A ternary eutectic solvent for cellulose nanocrystal production: exploring the recyclability and pre-pilot scale-up.

Deep eutectic solvents (DES) formed using choline chloride (ChCl), p-toluenesulfonic acid (pTSA) of stoichiometry ChCl: pTSA (1:1) and (1:2), and its ternary eutectic mixtures with phosphoric acid (PA) 85% as an additive (ChCl: pTSA: PA) were evaluated for cellulose nanocrystal (CNC) isolation. Initially, the hydrolytic efficiency to produce CNC of each DES was compared before and after adding phosphoric acid by Hammett acidity parameters and the Gutmann acceptor number. Moreover, different DES molar ratios and reaction time were studied at 80°C for CNC optimization. The nanomaterial characteristics were analyzed by field emission scanning electron microscopy (FESEM), X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FTIR), and thermogravimetric analysis (TGA). The ternary eutectic mixture ChCl: pTSA: PA molar ratio (1:1:1.35) was chosen as a suitable recyclable ternary system at the laboratory scale. A CNC yield of about 80% was obtained from the hydrolysis of commercial cellulose in five cycles of recovery, but it dropped to 35% in pre-pilot scaling. However, no variation in the average size of the resulting CNC was observed (132 ± 50 nm x 23 ± 4 nm), which presented high thermal stability (Tmax 362°C) and high crystallinity of about 80% after 3 h of reaction time.

Nucleophilic Neutralization of Organophosphates: Lack of Selectivity or Plenty of Versatility?

Neutralization of organophosphates is an issue of public health and safety, involving agrochemicals and chemical warfare. A promising approach is the nucleophilic neutralization, scope of this review, which focuses on the molecular nucleophiles: hydroxide, imidazole derivatives, alpha nucleophiles, amines and other nucleophiles. A reactivity mapping is given correlating the pathways and reaction efficiency with structural dependence of the nucleophile (basicity) and the organophosphate (electrophilic centers, P=O/P=S shift, leaving and non-leaving group). Reactions extremely unfavorable (>20 years) can be reduced to seconds with various nucleophiles, some which are catalytic. Although there is no universal nucleophile, a lack of selectivity in some cases accounts for plenty of versatility in other reactions. The ideal neutralization requires a solid mechanistic understanding, together with balancing factors such as milder conditions, fast process, selectivity and less toxic products.

Choline [Amino Acid] Ionic Liquid/Water Mixtures: A Triple Effect for the Degradation of an Organophosphorus Pesticide.

A series of ionic liquids (ILs) composed by choline (Ch) as a cation and different amino acids (AA) as anions and their respective aqueous mixtures were prepared using different [Ch][AA] contents in a range of 0.4-46 mol % IL. These solvents were used for the first time to achieve an eco-friendlier Paraoxon degradation. The results show that [Ch][AA]/water mixtures are an effective reaction medium to degrade Paraoxon, even when the IL content in the mixture is low (0.4 mol % IL) and without the need of an extra nucleophile. Both the kinetics and the degradation pathways of pesticides depend on the nature of the AA on [Ch][AA] and the amount of an IL present in the mixture. We have demonstrated that in those mixtures with a low amount of [Ch][AA], the hydrolysis reaction is the main pathway for Paraoxon degradation, showing a catalytic effect of the IL. However, as the percentage of [Ch][AA] increases in the mixture, the nucleophilic attack of [Ch][AA] is evident. Finally, the aim of this study was to provide evidence of a promising and biocompatible methodology to degrade a toxic compound (Paraoxon) using a minimal quantity of an IL designed totally from natural resources.

Microwave-assisted nucleophilic degradation of organophosphorus pesticides in propylene carbonate.

