Current Organic Synthesis - Volume 15, Issue 4, 2018

Background: Pericyclic reactions characterized by a cyclic transition state, have been established as a dominant approach for the synthesis of heterocyclic scaffolds owing to their tremendous efficacy, regioselectivity, and enantioselectivity. Pericyclic chemistry is a promising and creative route to various biologically significant five and six membered oxygen or nitrogen ring systems. Recognizing the reaction's potential, synthetic organic chemists have invested significant efforts in developing and applying a seemingly endless array of useful variations of pericyclic reactions. Objective: The driving force of this review is to focus the character of perfection and beauty inherent in these powerful reaction pathways that lead to unique and densely functionalized heterocylic assemblies. Conclusion: In this review, we have presented recent strategic applications of pericyclic reactions that provide quick access to molecular complexity with high efficiency. A summary of these illustrative examples will showcase the extensive role of pericyclic chemistry in the construction of synthetically intimidating structural motifs.

Background: Although the chemistry of heteroaromatic monoamino azoles has been surveyed more than once in the last decade, the chemistry of the di- and triaminoazoles has not been reviewed. In this article we will survey the synthesis, chemistry and utility of the diaminoazoles. In this review, the chemistry of the diaminoazoles as well as their most important utilities will be surveyed. Objective: The review focuses on recent progress in diaminoazoles (i.e. diaminopyrazoles, diaminoimidazoles, diaminotriazoles and diaminothiazole) with especial references to diaminopyrazoles. The synthesis as well as pharmaceutical utilities are reported. There are several methods for synthesis of diaminopyrazoles. 3,5- Diaminopyrazole and its derivatives are prepared through the reaction of malononitrile or arylhydrazononitrile with hydrazine derivatives. 3,4-Diaminopyrazoles are prepared via nitration of 3-aminopyrazole with subsequent reduction of the produced compound. The diaminopyrazoles have several applications in cosmetic and pharmaceutical industries. They also have useful utilities as a constituent in oxidative hair dyes. Conclusion: We managed to report the common methods for the synthesis of diaminoazoles with especial reference to aminopyrazoles that are prepared through the reaction of malononitrile or hydrazononitriles with hydrazine derivatives. Some important applications that include pharmaceutical utilities such as hair dye constituents are reported.

Background: Increasing use of the three-membered ring in drug development initiates the search for efficient methods of transformations of cyclopropane derivatives. Oxidation of methylene group activated by an adjacent cyclopropane represents a direct approach towards carbonylcyclopropanes, allows avoiding unnecessary synthetic stages and meets the requirements of atom economy. Objective: In this review all available data concerning the oxidation of cyclopropane-containing hydrocarbons and their functionally substituted derivatives are systematized, and the general regularities between the structure of the starting compound, the oxidant employed and the reaction outcome are underlined. Conclusion: The following regularities were distinguished for the oxidation of cyclopropane-containing compounds into cyclopropylketones. The main structural parameters of the starting compounds, which influence the distribution of the oxidation products, are the followings: the presence of competing C-H bonds, flexibility or rigidity of structure, electron and sterical substituents effects. A number of preparative methods of activated C(sp3)-H bonds oxygenation were elaborated, employing such powerful oxidants as ozone, dioxiranes, CrO3 and a variety of catalytic systems, based on transition metals. For the oxidation of cyclopropane derivatives all these oxidants may be employed. RuO4, generated in situ, usually behaves as selective and soft oxidant. TFDO often demonstrates lesser selectivity, but it may be the best choice when several activated CH2 groups should be oxidised. In the case of dihalocyclopropanes the use of CrO3 is preferable. Summarily, the oxidation of methylene group adjacent to cyclopropane has been undoubtedly developed into a reliable preparative approach to cyclopropylketones, which should find an active use in synthetic organic chemistry.

Aim and Objective: In this study, for the first time keplerate cluster [Cu20Cl(OH)24(H2O)12 (P8W48O184)]25- (hereafter [W48P8Cu20]) was supported on SMNP (Fe3O4-@SiO2) via amine functionality (ASMNP) as a magnetically-recoverable catalyst (hereafter [WPCu@ASMNP]). This nanocatalyst showed high activity for the synthesis of cyclic carbonates under solvent-free conditions. Materials and Methods: After preparation, the nanocatalyst was characterized by FT-IR, XRD, ICP-AES, TGA, TEM and SEM. Surface acidity was determined by a potentiometric titration with n-butyl amine. The effect of different parameters like catalyst amount, reaction time, temperature and pressure in the presence of [WPCu@ASMNP] were studied. Results: Optimal reaction conditions were obtained for 0.5mol% of catalyst, reaction temperature of 100°C and CO2 pressure of 1.5 MPa. The [WPCu@ASMNP] could be separated from the reaction and reused for five times with an external magnet without notable decrease in the activity. Finally, stability of the catalyst and its reusability were evaluated using a hot filtration method. The FT-IR and the control experiments (hot filtration) after five cycles confirmed the strongly catalyst immobilization to the ASMNP. Conclusion: The nanocatalyst is shown to be effective heterogeneous and recyclable catalyst for the synthesis of cyclic carbonates from CO2 and epoxides under mild conditions without any additional co-solvent and cocatalyst. This catalyst has a good substrate tolerance as demonstrated by its activity towards different epoxides. Importantly, the reaction could be carried out under solvent free conditions. The heterogeneous nature of the catalyst is proved by recovering and reusing this catalyst without any appreciable loss in catalytic activity and by the FT-IR spectroscopic characterization of the fresh and spent catalyst. The product separation and catalyst recycling are short using an external magnet.

