Molecules

Research

Jump to: Review

10 pages, 1287 KiB

Open AccessArticle

Synthesis of Spirocyclopropane-Containing 4H-Pyrazolo[1,5-a]indoles via Alkylative Dearomatization and Intramolecular N-Imination of an Indole–O-(Methylsulfonyl)oxime

by Jiann-Jyh Huang, Hung-Chun Liao, Cheng-En Hsu, Yan-Ru Liu, Yi-Fu Chang and Shan-Yen Chou

Molecules 2023, 28(17), 6374; https://doi.org/10.3390/molecules28176374 - 31 Aug 2023

Viewed by 668

Abstract

In this paper, we report the synthesis of spirocyclopropane-containing 4H-pyrazolo[1,5-a]indoles 6a–e via alkylative dearomatization and intramolecular N-imination of indole–O-(methylsulfonyl)oxime 11. Starting materials tryptophol (7) and 2-bromocyclopetanone (8) were reacted [...] Read more.

In this paper, we report the synthesis of spirocyclopropane-containing 4H-pyrazolo[1,5-a]indoles 6a–e via alkylative dearomatization and intramolecular N-imination of indole–O-(methylsulfonyl)oxime 11. Starting materials tryptophol (7) and 2-bromocyclopetanone (8) were reacted in the presence of HBF₄·OEt₂, providing 1,2,3,5,6,11-hexahydrocyclopenta[2,3]oxepino[4,5-b]indole (9) in a 63% yield. Compound 9 was reacted with hydroxylamine hydrochloride to afford oxime 10 (65% yield), which was subsequently bis-methanesulfonated to form 11 in a 85% yield. Heating 11 with various alcohols in the presence of N,N-diisopropylethylamine (DIPEA) triggered the alkylative dearomatization and intramolecular N-imination, forming the spirocyclopropane and 4H-pyrazolo[1,5-a]indole structures in the targets 6a–e with 67–84% yields. Full article

(This article belongs to the Special Issue Feature Papers in Organic Chemistry (Volume II))

► Show Figures

Graphical abstract

17 pages, 4032 KiB

Open AccessArticle

Synthesis of a Series of Trimeric Branched Glycoconjugates and Their Applications for Supramolecular Gels and Catalysis

by Jonathan Bietsch, Anji Chen, Dan Wang and Guijun Wang

Molecules 2023, 28(16), 6056; https://doi.org/10.3390/molecules28166056 - 14 Aug 2023

Cited by 1 | Viewed by 926

Abstract

Carbohydrate-derived molecular gelators have found many practical applications as soft materials. To better understand the structure and molecular gelation relationship and further explore the applications of sugar-based gelators, we designed and synthesized eight trimeric branched sugar triazole derivatives and studied their self-assembling properties. [...] Read more.

Carbohydrate-derived molecular gelators have found many practical applications as soft materials. To better understand the structure and molecular gelation relationship and further explore the applications of sugar-based gelators, we designed and synthesized eight trimeric branched sugar triazole derivatives and studied their self-assembling properties. These included glucose, glucosamine, galactose, and maltose derivatives. Interestingly, the gelation properties of these compounds exhibited correlations with the peripheral sugar structures. The maltose derivative did not form gels in the tested solvents, but all other compounds exhibited gelation properties in at least one of the solvents. Glucose derivatives showed superior performance, followed by glucosamine derivatives. They typically formed gels in toluene and alcohols; some formed gels in ethanol-water mixtures or DMSO water mixtures. The glycoclusters 9 and 10 demonstrated rate acceleration for the copper-catalyzed azide-alkyne cycloaddition (CuAAC) reactions. These were further studied for their metallogels formation properties, and the copper metallogels from compound 9 were successfully utilized to catalyze click reactions. These metallogels were able to form a gel column, which was effective in converting the reactants into the triazole products in multiple cycles. Moreover, the same gel column was used to transform a second click reaction using different reactants. The synthesis and characterization of these compounds and their applications for catalytic reactions were discussed. Full article

(This article belongs to the Special Issue Feature Papers in Organic Chemistry (Volume II))

