Catalytic Reductive N‐Alkylations Using CO2 and Carboxylic Acid Derivatives: Recent Progress and Developments

N‐Alkylamines are key intermediates in the synthesis of fine chemicals, dyes, and natural products, and hence are highly valuable building blocks in organic chemistry. Consequently, the development of greener and more efficient procedures for their production continues to attract the interest of both academic and industrial chemists. Reductive procedures such as reductive amination or N‐alkylation through hydrogen autotransfer by employing carbonyl compounds or alcohols as alkylating agents have prevailed for the synthesis of amines. In the last few years, carboxylic/carbonic acid derivatives and CO₂ have been introduced as alternative and convenient alkylating sources. The safety, easy accessibility, and high stability of these reagents makes the development of new reductive transformations with them as N‐alkylating agents a useful alternative to existing procedures. In this Review, we summarize reported examples of one‐pot reductive N‐alkylation methods that use carboxylic/carbonic acid derivatives or CO₂ as alkylating agents.     

Preparative synthesis of cyclohexanone oxime esters

Preparative procedures have been developed for the synthesis of cyclohexanone oxime esters by acylation of cyclohexanone oxime with carboxylic acid anhydrides in the presence of perchloric acid or with carboxylic acid chlorides in the presence of pyridine.     

Chemical Preparation of Graphene Materials Results in Extensive Unintentional Doping with Heteroatoms and Metals

Chemical synthesis of graphene relies on the usage of various chemical reagents. The initial synthesis step, in which graphite is oxidized to graphite oxide, is achieved by a combination of chemical oxidants and acids. A subsequent chemical reduction step eliminates/reduces most oxygen functionalities to yield graphene. We demonstrate here that these chemical treatments significantly contaminate graphene with heteroatoms/metals, depending on the procedures followed. Contaminations with heteroatoms (N, B, Cl, S) or metals (Mn, Al) were present at relatively high concentrations (up to 3 at %), with their chemical states dependent on the procedures. Such unintentional contaminations (unwanted doping) during chemical synthesis are rarely anticipated and reported, although the heteroatoms/metals may alter the electronic and catalytic properties of graphene. In fact, the levels of unintentionally introduced contaminants on graphene are often higher than typical levels found on intentionally doped graphene. Our findings are important for scientists applying chemical methods to prepare graphene.     

A Facile Synthesis of 1,2-Anhydro-6-O-acetyl-3,4-di-O-benzyl-d-glycopyranoses and 1,2-Anhydro-5-O-acetyl-3-O-benzyl-D-glycofuranoses

The ability to couple carbohydrate entities to produce glycosides or higher oligomers is an important goal of synthetic organic chemistry.¹ For the past several decades, methods to construct glycosidic linkages have improved as a result of the development of glycosidation procedures.² However, owing to their structural complexity, synthesis of oligosaccharides is still a laborious task compared with the synthesis of oligopeptides and oligonucleotides. Many additional sugar derivatives which can improve and simplifjr synthetic procedures of oligosaccharides are needed.     

Advances in polymer based Friedlander quinoline synthesis

Nitrogen containing heterocyclic compounds has acquired their remarkable and distinct place in the wide area of organic synthesis due to the broad range of applications. Among them, quinoline motifs have attracted researchers in the synthetic chemistry because of its presence in the large number of pharmacologically active compounds. Different methods for synthesis of quinoline derivatives are reported, among them the Friedlander synthesis have provided comparatively more efficient approach. Many of the reported conventional Friedlander methodologies have some problems such as difficult product isolation procedures, poor yields and use of expensive catalysts, etc. Recently, polymer or solid supported synthetic approaches have attracted the attention of researchers because of their easy execution, greater selectivity, increased product yields, simple work-up procedures, recoverability and reusability of the catalysts. In consideration with the advantages of polymer supported synthetic strategies, the proposed review covers the role of polymers in the Friedlander synthesis; which may use polymers of organic, inorganic or hybrid in nature and of nanolevel as well.     

Eco-Friendly Microwave-Assisted Scaleable Synthesis of 2-Cyanobenzothiazoles via N -Arylimino-1,2,3-dithiazoles

Abstract

The cyclization procedure of N-aryl iminodithiazoles into 2-cyanobenzothiazoles was re-investigated with the aim to develop original and environmentally friendly procedures. In this article, the benefits associated with the microwave methodology are reported and the opportunity to use solvent-free procedures in order to scale up organic synthesis is studied. The result obtained show that the strong thermal effects due to graphite/microwaves interaction can be efficiently used for the synthesis of heterocyclic molecules for which traditional methods failed or are less attractive.     

