Aromatic Acetals Research Articles

Protected syn-Aldol Compounds from Direct, Catalytic, and Enantioselective Reactions of N-Acyl-1,3-oxazinane-2-thiones with Aromatic Acetals.

A direct and asymmetric syn-aldol reaction of N-acyl-1,3-oxazinane-2-thiones with dialkyl acetals from aromatic acetals in the presence of 2-5 mol % [DTBM-SEGPHOS]NiCl2, TMSOTf, and lutidine has been developed. It has been established that the oxazinanethione heterocycle, used for the first time as a scaffold in asymmetric carbon-carbon bond-forming reactions, can be smoothly removed to give access to a variety of enantiomerically pure compounds with high synthetic value.

Practical access to (S)-heterocyclic aromatic acetates via CAL-B/Na2CO3-deacylation and Mitsunobu reaction protocol

Herein, we report the preparation of enantiomerically pure forms of 2,3-dihydrobenzofuran-3-ol (1), chroman-4-ol (2), thiochroman-4-ol (3), 1-(furan-2-yl) ethanol (5) and 1-(thiophen-2-yl) ethanol (6), through a kinetic resolution catalysed by Candida antarctica lipase B/Na2CO3 hydrolysis sequence in organic media. The (R)-furnished alcohols and the (S)-remained acetates are recovered enantiopures (ee >99%, E ≫ 200, Conv = 50%). Those ideal enzymatic kinetic resolution (EKRs) are well incorporated to the Mitsunobu inversion protocol in a one pot procedure to give (S)-heterocyclic acetates (1a–3a) in good to high enantiomeric excess (88%–92% ee). Whilst, the (S)-heteroaromatic acetates (5a and 6a) are given with moderate enantiomeric excess (51%–62% ee). All the (S)-acetates are given in good isolated chemical yields (>80%) allowing to overcome the maximum of 50% yield which could be usually reached in a regular kinetic resolution processes.

Zinc- and Copper-Loaded Nanosponges from Cellulose Nanofibers Hydrogels: New Heterogeneous Catalysts for the Synthesis of Aromatic Acetals.

Herein we report the synthesis of cellulose-based metal-loaded nano-sponges and their application as heterogeneous catalysts in organic synthesis. First, the combination in water solution of TEMPO-oxidized cellulose nanofibers (TOCNF) with branched polyethyleneimine (bPEI) and citric acid (CA), and the thermal treatment of the resulting hydrogel, leads to the synthesis of an eco-safe micro- and nano-porous cellulose nano-sponge (CNS). Subsequently, by exploiting the metal chelation characteristics of CNS, already extensively investigated in the field of environmental decontamination, this material is successfully loaded with Cu (II) or Zn (II) metal ions. Efficiency and homogeneity of metal-loading is confirmed by scanning electron microscopy (SEM) analysis with an energy dispersive X-ray spectroscopy (EDS) detector and by inductively coupled plasma-optical emission spectrometry (ICP-OES) analysis. The resulting materials perform superbly as heterogeneous catalysts for promoting the reaction between aromatic aldehydes and alcohols in the synthesis of aromatic acetals, which play a fundamental role as intermediates in organic synthesis. Optimized conditions allow one to obtain conversions higher than 90% and almost complete selectivity toward acetal products, minimizing, and in some cases eliminating, the formation of carboxylic acid by-products. ICP-OES analysis of the reaction medium allows one to exclude any possible metal-ion release, confirming that catalysis undergoes under heterogeneous conditions. The new metal-loaded CNS can be re-used and recycled five times without losing their catalytic activity.

Highly Site-selective Electrooxidation Providing Facile Entries to Functionalized Aromatic Acetals

Given the fact that aldehydes are among the most fundamental and versatile building blocks in organic synthesis, the development of highly efficient and selective methods for their preparation, especially for those delicately functionalized ones remains significant challenging. To address such an issue, Xu and co-workers have recently reported an elegant electrochemical approach realizing the highly regioselective oxidation of functionalized methyl aromatic hydrocarbons towards the desired aromatic acetals without the use of any chemical oxidants or transition metal catalysts. These acetals can be then conveniently converted into corresponding structurally diverse aldehydes via hydrolysis. In addition, the synthetic practicability of current method was further highlighted as the key step in the preparation of the antihypertensive drug telmisartan. This work has been published in the Nature Communications and can be reached at https://doi.org/10.1038/s41467-020-16519-8 .

