesis of β-carbonyl 1, 2, 3-triazoles at room temperature with short reaction time and high product yields. The catalyst could be easily recovered and reused in several successive runs.

An investigation of the reactions between azido alcohols and phosphoramidites.

The reactions of several β-, γ-, and δ-azido alcohols with dibenzyl and dimethyl N,N-diisopropylphosphoramidites were examined. Detailed analysis of the intermediates and products formed from the reactions under different conditions provided useful information to gain insights into their mechanisms involving intramolecular Staudinger reaction, as well as the structure-reactivity relationships of both substrates. The reactions of γ- and δ-azido alcohols with dibenzyl N,N-diisopropylphosphoramidite could produce 6- and 7-membered cyclic phosphoramidates, thereby providing a new synthetic method for these biologically important molecules.

Copper(II) Schiff Base Complexes with Catalyst Property: Experimental, Theoretical, Thermodynamic and Biological Studies.

Two novel copper(II) Schiff base complexes were synthesized and characterized by various physico-chemical and spectroscopic methods, revealing a distorted square planar geometry around the copper atom. The analytical data confirmed the 1:1 metal to ligand stoichiometry of the complexes. B3LYP/(LANL2DZ/6-311G**) density functional theory (DFT) were used to investigate structural and electronic properties of the synthesized compounds in gas phase. The computational results support the conclusion obtained by the experimental studies. Thermodynamic study of complex formation in solution was carried out spectrophotometrically at 25 °C. These compounds were also subjected to study in vitro antibacterial screening against some bacteria. Also, click reaction was investigated for its catalytic properties. The synthesized Schiff base copper complexes catalyzed 1,3-dipolar Huisgen cycloaddition of different functionalized ?-azido alcohols and alkynes in the presence of ascorbic acid in a solution of THF/H2O (2:1, V/V) at room temperature.

One-pot synthesis of oxazolidine-2-thione and thiozolidine-2-thione from sugar azido-alcohols

A controlled and facile synthesis of various glycosyl 1,3-oxazolidine-2-thiones and 1,3- thiozolidine-2-thiones has been accomplished from corresponding sugar azido alcohols utilizing Staudinger reaction (PPh3 and CS2) via isothiocynate route. A series of reactions were performed to investigate the effects of CS2 and PPh3 on the selectivity of product formed. The excessive addition of CS2 with PPh3(1.2 equiv) afforded oxazolidine-2-thione alone, while the solitary addition of PPh3 for 30 min followed by addition of CS2 to the reaction mixture resulted both the products in different ratios, which were successfully isolated using column chromatography (SiO2). Furthermore, synthesis of 1,3-oxathiolan-2-imine from glycosyl epoxide has also been attempted. Structures of all the developed compounds have been elucidated using extensive spectroscopic techniques including IR, NMR and MS analysis.

Advances towards the synthesis and characterization of five-membered cyclic alcohols and ketones

This study reports the synthesis of a group of differently substituted cyclopentane derivatives, which are of interest as intermediates in the preparation of compounds with potential pharmacological activities, such as the carbocyclic analogues of nucleosides. The azide group in the azido alcohol derivatives of type 4 was easily reduced by way of a Staudinger reaction and protected in situ as the Boc-amino derivatives 5. Subsequent oxidation with CrO3 gave the corresponding ketones 6. Similarly, conversion of 4b into the phthalimide derivative with the hydroxyl group protected as acetate allowed us to obtain the oxo derivative 11. All the new prepared compounds were fully characterised by NMR spectroscopy and mass spectrometry.