Propylene carbonate is becoming a suitable green alternative to volatile organic solvents in the study of chemical reactions. In this study, an efficient method for nucleophilic degradation of five organophosphorus pesticides, fenitrothion, malathion, diazinon, parathion, and paraoxon, using propylene carbonate as a solvent is proposed. The effect of changing the nature of the nucleophile and the influence of microwave (MW) heating were investigated. A screening of temperatures (50 °C-120 °C) was performed under microwave heating. The pesticide degradation was followed by 31P NMR, and the extent of conversion (%) was calculated by the integration of phosphorus signals. Keeping in mind that recently it has been reported that some ionic liquids play a nucleophilic role, in this work we report for the first time the degradation of organophosphorus pesticides by using an amino acid-based ionic liquid such as Bmim[Ala] as a nucleophile and a bio-based solvent (propylene carbonate) as a reaction medium in combination with microwave heating.

Dual function of amino acid ionic liquids (Bmim[AA]) on the degradation of the organophosphorus pesticide, Paraoxon®.

The synthesis of a series of ionic liquids using 1-butyl 3-methylimidazolium (Bmim+) as a cation and different amino acids (AA) as anions (Bmim[AA]) is described. These ILs were used for the first time as reaction media to achieve more eco-friendly Paraoxon degradation. The results show that the degradation of Paraoxon in these Bmim[AA]s is accomplished with great efficiency and without an extra nucleophilic agent. Therefore, we propose that all the Bmim[AA]s used in this study have a dual role in the outcome of this reaction; as a nucleophile and a solvent to carry out degradation of the organophosphorous pesticide, Paraoxon. Both kinetics and product distribution results found in this study for Paraoxon degradation turned out to be promising, because this process is achieved in a reaction medium with a better environmental profile.

Efficient Nucleophilic Degradation of an Organophosphorus Pesticide "Diazinon" Mediated by Green Solvents and Microwave Heating.

An efficient strategy for the degradation of organophosphate pesticide Diazinon was investigated. In this work, ionic liquids, bio-based solvents, and two conventional organic solvents were used as reaction media. Kinetics studies by means of half-life (t1/2,h) were followed by 31P NMR and the products analyzed by GC-MS, HPLC-MS and NMR techniques. These results have shown that t1/2 values in ionic liquids were the lowest and also they were able to activate two electrophilic centers in Diazinon, whilst degradation in bio-based solvents occurred slowly by only an aromatic pathway. In addition, a study to estimate the influence of green activation techniques was carried out by using Ultrasound irradiation and Microwave heating in combination with greener solvents and two conventional organic solvents. Under Microwave heating, faster degradation than under ultrasound irradiation was found. Finally, considering both families of solvent used here and their behavior under green activation techniques, we propose that the more efficient way for degradation of Diazinon with piperidine is by microwave heating using ionic liquids as solvents.

Correction: Reaction mechanisms in ionic liquids: the kinetics and mechanism of the reaction of O,O-diethyl (2,4-dinitrophenyl) phosphate triester with secondary alicyclic amines.

Correction for 'Reaction mechanisms in ionic liquids: the kinetics and mechanism of the reaction of O,O-diethyl (2,4-dinitrophenyl) phosphate triester with secondary alicyclic amines' by Paulina Pavez et al., Org. Biomol. Chem., 2016, DOI: 10.1039/c5ob02128f.

Reaction mechanisms in ionic liquids: the kinetics and mechanism of the reaction of O,O-diethyl (2,4-dinitrophenyl) phosphate triester with secondary alicyclic amines.

The reactions of O,O-diethyl 2,4-dinitrophenyl phosphate triester (1) with secondary alicyclic (SA) amines in the ionic liquids [Bmim]BF4 and [Bmim]DCA were subjected to a kinetic study. Eyring plots were obtained for the title reactions in the above ionic liquids (ILs) and also in aqueous ethanol (44 wt% ethanol). Two different reaction pathways were observed in [Bmim]BF4: nucleophilic attack at the phosphoryl center, SN2(P), and at the C-1 aromatic carbon, SN(Ar), where the product distribution remained constant and independent of the amine nature. In contrast, in [Bmim]DCA only the SN2(P) pathway was found. From the kinetic analysis of the SN2(P) pathway in both ILs, curved upwards plots of kobsdvs. 1-formylpiperazine concentration were obtained. Based on the kinetic behavior, a change in the mechanism of the SN2(P) pathway is proposed for the aminolysis of 1, from a concerted process in aqueous ethanol to a stepwise mechanism, through a zwitterionic pentacoordinate intermediate, when [Bmim]BF4 and [Bmim]DCA are used as the solvents of the reaction.

