A new design of cleavable acetal‐containing amphiphilic block copolymers triggered by light

We report a new design of photolabile acetal‐containing amphiphilic block copolymers. Acetals as protecting groups for carbonyls or diols can be hydrolyzed under acidic condition but very stable with respect to hydrolysis at pH > 7. When combining light‐capturing chromophores with acetals, the hydrolysis of acetals can be activated by light to design dual responsive acetal‐containing polymers. Using acetalization reaction of 2,3‐dihydroxypropyl methacrylate with benzaldehyde derivatives, two new acetal‐containing photolyzable monomers have been designed. Comparable to commonly used photolabile monomers containing nitrobenzyl esters, the two acetal‐containing monomers are easy to polymerize using atom transfer radical polymerization with excellent molecular weight and dispersity control. We studied the cleavage kinetics and mechanism of acetal groups in both monomers and polyethylene oxide (PEO)‐containing amphiphilic block copolymers using ¹H NMR and UV–vis spectroscopy. o‐Nitrobenzaldehyde acetal showed a Norrish Type II rearrangement to form benzoic ester; while, 2,5‐dimethoxy benzaldehyde acetal was photolabile to completely release 2,3‐dihydroxypropyl methacrylate. The photocleavage of acetals is a zero‐order reaction in regardless of molecular states of acetals; while, the acid‐cleavage of acetals proves to be a first‐order kinetics and the cleavage becomes much slower for polymers. The self‐assembly of acetal‐containing amphiphilic block copolymers and the acid‐/light‐controlled dissociation of their vesicles have been investigated. We demonstrate that those acetal‐containing polymers are potentially useful as smart drug delivery systems where the release kinetics of payloads is tunable using light and pH as triggers. © 2018 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2018 , 56, 1815–1824     

A Facile Method for the Preparation of Pure cis‐2,4‐Pentanediol

Abstract

The isolation of diastereomerically pure cis‐2,4‐pentanediol from a crude mixture of both cis‐ and trans‐2,4‐pentanediols is described through a short procedure involving thermodynamic acetal formation with acetophenone, followed by hydrogenolysis of the acetal protecting group.     

Synthesis and applications of acid-labile acrylic polymers

A variety of acrylic and methacrylic acetal esters were synthesized by reaction of unsaturated carboxylic acids with vinyl ethers. The acetal esters were converted by radical polymerization and GTP to acid-labile homo- and copolymers. Coatings of these polymeric acetal esters containing photosensitive acid-generating compounds are useful in image-formation through chemical amplification. Thus, poly(tetrahydropyranyl methacrylate-co-benzyl methacrylate) can be used in positive working deep UV microlithography. Poly(tetrahydropyranyl acrylate), coated in a thin layer over a tacky elastomer, provides a high resolution, water-developable negative working tonable composition. Several polymeric and nonpolymeric acetal esters can be used for positive working electrostatic imaging through changes in electrical conductivity.     

The synthesis of 4-substituted-4H-1,2,4-triazole-3-thiols and 3-methylthio-4-substituted-4H,2,4-triazoles

The synthesis of 4-substituted-4H-1,2,4-triazole-3-thiols and 3-methylthio-4-substituted-4H-1,2,4-triazoles by the condensation of 4-substituted-3-thiosemicarbazides with dimethylformamide dimethyl acetal or dimethylacetamide dimethyl acetal is described. A discussion of the mechanistic pathway is included.     

Model Studies towards the Synthesis of the Right‐Hand Part of Pederin

Bicyclic acetal derivatives of the type 3 were prepared based either on a dihydroxyaldehyde 5 or an oxiranebutanal 6 (cf. Scheme 2). Lewis acid catalyzed reaction of the bicyclic acetal with allyltrimethylsilane introduces the side chain (as yet unfunctionalized) and sets the stereogenic centers at the tetrahydro‐2H‐pyran ring of the pederin moiety.     

Notiz über einen Zugang zu β, γ-ungesättigten Carbonsäurederivaten mit Hilfe der Amidacetal-Claisenumlagerung. Über synthetische methoden, 17. Mitteilung

Note on a preparation of β, γ-unsaturated carboxylic acid derivatives using the amide acetal Claisen rearrangement 3-(Trimethylsilyl)allyl alcohols smoothly undergo the amide acetal Claisen rearrangement furnishing allyl silanes. Subsequent protolysis with HF at ?20° provides a convenient, stereoselective method for the preparation of β, γ-unsaturated carboxylic acid derivatives. Three model examples illustrate the procedure.     

