Naphthyl cyanoketene N,S-acetals in glycoside synthesis: a new preparative route to a new class of N-naphthylcyanoacrylamide thioglycosides and their conversions to naphthyl-pyrazole hybrids.

The novel N-naphthylcyanoacrylamide thioglycosides 4 were readily prepared by the reaction of N-napthylcyanoacetamide 1 with aryl isothiocyanates in the presence of potassium hydroxide, followed by coupling of the produced salts 2 with 2,3,4,6-tetra-O-acetyl-α-d-gluco- and galacto-pyranosyl bromides 3. The N-naphthyl acrylamide thioglycoside 12 was prepared by the reaction of N-napthylcyanoacetamide 1 with glucose isothiocyante 10 in the presence of potassium hydroxide, followed by alkylation of the produced salt 11 with methyl iodide. The reaction of thioglycoside compounds 4 with hydrazines afforded the corresponding naphthyl-pyrazole hybrids.

Aroyl-S,N-Ketene Acetals: Luminous Renaissance of a Class of Heterocyclic Compounds.

Aroyl-S,N-ketene acetals represent a peculiar class of heterocyclic merocyanines, compounds bearing pronounced and rather short dipoles with great push-pull characteristics that define their rich properties. They are accessible via a wide array of synthetic concepts and procedures, ranging from addition-elimination and condensation procedures up to rearrangement and metal-mediated reactions. With our work from 2020, aroyl-S,N-ketene acetals have been identified as powerful and promising dyes with pronounced and vastly tunable solid-state emission and aggregation-induced emission properties. One characteristic trademark of this class of dye molecules is the level of control that could be exerted, and which was thoroughly explored. Based on these results, the field was opened to extend the system to bi- and multichromophoric systems by the full toolkit of synthetic organic chemistry thus giving access to even more exciting properties and manifolded substance libraries capitalizing on the AIE properties. This review aims at outlining the reaction-based principles that allow for a swift and facile access to aroyl-S,N-ketene acetals, their methodical and structural evolution and the plethora of fluorescence and aggregation properties.

Diaroyl-S,N-ketene Acetals: Red-Shifted Solid-State and Aggregation-Induced Emitters from a One-Pot Synthesis.

Symmetric and unsymmetric diaroyl-S,N-ketene acetals can be readily accessed in consecutive syntheses in good to excellent yields by exploiting the inherent nucleophilic character of the methine position. Different aroyl-S,N-ketene acetals as well as acid chlorides yield a library of 19 diaroyl compounds with substitution and linker pattern-tunable emission properties, leading to a significant red-shift of emission in the solid and aggregated state, which was thoroughly investigated. Additionally, the stability of the luminescent aggregates is highly increased. In a follow-up one-pot procedure, pyrazolo-S,N-ketene acetals can easily be accessed employing a nucleophilic cyclocondensation.

p-Toluenesulfonic acid adorned on MCM-41: an efficient and mild catalyst for the regio/chemo-selective hydrolysis of terminal isopropylidene acetals.

Regio/chemo-selective hydrolysis of a 5,6-O-isopropylidene group over a 1,2-O-isopropylidene group is accomplished to obtain corresponding diols in good to excellent yields within 4-5 hours using the p-toluenesulfonic acid impregnated MCM-41 (PTSA-MCM-41) catalyst in acetonitrile and water (9:1, v/v) at room temperature. Other sensitive hydroxyl protecting groups such as naphthyl, toluoyl, pivaloyl, benzoyl, and benzyl are compatible with this methodology. The low cost of the PTSA-MCM-41 catalyst and ease of separation of product from the reaction mixture are significant advantages of this method, which makes it useful in the multigram scale operation.

Current Standing on Radical Ring-Opening Polymerizations of Cyclic Ketene Acetals as Homopolymers and Copolymers with one another.

