Letters in Organic Chemistry - Volume 13, Issue 1, 2016

Background: Fullerenes are of the most useful structures which could be used in making nano sized instruments. These small carbon cages are important in designing synthesized nano structures. In order to use the fullerenes in the nano structures, functionalizing the surface of these compounds may be required. Considering this fact, many attempts have been already taken to find certain ways to functionalize these substances. Methods: Several different geometries were assumed for each species in order to be used as input files, followed by optimization to give the most possible states. The structures corresponding to the reactants, TS, and product were optimized and the electronic structures and harmonic vibrational frequencies of all stationary points along the reaction pathway were calculated. Results: The present research introduces an ultra-fast way for the functionalization of C20 fullerene via its diels-alder reaction with 1,3-butadiene. The reaction proceeds via a transition state with a relatively high asynchronous mechanism. This method facilitates the attachment of C20 fullerene and its derivatives to chemical species with a 1,3-diene functional group, and therefore it could provide a suitable approach in synthesizing some of the nano-sized molecules, devices or machines. Conclusion: The present way seems to be faster than other methods which have been already reported on the functionalization of C20 fullerene. The results showed that at least in this case, pericyclic reaction could carry out the functionalization of this small carbon cage with no need to a solvent engagement or any other accelerating agents such as catalysts, light or heat.

Background: Sulforaphane [1-isothiocyanato-(4-methylsulfinyl)butane] identified from Brassicaceae appears to possess health benefits such as activities against breast, skin and prostate cancer and diabetes.in vitro and in vivo studies provide evidence that it can provide protection at every stage of cancer progression. Sulforaphane was firstly synthesized by Von Schmidt and P.Karrer in 1948 via phthalimide route but after Zhang and co-worker reported its bioactivity in 1992, the chemical synthesis of sulforaphane by alternate route has attracted several research groups in the past 20 years . Methods: The synthesis started with the preparation of S-methylthiolanium tetrafluoroborate by sonication of thiolane (1) with methyl iodide followed by anionic metathesis with NaBF4 in n-butanol to give thiolanium tetrafluorborate (2). The ring opening of 2 by SN2 is conducted in 16 hours at 60 °C (as indicated by TLC) to obtain 1-azido-(4- methylsulfinyl)butane (3). Conversion 3 into Erucin (4) was successfully obtained by Staudinger reaction, followed by oxidation of 4 in transition metal-free condition (H2O2/ glacial acetic acid) to give sulforaphane in racemic form. Results: Sulforaphane was obtained with 41% yield overall via only four steps with high purity without column chromatography. The approach not only opened up a new synthetic pathway to this naturally occurring isothiocyanate and its analogues, but also suggested a possible solution for converting by-products in petroleum refining processes into useful compounds. Conclusion: Sulforaphane was successfully synthesized from thiolane, a waste product in petroleum processing in a simpler and more efficient fashion, eco-friendy approach. All products were obtained in high yield and high purity. In comparison with previously reported strategies, this new approach is believed to be the shortest and the most efficient synthetic route to date.

Background: Now a day’s green synthesis for multicomponent reactions is a powerful tool for construction of five membered/six membered heterocyclic ring systems. The synthesis of regio and stereoselective complex architectural motifs following 1,3-dipolar cycloaddition reactions via ecofriendly methods are well reported. The synthesis of pyrrolidine/piperidine based heterocycles has been the center of attraction because of their pronounced biological activities. Methods: The present methodology deals with one pot three component cycloaddition reaction of isatin based azomethine ylide and substituted nitrochromene to synthesize new spirooxindole-pyrrolidine/piperidine fused nitrochromanes in refluxing ethanol within 2 hr. Results: A series of new spirooxindole-pyrrolidine/piperidine fused nitrochromanes were synthesized in good to excellent yield (78-89%) via one pot three component cycloaddition reactions. The obtained products were isolated in good yield by simple filtration. All the synthesized compounds were well characterized (1H, 13C, Mass and M.P). The regio/ stereochemical results were ascertained by X-ray crystallographic study. Conclusion: We have developed an ecofriendly method to synthesize twelve new and novel spirooxindolepyrrolidine/ piperidine fused nitrochromanes via one pot three component 1,3-dipolar cycloaddition reaction in nontoxic solvent in a shorter time. It offers several advantages such as regio/stereoselective synthesis of spirooxindolepyrrolidine/ piperidine fused nitrochromanes, shorter reaction time, mild reaction conditions, simple and environmentally friendly operational procedure.

