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Open AccessCommunication

Synthesis of 2-Aminonicotinonitriles via Photodecarboxylation of Azirine-2-Carboxylic Acids

by Julia I. Pavlenko, Mikhail S. Novikov and Anastasiya V. Agafonova

Molbank 2026, 2026(2), M2165; https://doi.org/10.3390/M2165 - 14 Apr 2026

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2-Aminonicotinonitriles represent an important class of heterocycles with diverse biological activities. Herein, we report an unexpected photochemical transformation of azirine-2-carboxylic acids leading to the formation of 2-aminonicotinonitrile derivatives. Optimization of the reaction conditions enabled the synthesis of the target products in moderate yields. [...] Read more.

2-Aminonicotinonitriles represent an important class of heterocycles with diverse biological activities. Herein, we report an unexpected photochemical transformation of azirine-2-carboxylic acids leading to the formation of 2-aminonicotinonitrile derivatives. Optimization of the reaction conditions enabled the synthesis of the target products in moderate yields. The structure of the obtained product was confirmed by NMR spectroscopy, HRMS, and single-crystal X-ray diffraction analysis. Full article

(This article belongs to the Section Organic Synthesis and Biosynthesis)

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5 pages, 465 KB

Open AccessShort Note

Methyl (1aRS,7aSR)-7-formyl-1a-phenyl-1,1a-dihydroazirino[2,3-b]benzo[e][1,4]thiazine-7a(7H)-carboxylate

by Ilya P. Filippov, Anastasiya V. Agafonova, Nikolai V. Rostovskii and Mikhail S. Novikov

Molbank 2025, 2025(4), M2101; https://doi.org/10.3390/M2101 - 4 Dec 2025

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Abstract

The first representative of the aziridine-fused benzo[e][1,4]thiazine series was synthesized from methyl 2-bromo-2-phenyl-2H-azirine-2-carboxylate and benzo[d]thiazole in 74% yield. The reaction proceeds via the S_N2′-S_N2′-cascade to form the azirinylthiazolium salt followed by a [...] Read more.

The first representative of the aziridine-fused benzo[e][1,4]thiazine series was synthesized from methyl 2-bromo-2-phenyl-2H-azirine-2-carboxylate and benzo[d]thiazole in 74% yield. The reaction proceeds via the S_N2′-S_N2′-cascade to form the azirinylthiazolium salt followed by a water-induced thiazole ring expansion. The structure of the title compound was established based on ¹H, ¹³C, 2D NMR spectroscopy and high-resolution mass spectrometry, and unambiguously confirmed by X-ray diffraction analysis. Full article

(This article belongs to the Section Organic Synthesis and Biosynthesis)

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33 pages, 1513 KB

Open AccessArticle

Azirinyl-Substituted Nitrile Oxides: Generation and Use in the Synthesis of Isoxazole Containing Heterocyclic Hybrids

by Alexander S. Dudik, Timur O. Zanakhov, Ekaterina E. Galenko, Mikhail S. Novikov and Alexander F. Khlebnikov

Molecules 2025, 30(13), 2834; https://doi.org/10.3390/molecules30132834 - 2 Jul 2025

Cited by 3 | Viewed by 2049

Abstract

The procedure for the generation of azirinyl-substituted nitrile oxides by the reaction of 2-(diazoacetyl)-2H-azirines with tert-butyl nitrite while preserving the azirine ring has been developed. The [3+2] cycloaddition of azirinyl-substituted nitrile oxides to terminal acetylenes produced azirinyl(isoxazolyl)ketones with various substituents [...] Read more.

