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18 pages, 1822 KiB

Open AccessArticle

Pyrrolopyrimidines: Design, Synthesis and Antitumor Properties of Novel Tricyclic Pyrrolo [2,3-d]pyrimidine Derivatives

by Buer Song, Zarifa Murtazaeva, Lifei Nie, Rustamkhon Kuryazov, Shukhrat Gaybullaev, Chao Niu, Khurshed Bozorov, Haji Akber Aisa and Jiangyu Zhao

Molecules 2025, 30(14), 2917; https://doi.org/10.3390/molecules30142917 - 10 Jul 2025

Viewed by 965

Abstract

The pyrrolo[2,3-d]pyrimidine (7-deazapurine) scaffold is a unique heterocyclic system included in the composition of most nucleotides. In this study, series of the pyrrolo[2,3-d]pyrimidine-imines and 3-halo-substituted pyrrolo[2,3-d]pyrimidines were designed and prepared in high yields. Condensed pyrimidines [...] Read more.

The pyrrolo[2,3-d]pyrimidine (7-deazapurine) scaffold is a unique heterocyclic system included in the composition of most nucleotides. In this study, series of the pyrrolo[2,3-d]pyrimidine-imines and 3-halo-substituted pyrrolo[2,3-d]pyrimidines were designed and prepared in high yields. Condensed pyrimidines are obtained via carbonyl-amine condensation and carbon-halogen bond formation. Pyrrolo[2,3-d]pyrimidine-imines containing a bromine substituent at position C-4 of the phenyl ring and azepine side-ring exhibited superior antitumor activity on the colon cancer HT-29 cell line; IC₅₀ values were 4.55 and 4.01 µM, respectively. These results revealed an interesting pattern, where condensed pyrimidinones containing an azepine ring demonstrated selective antitumor activity on the colon cancer cell line HT-29. In addition, the molecular docking results suggest that compound 8g provided a thorough understanding of its interactions with the DDR2 active site. This could pave the way for further development and optimization of DDR-targeting drugs, contributing to advancements in cancer therapeutics. This lead compound may serve as design templates for further studies. Full article

(This article belongs to the Special Issue Aromatic Heterocyclic Compounds: Synthesis, Reactivity and Applications)

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12 pages, 2080 KiB

Open AccessArticle

The Reactions of Alkenes with Phenyl-N-triflylimino-λ³-iodane: Solvent and Oxidant Impact

by Mikhail Yu. Moskalik, Anton S. Ganin and Bagrat A. Shainyan

Int. J. Mol. Sci. 2023, 24(21), 15947; https://doi.org/10.3390/ijms242115947 - 3 Nov 2023

Cited by 3 | Viewed by 1376

Abstract

The reactions of alkenes with phenyl-N-triflylimino-λ³-iodane PhI=NTf (1) have been studied in different conditions. In methylene chloride, in the presence of N-halosuccinimides, the products of mono and bis-triflamidation were obtained. In MeCN, the product of bromotriflamidation [...] Read more.

The reactions of alkenes with phenyl-N-triflylimino-λ³-iodane PhI=NTf (1) have been studied in different conditions. In methylene chloride, in the presence of N-halosuccinimides, the products of mono and bis-triflamidation were obtained. In MeCN, the product of bromotriflamidation (with NBS) with solvent interception or of bis-triflamidation (with NIS) is formed. The reaction with trans-stilbene in acetonitrile with NBS gave rise to cyclization to 2-methyl-4,5-diphenyl-1-triflyl-4,5-dihydro-1H-imidazole. In contrast, with NIS as an oxidant, both in CH₂Cl₂ and MeCN, the major product was 2,3-diphenyl-1-triflylaziridine formed in good yield. With NBS, aziridine is also formed but as a minor product, the major one being a mixture of diastereomers of the product of bromotriflamidation. The reaction of compound 1 with vinylcyclohexane in methylene chloride affords the mixtures of regioisomers of the products of halotriflamidation, whereas in acetonitrile, the products of solvent interception and cyclization to the imidazoline are formed. A mechanism explaining the formation of all isolated products is proposed. Full article

