Letters in Organic Chemistry - Volume 15, Issue 7, 2018

Background: 6-Fluoro-3-(4H-1,2,4-triazol-3-yl)quinolin-4(1H)-ones are potential antileukemic agents. Method: QSAR analysis of a series of previously synthesized 6-fluoro-3-(4H- 1,2,4-triazol-3-yl)quinolin- 4(1H)-ones (tested for their inhibitory activity against blood cancer) as analogues of fluoroquinolone, was performed with the aid of multiple regression analysis. This could facilitate the exploration of features responsible for the selectivity of the antileukemic activity against HL60 (Human promyelocytic leukemia cell line) among this congeneric series. Using random selection method, 25 analogues of the series were selected as training set while 12 analogues of 6-Fluoro-3-(4H-1,2,4-triazol-3-yl)quinolin- 4(1H)-one were taken as test set for current investigation. Inhibitory Concentration (IC50) values were used to build statistical models with the help of physicochemical and topological descriptors. Results: QSAR equations were developed and they worked well for all the predictions. QSAR models were validated by doing cross validation. Conclusion: The derived model has the capability to predict the activity of new compounds as well as it can also quantitatively explain the critical region to be focused in the molecule.

A Rice Husk based nanosilica anchored Ru(III) Schiff-base complex was found to be a very efficient and reusable heterogeneous catalyst for organic transformation of alcohol to carbonyl compounds. The catalyst was obtained by simple Schiff-base condensation between 3-aminopropyltriethoxysilane (APTES) functionalized nanosilica and acetamide. The characterization of the catalyst was carried out by various techniques such as FT-IR, XRD, ESR, BET surface area measurements, SEM-EDX mapping and ICP-AES. The alcohol oxidation reactions were performed at 50C using acetonitrile and TBHP as solvent and oxidant, respectively. The catalyst was found to be very effective towards alcohol oxidation with excellent product yield and reusable upto minimum 5th reaction cycle.

An efficient and convenient substitution protocol was developed for the synthesis of novel benzyl (1-methyl-1H-imidazol-5-yl) (aryl) methyl carbamate derivatives from α-amido sulphones with a solution 5-bromo-1-methyl-(1H)-imidazole in THF under Hexamethylphosphoramide (HMPA) and t-BuLi medium at -78°C to room temperature. The reactions were monitored with TLC for about 3-4 h. The yields obtained were also considerably good.

Background: In the present study, fourteen new 1,2,4-triazole Schiff bases and eight new 1,2,4-triazolo[3,4-b][1,3,4]thiadiazines incorporating a pyrimidine ring were synthesized and evaluated for their antibacterial activity. Methods: 1,2,4-Triazole Schiff bases were prepared from the condensation of 4-amino-3-mercapto-5- (2-thiomethylpyrimidyl)-1,2,4-triazole with a series of arylaldehydes in the presence of (+)-tartaric acid as catalyst. On the other hand, the reaction of 4-amino-3-mercapto-5-(2-thiomethylpyrimidyl)-1,2,4- triazole with substituted phenacyl bromides afforded the corresponding 1,2,4-triazolo[3,4-b][1,3,4]- thiadiazines. Results: The structures of 1,2,4-triazole Schiff bases and 1,2,4-triazolo[3,4-b][1,3,4]thiadiazines were characterized by IR, NMR and mass spectral data. All the synthesized compounds were screened for their antibacterial activities using 96-well microbroth dilution assay. Conclusion: Schiff base with p-hydroxylphenyl substituent and triazolothiadiazine containing 4- flurophenyl ring displayed moderate antibacterial activity against Pseudomonas aeruginosa at MIC 62.5 μg/ml.

We have developed a new chromium based reagent ‘DABCO−bis-CC' for the straightforward oxidation of alcohols to corresponding carbonyl compounds with high efficiency. The present results demonstrate a broad range of alcohols including primary, secondary, aliphatic, benzylic and heterocyclic alcohols are tolerated as substrates at room temperature.

CuFe2O4 nanoparticles were prepared by co-precipitation method. After the characterization of nanoparticles by XRD, SEM, EDS and TEM, their catalyst activity was investigated in the synthesis of β-acetamido ketones. CuFe2O4 nanoparticles were introduced as a recyclable, inexpensive and nontoxic catalyst in a four-component reaction of aromatic aldehydes, enolizable aromatic ketones, acetyl chloride and acetonitrile at room temperature.

Transition metal-free synthesis of synthetically valuable aryl iodides from aryl diazofluroborates in water under mild conditions has been described. Majority of synthesized aryl iodides are obtained in quantitative yields (>99 %) under present reaction conditions. The structural effects due to the substituents present on aryl diazofluoroborates did not show any satisfactory effect on the yields of the aryl iodides. Hence, the methodology presented here was found to be adventitious for the quantitative production of synthetically valuable aryl iodides.

An efficient Amberlite IRA-400 Cl resin catalyzed, solvent-free, one-pot synthesis of 1- aryl-1,2-dihydro-3H-naphtho[1,2-e][1,3]oxazin-3-ones via three-component reaction of arylaldehydes, urea, and β-naphthol are described. This method offers advantages such as easy work-up, low environmental impact, shortened reaction times, and high yields. The catalyst recovered was reused four times without significant loss of catalytic activity.

