Organics

13 pages, 5460 KiB

Open AccessArticle

Synthesis of Amino-Acid-Based Nitroalkenes

by Velisaria-Eleni Gerogianni, Giorgos S. Koutoulogenis, Dimitrios Triantafyllos Gerokonstantis and George Kokotos

Organics 2022, 3(2), 137-149; https://0-doi-org.brum.beds.ac.uk/10.3390/org3020011 - 14 Jun 2022

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Abstract

Fatty-acid-based nitroalkenes have recently received great attention because of their bioactivities. On the contrary, peptide- or amino-acid-based nitroalkenes have been scarcely explored so far, although they may exhibit interesting biological properties, for example, as enzyme inhibitors. In this work, we study protocols for [...] Read more.

Fatty-acid-based nitroalkenes have recently received great attention because of their bioactivities. On the contrary, peptide- or amino-acid-based nitroalkenes have been scarcely explored so far, although they may exhibit interesting biological properties, for example, as enzyme inhibitors. In this work, we study protocols for the efficient synthesis of nitroalkenes based on natural amino acids. A variety of N-protected amino alcohols and Weinreb amides, derived from α-amino acids, were converted to the corresponding N-protected amino aldehydes, and, through a Henry reaction with nitroalkanes, produced the corresponding nitro alcohols. The subsequent elimination reaction led to the (E)-isomer of amino-acid-based nitroalkenes in moderate to high yields. Full article

(This article belongs to the Collection Advanced Research Papers in Organics)

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15 pages, 3227 KiB

Open AccessArticle

A Molecular Electron Density Theory Study of the [3+2] Cycloaddition Reaction of Pseudo(mono)radical Azomethine Ylides with Phenyl Vinyl Sulphone

by Mar Ríos-Gutiérrez, Assem Barakat and Luis R. Domingo

Organics 2022, 3(2), 122-136; https://0-doi-org.brum.beds.ac.uk/10.3390/org3020010 - 06 Jun 2022

Cited by 13 | Viewed by 2225

Abstract

The [3+2] cycloaddition (32CA) reaction of an azomethine ylide (AY), derived from isatin and L-proline, with phenyl vinyl sulphone has been studied within Molecular Electron Density Theory (MEDT) at the ωB97X-D/6-311G(d,p) level. ELF topological analysis of AY classifies it as a pseudo(mono)radical [...] Read more.

The [3+2] cycloaddition (32CA) reaction of an azomethine ylide (AY), derived from isatin and L-proline, with phenyl vinyl sulphone has been studied within Molecular Electron Density Theory (MEDT) at the ωB97X-D/6-311G(d,p) level. ELF topological analysis of AY classifies it as a pseudo(mono)radical species with two monosynaptic basins at the C1 carbon, integrating a total of 0.76 e. While vinyl sulphone has a strong electrophilic character, AY is a supernucleophile, suggesting a high polar character and low activation energy for the reaction. The nucleophilic Parr functions indicate that the pseudoradical C1 carbon is the most nucleophilic center. The 32CA reaction presents an activation Gibbs free energy of 13.1 kcal·mol⁻¹ and is exergonic by −26.8 kcal·mol⁻¹. This reaction presents high endo stereoselectivity and high meta regioselectivity. Analysis of the global electron density transfer (GEDT) at the most favorable meta/endo TS, 0.31 e, accounts for the high polar character of this 32CA reaction, classified by forward electron density flux (FEDF). A Bonding Evolution Theory (BET) study along the most favorable meta/endo reaction path characterizes this 32CA reaction, taking place through a non-concerted two-stage one-step mechanism, as a pseudo(mono)radical-type 32CA reaction, in agreement with the ELF analysis of the AY. Full article

(This article belongs to the Special Issue Chemistry of Heterocycles)

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11 pages, 10938 KiB

Open AccessArticle

Acid Catalyzed N-Alkylation of Pyrazoles with Trichloroacetimidates

by Rowan I. L. Meador, Nilamber A. Mate and John D. Chisholm

Organics 2022, 3(2), 111-121; https://0-doi-org.brum.beds.ac.uk/10.3390/org3020009 - 24 May 2022

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Abstract

N-Alkyl pyrazoles are important heterocycles in organic and medicinal chemistry, demonstrating a wide range of biological activity. A new method for the N-alkylation of pyrazoles has been developed using trichloroacetimidate electrophiles and a Brønsted acid catalyst. These reactions provide ready access [...] Read more.

N-Alkyl pyrazoles are important heterocycles in organic and medicinal chemistry, demonstrating a wide range of biological activity. A new method for the N-alkylation of pyrazoles has been developed using trichloroacetimidate electrophiles and a Brønsted acid catalyst. These reactions provide ready access to N-alkyl pyrazoles which are present in a variety of medicinally relevant lead structures. Benzylic, phenethyl and benzhydryl trichloroacetimidates provide good yields of the N-alkyl pyrazole products. Unsymmetrical pyrazoles provide a mixture of the two possible regioisomers, with the major product being controlled by sterics. This methodology provides an alternative to other alkylation methods that require strong base or high temperature. Full article

(This article belongs to the Collection Advanced Research Papers in Organics)

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9 pages, 701 KiB

Open AccessReview

Diels–Alder Polar Reactions of Azaheterocycles: A Theoretical and Experimental Study

by Carla M. Ormachea, María Nélida Kneeteman and Pedro M. E. Mancini

Organics 2022, 3(2), 102-110; https://0-doi-org.brum.beds.ac.uk/10.3390/org3020008 - 22 May 2022

Cited by 1 | Viewed by 1585

Abstract

A number of azaheterocycles (pyridines, pyrroles and indoles) have been properly functionalized so that they can act as dienophiles in cycloaddition Diels–Alder processes. This work analyzed the reactive behavior of these molecules through mechanistic analysis and the regioselectivity of the process using computational [...] Read more.

