Β-azido Alcohols Research Articles

Synthesis, cytotoxic evaluation, molecular docking studies and molecular dynamic simulation of some metronidazole analogues

In the current study, a set of 1,2,3-triazolyl-based metronidazole hybrids (7a-m) was synthesized from the reaction of 2-methyl-5-nitro-1-(prop‑2-yn-1-yl)-1H-imidazole with β-azido alcohols in the presence of [CuL] as catalyst. The chemical structures of the synthesized compounds were characterized using different spectroscopic techniques (IR, 1H NMR, 13C NMR, Mass) and elemental analysis. Then, the in vitro cytotoxic activity of the synthesized compounds 7a-m were investigated against human melanoma cell line A375, using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The cytotoxic results showed that these compounds have moderate anticancer activity compared to methotrexate as a reference drug. Among all the synthesized compounds, compound 7l was found to be the most potent derivative with IC50 value of 62.5 µM. Finally, the molecular docking studies and molecular dynamic simulation were carried out to obtain the binding mode of these derivatives in the binding site of receptor. The results of docking studies were in good agreement with the in vitro cytotoxic results.

Catalytic Lewis and Brønsted acid syn-diastereoselective benzylic substitutions of α-hydroxy-β-nitro- and α-hydroxy-β-azido-alkyl arenes

A series of alkyl and alkenyl p-methoxy arenes containing α,β-disubstituted diamino and amino alcohol groups were synthesized from β-nitro and β-azido benzylic alcohols in the presence of AuCl3 as catalyst. The formation of predominantly syn-disubstituted products were rationalized on the basis of mechanistic considerations and transition state models relying on A1,3-allylic strain. The products could have utility in the design of medicinally relevant compounds and as chiral ligands for asymmetric catalysis. A new synthesis of (+)-sertraline (Zoloft) was achieved.

Synthesis of a new Ag supported on hydroxyapatite-core-shell-γ-Fe2O3 nanoparticles (γ-Fe2O3@HAp-Ag NPs) and its application as a Lewis acid catalyst in the preparation of β-azidoalcohols and β-thiocyanohydrins from epoxides

In this study, we synthesized Ag supported on hydroxyapatite-core-shell-γ-Fe2O3 nanoparticles (γ-Fe2O3@HAp-Ag NPs) as a new, lewis acid, and reusable heterogeneous nancatalyst. Then, it was successfully used for the synthesis of β-azido alcohols and β-thiocyanohydrins from the regioselective conversation of some epoxides by azide and thiocyanate anions in water. The reaction afforded the corresponding products with high regioselectivity under mild reaction conditions.

Frontispiece: Iron‐Catalysed Remote C(sp3)−H Azidation of O‐Acyl Oximes and N‐Acyloxy Imidates Enabled by 1,5‐Hydrogen Atom Transfer of Iminyl and Imidate Radicals: Synthesis of γ‐Azido Ketones and β‐Azido Alcohols

An efficient distal C(sp3)−H azidation of both ketoxime esters and N-acyloxy imidates for the synthesis of γ-azido ketones and β-azido alcohols is reported in the Full Paper by J. Zhu, et al. on page 9477 ff. The artwork represents two essential processes of the proposed mechanism: the 1,5-hydrogen atom transfer of an imine/imidate radical through a chair-like transition state, and the iron-mediated redox azido transfer to the translocated carbon radical.

Synthesis and Characterization of γ-Fe2O3@HAp@β-CD Core-Shell Nanoparticles as a Novel Magnetic Nanoreactor and Its Application in the One-Pot Preparation of β-azido Alcohols, β-nitro Alcohols, and β-cyanohydrins

In this study, β-cyclodextrin(β-CD) supported, hydroxyapatite encapsulated γ-Fe2O3 (γ-Fe2O3@HAp@β-CD) was successfully prepared and evaluated as a solid-liquid phase transfer catalyst and also a molecular host system and nanoreactor for the nucleophilic ring-opening of epoxides in water for the preparation of β-azido alcohols, β-nitro alcohols, and β-cyanohydrins. The catalyst was characterized by FT-IR, XRD, TGA, and SEM. This procedure offers several advantages including excellent regioselectivity, high yields, short reaction times, recyclable catalyst, easy separation of the catalyst through external magnet, and easy work-up.

CuO supported 1-methyl-3-(3-(trimethoxysilyl) propyl) imidazolium chloride (MTMSP-Im/Cl) nanoparticles as an efficient simple heterogeneous catalysts for synthesis of β-azido alcohols

In the present study, CuO supported 1-methyl-3-(3-(trimethoxysilyl) propyl) imidazolium chloride (MTMSP-Im/Cl) is synthesized as a novel, efficient and eco-friendly heterogeneous nanocatalyst. This nanocatalyst was applied for selective ring opening of epoxides with azide anion in water. Structure and morphology of the obtained catalyst were investigated by FT-IR spectroscopy, XRD, TGA, FE-SEM, and EDX techniques. All the results confirmed that MTMSP-Im/Cl is grafted on to CuO nanoparticles. The synthesized nanohybrid can be easily separated after completion of the reaction and reused for four cycles without any significant reduction of its catalytic activity.