Radical Ring-opening polymerization (RROP) of cyclic ketene acetals (CKAs) emerges to be a valuable polymerization technique. In attracting more attention, RROP has seen a new spike in publications, which the authors will put into perspective. This review will hence address the progress made on the number of available CKAs and the synthetic strategies to get them. In grouping, the available monomers into distinct categories, the enormous variety of available CKAs will be highlighted. Polymerizations of CKAs without vinylenes have the potential to yield fully biodegradable polymers, which is why this kind of polymerization is the focus of this review. Detailing the current understanding of the mechanism, the various side reactions will be noted and also their effect on the overall properties of the final polymers. Current attempts to control the ring-retaining and branching reactions will be discussed as well. In addition to the polymerization itself, the available materials will be discussed as well as homopolymers, copolymers of CKAs, and block-copolymers with pure CKA-blocks have significantly widened the range of possible applications of materials from RROP. Altogether this review highlights the progress in the entire field of RROP just of CKAs to give a holistic overview of the field.

O,S-Acetals in a New Modification of oxo-Friedel-Crafts-Bradsher Cyclization-Synthesis of Fluorescent (Hetero)acenes and Mechanistic Considerations.

This paper presents the use of O,S-acetals in a new modification of the oxo-Friedel-Crafts-Bradsher cyclization. In this reaction, under mild reaction conditions (25 °C), three- and four-ring fused RO-acenes (major) and/or HO(CH2)2S-acenes (minor) are formed, the latter products having never been observed before in this type of cyclization. In this way, two electronically different fluorophores could be obtained in a single cyclization reaction, one of them having strong electron donor properties (+M effect of alkoxy groups) and the other having donor-acceptor properties (+M and -I effects of the HO(CH2)2S-group, Hammett's constants). Further increasing the reaction temperature, HCl concentration or prolonging reaction time, surprisingly, yielded a 2:1 mixture of cis and trans dimeric isomers, as the only products of this cyclization. The DFT calculations confirmed a greater stability of the cis isomer compared to the trans isomer. The formation of unexpected dimeric products and HO(CH2)2S-acenes sheds light on the mechanism of oxo-Friedel-Crafts-Bradsher cyclization, involving competitive O/S atom protonation in strained O,S-acetals and in strain-free side groups of intermediate species.

Lewis Acid-Catalyzed 2,3-Dihydrofuran Acetal Ring-Opening Benzannulations toward Functionalized 1-Hydroxycarbazoles.

The development of a Lewis acid-catalyzed, intramolecular ring-opening benzannulation of 5-(indolyl)2,3-dihydrofuran acetals is described. The resulting 1-hydroxycarbazole-2-carboxylates are formed in up to 90% yield in 1 h. The dihydrofuran acetals are readily accessed from the reactions of enol ethers and α-diazo-ß-indolyl-ß-ketoesters. To highlight the method's synthetic utility, a formal total synthesis of murrayafoline A, a bioactive carbazole-containing natural product, was undertaken.

Solid-State Emission and Aggregate Emission of Aroyl- S,N-Ketene Acetals Are Controlled and Tuned by Their Substitution Pattern.

Aroyl-S,N-ketene acetals are a novel highly diverse class of aggregation-induced emission fluorogens (AIEgens) with a plethora of interesting properties. An expanded compound library of more than 110 dyes set the stage for the first qualitative control and tuneability of all aspects of their photophysical properties. The interplay of substituents not only allows tuning and prediction of the emission color, but also of the intensity, and quantum yields both in solids and in the aggregated state; these can be rationalized by scrutinizing intermolecular interactions in the crystalline solid state.

Advances in mosquito repellents: effectiveness of citronellal derivatives in laboratory and field trials.

BACKGROUND: Several essential oils, including citronella (lemongrass, Cymbopogon sp., Poaceae), are well-known mosquito repellents. A drawback of such products is their limited protection time resulting from the high volatility of their active components. In particular, citronella oil protects for <2 h, although formulations with fixatives can increase this time. RESULTS: We synthesized hydroxylated cyclic acetals of citronellal, the main component of citronella, to obtain derivatives with lower volatility and weaker odour. The crude mixture of isomers obtained in the reaction was tested under laboratory conditions for its repellency against two mosquito species, the major malaria vector Anopheles gambiae and the arbovirus vector Aedes albopictus, and found to be endowed with longer protection time with respect to DEET (N,N-diethyl-meta-toluamide) at the same concentration. Formulated products were tested in a latin square human field trial, in an area at a high density of A. albopictus for 8 h from the application. We found that the performance of the citronellal derivatives mixture is comparable (95% protection for ≤3.5 h) with those of the most widespread synthetic repellents DEET and Icaridin, tested at a four-fold higher doses. CONCLUSIONS: Modifying the hydrophilicity and volatility of natural repellents is a valuable strategy to design insect repellents with a long-lasting effect. © 2022 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

Diversity-Oriented Metal-Free Synthesis of Nitrogen-Containing Heterocycles Using Atropaldehyde Acetals as a Dual C3/C2-Synthon.