The procedure for the generation of azirinyl-substituted nitrile oxides by the reaction of 2-(diazoacetyl)-2H-azirines with tert-butyl nitrite while preserving the azirine ring has been developed. The [3+2] cycloaddition of azirinyl-substituted nitrile oxides to terminal acetylenes produced azirinyl(isoxazolyl)ketones with various substituents in position 3 of azirine and position 5 of isoxazole fragments in a 51–91% yield at room temperature in DCM. DFT calculations and experimental data are consistent with the assumption that the formation of azirinyl-substituted nitrile oxides is accelerated by the acid catalyst. Cycloadducts of nitrile oxides with aryl/hetarylacetylenes and DMAD can be obtained by catalysis with boron trifluoride etherate, which significantly expands the scope of application of the reaction. Expansion of the azirine ring of the prepared cycloadducts allows obtaining a wide range of structurally diverse functionalized isoxazole-containing heterocyclic hybrids. LED light induces isomerization of the azirinecarbonyl moiety of the azirinyl(isoxazolyl)ketones, resulting in the formation of a set of 3,5’-biisoxazoles in a 40–71% yield, while the catalytic reaction of the azirine moiety with 1,3-diketones opens the way to pyrrole- and isoxazole-containing hybrids. 2-(Isoxazole-3-ylcarbonyl)-3-arylazirines were also easily isomerized to 3-(oxazol-5-yl)isoxazoles in methanol in the presence of excess potassium carbonate at room temperature. Full article

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24 pages, 3618 KB

Open AccessArticle

Acridine–Isoxazole and Acridine–Azirine Hybrids: Synthesis, Photochemical Transformations in the UV/Visible Radiation Boundary Region, and Anticancer Activity

by Ekaterina E. Galenko, Mikhail S. Novikov, Alexander S. Bunev and Alexander F. Khlebnikov

Molecules 2024, 29(7), 1538; https://doi.org/10.3390/molecules29071538 - 29 Mar 2024

Cited by 5 | Viewed by 2484

Abstract

Easy-to-handle N-hydroxyacridinecarbimidoyl chloride hydrochlorides were synthesized as convenient nitrile oxide precursors in the preparation of 3-(acridin-9/2-yl)isoxazole derivatives via 1,3-dipolar cycloaddition with terminal alkynes, 1,1-dichloroethene, and acrylonitrile. Azirines with an acridin-9/2-yl substituent attached directly or via the 1,2,3-triazole linker to the azirine C2 [...] Read more.

Easy-to-handle N-hydroxyacridinecarbimidoyl chloride hydrochlorides were synthesized as convenient nitrile oxide precursors in the preparation of 3-(acridin-9/2-yl)isoxazole derivatives via 1,3-dipolar cycloaddition with terminal alkynes, 1,1-dichloroethene, and acrylonitrile. Azirines with an acridin-9/2-yl substituent attached directly or via the 1,2,3-triazole linker to the azirine C2 were also synthesized. The three-membered rings of the acridine–azirine hybrids were found to be resistant to irradiation in the UV/visible boundary region, despite their long-wave absorption at 320–420 nm, indicating that the acridine moiety cannot be used as an antenna to transfer light energy to generate nitrile ylides from azirines for photoclick cycloaddition. The acridine–isoxazole hybrids linked at the C9–C3 or C2–C3 atoms under blue light irradiation underwent the addition of such hydrogen donor solvents, such as, toluene, o-xylene, mesitylene, 4-chlorotoluene, THF, 1,4-dioxane, or methyl tert-butyl ether (MTBE), to the acridine system to give the corresponding 9-substituted acridanes in good yields. The synthesized acridine–azirine, acridine–isoxazole, and acridane–isoxazole hybrids exhibited cytotoxicity toward both all tested cancer cell lines (HCT 116, MCF7, and A704) and normal cells (WI-26 VA4). Full article

(This article belongs to the Section Organic Chemistry)

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25 pages, 2974 KB

Open AccessArticle

Diastereoselective ZnCl₂-Mediated Joullié–Ugi Three-Component Reaction for the Preparation of Phosphorylated N-Acylaziridines from 2H-Azirines

by Julene Allende, Iurre Olaizola, Ana M. Ochoa de Retana, Francisco Palacios and Jesús M. de los Santos

Molecules 2024, 29(5), 1023; https://doi.org/10.3390/molecules29051023 - 27 Feb 2024

Cited by 5 | Viewed by 2350

Abstract

We disclose a direct approach to the diastereoselective synthesis of phosphorus substituted N-acylaziridines based on a one-pot ZnCl₂-catalyzed Joullié–Ugi three-component reaction of phosphorylated 2H-azirines, carboxylic acids and isocyanides. Hence, this robust protocol offers rapid access to an array [...] Read more.