Toward a pK(a) scale of N-base amines in ionic liquids.

An electrochemical technique was used to investigate pKa values of some substituted secondary alicyclic (SA) amines, pyridines (py), anilines (AN), and triethylamine (Et3N) in different ionic liquids. The method involves cyclic voltammetry at a platinized Pt electrode. The experimental data were correlated with pKa values reported previously in aqueous solution, and Hammett parameters were correlated with pKa values in ionic liquids to determine ρ values in these media.

Coumarin-based fluorescent probes for dual recognition of copper(II) and iron(III) ions and their application in bio-imaging.

Two new coumarin-based "turn-off" fluorescent probes, (E)-3-((3,4-dihydroxybenzylidene)amino)-7-hydroxy-2H-chromen-2-one (BS1) and (E)-3-((2,4-dihydroxybenzylidene)amino)-7-hydroxy-2H-chromen-2-one (BS2), were synthesized and their detection of copper(II) and iron(III) ions was studied. Results show that both compounds are highly selective for Cu²âº and Fe³âº ions over other metal ions. However, BS2 is detected directly, while detection of BS1 involves a hydrolysis reaction to regenerate 3-amino-7-hydroxycoumarin (3) and 3,4-dihydroxybenzaldehyde, of which 3 is able to react with copper(II) or iron(III) ions. The interaction between the tested compounds and copper or iron ions is associated with a large fluorescence decrease, showing detection limits of ca. 10⁻5 M. Preliminary studies employing epifluorescence microscopy demonstrate that Cu²âº and Fe³âº ions can be imaged in human neuroblastoma SH-SY5Y cells treated with the tested probes.

Mechanisms of degradation of paraoxon in different ionic liquids.

Herein, the reactivity and selectivity of the reaction of O,O-diethyl 4-nitrophenyl phosphate triester (Paraxon, 1) with piperidine in ionic liquids (ILs), three conventional organic solvents (COS), and water is studied by (31)P NMR, UV-vis, and GC/MS. Three phosphorylated products are identified as follows: O,O-diethyl piperidinophosphate diester (2), O,O-diethyl phosphate (3), and O-ethyl 4-nitrophenyl phosphate diester (4). Compound 4 also reacts with piperidine to yield O-ethyl piperidinophosphate monoester (5). The results show that both the rate and products distribution of this reaction depend on peculiar features of ILs as reaction media and the polarity of COS.

Dephosphorylation reactions of mono-, di-, and triesters of 2,4-dinitrophenyl phosphate with deferoxamine and benzohydroxamic acid.

This work presents a detailed kinetic and mechanistic study of biologically interesting dephosphorylation reactions involving the exceptionally reactive nucleophilic group, hydroxamate. We compare results for hydroxamate groups anchored on the simple molecular backbone of benzohydroxamate (BHA) and on the more complex structure of the widely used drug, deferoxamine (DFO). BHA shows extraordinary reactivity toward the triester diethyl 2,4-dinitrophenyl phosphate (DEDNPP) and the diester ethyl 2,4-dinitrophenyl phosphate (EDNPP) but reacts very slowly with the monoester 2,4-dinitrophenyl phosphate (DNPP). Nucleophilic attack on phosphorus is confirmed by the detection of the phosphorylated intermediates formed. These undergo Lossen-type rearrangements, resulting in the decomposition of the nucleophile. DFO, which is used therapeutically for the treatment of acute iron intoxication, carries three hydroxamate groups and shows correspondingly high nucleophilic activity toward both triester DEDNPP and diester EDNPP. This result suggests a potential use for DFO in cases of acute poisoning with phosphorus pesticides.

Photophysics and photochemical studies of the vitamin B6 group and related derivatives.