► Show Figures

Graphical abstract

11 pages, 868 KiB

Open AccessArticle

Bayesian Optimization-Assisted Screening to Identify Improved Reaction Conditions for Spiro-Dithiolane Synthesis

by Masaru Kondo, Hettiarachchige Dona Piyumi Wathsala, Kazunori Ishikawa, Daisuke Yamashita, Takeshi Miyazaki, Yoji Ohno, Hiroaki Sasai, Takashi Washio and Shinobu Takizawa

Molecules 2023, 28(13), 5180; https://doi.org/10.3390/molecules28135180 - 3 Jul 2023

Cited by 2 | Viewed by 1317

Abstract

Bayesian optimization (BO)-assisted screening was applied to identify improved reaction conditions toward a hundred-gram scale-up synthesis of 2,3,7,8-tetrathiaspiro[4.4]nonane (1), a key synthetic intermediate of 2,2-bis(mercaptomethyl)propane-1,3-dithiol [tetramercaptan pentaerythritol]. Starting from the initial training set (ITS) consisting of six trials sampled by random [...] Read more.

Bayesian optimization (BO)-assisted screening was applied to identify improved reaction conditions toward a hundred-gram scale-up synthesis of 2,3,7,8-tetrathiaspiro[4.4]nonane (1), a key synthetic intermediate of 2,2-bis(mercaptomethyl)propane-1,3-dithiol [tetramercaptan pentaerythritol]. Starting from the initial training set (ITS) consisting of six trials sampled by random screening for BO, suitable parameters were predicted (78% conversion yield of spiro-dithiolane 1) within seven experiments. Moreover, BO-assisted screening with the ITS selected by Latin hypercube sampling (LHS) further improved the yield of 1 to 89% within the eight trials. The established conditions were confirmed to be satisfactory for a hundred grams scale-up synthesis of 1. Full article

(This article belongs to the Special Issue Feature Papers in Organic Chemistry (Volume II))

► Show Figures

Figure 1

23 pages, 3422 KiB

Open AccessArticle

Are (Co)Polymers of 1,1,3,3,3-Pentafluoropropene Possible?

by Frédéric Boschet, Georgi Kostov, Hristina Raynova and Bruno Améduri

Molecules 2023, 28(12), 4618; https://doi.org/10.3390/molecules28124618 - 7 Jun 2023

Cited by 1 | Viewed by 1121

Abstract

The copolymerization and terpolymerization of 1,1,3,3,3-pentafluoropropene (PFP) with various combinations of fluorinated and hydrogenated comonomers were investigated. The chosen fluoromonomers were vinylidene fluoride (VDF), 3,3,3-trifluoropropene (TFP), hexafluoropropene (HFP), perfluoromethylvinyl ether (PMVE), chlorotrifluoroethylene (CTFE) and tert-butyl-2-trifluoromethacrylate (MAF-TBE), while the hydrocarbon comonomers were vinylene [...] Read more.

The copolymerization and terpolymerization of 1,1,3,3,3-pentafluoropropene (PFP) with various combinations of fluorinated and hydrogenated comonomers were investigated. The chosen fluoromonomers were vinylidene fluoride (VDF), 3,3,3-trifluoropropene (TFP), hexafluoropropene (HFP), perfluoromethylvinyl ether (PMVE), chlorotrifluoroethylene (CTFE) and tert-butyl-2-trifluoromethacrylate (MAF-TBE), while the hydrocarbon comonomers were vinylene carbonate (VCA), ethyl vinyl ether (EVE) and 3-isopropenyl-α,α-dimethylbenzyl isocyanate (m-TMI). Copolymers of PFP with non-homopolymerizable monomers (HFP, PMVE and MAF-TBE) led to quite low yields, while the introduction of VDF enabled the synthesis of poly(PFP-ter-VDF-ter-M₃) terpolymers with improved yields. PFP does not homopolymerize and delays the copolymerizations. All polymers were either amorphous fluoroelastomers or fluorothermoplastics with glass transition temperatures ranging from −56 °C to +59 °C, and they exhibited good thermal stability in air. Full article

(This article belongs to the Special Issue Feature Papers in Organic Chemistry (Volume II))