Background: The presence of bicyclic lactams is reflected in various pharmaceuticals, natural products, agrochemicals and active components of various dyes. Nowadays, to see the increasing rate of antimicrobial resistance and high incidence of microbial infections, there is a strong need to develop novel antimicrobial agents. In this study, we synthesized some benzofused six membered ring lactams and their alkyl derivatives as a trial to obtain valuable precursors for the discovery of future antimicrobial drugs. Methods: The substituted lactams 3,4-dihydro-2(1H)-quinolinones 3a-c and 3,4-dihydro-1(2H)- isoquinolinones 4a-c were synthesized by Schmidt reaction on indanones 2a-c which were obtained by Friedel-Crafts reaction on β-substituted α,β-unsaturated carboxylic acids 1a-c. Lactams 6 and 7 were obtained by N-alkylation on benzofused lactams 3a-c and 4a-c in good to excellent yields. Structures of all products were well characterized by the rigorous analysis of their IR, 1H NMR, 13C NMR, MS and elemental analysis. The in vitro antimicrobial activities of all the synthesized compounds 6 and 7 were determined against Gram-positive, Gram-negative bacteria and the fungal species Candida albicans using broth macrodilution method. Results: The Schmidt reaction of 3-methylindanone, 3-phenylindanone and 3,3-dimethylindanone using methane sulphonic acid was found to behave differently with respect to isolated yield as well as isomeric ratio of both lactams. Bacterial growth inhibition was observed with bicyclic lactam derivatives although their MIC values were higher than ampicillin. The significant inhibitory effects were shown by majority of compounds with MIC values 125-250 μg/ml. Antifungal activity of bicyclic lactam derivatives was observed against C. albicans. However, MICs values of all tested compounds were higher compared to standard antifungal agent miconazole. Conclusion: The four Schmidt experimental conditions were tried with the aim of achieving both 6- membered ring lactams in equal ratio and NaN3/MeSO3H was identified to fulfill our purpose. As evident by structure-activity relationship, the tested compounds have not resulted in superior antibacterial or antifungal compounds compared to standard antimicrobials. Hence, there is still a need to carry out further modifications in bicyclic lactams structure in order to more efficacious antimicrobial lead molecules.

Background: The GlcNAc related sulfated disaccharides were reported to show inhibitory activity on breast tumor cells (MDA-MB-231). However, synthesis of sulfated disaccharides is laborious and time consuming, and there is a need to find more efficient methods to generate the sulfated disaccharide libraries in acceptable ratios and in respectable yields. Random glycosylation followed by sulfation may be a good method to synthesize sulfated disaccharide library. However, there is a dearth of simple methods to generate the GalNAc and GlcNAc related disaccharides with acceptable ratio by random glycosylation. Results: Following a generic procedure, random glycosylation of unprotected monosaccharides and followed by deprotection, acetylation, deacetylation, and purification, yielded the GalNAc-GlcNAc disaccharide library containing three β-linked disaccharides with a 1:1:1 ratio and the GlcNAc-Gal disaccharide library containing four β-linked disaccharides with 1:1:2:2 ratio. These results were confirmed by comparison of their proton NMR spectra with that of standard disaccharides. Conclusion: Random glycosylation was employed to generate GalNAc and GlcNAc related disaccharide libraries and was demonstrated as the most efficient method thus far for the synthesis of GalNAc and GlcNAc related disaccharide libraries with excellent ratios, which further can be used as the starting materials for random sulfation to synthesize the sulfated disaccharide libraries.

Synthesis of seven odorant Schiff bases of methylanthranilate, an aroma constituent of blossom essential oils, with naturally occurring carbonyl compounds (citral, citronellal, cuminaldehyde, vanillin, veratraldehyde, acetophenone and α-ionone) employing conventional and microwave irradiation methods was carried out. Elemental and spectral (FT-IR, 1H NMR and 13C NMR) analysis of these compounds supported their structures. These Schiff bases had olfactory attributes suitable for various fragrance compositions. Microwave irradiation method was efficient in terms of reduced reaction time, solvent use, and increased yields of these compounds without affecting their olfactory characteristics. These compounds also displayed varied antimicrobial activity against Aspergillus niger, Penicillium chrysogenum, Staphylococcus aureus and Escherichia coli.

A non-metal catalytic method for the aerobic conversion of primary alcohols to aromatic nitriles via a single-step operation was developed. A series of primary benzyl alcohols underwent this transformation to give the targeted products in moderate to high yields under the catalysis of TEMPO/ HNO3.

In the present study a series of metal complex of [bis (2-amino-5-aryl-1,3,4-thiadiazole]2Cl (S1-S9) was synthesized by using ultrasound irradiation technique. The metal complex was synthesized by the reaction between ligand and appropriate metal salts (CuCl2. 2H2O, CoCl2. 6H2O, ZnCl2, MgCl2. 4H2O, NiCl2. 6H2O). The products were obtained in high yield and the reaction time was found to be shorter. The synthesized metal complexes were characterized by using UV-visible spectroscopy, FTIR, 1H NMR and Mass spectroscopy. The synthesized compounds were investigated for antibacterial potential against gram positive bacteria (Bacillus subtilis, Staphylococcus aureus) and gram negative bacteria (Pseudomonas aeruginosa, Escherichia coli). Significant activity was observed for synthesized metal complexes S6 and S7 against B. subtilis and S. aureus.