A Green approach towards the synthesis of chiral alcohols using functionalized alginate immobilized Saccharomyces cerevisiae cells

The stereochemistry of the drug molecule is gaining greater therapeutic importance and thus much attention was drawn in synthesis of chiral compounds by the pharmaceutical industry. In this study Saccharomyces cerevisiae cells immobilized on functionalized alginate beads, catalyze the bio-reduction of prochiral ketones 1a–12a to their corresponding chiral alcohols 1b–12b in higher yields of 60–99% and.excellent optical purity 75–97%. The synthesized chiral azido alcohols 10b-12b were further subjected to hydrogenation using Palladium(Pd) nanoparticles (≤5nm), to obtain chiral amino alcohols 10c–12c of therapeutic importance. Thus, a simple, green and inexpensive continuous chemo-enzymatic process has been developed in the synthesis of chiral alcohols/amino alcohols to enhance the scope of the methodology towards industrial application.

Asymmetric routes toward polyhydroxylated pyrrolidines: Synthesis of 1,4-dideoxy-1,4-imino-d-galactitol and 1,4-dideoxy-1,4-imino-d-glucitol

Herein the total synthesis of the pyrrolidine alkaloids 1,4-dideoxy-1,4-imino-d-galactitol and its diastereoisomer 1,4-dideoxy-1,4-imino-d-glucitol is described, starting from a common optically active precursor. The key step in our approach was the double diastereoselection in the asymmetric dihydroxylation of chiral vinyl azido alcohols, obtained by means of two different regio- and stereoselective nucleophilic openings of the corresponding chiral vinyl epoxide.

Influence of molecular organization of an azido alcohol solution on the urethane formation kinetics

The quantitative data on the influence of molecular organization of CH2Cl2 solutions of diazidopropanol and its non-azide analog (isopropanol) and the concentrations of the alcohols and catalyst (dibutyltin dilaurinate) on the kinetics of urethane formation via the reaction with 1,6-hexamethylene diisocyanate were obtained. The series of reactivity were composed for various associates of hydroxyl groups of these alcohols in solutions in the catalytic and non-catalytic reactions.

Design, synthesis and biological evaluation of novel 1,2,3-triazolyl β-hydroxy alkyl/carbazole hybrid molecules.

The design, synthesis and biological study of several novel 1,2,3-triazolyl [Formula: see text]-hydroxy alkyl/carbazole hybrid molecules as a new type of antifungal agent has been described. In this synthesis, the N-alkylation reaction of carbazol-9-ide potassium salt with 3-bromoprop-1-yne afforded 9-(prop-2-ynyl)-9H-carbazole. The 'Click' Huisgen cycloaddition reaction of 9-(prop-2-ynyl)-9H-carbazole with diverse [Formula: see text]-azido alcohols in the presence of copper-doped silica cuprous sulphate led to target molecules in excellent yields. The in vitro antifungal and antibacterial activities of title compounds were screened against various pathogenic fungal strains, Gram-positive and/or Gram-negative bacteria. In particular, 1-(4-((9H-carbazol-9-yl) methyl)-1H-1,2,3-triazol-1-yl)-3-butoxypropan-2-ol (10e) proved to have potent antifungal activity against all fungal tests compared with fluconazole and clotrimazole as studied reference drugs. Our molecular docking analysis revealed an appropriate fitting and a potential powerful interaction between compound 10e and an active site of the Mycobacterium P450DM enzyme. The strong hydrogen bondings between [Formula: see text]-hydroxyl and ether groups in 10e were found to be the main factors that drive the molecule to fit in the active site of enzyme. The in silico pharmacokinetic studies were used for a better description of 10a-10n as potential lead antifungal agents for future investigations.

1-(1-Alkylsulfonic)-3-methylimidazolium chloride as a reusable Brønsted acid catalyst for the regioselective azidolysis of epoxides under solvent-free conditions

Abstract In this study, 1-(1-alkylsulfonic)-3-methylimidazolium chloride as a new, green, and reusable Bronsted acid catalyst was prepared. In this protocol, we used for the regioselective ring-opening reactions of various epoxiodes with sodium azide to afford the corresponding β -azido alcohols in excellent yields and short reaction time under mild and neutral reaction conditions. This method offers several advantages including excellent regioselectivity, clean reactions, simple work-up procedure, a recyclable catalyst, and use of an eco-friendly catalyst.