Zn3(BTC)2 as a Metal–Organic Framework and Effective Catalyst for the Regioselective β-Azidoalcohols and β-Thiocyanohydrins of Epoxides in Water

In this research, Zn3(BTC)2 as a novel, metal–organic framework, biodegradable, and reusable heterogeneous nanoporous catalyst according to the aims of green chemistry was synthesized and characterized by scanning electron microscopy, energy-dispersive X-ray spectroscopy, X-ray diffraction, and FT-IR analysis. Then, Zn3(BTC)2 as a novel and full-fledged catalyst was used for the synthesis of β-azido alcohols and β-thiocyanohydrins from the regioselective conversation of some epoxides by sodium azide (NaN3) and thiocyanate (SCN) anion in aqueous. The some advantages of this method are as follows: work-up procedure, excellent regioselectivity, an environmentally benign, mild reaction conditions, and recyclability of the catalyst without loosing its activity. We report the synthesis of Zn3(BTC)2 as metal–organic framework, biodegradable, and reusable heterogeneous nanoporous catalyst for the synthesis of β-azido alcohols and β-thiocyano hydrins. Zn3(BTC)2 showed excellent activity for ring opening of epoxides in water.

Visible-Light-Promoted Metal-Free Aerobic Hydroxyazidation of Alkenes

A highly efficient visible-light-promoted metal-free aerobic hydroxyazidation of alkenes has been developed. This protocol was operationally simple with broad substrate scope using relatively simple and readily available starting materials, such as alkenes and air, to construct valuable β-azido alcohols which are significant building blocks to build N-containing compounds. The distinct possible mechanisms were proposed via the generation of azido radical and alkene radical cation.

Oxygenation via C-H/C-C Bond Activation with Molecular Oxygen.

The selective oxidation of organic molecules is a fundamentally important component of modern synthetic chemistry. In the past decades, direct oxidative C-H and C-C bond functionalization has proved to be one of the most efficient and straightforward methods to synthesize complex products from simple and readily available starting materials. Among these oxidative processes, the use of molecular oxygen as a green and sustainable oxidant has attracted considerable attention because of its highly atom-economical, abundant, and environmentally friendly characteristics. The development of new protocols using molecular oxygen as an ideal oxidant is highly desirable in oxidation chemistry. More importantly, the oxygenation reaction of simple molecules using molecular oxygen as the oxygen source offers one of the most ideal processes for the construction of O-containing compounds. Aerobic oxidation and oxygenation by enzymes, such as monooxygenase, tyrosinase, and dopamine β-monooxygenase, have been observed in some biological C-H bond hydroxylation processes. Encouraged by these biological transformations, transition-metal- or organocatalyst-catalyzed oxygenation through dioxygen activation has attracted academic and industrial prospects. In this Account, we describe some advances from our group in oxygenation via C-H/C-C bond activation with molecular oxygen as the oxidant and oxygen source for the synthesis of O-containing compounds. Under an atmosphere of O2 (1 atm) or air (1 atm), we have successfully incorporated one or two O atoms from O2 into simple and readily available substrates through C-H, C-C, C═C, and C≡C bond cleavage by transition-metal catalysis, organocatalysis, and photocatalysis. Moreover, we have devised cyclization reactions with molecular oxygen to construct O-heterocycles. Most of these transformations can tolerate a broad range of functional groups. Furthermore, on the basis of isotope labeling experiments, electron paramagnetic resonance spectral analysis, and other mechanistic studies, we have demonstrated that a single electron transfer process via a carbon radical, peroxide radical, or hydroxyl radical is involved in these aerobic oxidation and oxygenation reactions. These protocols provide new approaches for the green synthesis of various α-keto amides, α-keto esters, esters, ketones, aldehydes, formamides, 2-oxoacetamidines, 2-(1H)-pyridones, phenols, tertiary α-hydroxy carbonyls, p-quinols, β-azido alcohols, benzyl alcohols, tryptophols, and oxazoles, which have potential applications in the preparation of natural products, bioactive compounds, and functional materials. In most cases, inexpensive and low-toxicity Cu, Fe, Mn, or NHPI was found to be an efficient catalyst for the transformation. The high efficiency, low cost, high oxygen atom economy, broad substrate scope, and practical operation make the developed oxygenation system very attractive and practical. Moreover, the design of new types of molecular-oxygen- or air-based oxidation and oxygenation reactions can be anticipated.