(This article belongs to the Special Issue Recent Advances on Fluorine Chemistry)

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9 pages, 4383 KiB

Open AccessArticle

N-Iodosuccinimide as a Precatalyst for C–N Bond-Forming Reactions from Alcohols under Mild Reaction Conditions

by Njomza Ajvazi and Stojan Stavber

Catalysts 2022, 12(11), 1368; https://doi.org/10.3390/catal12111368 - 4 Nov 2022

Viewed by 2574

Abstract

We report an efficient and selective methodology for the direct cross-coupling of alcohols with N-nucleophiles mediated by N-iodosuccinimide (NIS) as the non-metal, commercially available, low-cost, and most effective precatalyst among the N-halosuccinimides (NXSs) under mild reaction conditions enhancing the green [...] Read more.

We report an efficient and selective methodology for the direct cross-coupling of alcohols with N-nucleophiles mediated by N-iodosuccinimide (NIS) as the non-metal, commercially available, low-cost, and most effective precatalyst among the N-halosuccinimides (NXSs) under mild reaction conditions enhancing the green chemical profiles of these reactions. The scale-up procedure was accomplished with almost quantitative yield, verifying the presented method’s synthetic applicability and potential for industrial application. Full article

(This article belongs to the Special Issue Feature Papers in Catalysis in Organic and Polymer Chemistry)

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11 pages, 4222 KiB

Open AccessArticle

Direct Cross-Coupling of Alcohols with O-Nucleophiles Mediated by N-Iodosuccinimide as a Precatalyst under Mild Reaction Conditions

by Njomza Ajvazi and Stojan Stavber

Catalysts 2021, 11(7), 858; https://doi.org/10.3390/catal11070858 - 17 Jul 2021

Cited by 3 | Viewed by 3864

Abstract

We report N-iodosuccinimide as the most efficient and selective precatalyst among the N-halosuccinimides for dehydrative O-alkylation reactions between various alcohols under high-substrate concentration reaction conditions. The protocol is non-metal, one-pot, selective, and easily scalable, with excellent yields; enhancing the green [...] Read more.

We report N-iodosuccinimide as the most efficient and selective precatalyst among the N-halosuccinimides for dehydrative O-alkylation reactions between various alcohols under high-substrate concentration reaction conditions. The protocol is non-metal, one-pot, selective, and easily scalable, with excellent yields; enhancing the green chemical profiles of these transformations. Full article

(This article belongs to the Special Issue Current State-of-the-Art of Catalysts)

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8 pages, 2783 KiB

Open AccessArticle

N-Iodosuccinimide as a Precatalyst for Direct Cross-Coupling of Alcohols with C-Nucleophiles under Solvent-Free Reaction Conditions

by Njomza Ajvazi and Stojan Stavber

Catalysts 2020, 10(8), 850; https://doi.org/10.3390/catal10080850 - 1 Aug 2020

Cited by 5 | Viewed by 4370

Abstract

C–C bond formation is one of the most important implements in synthetic organic chemistry. In pursuit of effective synthetic routes functioning under greener pathways to achieve direct C–C bond formation, we report N-iodosuccinimide (NIS) as the most effective precatalyst among the N [...] Read more.