Effect of metal ions in organic synthesis. Part XIV. A mild,simple, and convenient method for the synthesis of 1-(arylamino)pyrrole derivatives by copper(II) ion-catalyzed reaction of (arylazo)alkenes and 1,3-dicarbonyl compounds

A mild, simple and convenient method for the synthesis of some 1-(arylamino)pyrrole derivatives by copper(II) ion-catalyzed reaction of (arylazo)alkenes and 1, 3-dicarbonyl compounds is reported. These reactions take place under magnetic stirring at room temperature, do not require a strong acid or base, nor expensive or difficultly available reagents, nor even complicated procedures. The synthesis seems to be successfully applicable to different (arylazo)alkenes, 1, 3-diketones and ß-ketoesters, and frequently occurs with good yields.     

Zirconia‐based Aerogels via Hydrolysis of Salts and Alkoxides: The Influence of the Synthesis Procedures on the Properties of the Aerogels

This contribution aims at evaluating different synthesis procedures leading to zirconia‐based aerogels. A series of undoped and yttrium‐doped zirconia aerogels have been prepared via hydrolysis and condensation reaction of different alkoxy‐ and different inorganic salt‐based precursors followed by supercritical drying. Well‐established but deleterious zirconium n‐propoxide (TPOZ) or zirconium n‐butoxide (TBOZ) were used as metal precursors in combination with acids like nitric acid and acetic acid as auxiliary agent for the generation of non‐yttrium stabilized zirconia aerogels. Yttrium‐stabilized zirconia aerogels as well as pure zirconia aerogels were obtained by the salt route starting from ZrCl₄ and crosslinking agents like propylene oxide or acetylacetone. The characteristics of the products were analyzed by nitrogen adsorption measurements, electron microscopy, and X‐ray scattering. It turned out that with respect to all relevant properties of the aerogels as well as the practicability of the synthesis procedures, approaches based on inexpensive non‐toxic salt precursors are the methods of choice. The salt‐based approaches allow not only for low‐cost, easy‐to‐handle synthesis procedures with realizable gelation times of less than 60 seconds, but also delivered the products with the highest surface area (449 m² g^?1 for ZrCl₄) within this series of syntheses.     

Oxidative intramolecular coupling of 2, 3-disubstituted phenyl acrylic acids and derivatives promoted by di-tert-butylperoxide

Polymethoxy-substituted phenanthrene-9-carboxylic acids or their methylate are key intermediates for the synthesis of tylophora alkaloids and their analogs. An intramolecular oxidative coupling reaction of unfunctionalized 2,3-disubstituted phenyl acrylic acids and derivatives promoted by di-tert-butylper- oxide gave above intermediates in high yields. The mild reaction conditions and easy purification procedures of this method provide a new approach for the synthesis of phenanthrenes.     

Efficient and selective reduction protocols of the 2,2-dimethyl-1,3-benzodioxan-4-one functional group to readily provide both substituted salicylaldehydes and 2-hydroxybenzyl alcohols

Two complementary procedures have been developed that selectively allow for the synthesis of either substituted salicylaldehydes or the corresponding 2-hydroxylbenzyl alcohols upon treatment of the 2,2-dimethyl-1,3-benzodioxan-4-one functional group with DIBAL-H or LAH, respectively.     

Tunable magnetic arrangement of iron oxide nanoparticles in situ synthesized on the solid substrate from diblock copolymer micelles

Hexagonal arrangement of iron oxide nanoparticles was fabricated by utilizing a single-layered film of diblock copolymer micelles. The synthesis was directly performed on the solid substrate by oxygen plasma with preserving the dimensional order of micelles so that separate procedures for synthesis and deposition of nanoparticles were not necessary. Since the oxygen plasma treatment also eliminated polymers, pure patterns of iron oxide nanoparticles were obtained. Moreover, easy control over the size of nanoparticles enabled us to selectively create a ferrimagnetic or a superparamagnetic pattern of iron oxide nanoparticles without altering the fabrication process.     

