Electricity originating from renewable resources can be used for highly sustainable and economically attractive applications. With electrons as the mass-free reagent, the use of a stoichiometric ...amount of oxidants in annulation reactions can be avoided, thereby eliminating the production of waste. Considered as a modern reaction configuration, the availability of electrochemical methods is expanding synthetic applications in the field of organic chemistry. Electrochemical transformations possess many benefits over traditional reagent-based methodologies, such as high functional group tolerance, mild conditions, easy scale up setup, high yields and selective transformations. In this review, we targeted electrochemical annulation reactions involving mediators and mediator-free conditions with generation of new C-C, C-heteroatom and heteroatom-heteroatom bonds, their mechanistic insights, as well as the reactivity of substrates. We also explain the recent use of sacrificial electrodes in annulation reactions.
Herein, electrochemical annulations involving mediators and mediator-free conditions have been discussed. Also, the use of sacrificial electrodes has been explored.
Insights into the occurrence of packing and conformational polymorphs and anhydrous/hydrate forms of 1,2-bis(aminocarbonyl(1-tert-butyl-1H-pyrazol-35-yl))ethanes with the substituents R = Me (a), ...F-4-Ph (b), Cl-4-Ph (c), and Br-4-Ph (d) in positions 5 (1) and 3 (2) of the pyrazole rings are presented. In this series, two molecular forms were observed, linear and folded. Compound 1a revealed an illuminating and rare example of a highly flexible molecule with packing polymorphism. The molecular stacking and absence of NH···OC interactions promoted polymorph growth. Structure 2a showed chains driven by NH···OC bonds in the anhydrous form and closed dimers by water binding the molecules (NHamide···OHwt···COamide) in the hydrate form. Two different forms were observed for conformational polymorph 2d (linear and folded). The folded form was about −10 kcal mol–1 more stable than the linear form, showing significant crystalline packing differences. This occurrence is attributed to the rotation of the amide groups through the NH···OC bonds. The linear shape showed a higher stabilization energy for NH···OC bonds and a cluster −6 kcal mol–1 more stable than polymorph 2dI. Compounds 1b–d and 2b-c also had their crystal growth proposed and features highlighted.
The supramolecular architectures of amide-containing compounds are highly dependent on the side-chain substituents, although the potential impact of isoxazole substituents on polymorph formation has ...not been thoroughly explored. Hence, three distinct forms of N 1 , N 3 -bis(5-methylisoxazol-3-yl)malonamide (1) were obtained and characterized: two polymorphic forms and one solvate. An in-depth analysis of the interactions and energy content of the crystals based on supramolecular clusters allowed us to propose crystallization mechanisms (crystal retrosynthesis). Specifically, the energy similarities between the interaction of the first sites NH amide ⋯OC amide (form 1I) and the symmetric sites NH amide ⋯N isox (form 1II) were found to contribute to their formation. Nonetheless, the presence of DMSO resulted in the formation of form 1III, where the solvent molecule disrupted amide-amide interactions. The first nuclei are more stable than forms 1I and 1II. The compound of N 1 , N 2 -bis(5-methylisoxazol-3-yl)oxalamide (2) was used as a comparison, and through the absence of polymorphs, revealed that the central carbon in molecule 1 allows a flexible adaptation that leads to the three forms. These findings suggest that variations in solvents, flexibility, and the presence/absence of amide–amide interactions can modulate the competition between amide-containing isoxazole compounds.
A series of 5(3)-aryl-3(5)-carboxyethyl-1- tert -butylpyrazoles (aryl, 4-X-C 6 H 4 , where X = H, F, Cl and Br) were studied in the solid state. The 1,3-regioisomers (carboxyethyl group in ...3-position) of t -butylpyrazoles crystalized in three different forms: s- cis , s- trans or s- cis + s- trans . On the other hand, the 1,5-regioisomers (carboxyethyl group in 5-position) of t -butylpyrazoles showed only s- trans conformation. The 13 C CPMAS and SCXRD data confirmed that each 1,3- and 1,5-regioisomers of t -butylpyrazoles crystallized only one of the three mentioned forms. The potential energy surface (PES) yielded insights regarding the formation of each conformer. In general, quantum mechanical calculations showed that the conformer s- trans is more stable than s- cis , and the calculated stability difference was 0.7 kcal mol −1 for the 1,3-regioisomers and 3.5 kcal mol −1 for the 1,5-regioisomers. Moreover, 1,5-regioisomers of t -butylpyrazoles showed intramolecular interactions of type CH⋯OC between the carbonyl and t -butyl group, which was obtained by QTAIM analysis. This interaction can influence the stabilization for s- trans conformation in the solid state. In contrast, the 1,3-regioisomers did not show intramolecular interaction with the COOEt group, and the conformation adopted in the solid state should be the consequence of the crystalline packing. The QTAIM analysis of the more stable dimers of s- trans -conformation for X = Cl, Br showed that the halogen atoms interact with the COOEt group, helping stabilize this conformation. On the other hand, in the s- cis ⋯s- cis conformation dimer (X = Cl, Br), the COOEt group was stabilized by the phenyl group, which is the same stabilization for X = H.