The photophysics and photochemical properties of vitamin B6 constituents and analogs were studied as function of pH and solvent. The pK of the phenolic oxygen and the pyridine ring nitrogen depends on the electron donor-acceptor ability of the 4-substituent, and agrees with the calculated proton affinity. For all studied compounds, the fluorescence properties showed that the phenolic oxygen is 8 units more acidic in the lowest singlet excited state than in the ground state. The pyridine N-atom is slightly more basic in the excited state. At pH of biological significance, pH 6-8, pyridoxamine and 4-pyridoxic acid are the more efficient chromophores with higher fluorescence yield and longer lifetime. Spectroscopic studies showed that the tautomeric equilibrium depends on the nature of the 4-substituent. The quenching of the singlet excited state of pyridoxamine and 4-pyridoxic acid by amino acids, free or in a peptide, and DNA bases at pH 7 was studied by time-resolved fluorescence techniques. The quenching rate constants are well correlated with the redox properties of the pyridoxinic compound and amino acids, and are related to the free energy change in the electron transfer process. Guanosine and pyrimidine bases also are efficient quenchers, involving an electron transfer reaction.

Structure and medium effects on the photochemical behavior of nonfluorinated quinolone antibiotics.

The photophysical behavior of the quinolone antibiotics, oxolinic (OX), cinoxacin (CNX) and pipemidic (PM) acids was studied as a function of pH and solvent properties. The ground state of these compounds exhibits different protonated forms, which also exist in the first excited states. Theoretical calculations of the Fukui indexes allowed to assigning the different protonation equilibria. The pK values indicate that the acidity of the 3-carboxylic and 4-carbonyl groups increases with the N-atom at position 2 in CNX. It has been found that fluorescence properties are strongly affected by pH, the more fluorescent species is that with protonated carboxylic acid, protonated species at the carbonyl group and the totally deprotonated form present very low fluorescence. The fluorescence behavior also depends on the chemical structure of the quinolone and on the solvent properties. The analysis of the solvent effect on the maximum and the width of the fluorescence band of OX, using the linear solvent-energy relation solvatochromic equation, indicates that the polarizability and hydrogen bond donor ability are the parameters that condition the spectral changes. The hydrogen bond acceptor ability of the solvents also contributes to the spectral shifts of CNX. The compound bearing the piperazinyl group at the position 7, PM only is fluorescent in high protic solvents. These results are discussed in terms of the competition between the intra- and intermolecular hydrogen bonds. The irradiation of OX, CNX and PM using 300 nm UV light led to a very low photodecomposition rate. Under the same conditions the nalidixic acid (NA), a structurally related quinolone, photodecomposes two orders of magnitude faster.

Photophysics and photochemical studies of 1,4-dihydropyridine derivatives.

The absorption and fluorescence properties of nifedipine (NPDHP), felodipine (CPDHP) and a series of structurally related 1,4-dihydropyridines were studied in aqueous solution and organic solvents of different properties. The absorption and fluorescence spectra were found to depend on the chemical nature of the substituents at the position 4 of the 1,4-dihydropyridine ring (DHP) and on solvent properties. In aqueous solution, the fluorescence spectra of 4-phenyl substituted compounds are blue-shifted with respect to the alkyl substituted compounds. The more fluorescent compound is CPDHP. Nifedipine is not fluorescent. All compounds, with the exception of CPDHP, present monoexponential fluorescence decay with very short lifetime (0.2-0.4 ns). CPDHP showed a biexponential emission decay with a long-lived component of 1.7 ns; this behavior is explained in terms of different conformers because of the hindered rotation of the phenyl group by the ortho-substitution. Analysis of the solvent effect on the maximum of the absorption spectrum by using the linear solvent-energy relation solvato-chromic equation indicates the redshifts are influenced by the polarizability, hydrogen bonding ability and the hydrogen bond acceptance of the solvent. Whereas, the fluorescence characteristics (spectra, quantum yields and lifetimes) are sensitive to the polarizabilty and hydrogen bond ability of the solvents. Photo-decomposition of nifedipine is dependent on the solvent properties. Faster decomposition rates were obtained in nonprotic solvents. The 4-carboxylic derivative goes to decarboxylation. Under similar conditions, the other DHP compounds did not show appreciable photodecomposition.

