Dehydrative Cyclization Research Articles

Asymmetric Dehydrative Cyclization of Allyl Alcohol to Cyclic Ether Using Chiral Brønsted Acid/CpRu(II) Hybrid Catalysts: A DFT Study of the Origin of Enantioselectivity

To elucidate the reaction mechanism and the origin of the enantioselectivity of the asymmetric dehydrative cyclization of allyl alcohol to cyclic ether catalyzed by a Cp-ruthenium complex and a chiral pyridinecarboxylic acid, (R)-X-Naph-PyCOOH, density functional theory (DFT) calculations were performed. According to the DFT calculations, the rate-determining step is the dehydrative σ-allyl formation step with ΔG‡ = 18.1 kcal mol-1 at 80 °C. This agrees well with the experimental data (ΔG‡ = 19.01 kcal mol-1 at 80 °C). The DFT result showed that both hydrogen and halogen bonds play a key role in the high enantioselectivity by facilitating the major R,SRu-catalyzed reaction pathway via a σ-allyl Ru intermediate to generate the major (S)-product. In contrast, the reaction is sluggish in the presence of the diastereomeric R,RRu catalyst with an apparent activation energy of 33.1 kcal mol-1; the minor (R)-product is formed via a typical π-allyl Ru intermediate and via a minor pathway for the cyclization step. In addition, the calculated activation Gibbs free energies, 14.4 kcal mol-1 for I < 16.8 kcal mol-1 for Br < 18.1 kcal mol-1 for Cl, reproduced the observed halogen-dependent reactivity with the (R)-X-Naph-PyCOOH ligands. The origin of the halogen trend was clarified by a structural decomposition analysis.

Unified Approach to Diverse Fused Fragments via Catalytic Dehydrative Cyclization.

A range of highly functionalized polycyclic fragments have been synthesized, employing a catalytic dehydrative cyclization. A range of nucleophiles are shown to be successful, with the reaction producing numerous high value motifs.

The first quantitative investigation of compounds generated from PFAS, PFAS-containing aqueous film-forming foams and commercial fluorosurfactants in pyrolytic processes

Pyrolysis as a thermochemical technology is commonly used in waste management and remediation of organic-contaminated soil. This study, for the first time, investigated fluorinated and non-fluorinated compounds emitted from per- and polyfluoroalkyl substances (PFAS) and relevant products upon pyrolysis (200–890 °C) and their formation mechanisms. Approximately 30 non-fluorinated compounds were detected from PFAS-containing aqueous film-forming foams (AFFFs) and commercial surfactant concentrates (SCs) after heating, including glycols and glycol ethers that were predominant at 200 °C. Oxygen (e.g., 1,4-dioxane) and nitrogen heterocycles and benzene were unexpectedly observed at higher temperatures (300–890 °C), which were likely formed as a consequence of the thermal dehydration, dehydrogenation, and intermolecular cyclization of glycols and glycol ethers. Fluorinated volatiles in six major classes were detected at low and moderate temperatures (200–500 °C), including perfluoroalkenes, perfluoroalkyl aldehydes, fluorotelomer alcohols, and polyfluorinated alkanes/alkenes. Several features of the pyrolyses of PFAS suggest that the underlying decomposition mechanism is radical-mediated. Perfluoroheptene thermally decomposed at 200 °C to shorter-chain homologues following a radical chain-scission mechanism. Most of these volatiles observed at low/moderate temperatures were not detected at 890 °C. Ultra-short-chain fluorinated greenhouse gases (e.g., perfluoromethane) were not found.