Immobilized [Cu(cdsalMeen)] on silica gel: a highly efficient heterogeneous catalyst for ‘Click’ [3 + 2] Huisgen cycloaddition

A facile and simple protocol for the ‘Click’ cycloaddition of organic azides with terminal alkynes catalyzed by immobilized [Cu(cdsalMeen)] on silica as a new and convenient heterogeneous catalyst is described. In this synthetic methodology, [Cu(cdsalMeen)]–SiO2 catalyzes 1,3-dipolar Huisgen cycloaddition of different functionalized β-azido alcohols and alkynes in the presence of ascorbic acid and a solution of THF/H2O (2:1, V/V) at room temperature. Good to excellent yields of β-hydroxytriazolylalkyl derivatives were afforded using [Cu(cdsalMeen)]–SiO2. Immobilization of [Cu(cdsalMeen)] on silica was approved as a chemically and thermally stable catalyst that can be reused for many consecutive trials without a significant decline in its reactivity.

Azidolysis of epoxides catalysed by the halohydrin dehalogenase from Arthrobacter sp. AD2 and a mutant with enhanced enantioselectivity: an (S)-selective HHDH

Halohydrin dehalogenase from Arthrobacter sp. AD2 catalysed azidolysis of epoxides with high regioselectivity and low to moderate (S)-enantioselectivity (E=1–16). Mutation of the asparagine 178 to alanine (N178A) showed increased enantioselectivity towards styrene oxide derivatives and glycidyl ethers. Conversion of aromatic epoxides was catalysed by HheA-N178A with complete enantioselectivity, however the regioselectivity was reduced. As a result of the enzyme-catalysed reaction, enantiomerically pure (S)-β-azido alcohols and (R)-α-azido alcohols (ee⩾99%) were obtained.

Synthesis and characterization of a novel Fe3O4@SiO2/bipyridinium dichloride nanocomposite and its application as a magnetic and recyclable phase-transfer catalyst in the preparation of β-azidoalcohols, β-cyanohydrins, and β-acetoxy alcohols

One-pot preparation of β-azido alcohols, β-cyanohydrins, and β-acetoxy alcohols using Fe 3 O 4 @SiO 2 /BNC, as catalyst. β-Azidoalcohols, β-cyanohydrins, and β-acetoxy alcohols have been synthesized in the presence of a Fe 3 O 4 @SiO 2 /bipyridinium nanocomposite (Fe 3 O 4 @SiO 2 /BNC) as a novel magnetic and recyclable phase-transfer catalyst (PTC) in water. The catalyst was characterized with FT–IR, SEM, XRD, VSM, and TGA. This methodology offers several advantages, including easy work-up procedure, excellent regioselectivity, high yields, short reaction times, recyclable catalyst, easy separation of the catalyst through an external magnet and eco-friendly procedure.

Mn-Catalyzed Highly Efficient Aerobic Oxidative Hydroxyazidation of Olefins: A Direct Approach to β-Azido Alcohols.

An efficient Mn-catalyzed aerobic oxidative hydroxyazidation of olefins for synthesis of β-azido alcohols has been developed. The aerobic oxidative generation of azido radical employing air as the terminal oxidant is disclosed as the key process for this transformation. The reaction is appreciated by its broad substrate scope, inexpensive Mn-catalyst, high efficiency, easy operation under air, and mild conditions at room temperature. This chemistry provides a novel approach to high value-added β-azido alcohols, which are useful precursors of aziridines, β-amino alcohols, and other important N- and O-containing heterocyclic compounds. This chemistry also provides an unexpected approach to azido substituted cyclic peroxy alcohol esters. A DFT calculation indicates that Mn catalyst plays key dual roles as an efficient catalyst for the generation of azido radical and a stabilizer for peroxyl radical intermediate. Further calculation reasonably explains the proposed mechanism for the control of C-C bond cleavage or for the formation of β-azido alcohols.

Synthesis and characterization of a novel nano-Fe3O4-copoly[(styrene/acrylic acid)/grafted ethylene oxide and its application as a magnetic and recyclable phase-transfer catalyst in the preparation of β-azido alcohols and β-nitro alcohols

A facile method was developed for the synthesis of β-azido alcohols and β-nitro alcohols in the presence of a novel nano-Fe3O4-copoly[(styrene/acrylic acid)/grafted ethylene oxide (nano-Fe3O4-PS-Co-[PAA-g-PEG]) as a phase-transfer catalyst in water. The catalyst was characterized with IR, SEM, and TGA. This procedure offers several advantages, including excellent regioselectivity, high yields, short reaction times, a recyclable catalyst, easy separation of the catalyst through an external magnet, and easy workup .

