Current Organic Synthesis - Volume 13, Issue 3, 2016

The reactions of sulfur ylides with carbonyl, olefin or imine compounds named as the Corey- Chaykovsky, provide oxiranes, cyclopropane or aziridine, respectively. In this report, we try to introduce this important name reaction and highlight a comprehensive overview on the applications of this useful reaction in synthetic organic chemistry and total synthesis of natural products.

This review involves the chemistry and biochemistry of lapachol, β-lapachone and lawsone, examples of bioactive natural products that still being under biological evaluation and stimulated several research groups to prepare derivatives and analogues and test them against several anticancer, trypanocidal, antinflammatory, tuberculostatic, and antimalarial targets, as well as other parasitology targets related to important infectious diseases.

The article covers some of the important prior art on solar-mediated organic transformations. It additionally highlights recent initiatives from our laboratory toward use of concentrated solar radiation to drive thermochemical and photo-thermochemical organic reactions. Solar radiation (800-1000 W m-2) comprises a continuum of photons of various wavelengths – from ultraviolet (uv) to visible (vis) to infrared (IR) – covering a part of the electromagnetic spectrum. In the context of organic synthesis, uv-vis radiation helps drive reactions via the excited state of substrate or reagent while IR radiation can provide thermal energy. Single sun exposure limits the photon flux and maximum attainable temperature. On the other hand, concentrated radiation provides higher photon flux and also helps generate higher temperatures. This assists in speeding up reactions and/or conducting reactions at larger scale. A laboratory scale solar photo-thermochemical reactor in V-trough configuration was developed that generated reaction temperatures up to 80 °C besides providing ca. two fold higher photon flux. It was used successfully to conduct a variety of photo-thermochemical bromination reactions in efficient manner. Benzylic bromination of p-methylstyrene-based inter-polymer film was also carried out successfully. Tandem reactions were also developed for the synthesis of more complex molecules such as oxazole derivatives from simple building blocks. The reactions presumably occurred via intermediate formation of halo derivatives. Radiation from parabolic dish concentrators provide still higher levels of concentration of solar radiation. These were used to drive useful thermochemical processes such as the energetically uphill conversion of dicyclopentadiene to cyclopentadiene (Cp) and further downstream processes such as Diels-Alder synthesis of a norbonadiene derivative from Cp. A continuous process of production of β-bromostyrene from cinnamic acid was also explored using radiation from a parabolic trough. Concentrated radiation was additionally employed for distillation of a variety of organic solvents.

Indan-1,3-dione is a versatile building block in organic synthesis. This review focuses on the applications of indan-1,3-dione to generate a large variety of indeno fused heterocycles such as Indeno-pyridine, diindenopyridine, indenoquinoline and indeno-cyclopenta-pyridine, indenofuran, indeno-indoloquinones, indenopyran, indenopyrimidine, indenotriazin-5-one, Indenoimidazole, indenopyrazoles and many others. Many of these molecules exhibit promising biological activities.

This review reports the methods developed for the synthesis of functionalized 1,2,4-triazines bearing phosphorus-amides as donor-acceptor interactions. These methods depend on the phosphorylation or phosphoimination of side functional groups of 1,2,4-triazine to produce isolated or fused phosphorus heterocyclic systems in view of their biocidal properties.

A new class of compounds, namely furo-imidazo-[3.3.3]propellanes can be synthesized by reaction of (1,3-dioxo-2,3-dihydro-1H-inden-2-ylidene)propanedinitrile with N-substituted (2-picolinoyl-, thiophene-2- carbonyl)hydrazinecarbo-thioamides 1a-f. 2,5-Disubstituted-2,3,4-oxadiazoles were also separated from this reaction as a minor product. The structures of products have been confirmed by using IR, NMR, mass spectrometry and single crystal X-ray analyses. A mechanism for the formation of the products is presented.

We have developed a simple, efficient and green method for the preparation of 2,4,5-triaryl imidazoles using propylene carbonate (PC) as an alternative solvent in the Radziszewski reaction, avoiding other organic solvents such as AcOH, MeOH, EtOH, DMSO and DMF. A wide range of 2,4,5-triaryl substituted imidazoles were synthesized. The nature of the substituents on the aromatic aldehyde had no significant effect on the reaction yield. PC offers advantages not only in the yield of the reaction but also in isolation of the product, which consists of a simple filtration followed by washes with warm water. The product was purified to a high analytical purity level by washing with hot hexane, (simple, single-step work-up). Thus, this protocol is practical and economically attractive.