► Show Figures

Figure 1

17 pages, 3511 KiB

Open AccessArticle

The Unexpected Chemistry of Thiacalix[4]arene Monosulfoxide

by Kamil Mamleev, Václav Eigner, Hana Dvořáková and Pavel Lhoták

Molecules 2023, 28(9), 3914; https://doi.org/10.3390/molecules28093914 - 5 May 2023

Viewed by 1267

Abstract

Thiacalix[4]arene monosulfoxide 4 possesses a very unusual chemistry, as demonstrated by several unprecedented derivatives in calixarene chemistry. Interestingly, compound 4 cannot be prepared by the dealkylation of its corresponding tetramethoxy derivative using BBr₃. Instead, the borate complex is formed with a [...] Read more.

Thiacalix[4]arene monosulfoxide 4 possesses a very unusual chemistry, as demonstrated by several unprecedented derivatives in calixarene chemistry. Interestingly, compound 4 cannot be prepared by the dealkylation of its corresponding tetramethoxy derivative using BBr₃. Instead, the borate complex is formed with a boron bound by the two neighboring phenolic oxygens and a sulfoxide group. A similar type of borate complex with a spirodienone fragment was then isolated as a by-product. The oxidation of monosulfoxide with Chloramine-T did not provide the expected spirodienone moiety, but rather a complex oxathiane-based spiroheterocyclic part containing a chlorine atom. X-ray analyses confirmed the structures of the unusual products and feasible formation mechanisms were proposed. These results provide further evidence of the distinction between thiacalixarene chemistry and the chemistry of classical CH₂ analogues. Full article

(This article belongs to the Special Issue Feature Papers in Organic Chemistry (Volume II))

► Show Figures

Figure 1

0 pages, 2657 KiB

Open AccessArticle

New Insight into the Reactivity of S,S-Bis-ylide

by Ugo Authesserre, V. S. V. S. N. Swamy, Nathalie Saffon-Merceron, Antoine Baceiredo, Tsuyoshi Kato and Eddy Maerten

Molecules 2023, 28(8), 3295; https://doi.org/10.3390/molecules28083295 - 7 Apr 2023

Viewed by 1679

Abstract

The present work focuses on the reactivity of S,S-bis-ylide 2, which presents a strong nucleophilic character, as evidenced by reactions with methyl iodide and CO₂, affording C-methylated salts 3 and betaine 4, respectively. The derivatization of betaine 4 affords [...] Read more.

The present work focuses on the reactivity of S,S-bis-ylide 2, which presents a strong nucleophilic character, as evidenced by reactions with methyl iodide and CO₂, affording C-methylated salts 3 and betaine 4, respectively. The derivatization of betaine 4 affords the corresponding ester derivative 6, which is fully characterized by using NMR spectroscopy and X-ray diffraction analysis. Furthermore, an original reaction with phosphenium ions leads to the formation of a transient push–pull phosphino(sulfonio)carbene 8, which rearranges to give stabilized sulfonium ylide derivative 7. Full article

(This article belongs to the Special Issue Feature Papers in Organic Chemistry (Volume II))

► Show Figures

Figure 1

15 pages, 7171 KiB

Open AccessArticle

Thermal Rearrangement of 5-(2-Hydroxy-6-oxocyclohexyl)-5H-chromeno[2,3-b]pyridines

by Yuliya E. Ryzhkova, Fedor V. Ryzhkov, Michail N. Elinson, Anatoly N. Vereshchagin, Roman A. Novikov and Artem N. Fakhrutdinov

Molecules 2023, 28(7), 3139; https://doi.org/10.3390/molecules28073139 - 31 Mar 2023

Viewed by 1067

Abstract

Some of the most important transformations in organic chemistry are rearrangement reactions, which play a crucial role in increasing synthetic efficiency and molecular complexity. The development of synthetic strategies involving rearrangement reactions, which can accomplish synthetic goals in a very efficient manner, has [...] Read more.