Synthesis and Characterization of Bio-Based Poly(amide imide)s Derived from 11-Aminoundecanoic Acid and 1,10-Diaminodecane

Three diimide diacid (DIDA) monomers possessing different rigid groups (phenyl, biphenyl and diphenyl ether group) between two imide rings were prepared through the dehydration cyclization reaction of 11-aminoundecanoic acid and aromatic dianhydride. These DIDA monomers were polymerized with 1,10-diaminodecane to produce bio-based poly(amide imide)s (PAIs) by the ecofriendly and low-cost two-step polymerization method. All the PAIs have high thermal stabilities, and their initial thermal decomposition temperatures are above 400 °C at 5% weight loss. When the rigid group between two imide rings is changed from phenyl to diphenyl ether group, the glass transition temperature of PAI shows a decreasing trend from 54.7 °C to 42.4 °C, the tensile strength also reduces from 62.4 MPa to 49.5 MPa, but elongation at break increases from 3.7% to 6.8%. Moreover, the PAI with phenyl group between two imide rings is a semicrystalline polymer, while the PAI with biphenyl or diphenyl ether group is an amorphous polymer. It is a viable way to regulate the properties of PAIs by changing the structure of rigid group between two imide rings. Such bio-based PAIs with high thermal stabilities, low glass transition temperatures and good mechanical strength will provide great promise for their wider applications.

Recyclable Polyethylene Glycol Ubiquinol Succinate-Bound N-Heterocyclic Carbene–Gold(I) Complexes: Sustainable Micellar Catalysis in Water

An efficient synthesis of three amphiphilic polyethylene glycol ubiquinol succinate (PQS)-bound N-heterocyclic carbene (NHC)–gold(I) complexes as micellar catalysts in bulk water was developed. The surfactant-bound gold catalysts were applied in three different cyclization reactions of acetylenic or allenic substrates, with the main focus being the gold-catalyzed dehydrative cyclization of alkynediols to furans. An effective recycling of the designer surfactant-bound NHC–gold(I) catalysts in water was demonstrated for all cyclization reactions. With sodium dodecyl sulfate as the cosurfactant, a significant acceleration of the catalytic reactions was observed. Mechanistic investigations of the gold-catalyzed dehydrative cyclization of alkynediols point to possible causes for this acceleration effect.

Synthesis of Substituted Thiophenes through Dehydration and Heterocyclization of Alkynols.

A protocol was described for obtaining a variety of substituted thiophenes with functional potential via metal-free dehydration and sulfur cyclization of alkynols with elemental sulfur (S8) or EtOCS2K in moderate-to-good yields. The method provides the base-free generation of a trisulfur radical anion (S3•-) and its addition to alkynes as an initiator. This research broadens the applications of S3•- in the synthesis of sulfur-containing heterocycles.

Synthesis and characterization of dendritic compounds containing nitrogen: monomer precursors in the construction of biomimetic membranes

In this article, we synthesized a novel dendritic 2-oxazoline, 2-(3,4,5-tris(4-dodecyloxybenzyloxy)phenyl)-4,5-dihydro-1,3-oxazole), and its amide precursor N-(2-hydroxyethyl)-3,4,5-tris(4-dodecyloxybenzyloxy)benzamide. Of the distinct synthetic routes explored, it was established that the direct amidation of esters with sodium methoxide followed by the dehydrative cyclisation with 2,3-dichloro-5,6-dicyano-1,4-benzoquinone as oxidizing agent and triphenylphosphine was the most efficient route to synthesize the dendritic 2-oxazoline. Besides, N-(2-hydroxyethyl)-3,4,5-tris(4-dodecyloxybenzyloxy)benzamide exhibited a monotropic columnar mesophase, whilst the dendritic 2-oxazoline does not exhibited a liquid crystalline mesophase. At the end, the first attempts to polymerize the 2-oxazoline monomer via cationic ring opening polymerization showed promising results. Therefore, the dendritic 2-oxazoline could be used as a mesogenic monomer in the synthesis of side-chain liquid-crystalline polyoxazolines that might self-assembly into columnar structures.

Synthetic and Reactions Routes to Tetrahydrothieno[3,2-b]Quinoline Derivatives (Part IV)

Abstract:This review describes the synthesis and chemical reactivity of tetrahydrothieno[3,2-b] quinoline derivatives from through many of the reagents such as; 1, 2-dihydropyridine-3-carbonitrile; 1,6-dihydropyrimidine-5-carbonitrile; 2,3-dihydropyridazine-4-carbonitrile; 3-amino-thiophene-2-carboxylate; 3-amino-thiophene-2-carbonitrile; 3,4-diaminothieno[2,3-b] thiophene-2,5-dicarbo- nitrile; 2-(3-bromo-1-iodoisoquinolin-8-yl) benzonitrile and 3-mercapto-benzo[g]quinolin-4(1H)-one derivatives. The synthesis of the tetrahydrothieno [3, 2-b] quinoline derivatives were explained through the following chemical reactions: Aldol condensation, alkylation, cyclocondensation, dehydration, chlorination, Wolff-Kishner reduction, acylation, Friedlander reaction and intramolecular cyclization.