Rotaxanes are designated as molecular machines due their different movements. Systematic studies regarding the different conformations adopted by these systems and the factors that lead to the ...distribution of the conformations, in both solution and the solid state, have not been widely explored, especially for rotaxanes with nonsymmetric stoppers. Therefore, in this study we have investigated three novel 2rotaxanes containing threads derived from nonsymmetric succinamides R1R2NC(O)‐CH2CH2‐C(O)NR2R1, with R1/R2 = Bu/Bn, Bu/2‐furylmethyl, and 5‐methylisoxazol‐3‐yl/2‐furylmethyl. The proportions of rotamers were investigated for threads and rotaxanes by solution and solid‐state NMR spectroscopy as well as by single‐crystal and powder X‐ray diffraction. In solution, the threads present different proportions of conformer, with the E,Z conformation prevailing, whereas only one conformer is observed in the solid state. For the rotaxanes, only one conformer prevails in the single crystal, whereas the solution and solid (bulk) states present more than one rotamer. These proportions are modified when the threads are incorporated into the macrocycle during rotaxane formation. The intramolecular interactions in each rotamer were investigated by QTAIM and variable‐temperature 1H NMR experiments. The changes in conformational population between the threads and respective rotaxanes can be explained by a set of different intramolecular interactions, with trifurcated hydrogen bonds responsible for most of the stabilization energy.
A conformational study of rotaxanes has been performed. The proportion of different rotamers was investigated for threads and for threads incorporated into rotaxanes. This investigation was performed by using solution and solid‐state NMR spectroscopy, single‐crystal XRD, and PXRD. How the conformational population is affected when the thread is incorporated into the macrocycle has been evaluated.
•Unprecedented trifluoromethyltriazolylpyrimidines were synthetized by click chemistry•The hydrogenation of trifluoromethyltetrazolo1,5-apyrimidines using Pd/C-H2 was performed•Aryl-brominated ...substrates was reduced without dehalogenation by photochemical hydrogenation•The chemoselectivity of the hydrogenation was affected by trifluoromethyl in pyrimidine.
We explored the synthetic potential of tetrazolo1,5-apyrimidines to obtain new pyrimidine derivatives via click chemistry and hydrogenation. Click chemistry reactions of trifluoromethyl-tetrazolo1,5-apyrimidines with terminal acetylenes produced unprecedented trifluoromethylated triazolylpyrimidines at excellent yields (84–98 %), and one of them was active against all tested microorganisms, with moderate minimum inhibitory concentration values (62.5–15.62 μg/mL). Hydrogenation was performed using Pd/C-H2 in MeOH under conventional, photochemical, and pressure (5 bar) conditions. Hydrogenation was an excellent method for obtaining 2-amino-6-aryl-4-trifluoromethylpyrimidines and/or 2-amino-6-aryl-4-trifluoromethyltetrahydropyrimidines with a preference for 2-aminopyrimidine formation. Photochemical hydrogenation was the only pathway for reducing aryl-brominated substrates without dehalogenation. The reduction of trifluoromethyl-substituted tetrazolo1,5-apyrimidines furnished 2-amino-6-aryl-4-trifluoromethylpyrimidines instead of the corresponding tetrahydropyrimidines. However, the hydrogenation of non-trifluoromethylated tetrazolo1,5-apyrimidines showed a preference for tetrahydropyrimidine formation.