We disclose a direct approach to the diastereoselective synthesis of phosphorus substituted N-acylaziridines based on a one-pot ZnCl₂-catalyzed Joullié–Ugi three-component reaction of phosphorylated 2H-azirines, carboxylic acids and isocyanides. Hence, this robust protocol offers rapid access to an array of N-acylaziridines in moderate-to-good yields and up to 98:2 dr for substrates over a wide scope. The relevance of this synthetic methodology was achieved via a gram-scale reaction and the further derivatization of the nitrogen-containing three-membered heterocycle. The diastereo- and regioselective ring expansion of the obtained N-acylaziridines to oxazole derivatives was accomplished in the presence of BF₃·OEt₂ as an efficient Lewid acid catalyst. Full article

(This article belongs to the Special Issue Organophosphorus Chemistry: A New Perspective, 2nd Edition)

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16 pages, 3029 KB

Open AccessArticle

Triethylamine-Promoted Oxidative Cyclodimerization of 2H-Azirine-2-carboxylates to Pyrimidine-4,6-dicarboxylates: Experimental and DFT Study

by Timofei N. Zakharov, Pavel A. Sakharov, Mikhail S. Novikov, Alexander F. Khlebnikov and Nikolai V. Rostovskii

Molecules 2023, 28(11), 4315; https://doi.org/10.3390/molecules28114315 - 24 May 2023

Cited by 8 | Viewed by 3681

Abstract

An unprecedented oxidative cyclodimerization reaction of 2H-azirine-2-carboxylates to pyrimidine-4,6-dicarboxylates under heating with triethylamine in air is described. In this reaction, one azirine molecule undergoes formal cleavage across the C-C bond and another across the C=N bond. According to the experimental study [...] Read more.

An unprecedented oxidative cyclodimerization reaction of 2H-azirine-2-carboxylates to pyrimidine-4,6-dicarboxylates under heating with triethylamine in air is described. In this reaction, one azirine molecule undergoes formal cleavage across the C-C bond and another across the C=N bond. According to the experimental study and DFT calculations, the key steps of the reaction mechanism include nucleophilic addition of N,N-diethylhydroxylamine to an azirine to form an (aminooxy)aziridine, generation of an azomethine ylide, and its 1,3-dipolar cycloaddition to the second azirine molecule. The crucial condition for the synthesis of pyrimidines is generation of N,N-diethylhydroxylamine in the reaction mixture in a very low concentration, which is ensured by the slow oxidation of triethylamine with air oxygen. Addition of a radical initiator accelerated the reaction and resulted in higher yields of the pyrimidines. Under these conditions, the scope of the pyrimidine formation was elucidated, and a series of pyrimidines was synthesized. Full article

(This article belongs to the Special Issue Chemistry of Nitrogen Heterocyclic Compounds)

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18 pages, 7344 KB

Open AccessArticle

5-Chloroisoxazoles: A Versatile Starting Material for the Preparation of Amides, Anhydrides, Esters, and Thioesters of 2H-Azirine-2-carboxylic Acids

by Anastasiya V. Agafonova, Mikhail S. Novikov and Alexander F. Khlebnikov

Molecules 2023, 28(1), 275; https://doi.org/10.3390/molecules28010275 - 29 Dec 2022

Cited by 8 | Viewed by 3528

Abstract

Amides, anhydrides, esters, and thioesters of 2H-azirine-2-carboxylic acids were prepared by a rapid procedure at room temperature involving FeCl₂-catalyzed isomerization of 5-chloroisoxazoles to 2H-azirine-2-carbonyl chlorides, followed by reaction with N-, O-, or S-nucleophiles mediated by an ortho [...] Read more.