A number of azaheterocycles (pyridines, pyrroles and indoles) have been properly functionalized so that they can act as dienophiles in cycloaddition Diels–Alder processes. This work analyzed the reactive behavior of these molecules through mechanistic analysis and the regioselectivity of the process using computational calculation tools. Based on this knowledge, a study was conducted on the influences of reaction variables, in particular solvent, catalyst and microwave irradiation, to achieve favorable changes—shorter reaction times, more acceptable temperatures and better yields. Theoretical calculations allowed the development of predictive approaches, which were later experimentally corroborated. This analysis allowed us to make reasonable assumptions related to reaction mechanisms, which allowed—through the analysis of corresponding transition states—us to consider such reactions at the boundary between pericyclic and polar processes. Full article

(This article belongs to the Special Issue Chemistry of Heterocycles)

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7 pages, 2400 KiB

Open AccessArticle

A Theoretical Study on the Photochemical Isomerization of 2,6-Dimethylpyrazine

by Maurizio D’Auria

Organics 2022, 3(2), 95-101; https://0-doi-org.brum.beds.ac.uk/10.3390/org3020007 - 12 May 2022

Cited by 1 | Viewed by 1546

Abstract

DFT calculations on the photoisomerization of 2,6-dimethylpyrazine allowed us to confirm the role of benzvalene isomers in the isomerization of hexatomic heterocyclic compounds. 2,6-Dimethylpyrazine in the excited singlet states can be converted into the corresponding Dewar isomers. If the S₂ state is [...] Read more.

DFT calculations on the photoisomerization of 2,6-dimethylpyrazine allowed us to confirm the role of benzvalene isomers in the isomerization of hexatomic heterocyclic compounds. 2,6-Dimethylpyrazine in the excited singlet states can be converted into the corresponding Dewar isomers. If the S₂ state is populated, two Dewar isomers can be obtained, while the S₁ state allows the formation of only one of the possible Dewar isomers. Both Dewar isomers can be converted into the benzvalene isomer, that is, the precursor of 4,5-dimethylpyrimidine, the reaction product. In fact, the benzvalene isomer can be obtained from the Dewar isomers in processes that occur without an activation energy, and it is the more stable benzvalene isomers that can be obtained from the Dewar isomers. CASSCF study indicates the presence of a conical intersection allowing the direct formation of the benzvalene isomer. Full article

(This article belongs to the Collection Advanced Research Papers in Organics)

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8 pages, 1920 KiB

Open AccessArticle

Stabilized Arylzinc Iodides in Negishi Acylative Cross-Coupling: A Modular Synthesis of Chalcones

by Michele Pierigé, Anna Iuliano, Gaetano Angelici and Gianluca Casotti

Organics 2022, 3(2), 87-94; https://0-doi-org.brum.beds.ac.uk/10.3390/org3020006 - 23 Apr 2022

Cited by 2 | Viewed by 2377

Abstract

Stabilized arylzinc iodides, synthesized by direct insertion of zinc into the corresponding halides, were used as nucleophiles into an acylative Negishi coupling reaction to synthesize chalcones. The reaction conditions were optimized to afford optimal results on a model reaction and then applied to [...] Read more.

Stabilized arylzinc iodides, synthesized by direct insertion of zinc into the corresponding halides, were used as nucleophiles into an acylative Negishi coupling reaction to synthesize chalcones. The reaction conditions were optimized to afford optimal results on a model reaction and then applied to synthesize nine compounds. Esters, chlorides, electron-rich, electron-poor and sterically hindered substrates are well tolerated and even heteroaryl derivatives can be synthesized. Full article

(This article belongs to the Collection Advanced Research Papers in Organics)

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10 pages, 1141 KiB

Open AccessArticle

β-Cyclodextrin Supramolecular Recognition of bis-Cationic Dithienylethenes

by Giulio Bianchini, Mattia Bazan, Fabrizio Fabris and Alessandro Scarso

Organics 2022, 3(2), 77-86; https://0-doi-org.brum.beds.ac.uk/10.3390/org3020005 - 06 Apr 2022

Viewed by 1712

Abstract

The supramolecular interactions in water between β-cyclodextrin and the open and closed photochromic forms of two bis-cationic dithienylethenes, characterized by different electronic properties, were investigated aiming at underlying the key aspects of the recognition process. The dithienylethene equipped with the cyclopentenyl [...] Read more.

The supramolecular interactions in water between β-cyclodextrin and the open and closed photochromic forms of two bis-cationic dithienylethenes, characterized by different electronic properties, were investigated aiming at underlying the key aspects of the recognition process. The dithienylethene equipped with the cyclopentenyl unit showed a difference in binding free energies to the β-cyclodextrin between the open and closed photochromic forms of about 1 kJ/mol. Conversely, the dithienylethene equipped with the perfluorinated cyclopentenyl unit not only was a better guest but showed a three times higher difference in the binding of free energies between the open and closed isomers. Full article

(This article belongs to the Special Issue Supramolecular Organic Chemistry)

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Organics, Volume 3, Issue 2 (June 2022) – 7 articles

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