Background: Several steroid derivatives have been prepared using different protocols. The aim of study involved the synthesis of a diazepin-steroid derivative using androsterone as chemical tool. Methods: Diazepin-steroid derivative was prepared by a series of reactions that involve; 1) Protection of the hydroxyl group from androsterone with tert-Butyldimethylsilyl chloride to form (3R,10S,13S)-3-((tert-butyldimethylsilyl)oxy)- 10,13-dimethylhexadecahydro-17H-cyclopenta[a]phenanthren-17-one (3-TBDS-androst-17-one); 2) catalytic α-hydroxylation of 3-TBDS-androst-17-one for preparation of 3-TBDS-16-hydroxy-steroid-17-one; 3) Reaction of 3-TBDS-16- hydroxy-steroid-17-one with p-nitrobenzoyl azide to form 3-TBS-17-oxo-steroid-triazadienium; 4) synthesis of a triazolsteroid derivative by reaction of 3-OTBS-17-oxo-steroid-triazadienium with 1-hexyne; 5) Removal of tert-Butyldimethyl- silanyloxy of the triazol-steroid derivative with hydrofluoric acid to form 16-triazole-3-hydroxy-steroid-17-one; 6) Reaction of 16-triazole-3-hydroxy-steroid-17-one with dimethyl sulfoxide to form the 16-triazole-steroid-3- carbaldehyde derivative; 7) synthesis of a enone-steroid derivative by the reaction of 16-triazole-steroid-3-carbaldehyde with acetophenone; 8) Reaction of ethylenediamine with the enone-steroid derivative for synthesis of a diazepin-steroid derivative. The structure of all compounds obtained was confirmed by spectroscopic and spectrometric methods. Results: The 1H NMR spectrum of diazepin-steroid shows signals at 0.85 and 1.06 ppm for methyl groups bound to steroid nucleus; at 0.90 for methyl group of arm bound to triazole ring; at 0.93-1.04, 1.14-1.36, 1.44-1.74, 1.90, 2.30, 2.60- 2.80 and 5.40 ppm for steroid moiety; at, 1.40, 1.80 and 2.44 ppm for methylene groups of arm bound to triazole ring; at 3.10, 3.12, 3.60 and 3.82 ppm for methylene bound to both amino and imino groups; at 3.22-3.56, 3.66 and 4.80 ppm for diazepine ring; 3.10, 3.12, 3.60 and 3.82 ppm for methylene groups bound to both amino and imino groups; at 5.60 ppm for amino groups; at 6.84 ppm for triazole ring; at 6.62-6.80 and 7.34-7.90 ppm for phenyl groups. The 13C NMR spectra displays chemical shifts at 14.30 ppm for methyl group of arm bound to triazole ring; at 11.66 and 16.30 ppm for methyl groups bound to steroid nucleus; at 20.62, 27.60-36.70, 41.20, 42.58, 46.70-48.88, 54.32 and 55.00 and 82.00 ppm for steroid moiety; at 24.18-27.16 ppm for methylene groups of arm bound to triazole ring; at 115.70, 142.60 ppm for triazole ring; at 41.00, 41.32, 54.46, 57.77 and 163.18-165.30 ppm for methylene groups bound to both amino and imino groups; at 44.38, 53.00 and 95.60 ppm for diazepine ring; at 116-138.30 and 154.40 ppm for phenyl groups; at 148.50 and 172.62 ppm for imino groups. In addition, the presence of compound diazepin-steroid was confirmed with mass spectrum which showed a molecular ion at m/z 773.54. Conclusions: In this study is reported a straightforward route for synthesis of a Diazepin-steroid derivative using some strategies. The proposed methods offer some advantages such as simple procedure and ease of workup.

Background: Recently, the author of the article proposed a new index for the estimation of the aromatic character. The aromaticity index D, D usually obtained by using DFT/B3LYP/6-311G+(d,p) theoretical method. Method: The D index was tested using different functionals: LSDA, BVP86, B3LYP, CAM-B3LYP, B3PW91, mPW1PW91, PBEPBE, HSE1PBE, HCTH, TPSSTPSS, and wB97XD. Results: The results showed that the D values for monocyclic aromatic compounds are not largely sensible to the variation of the functional. Large variations of D values were observed for polycyclic aromatic compounds. D values were correlated to ERE (experimental resonance energy) and ASE (aromatic stabilization energy). ERE and ASE gave different correlations with D. Conclusion: The best correlation between D and ERE was obtained by using CAM-B3LYP. The best correlation between D and ASE was obtained by using CAM-B3LYP.