C–C bond formation is one of the most important implements in synthetic organic chemistry. In pursuit of effective synthetic routes functioning under greener pathways to achieve direct C–C bond formation, we report N-iodosuccinimide (NIS) as the most effective precatalyst among the N-halosuccinimides (NXSs) for the direct cross-coupling of benzyl alcohols with C-nucleophiles under solvent-free reaction conditions (SFRC). The protocol is metal-free, and air- and water-tolerant, providing a large-scale synthesis with almost quantitative yields. Full article

(This article belongs to the Special Issue Organohalogen Chemistry and Catalysis)

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12 pages, 5331 KiB

Open AccessArticle

N-Halosuccinimides as Precatalysts for C-, N-, O-, and X-Nucleophilic Substitution Reactions of Alcohols under Mild Reaction Conditions

by Njomza Ajvazi and Stojan Stavber

Catalysts 2020, 10(4), 460; https://doi.org/10.3390/catal10040460 - 24 Apr 2020

Cited by 7 | Viewed by 4944

Abstract

N-halosuccinimides (chloro, bromo, and iodo, respectively) were introduced, tested, and applied as efficient and non-metal precatalysts for C-, N-, O-, and X-nucleophilic substitution reactions of alcohols under solvent-free reaction conditions (SFRC) or under high substrate concentration reaction conditions [...] Read more.

N-halosuccinimides (chloro, bromo, and iodo, respectively) were introduced, tested, and applied as efficient and non-metal precatalysts for C-, N-, O-, and X-nucleophilic substitution reactions of alcohols under solvent-free reaction conditions (SFRC) or under high substrate concentration reaction conditions (HCRC) efficiently and selectively, into the corresponding products. Full article

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17 pages, 4023 KiB

Open AccessArticle

Esterification of Aryl/Alkyl Acids Catalysed by N-bromosuccinimide under Mild Reaction Conditions

by Klara Čebular, Bojan Đ. Božić and Stojan Stavber

Molecules 2018, 23(9), 2235; https://doi.org/10.3390/molecules23092235 - 2 Sep 2018

Cited by 11 | Viewed by 8756

Abstract

N-halosuccinimides (NXSs) are well-known to be convenient, easily manipulable and low-priced halogenation reagents in organic synthesis. In the present work, N-bromosuccinimide (NBS) has been promoted as the most efficient and selective catalyst among the NXSs in the reaction of direct esterification [...] Read more.

N-halosuccinimides (NXSs) are well-known to be convenient, easily manipulable and low-priced halogenation reagents in organic synthesis. In the present work, N-bromosuccinimide (NBS) has been promoted as the most efficient and selective catalyst among the NXSs in the reaction of direct esterification of aryl and alkyl carboxylic acids. Comprehensive esterification of substituted benzoic acids, mono-, di- and tri-carboxy alkyl derivatives has been performed under neat reaction conditions. The method is metal-free, air- and moisture-tolerant, allowing for a simple synthetic and isolation procedure as well as the large-scale synthesis of aromatic and alkyl esters with yields up to 100%. Protocol for the recycling of the catalyst has been proposed. Full article

(This article belongs to the Special Issue Sustainable Synthesis)

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9 pages, 985 KiB

Open AccessArticle

Transformation of Tertiary Benzyl Alcohols into the Vicinal Halo-Substituted Derivatives Using N-Halosuccinimides

by Njomza Ajvazi and Stojan Stavber

Molecules 2016, 21(10), 1325; https://doi.org/10.3390/molecules21101325 - 2 Oct 2016

Cited by 11 | Viewed by 8285

Abstract

The efficiency of direct conversion of tertiary alcohols bearing a β-hydrogen atom to vicinal halohydrins—chlorohydrins and bromohydrins—under green reaction conditions was tested preliminarily on model tertiary benzyl alcohols. Tertiary alcohols were successfully directly halogenated to vicinal halohydrins with N-halosuccinimide in aqueous media. [...] Read more.

