The authors report on the use of the reaction system BrCCl₃/PPh₃ in the amidation of carboxylic acids, in the preparation of anhydrides from carboxylic acids and in the esterification of carboxylic acids with cholesterol, where cinnamic acids were used as acid component in all three transformations. Furthermore, the use of BrCCl₃/PPh₃ in the dehydration of benzcarboxamides to benzonitriles was studied as well as the preparation of N-(phenylsulfonyl)-triphenylphosphoranylideneamide from benzenesulfonamide.

Amines are present in many naturally occurring bioactive molecules showing interesting herbicidal and fungicidal activities, and they are also utilised as versatile intermediates for the synthesis of pharmaceuticals, agrochemicals, dyes, and as valuable building blocks in synthetic organic chemistry. Amines can be synthesized by the reaction of aldehydes or ketones with ammonia, primary or secondary amines in presence of different reducing agents. This is the so-called reductive amination reaction which is described as direct when the carbonyl compound and the amine are mixed together with a suitable reducing agent in a single operation, without preformation of an imine or an iminium salt. On the other hand, the reducing systems based on the use of alkali-metals in combination with arenes in aprotic media, with the arene acting as electron carrier have received much attention. In the last years, we have been working on the preparation of transition metal nanoparticles by fast reduction of the corresponding metal chlorides with lithium and a catalytic amount of an arene [naphthalene, 4,4´-di-tert-butylbiphenyl (DTBB)] as electron carrier. In this work we want to introduce a simple and efficient procedure for the direct reductive amination of aldehydes for the one-pot synthesis of secondary amines, using primary amines as starting materials in the presence of lithium powder and a catalytic amount of DTBB or a polymer supported naphthalene as electron carrier. The direct reductive amination of a variety of aldehydes was achieved simply by adding a mixture of the corresponding carbonyl compound and the amine, over a solution of the lithium arenide in THF at room temperature. For most of the substrates tested the main reaction products were the secondary amines along with variable amounts of the corresponding alcohol and imine products. DFT methods have been applied in order to explain the differences in reactivity observed.

Our group has been involved in searching new synthetic routes to organostannanes by the S_RN1 mechanism.¹ Based on our experience we consider of interest to study the scope of S_RN1 in the polystannylation of an aromatic ring. Now we inform the experimental results obtained in the reaction of trimethylstannylsodium (1) with aryl phosphates supporting three nucleofugal groups, in liquid ammonia as solvent, and a DFT study which support the notable differences observed between isomeric substrates. In order to synthesize 1,2,4-tris(trimethylstannyl)benzene (2) we use as starting substrates 1,3-bis(diethoxyphosphoryloxy)-4-chlorobenzene (3) and 1,4-bis(diethoxyphosphoryloxy)-3-chlorobenzene (4). Under photostimulation 3 and 4 led to entirely different products distributions. Meanwhile 3 afforded 2 together with 1,3- and 1,4-bis(trimethylstannyl)benzene in a 63:23:10 ratio, 4 yielded a mixture of 2 and 1,4- bis(trimethylstannyl)benzene in a 32:68 ratio. Starting substrates were almost recovered in dark reactions supporting an S_RN1 mechanism. These results were unexpected since the substrates would have similar electron affinities. We have previously demonstrated that differences in spin density on radical anions affect products distributions,² so, we started a systematic theoretical study over 3 and 4 with the B3LYP functional, the LACVP pseudopotential (Sn) and the 6-31+G* (C, H, O, P) with GAUSSIAN03. We observed meaningful differences in SOMOs MO, spin density distribution and activation energies of the corresponding radical anions intermediate, which support the experimental outcome and allow us to interpret the distribution of stannylated end-products in terms of the structural features of the starting isomers. ¹ Silbestri, G. F.; Lo Fiego, M. J.; Lockhart, M. T.; Chopa, A. B. J. Organometal. Chem. 2010, 695, 2578-95 and references therein. ² Dorn, V. B.; Badajoz, M. A.; Lockhart, M. T.; Chopa, A. B.; Pierini, A. B. J. Organometal. Chem. 2008, 693, 2458-62.

