Rapid swelling and deswelling in cryogels of crosslinked poly(N-isopropylacrylamide-co-acrylic acid)

Thermally sensitive hydrogels of poly[N-isopropylacrylamide (NIPA)-co-acrylic acid (AA)] hydrogels with N,N-methylene bisacrylamide (BIS) as crosslinker have been synthesized via a two-step procedure in which, the initial polymerisation is conducted for various times at 18 °C, this step being followed by polymerisation for one fixed time at −22 °C. The gravimetrically determined rates of swelling/deswelling for these materials termed “cryogels” prepared by this two-step polymerisation are much higher than those for the same type of hydrogel prepared via conventional methods (30 °C for 24 h). For example the time for the former xerogel to take up 70% of its final water content at 25 °C is just 18 min, compared with a time 300 min for the latter to attain the same uptake of water. During deswelling (shrinking) at 50 °C, which is above the lower critical temperature, the hydrogel loses 60 and 90 wt% water in 1 and 10 min respectively, compared to a timescale for the corresponding crosslinked copolymers prepared by conventional methods of about 100 min for 50 wt% water loss. A third type of hydrogel was made by a cold treatment (CT), for which the hydrogel prepared by conventional polymerization was stored in the frozen state. The swelling rate of these CT xerogels was the same as that for xerogels prepared by conventional polymerization, but the deswelling rate of the former was higher than that of the latter; for example, during deswelling, a loss of 90% water is attained within a few minutes.Scanning electron microscopy, digital photographs and flotation experiments together with swelling ratio studies reveal that the polymeric network of cryogel produced by the two-step polymerization method is characterized by an open structure with more pores and higher swelling ratio but lower mechanical strength compared to the conventional hydrogels. Such rapid response hydrogels have potential applications in separation and drug release technologies for example.     

Efficient iodine catalyzed chemoselective synthesis of aminals—an access to N,N-acetals by the addition of lactams to N-acyl imines

A highly efficient protocol has been developed for the synthesis of aminals from γ-butyrolactam and benzaldehyde using iodine as Lewis acid catalyst. The attack of γ-butyrolactam nucleophile to intermediate N-acyliminium ion was more favorable, when aryl aldehyde bears the electron donating group (EDG). Iodine plays a key role in these reaction transformations. This current mild protocol is environmentally benign and cost-effective method for the synthesis of industrially and pharmaceutically useful scaffolds.     

Palladium-catalyzed arylation of N,N-dialkylhydrazines and the subsequent conversion to anilines

Palladium-catalyzed aminations of different ArBr with N,N-dialkylhydrazines are described. The reaction proceeded in moderate to excellent yield (up to 90%) with good functional groups compatibilities as cyano, ester, ketone and Boc-amine groups are all well tolerated. Several hydrazines were proved to be good coupling partners and this process provided a general method for the isosteric replacement of benzyl amines with arylhydrazines. Moreover, a method for the N-N bond cleavage of arylhydrazines was discovered, and this two-step sequence could be employed as an alternative synthesis of aniline derivatives.     

Environmentally benign process for the synthesis of N-formyl amino acid esters

Several amino acid ester hydrochlorides were reacted with ammonium formate to give N-formyl amino acid esters in good yields.     

An expedient route for the reduction of carboxylic acids to alcohols employing 1-propanephosphonic acid cyclic anhydride as acid activator

A simple and efficient method for the synthesis of alcohols from the corresponding carboxylic acids is described. Activation of carboxylic acid with 1-propanephosphonic acid cyclic anhydride (T3P) and subsequent reduction using NaBH₄ yield the alcohol in excellent yields with good purity. Reduction of several alkyl/aryl carboxylic acids and N^α-protected amino acids/peptide acids as well as N^β-protected amino acids was successfully carried out to obtain corresponding alcohols in good yields. All the products were fully characterized by ¹H NMR and mass spectral analyses. The procedure is mild, simple and the isolation of the products is easy.     

Remarkable Chichibabin-type cyclotrimerisation of 3-nitrotyrosine, tyrosine and phenylalanine to 3,5-diphenylpyridine derivatives induced by hypochlorous acid

Reaction of 3-nitrotyrosine with HOCl in aqueous phosphate buffer (pH 7.4) leads to a mixture of extractable products, including 3,5-di(4-hydroxy-3-nitrophenyl)pyridine (15% isolated yield) and 3,5-di(4-hydroxy-3-nitrophenyl)-2-(4-hydroxy-3-nitrophenylmethyl)pyridine (3%) arising by a Chichibabin-like pyridine synthesis via N-chloroimine intermediates. Under the same conditions, phenylalanine gives 3,5-diphenylpyridine in 9% isolated yield, while tyrosine leads to 3,5-di(4-hydroxyphenyl)pyridine (3%) and 3-(3-chloro-4-hydroxyphenyl)-5-(4-hydroxyphenyl)pyridine (3%).     