Photophysics and photochemistry of nalidixic acid.

The photophysics and photochemistry of nalidixic acid (NA) were studied as function of pH and solvent properties. The ground state of NA exhibits different protonated forms in the range of pH 1.8-10.0. Fluorescence studies showed that the same species exist at the lowest singlet excited state. Absorption experiments were carried out with NA and with the methylated analog of nalidixic acid (MNE) in different organic solvents and water pH 3, where the main species corresponds to that protonated at the carboxylic group. These studies and the DFT calculation of torsional potential energy profiles suggest that the most stable conformation of the NA in nonprotic solvents corresponds to a closed structure caused by the existence of intramolecular hydrogen bond. Absorption and fluorescence spectra were studied in sulfuric acid solution. The pK value (Ho -1.0) found in these conditions was attributed to the protonation of the 4' keto oxygen atom of the heterocyclic ring. Theoretical calculations (DFT/B3LYP/6-311G*) of the energies of the different monoprotonated forms of the NA and Fukui indexes (f(x)-) showed that the species with the proton attached to 4' keto oxygen atom is the most stable of all the cationic forms. MNE and enoxacin also showed the protonation of the 4' keto oxygen atom with similar pK values. The photodecomposition of NA is dependent on the medium properties. Faster decomposition rates were obtained in strong acid solution. In nonprotic solvents, a very slow decomposition rate was observed.

Kinetics and mechanism of the benzenethiolysis of O-ethylS-(2,4-dinitrophenyl) and O-ethyl S-(2,4,6-trinitrophenyl) dithiocarbonates and O-methyl O-(2,4-dinitrophenyl) thiocarbonate.

Reactions of O-ethyl 2,4-dinitrophenyl dithiocarbonate (EDNPDTC), O-ethyl 2,4,6-trinitrophenyl dithiocarbonate (ETNPDTC), and O-methyl O-(2,4-dinitrophenyl) thiocarbonate (MDNPTOC) with a series of benzenethiolate anions in aqueous solution, at 25.0 degrees C and an ionic strength of 0.2 M (KCl), are subjected to a kinetic investigation. Under excess benzenethiolate, these reactions obey pseudo-first-order kinetics and are first order in benzenethiolate. Nonetheless, similar reactant concentrations were used in the reactions of 4-nitrobenzenethiolate anion with the ethyl trinitrophenyl ester (ETNPDTC), which showed overall second-order kinetics. The nucleophilic rate constants (k(N)) are pH independent, except those for the reactions of ETNPDTC with the X-benzenethiolates with X = H, 4-Cl, and 3-Cl, which increase as pH decreases. The Brønsted-type plots (log k(N) vs pK(a) of benzenethiols) are linear with slopes beta = 0.66 for the reactions of both ethyl dinitrophenyl ester (EDNPDTC) and ethyl trinitrophenyl ester (ETNPDTC) and beta = 0.58 for those of the thiocarbonate ester (MDNPTOC). For the benzenethiolysis of MDNPTOC and EDNPDTC, no breaks were found in the Brønsted-type plots at pK(a) 4.1 and 3.4, respectively, consistent with concerted mechanisms. Benzenethiolysis of the ethyl trinitrophenyl ester (ETNPDTC) should also be concerted in view of the even more unstable tetrahedral "intermediate" that would have been formed had this reaction been stepwise. ETNPDTC is more reactive toward benzenethiolate anions than EDNPDTC due to the better leaving group involved in the former substrate. The k(N) values found for the reactions of EDNPDTC with benzenethiolates are larger than those obtained for the concerted reactions of the same substrate with isobasic phenoxide anions. This is explained by Pearson's "hard and soft acids and bases" principle. The concerted mechanism for the benzenethiolysis of MDNPTOC, in contrast to the stepwise mechanism found for the phenolysis of this substrate, is attributed to the greater kinetic instability of the hypothetical tetrahedral "intermediate" formed in the former reaction, due to the greater nucleofugality of ArS(-) compared with an isobasic ArO(-). Benzenethiolates are more reactive toward MDNPTOC and EDNPDTC than the corresponding carbonate and thiolcarbonate, respectively. This is also in accordance with the HSAB principle, since benzenthiolates are relatively soft bases that prefer to bind to a relatively soft thiocarbonyl center rather than a relatively hard carbonyl center.