Site-selective electrooxidation of methylarenes to aromatic acetals

Aldehyde is one of most synthetically versatile functional groups and can participate in numerous chemical transformations. While a variety of simple aromatic aldehydes are commercially available, those with a more complex substitution pattern are often difficult to obtain. Benzylic oxygenation of methylarenes is a highly attractive method for aldehyde synthesis as the starting materials are easy to obtain and handle. However, regioselective oxidation of functionalized methylarenes, especially those that contain heterocyclic moieties, to aromatic aldehydes remains a significant challenge. Here we show an efficient electrochemical method that achieves site-selective electrooxidation of methyl benzoheterocycles to aromatic acetals without using chemical oxidants or transition-metal catalysts. The acetals can be converted to the corresponding aldehydes through hydrolysis in one-pot or in a separate step. The synthetic utility of our method is highlighted by its application to the efficient preparation of the antihypertensive drug telmisartan.

Unique chemoselective Strecker-type reaction of acetals with TMSCN catalyzed by MgI2 etherate

An efficient and convenient Strecker-type addition of various substituted aromatic acetals, heteroaromatic acetals and α, β-unsaturated acetals with trimethylsilyl cyanide (TMSCN) is achieved catalyzed by 10 mol% of MgI2 etherate (MgI2•(Et2O)n) in a mild, and high chemoselective manner with good to excellent yields. A non-coordinating reaction media (i.e., CH2Cl2) played a vital role in this catalytic process.

KCC-1-NH2-DPA: an efficient heterogeneous recyclable nanocomposite for the catalytic synthesis of tetrahydrodipyrazolopyridines as a well-known organic scaffold in various bioactive derivatives

In this study, a novel approach has been used for the efficient synthesis of tetrahydrodipyrazolopyridine derivatives (5a–m) via a four-component one-pot condensation reaction of aromatic aldehydes, hydrazinehydrate, ethyl acetoacetate, and ammonium acetate in the presence of KCC-1-npr-NH2-DPA as an advanced nano-catalyst in ethanol under reflux conditions at 30 min. For this purpose, mesoporous fibrous nano-silica functionalized by dipenicillamine as a novel nanocatalyst (KCC-1-npr-NH2-DPA) was synthesized using a hydrothermal protocol. KCC-1-npr-NH2-DPA nano-catalyst is easily recyclable eight times without the considerable loss of catalytic activity. Other remarkable features include the short reaction time, simple work-up procedure and providing excellent yields (89–98%) of the products under mild reaction conditions. Furthermore, the effects of solvent, concentration of catalyst, time and temperature for the synthesis of tetrahydrodipyrazolopyridine (5a) were studied.

Platinum on Carbon–Catalyzed and Chemoselective Aqueous Oxygen Oxidation of Aromatic Acetals to Benzoic Acids

Platinum on Carbon–Catalyzed and Chemoselective Aqueous Oxygen Oxidation of Aromatic Acetals to Benzoic Acids

Modulating Fermentative, Varietal and Aging Aromas of Wine Using non-Saccharomyces Yeasts in a Sequential Inoculation Approach.

The goal of this study is to assess to what extent non-Saccharomyces yeasts can introduce aromatic changes of industrial interest in fermentative, varietal and aged aromas of wine. Aroma precursors from Riesling and Garnacha grapes were extracted and used in two independent sequential experiments. Synthetic musts were inoculated, either with Saccharomyces cerevisiae (Sc) or with Pichia kluyveri (Pk), Torulaspora delbrueckii (Td) or Lachancea thermotolerans (Lt), followed by Sc. The fermented samples were subjected to anoxic aging at 50 °C for 0, 1, 2 or 5 weeks before an aroma analysis. The fermentative aroma profiles were consistently changed by non-Saccharomyces: all strains induced smaller levels of isoamyl alcohol; Pk produced huge levels of aromatic acetates and can induce high levels of fatty acids (FA) and their ethyl esters (EE); Td produced large levels of branched acids and of their EE after aging, and induced smaller levels of FA and their EE; Lt produced reduced levels of FA and their EE. The varietal aroma was also deeply affected: TDN (1,1,6-trimethyl-1,2- dihydronaphthalene) levels in aged wines were reduced by Pk and enhanced by Lt in Garnacha; the levels of vinylphenols can be much reduced, particularly by Lt and Pk. TD and Lt can increase linalool and geraniol in young, but not in aged wines.

Hydrotalcite Clay+[TBA][OH] Ionic Liquid Combination for Selective Dihydroquinazolines

Background: We are submitting an easy, effective and environmentally benign protocol for the synthesis of 18 different 1,2-dihydroquinazoline derivatives. Methods: We implemented [TMA][OH] ionic liquid mediated hydrotalcite clay catalytic system as a green catalyst to perform this reaction. Results: Three-component reaction pathway was utilized to synthesize 1,2-dihydroquinazoline derivatives using aromatic aldehydes, 2-amino benzophenones, and ammonium acetate with green and recyclable ionic liquid mediated hydrotalcite clay catalytic system. Conclusion: The notable highlights of this method comprise short reaction time, operational simplicity, high yields, and high selectivity. Additionally, the catalyst can be recovered and recycled for up to eight cycles without any loss in catalytic activity.