A strategy for stabilizing of N8 type energetic materials by introducing 4-Nitro-1,2,3-Triazole scaffolds

A series of multi-functionalized 4-nitro-1,2,3-triazole based C–N linked biheterocyclic energetic compounds were synthesized using CDI (1,1′-carbonyldiimidazole) induced dehydrative cyclization. Among these energetic analogues, the representative compounds 2 and 6 exhibit great potential as melt-castable explosive (2: Tm = 72 °C , Td = 231 °C) and high-performance insensitive energetic material (6: d = 1.82 g cm−3, D = 8688 m s−1, IS > 40 J), respectively. More importantly, employing THA (O-tosylhydroxylamine) and SDIC(sodium dichloroisocyanurate), functionalized N8-branched compound (F-N8B, (E)-1,2-bis(4,5′-dinitro-2′H-[2,4′-bi(1,2,3-triazol)]-2′-yl)diazene) was synthesized via N-amination and oxidative azo coupling. In comparison to previously reported N8 type of energetic compounds, F-N8B exhibits improved impact sensitivity and friction sensitivity (IS = 7 J, FS = 72 N).

Asymmetric Total Synthesis of Toxicodenane A by Samarium-Iodide-Induced Barbier-Type Cyclization and Its Cell-Protective Effect against Lipotoxicity.

The asymmetric total synthesis of toxicodenane A, a sesquiterpenoid expected to be promising for diabetic nephropathy, was achieved. In the synthesis, a samarium iodide (SmI2)-induced Barbier-type cyclization and a regio- and stereoselective allylic oxidation followed by a dehydration cyclization were employed as key steps. Furthermore, the first asymmetric syntheses of both enantiomers were accomplished using the previously mentioned synthetic strategy. Finally, the synthetic compounds significantly inhibited lipotoxicity-mediated inflammatory and fibrotic responses in mouse renal proximal tubular cells.

Asymmetric Synthesis of Hydroquinazolines Bearing C4-Tetrasubstituted Stereocenters via Kinetic Resolution of α-Tertiary Amines.

A novel protocol for asymmetric synthesis of hydroquinazolines bearing C4-tetrasubstituted stereocenters has been achieved through kinetic resolution of 2-amido α-tertiary benzylamines via chiral phosphoric acid catalyzed intramolecular dehydrative cyclizations. This method gave access to both α-tertiary benzylamines and hydroquinazolines with broad scope and high enantioselectivities. An intriguing restricted rotation of the C-N bond was observed for hydroquinazoline products bearing C4-tetrasubstituted stereocenters.

Phosphorus-Based Organocatalysis for the Dehydrative Cyclization of N-(2-Hydroxyethyl)amides into 2-Oxazolines

A metal-free, biomimetic catalytic protocol for the cyclization of N-(2-hydroxyethyl)amides to the corresponding 2-oxazolines (4,5-dihydrooxazoles), promoted by the 1,3,5,2,4,6-triazatriphosphorine (TAP)-derived organocatalyst tris(o-phenylenedioxy)cyclotriphosphazene (TAP-1) has been developed. This approach requires less precatalyst compared to the reported relevant systems, with respect to the phosphorus atom (the maximum turnover number (TON) ∼ 30), and exhibits a broader substrate scope and higher functional-group tolerance, providing the functionalized 2-oxazolines with retention of the configuration at the C(4) stereogenic center of the 2-oxazolines. Widely accessible β-amino alcohols can be used in this approach, and the cyclization of N-(2-hydroxyethyl)amides provides the desired 2-oxazolines in up to 99% yield. The mechanism of the reaction was studied by monitoring the reaction using spectral and analytical methods, whereby an 18O-labeling experiment furnished valuable insights. The initial step involves a stoichiometric reaction between the substrate and TAP-1, which leads to the in situ generation of the catalyst, a catechol cyclic phosphate, as well as to a pyrocatechol phosphate and two possible active intermediates. The dehydrative cyclization was also successfully conducted on the gram scale.