A highly efficient and elegant diversity-oriented reaction paradigm employing atropaldehyde acetals as new dual C2/C3 synthons was developed under metal-free conditions using glycine esters as the counterpart reagents, which allowed rapid synthesis of two important nitrogen-containing heterocycles, pyrrolo[1,2-a]quinolines and 3,5-diarylpyridines. The divergent products are subtly controlled by the manipulation of the substitutional groups of glycine esters. When a N-arylglycine ester was used, pyrrolo[1,2-a]quinolines can be formed through cascade oxidative C-C cleavage/multiple cyclization. Instead, N-benzylglycine ester as the counter-reagent led to the synthesis of 3,5-diarylpyridines via two key C-N cleavages. Mild conditions, broad substrate scope, scalability and environmentally acceptable organic solvents rendered this method practical and attractive.

Sulfuric Acid Immobilized on Activated Carbon Aminated with Ethylenediamine: An Efficient Reusable Catalyst for the Synthesis of Acetals (Ketals).

Through the amination of oxidized activated carbon with ethylenediamine and then the adsorption of sulfuric acid, a strong carbon-based solid acid catalyst with hydrogen sulfate (denoted as AC-N-SO4H) was prepared, of which the surface acid density was 0.85 mmol/g. The acetalization of benzaldehyde with ethylene glycol catalyzed by AC-N-SO4H was investigated. The optimized catalyst dosage accounted for 5 wt.% of the benzaldehyde mass, and the molar ratio of glycol to benzaldehyde was 1.75. After reacting such mixture at 80 °C for 5 h, the benzaldehyde was almost quantitatively converted into acetal; the conversion yield was up to 99.4%, and no byproduct was detected. It is surprising that the catalyst could be easily recovered and reused ten times without significant deactivation, with the conversion yield remaining above 99%. The catalyst also exhibited good substrate suitability for the acetalization of aliphatic aldehydes and the ketalization of ketones with different 1,2-diols.

Synthesis and removal of trichloroethylidene derivatives of carbohydrates.

Two hexoses and two pentoses have been reacted with two equivalents of trichloroacetaldehyde using boron trifluoride etherate as promoter in dioxane at reflux. The major products are exo-1,2-O-trichloroethylidenealdofuranoses in every case in varying yields, identical to the products previously obtained in lower yields using sulfuric acid or hydrochloric acid as promoter in trichloroacetaldehyde as solvent. Careful fractionation of the remainders of the product mixtures showed that the other isomer in the acetal ring was also produced in most cases but small amounts of the two 1,2-O-trichloroethylidenealdopyranose isomers were also produced. In addition, very small amounts of other products were identified that were derived from boron trifluoride etherate and the solvent. A mechanism involving rate-determining acetal ring closure was proposed to explain the formation of furanose derivatives, rather than pyranose derivatives. Methods for removal of the trichloroethylidene acetals were investigated for substituted derivatives and it was found that a process involving reduction with tributyltin hydride was effective.

Co-occurrence of odor-causing dioxanes and dioxolanes with bis(2-chloro-1-methylethyl) ether in Huangpu River source water and fates in O3-BAC process.