Chemoselective Nucleophilic Functionalizations of Aromatic Aldehydes and Acetals via Pyridinium Salt Intermediates.

The development of a novel chemoselective functionalization can diversify the strategy for synthesizing the target molecules. The perfect chemoselectivity between aromatic and aliphatic aldehydes is difficult to achieve by the previous methods. The aromatic aldehyde-selective nucleophilic addition in the presence of aliphatic aldehydes was newly accomplished. Namely, the aromatic aldehyde-selective nucleophilic addition using arenes and allyl silanes proceeded in the presence of trialkylsilyl triflate and 2,2'-bipyridyl, while the aliphatic aldehydes completely remained unchanged. The reactive pyridinium-type salt intermediate derived from an aromatic aldehyde chemoselectively underwent the nucleophilic substitution. Moreover, the aromatic acetals as the protected aldehydes could be directly transformed into similar pyridinium salt intermediates, which reacted with various nucleophiles coexisting with the aliphatic aldehydes.

Synthesis of Fused 2Н-Pyridin-2-ones under the Conditions of Multicomponent Hantzsch Reaction

One-pot process was studied between a substituted 4-hydroxy-2Н-pyran-2-one and aromatic aldehydes and ammonium acetate in the conditions of modified Hantzsch reaction in acid environment under thermal and microwave activation. Arylmethylenebis-4-hydroxy-2Н-pyridin-2-ones, hydrochromenopyridinone, and their oxygen-containing heteroanalogs were isolated. A primary condensation was confirmed into bispyran-2-one adducts, and at the use of salicilaldehyde, into pyranochromene with subsequent recyclization of pyranone fragments in pyridinone ones.

Dual Catalytic Activity of an Ionic Liquid in Lignin Acetylation and Deacetylation

An ionic liquid, 1-ethyl-3-methylimidazolium acetate (EmimOAc) better catalyzed the acetylation of the aliphatic hydroxyl groups of lignin than the phenolic hydroxyl groups using isopropenyl acetate as an acetyl donor. However, in situ 1H NMR analyses performed on model compounds revealed that EmimOAc more effectively promoted the acetylation of phenol than 2-phenethyl alcohol. EmimOAc was also found to selectively catalyze the deacetylation of aromatic acetate, and thus the aliphatic hydroxyl groups of lignin were preferentially acetylated.

Solvent-Free One-Pot Synthesis of 1,8-Dioxo-Decahydroacridines by a [Et3NH][HSO4] Catalyzed Multicomponent Reaction

ABSTRACT[Et3NH][HSO4] has been used as an effective catalyst for one-pot, three-component condensation of an aromatic aldehyde, 5,5-dimethyl-1,3-cyclohexanedione and ammonium acetate for the synthesis of 1,8-dioxo-decahydroacridines under solvent-free conditions. The present methodology offers several advantages, such as high yields, short reaction times, mild condition, and a recyclable catalyst with a very easy work-up.

Synthesis, characterization and heterogeneous catalytic application of a nickel(II) Schiff base complex immobilized on MWCNTs for the Hantzsch four-component condensation

A nickel(II) Schiff base complex immobilized on multi-wall carbon nanotubes (MWCNTs) surface as a highly efficient heterogeneous catalyst was synthesized and characterized by IR, X-ray diffraction patterns, scanning electron microscopy, energy-dispersive X-ray spectroscopy, inductively coupled plasma, elemental analysis, and thermal gravimetric analysis. Then a facile and environmentally benign procedure was developed for synthesis of polyhydroquinoline derivatives via Hantzsch one-pot condensation reaction of aromatic aldehydes, 1,3-diones, ethyl acetoacetate, and ammonium acetate in the presence of above synthesized catalyst under solvent-free conditions. This protocol has the advantages of stability, easy availability, recyclability and eco-friendly nature of catalyst, simple experimental and work-up procedure, and also high to excellent yields. Considering the solvent-free condition and also temperature, time, and yield of the model reaction, the nanocatalyst reported here is among the best catalysts reported so far for synthesis of polyhydroquinolines.

Palladium on Carbon-Catalyzed Chemoselective Oxygen Oxidation of Aromatic Acetals

The development of an unprecedented chemoselective transformation has contributed to forming a novel synthetic process for target molecules. Chemoselective oxidation of aromatic acetals has been accomplished using a reusable palladium on carbon catalyst under atmospheric oxygen conditions to form ester derivatives with tolerance of aliphatic acetals and ketals.