Derivatives of quinoline and its isosters are remarkable compounds with many different kinds of biological effects. A number of quinoline related compounds expressed antifungal, antibacterial, antiviral, antineoplastic, and other activities. In order to perform the classical synthesis of amides activation of quinoline-2-carboxylic acid is usually required. When activation is carried out under standard conditions with thionyl chloride, formation of undesired chloro compound where chlorine is attached in position 4 of quinoline ring is observed. In this study we have developed a method for preparation of substituted anilides in one step, based on the direct reaction of an acid or ester with substituted anilines using microwave irradiation. In recent developments, the use of microwave irradiation to simplify and improve classic organic reactions has become a very popular method, because it often leads to higher yields, cleaner reactions and shorter reaction times. In connections with solvent-free conditions, microwave-assisted methods result in very efficient and environmentally friendly technology. The method was tested on compounds: 2-quinaldic acid and its methyl and phenyl ester, 2-naphthoic acid and its ethyl ester. All those compounds reacted with 4-bromaniline as a model aniline. The synthesis was carried out under solvent-free conditions or in solvents: DMF and chlorobenzene. Despite the fact, that formation of anilides under microwave irradiation is hampered by competitive decarboxylation of quinaldic acid to quinoline, this technique showed certain advantages like shorter reaction time, no use of aggressive chemicals and simpler work-up. From the series of experiments is evident, that the use of phenyl ester is the most effective for microwave accelerated synthesis of anilides. A series of substituted anilides of quinaldic acid were prepared by developed method.

Over the last decades triterpenoids have drawn attention because of their anti-inflammatory, anti-oedematous, antitumor, and anti-HIV activities. Abundant in many plants, these metabolites are valuable natural raw materials to perform chemicals modifications and obtain semisynthetic analogs for structure-activity relationship studies. Asteraceae family constitutes a rich source of several pentacyclic mono-alcohols, diols and triols terpenes such as calenduladiol, faradiol, heliantriol B2, taraxasterol, arnidiol, lupeol, etc. Acetylcholine serves as a neurotransmitter in the central and peripheral nervous system. Acetylcholinesterase (AChE) stops the function of acetylcholine by its hydrolytic destruction in the cholinergic synapses. Enhancement of acetylcholine level in the brain inhibiting AChE is considered one of the most promising approaches for treating Alzheimer\'s disease. In the course of our ongoing search of natural AChE inhibitors, we isolated calenduladiol (1), in good yields, from ethanolic extract of Chuquiraga erinacea D. don. subsp. erinacea (Asteraceae), collected in southwest of Buenos Aires province, Argentina. This triterpene elicited moderate AChE inhibition which encouraged us to synthesize five calenduladiol derivatives: 30-oxo-calenduladiol (2), 30-hydroxy-calenduladiol (3), calenduladiol diacetate (4), 30-oxo-calenduladiol diacetate (5) and 30-hydroxy-calenduladiol triacetate (6). Compounds 2 and 3 were obtained by oxidation with SeO₂ and, 4, 5 and 6 by esterification with Ac₂O and pyridine from compounds 1, 2 and 3 respectively. Compounds 2-6 which were obtained in good yields and characterized by ¹H and ¹³C NMR spectroscopy. The oxidized analogs, 2 and 3 resulted to be the most active ones with a 43 % and 40 % of AChE inhibition at 0.2 mM, respectively, in the Ellman\'s assay. Acetylated derivatives (4-6) elicited a weak activity compared with 1, at the same concentration. Our results indicate that calenduladiol analogues oxidized at C-30 could be a promising strategy for the enhancement of pharmacological properties of this type of triterpene alcohols.

Fluorescent probes are widely used in membrane biophysical studies to investigate the properties of the molecular environment of cell membrane and biochemical processes related to it. These probes provide information of the molecular environment trough changes of their photophysical properties. While these probes can provide valuable information of the membrane molecular properties, a clear structural description, at the molecular scale, of the membrane properties surrounding the fluorescent molecular probe, is essential for the interpretation of the experimental fluorescent signal. In this work, we studied the membrane permeation properties of four benzo[a]phenoxazinium fluorescent probes with different alkyl chains in the tetracyclic ring in DPPC membranes using molecular modelling techniques . We describe the molecular mechanism of interaction between the molecular probes and the DPPC lipids. We show that probes can be preferentially located at the membrane water interface interaction with the lipid polar groups, while others can be cross the membrane in a passive way. This processes is dependent on the tetracyclic substitutions and alkyl chain present in the fluorescent probe. These findings can provide a detailed rational of the structural properties surrounding the molecular probes that could be correlated with the experimentally measured fluorescence.