Synthesis of an amphiphilic polymer having hydrophobic acetal and hydrophilic pyrrolidone moieties and its application to persisting release of aldehyde as a pro‐fragrance

A polymer having acetal moiety in the side chain was synthesized by a reaction of 1,3‐diol structure of poly(vinyl alcohol‐co‐N‐vinylpyrrolidone) and octanal. The hydrophobicity of the resulting acetal moiety and the hydrophilicity of the pyrrolidone moiety allowed the polymer to exhibit amphiphilicity. The polymer released octanal by hydrolysis of the acetal side chains under acidic conditions. The release of octanal was enhanced by the increased hydrophilicity of the polymer because of the presence of pyrrolidone moiety. © 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 48: 3816–3822, 2010     

Neighbouring-group Influence on the Ring Opening of Some 2-Alkyl-1,1,2-tribromocyclopropanes under Phase-transfer Conditions

Several 2-alkyl-1,1,2-tribromocyclopropanes were treated with sodium hydroxide and ethanol under phase-transfer conditions. Ring opening gave mixtures of the corresponding acetylenic diethyl ketals and acetals. When the steric bulk of the alkyl substituent was increased acetal formation dominated, and in the case of 1,1,2-tribromo-2-(tert-butyl)cyclopropane, the acetal was formed as the only product.     

Synthesis and properties of <Emphasis Type="Italic">N</Emphasis>-[2,2-bis(2,4-dihydroxyaryl)ethyl]-<Emphasis Type="Italic">N</Emphasis>-methylamines and their hydrohalides

Condensation of one molecule of α-methylaminoacetaldehyde dimethyl acetal with two molecules of resorcinol or methylresorcinol in hydrohalogen acid solutions led to substituted N-(2,2-diarylethyl)-N-methylamine hydrohalides. Reactions of the corresponding amines with acetic anhydride, mono-and diisocyanates, and formaldehyde were studied. Conditions for formation of calixarene from resorcinol and α-methylaminoacetaldehyde dimethyl acetal were invented. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 2, pp. 319–324, February, 2007.     

Neighbouring-group Influence on the Ring Opening of Some 2-Alkyl-1,1,2-tribromocyclopropanes under Phase-transfer Conditions

Summary. Several 2-alkyl-1,1,2-tribromocyclopropanes were treated with sodium hydroxide and ethanol under phase-transfer conditions. Ring opening gave mixtures of the corresponding acetylenic diethyl ketals and acetals. When the steric bulk of the alkyl substituent was increased acetal formation dominated, and in the case of 1,1,2-tribromo-2-(tert-butyl)cyclopropane, the acetal was formed as the only product.     

Separation and confirmation of the product and by products of the reaction of cyclododecanone with phenyl ethylene glycol

It has been proved, by TLC and synthetic methods, that the odoriferous material formed in the reaction of cyclododecanone and phenyl ethylene glycol under acidic condition, was not the ketal of cyclododecanone, but an acetal of phenylacetaldehyde with phenyl ethylene glycol—the by-product formed from phenyl ethylene glycol. The cis-trans isomers of the acetal were separated by chromatography, the configurations were confirmed via the analysis of their ¹H NMR spectra, and the odors were evaluated as well.     

1,2‐Bis(trifluoromethyl)ethene‐1,2‐dicarbonitrile: Enol Ethers and Ketene Acetals as Cycloaddition Partners

(E)‐ and (Z)‐1,2‐bis(trifluoromethyl)ethene‐1,2‐dicarbonitrile ((E)‐ and (Z)‐BTE, resp., =(E)‐ and (Z)‐2,3‐bis(trifluoromethyl)but‐2‐enedinitrile) were used as a stereochemical probe in studying (2+2) cycloadditions of acceptor with donor alkenes. The additions to methyl (E)‐ and (Z)‐propenyl ether gave rise to the eight conceivable cyclobutanes 8 , although in different ratios in reactions of (E)‐ and (Z)‐BTE. The ¹⁹F‐NMR data served the structural assignment and the quantitative analysis. The mechanistic discussion is based on rotations and ring closures of the assumed 1,4‐zwitterionic intermediates. Dimethylketene dimethyl acetal, methylketene dimethyl acetal, and ketene diethyl acetal show an increasing rate in their reactions with BTE as well as in the equilibration of the cycloadducts.     

Preparation and characterization of cyclic poly(oxypropylene)

Poly(propylene glycol) [α-hydro-ω-hydroxypoly(oxypropylene)] of number-average molar mass M̄_n ≈ 2000 g · mol⁻¹ (PPG2000) was cyclised with high conversion (ca. 75%) by reaction with dichloromethane in the presence of powdered KOH. The cyclic product was separated from chain extended polymer by preparative GPC, giving an overall yield of polymer (M̄_n ≈ 2000 g · mol⁻¹, narrow molar mass distribution) in excess of 50%. Characterisation by analytical GPC and ¹³C NMR spectroscopy confirmed cyclisation. DEPT and ¹H-coupled NMR spectra were used to show that the links in cyclic poly(oxypropylene) were 77% single acetal, 12% double acetal and 11% triple acetal (or higher). This complexity probably results from competitive reaction with water introduced with KOH.     