Brønsted acid catalyzed azlactone ring opening by amino acids leading to the synthesis of dipeptides is presented. Eleven compounds were synthesized in good to excellent isolated yields. Catalyst loading revealed that 5.0 mol % of (+/-)-CSA as an organocatalyst, under room temperature for 24 h, was suitable to promote this transformation.

New thiazole and 1,3,4-thiadiazole derivatives were synthesized from the reaction of hydrazonoyl halides and each of 3-(4-fluorophenyl)-3,4,5,6-tetrahydrobenzo[6,7]cyclohepta[1,2-c]pyrazole-2(1H)-carbothioamide and (E)-3-[mercapto(phenylamino)methylene]-thiochroman-4-one, respectively. The structures of all the newly synthesized compounds were established by elemental and spectral analyses. All of the synthesized compounds were tested for anticancer activity against colon cancer cell line HT29, human breast cancer cells MCF-7 and human hepatocellular carcinoma cell line HepG2. Many derivatives of the tested compounds showed moderate to high anticancer activity. Also, molecular docking against HER2 kinase domain revealed high free binding energy and good binding mode. The structure activity relationship (SAR) of tested compounds was studied.

New series of substituted thiazole were prepared starting from thiosemicarbazone derivatives 1a,b by reacting with different reagents namely, hydrazonoyl chlorides, dimethyl acetylene dicarboxylate, phenacyl bromide, chloroacetone, and chloroacetic acid. The structures of the newly synthesized compounds were elucidated on the basis of elemental analyses and spectral data. Some representative examples of the newly synthesized compounds were screened as antitumor agents against all the 60 cell lines of the NCI-60 cell panels. The tested compounds were active only against MCF7, SF268, SF295, HT29, HT29, COLO205, COLO205, K562, HL60, A549-ATCC, H460, LOXIMVI, OVCAR3, OVCAR4, OVCAR5, OVCAR8, SKOV3, PC39, DU145 and A498 while inactive against other cell lines in the panel.

A series of new 5-imino-4-thioxo-2-imidazolidinone derivatives 3 with various halogenated and alkylated aromatic substituents at N1 and N3 was synthesized. Imidazolidineiminothione derivatives 3 were prepared from the reaction of N-arylcyanothioformamide derivatives with aryl isocyanates. These compounds were used as key synthons for the preparation of wide variety of new substituted imidazole compounds. Imine hydrolysis of 3 with ethanolic HCl produced the corresponding 4-thioxo-2,5-imidazolidindiones 4. Condensation of 3 with benzophenonhydrazone furnished the corresponding 4-azine derivatives 5. Monohydrazono and dihydrazono derivatives 6 and 8 were obtained upon treatment of imidazolidinone derivatives 3 with hydrazine hydrate. Finally, imidazolidinones 3 were reacted with o-phenylenediamines or pyrazol- 5(4H)-ones and afforded the corresponding imidazoquinoxaline and imidazolidin-4-ylidenepyrazolone-5(4H)-one derivatives 11 and 12, respectively. Evaluation of the antibacterial and antifungal activities for the synthesized compounds was carried out to probe their activities. Most of the tested compounds showed significant activities. The best antimicrobial activity was observed for 1-(3-ethoxyphenyl)-6- methyl-1-phenyl-1H-imidazo[4,5-b]quinoxalin-2(3H)-ones (11c) followed by 5-imino-3-(3-methoxy- phenyl)-1-phenyl-4- thioxoimidazolidin-2-one (3f).

Interesting and unexpected results on the cyanation of prochiral aldehydes catalyzed by chiral copper complexes of R-(+)/(S)-(-) α-ethylphenyl amine (I/II) in anhydrous methanol are presented. The cyanation reaction with chiral copper complexes of R-(+)/S-(-) α-ethylphenyl amines, acetols in methanol perform to afford a series of chiral products such as amines and acetonitriles (compounds 4-6, 8, 10 and 11). The obtained products are fully characterized by NMR, IR and X-ray analysis. The proposed mechanism for the formation of a series of chiral products can be concluded that methanol firstly promotes the decomposition of the copper complexes bearing R- (+)/S-(-) α-ethylphenyl amines to the ligand R-(+)/ S-(-)-α-ethylphenyl amine, which then conjugated with the initial TMS ether of the cyanohydrin or cyanohydrin to afford the chiral compounds 4-6, 8, 10 and 11.