Extending the possibility of an N-Troc-protected sialic acid donor toward variant sialo-glycoside synthesis

The potential of an N-Troc-protected sialic acid donor, equipped with phenylsulfenyl functionality as a leaving group, has been explored. As a result, the entitled donor was proven to be highly reactive and to have broad applicability toward the synthesis of variant sialo-glycans, which have N-glycolyl, de-N-acetyl, 1,5-lactam and 8-O-sulfo sialic acid analogs.     

Comparison of carbene and imidazole bonding to a copper(I) center

The bonding of (1,4,7-trithiacyclononane)copper(I) to N-methylimidazole and to N,N′-dimethylimidazol-2-ylidene (IMe) as its pseudo-tautomer has been compared by crystallography, spectroscopy, and electrochemical analyses. In the solid state, a shorter Cu-L bond is observed for L = carbene than for L = imidazole, which indicates that electronic effects override potential steric hindrance in this pair of complexes. The oxidation potential difference reveals that the imidazole is a substantially stronger donor than the carbene ligand, and it allowed for estimating the Lever electronic parameter for the carbene ligand, E_IMe = +0.30 V.     

Description of the turbidity measurements near the phase transition temperature of poly(N-isopropyl acrylamide) copolymers: the effect of pH, concentration, hydrophilic and hydrophobic content on the turbidity

Absorbance values between 300 and 800 nm of aqueous solutions of poly(N-isopropyl acrylamide-co-itaconic acid-9.80), poly(N-isopropyl acrylamide-co-itaconic acid-52.05) and poly(N-isopropyl acrylamide)s containing Tegomer H-Si 2111 end groups and/or blocks were measured using a Shimadzu 160-A UV-visible spectrometer. Turbidities obtained from these absorbance values were used to interpret the macromolecular phase transition from a hydrophilic to a hydrophobic structure of the polymers. The effects of comonomer type and content, concentration of the solutions, pH and temperature on the coil-globule transition were discussed in terms of turbidity form factor, β related to size and shapes of particles and calculated by using the simplified form of Debye equation.The results presented in this work show that the presence of Tegomer H-Si 2111 (Si containing end groups and/or blocks) or high amount of itaconic acid (IA) in the chains prevent a collapse transition from hydrated extended coils to hydrophobic globules, which aggregate and form a separate phase (β<2). Furthermore, it was observed that in the case of concentrated solutions intermolecular hydrophobic interactions between isopropyl groups overcame the repulsive forces resulting from the ionized carboxylic acid groups of IA or surface active nature of Si containing hydrophobic groups (β>2). This stage of the transition corresponds to macroscopic phase separation after an intramolecular process.     

Phosphite-based sialic acid donors in the synthesis of α(2→9) oligosialic acids

The combination of a phosphite donor and an anomeric thiocresol-protected acceptor, both with a TFA protecting group at C-5 of the sialic acid, provides good α-selectivity and yield in sialylation. Although the convergent synthetic strategy of using a phosphite disialo-donor and a disialo-acceptor assembles tetra-sialic acid efficiently, overcoming the low α-selectivity of α-anomer and purifying it remain to be achieved. Furthermore, mono- and di-sialic acids were, respectively, conjugated on carrier protein, keyhole limpet hemocyanin. The enzymatic hydrolysis method is recommended for estimating the amount of sialic acid on a protein conjugate.     

Lewis acid catalyzed asymmetric halohydrin reactions of chiral α,β-unsaturated carboxylic acid derivatives with N-halosuccinimide (NXS) as the halogen source

Lewis acid catalyzed asymmetric halohydrin reactions—(halohydroxylation as well as halomethoxylation) of chiral α,β-unsaturated carboxylic acid derivatives were performed using N-halosuccinimide (NXS; X = Br, I) as the halogen source. Regio- and anti-selectivity of 100% and moderate to good diastereoselectivity with good yields were observed when Oppolzer’s sultam was used as the chiral auxiliary. Among the Lewis acids, Yb(OTf)₃ was found to be the best catalyst. Alkenoyl and cinnamoyl substrates smoothly underwent bromohydrin reactions and the more electron-rich cinnamoyl substrates preferred to undergo iodohydrin reactions. However, electron-deficient cinnamoyl substrates did not respond to this Lewis acid catalyzed halohydrin reaction with NXS (X = Cl, Br, I).     

An unexpected oxidative decarboxylation reaction of 2,3-dihydroxybenzoic acid in the synthesis of new dibenzyltetrahydroquinoxalinediones

Chemical and electrochemical oxidation of different catechols were carried out in the presence of N,N′-dibenzylethylenediamine (DBEDA) in a phosphate buffer/acetonitrile solution for the synthesis of different new dibenzyltetrahydroquinoxalinedione derivatives. The oxidation of catechol (1a), 2,3-dihydroxybenzoic acid (1e), and 3,4-dihydroxybenzoic acid (1d) led to the same product, probably due to the decarboxylation reaction of intermediates. An oxidative decarboxylation reaction of 3,4-dihydroxybenzoic acid (1d) has been reported before, while an unexpected oxidative decarboxylation reaction of 2,3-dihydroxybenzoic acid (1e) in the presence of DBEDA is reported for the first time.     