In recent years, dioxanes and dioxolanes have been intermittently detected in water environment and have caused several offensive drinking water odor incidents worldwide. In this study, the co-occurrence of eight dioxanes, twelve dioxolanes and bis(2-chloro-1-methylethyl) ether was investigated in Huangpu River watershed to explore potential sources and contributions to septic/chemical odor. Totally 8 dioxanes and dioxolanes were detected in river, with 1,4-dioxane (212 -8310 ng/L) and 2,5,5-trimethyl-1,3-dioxane (n.d.-133 ng/L) as the dominated dioxanes, 2-methyl-1,3-dioxolane (49.5 -2278 ng/L), 2-ethy-4-methyl-1,3-dioxolane (n.d.-167 ng/L) and 1,3-dioxolane (n.d.-225 ng/L) as the major dioxolanes. Bis(2-chloro-1-methylethyl) ether was detected (n.d.-1094 ng/L) with significant correlation with dioxanes and dioxolanes, illustrating their similar polyester resin-related industrial origins. 2-Ethy-4-methyl-1,3-dioxolane, 2,5,5-trimethyl-1,3-dioxane and bis(2-chloro-1-methylethyl) ether with individual maximum odor activity value above 1, should contribute to septic/chemical odor in Huangpu River water. The increased concentrations of these chemicals in the downstream of some industrial areas illustrated the association with industrial discharge. Fates in a waterworks using the river water as source water were further explored. The adopting ozone-biological activated carbon treatment could permit a relatively high removal for bis(2-chloro-1-methylethyl) ether and 2,5,5-trimethyl-1,3-dioxane (> 80%), while limited removal for other chemicals. This study provides valuable information for the management of drinking source water and water environment.

A Facile and Unprecedented Route to a Library of Thermostable Formaldehyde-Derived Polyesters: Highly Active and Selective Copolymerization of Cyclic Acetals and Anhydrides.

The development of new strategies for producing polyesters can expand the category of biodegradable materials. Here, we disclose the alternating copolymerization of cyclic acetals (made from formaldehyde and diols) and anhydrides for the first time, using 5 cyclic acetals and 9 anhydrides to afford 45 unprecedented polyesters. At a wide range of reaction temperatures (25 to 140 °C), diverse metal-free Lewis/Brønsted acids are highly active catalysts for these copolymerizations via the cationic mechanism. Of interest, kinetic studies indicate that the copolymerization of cyclic acetals and anhydrides shifts the chemical equilibrium of "cyclic acetals ⇌ polyacetals" to the left, thus yielding polyesters with up to >99 % alternating degree. The obtained polyesters possess high oxygen content ([O] : [C] up to 6 : 7), molecular weights of 2.0-33.3 kDa, narrow polydispersities of 1.2-1.5, low glass transition temperatures (-64 to -27 °C), as well as high decomposition temperatures (275 to 324 °C).

Chitosan Cross-Linking with Acetaldehyde Acetals.

Here we demonstrate the possibility of using acyclic diethylacetal of acetaldehyde (ADA) with low cytotoxicity for the fabrication of hydrogels via Schiff bases formation between chitosan and acetaldehyde generated in situ from acetals in chitosan acetate solution. This approach is more convenient than a direct reaction between chitosan and acetaldehyde due to the better commercial availability and higher boiling point of the acetals. Rheological data confirmed the formation of intermolecular bonds in chitosan solution after the addition of acetaldehyde diethyl acetal at an equimolar NH2: acetal ratio. The chemical structure of the reaction products was determined using elemental analysis and 13C NMR and FT-IR spectroscopy. The formed chitosan-acetylimine underwent further irreversible redox transformations yielding a mechanically stable hydrogel insoluble in a broad pH range. The reported reaction is an example of when an inappropriate selection of acid type for chitosan dissolution prevents hydrogel formation.

Formaldehyde analysis of seized cosmetic products by HS-GC-MS of methylal, ethoxymethoxymethane, and ethylal derivatives

Abstract Formaldehyde is a carcinogenic compound used as preservative in cosmetic products. In this study, a derivatization procedure using MeOH, EtOH and HCl (25:25:1), and incubation at 60ºC for 4 hours was optimized, and the derivatized products - methylal, ethoxymethoxymethane (EMM), and ethylal - were directly analyzed by headspace-gas chromatography-mass spectrometry (HS-GC-MS) to determine formaldehyde concentrations. The validated method provided good linearity of the standard curve, selectivity, recovery (89.6-106.6%), repeatability, and intermediate precision (RSD < 12%), with an LOD of 0.0015% and an LOQ of 0.005% for all derivatized analytes. The validated method showed to be fast, clean, and easy to implement in a laboratory. To the best of our knowledge, this is the first reported HS-GC-MS procedure to determine formaldehyde as methylal, ethylal, and EMM as derivatized compounds. The method was satisfactorily applied for the analysis of nine hair-straightener cream samples seized by the Civil Police of the Federal District, Brazil. Eight samples contained formaldehyde, at levels ranging from 0.33 to 4.02 %, higher than the legal levels, indicating the need to control the levels of this toxic compound in cosmetic products