A Simple Synthesis of a Model of the Tetracyclic Bisketal Lactone Mainframe of Saudin

The partial structure 2 of the bisketal‐type, tetracyclic saudin ( 1 ), an important natural product, was de novo synthesized. A key step was the Jones oxidation of the epoxide 3 , which gave rise to epoxide‐ring opening, followed by acetal hydrolysis, alcohol oxidation, and, finally, intramolecular acetal formation. The resulting key intermediate was finally oxidized to the target lactone 2 .     

A Study of the Constituents of the Heartwood of Tsuga Chinensis Pritz. Var. Formosana (Hay.)

By means of spectroscopic analysis, X-ray crystallography and chemical correlation the heartwood of Taiwan hemlock was found to contain compounds of sterols, carboxylic acids, 13-epimanool, o methoxyphenolics, coniferaldehyde, benzofuranoid neolignan, α-conidendrin, tsugacetal, isolariciresinol, secoisolariciresinol, matairesinol, hydroxymatairesinol and oxomatairesinol. Among them (+)-tsugacetal is a novel lignan acetal having an α-conidendrin related structure with the acetal methoxy group at the β-position.     

Lignin Biodegradation by a Cytochrome P450 Enzyme: A Computational Study into Syringol Activation by GcoA

A recently characterized cytochrome P450 isozyme GcoA activates lignin components through a selective O-demethylation or alternatively an acetal formation reaction. These are important reactions in biotechnology and, because lignin is readily available; it being the main component in plant cell walls. In this work we present a density functional theory study on a large active site model of GcoA to investigate syringol activation by an iron(IV)-oxo heme cation radical oxidant (Compound I) leading to hemiacetal and acetal products. Several substrate-binding positions were tested and full energy landscapes calculated. The study shows that substrate positioning determines the product distributions. Thus, with the phenol group pointing away from the heme, an O-demethylation is predicted, whereas an initial hydrogen-atom abstraction of the weak phenolic O-H group would trigger a pathway leading to ring-closure to form acetal products. Predictions on how to engineer P450 GcoA to get more selective product distributions are given.     

Carbene‐Catalyzed Enantioselective Aromatic N‐Nucleophilic Addition of Heteroarenes to Ketones

The aromatic nitrogen atoms of heteroarylaldehydes are activated by carbene catalysts to react with ketone electrophiles. Multi‐functionalized cyclic N,O‐acetal products are afforded in good to excellent yields and optical purities. Our reaction involves the formation of an unprecedented aza‐fulvene‐type acylazolium intermediate. A broad range of N‐heteroaromatic aldehydes and electron‐deficient ketone substrates works effectively in this transformation. Several of the chiral N,O‐acetal products afforded through this protocol exhibit excellent antibacterial activities against Ralstonia solanacearum (Rs) and are valuable in the development of novel agrichemicals for plant protection.     

An entry into the novel tetracyclic system 6H-pyrido[1′,2′:4,5]pyrazino[1,2-a]benzimidazole. Synthesis and conformational study of the 1,2,3,4,13,13a-hexahydro-3,3-ethylenedioxy and 3-ketone derivatives

The synthesis of the tetracyclic title compounds, acetal 5 and ketone 6 , is presented. The key step, formation of the imidazole ring to give compound 5 , involved the acid catalysed dehydration of the 2-(o-aminophenyl)lactam 7b . This was generated from lactam 4 via N-substitution with o-nitrofluorobenzene and reduction of the nitro group. Deprotection of acetal 5 afforded ketone 6 which through a temperature dependence study of vicinal coupling constants was shown to occur as an equilibrium of trans- and cis-fused forms A and B .     

Poly(ester-acetals) from azelaaldehydic acid-glycerol compounds

Poly(ester-acetals) have been prepared from isopropylideneglyceryl azelaaldehydate dimethyl acetal and from methyl azelaaldehydate glycerol acetal. Acid hydrolysis of isopropylideneglyceryl azelaaldehydate led to oligomeric poly(ester-acetals) with six to seven repeating units and carboxylic acid endgroups from which the sodium salt and the methyl ester could be prepared. The polymer sodium salt showed some surfactant properties. Methyl azelaaldehydate glycerol acetal, a mixture of geometric and structural isomers, was polymerized under typical polyesterification conditions. Lime was the best catalyst found. Molecular weights of 5000 to 12000 were obtained. Some of these polymers contained significant quantities of calcium as the carboxylate salt. A tough elastomer was prepared by heating a poly(ester-acetal) with p-toluenesulfonic acid and zine oxide.     

Use of 3–(2′-formyl-1′-chlorovinyl)coumarin in the syntheses of pyrazol,salicylaldazine and pyrimidine derivatives

3–(Pyrazol-5-yl)coumarin (3) was prepared from condensation of 3–(2′-formyl-l-chlorovinyl)-coumarin (1) with hydrazine hydrate at room temperature, followed by cyclyzation with base. Salicylaldazine was prepared from methoxylation of 1 to give acetal 7 , followed by condensation of 7 with hydrazine hydrate at 80°C: Treatment of acetal 7 with thiourea yielded the corresponding 4-substituted-2-thioxo-2H-pyrimidine[3, 4-b]-coumarin (12).