Synthetic studies toward the immunosuppressant FR901483. Facile construction of the azatricyclic skeleton

A concise synthesis of the azatricyclic core structure of FR901483, a potent immunosuppressant, has been accomplished. The key elements of the approach involve a nucleophilic addition to an acyl iminium ion, a ring closing metathesis and a lactone-lactam rearrangement to provide the tricyclic structure.     

Simple and efficient cleavage of the N-(1-phenylethyl) unit of carboxamides with methanesulfonic acid

Cleavage of the N-(1-phenylethyl) unit of carboxamides using less than 1 equiv of MsOH in refluxing toluene was found to be simple and very efficient leading to the desired amides in good to excellent yields, and also proved to be more effective compared with reductive methods using hydrogen sources, or acid hydrolysis reagents such as TFA and TsOH. The method selectively cleaved only the N-(1-phenylethyl) group of N-benzyl-N-(1-phenylethyl)amides.     

Study of the oxidation of 3-hydroxypyrroloindoles to pyrrolobenzoxazine alkaloids

This report describes a detailed study of the oxidation-Meisenheimer rearrangement of N-methyl-3-hydroxy-7-chloropyrroloindoline ethyl ester and the corresponding O-Boc and N-Boc derivatives. Experimental conditions were found, which allowed the selective Boc protection of either the tertiary alcohol substituent or the NH group of the aminal function. It was shown that both the parent compound and its O-Boc derivative yielded a mixture of oxazines and, in some cases, N-oxides upon treatment with m-CPBA. MS fragmentation (APCI) clearly differentiates formation of N-oxides and oxazines. The N-Boc derivatives exclusively yielded the N-oxides showing that the Meisenheimer rearrangement requires the presence of a high energy lone pair on the neighbouring nitrogen atom. Both the parent compound and the O-Boc derivative gave a mixture of rearranged products and N-oxide depending on the reaction conditions.     

Me3SiCl-promoted intramolecular cyclization of aromatic compounds tethered with N,O-acetals leading to the facile preparation of 1,4-benzodiazepine skeletons

The Me₃SiCl-promoted intramolecular aminomethylation of a novel type of N,O-acetals, which were prepared via a facile three-step synthesis from N-alkylaniline derivatives and N-alkyl-2-oxazolidinones that leads to the production of pharmaceutically useful 1,4-benzodiazepine skeletons with a variety of functional groups is described. This method was successfully applied to the facile preparation of both tricyclic benzodiazepine derivatives and a 1,4-benzoxazepine derivative via 7-exo-trig cyclization.     

A novel fluorescent and chromogenic probe for cyanide detection in water based on the nucleophilic addition of cyanide to imine group

A fluorescent and colorimetric probe bearing salicylaldehyde hydrazone functionality has been prepared for cyanide sensing. The detection of cyanide was performed via the nucleophilic attack of cyanide anion on the imine group of the probe with a 1:1 binding stoichiometry, which could be confirmed by ¹H NMR and MS studies. The specific reaction results in a prominent fluorescence enhancement and a color change from colorless to yellow.     

A simplified approach to the determination of N-nitroso glyphosate in technical glyphosate using HPLC with post-derivatization and colorimetric detection

A simple and sensitive HPLC post-derivatization method with colorimetric detection has been developed for the determination of N-nitroso glyphosate in samples of technical glyphosate. Separation of the analyte was accomplished using an anionic exchange resin (2.50 mm × 4.00 mm i.d., 15 μm particle size, functional group: quaternary ammonium salt) with Na₂SO₄ 0.0075 M (pH 11.5) (flow rate: 1.0 mL min⁻¹) as mobile phase. After separation, the eluate was derivatized with a colorimetric reagent containing sulfanilamide 0.3% (w/v), [N-(1-naphtil)ethilendiamine] 0.03% (w/v) and HCl 4.5 M in a thermostatized bath at 95 °C. Detection was performed at 546 nm. All stages of the analytical procedure were optimized taking into account the concept of analytical minimalism: less operation times and costs; lower sample, reagents and energy consumption and minimal waste. The limit of detection (k = 3) calculated for 10 blank replicates was 0.04 mg L⁻¹ (0.8 mg kg⁻¹) in the solid sample which is lower than the maximum tolerable accepted by the Food and Agriculture Organization of the United Nations.     

Oxidative addition of N-aminophthalimide to thiophene and selenophene: the first example of a 5-thia(seleno)-3,7-diazatricyclo[4.1.0.0]heptane system

The first examples of condensed saturated heterocycles containing a central tricyclic bisaziridine core were obtained by oxidative addition of N-aminophthalimide to thiophene and selenophene. Their structures and spectral features are described.