Kinetic study of the phenolysis of O-methyl and O-phenyl O-2,4-dinitrophenyl thiocarbonates and O-ethyl 2,4-dinitrophenyl dithiocarbonate.

The reactions of a series of phenols with O-methyl O-2,4-dinitrophenyl thiocarbonate (MDNPTOC), O-phenyl O-2,4-dinitrophenyl thiocarbonate (PDNPTOC), and O-ethyl 2,4-dinitrophenyl dithiocarbonate (EDNPDTC) are studied kinetically in water, at 25.0 degrees C and an ionic strength of 0.2 M (KCl). All reactions show pseudo-first-order kinetics under an excess of phenol over the substrate, and are first order in phenoxide anion. The reactions of EDNPDTC show a linear Brønsted-type plot of slope beta = 0.67, suggesting a concerted mechanism. On the other hand, the phenolyses of MDNPTOC and PDNPTOC exhibit linear Brønsted-type plots of slopes beta = 0.27 and 0.28, respectively, consistent with stepwise mechanisms where the formation of an anionic tetrahedral intermediate (T(-)) is rate determining. By comparison of the kinetics and mechanisms of the reactions under investigation with similar reactions, the following conclusions arise: (i). Substitution of S(-) by O(-) in the intermediate T(-) destabilizes this species. (ii). The change of DNPO in T(-) to DNPS also destabilizes this intermediate. (iii). Substitution of MeO by PhO as the nonleaving group of the substrate does not affect the kinetics, probably by a compensation of electronic and steric effects. (iv). The change of an amino group in a tetrahedral intermediate to a phenoxy group destabilizes the intermediate.

Kinetics and mechanism of the benzenethiolysis of 2,4-dinitrophenyl and 2,4,6-trinitrophenyl methyl carbonates and S-(2,4-dinitrophenyl) and S-(2,4,6-trinitrophenyl) ethyl thiolcarbonates.

The reactions of 2,4-dinitrophenyl and 2,4,6-trinitrophenyl methyl carbonates (DNPC and TNPC, respectively) and S-(2,4-dinitrophenyl) and S-(2,4,6-trinitrophenyl) ethyl thiolcarbonates (DNPTC and TNPTC, respectively) with a series of benzenethiolate anions were subjected to a kinetic investigation in water, at 25.0 degrees C, and an ionic strength of 0.2 M (KCl). These reactions obey pseudo-first-order kinetics, under excess of benzenethiolate, and are first order in the latter reactant. However, comparable reactant concentrations were used in the reactions of 4-nitrobenzenethiolate anion with TNPC and TNPTC, which showed second-order kinetics. The nucleophilic rate constants are pH independent, except those for the reactions of TNPC with 4-methoxy- and pentafluorobenzenethiolates, and TNPTC with benzenethiolate and 4-chloro- and 3-chlorobenzenethiolates, which show acid dependence. The Brønsted-type plots for the nucleophilic rate constants are linear with slopes beta = 0.9, 1.0, 0.9, and 0.9 for the reactions of DNPC, TNPC, DNPTC, and TNPTC, respectively. No break in the Brønsted plot was found for the reactions of DNPC and DNPTC at pK(a) ca. 4.1 and 3.4, respectively, consistent with concerted mechanisms. TNPC is more reactive toward benzenethiolate anions than DNPC, and TNPTC more than DNPTC due to the better leaving groups involved. Comparison of the kinetic results obtained in this work with those for the concerted phenolysis of the same substrates shows that benzenethiolate anions are better nucleophiles toward carbonates than isobasic phenoxide anions. This is explained by Pearson's "hard and soft acids and bases" principle.