Aim and Objective: The development of small molecules that can interact with key therapeutic target represents an active field of research. Therefore, new approaches for increasing the molecular diversity of a starting material, such as a natural product, are needed. Herein, the carbonyl group present on a pregnane scaffold, or easily obtained from the oxidation of the corresponding alcohol, was used to obtain a series of diversified steroidal morpholinone derivatives. Materials and Methods: Using chemical synthesis, two levels of molecular diversity were introduced at position 20 of a C21-steroid scaffold. Nuclear magnetic resonance (NMR) spectroscopy and x-ray analysis were next used to characterize the morpholinone derivatives. Results: The C-20 carbonyl of pregnenolone was first transformed into an oxirane that reacted with an amino acid and the resulting amino alcohol was then cyclized to generate different spiro-2-morpholinones. X-ray analysis of one representative compound confirmed the 3-dimensional representation of this new family of diversified steroid derivatives. NMR analysis supported the expected structure and identified key markers of the chiral center configuration found in the 2-morpholinone moiety. Finally, the NH of the morpholinone ring was alkylated, thus increasing structural diversity. Conclusion: Considering the huge amount of building blocks (amino acids, bromobenzyl derivatives and ketones) that are commercially available, the strategy reported herein opens the door to the synthesis of diversified libraries of new compounds.

Aim and Objective: The aim of our work is to demonstrate catalytic application of our previously reported simple Cu(I) ion supported on weakly acidic polyacrylate resin for Azide-Alkyne cycloaddition (CuAAC), Azide-Nitrile cycloaddition and in synthesis of 1-azido-4-methoxybenzene. Material and Method: To investigate the catalytic ability of title Cu(I) catalyst we performed the reaction of different aryl azide with a broader spectrum of different terminal alkyne and nitrile compounds. Results: The title supported Cu(I) catalyzes cycloaddition reactions of aryl azide with aliphatic, aromatic, and heterocyclic terminal alkynes and corresponding 1,4-disubstituted 1,2,3-triazoles were obtained almost in the quantitative yields. The cycloaddition reactions of aryl azide with nitriles consisting α-hydrogen on carbon attached to cyano group under catalytic action of the title supported Cu(I) ended up with the formation of 1,4- disubstituted 1,2,3-triazol-5-amines in quantitative yields. The title catalyst found to be active for nucleophilic substitution of aide group (-N3) to 4-Iodoanisole. Conclusion: It was found that both studied Azide-Alkyne cycloaddition and Azide-Nitrile cycloaddition syntheses are regioselective and quantitative in yield. The title catalyst used is economical, easily preparable, separable, and recyclable. Therefore, the studied syntheses may be regarded as environmentally clean and green processes.

Background: Ring opening metathesis polymerization of lactones using alkylidene catalysts is an alternative to obtain unsaturated linear polyesters with remarkable thermal and mechanical properties. Also, these polyesters have properties of biodegradability which opens up a wide range of applications as environmentally friendly thermoplastics and biomaterials. Objective: This research aims to present one route to obtain an unsaturated linear polyester poly(ω-6- hexadecenlactone) via ring opening-metathesis polymerization of ω-6-hexadecenlactone using the rutheniumalkylidene [Ru(Cl)2(=CHPh)(PCy3)2] (I), [Ru(Cl2)(=CHPh)(1,3-bis(2,4,6-trimethylphenyl)-2-imidazolidinylidene)( PCy3)] (II) and [Ru(Cl2)(=CH(o-isopropoxyphenylmethylene))(1,3-bis(2,4,6-trimethylphenyl)-2-imidazolidinylidene)] (III) and the ruthenium-vinylidene [RuCl2(=C=CH(p-C6H4CF3))(PCy3)2] (IV) catalysts. Conclusion: The high number-average molecular weights of the poly(ω-6-hexadecenlactone) between Mn = 114,800-155,400 g/mol and yields ranging from 96 to 98 % can be achieved by II and III catalysts. The catalysts II and III with the N-heterocyclic carbene ligand showed superior activity and stability upon catalysts I and IV bearing PCy3 ligands. The hydrogenation of poly(ω-6-hexadecenlactone) using Wilkinson catalyst [RhCl(PPh3)3] was studied. The percent crystallinity of the unsaturated poly(ω-6-hexadecenlactone) was 31% with a melting temperature 47.60ºC. Stress-strain measurements of several poly(ω-6-hexadecenlactone) were determined.

Aim and Objective: Itopride is a prokinetic agent used for treating conditions like non-ulcer dyspepsia. Itopride is administered as its hydrochloride salt. Trimethobenzamide is used for treating nausea and vomiting and administered as its hydrochloride salt. The aim is to develop a novel and environmental friendly method for large-scale production of itopride and trimethobenzamide. Materials and Methods: Itopride and trimethobenzamide can be prepared from a common intermediate 4- (dimethylaminoethoxy) benzyl amine. The intermediate is prepared from one pot synthesis using Phyrdroxybenzaldehye and zinc dust and further reaction of the intermediate with substituted methoxy benzoic acid along with boric acid and PEG gives itopride and trimethobenzamide. Results: The intermediate 4-(dimethylaminoethoxy) benzylamine is prepared by treating p-hydroxybenzaldehyde and 2-dimethylaminoethyl chloride. The aldehyde formed is treated with hydroxylamine hydrochloride. The intermediate is confirmed by NMR and the purity is analysed by HPLC. Conclusion: Both itopride and trimethobenzamide were successfully synthesized by this method. The developed method is environmental friendly, economical for large-scale production with good yield and purity.