Physical Properties of Thermally Crosslinked Fluorinated Polyimide and Its Application to a Liquid Crystal Alignment Layer.

This study demonstrated the use of a thermally crosslinked polyimide (PI) for the liquid crystal (LC) alignment layer of an LC display (LCD) cell. Polyamic acid was prepared using 4,4′-oxydianiline (ODA) and 4,4′-(hexafluoroisopropylidene) diphthalic anhydride (6FDA). The 6FDA−ODA-based polyimide (PI) prepared by the thermal cyclic dehydration of the polyamic acid (PAA) was soluble in various polar solvents. After forming a thin film by mixing trifunctional epoxide [4-(oxiran-2-ylmethoxy)-N,N-bis(oxiran-2-ylmethyl)aniline] with the 6FDA−ODA-based PAA, it was confirmed that thermal curing at −110 °C caused an epoxy ring opening reaction, which could result in the formation of a networked polyimide not soluble in tetrahydrofuran. The crosslinked PI film showed a higher rigidity than the neat PI films, as measured by the elastic modulus. Furthermore, based on a dynamic mechanical analysis of the neat PI and crosslinked PI films, the glass transition temperatures (Tgs) were 217 and 339 °C, respectively, which provided further evidence of the formation of crosslinking by the addition of the epoxy reagent. After mechanical rubbing using these two PI films, an LC cell was fabricated using an anisotropic PI film as an LC alignment film. LC cells with crosslinked PI layers showed a high voltage holding ratio and low residual direct current voltage. This suggests that the crosslinked PI has good potential for use as an LC alignment layer material in advanced LCD technologies that require high performance and reliability.

Direct synthesis of 3,5‐diaryl‐1,2,4‐oxadiazoles using 1‐(2‐oxo‐2‐arylethyl)pyridin‐1‐iums with benzamidines

AbstractAn efficient domino protocol for the synthesis of 1,2,4‐oxadiazole derivatives from readily available 1‐(2‐oxo‐2‐arylethyl)pyridin‐1‐iums and amidine hydrochlorides was developed. In this practical approach, N‐acyl amidine precursors were formed firstly via a simple nucleophilic substitution, without the purification of N‐acylamidine intermediates, and the following intramolecularly dehydrative cyclization gave 1,2,4‐oxadiazole derivatives in the presence of I2/K2CO3/DMSO, which exhibited excellent functional group tolerance and proceeded under simple experimental conditions.

Synthesis, characterizations and conformational analysis of some new 2-arylidene N-(1,3-dioxoisoindolin-2-yl)aminothiocarbohydrazides and their conversion to functionalized hybrids of isoindole core with thiadiazoline

A novel series of thiosemicarbazone derivatives having 1,3-dioxoisoindole core were synthesized from the reaction of N-(1,3-dioxoisoindolin-2-yl)aminothiocarbohydrazide (3) with a variety of aldehydes and ketones. Their geometrical and conformational isomers were investigated based on the analysis of their 1HNMR and 13CNMR spectra. The thiosemicarbazones were found to exist in the more stable structure III with an E configuration and a syn, syn disposition of both NH protons around the C=S bond. However, compounds 5b and 9c were existed as a mixture of E (major) and Z (minor) stereoisomers with a syn, syn conformation of both NH protons around the C=S bond as in structure III and VI, respectively. On the other hand, the thiosemicarbazones 9e,f and 15 derived from p-chloro-, p-bromoacetophenone and cyclopropylmethyl ketone 14 showed different behavior. They existed in solution of DMSO-d6 as a mixture of E (major) and Z (minor) geometrical isomers with syn, syn and, anti, anti disposition of both NH protons as in structure III and IV, respectively. Dehydrative cyclization of compounds 5b–g, i, 9a–d and 15 with acetic anhydride afforded only one stereoisomer of the hybrid heterocycles of the dioxoisoindole and thiadiazoline rings 16a–l as confirmed by 1H and 13C NMR spectra. DFT calculations revealed the extrastability of the E isomer relative to the Z one 5b, d and 15 as representative examples. The relative energies are small (5.1–5.8 kcal/mol) which further confirm their coexistence in solution.