Clarifying the Use of Benzylidene Protecting Group for D-(+)-Ribono-1,4-Lactone, an Essential Building Block in the Synthesis of C-Nucleosides.

In the last two years, nucleosides analogues, a class of well-established bioactive compounds, have been the subject of renewed interest from the scientific community thanks to their antiviral activity. The COVID-19 global pandemic, indeed, spread light on the antiviral drug Remdesivir, an adenine C-nucleoside analogue. This new attention of the medical community on Remdesivir prompts the medicinal chemists to investigate once again C-nucleosides. One of the essential building blocks to synthetize these compounds is the D-(+)-ribono-1,4-lactone, but some mechanistic aspects linked to the use of different carbohydrate protecting groups remain unclear. Here, we present our investigations on the use of benzylidene as a ribonolactone protecting group useful in the synthesis of C-purine nucleosides analogues. A detailed 1D and 2D NMR structural study of the obtained compounds under different reaction conditions is presented. In addition, a molecular modeling study at the B3LYP/6-31G* level of theory with the SM8 solvation model for CHCl3 and DMSO to support the obtained results is used. This study allows for clarifying mechanistic aspects as the side reactions and structural rearrangements liked to the use of the benzylidene protecting group.

Acetal-Based Functional Epoxide Monomers: Polymerizations and Applications.

Protecting group chemistry is essential for various organic transformation and polymerization processes. In particular, conventional anionic ring-opening polymerization (AROP) often requires proper protecting group chemistry because it is typically incompatible with most functional groups due to the highly basic and nucleophilic conditions. In this context, many functional epoxide monomers with proper protecting groups are developed, including the acetal group as a representative example. Since the early introduction of ethoxyethyl glycidyl ether, there is significant development of acetal-based monomers in the polyethers. These monomers are now utilized not only as protecting groups for hydroxyl groups under AROP conditions but also as pH-responsive moieties for biomedical applications, further expanding their utility in the use of functionalized polyethers. Recent progress in this field is outlined from their synthesis, polymerization, and biomedical applications.

Communication of Bichromophore Emission upon Aggregation - Aroyl-S,N-ketene Acetals as Multifunctional Sensor Merocyanines.

Aroyl-S,N-ketene acetal-based bichromophores can be readily synthesized in a consecutive three-component synthesis in good to excellent yields by condensation of aroyl chlorides and an N-(p-bromobenzyl) 2-methyl benzothiazolium salt followed by a Suzuki coupling, yielding a library of 31 bichromophoric fluorophores with substitution pattern-tunable emission properties. Varying both chromophores enables different communication pathways between the chromophores, exploiting aggregation-induced emission (AIE) and energy transfer (ET) properties, and thus, furnishing aggregation-based fluorescence switches. Possible applications range from fluorometric analysis of alcoholic beverages to pH sensors.

Alkene Isomerization Revitalizes the Coates-Claisen Rearrangement.

The [3,3]-sigmatropic rearrangement of allylic vinyl acetals, first investigated by Coates nearly four decades ago, is set apart from other variants of the Claisen rearrangement owing to the versatile monoprotected 1,5-dicarbonyl motif featured in the products. Unfortunately, the synthetically elusive nature of the substrates has thus far precluded the widespread application of this attractive transformation. Herein, we show that the key allylic vinyl acetals can be efficiently generated through alkene isomerization of their readily available regioisomeric counterparts (derived from allylic alcohols and α,ß-unsaturated aldehydes), thus enabling the first systematic study of the substrate scope of this rearrangement, as well as the discovery of exceptionally mild conditions for its mediation by Lewis and Brønsted acids.