Some of the most important transformations in organic chemistry are rearrangement reactions, which play a crucial role in increasing synthetic efficiency and molecular complexity. The development of synthetic strategies involving rearrangement reactions, which can accomplish synthetic goals in a very efficient manner, has been an evergreen topic in the synthetic chemistry community. Xanthenes, pyridin-2(1H)-ones, and 1,6-naphthyridines have a wide range of biological activities. In this work, we propose the thermal rearrangement of 7,9-dihalogen-substituted 5-(2-hydroxy-6-oxocyclohexyl)-5H-chromeno[2,3-b]pyridines in DMSO. Previously unknown 5,7-dihalogenated 5-(2,3,4,9-tetrahydro-1H-xanthen-9-yl)-6-oxo-1,6-dihydropyridines and 10-(3,5-dihalogen-2-hydroxyphenyl)-5,6,7,8,9,10-hexahydrobenzo[b][1,6]naphthyridines were synthesized with excellent yields (90–99%). The investigation of the transformation using ¹H-NMR monitoring made it possible to confirm the ANRORC mechanism. The structures of synthesized compounds were confirmed by 2D-NMR spectroscopy. Full article

(This article belongs to the Special Issue Feature Papers in Organic Chemistry (Volume II))

► Show Figures

Graphical abstract

Review

Jump to: Research

34 pages, 5195 KiB

Open AccessFeature PaperReview

Tinker, Tailor, Soldier, Spy: The Diverse Roles That Fluorine Can Play within Amino Acid Side Chains

by Samantha A. Miles, Joshua Andrew Nillama and Luke Hunter

Molecules 2023, 28(17), 6192; https://doi.org/10.3390/molecules28176192 - 22 Aug 2023

Cited by 5 | Viewed by 2072

Abstract

Side chain-fluorinated amino acids are useful tools in medicinal chemistry and protein science. In this review, we outline some general strategies for incorporating fluorine atom(s) into amino acid side chains and for elaborating such building blocks into more complex fluorinated peptides and proteins. [...] Read more.

Side chain-fluorinated amino acids are useful tools in medicinal chemistry and protein science. In this review, we outline some general strategies for incorporating fluorine atom(s) into amino acid side chains and for elaborating such building blocks into more complex fluorinated peptides and proteins. We then describe the diverse benefits that fluorine can offer when located within amino acid side chains, including enabling ¹⁹F NMR and ¹⁸F PET imaging applications, enhancing pharmacokinetic properties, controlling molecular conformation, and optimizing target-binding. Full article

(This article belongs to the Special Issue Feature Papers in Organic Chemistry (Volume II))

► Show Figures

Figure 1

23 pages, 7214 KiB

Open AccessReview

The Last Decade of Optically Active α-Aminophosphonates

by Petra R. Varga and György Keglevich

Molecules 2023, 28(16), 6150; https://doi.org/10.3390/molecules28166150 - 20 Aug 2023

Cited by 2 | Viewed by 1017

Abstract

α-Aminophosphonates and related compounds are important due to their real and potential biological activity. α-Aminophosphonates may be prepared by the Kabachnik–Fields condensation of oxo compounds, amines and dialkyl phosphites, or by the aza-Pudovik addition of the same P-reagents to imines. In this review, [...] Read more.

α-Aminophosphonates and related compounds are important due to their real and potential biological activity. α-Aminophosphonates may be prepared by the Kabachnik–Fields condensation of oxo compounds, amines and dialkyl phosphites, or by the aza-Pudovik addition of the same P-reagents to imines. In this review, the methods that allow for the synthesis of α-aminophosphonates with optical activity are surveyed. On the one hand, optically active catalysts or ligands may induce enantioselectivity during the Kabachnik–Fields reaction. On the other hand, asymmetric catalysis during the aza-Pudovik reaction, or hydrogenations of iminophosphonates, may prove to be a useful tool. Lastly yet importantly, it is possible to start from optically active reagents that may be associated with diastereoselectivity. The “green” aspects of the different syntheses are also considered. Full article

(This article belongs to the Special Issue Feature Papers in Organic Chemistry (Volume II))