The copper catalyzed Huisgen reaction was used for the synthesis of two derivatives of 1H-1,2,3-triazol-1,3,5-triazinane-2,4,6-trione. One from tris(2-azidoethyl)-1,3,5-triazinane-2,4,6-trione and phenylacetylene, and the other by coupling of 1,3,5-tri(prop-2-yn-1-yl)-1,3,5-triazinane-2,4,6-trione with benzyl azide.

The reaction of tris(oxiran-2-ylmethyl)-1,3,5-triazinane-2,4,6-trione with phenol or N-methylaniline promoted by microwave heating, under solventless conditions, led to the opening of the oxirane ring through the less hindered carbon, leading to tripodal triols with C₃ symmetry in good yields.

Today the aminoglycosides are still the most commonly used antibiotics worldwide thanks to the combination of their high efficacy with low cost. The interest of aminoglycoside antibiotics is due to their use in treatment of wide variety infections. These compounds act on gram-positive and gram-negative bacteria as protein synthesis inhibitors.[1] However, they are nephrotoxic and ototoxic in some cases, thus limiting its use. Kanamycin is an aminoglycoside antibiotic with multiple therapeutic applications. A previous step of their synthesis is the formation of 3-amino-3-deoxy-D-glucose from commercial available products. Integration of phenylhydrazine with a sugar derived dialdehyde (2) in water, as a key step, has been used[2] as an elegant and easy strategy synthesis. However, a low reproducibility of this method makes synthetic chemists reluctant to its use, in such a way that other routes of synthesis of 3-amino-3-deoxy-D-glucose are preferred.[3] All this, despite the fact that the above mentioned integration reaction can be considered as a representative example of green chemistry.[4] We have revisited this process and we report herein new NMR and IR data of compounds 2 and 3 that they confirm the structures proposed in literature. In addition, we describe novel different conditions for their synthesis that reduce the time of reactions, especially in case of dialdehyde 2. We thank the AECID (Projects A/023577/09 and A/040322/10) and the \'Junta de Andalucía\' (FQM 142 and Project P09-AGR-4597) for financial support. [1] a) Li, J.; Chang. T., Anti-Infec. Agents in Med. Chem. 2006, 5, 255.; b) Corey, E. J.; Czakó, B.; Kürti, L., Molecules and Medicine. John Wiley & Sons, New Jersey, 2007 [2] Patroni, J.; Stick, R. Aust. J. Chem, 1985, 38, 947 and reference therein. [3] Faghih, R.; Cabrera-Escribano, F. et al, J. Org. Chem. 1986, 51, 4558 [4] Anastas, Y.; Warner, J.C. Green Chemistry: theory and practice.Oxford University Press, New York, 1998

The interest of fluorescent carbohydrates is due to wide applications in biology and environmental technology. For example, water soluble glucose based imino-anthracenyl derivatives have been shown to recognize specifically Hg²⁺ (which is highly toxic and causes DNA damage and impair mitosis) by switch-on fluorescence.[1] Fluorescence is a powerful technique as a consequence of its highly sensible and specific detection methods. [2]^,[3] With the aim to generate new derivatives with biological, pharmacological and technological properties, we design the here presented compounds using as diversity point (see Scheme), the amino group. We have selected coumarins as chromophore units (CU), due to their demonstrated anticoagulant activity and easy availability. On the other hand, fluorescent aldehydes have been chosen as fluorescence sources for their chemosensor potential activity in a wide variety of fields. We report here on new fluorescent derivatives of D-glucosamine (1) previous protection of its hydroxyl groups. These derivatives having general structures 2 and 3, have been prepared in good yields by: a) nucleophilic attack of the amino group to activated carboxycoumarins, and b) by reductive amination, respectively. We thank the AECID (Projects A/023577/09 and A/040322/10) and the \'Junta de Andalucía\' (FQM 142 and Project P09-AGR-4597) for financial support. [1] Mitra, A.; Mittal, K. A. and Rao, P. C. Chem. Comm., 2011, 47, 2565 and references therein. [2] Lee, D.Y.; Singh, N. and Jang, D. O. Tetrahedron Lett. 2010, 51, 1103 [3] a) Rettig, W. Applied Fluorescence in Chemistry, Biology and Medicine; Springer: New York, 1999. b) Christensen, L.; Norgaard, R.; Bro, S. and Engelsen, B. Chem. Rev. 2006, 106, 1979.