Amides, anhydrides, esters, and thioesters of 2H-azirine-2-carboxylic acids were prepared by a rapid procedure at room temperature involving FeCl₂-catalyzed isomerization of 5-chloroisoxazoles to 2H-azirine-2-carbonyl chlorides, followed by reaction with N-, O-, or S-nucleophiles mediated by an ortho-substituted pyridine. With readily available chloroisoxazoles and a nucleophile, 2-picoline can be used as an inexpensive base. When a high yield of the acylation product is important, the reagent 2-(trimethylsilyl)pyridine/ethyl chloroformate is more suitable for the acylation with 2H-azirine-2-carbonyl chlorides. Full article

(This article belongs to the Special Issue Chemistry of Nitrogen Heterocyclic Compounds)

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15 pages, 1773 KB

Open AccessFeature PaperArticle

Electrochemically Induced Synthesis of Imidazoles from Vinyl Azides and Benzyl Amines

by Vera A. Vil’, Sergei S. Grishin and Alexander O. Terent’ev

Molecules 2022, 27(22), 7721; https://doi.org/10.3390/molecules27227721 - 9 Nov 2022

Cited by 2 | Viewed by 3680

Abstract

An electrochemically induced synthesis of imidazoles from vinyl azides and benzyl amines was developed. A wide range of imidazoles were obtained, with yields of 30 to 64%. The discovered transformation is a multistep process whose main steps include the generation of electrophilic iodine [...] Read more.

An electrochemically induced synthesis of imidazoles from vinyl azides and benzyl amines was developed. A wide range of imidazoles were obtained, with yields of 30 to 64%. The discovered transformation is a multistep process whose main steps include the generation of electrophilic iodine species, 2H-azirine formation from the vinyl azide, followed by its reactions with benzyl amine and with imine generated from benzyl amine. The cyclization and aromatization of the obtained intermediate lead to the target imidazole. The synthesis proceeds under constant current conditions in an undivided cell. Despite possible cathodic reduction of various unsaturated intermediates with C=N bonds, the efficient electrochemically induced synthesis of imidazoles was carried out. Full article

(This article belongs to the Special Issue Recent Developments in the Synthesis and Functionalization of Nitrogen Heterocycles)

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17 pages, 2685 KB

Open AccessArticle

Copper(II)-Catalyzed (3+2) Cycloaddition of 2H-Azirines to Six-Membered Cyclic Enols as a Route to Pyrrolo[3,2-c]quinolone, Chromeno[3,4-b]pyrrole, and Naphtho[1,8-ef]indole Scaffolds

by Pavel A. Sakharov, Nikolai V. Rostovskii, Alexander F. Khlebnikov and Mikhail S. Novikov

Molecules 2022, 27(17), 5681; https://doi.org/10.3390/molecules27175681 - 2 Sep 2022

Cited by 10 | Viewed by 4110

Abstract

A method for the [2+3] pyrroline annulation to the six-membered non-aromatic enols using 3-aryl-2H-azirines as annulation agents is developed in the current study. The reaction proceeds as a formal (3+2) cycloaddition via the N1-C2 azirine bond cleavage and is catalyzed by [...] Read more.

A method for the [2+3] pyrroline annulation to the six-membered non-aromatic enols using 3-aryl-2H-azirines as annulation agents is developed in the current study. The reaction proceeds as a formal (3+2) cycloaddition via the N1-C2 azirine bond cleavage and is catalyzed by both Cu(II) and Cu(I) compounds. The new annulation method can be applied to prepare pyrrolo[3,2-c]quinoline, chromeno[3,4-b]pyrrole, and naphtho[1,8-ef]indole derivatives in good to excellent yields from enols of the quinolin-2-one, 2H-chromen-2-one, and 1H-phenalen-1-one series. Full article