Background: Total water resources account for only 2.5% of freshwater on earth, and only 1% of total water resources can be exploited by humans. The development of practical methods of seawater desalination and comprehensive utilization technology can help address the shortage of freshwater resources in the world, and achieve sustainable use of water resources to ensure sustainable development in a society. Direct seawater utilization currently involves industrial cooling water, water for agricultural irrigation, and flushing water. Applications in aqueous phase organic reactions, particularly the direct use of seawater in industrial organic synthesis reactions, are seldom reported. Methods: we used seawater instead of freshwater in selected basic organic chemical reactions. The application of seawater in aqueous phase organic reactions was systematically investigated. Six types of reactions were studied using freshwater and seawater, namely, preparation of acetanilide, synthesis of mandelic acid, Cannizzaro reaction, Hofmann degradation reaction, preparation of quinazolin-4-one, and preparation of adipic acid. Results: Seven organic compounds were produced. Results show that some organic reactions could directly use seawater or treated seawater as an alternative to freshwater. The yields of the reactions using seawater could be compared with literature values, or were even better than literature values. Conclusion: This research provides new opportunities for the comprehensive utilization of seawater. Some organic reactions could directly use seawater or treated seawater instead of freshwater. The use of seawater instead of freshwater for organic reactions in industrial production may greatly conserve freshwater resources and protect the environment.

Background: In the current decade, organotrifluoroborates have attained remarkable development in Chemistry and Materials. This can be evidenced by the increasing number of articles, review articles and patents devoted to this subject. As a consequence, the number of citations derived from papers dealing with this subject has experienced an exponential growth in the last years. The aim of this paper to describe a methodology based on the use of potassium allyltrifluoroborate for the synthesis of homoallylic alcohols using water as a co-solvent and under mild reaction conditions. Methods: The methodology is very robust (wide range of aldehydes) and simple, it uses low catalyst loadings and it is synthetically useful because it could be applied for the synthesis of more complex compounds. In addition, detailed experimental procedures, including the preparation of the starting materials, as well as the corresponding 1H, 13C, 19F and 11B spectra for all synthesized compounds are provided. Results: The method is environmentally friendly while it uses water as a solvent and the desired compounds containing different functionalities were obtained in moderate to good yields (60-93%) without the need of further purification in a very chemo- and regioselective way. Conclusion: Salicylic acid can efficiently promote the allylation of aldehydes using potassium allyltrifluoroborate at room temperature to yield the corresponding homoallylic alcohols in moderate to good yields. The method is efficient and environmentally friendly while it uses water as co-solvent. In addition the method is regio- and chemoselective and could be applied in the synthesis of more complex homoallylic alcohols.

An expeditious and environmentally friendly approach for the synthesis of 14-aryl-14 Hdibenzo[ a,j]xanthenes via the multicomponent condensation reaction between different aromatic aldehydes and β-naphthol catalyzed by Nano-alumina sulfuric acid (N-ASA) under thermal and solventfree conditions has been studied. Notably, the present method offers desirable advantages of high yields, simplicity of work-up procedure, easy purification, reduced reaction times and reusability of the catalyst. Characteristics of nano-alumina sulfuric acid were determined using X-Ray diffraction (XRD), scanning electron microscope (SEM), transmission electron microscope (TEM) and FT-IR spectroscopy.

Background: Benzimidazoles exhibit a wide range of biological activities, including antiparasitic, antiulcer, antihypertensive, antihistaminic, anticancer, antiemetic and antiinflammatory agents. Methods: Tetraethylammonium superoxide has been generated in situ by the phase transfer reaction of potassium superoxide and tetraethylammonium bromide in dry dimethylformamide at room temperature and subsequently allowed to react with a number of Schiff's bases. Results: The Synthesis of 2-arylbenzimidazoles from Schiff bases using in situ generated tetraethylammonium superoxide in dry DMF, at room temperature. Conclusion: The role of in situ generated Et4NO2 as an efficient agent to promote the synthesis of 2-arylbenzimidazole from Schiff base has been demonstrated under mild conditions.