Direct Access to S-Heterocycles by Scandium(III) Triflate Catalyzed Cyclization of Aromatic Thiols and Diols

AbstractA simple and environmentally friendly method to prepare S-heterocycles by cyclization of aromatic thiols and diols with H2O as a byproduct is described. The Sc(OTf)3-catalyzed dehydrative cyclizations of aromatic thiols and diols provided the corresponding thiopyran and thiophene derivatives. Control experiments were also performed to obtain insights into the reaction pathway

Hydrogen-bond donor and acceptor cooperative catalysis strategy for cyclic dehydration of diols to access O-heterocycles.

Dehydrative cyclization of diols to O-heterocycles is attractive, but acid and/or metal-based catalysts are generally required. Here, we present a hydrogen-bond donor and acceptor cooperative catalysis strategy for the synthesis of O-heterocycles from diols in ionic liquids [ILs; e.g., 1-hydroxyethyl-3-methyl imidazolium trifluoromethanesulfonate ([HO-EtMIm][OTf])] under metal-free, acid-free, and mild conditions. [HO-EtMIm][OTf] is tolerant to a wide diol scope, shows performance even better than H2SO4, and affords a series of O-heterocycles including tetrahydrofurans, tetrahydropyrans, morpholines, dioxanes, and thioxane in high yields. Mechanism investigation indicates that the IL cation and anion serve as hydrogen-bond donor and acceptor, respectively, to activate the C─O and O─H bonds of alcohol via hydrogen bonds, which synergistically catalyze dehydrative cyclization of diols to O-heterocycles. Notably, the products could be spontaneously separated after reaction because of their immiscibility with the IL, and the IL could be recycled. This green strategy has great potential for application in industry.

Biomimetic Total Syntheses of Amorfrutins A, B, (S)‐D and (R)‐D and Formal Synthesis of Amorfrutin C

AbstractBibenzyl natural products, such as the amorfrutins, contain a heavily substituted aromatic core and display a diverse range of biological activities (anti‐tumor, anti‐diabetic, antimicrobial, and antibiotic). In this study, we report unified syntheses of amorfrutin A to D either through total or formal synthesis by employing a dual biomimetic strategy of polyketide aromatization followed by remote terpene functionalization. The key core structures were synthesized from β‐keto dioxinone esters through a magnesium(II) mediated regioselective C‐acylation, palladium catalyzed decarboxylative allylic rearrangement, and dehydrative cyclization.

Wittig Reactions of Maleimide-Derived Stabilized Ylides with Alkyl Pyruvates: Concise Approach to Methyl Ester of (±)-Chaetogline A

AbstractA facile synthesis of methyl ester of chaetogline A is reported starting from the corresponding methyl 1-methyltryptophanate-derived­ maleimide. A stereoselective Wittig olefination with a carbonyl function in methyl pyruvate followed by phosphorous pentoxide-induced­ regioselective dehydrative cyclization are the essential reactions. An acid-induced thermodynamically driven stereoselective β- to α-position migration of the exocyclic C=C bond unit in ethyl tetrahydroindolizinoindolylidenepropanoate is described.

Synthesis and Stereochemical Behavior of Dioxa[6]helicene Derivatives

AbstractWe constructed a helically chiral dioxa[6]helicene by assembling simple phenol building blocks by a combination of two simple reactions involving oxidative cross‐coupling followed by dehydrative cyclization. X‐ray analysis and density functional calculations (DFT) revealed that the compound dioxa[6]helicene has a helical structure that undergoes helical inversion rapidly at room temperature. We were able to detect the presence of resolvable helical isomers of (−)‐menthyloxycarbonyl derivative of dioxa[6]helicene by recording 1H NMR spectra below 0 °C. The investigations of photo physical properties by cyclic voltammetry, UV/Vis‐ and fluorescence properties with the aid of time‐dependent DFT calculations were undertaken.