Oligomeric guanidine synthesis assisted by TFA-sensitive arylsulfonylthiourea

Through arylsulfonyl activation of thiourea, efficient synthesis of oligomeric guanidines can be achieved in either solution or solid-phase. Incorporation of TFA-sensitive arylsulfonyl groups, such as Pbf, during the synthesis greatly simplifies deprotection procedures for obtaining the final oligomeric guanidine products.     

Efficient split synthesis for targeted libraries

We propose a new approach for fabricating more sophisticated combinatorial chemistry libraries via split synthesis and evaluate its potential through extensive simulation. Our algorithmically intensive method promises to reduce the time and materials costs of synthesizing libraries which are (1) too large to synthesize economically by sequential or parallel synthesis, (2) too long or irregular for conventional split synthesis generation techniques, and (3) not used in sufficient quantity to justify the setup costs of array makers. It also encourages the design of more focused and interesting libraries than are typically constructed using split synthesis. Our algorithms automate the design of efficient synthesis procedures for motif-based libraries which are too complex to design by hand. Our software allows the user to select the most desirable tradeoff between minimizing the number of steps in the synthesis process and containing the combinatorial explosion of the number of compounds synthesized.     

Enantioselective synthesis of non-natural aromatic alpha-amino acids

We present two complementary methods for the stereoselective synthesis of non-natural alpha-amino acids with aromatic or heteroaromatic side chains. One approach is based on the chemical transformation of methionine, whereas the other applies the stereoselective Myers alkylation of glycine. The resulting product types differ in the linker length between glycine and the aromatic substituent. Since methionine and pseudoephedrine are available in both absolute configurations, R- or S-configured enantiopure amino acids with either C(2) or C(3) linkers can be obtained on gram scales. In each case the key step of the synthesis is hydroboration of the unsaturated building blocks 9 and 17, followed by palladium-catalyzed Suzuki cross-coupling with aryl halides. Attention must in certain cases be paid to the stereochemical integrity when basic Suzuki conditions are applied. Our initial difficulties are reported as well as the final "racemization-proof" procedures. The protecting groups chosen for the alpha-amino acids should be compatible with solid-phase peptide synthesis. This was confirmed by the successful synthesis of a series of tripeptides.     

A facile synthesis of a polyhydroxylated 2-azabicyclo[3.2.1]octane

Synthetic or natural aza-sugars have shown promise as a therapeutic approach to a variety of disease states by acting as transition state mimics to sugar processing enzymes. Although the synthesis of functionalized bicyclo[3.2.1]octanes has been reported, the procedures are relatively long and low yielding. Herein, we report the facile synthesis of polyhydroxylated 2-azabicyclo[3.2.1]octane that can be selectively functionalized.     

Improved Methods for the Synthesis of N-Acyltetrahydroisoquinolines

One-pot procedures for the synthesis of N-acyltetrahydroisoquinolines have been developed from 2-phenylethylamines, acyl chlorides or carboxylic acids and aldehydes.     

New Synthetic Route to γ-Mercaptomethyl PNA Monomers

Peptide nucleic acids (PNAs) are oligonucleotide mimics widely used as antisense, antigene molecules, and biotechnological tools. Recently, several microarrays and other biosensors based on PNAs have been developed. The construction of PNA molecular beacons or light-up probes for DNA detection requires the labelling of the PNA moiety. Labels are usually attached at the C or N terminal end by a flexible linker or in the middle of a PNA sequence, substituting one PNA base with an artificial base or by attaching fluorophores to a modified PNA backbone. The need to develop simple protocols to label PNAs encouraged us to design a new procedure for the synthesis of γ-mercaptomethyl-modified PNA. Here we propose a new strategy for the synthesis of modified PNAs, bearing amino acid side chains. The synthesis is straightforward and is an improvement to the procedures reported so far, as it uses stable intermediates and proceeds with better yields.     

Zur Herstellung von 1,2,3-Tricarbonylverbindungen aus 1,3-Dicarbonylverbindungen. 27. Mitteilung über Reduktone und Tricarbonylverbindungen [1]

The synthesis of 22 substituted tricarbonyl compounds is reported. They were obtained either by oxidation of β-dicarbonyl compounds with SeO₂ or nitrous oxides or by oxidation of the α-bromo-β-dicarbonyl compounds with DMSO. The procedures using SeO₂ or DMSO are more rapid and give in general better yields than other methods described in the literature.