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A series of seven N-phenylamides R–C(O)NHPh, in which R: CH3, C(CH3)3, Ph, CF3, CCl3, CBr3, and H were used as models in this study. Molecular packing and intermolecular interactions were ...evaluated by theoretical calculations, solution NMR, and quantum theory of atoms in molecules analyses. Crystallization mechanisms were proposed based on the energetic and topological parameters using the supramolecular cluster as demarcation. Concentration-dependent 1H NMR experiments corroborated the proposed interactions between molecules. For all compounds (except for R: H, which initially formed tetramers), layers (two-dimensional) or chains (one-dimensional) were formed in the first stage of the proposed crystallization mechanisms. The presence of strong intermolecular NH···OC interactions promoted the first stages. The study in solution provided different values of association constant (K ass) governed by the hydrogen bond NH···OC, showing that the stronger interactions are directly influenced by the substituent steric hindrance. A correlation between K ass(NH···OC) from the solution and the NH···OC interaction energy in the crystal showed a good trend.
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•The dissipated ultrasonic power of 25 solvents was determined.•BMIMBF4 and water had the highest dissipated ultrasonic power.•Toluene and toluene doped with BMIMBF4 were evaluated in ...an SN2 reaction.•Conversion in neat toluene was 46%.•Conversions in toluene doped with BMIMBF4 was 100%.
The heating profile for 25 solvents was determined in ultrasonic probe equipment at amplitudes of 20%, 25%, and 30%. Each solvent was heated in accordance with its boiling point. The effect of vapor pressure, surface tension, and viscosity of the solvents in dissipated ultrasonic power (Up) was evaluated. Multiple regression analysis of these solvent properties and dissipated Up reveals that solvent viscosity is the property that most strongly affected dissipated Up. Experimentation involving acetonitrile doped with BMIMBF4 indicated faster heating than MeCN. Aprotic polar solvents such as DMSO, DMF, and MeCN were tested in the N-alkylation of pyrazoles under ultrasonic conditions. After 5min at 90°C, the reactants had been totally converted into product in these solvents. Solvents, with low dissipated Up (e.g., toluene) were tested. Conversions were lower compared to those of aprotic polar solvents. When the reactions were done in hexane, no conversion to product was observed. To check the effect of doping in solvents with low Up, BMIMBF4, DMSO, and DMF were selected. The conversions for toluene doped with BMIMBF4, DMSO, and DMF were 100%, 59%, and 25%, respectively. These conversions were greater than when done in just toluene (46%). Thus, BMIMBF4 was the best polar doping solvent, followed by DMSO. DMF was not considered to be a satisfactory doping solvent. No conversion was observed for reactions in the absence of base performed in DMSO, DMF, and MeCN doped with BMIMBF4.
This work reports the synthesis of thiazolidin‐4‐ones and thiazinan‐4‐ones analogous to rosiglitazone, a potent antidiabetic drug. The desired compounds were synthesized with moderate to good yields ...by one‐pot reactions between different primary amines, mercaptoacetic or mercaptopropionic acids, and the 4‐(2‐(methyl(pyridin‐2‐yl)amino)ethoxy)benzaldehyde. The cyclocondensation reactions were carried out for 20 h, and all the products were characterized by 1H and 13C nuclear magnetic resonance spectroscopy, mass spectrometry, and one example by X‐ray diffraction.
A series of novel trifluoromethylated tetrazolo1,5-
a
pyrimidines were easily prepared via a highly regioselective cyclocondensation reaction between β-alkoxyvinyl trifluoromethyl ketones CF
3
...C(O)CH=C(R)OMe (in which R = Ph, 4-F–C
6
H
4
, 4-Cl–C
6
H4, 4-Br–C
6
H
4
, 4-I–C
6
H
4
, 4-CH
3
–C
6
H
4
, 4-OCH
3
–C
6
H
4
, Thien-2-yl, 4-Ph–C
6
H
4
, Me) and 5-aminotetrazole, using conventional heating in an oil bath or microwave irradiation. The results showed that when ionic liquid was used as the reaction medium, the reaction time drastically decreased and the yield improved. Additionally, all the newly synthesized compounds were evaluated to determine their antimicrobial activity. Two of the compounds tested were the most promising because they displayed activity against the Gram-positive and Gram-negative bacteria used in the tests, and they were moderately active against the yeast
Candida albicans
. And finally, the cytotoxicity of lymphocytes of the two compounds was evaluated by using MTT assay. Results showed at active concentration such compounds would be safe.
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