Background: Cytofectins are a class of positively charged lipid molecules that can facilitate the functional entry of polynucleotides, macromolecules, and small molecules into living cells, escaping lysosomal degradation. One of the most potent cytofectins, dimyristoyl Rosenthal inhibitor ether (DMRIE), is presently being used to deliver differents active molecules into animal and human diseased tissues. To our knowledge, two synthetic routes for the preparation of DMRIE have so far been reported. One of them is based on the reaction of epichlorhydrin with either dimethylamine chloride or dimethylamine using an alkaline solution as solvent. The main disadvantage of these routes is the formation of 3-(N,N-diamino)-1,2-propanediol. In summary, the synthetic routes mentioned use epichlorohydrin or glycidol as starting materials, both of which have been described as carcinogenic agents. Additionally, sometimes the reaction conditions are drastic. An alternative route for the preparation of other cytofectins is the use of glycerol as the starting material. Glycerol is a non-carcinogenic compound, but its use as starting material results in an increased number of steps of this reaction, generating an increase in the total time of synthesis and the formation of a greater amount of waste and scrap. Based on the above, here we propose a new chemoenzymatic synthetic strategy using glycerol as a starting material. Methods: Initially, glycerol and vinyl benzoate were mixed in presence of Mucor miehei lipase (Lipozyme), it is converted into corresponding mono-benzoate (±)-1. Finally, DMRIE was obtained by the reaction of bromide (±)-3 with 2- dimethylaminoethanol (DMAE). Results: We studied the stability of compound (±)-1 under the working conditions applied in the preparation of intermediate alcohol (±)-2. Additionally, we study different experimental parameters. Conclusion: In summary, a new chemoenzymatic synthetic route was developed for the DMRIE using glycerol as the starting material. We studied and optimized various experimental parameters of the various synthetic steps, and reached to develop the methodology to multigram scale, which compared to processes reported so far, has the advantages of fewer synthetic steps, the use of less aggressive reagents environment and generating fewer waste allowed to obtain the desired product; which results in a viable method for synthesizing analogs to DMRIE.

Background: Now a days, organic synthesis in aqueous phase or including water and water/organic mixture as a solvent has been received great attention in the field of organic chemistry. As the microwave assisted organic synthesis (MAOS) is environmental friendly, inflammable, and allows simple separation and catalyst recycling. So, by the microwave assisted synthesis using water as a solvent, one can easily achieve the purpose of green chemistry. In view of the potential bioactivity of benzofuran and coumarin moieties, we have taken up the synthesis of some new furocoumarin-biaryl derivatives using Suzuki coupling by the combination of two prominent green chemistry principles, namely microwave assisted synthesis and aqueous phase reactions. We have taken up the synthesis by microwave as well as conventional methods. Methods: The reaction of 8-acetyl-7-hydroxy-4-methyl Coumarin (1) with 2-bromo-1-(4-bromophenyl)ethanone (2) in presence of potassium carbonate, acetone yielded new furocoumarin, 4-(p-Bromobenzoyl)-3,10-dimethyl-5.13-dioxatricyclo[ 7.4.0.02,6]trideca-1(9),2(6),3,7,10-pentaen-12-one (3). Compound 3 on Suzuki coupling with different aryl boronic acids (4a-i) yielded the target molecules 4-[(4-Biphenylyl)carbonyl]-3,10-dimethyl-5.13-dioxatricyclo[7.4.0.02,6] trideca-1(9),2(6),3,7,10-pentaen-12-one analogues (5a-i) Results: Compound 3 was characterized as 4-(p-Bromobenzoyl)-3,10-dimethyl-5.13-dioxatricyclo[7.4.0.02,6] trideca- 1(9),2(6),3,7,10-pentaen-12-one. In the IR spectrum of 3, a peak at 1078 cm-1 confirms the presence of C-O-C group. In 1H NMR spectrum of 5a showed a singlet at δ 2.96 ppm corresponding to C3-CH3. In 13C NMR peak at δ 19.55 ppm, corresponding to methyl carbon attached to C3, other peak at δ 184.2 ppm, corresponding to conjugated ketone functionality confirms the formation of furocoumarin skeleton. In the MS of 3 the base peak appeared at 397 corresponding to (M+H)+. Similarly, Compound 5a was characterized as 4-[(4-biphenylyl)carbonyl]-3,10-dimethyl-5.13- dioxatricyclo[7.4.0.02,6] trideca-1(9),2(6),3,7,10-pentaen-12-one. In the MS of 5a the appearance of base peak at 395 corresponding to (M+H)+ confirms the formation of Suzuki coupled product. Conclusion: In conclusion, we have successfully synthesized a new series of 4-[(4-Biphenylyl)carbonyl]-3,10-dimethyl- 5.13-dioxatricyclo[7.4.0.02,6]trideca-1(9),2(6),3,7,10-pentaen-12-one derivatives (4.16a-i) under conventional and microwave irradiation methods using water as solvent. The microwave irradiation method was proved to be high yielding with higher rate of acceleration and eco-friendly.