Quantitative Analysis of the Etherification Degree of Phenolic Hydroxyl Groups in Oxyethylated Lignins: Correlation of Selective Aminolysis with FTIR Spectroscopy

PEGylated or oxyethylated lignins (OEL) have recently become a hot topic as precursors for novel lignin-based and sustainable materials or active substances such as hydrogels, aerogels, carbogels, dispersants, and surfactants. Since functional properties of OEL and the resulting materials are strongly affected by the degree of oxyethylation (DOE) of phenolic hydroxyl groups (OHphen), analytical techniques for its determination are crucial. OELs with different levels of modification were obtained by reacting lignins from different pulping procedures with varying amounts of poly(ethylene) glycol-α,ω-diglycidyl ether (PEGDGE). Parent lignins and OELs were characterized by means of selective aminolysis that is subsequent preacetylation and selective deacetylation of aromatic acetates of preacetylated lignin/OEL with pyrrolidine. The reaction product 1-acetyl pyrrolidine was quantified using GC/FID. The DOE of OEL, obtained by subtraction of OHphen content before and after lignin oxyethylation, was found to be...

New mechanistic insight into the aerobic oxidation of methylaromatic compounds catalyzed by Co–Mn–Br and its applications

The mechanism for aerobic oxidation of methylaromatic compounds using Co(CH3COO)2–Mn(CH3COO)2–KBr was further studied. The experimental results suggested that the intermediates (aromatic alcohols) are unexpectedly inert to direct oxidation via Co–Mn–Br catalysts under moderate conditions. In addition, it is found that both aromatic and aliphatic alcohols can inhibit the oxidation of the substrates and other intermediates (aromatic esters, aromatic aldehydes). UV–vis spectra indicated that oxidation from Co(II) to Co(III) would be interrupted in the presence of a given amount of alcohol. A plausible mechanism was also proposed. The intermediates analyzed by LC–MS and control experiments showed that aromatic alcohols prefer to undergo esterification rather than being directly oxidized as described in previous studies, and aromatic acetates are subsequently oxidized to corresponding aldehydes. According to the new mechanism, a strategy of highly selectively synthesizing aromatic alcohols and aldehydes from corresponding methylaromatic compounds was designed. The selectivities of aromatic alcohols and aldehydes could also be tuned by the added amount of CH3COOK.

Tribromo melamine-catalyzed one-pot synthesis of a series of 4-aryl-4,5-dihydro-1H-indeno[1,2-b]pyridine derivatives

A simple and efficient synthesis of 4-aryl-4,5-dihydro-1H-indeno[1,2-b]pyridine derivatives was achieved in one pot via a four-component cyclocondensation of aromatic aldehydes, 1,3-indanedione, β-ketoesters and ammonium acetate in the presence of tribromomelamine (TBM) as the catalyst under neat conditions. The present approach offers several advantages, such as shorter reaction times, higher yields, low cost, simple work-up and easy purification compared with the other available methods.

Phenylpropanoid esters of lesquerella and castor oil

Lesquerella (LO) and castor oil (CO) were esterified at the secondary hydroxyl groups of their 14-hydroxyeicos-cis-11-enoic fatty acids and 12-hydroxyoctadec-cis-9-enoic fatty acids, respectively, with 4-acetoxy-3-methoxycinnamic acid (acetoxyferulic acid). The unconventional esterifications were conducted under inert nitrogen atmospheres without solvent at 175–200°C in sealed ampules. 1H NMR was used to measure the degree of acetoxyferuloyl esterification using a modified esterification number (EN). Reactions at 200°C resulted in ∼43% conversions to the acetoxyferuloylated LO and CO but promoted significant degradation/loss of the acetoxyferulic acid as evidenced by the low quantity of acetoxyferulic acid found in the reaction products as determined by HPLC. Reactions at 175°C resulted in significantly lower conversions to the acetoxyferuloylated LO and CO, 9–17%, but did not result in as severe acetoxyferulic acid degradation. The addition of tin (II) 2-ethylhexanoate catalyst to the 175°C reactions increased esterification conversion to ∼45% without significant loss of acetoxyferulic acid to degradation. The aromatic acetate of the acetoxyferuloylated LO and CO was selectively deacylated using excess pyrrolidine without affecting the aliphatic esters to give feruloylated LO and CO. The feruloylated LO and CO absorbed ultraviolet (UV) radiation from 280 to 360nm with a λmax at 327nm, bridging the absorbance gap of commercial UV absorbing ingredients. The feruloylated LO and CO are also presumably good antioxidants and are potential candidates for incorporation into lipid bilayers to protect liposomes and their contents from reactive oxygen species.