(This article belongs to the Special Issue Recent Developments in the Synthesis and Functionalization of Nitrogen Heterocycles)

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20 pages, 7485 KB

Open AccessReview

Non-Aziridination Approaches to 3-Arylaziridine-2-carboxylic Acid Derivatives and 3-Aryl-(aziridin-2-yl)ketones

by Boriss Strumfs, Kirils Velikijs, Romans Uljanovs, Stanislavs Sinkarevs and Ilze Strumfa

Int. J. Mol. Sci. 2022, 23(11), 5919; https://doi.org/10.3390/ijms23115919 - 25 May 2022

Cited by 1 | Viewed by 2399

Abstract

Highly functionalized aziridines, including compounds with aromatic moieties, are attractive substrates both in synthetic and medical areas of chemistry. There is a broad and interesting set of synthetic methods for reaching these compounds. Aziridination represents the most explored tool, but there are several [...] Read more.

Highly functionalized aziridines, including compounds with aromatic moieties, are attractive substrates both in synthetic and medical areas of chemistry. There is a broad and interesting set of synthetic methods for reaching these compounds. Aziridination represents the most explored tool, but there are several other more specific, less well-known, but highly promising approaches. Therefore, the current review focuses on recently described or updated ways to obtain 3-arylated aziridines via different non-aziridination-based synthetic methods, reported mainly since 2000. The presented methods belong to two main directions of synthesis, namely, cyclization of open-chain substrates and rearrangement of other heterocycles. Cyclization of open-chain substrates includes the classic Gabriel-Cromwell type cyclization of halogenated substrates with amines, base-promoted cyclization of activated aminoalcohols (or its analogues), and the oxidative cyclization of β-dicarbonyls. Rearrangements of other heterocycles are presented as the Baldwin rearrangement of 4-isoxazolines, the cycloaddition of 1.3-dipoles or dienes to 2H-azirines, and the addition of C- and N-nucleophiles to the double bond of azirines. Full article

(This article belongs to the Special Issue Heterocyclic Compounds: Advanced Syntheses and Applications)

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9 pages, 1555 KB

Open AccessArticle

Anti-Inflammatory Dysidazirine Carboxylic Acid from the Marine Cyanobacterium Caldora sp. Collected from the Reefs of Fort Lauderdale, Florida

by Sarath P. Gunasekera, Sofia Kokkaliari, Ranjala Ratnayake, Thomas Sauvage, Larissa A. H. dos Santos, Hendrik Luesch and Valerie J. Paul

Molecules 2022, 27(5), 1717; https://doi.org/10.3390/molecules27051717 - 6 Mar 2022

Cited by 15 | Viewed by 3606

Abstract

Dysidazirine carboxylic acid (1) was isolated from the lipophilic extract of a collection of the benthic marine cyanobacterium Caldora sp. from reefs near Fort Lauderdale, Florida. The planar structure of this new compound was determined by spectroscopic methods and comparisons between [...] Read more.

Dysidazirine carboxylic acid (1) was isolated from the lipophilic extract of a collection of the benthic marine cyanobacterium Caldora sp. from reefs near Fort Lauderdale, Florida. The planar structure of this new compound was determined by spectroscopic methods and comparisons between HRMS and NMR data with its reported methyl ester. The absolute configuration of the single chiral center was determined by the conversion of 1 to the methyl ester and the comparison of its specific rotation data with the two known methyl ester isomers, 2 and 3. Molecular sequencing with 16S rDNA indicated that this cyanobacterium differs from Caldora penicillata (Oscillatoriales) and represents a previously undocumented and novel Caldora species. Dysidazirine (2) showed weak cytotoxicity against HCT116 colorectal cancer cells (IC₅₀ 9.1 µM), while dysidazirine carboxylic acid (1) was non-cytotoxic. Similar cell viability patterns were observed in RAW264.7 cells with dysidazirine only (2), displaying cytotoxicity at the highest concentration tested (50 µM). The non-cytotoxic dysidazirine carboxylic acid (1) demonstrated anti-inflammatory activity in RAW264.7 cells stimulated with LPS. After 24 h, 1 inhibited the production of NO by almost 50% at 50 µM, without inducing cytotoxicity. Compound 1 rapidly decreased gene expression of the pro-inflammatory gene iNOS after 3 h post-LPS treatment and in a dose-dependent manner (IC₅₀ ~1 µM); the downregulation of iNOS persisted at least until 12 h. Full article