► Show Figures

Scheme 1

26 pages, 6891 KiB

Open AccessReview

Arylcyanomethylenequinone Oximes: An Overview of Synthesis, Chemical Transformations, and Biological Activity

by Karolina Kula, Roman Nagatsky, Mikołaj Sadowski, Yevheniia Siumka and Oleg M. Demchuk

Molecules 2023, 28(13), 5229; https://doi.org/10.3390/molecules28135229 - 5 Jul 2023

Cited by 2 | Viewed by 1268

Abstract

Quinone methides are a class of biologically active compounds that can be used in medicine as antibacterial, antifungal, antiviral, antioxidant, and anti-inflammatory agents. In addition, quinone methides have the potential to be used as pesticides, dyes, and additives for rubber and plastics. In [...] Read more.

Quinone methides are a class of biologically active compounds that can be used in medicine as antibacterial, antifungal, antiviral, antioxidant, and anti-inflammatory agents. In addition, quinone methides have the potential to be used as pesticides, dyes, and additives for rubber and plastics. In this paper, we discuss a subclass of quinone methides: methylenequinone oximes. Although the first representatives of the subgroup were synthesized in the distant past, they still need to be additionally studied, while their chemistry, biological properties, and perspective of practical applications require to be comprehensively summarised. Based on the analysis of the literature, it can be concluded that methylenequinone oximes exhibit a diversified profile of properties and outstanding potential as new drug candidates and reagents in organic synthesis, both of electrophilic and nucleophilic nature, worthy of wide-ranging further research. Full article

(This article belongs to the Special Issue Feature Papers in Organic Chemistry (Volume II))

► Show Figures

Figure 1

21 pages, 6263 KiB

Open AccessReview

Analogy of the Reactions of Aromatic and Aliphatic π-Electrophiles with Nucleophiles

by Michał Barbasiewicz, Michał Fedoryński, Rafał Loska and Mieczysław Mąkosza

Molecules 2023, 28(10), 4015; https://doi.org/10.3390/molecules28104015 - 11 May 2023

Viewed by 1990

Abstract

The aim of this essay is to disclose the similarity of a great variety of reactions that proceed between nucleophiles and π-electrophiles—both aromatic and aliphatic. These reactions proceed via initial reversible addition, followed by a variety of transformations that are common for the [...] Read more.

The aim of this essay is to disclose the similarity of a great variety of reactions that proceed between nucleophiles and π-electrophiles—both aromatic and aliphatic. These reactions proceed via initial reversible addition, followed by a variety of transformations that are common for the adducts of both aliphatic and aromatic electrophiles. We hope that understanding of this analogy should help to expand the scope of the known reactions and inspire the search for new reactions that were overlooked. Full article

(This article belongs to the Special Issue Feature Papers in Organic Chemistry (Volume II))

► Show Figures

Graphical abstract

61 pages, 18718 KiB

Open AccessReview

Recent Advances in the Synthesis of Propargyl Derivatives, and Their Application as Synthetic Intermediates and Building Blocks

by Rodrigo Abonia, Daniel Insuasty and Kenneth K. Laali

Molecules 2023, 28(8), 3379; https://doi.org/10.3390/molecules28083379 - 11 Apr 2023

Cited by 4 | Viewed by 2683

Abstract

The propargyl group is a highly versatile moiety whose introduction into small-molecule building blocks opens up new synthetic pathways for further elaboration. The last decade has witnessed remarkable progress in both the synthesis of propargylation agents and their application in the synthesis and [...] Read more.

The propargyl group is a highly versatile moiety whose introduction into small-molecule building blocks opens up new synthetic pathways for further elaboration. The last decade has witnessed remarkable progress in both the synthesis of propargylation agents and their application in the synthesis and functionalization of more elaborate/complex building blocks and intermediates. The goal of this review is to highlight these exciting advances and to underscore their impact. Full article

(This article belongs to the Special Issue Feature Papers in Organic Chemistry (Volume II))

► Show Figures

Scheme 1

Journal Menu

Journal Browser

Feature Papers in Organic Chemistry (Volume II)

Share This Special Issue

Special Issue Editors

Special Issue Information

Published Papers (12 papers)

Research

Review

Further Information

Guidelines

MDPI Initiatives

Follow MDPI