Fe3O4 nanoparticle-bonded β-cyclodextrin as an efficient and magnetically retrievable catalyst for the preparation of β-azido alcohols and β-hydroxy thiocyanate

A novel Fe3O4 nanoparticle-bonded β-cyclodextrin (β-CD@MNP) has been synthesized and characterized by scanning electron microscopy, vibrating sample magnetometry, and thermogravimetric analysis. It is found that the nanoparticles can be used as an efficient and magnetically retrievable nanocatalyst for the preparation of β-azido alcohols and β-hydroxy thiocyanates under ultrasound irradiation.

Facile synthesis of an organic–inorganic nanocomposite, PEG–silica, by sol–gel method; its characterization and application as an efficient catalyst in regioselective nucleophilic ring opening of epoxides: Preparation of β-azido alcohols and β-cyanohydrins

Abstract The sol–gel method was used for the synthesis of a PEG–silica hybrid. In order to introduce PEG into the cavities of silica gel, first, the bis(3-trimethoxysilylpropyl)-polyethylene glycol precursor was synthesized by the reaction of 3-chloropropyltrimethoxysilane with alkoxides formed on the PEG terminals. The organic–inorganic hybrid silica was then synthesized by hydrolysis and polycondensation of the precursor under mild acidic conditions. The characteristics results of FT–IR, XRD and TGA confirmed the coexistence of silica and PEG networks. The catalytic ability of this heterogeneous catalyst to the regioselective ring opening of epoxides by azide and cyanide anions in H 2 O was also investigated.

ChemInform Abstract: 1,1′‐Bis‐methyl‐3,3‐methylenebisimidazolium Dichloride as an Efficient Phase Transfer Catalyst for Ring Opening of Epoxides Using SCN‐ and N3‐ in Water.

An efficient synthesis of β-azido alcohols and β-hydroxy thiocyanates has been achieved by ring opening of epoxides using 1,1'-bis-methyl-3, 3-methylene-bisimidazolium dichloride as a phase transfe...

Copper-doped silica cuprous sulfate (CDSCS) as a highly efficient and new heterogeneous nano catalyst for [3+2] Huisgen cycloaddition

The synthesis and characterization of copper-doped silica cuprous sulfate (CDSCS) as a new and efficient heterogeneous nano catalyst are described. CDSCS has been fully characterized by different microscopic, spectroscopic and physical techniques, including scanning electron microscopy (SEM), transmission electron microscopy (TEM), atomic forced microscopy (AFM), X-ray diffraction (XRD), inductively coupled plasma (ICP) analysis, thermogravimetric analysis (TGA) and FT-IR. CDSCS is proved to be a useful heterogeneous nano catalyst in Cu(I)-catalyzed ‘Click’ cycloaddition of organic azides with terminal alkynes. CDSCS catalyzes the 1,3-dipolar cycloaddition reactions of β-azido alcohols and alkynes at room temperature, in THF/H2O (1:1, v/v) solution. Using CDSCS, 1,4-disubstituted 1,2,3-triazole adducts are mainly obtained, in good to excellent yields and in short reaction times. These compounds have featural resemblance to β-adrenoceptor blocking agents. CDSCS was approved as a chemically and thermally stable nano catalyst that can be reused for many consecutive trials without a significant decline in its reactivity.

1,1'-Bis-Methyl-3, 3-Methylenebisimidazolium Dichloride as an Efficient Phase Transfer Catalyst for Ring Opening of Epoxides Using SCN- and N3- in water

An efficient synthesis of β-azido alcohols and β-hydroxy thiocyanates has been achieved by ring opening of epoxides using 1,1'-bis-methyl-3, 3-methylene-bisimidazolium dichloride as a phase transfer catalyst at room temperature in water. The reaction is regioselective and afforded the corresponding products in moderate to excellent yields.

‘Click Synthesis’ of Some Novel O‐Substituted Oximes Containing 1,2,3‐Triazole‐1,4‐diyl Residues as New Analogs of β‐Adrenoceptor Antagonists

AbstractThe ‘click synthesis’ of some novel O‐substituted oximes, 7a–7t, which contain 1,2,3‐triazolediyl residues, as new analogs of β‐adrenoceptor antagonists is described (Schemes 1–4). The synthesis of these compounds was achieved in four to five steps. The formation of oximes of 9H‐fluoren‐9‐one and benzophenone, i.e., 9a and 9b, respectively, followed by their reaction with propargyl bromide, afforded O‐propargyl oximes 10a and 10b, respectively, which by a subsequent CuI‐catalyzed Huisgen cycloaddition with prepared β‐azido alcohols 11a–11j (Schemes 2 and 3), led to the target compounds 7a–7t in good yields.