(This article belongs to the Special Issue Methodological Developments in Marine Natural Product Sciences—A Themed Issue in Honor of Professor William Fenical)

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25 pages, 31428 KB

Open AccessReview

Electrocyclizations of Conjugated Azapolyenes Produced in Reactions of Azaheterocycles with Metal Carbenes

by Nikolai V. Rostovskii, Mikhail S. Novikov and Alexander F. Khlebnikov

Organics 2021, 2(3), 313-336; https://doi.org/10.3390/org2030017 - 14 Sep 2021

Cited by 8 | Viewed by 5016

Abstract

Conjugated azapolyenes (azabuta-1,3-dienes, aza-/diaza-/oxaza-/oxadiazahexa-1,3,5-trienes) are highly reactive in electrocyclization reactions, which makes them convenient precursors for the synthesis of a wide range of four-, five-, and six-membered nitrogen heterocycles that are of relevance for medicinal chemistry. Ring opening reactions of 2H-azirines [...] Read more.

Conjugated azapolyenes (azabuta-1,3-dienes, aza-/diaza-/oxaza-/oxadiazahexa-1,3,5-trienes) are highly reactive in electrocyclization reactions, which makes them convenient precursors for the synthesis of a wide range of four-, five-, and six-membered nitrogen heterocycles that are of relevance for medicinal chemistry. Ring opening reactions of 2H-azirines and azoles containing an N–N or N–O bond, initiated by a transition metal carbene, have become increasingly important in recent years, since they easily allow the generation of azapolyenes with different numbers of double bonds and heteroatoms in various positions. This review summarizes the literature, published mainly in the last decade, on the synthetic and mechanistic aspects of electrocyclizations of azapolyenes generated by the carbene method. Full article

(This article belongs to the Special Issue Pericyclic Reactions in Organic Synthesis)

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15 pages, 2877 KB

Open AccessArticle

Isomerization of 5-(2H-Azirin-2-yl)oxazoles: An Atom-Economic Approach to 4H-Pyrrolo[2,3-d]oxazoles

by Timur O. Zanakhov, Ekaterina E. Galenko, Mariya A. Kryukova, Mikhail S. Novikov and Alexander A. Khlebnikov

Molecules 2021, 26(7), 1881; https://doi.org/10.3390/molecules26071881 - 26 Mar 2021

Cited by 7 | Viewed by 4068

Abstract

An atom economical method for the preparation of variously substituted 4H-pyrrolo[2,3-d]oxazoles was developed on the basis of thermal isomerization of 5-(2H-azirin-2-yl)oxazoles. The latter were prepared by Rh₂(oct)₄ catalyzed reaction of 2-(3-aryl/heteroaryl)-2-diazoacetyl-2H-azirines with [...] Read more.

An atom economical method for the preparation of variously substituted 4H-pyrrolo[2,3-d]oxazoles was developed on the basis of thermal isomerization of 5-(2H-azirin-2-yl)oxazoles. The latter were prepared by Rh₂(oct)₄ catalyzed reaction of 2-(3-aryl/heteroaryl)-2-diazoacetyl-2H-azirines with a set of substituted acetonitriles, benzonitriles, acrylonitrile and fumaronitrile. According to DFT calculations the transformation of 5-(2H-azirin-2-yl)oxazole to 4H-pyrrolo[2,3-d]oxazole occurs through the nitrenoid-like transition state to give a 3aH-pyrrolo[2,3-d]oxazole intermediate, followed by 1,5-H-shift. Full article