The efficiency of direct conversion of tertiary alcohols bearing a β-hydrogen atom to vicinal halohydrins—chlorohydrins and bromohydrins—under green reaction conditions was tested preliminarily on model tertiary benzyl alcohols. Tertiary alcohols were successfully directly halogenated to vicinal halohydrins with N-halosuccinimide in aqueous media. The efficiency of the reaction in water was significantly improved in the presence of sodium dodecyl sulphate as the surfactant. Full article

(This article belongs to the Special Issue Organic Reaction in Green Solvents)

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13 pages, 2315 KiB

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 18 | Viewed by 6668

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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19 pages, 889 KiB

Open AccessCommunication

Synthesis of Phenolic Compounds by Trapping Arynes with a Hydroxy Surrogate

by Rajdip Karmakar, Sourav Ghorai, Yuanzhi Xia and Daesung Lee

Molecules 2015, 20(9), 15862-15880; https://doi.org/10.3390/molecules200915862 - 31 Aug 2015

Cited by 33 | Viewed by 9375

Abstract

Trapping of arynes with various nucleophiles provides a range of heteroatom-functionalized arene derivatives, but the corresponding reaction with water does not provide phenol derivatives. Silver trifluroacetate (AgO₂CCF₃) can nicely solve this problem. It was found that in typical organic [...] Read more.

Trapping of arynes with various nucleophiles provides a range of heteroatom-functionalized arene derivatives, but the corresponding reaction with water does not provide phenol derivatives. Silver trifluroacetate (AgO₂CCF₃) can nicely solve this problem. It was found that in typical organic solvent, AgO₂CCF₃ readily reacts with arynes to generate trifluoroacetoxy organosilver arene intermediate, which, upon treating with silica gel, provides phenolic products. This protocol can be extended to the synthesis of α-halofunctionalized phenol derivatives by simply adding NBS (N-bromosuccinimides) or NIS (N-iodosuccinimides) to the reaction along with silver trifluroacetate, which provided α-bromo or α-iodophenol derivatives in good yield. However, the similar reactions with NCS (N-chlorosuccinimides) afforded only the protonated product instead of the expected α-chlorophenols derivatives. Interestingly, substrates containing silyl substituents on 1,3-diynes resulted in α-halotrifluoroacetates rather than their hydrolyzed product. Additionally, trapping the same arynes with other oxygen-based nucleophiles containing silver counter cation, along with NXS (N-halosuccinimides), generated α-halooxyfunctionalized products. Full article

(This article belongs to the Special Issue Development and Application of Aryne Chemistry in Organic Synthesis)

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23 pages, 591 KiB

Open AccessArticle

Brønsted Acidic Ionic Liquid Accelerated Halogenation of Organic Compounds with N-Halosuccinimides (NXS)

by Dejan Vražič, Marjan Jereb, Kenneth K. Laali and Stojan Stavber

Molecules 2013, 18(1), 74-96; https://doi.org/10.3390/molecules18010074 - 21 Dec 2012

Cited by 36 | Viewed by 8307

Abstract

The Brønsted-acidic ionic liquid 1-methyl-3-(4-sulfobutyl)imidazolium triflate [BMIM(SO₃H)][OTf] was demonstrated to act efficiently as solvent and catalyst for the halogenation of activated organic compounds with N-halosuccinimides (NXS) under mild conditions with short reaction times. Methyl aryl ketones were converted into α-halo [...] Read more.

The Brønsted-acidic ionic liquid 1-methyl-3-(4-sulfobutyl)imidazolium triflate [BMIM(SO₃H)][OTf] was demonstrated to act efficiently as solvent and catalyst for the halogenation of activated organic compounds with N-halosuccinimides (NXS) under mild conditions with short reaction times. Methyl aryl ketones were converted into α-halo and α,α-dihaloketones, depending on the quantity of NXS used. Ketones with activated aromatic rings were selectively halogenated, however in some cases mixtures of α-halogenated ketone and ring-halogenated ketones were obtained. Activated aromatics were regioselectively ring halogenated to give mono- and dihalo-substituted products. The [BMIM(SO₃H)][OTf] ionic liquid (IL-A) was successfully reused eight times in a representative monohalogenation reaction with no noticeable decrease in efficiency. An effective halogenation scale-up in this IL is also presented. The reactivity trend and the observed chemo- and regioselectiivities point to an ET process in these IL-promoted halofunctionalization reactions. Full article

(This article belongs to the Section Organic Chemistry)

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