(This article belongs to the Special Issue Diazo Chemistry)

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25 pages, 2953 KB

Open AccessArticle

Synthesis of α-Aminophosphonic Acid Derivatives Through the Addition of O- and S-Nucleophiles to 2H-Azirines and Their Antiproliferative Effect on A549 Human Lung Adenocarcinoma Cells

by Victor Carramiñana, Ana M. Ochoa de Retana, Francisco Palacios and Jesús M. de los Santos

Molecules 2020, 25(15), 3332; https://doi.org/10.3390/molecules25153332 - 22 Jul 2020

Cited by 13 | Viewed by 4768

Abstract

This work reports a straightforward regioselective synthetic methodology to prepare α-aminophosphine oxides and phosphonates through the addition of oxygen and sulfur nucleophiles to the C–N double bond of 2H-azirine derivatives. Determined by the nature of the nucleophile, different α-aminophosphorus compounds may [...] Read more.

This work reports a straightforward regioselective synthetic methodology to prepare α-aminophosphine oxides and phosphonates through the addition of oxygen and sulfur nucleophiles to the C–N double bond of 2H-azirine derivatives. Determined by the nature of the nucleophile, different α-aminophosphorus compounds may be obtained. For instance, aliphatic alcohols such as methanol or ethanol afford α-aminophosphine oxide and phosphonate acetals after N–C3 ring opening of the intermediate aziridine. However, addition of 2,2,2-trifluoroethanol, phenols, substituted benzenthiols or ethanethiol to 2H-azirine phosphine oxides or phosphonates yields allylic α-aminophosphine oxides and phosphonates in good to high general yields. In some cases, the intermediate aziridine attained by the nucleophilic addition of O- or S-nucleophiles to the starting 2H-azirine may be isolated and characterized before ring opening. Additionally, the cytotoxic effect on cell lines derived from human lung adenocarcinoma (A549) and non-malignant cells (MCR-5) was also screened. Some α-aminophosphorus derivatives exhibited very good activity against the A549 cell line in vitro. Furthermore, selectivity towards cancer cell (A549) over non-malignant cells (MCR-5) has been detected in almost all compounds tested. Full article

(This article belongs to the Special Issue 25th Anniversary of Molecules—Recent Advances in Medicinal Chemistry)

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13 pages, 2315 KB

Open AccessArticle

Synthesis of New 2-Halo-2-(1H-tetrazol-5-yl)-2H-azirines via a Non-Classical Wittig Reaction

by Ana L. Cardoso, Carmo Sousa, Marta S. C. Henriques, José A. Paixão and Teresa M. V. D. Pinho e Melo

Molecules 2015, 20(12), 22351-22363; https://doi.org/10.3390/molecules201219848 - 12 Dec 2015

Cited by 19 | Viewed by 7129

Abstract

The synthesis and reactivity of tetrazol-5-yl-phosphorus ylides towards N-halosuccinimide/TMSN₃ reagent systems was explored, opening the way to new haloazidoalkenes bearing a tetrazol-5-yl substituent. These compounds were obtained as single isomers, except in one case. X-ray crystal structures were determined for three [...] Read more.

The synthesis and reactivity of tetrazol-5-yl-phosphorus ylides towards N-halosuccinimide/TMSN₃ reagent systems was explored, opening the way to new haloazidoalkenes bearing a tetrazol-5-yl substituent. These compounds were obtained as single isomers, except in one case. X-ray crystal structures were determined for three derivatives, establishing that the non-classical Wittig reaction leads to the selective synthesis of haloazidoalkenes with (Z)-configuration. The thermolysis of the haloazidoalkenes afforded new 2-halo-2-(tetrazol-5-yl)-2H-azirines in high yields. Thus, the reported synthetic methodologies gave access to important building blocks in organic synthesis, vinyl tetrazoles and 2-halo-2-(tetrazol-5-yl)-2H-azirine derivatives. Full article

(This article belongs to the Special Issue Organic Azides)

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